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![American Family Physician
during labor.44 Suppressive therapy reduces the risk
of recurrence by 75 percent and the rate of cesarean
delivery because of HSV lesions by 40 percent.45
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herpes-fact-sheet-lowres-2010.pdf. Accessed September
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7. U.S. Department of Health and Human Services, Centers
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disease surveillance 2009. http://www.cdc.gov/std/
stats09/surv2009-Complete.pdf. Accessed May 8, 2011.
8. Centers for Disease Control and Prevention. CDC fact
sheet. Syphilis. http://www.cdc.gov/std/syphilis/syphilisfact-sheet-press.pdf. Accessed September 27, 2010.
9. Centers for Disease Control and Prevention. Chancroid:
tracking the hidden epidemics. Trends in STDs in the
United States. 2000. http://www.cdc.gov/std/Trends2000/
chancroid.htm. Accessed September 14, 2011.
10. Centers for Disease Control and Prevention. CDC fact
sheet. LGV. http://www.cdc.gov/std/lgv/LGV-Fact-Sheet.
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11. de Menthon M, Lavalley MP, Maldini C, Guillevin
L, Mahr A. HLA-B51/B5 and the risk of Behçet’s
disease: a systematic review and meta-analysis of casecontrol genetic association studies. Arthritis Rheum.
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12. Schiffer JT, Corey L. Herpes simplex virus. In: Mandell GL,
Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett’s
Principles and Practice of Infectious Diseases. 7th ed.
Philadelphia, Pa.: Churchill Livingstone; 2009:1943-1962.
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13. Burstein GR. Sexually transmitted infections. In: Kliegman
R, Nelson WE, eds. Nelson Textbook of Pediatrics. 19th
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14. Alpsoy E, Durusoy C, Yilmaz E, et al. Interferon alfa-2a
in the treatment of Behçet disease: a randomized placebocontrolled and double-blind study. Arch Dermatol.
2002;138(4):467-471.
15. Warts, herpes simplex and other viral infections. In:
Clinical Dermatology: A Color Guide to Diagnosis and
Therapy. Habif TP, ed. 5th ed. Edinburgh, Scotland:
Mosby; 2010:454-490.
16. O’Meara SM, Cullum NA, Majid M, Sheldon TA.
Systematic review of antimicrobial agents used for
chronic wounds. Br J Surg. 2001;88(1):4-21.
17. Sharma R, Dronen SC. Herpes simplex in emergency
medicine. Medscape Reference. http://emedicine.medscape.
com/article/783113-overview. Accessed September 13, 2011.
18. Wald A, Zeh J, Selke S, et al. Reactivation of genital
herpes simplex virus type 2 infection in asymptomatic
seropositive persons. N Engl J Med. 2000;342(12):844-850.
19. Kimberlin DW, Rouse DJ. Clinical practice. Genital herpes.
N Engl J Med. 2004;350(19):1970-1977.
20. Lewis DA. Chancroid: clinical manifestations, diagnosis,
and management. Sex Transm Infect. 2003;79(1):68-71.
21. Sethi G, Allason-Jones E, Richens J, et al. Lymphogranuloma
venereum presenting as genital ulceration and inguinal
syndrome in men who have sex with men in London,
UK [published correction appears in Sex Transm Infect.
2009;85(5):406]. Sex Transm Infect. 2009;85(3):165-170.
22. Velho PE, Souza EM, Belda Junior W. Donovanosis. Braz J
Infect Dis. 2008;12(6):521-525.
23. Klippel JH, Weyand CM. Wortmann R, eds. Primer on
the Rheumatic Diseases. 11th ed. Atlanta, Ga.: Arthritis
Foundation; 1997:89.
24. Mat MC, Goksugur N, Engin B, Yurdakul S, Yazici
H. The frequency of scarring after genital ulcers in
Behçet’s syndrome: a prospective study. Int J Dermatol.
2006;45(5):554-556.
25. Ashley RL. Sorting out the new HSV type specific
antibody tests. Sex Transm Infect. 2001;77(4):232-237.
26. Wald A, Huang ML, Carrell D, Selke S, Corey L.
Polymerase chain reaction for detection of herpes simplex
virus (HSV) DNA on mucosal surfaces: comparison with
HSV isolation in cell culture. J Infect Dis. 2003;188(9):
1345-1351.
27. Fleming DT, McQuillan GM, Johnson RE, et al. Herpes
simplex virus type 2 in the United States, 1976 to 1994.
N Engl J Med. 1997;337:1105-1111.
28. Bruisten SM, Cairo I, Fennema H, et al. Diagnosing genital
ulcer disease in a clinic for sexually transmitted diseases
in Amsterdam, The Netherlands. J Clin Microbiol.
2001;39(2):601-605.
29. Fife KH, Barbarash RA, Rudolph T, Degregorio B, Roth
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episode genital herpes infection. Results of an international,
multicenter, double-blind, randomized clinical trial. The
Valaciclovir International Herpes Simplex Virus Study
Group. Sex Transm Dis. 1997;24(8):481-486.
30. Saenz A, Ausejo M, Shea B, Wells G, Welch V, Tugwell
P. Pharmacotherapy for Behcet’s syndrome. Cochrane
Database Syst Rev. 2000;(2):CD001084.
31. Alpsoy E, Er H, Durusoy C, Yilmaz E. The use of sucralfate
suspension in the treatment of oral and genital ulceration
of Behçet disease: a randomized, placebo-controlled,
double-blind study. Arch Dermatol. 1999;135(5):529-532.
32. Powers KA, Poole C, Pettifor AE, Cohen MS. Rethinking
the heterosexual infectivity of HIV-1: a systematic review
and meta-analysis. Lancet Infect Dis. 2008;8(9):553-563.
33. Krieger JN. Prostatitis, epididymitis, and orchitis: semen
as a vector for human immunodeficiency virus. In:
Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas,
and Bennett’s Principles and Practice of Infectious
Diseases. 7th ed. Philadelphia, Pa.: Churchill Livingstone;
2009:1521-1527.
34. U.S. Preventive Services Task Force. Screening
for syphilis infection. July 2004. http://www.
uspreventiveservicestaskforce.org/uspstf/uspssyph.htm.
Accessed September 13, 2011.
35. U.S. Preventive Services Task Force. Screening
for genital herpes. March 2005. http://www.
uspreventiveservicestaskforce.org/uspstf05/herpes/
herpesrs.htm. Accessed September 13, 2011.
36. Kim HN, Wald A, Harris J, Almekinder J, Heitman C, Corey
L. Does frequency of genital herpes recurrences predict
risk of transmission? Further analysis of the valacyclovir
transmission study. Sex Transm Dis. 2008;35(2):124-128.
37. Martin ET, Krantz E, Gottlieb SL, et al. A pooled analysis
of the effect of condoms in preventing HSV-2 acquisition
[published correction appears in Arch Intern Med.
2010;170(11):929]. Arch Intern Med. 2009;169(13):12331240.
38. Wald A, Langenberg AG, Link K, et al. Effect of condoms
on reducing the transmission of herpes simplex virus type
2 from men to women. JAMA. 2001;285(24):3100-3106.
39. American College of Obstetricians and Gynecologists.
Gynecologic herpes simplex virus infections. ACOG
Practice Bulletin no. 57. Washington, DC: American
College of Obstetricians and Gynecologists; 2004.
40. Corey L, Wald A, Patel R, et al.; Valacyclovir HSV
Transmission Study Group. Once-daily valacyclovir to
reduce the risk of transmission of genital herpes. N Engl J
Med. 2004;350(1):11-20.
41. Diaz-Mitoma F, Sibbald RG, Shafran SD, Boon R,
Saltzman RL. Oral famciclovir for the suppression of
recurrent genital herpes: a randomized controlled trial.
Collaborative Famciclovir Genital Herpes Research
Group. JAMA. 1998;280(10):887-892.
42. Bodsworth NJ, Crooks RJ, Borelli S, et al. Valaciclovir
versus aciclovir in patient initiated treatment of recurrent
genital herpes: a randomised, double blind clinical trial.
International Valaciclovir HSV Study Group. Genitourin
Med. 1997;73(2):110-116.
43. Wald A, Selke S, Warren T, et al. Comparative efficacy of
famciclovir and valacyclovir for suppression of recurrent
genital herpes and viral shedding. Sex Transm Dis.
2006;33:529-533.
44. Randolph AG, Hartshorn RM, Washington AE. Acyclovir
prophylaxis in late pregnancy to prevent neonatal herpes:
a cost-effectiveness analysis. Obstet Gynecol. 1996;88(4 pt
1):603-610.
45. Sheffield JS, Hollier LM, Hill JB, Stuart GS, Wendel
GD. Acyclovir prophylaxis to prevent herpes simplex
virus recurrence at delivery: a systematic review. Obstet
Gynecol. 2003;102(6):1396-1403.
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Table 1. Vaccines for the 2013-2014 Influenza Season (continued)
Vaccine
Dispensing method
Mercury
content (mcg
per 0.5-mL
dose)
Ovalbumin
content (mcg
per 0.5-mL
dose)
Approved
ages
Route of
administration
0
—
≥ 65 years
Intramuscular†
Inactivated influenza vaccine, trivalent, high dose
Fluzone High-Dose** 0.5-mL single-dose prefilled syringe
Inactivated influenza vaccine, quadrivalent, standard dose
Fluarix quadrivalent
0.5-mL single-dose prefilled syringe
0
≤ 0.05
≥ 3 years
Intramuscular†
Flulaval quadrivalent
5.0-mL multidose vial
< 25.0
≤ 0.3
≥ 3 years
Intramuscular†
0
—
6 to 35 months
Intramuscular†
0.5-mL single-dose prefilled syringe
0
—
≥ 36 months
Intramuscular†
0.5-mL single-dose vial
0
—
≥ 36 months
Intramuscular†
0
0
18 to 49 years
Intramuscular†
0 (per 0.2-mL
dose)
< 0.24 (per 0.2mL dose)
2 to 49 years‡‡
Intranasal
Fluzone quadrivalent 0.25-mL single-dose prefilled syringe
Recombinant influenza vaccine, trivalent
Flublok
0.5-mL single-dose vial
Live attenuated influenza vaccine, quadrivalent
Flumist
quadrivalent††
0.2-mL single-dose prefilled
intranasal sprayer
Note: Immunization providers should check U.S. Food and Drug Administration–approved prescribing information for 2013-2014 influenza vaccines for
the most complete and updated information, including (but not limited to) indications, contraindications, and precautions. Package inserts for U.S.licensed vaccines are available at http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm093833.htm.
*Age indication per package insert is 5 years or older; however, the Advisory Committee on Immunization Practices recommends that Afluria not be used
in children 6 months to 8 years of age because of increased risk of febrile reactions noted in this age group with 2010 Southern Hemisphere trivalent
inactivated vaccine. If no other age-appropriate, licensed inactivated seasonal influenza vaccine is available for a child 5 to 8 years of age who has a medical
condition that increases the child’s risk of influenza complications, Afluria can be used; however, health care professionals should discuss with the parents
or caregivers the benefits and risks of influenza vaccination with Afluria before administering this vaccine. Afluria may be used in persons 9 years or older.
†For adults and older children, the recommended site of vaccination is the deltoid muscle. The preferred site for infants and young children is the anterolateral
aspect of the thigh. Specific guidance regarding site and needle length for intramuscular administration may be found in the Advisory Committee on
Immunization Practices General Recommendations on Immunization (Centers for Disease Control and Prevention. General recommendations on immunization:
recommendations of the Advisory Committee on Immunization Practices, 2011. MMWR. 2011;60[RR-2].).
‡Information not included in package insert. The total egg protein is estimated to be less than 50 femtograms (5 × 1014 g) total egg protein (of which a
fraction is ovalbumin) per 0.5-mL dose of Flucelvax.
§Available on request from Sanofi Pasteur (1-800-822-2463 or MIS.Emails@sanofipasteur.com).
||Inactivated influenza vaccine, intradermal: a 0.1-mL dose contains 9 mcg of each vaccine antigen (27 mcg total).
¶The preferred site is over the deltoid muscle. Fluzone intradermal is administered using the delivery system included with the vaccine.
**Inactivated influenza vaccine, high dose: a 0.5-mL dose contains 60 mcg of each vaccine antigen (180 mcg total).
††It is anticipated that the quadrivalent formulation of Flumist will replace the trivalent formulation for the 2013-2014 season. Flumist is shipped refrigerated
and stored in the refrigerator at 35°F to 46°F (2°C to 8°C) after arrival in the vaccination clinic. The dose is 0.2 mL divided equally between each nostril.
Health care professionals should consult the medical record, when available, to identify children 2 to 4 years of age with asthma or recurrent wheezing that
might indicate asthma. In addition, to identify children who might be at greater risk of asthma and possibly at increased risk of wheezing after receiving live
attenuated influenza vaccine, parents or caregivers of children 2 to 4 years of age should be asked, “In the past 12 months, has a health care professional
ever told you that your child had wheezing or asthma?” Children whose parents or caregivers answer “yes” to this question and children who have asthma
or who had a wheezing episode noted in the medical record within the past 12 months should not receive Flumist.
‡‡Flumist is indicated for healthy, nonpregnant persons 2 to 49 years of age. Persons who care for severely immunosuppressed persons who require a
protective environment should not receive Flumist given the theoretical risk of transmission of the live attenuated vaccine virus.
Dose) is approved for persons 65 years or older. Three
prelicensure studies among persons in this age group
showed that, compared with the standard dose, the
high-dose vaccine elicited higher hemagglutination
inhibition antibody titers against the three virus strains
included in the seasonal influenza vaccine during the
study period. However, there is no recommendation
for using the high-dose vaccine vs. the standard-dose
vaccine in this population.
Persons 18 to 49 years of age who have an egg allergy of
any severity now have the option of receiving trivalent
recombinant influenza vaccine, an egg-free vaccine. In
persons who have no known history of egg exposure
but who have received allergy test results suggestive of
an egg allergy, consultation with a physician who has
expertise in allergy management is recommended before
vaccination. Figure 1 provides an algorithm for influenza
vaccination in persons who report an allergy to eggs.
Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013
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![DENTISTRY
ÂÂ
Inhibition of specific organisms
Inhibition of pathogen adhesion, colonization and
biofilm formation
Inhibition of pathogen growth by various substances
such as organic acids, hydrogen peroxide and
bacteriocins against oral pathogens
Effects on host response
Inhibition of collagenases and reduction of
inflammation-associated molecules
Induction of expression of cytoprotective proteins
on host cell surfaces
Modulation of proinflammatory pathways induced
by pathogens
Prevention of cytokine-induced apoptosis
ÂÂ
Modulation of host immune response
ÂÂ
ÂÂ
ÂÂ
ÂÂ
ÂÂ
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Probiotics: Role in prevention of
periodontal disease
Various studies have reported the capacity of lactobacilli
to inhibit the growth of periodontopathogens,
including P. gingivalis, Prevotella intermedia and
A. actinomycetemcomitans.10,11
Krasse and colleagues12 assessed the beneficial effect
of L. reuteri against gingivitis. First, L. reuteri is known
for its secretion of two bacteriocins, reuterin and
reutericyclin, that inhibit the growth of a wide variety
of pathogens;13,14 second, L. reuteri has a strong capacity
to adhere to host tissues, thereby competing with
pathogenic bacteria.15
periodontitis.19 Hojo et al suggested that Bifidobacterium
inhibited some black-pigmented anaerobes by
competing for an essential growth factor vitamin K.20
Shimauchi et al demonstrated that the oral
administration of a tablet containing L. salivarius
WB21 decreased plaque index significantly and pocket
probing depth markedly in smokers and reduced
salivary lactoferrin at the end of 8-week trial.21
Twetman et al used L. reuteri-containing chewing gum in
42 healthy patients and assessed its effects on crevicular
fluid volume, cytokine (interleukin-1β, interleukin-6,
interleukin-10 and tumor necrosis factor-α [TNF-α])
levels and bleeding on probing. Crevicular fluid
volume, as well as TNF-α and interleukin-8 levels and
bleeding were significantly reduced.22
When the probiotic Streptococcus salivarius K12 was
added to this bacterial model, the amount of cytokine
release was greatly reduced after eight hours. This
strongly suggests that S. salivarius K12 was able to
dramatically downregulate the cytokine release from
the pathogenic bacteria.23
Probiotics and Halitosis
Kang and colleagues24 reported the capacity of various
strains of W. cibaria to inhibit the production of volatile
sulfur compounds by F. nucleatum. They concluded
that this beneficial effect resulted from the production
of hydrogen peroxide by W. cibaria, which inhibited the
proliferation of F. nucleatum.24
Staab et al observed reduction in activity of matrix
metalloprotein-3 (MMP-3) and elastase enzymes in
subjects with plaque-induced gingivitis after consuming
probiotic milk containing Lactobacillus casei species for a
period of eight weeks.16
Currently Available Probiotic Agents in
Periodontal Disease Management
Riccia et al studied the anti-inflammatory effects of
Lactobacillus brevis in a group of patients with chronic
periodontitis. Anti-inflammatory effects of L. brevis
could be attributed to its capacity to prevent the
production of nitric oxide and consequently the release
of prostaglandin E2(PGE2) and the activation of MMPs
induced by nitric oxide.17
ÂÂ
Probiotics in the form of tablets, lozenges, chewing
gums or toothpastes are available:
Another probiotic lozenge is avaliable, which
is a blend of two L. reuteri strains containing a
minimum of 1 × 108 colony forming units (CFU)
for each of the strains DSM 17938 and ATCC PTA
5289.26
Ishikawa et al observed in vitro inhibition of P. gingivalis,
P. intermedia and P. nigrescens by daily ingestion of
L. salivarius in tablet form.18
Van Essche et al have reported that B. bacteriovorus
attack, prey on and kill A. actinomycetemcomitans,
thus suggesting a potential scope for the role of
B. bacteriovorus in the prevention and treatment of
Lozenges: One of the first probiotic specifically
formulated to fight periodontal disease, contained
a patented combination of two strains of L. reuteri
selected for their synergistic properties in fighting
cariogenic bacteria and periodontopathogens. Each
dose of lozenge contained at least 2 × 108 living
cells of L. reuteri Prodentis.25
ÂÂ
Toothpastes: Toothpastes containing Dental-Lac,
a functional Lactobacillus paracasei probiotic are
available.25
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![ENDOCRINOLOGY
Effectiveness and Tolerability of Vildagliptin in Indian
Patients with Type 2 Diabetes Mellitus: Results From
Edge−A Real-World Observational Study
Subhash K Wangnoo*, Giovanni Bader**, Apurva Gawai†, Shradhanand Singh‡
Abstract
Objective: To assess the effectiveness and tolerability of vildagliptin in combination with another oral antidiabetic drug (OAD)
versus any other two-agent OAD combinations in Indian patients with type 2 diabetes mellitus (T2DM) in a real-world setting.
Study design: This was a post hoc analysis of a multicenter, prospective, 1-year, observational EDGE study for patients enrolled in
India. The primary efficacy endpoint of the study was proportion of patients achieving glycosylated hemoglobin (HbA1C) reduction
of >0.3% without peripheral edema, hypoglycemic event, discontinuation due to a gastrointestinal event or weight gain. One of the
secondary efficacy endpoints was proportion of patients achieving HbA1C <7% without hypoglycemia and weight gain. Results:
The mean age, body mass index, HbA1C and duration of T2DM were 51.8 years, 26.6 kg/m2, 8.6% and 4.3 years, respectively.
The proportion of patients achieving the efficacy endpoints was significantly higher in the vildagliptin cohort compared with the
comparator cohort (p < 0.0001). The vildagliptin cohort showed a numerically greater reduction in HbA1C than the comparator cohort
(1.4 vs 1.1%; analysis not pre-specified). Adverse events were comparable in both groups (4.2% vs 4.9%). Conclusion: In India, in
a real-world setting, vildagliptin showed better overall clinical benefits compared with comparator OADs in patients with T2DM.
Keywords: Dipeptidyl peptidase-4 inhibitor, dual combination, India, oral antidiabetic drug, real-world, type 2
diabetes, vildagliptin
T
ype 2 diabetes mellitus (T2DM), a major
lifestyle disorder, has transitioned from being
a class disease to a mass epidemic and poses a
rapidly emerging global threat to public health with
a worldwide prevalence of 366 million.1 India, once
known as the ‘diabetes capital of the world’2, was home
to 61.3 million patients with T2DM in 2011 and this
figure is expected to rise to 101.2 million by 2030.1
Various phenotypic and genotypic characteristics in
Indians may lead to increased insulin resistance, lower
*Senior Consultant Endocrinologist and Diabetologist
Apollo Centre for Obesity, Diabetes and Endocrinology (ACODE)
Indraprastha Apollo Hospital, Sarita Vihar, New Delhi
**Principal Medical Scientific Expert, Global Medical Affairs - Diabetes, Novartis
Pharma AG, Postfach, Switzerland
†Medical Advisor
Novartis Healthcare Private Limited, Worli, Mumbai
‡Clinical Research Medical Advisor
Novartis Healthcare Private Limited, Worli, Mumbai
Address for correspondence
Dr Apurva Gawai
Medical Advisor
Novartis Healthcare Private Limited
Sandoz House, 7th Floor, Shivsagar Estate
Dr Annie Besant Road, Worli, Mumbai - 400 018
E-mail: apurva.gawai@novartis.com
adiponectin, greater abdominal adiposity (higher
waist circumference despite lower body mass index
[BMI]) and a higher prevalence of impaired glucose
tolerance; all of these factors contribute to a higher
risk of developing T2DM at a comparatively young
age.3 Physical inactivity, changes in dietary habits, a
carbohydrate rich diet, urbanization and environmental
factors also add to this risk.4 In addition, patients and
healthcare professionals in India face challenges such
as clinical inertia (failure to initiate or intensify the
treatment) in achieving glycemic control, inadequate
treatment follow-up and lack of disease awareness
among patients.4
Guidelines suggest the use of combination therapies
including diverse oral antidiabetic drugs (OADs),
acting via multiple mechanisms, to effectively manage
hyperglycemia, while dealing with the challenges of the
progressive nature of T2DM and monotherapy failure.5
Vildagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor
improves pancreatic α- and β-cell responsiveness
to glucose, and consequently provides improved
glycemic control as monotherapy, or as a component
of combination therapy, without weight gain and
hypoglycemia.6-8
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![ENDOCRINOLOGY
Pragmatic real-world observational studies are
designed to provide a closer look into routine clinical
practice.9 EDGE (Effectiveness of Diabetes control
with vildaGliptin and vildagliptin/mEtformin) was
a prospective, 1-year, observational study conducted
across 27 countries from Europe, Central and Latin
America, Asia and Middle East to evaluate the efficacy,
safety and tolerability of vildagliptin in combination
with another OAD versus all other two-agent OAD
combinations in real-world settings.10 In these post hoc
analyses, we assessed the effectiveness and tolerability
of vildagliptin combination versus all other two-agent
OAD combinations in patients enrolled from India in
the EDGE study.
Subjects and Study Design
Of the 45,868 patients enrolled in the EDGE study,10
11,057 were enrolled across 472 sites in India. Patients
with T2DM, aged ≥18 years, who had inadequate
glycemic control, while receiving OAD monotherapy
with a sulfonylurea (SU), metformin, thiazolidinedione,
glinide or α-glucosidase inhibitor were eligible. Patients
receiving DPP-4 inhibitors other than vildagliptin,
incretinmimetics/analogs or insulin, requiring three or
more OADs, or who had a history of hypersensitivity
to study drugs were excluded.
Physicians chose antidiabetic treatment for their
patients at their own discretion. To avoid physician
bias for a particular choice of treatment, patients were
asked for informed consent and enrolled in the study
only after the treatment decision was made (Fig. 1).
The term index therapy was used to represent the
combination treatment initiated at enrolment. Further
details of the subjects and study design are reported
elsewhere.10
Materials and Methods
Efficacy Endpoints
The primary efficacy endpoint of the study was the
proportion of patients responding to the treatment
(reduction in glycosylated hemoglobin [HbA1C] >.3%
from baseline to 12 months) with no intolerability
findings (peripheral edema, hypoglycemic event,
discontinuation due to a gastrointestinal event or
weight gain ≥5%). One of the secondary efficacy
endpoints was the proportion of patients with baseline
HbA1C ≥7% who achieved target HbA1C <7% without
hypoglycemia and weight gain ≥3%. Change in HbA1C
from baseline to study endpoint was also evaluated in
538
Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013
these post hoc analyses (an analysis not pre-specified in
the protocol). Hypoglycemia was defined as symptoms
suggestive of hypoglycemia that resolved promptly on
administration of oral carbohydrate (including mild
and severe events).
Statistical Analysis
Descriptive statistics were used for these post hoc
analyses. Inference is provided for primary and
secondary efficacy endpoints. The per protocol (PP:
Patients who completed the study without any major
protocol deviation) population was used for analyses
of the efficacy endpoints. Data were censored if
patients changed index therapy. The probability of
success was analyzed for the efficacy endpoints using
a binary logistic regression model to calculate odds
ratios (ORs) with 95% confidence intervals (CIs). The
OR expresses odds in favor of success with vildagliptin
combinations relative to odds in favor of success with
comparator OADs. Patients whose outcomes could
not be categorized as a success or failure (e.g., due to
missing HbA1C or body weight data at the 12-month
endpoint) were considered nonevaluable. These nonevaluable patient data were considered failures in
calculation of the OR for success. Only unadjusted ORs
were reported for the primary and secondary efficacy
endpoints in these post hoc analyses. HbA1C drop was
adjusted with baseline value by using an analysis of
covariance (ANCOVA) model.
Results
Of the 11,057 patients enrolled from India in the
EDGE study, 365 patients (198 in the vildagliptin and
167 in the comparator cohort) were excluded due to
inadequate source documentation or problems with
quality or accuracy of data entry. The remaining
intention-to-treat (ITT) population received newly
prescribed vildagliptin (5,621) or a nonvildagliptin
OAD (5,071) added to prior monotherapy (Table 1).
The PP population, a subset of the ITT population
comprising 5,606 patients in the vildagliptin cohort
and 5,070 patients in the comparator cohort, was used
for the analyses of efficacy endpoints.
The demographic and baseline characteristics of
patients in the ITT population are summarized in
Table 2. Overall, 61.4% patients were male. The mean
values of age, BMI, HbA1C and duration of T2DM
at baseline were 51.8 years, 26.6 kg/m2, 8.6% and
4.3 years, respectively. Despite the fact that this was a
nonrandomized study, the baseline characteristics were
comparable across the groups (Table 2).](https://image.slidesharecdn.com/ijcp-140222021057-phpapp01/75/Ijcp-38-2048.jpg)
![ENDOCRINOLOGY
A
Patients achieved study endpoints (%)
80
70
60
Vildagliptin
68.5
Comparator
56.8
50
40
30
25.7
20
14.6
10
0
B
Primary efficacy endpoint
Secondary efficacy endpoint
0.0
Change in HbA1C from baseline (%)
−0.2
−0.4
−0.6
−0.8
−1.0
−1.1
−1.2
−1.4
−1.4
−1.6
Figure 2. (A) Primary and secondary efficacy endpoints
(PP population); (B) Change in HbA1C after 12 months of
treatment (ITT population).
(A) Percentage of patients achieving study endpoints in PP population;
unadjusted odds ratios (95% CI): 1.65 (1.53, 1.79) for primary endpoint and
2.03 (1.83, 2.25) for secondary endpoint; both p <0.0001. (B) Mean HbA1C
change (± standard error) from baseline to study endpoint in ITT population
using an ANCOVA model.
These post hoc analyses demonstrated that vildagliptin
in combination with another OAD provides better
glycemic control than any other two-agent OAD
combination. After 12 months of treatment, the
vildagliptin cohort exhibited a greater proportion
of patients (unadjusted OR 1.65 [95% CI: 1.53, 1.79])
achieving the primary efficacy endpoint (reduction in
HbA1C >0.3% without peripheral edema, hypoglycemic
event, discontinuation due to a gastrointestinal event or
weight gain ≥5%) and the secondary efficacy endpoint
of HbA1C<7% without hypoglycemia and weight gain
≥3% from a baseline HbA1C of ≥7% (unadjusted OR 2.03
[95% CI: 1.83, 2.25]) versus all other two-agent OAD
combinations.
The results for this secondary efficacy endpoint
confirm results from other studies, which consistently
showed better responder rates with vildagliptin
versus comparators, although such comparisons have
limitations.14,15
The reduction in HbA1C was numerically greater with
vildagliptin combinations versus other two-agent
OAD combinations, as in the overall EDGE study
population.10 However, the vildagliptin cohort in
the Indian population showed a numerically greater
reduction (1.4%) when compared with the vildagliptin
cohort in the overall EDGE study population (1.2%).10
This larger reduction in HbA1C in Indian patients may
be partly explained by the higher baseline HbA1C in the
Indian patients.
The vildagliptin cohort showed a good safety and
tolerability profile without any clinically relevant trends,
which further corroborates the good safety profile of
vildagliptin.16,17 The study revealed that fewer patients
in the vildagliptin cohort reported hypoglycemia than
in the comparator cohort; the majority of patients
reporting hypoglycemia were using a metformin and
SU combination. This is consistent with results from
a previously reported large pooled analysis of safety
data, which showed that vildagliptin, as monotherapy
or in combination with metformin, thiazolidinedione
or an SU, is associated with significantly fewer
hypoglycemic events than comparators.17
There were some limitations to our study. Because
physicians were required to select any drug-based on
their clinical judgment, the open study design resulted
in a possible imbalance favoring the vildagliptin arm in
the overall EDGE study population, although this did
not seem to be the case in the Indian patients. Moreover,
the patients were recruited both in specialty and
routine care centers, which may have had an impact on
the overall results because of poor quality and missing
data that needed to be excluded from the effectiveness
analyses. In addition, unlike in randomized controlled
trials, reporting of AEs was based on a voluntary
reporting scheme, which might have led to unnoticed
or under-reported events.
conclusion
These post hoc analyses of the EDGE study confirmed
that vildagliptin in combination with another OAD
showed better overall clinical benefit versus any
other two-agent OAD combination, as measured
by a composite endpoint assessing effectiveness
(HbA1C reduction) and tolerability (peripheral edema,
Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013
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![infectious diseases
Overall, AILD has a moderately aggressive course,
with occasional spontaneous remissions or protracted
responses to therapy. The median survival is 24 months.
AILD can evolve into high-grade lymphomas of T- or
B-cell type, EBV-positive B-cell lymphomas and chronic
lymphatic leukemia, among other kinds of lymphoma
and leukemia. Most patients eventually die of infections
due to immunologic compromise.
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neoplastic cells in angioimmunoblastic T-cell lymphoma
is consistent with activated follicular B helper T cells.
Blood 2006;108(3):1110-1.
3. Dunleavy K, Wilson WH, Jaffe ES. Angioimmunoblastic
T cell lymphoma: pathobiological insights and clinical
implications. Curr Opin Hematol 2007;14(4):348-53.
4. Murakami YI, Yatabe Y, Sakaguchi T, Sasaki E, Yamashita
Y, Morito N, et al. c-Maf expression in angioimmunoblastic
T-cell lymphoma. Am J Surg Pathol 2007;31(11):1695-702.
5. Tripodo C, Gri G, Piccaluga PP, Frossi B, Guarnotta C,
Piconese S, et al. Mast cells and Th17 cells contribute
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6. Saito M, Fukuda T, Shiohara T, Homori M.
Angioimmunoblastic T-cell lymphoma: a relatively
common type of T-cell lymphoma in Sjögren’s syndrome.
Clin Exp Rheumatol 2005;23(6):888-90.
12. Rahmani R, Brenner S, Krakowski A, Lipitz R, Ilie B,
Behar AJ. Angioimmunoblastic lymphadenopathy with
scleromyxedema-like lesions and serum monoclonal
protein. Isr J Med Sci 1983;19(3):235-9.
13. Sellier S, Levesque H, Courville P, Joly P.
[Cyclophosphamide-induced neutrophilic disease in a
patient with angioimmunoblastic lymphadenopathy and
myelodysplastic syndrome]. Ann Dermatol Venereol
2006;133(5 Pt 1):459-62.
14. Jones B, Vun Y, Sabah M, Egan CA. Toxic epidermal
necrolysis secondary to angioimmunoblastic T-cell
lymphoma. Australas J Dermatol 2005;46(3):187-91.
15. Jarrett R, Walk N, Castellano-Sanchez AA, Kreisel FH. A
68-year-old man with shortness of breath and peripheral
edema. Angioimmunoblastic T-cell lymphoma. Arch
Pathol Lab Med 2006;130(2):219-22.
16. Goenka MK, Vaiphei K, Nagi B, Sriram PV, Joshi K,
Kochhar R. Angioimmunoblastic lymphadenopathy: an
etiology for gastrointestinal lymphomatous polyposis.
Am J Gastroenterol 1996;91(6):1236-8.
17. Matsumiya H, Arai A, Nagai A. [A case of angioimmunoblastic T-cell lymphoma with interstitial shadow which
disappeared after injection of hydrocortisone]. Nihon
Kokyuki Gakkai Zasshi 2006;44(7):537-40.
18. Alizadeh AA, Advani RH. Evaluation and management of
angioimmunoblastic T-cell lymphoma: a review of current
approaches and future strategies. Clin Adv Hematol
Oncol 2008;6(12):899-909.
19. Pautier P, Devidas A, Delmer A, Dombret H, Sutton L, Zini
JM, et al. Angioimmunoblastic-like T-cell non Hodgkin’s
lymphoma: outcome after chemotherapy in 33 patients
and review of the literature. Leuk Lymphoma 1999;32
(5-6):545-52.
7. Martel P, Laroche L, Courville P, Larroche C, Wechsler J,
Lenormand B, et al. Cutaneous involvement in patients
with angioimmunoblastic lymphadenopathy with
dysproteinemia: a clinical, immunohistological, and
molecular analysis. Arch Dermatol 2000;136(7):881-6.
20. Rodríguez J, Conde E, Gutiérrez A, Arranz R, Gandarillas
M, Leon A, et al. Prolonged survival of patients with
angioimmunoblastic T-cell lymphoma after high-dose
chemotherapy and autologous stem cell transplantation: the
GELTAMO experience. Eur J Haematol 2007;78(4):290-6.
8. Siegert W, Nerl C, Agthe A, Engelhard M, Brittinger G,
Tiemann M, et al. Angioimmunoblastic lymphadenopathy
(AILD)-type T-cell lymphoma: prognostic impact
of clinical observations and laboratory findings at
presentation. The Kiel Lymphoma Study Group. Ann
Oncol 1995;6(7):659-64.
21. Shinohara A, Asai T, Izutsu K, Ota Y, Takeuchi K,
Hangaishi A, et al. Durable remission after the administration of rituximab for EBV-negative, diffuse large
B-cell lymphoma following autologous peripheral blood
stem cell transplantation for angioimmunoblastic T-cell
lymphoma. Leuk Lymphoma 2007;48(2):418-20.
9. Singh MK, Solanki RN, Shah NJ, Tanna D, Patel DR,
Desai IM. Angioimmunoblastic lymphadenopathy with
dysproteinemia: thoracic involvement. Indian J Chest Dis
Allied Sci 2004;46(2):125-8.
22. Halene S, Zieske A, Berliner N. Sustained remission
from angioimmunoblastic T-cell lymphoma induced
by alemtuzumab. Nat Clin Pract Oncol 2006;3(3):165-8;
quiz 169.
10. Hosoki K, Okada S, Ichinohasama R, Yamaguchi M,
Uchiyama B, Maeyama T. Angioimmunoblastic T-cell
lymphoma developed with lymphocytic pleural effusion.
Intern Med 2007;46(11):739-42.
23. Amengual JE, Raphael BG. Sustained, durable responses
with alemtuzumab in refractory angioimmunoblastic
T-cell lymphoma. Leuk Lymphoma 2010;51(7):1347-50.
11. Ferran M, Gallardo F, Baena V, Ferrer A, Florensa L,
Pujol RM. The ‘deck chair sign’ in specific cutaneous
involvement by angioimmunoblastic T cell lymphoma.
Dermatology 2006;213(1):50-2.
552
Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013
24. Nakashima M, Suzuki K, Okada M, Takada K, Kobayashi
H, Hama Y. Successful coil embolization of a ruptured
hepatic aneurysm in a patient with polyarteritis nodosa
accompanied by angioimmunoblastic T cell lymphoma.
Clin Rheumatol 2007;26(8):1362-4.](https://image.slidesharecdn.com/ijcp-140222021057-phpapp01/75/Ijcp-52-2048.jpg)
![INTERNAL MEDICINE
Cerebral Venous Thrombosis Due to Abrin Toxicity:
A Case Report
KV Rajalakshmi*, G Shivkumar**, S Karthikeyan, V Punitha, K Sangeetha
Abstract
Abrus precatorius (jequirity bean) is a common cause of accidental or intentional poisoning in the tropics. The data on exact
incidence of abrus poisoning is largely insufficient in our country, due to lack of reporting. The estimated lethal dose for humans
is 0.1-1 µg/kg. The toxic component is the protein abrin that causes widespread endothelial damage. Abrin causes a variety of
manifestations like hemorrhagic gastroenteritis with erosions, hemolysis, acute renal damage, dyselectrolytemia, hepatotoxicity
with elevated liver enzymes and seizures. Apart from the common manifestation of hemorrhagic gastroenteritis, patients
experiencing mental status perturbations have been identified and documented earlier. There have been previous reports of
elevated intracranial tension (ICT) in abrus poisoning, however, the exact cause for this phenomenon had not been elucidated.
We herein report a case of intentional A. precatorius poisoning in a young girl that caused cerebral venous thrombosis (CVT).
Keywords: Abrus precatorius poisoning, abrin poisoning, cerebral venous thrombosis, increased intracranial tension
A
brus precatorius seeds are often ingested with
suicidal intent in India, however, data on exact
incidence is lacking. Abrin is a potentially fatal
toxalbumin obtained from the seeds of A. precatorius
(jequirity bean, gundumani [Tamil]), which is similar
in structure and properties to ricin.1
We herein report a case of A. precatorius poisoning with
cerebral venous sinus thrombosis and intracerebral
bleed that has never been documented earlier.
CASE REPORT
An 18-year-old girl, a school dropout, was brought with
an alleged history of consumption of approximately
10-15 crushed abrus seeds on July 31, 2013 at 22:00
hours, following a family dispute. She was given local
indigenous treatment and taken to Taluk HQ Hospital,
Ulundurpet at 08:50 hours on August 1, 2013. There
she was instituted emergency care and subsequently
transferred to the Govt. Villupuram Medical College, at
19:35 hours, the same day. Upon arrival, the patient was
*Associate Professor
**Assistant Professor
Dept. of Internal Medicine
Govt. Villupuram Medical College, Villupuram,Tamil Nadu
Address for correspondence
Dr (Major) G Shivkumar
Assistant Professor
Dept. of Internal Medicine
Govt. Villupuram Medical College, Villupuram, Tamil Nadu - 605 601
E-mail: majorshivk@yahoo.com
dehydrated and had recurrent diarrhea and vomiting.
She was actively resuscitated with oral and intravenous
fluid replacement. Her hydration status improved and
vital parameters were stabilized. Her blood counts,
biochemical analysis and liver function tests (LFTs)
were within normal limits. Serum Na+ 158 mEq/l, K+
2.3 mEq/l, Cl- 126 mEq/l, HCO3- 26 mEq/l.
Patient’s vomit improved but diarrhea persisted despite
supportive treatment. On Day 4, patient developed
bloody diarrhea for which 1 unit of compatible group
blood was transfused. Biochemical analysis revealed
serum creatinine of 1.1 mg%, Na+ 143 mEq/l, K+ 2.4
mEq/l, Cl- 110 mEq/l and HCO3- 23 mEq/l. Repeat
LFTs including prothrombin time/INR (international
normalized ratio) were within normal limits. Her blood
pressure was 120/86 mmHg and urine output was 2,100
ml/24 hours. On Day 6, the patient experienced one
episode of generalized tonic-clonic seizures. She was
managed with intravenous loading and maintenance
dose of phenytoin. She became progressively drowsy
thereafter with persistent depressed mentation.
Fundus examination revealed bilateral papilledema. A
noncontrast computed tomography (CT) scan of brain
revealed a hyperdense lesion with perilesional edema
in left occipital region with hyperdense appearance
of sagittal sinus (filled delta sign). The features were
suggestive of superior sagittal sinus thrombosis with
hemorrhage in left occipital lobe. CT contrast study
was advised. Anti-edema and anticoagulant treatment
with unfractionated heparin commenced.
Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013
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![ONCOLOGY
lytic lesion in superior aspect of left acetabulum.
X-ray skull showed lytic lesion in right parietal bone.
Computed tomography (CT) revealed an irregular
osteolytic lesion in right parietal bone that invaded and
expanded through both inner and outer tables of the
skull in full thickness with normal brain parenchyma
(Fig. 1a). X-ray chest showed consolidation in left lower
zone (Fig. 1b). Ultrasound abdomen was normal. He
underwent gross total removal of the lesion to establish
the diagnosis. Histological examination of the tumor
revealed a metastatic adenocarcinoma.
initial treatment, modified follow-up or reconsideration
of surgical therapy for the primary tumor.9,11
Discussion
3. Wong GK, Boet R, Poon WS, Ng HK. Lytic skull metastasis
secondary to thyroid carcinoma in an adolescent. Hong
Kong Med J 2002;8(2):149-51.
Lung cancer is the most common cancer in the world
and accounts for 12.3% of all new cancer cases with
millions of deaths per year.5 According to reports by
the American Lung Association, the vast majority of
patients with lung cancer (85%) have metastatic disease
at the time of presentation.6 Patients with metastatic lung
cancer have a 5-year survival rate of 2.1%, compared
to those who have disease limited to the lungs at
48.5%.7 Hematogenous skull metastases can be caused
by nearly all types of tumors including breast, lung,
prostate, thyroid carcinoma, malignant melanoma).1,3,8
However, the most common sites for metastases from
lung cancer are the upper abdomen followed by lung
and pleura and lastly bone.2 Metastases from lung
cancer involve spine and hip but skull involvement
is uncommon.9 X-ray and CT is a keystone in the
diagnostic evaluation of suspected lung cancer, because
it provides the most detailed anatomical images.10
Multiplicity, irregular edges and absence of peripheral
sclerosis should arouse suspicion of malignancy and
a biopsy is warranted in these cases.3 Preoperative
contrast-enhanced Magnetic resonance imaging of the
brain and skeleton is recommended for the detection
of parenchymal and osseous lesions in patients with
large pulmonary lesions (>3 cm diameter or higher
than T1 stage).9,11 The correct staging of patients with
lung cancer is essential for appropriate care and cost
containment as patients with nonresectable metastatic
disease may need additional therapy at the time of
References
1. Stark AM, Eichmann T, Mehdorn HM. Skull metastases:
clinical features, differential diagnosis, and review of the
literature. Surg Neurol 2003;60(3):219-25; discussion 225-6.
2. Aquino SL, Fischman AJ. Does whole-body 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography
have an advantage over thoracic positron emission
tomography for staging patients with lung cancer? Chest
2004;126(3):755-60.
4. Kim SH, Kosnik E, Madden C, Morran S, Rusin J, Gordon
T, et al. Lytic skull metastasis from a follicular thyroid
carcinoma in a child. Pediatr Neurosurg 1998;28(2):84-8.
5. Tyczynski JE, Bray F, Parkin DM. Lung cancer in Europe
in 2000: epidemiology, prevention, and early detection.
Lancet Oncol 2003;4(1):45-55.
6. Pretreatment evaluation of non-small-cell lung cancer. The
American Thoracic Society and The European Respiratory
Society. Am J Respir Crit Care Med 1997;156(1):320-32.
7. Trends in lung cancer morbidity and mortality. American
Lung Association Epidemiology and Statistics Unit,
Research and Scientific Affairs, June 2003. Available at:
http://www. lungusa.org/atf/cf/. Accessed March 12, 2008.
8. Bontoux D, Plazanet F, Azais I. Distribution of bone
metastases of cancers. A scintigraphic study of 376 cases.
Bull Acad Natl Med 1998;182(5):997-1008; discussion
1008-9.
9. Earnest F 4th, Ryu JH, Miller GM, Luetmer PH, Forstrom
LA, Burnett OL, et al. Suspected non-small cell lung
cancer: incidence of occult brain and skeletal metastases
and effectiveness of imaging for detection - pilot study.
Radiology 1999;211(1):137-45.
10. Verschakelen JA, Bogaert J, De Wever W. Computed
tomography in staging for lung cancer. Eur Respir J Suppl
2002;35:40s-48s.
11. Akeson P, Larsson EM, Kristoffersen DT, Jonsson E,
Holtås S. Brain metastases--comparison of gadodiamide
injection-enhanced MR imaging at standard and high
dose, contrast-enhanced CT and non-contrast-enhanced
MR imaging. Acta Radiol 1995;36(3):300-6.
■■■■
For HIV-infected patients with cancer undergoing chemotherapy, the integrase strand-transfer inhibitor raltegravir
is the best choice for viral suppression, according to a new study presented at the 53rd Interscience Conference
on Antimicrobial Agents and Chemotherapy. The efficacy of raltegravir is similar to that of nonnucleoside reversetranscriptase inhibitors, but the rate of adverse events is lower.
Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013
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![ORTHOPEDICS
are the common orthopedic problems and large
number of these health problems can be prevented and
managed by simple measures like exercise, diet and
proper healthcare.
Acknowledgment
7. Popkess-Vawter S, Patzel B. Compounded problem:
chronic low back pain and overweight in adult females.
Orthop Nurs 1992;11(6):31-5, 43.
8. Felson DT. The epidemiology of knee osteoarthritis:
results from the Framingham Osteoarthritis Study. Semin
Arthritis Rheum 1990;20(3 Suppl 1):42-50.
We are thankful to the management of Pravara Medical Trust,
Dept. of Orthopedic, Pravara Rural Hospital, for allowing
the study and the interns Miss Bajpayee and Sharmin Bala
for their help.
9. Kellgren JH, Lawrence JS, Bier F. Genetic factors in
generalized osteoarthrosis. Ann Rheum Dis 1963;22:
237-55.
References
11. Mandal PK, Chakrabarty D, Manna N, Mallik S. Disability
among geriatric females: an uncared agenda in rural
India. Sudanese J Pub Health 2009;4(4):377-82.
1. Sengupta A. The emergence of the menopause in India.
Climacteric 2003;6(2):92-5.
2. World Health Organization. Women Aging and Health.
WHO: Geneva, 2000. Fact sheet No. 252.
3. Genazzani AR, Gambacciani M, Schneider HP,
Christiansen C. International Menopause Society Expert
Workshop. Postmenopausal osteoporosis: therapeutic
options. Climacteric 2005;8(2):99-109.
4. Isles CG, Hole DJ, Hawthorne VM, Lever AF. Relation
between coronary risk and coronary mortality in women
of the Renfrew and Paisley survey: comparison with men.
Lancet 1992;339(8795):702-6.
5. Gupta A. Osteoporosis in India - the nutritional
hypothesis. Natl Med J India 1996;9(6):268-74.
6. Osteoporosis in Postmenopausal Women: Diagnosis and
Monitoring. Summary, Evidence Report/Technology
Assessment: No.28. Agency for Healthcare Research and
Quality Publication No. 01-E031, Feb 2001. Available at:
http://www.ahrq.gov/clinic/epcsums/osteosum.htm
10. Kumar P. Social classification - need for constant updating.
IJCM 1993;18(2):60-1.
12. Scharla S, Oertel H, Helsberg, et al. Skeletal pain in
postmenopausal women with osteoporosis. J Bone Miner
Res 2005;20(Suppl 1):318-98.
13. Felson DT. The epidemiology of knee osteoarthritis:
results from the Framingham Osteoarthritis Study. Semin
Arthritis Rheum 1990;20(3 Suppl 1):42-50.
14. Slemenda CW. The epidemiology of osteoarthritis of the
knee. Curr Opin Rheumatol 1992;4(4):546-51.
15. Eti E, Kouakou HB, Daboiko JC, Ouali B, Ouattara B, Gabla
KA, et al. Epidemiology and features of knee osteoarthritis
in the Ivory Coast. Rev Rhum Engl Ed 1998;65(12):
766-70.
16. Lena A, Ashok K, Padma M, Kamath V, Kamath A. Health
and social problems of the elderly: a cross-sectional study
in Udupi Taluk, Karnataka. Indian J Community Med
2009;34(2):131-4.
Diet Combined with Exercise Relieves Arthritic Knee Pain
Osteoarthritis (OA) is a common trouble in old age. Symptoms of OA may include joint pain, tenderness, stiffness,
locking and sometimes an effusion. Generally, doctors advise the patients to reduce weight to help reduce knee
pain. A study was published recently that aimed to assess the clinical and functional outcome in knee pain in
arthritic patients by modifying diet alone (Group A), modifying diet and combining it with exercise (Group B),
and by exercise only (Group C). It was single-blind, randomized clinical trial, which was done for 18 months to
study the outcome of pain on 454 overweight and obese people aged >55 years with positive radiographic knee
OA findings. It was observed that slightly changing the lifestyle by doing some amount of exercise along with
diet control were more effective in reducing weight, inflammation and pain. Their quality-of-life improved as
they had less pain and more mobility. On the contrary, the group that performed only diet modifications or only
exercised did not experience such positive results. In diet modifications, two meals consisted of only nutritional
shakes while the third meal had very less fats but was rich in vegetables. Average weight loss was greater in the
diet and exercise group (−10.6 kg; 95% confidence interval [CI], −14.1 to −7.1 kg) and the diet group (−8.9 kg; 95%
CI, −12.4 to −5.3 kg) compared with the exercise group (−1.8 kg; 95% CI, −5.7 to 1.8 kg) at the 18-month follow-up.
On 6-month follow-up, all the three groups had similar amount of pain reduction, but on 18-month follow-up
it was noticed that the group with diet modifications combined with exercises provided more relief in pain and
better mobility. So, it was concluded that diet or exercise alone would be less effective than diet clubbed with
exercise in knee OA.
(Source: JAMA 2013;310:1263-73.)
Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013
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- 1. Indexed with IndMED ISSN0971-0876 www.ijcpgroup.com Volume 24, Number 6 November 2013, Pages 501-600 Peer Reviewed Journal yy American Family Physician yy Cardiology yy Dentistry yy Dermatology yy Endocrinology yy ENT yy Infectious Diseases yy Internal Medicine yy Neurology yy Obstetrics and Gynecology an siciains y PhPhysic ly yy Oncology yy Orthopedics i ly amy of Fami n F em yy Preventive and Social Medicine a ad erimcrican Ac m e g A f the A yy Urology yy Medilaw yy Medifinance n lo rateid Journa po w coreer-revie In P A Full text online: http://ebook.ijcpgroup.com/ijcp/ Single Copy Rs. 300/-
- 3. Online Submission IJCP Groupof Publications Dr Sanjiv Chopra Prof. of Medicine & Faculty Dean Harvard Medical School Group Consultant Editor Volume 24, Number 6, November 2013 from the desk of THE group editor-in-chief 505 50 Ps to Know All About Dengue Fever Dr Deepak Chopra Chief Editorial Advisor Padma Shri and Dr BC Roy National Awardee Dr KK Aggarwal Group Editor-in-Chief Dr Veena Aggarwal MD, Group Executive Editor IJCP Editorial Board Obstetrics and Gynaecology Dr Alka Kriplani Dr Thankam Verma, Dr Kamala Selvaraj Cardiology Dr Praveen Chandra, Dr SK Parashar Paediatrics Dr Swati Y Bhave Diabetology Dr CR Anand Moses, Dr Sidhartha Das Dr A Ramachandran, Dr Samith A Shetty ENT Dr Jasveer Singh Dr Chanchal Pal Dentistry Dr KMK Masthan Dr Rajesh Chandna Gastroenterology Dr Ajay Kumar Dr Rajiv Khosla Dermatology Dr Hasmukh J Shroff Dr Pasricha Dr Koushik Lahiri Nephrology Dr Georgi Abraham Neurology Dr V Nagarajan Dr Vineet Suri Journal of Applied Medicine & Surgery Dr SM Rajendran, Dr Jayakar Thomas Orthopedics Dr J Maheshwari American Family Physician 507 Diagnosis and Management of Genital Ulcers Non-Resident Indians Chamber of Commerce & Industry World Fellowship of Religions This journal is indexed in IndMED (http://indmed.nic.in) and full-text of articles are included in medIND databases (http://mednic.in) hosted by National Informatics Centre, New Delhi. Michelle A. Roett, Mejebi T. Mayor, Kelechi A. Uduhiri 516 Practice Guidelines 519 Photo Quiz CARDIOLOGY 521 Systolic and Diastolic Ratio and Rate Pressure Product in Anemia K Singh DENTISTRY 524 Probiotics: How Promising are they in Promoting Periodontal Health? R Hemalatha, A Sivachandran DERMATOLOGY 527 Herpes Zoster: Multiple Presentations in a Single Patient Sonia Jain 531 Lichen Sclerosus et Atrophicus in a Young Girl YS Marfatia, Sonia Jain ENDOCRINOLOGY 537 Effectiveness and Tolerability of Vildagliptin in Indian Patients with Type 2 Diabetes Mellitus: Results From Edge−A Real-World Observational Study Subhash K Wangnoo, Giovanni Bader, Apurva Gawai, Shradhanand Singh ENT 543 Impact of Tonsillectomy on Quality-of-life in Children: Our Experience Neelima Gupta, Lakshmi Vaid, PP Singh infectious diseases 547 A Rare Case of Angioimmunoblastic Lymphoma: A Report Anand Gopal Bhatnagar Editorial Anchor Advisory Bodies Heart Care Foundation of India KK Aggarwal Ramesh B, Mohammed Moinuddin Nawazi, Shyamala K INTERNAL MEDICINE 553 Cerebral Venous Thrombosis Due to Abrin Toxicity: A Case Report KV Rajalakshmi, G Shivkumar, S Karthikeyan, V Punitha, K Sangeetha NEUROLOGY 556 Encephalopathy: An Unusual Neurological Manifestation Following Snakebite Shubha Laxmi Margekar, Rakesh Gaharwar, Satyam Singh Jayant, Om Prakash Jatav, Ashish Singhal, Venu Gopal Margekar
- 4. Obstetrics and Gynecology Published,Printed and Edited by Dr KK Aggarwal, on behalf of IJCP Publications Ltd. and Published at E - 219, Greater Kailash, Part - 1 New Delhi - 110 048 E-mail: editorial@ijcp.com 559 Evaluation of Perinatal Outcome by Antenatal CTG and Umbilical Artery Doppler in Pre-eclamptic Mothers Barunoday Chakraborty, Tamal Kumar Mondal, Sannyasi Charan Barman, Biswa Pratim Rudra, Ramkrishna Sahana, Prabhat Chandra Mondal 566 A Rare Case of Prolapse Uterus Printed at New Edge Communications Pvt. Ltd., New Delhi E-mail: edgecommunication@gmail.com S Sampathkumari, Mohanambal, Rajamaheswari, Meena Umachander 568 Comparative Study of Obstetrics Outcome Between Scarred and Unscarred Uterus in Placenta Previa Cases © Copyright 2013 IJCP Publications Ltd. All rights reserved. The copyright for all the editorial material contained in this journal, in the form of layout, content including images and design, is held by IJCP Publications Ltd. No part of this publication may be published in any form whatsoever without the prior written permission of the publisher. Gayatri Mathuriya, Pallavi Lokhande ONCOLOGY 572 Lytic Skeletal Metastasis from Lung Cancer Amit Agrawal ORTHOPEDICS Editorial Policies 574 Study of Orthopedic Morbidities Among Postmenopausal Women in a Medical College Hospital in Rural Area of Western Maharashtra, India The purpose of IJCP Academy of CME is to serve the medical profession and provide print continuing medical education as a part of their social commitment. The information and opinions presented in IJCP group publications reflect the views of the authors, not those of the journal, unless so stated. Advertising is accepted only if judged to be in harmony with the purpose of the journal; however, IJCP group reserves the right to reject any advertising at its sole discretion. Neither acceptance nor rejection constitutes an endorsement by IJCP group of a particular policy, product or procedure. We believe that readers need to be aware of any affiliation or financial relationship (employment, consultancies, stock ownership, honoraria, etc.) between an author and any organization or entity that has a direct financial interest in the subject matter or materials the author is writing about. We inform the reader of any pertinent relationships disclosed. A disclosure statement, where appropriate, is published at the end of the relevant article. Shubhada Sunil Avachat, Shrikant Balkrishna Deshpande, Mrinal Balbhim Zambare, Deepak Baburao Phalke Preventive and social medicine 578 A Quantitative Assessment of RNTCP in Meerut District of Uttar Pradesh Sanjay Gupta UROLOGY 581 Nephrotic Syndrome: A Rare Presentation of AIDS Prabhat Agrawal, Ashish Gautam, Manish Kumar Bansal, Ayush Agrawal mediLAW 584 Judges have to Follow the Laws of the Country KK Aggarwal Medifinance Note: Indian Journal of Clinical Practice does not guarantee, directly or indirectly, the quality or efficacy of any product or service described in the advertisements or other material which is commercial in nature in this issue. 585 Bonds, Shares and Gold: Capital Loss Offset Strategy eMedi Quiz 589 Quiz Time emedinews inspiration 590 The Last Cab Ride IJCP’s Editorial & Business Offices Delhi Mumbai Kolkata Bangalore Chennai Hyderabad Dr Veena Aggarwal 9811036687 E - 219, Greater Kailash, Part - I, New Delhi - 110 048 Cont.: 011-40587513 editorial@ijcp.com drveenaijcp@gmail.com Subscription Dinesh: 9891272006 subscribe@ijcp.com Ritu: 09831363901 ritu@ijcp.com Mr. Nilesh Aggarwal 9818421222 Mr. Pravin Dhakne 8655611025, 24452066 Ritu Saigal Sr. BM 9831363901 H Chandrashekar GM Sales & Marketing 9845232974 Chitra Mohan Sr. BM 9841213823 40A, Ganapathypuram Main Road Radhanagar Chromepet Chennai - 600 044 Cont.: 22650144 chitra@ijcp.com Venugopal GM Sales & Marketing 9849083558 Unit No: 210, 2nd Floor, Shreepal Complex Suren Road, Near Cine Magic Cinema Andheri (East) 7E, Merlin Jabakusum 28A, SN Roy Road Kolkata - 700 038 Cont.: 24452066 ritu@ijcp.com Mumbai - 400 093 nilesh.ijcp@gmail.com Sr.: Senior; BM: Business Manager; GM: General Manager Arora Business Centre, 111/1 & 111/2, Dickenson Road (Near Manipal Centre) Bangalore - 560 042 Cont.: 25586337 chandra@ijcp.com H. No. 16-2-751/A/70 First Floor Karan Bagh Gaddiannaram Dil Sukh Nagar Hyderabad 500 059 Cont.: 65454254 venu@ijcp.com
- 5. from the deskof THE group editor-in-chief Dr KK Aggarwal Padma Shri and Dr BC Roy National Awardee Sr. Physician and Cardiologist, Moolchand Medcity, New Delhi President, Heart Care Foundation of India Group Editor-in-Chief, IJCP Group and eMedinewS National Vice President Elect, IMA Member, Ethics Committee, MCI Chairman, Ethics Committee, Delhi Medical Council Director, IMA AKN Sinha Institute (08-09) Hony. Finance Secretary, IMA (07-08) Chairman, IMA AMS (06-07) President, Delhi Medical Association (05-06) emedinews@gmail.com http://twitter.com/DrKKAggarwal Krishan Kumar Aggarwal (Facebook) 50 Ps to Know All About Dengue Fever 1. Pathogenesis is an endothermic dysfunction. 2. Plasma leakage is the cause of severe dengue. 3. Pregnancy is an indication for admission. 4. Paani (water) resuscitation is the treatment. 5. Pulse, if rises by 20, is a bad sign. 6. Pressure: If systolic blood pressure falls by 20, this is a red flag. 7. Pulse pressure <20, is a red flag. 8. Paracetamol is the drug of choice for fever. 9. Patti: If fever does not respond to paracetamol do tap water patti. 10. Pigment volume concentration (PCV), if rises by 20%, is a red flag. 11. Platelets count is not reliable and no transfusion if no active bleeding. 12. Piss: Make sure that the patient pisses (urinates) every three hours. 13. Papaya leaves have no scientific role. 14. Peeli haldi (yellow turmeric) can reduce plasma leakage. 15. Pancreatitis can occur in dengue. 16. Peelia (jaundice) can occur due to dengue but invariably is mild. Serum glutamic oxaloacetic (SGOT) will be higher than serum glutamic pyruvic transaminase (SGPT). 17. Pot, if filled with fresh stagnant water, can grow dengue. 18. Potty: Dengue can present with loose motions. 19. Pasina: Dengue fever may be high with sweating. 20. Pediatric age: Dengue is more serious in children. 21. Pain in the head: There can be severe pain in the head (retro-orbital area) in dengue. 22. Pantoprazole with domperidone may be required to stop vomiting. 23. Palang: Extreme weakness in dengue may require rest. 24. Paisa: Do not waste paisa (money) on unnecessary treatments. 25. Positive: Always think positive and do not be afraid of mortality. 26. Panic: Do not panic; dengue is not all that dangerous. 27. Pareshani: Do not trouble hospitals for unnecessary admissions. 28. People: Multiple people may get dengue in one family. Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 505
- 6. from the deskof THE group editor-in-chief 29. Protect people from dengue by taking precautions. 30. Precautions: Take anti-mosquito precautions. 31. Prognosis is bad in second dengue. 32. Post-febrile period is the dangerous period. 33. Prayers may have a role in terminal cases of dengue. 34. Pradesh: Keep your pradesh free of dengue mosquitoes. 35. Patience: Be patient in dengue. 36. Picture: A picture of how a dengue patient looks should be in every house. 37. Population: Dengue affects 10% of the population in any epidemic. 38. Pagalpan: Dengue can cause encephalitis. 39. Pleural effusion: Dengue can cause pleural effusion. 40. Pericardial effusion: Dengue can cause pericardial effusion. 41. Patila: Do not keep empty patila (vessels) on the roof of your house. 42. Purify atmosphere with yagna smoke to kill mosquitoes. 43. Prem: Dengue is not a sexually transmitted illness. 44. Past-dengue illness history should be taken. 45. Plot: Workers working in construction sites are at risk. 46. Pehnava: Wearing full-sleeved clothes can prevent dengue. 47. Pajama: Wear full pajama in the day-time. 48. Passengers can carry mosquito to far-off places via car or train. 49. Posture is normal in dengue unlike in chikungunya, where the person comes with flexed posture. 50. Prepare: The government should be prepared in advance to prevent dengue fever. ■■■■ 506 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013
- 7. American Family Physician Diagnosisand Management of Genital Ulcers MICHELLE A. ROETT, MEJEBI T. MAYOR, KELECHI A. UDUHIRI Abstract Herpes simplex virus infection and syphilis are the most common causes of genital ulcers in the United States. Other infectious causes include chancroid, lymphogranuloma venereum, granuloma inguinale (donovanosis), secondary bacterial infections, and fungi. Noninfectious etiologies, including sexual trauma, psoriasis, Behçet syndrome, and fixed drug eruptions, can also lead to genital ulcers. Although initial treatment of genital ulcers is generally based on clinical presentation, the following tests should be considered in all patients: serologic tests for syphilis and darkfield microscopy or direct fluorescent antibody testing for Treponema pallidum, culture or polymerase chain reaction test for herpes simplex virus, and culture for Haemophilus ducreyi in settings with a high prevalence of chancroid. No pathogen is identified in up to 25 percent of patients with genital ulcers. The first episode of herpes simplex virus infection is usually treated with seven to 10 days of oral acyclovir (five days for recurrent episodes). Famciclovir and valacyclovir are alternative therapies. One dose of intramuscular penicillin G benzathine is recommended to treat genital ulcers caused by primary syphilis. Treatment options for chancroid include a single dose of intramuscular ceftriaxone or oral azithromycin, ciprofloxacin, or erythromycin. Lymphogranuloma venereum and donovanosis are treated with 21 days of oral doxycycline. Treatment of noninfectious causes of genital ulcers varies by etiology, and ranges from topical wound care for ulcers caused by sexual trauma to consideration of subcutaneous pegylated interferon alfa-2a for ulcers caused by Behçet syndrome. Keywords: Herpes simplex, syphilis, genital ulcers, sexual trauma, oral acyclovir, penicillin G benzathine, doxycycline G enital ulcers may be caused by infectious or noninfectious etiologies (Table 1).1-3 Sexually transmitted infections (STIs) characterized by genital ulcers include genital herpes simplex virus (HSV) infection, syphilis (Treponema pallidum), chancroid (Haemophilus ducreyi), granuloma inguinale (donovanosis; Calymmatobacterium granulomatis), and lymphogranuloma venereum (Chlamydia trachomatis serotypes L1, L2, and L3). Secondary bacterial infections or fungi can also cause genital ulcers. Noninfectious etiologies include psoriasis, sexual trauma, Behçet syndrome, Wegener granulomatosis, and fixed drug eruptions.1,4 In the United States, most young, sexually active patients who present with genital ulcers have HSV infection or syphilis.1,4 Lymphogranuloma MICHELLE A. ROETT, MD, MPH, FAAFP, is an associate professor in the Department of Family Medicine at Georgetown University Medical Center, Washington, DC. She is also associate program director at the Georgetown University/Providence Hospital Family Medicine Residency Program and medical director at Fort Lincoln Family Medicine Center, Colmar Manor, Md. MEJEBI T. MAYOR, MD, JD, FACOG, is chair of the Department of Obstetrics and Gynecology at Providence Hospital. She is also an assistant professor in the Department of Obstetrics and Gynecology at Howard University,Washington, DC. KELECHI A. UDUHIRI, MD, MPH, MS, is medical director of Health Care for the Homeless, Baltimore, Md., and is a faculty member with the Franklin Square Hospital Family Medicine Residency Program in Baltimore. Source: Adapted from Am Fam Physician. 2012;85(3):254-262. venereum, donovanosis, secondary bacterial infections, fungi, and noninfectious etiologies are rare. Epidemiology The global incidence of genital ulcer disease is estimated to be more than 20 million cases annually.4 HSV types 1 and 2 are the most common causes of genital ulcers in the United States, followed by syphilis and chancroid.5 One in five women and one in nine men 14 to 49 years of age has genital HSV type 2 infection.6 In 2009, the rate of syphilis was highest in men and women 20 to 24 years of age (20.7 and 5.6 cases per Table 1. Differential Diagnosis of Genital Ulcers Infectious (most common)* Noninfectious (less common) Genital herpes simplex virus Behçet syndrome Syphilis Fixed drug eruption Chancroid Psoriasis Lymphogranuloma venereum Sexual trauma Granuloma inguinale (donovanosis) Wegener granulomatosis Fungal infection (e.g., Candida) Secondary bacterial infection *Listed in order of frequency. Information from references 1 through 3. Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 507
- 8. American Family Physician Table2. Risk Factors for Genital Ulcers History of inflammatory disease (e.g., psoriasis) and exposure to trauma or medications such as nonsteroidal anti-inflammatory drugs, antimalarials, angiotensin-converting enzyme inhibitors, beta blockers, lithium, salicylates, or corticosteroids Lack of male circumcision Multiple sex partners, lifetime or current Nonrecognition of ulcers in prodrome stage Serodiscordant sex partners (i.e., one partner with herpes simplex virus and one without) Unprotected sexual contact Unprotected skin-to-skin contact with ulcers Information from references 1 through 3, 5, and 6. 100,000 persons, respectively). However, syphilis rates increased in persons 15 to 19 years of age between 2002 and 2009 (1.3 versus 6.0 cases per 100,000 males and 1.5 versus 3.3 cases per 100,000 females).7,8 In 2006, most cases of primary and secondary syphilis occurred in men who have sex with men.7,8 Chancroid usually occurs in discrete outbreaks, but the disease may be endemic in some regions. The incidence of chancroid has been declining in the United States, with only 28 cases reported to state health departments in 2009.9 However, H. ducreyi infection is challenging to confirm, likely leading to underreporting.9 Approximately 10 percent of patients with chancroid are coinfected with syphilis or HSV; these are even more common coinfections for patients who acquired chancroid outside the United States.5 Lymphogranuloma venereum primarily occurs in men who have sex with men.10 Behçet syndrome is most common in young adults in the Eastern Mediterranean and in men in the Far East, whereas women are predominantly affected in the United States.2 Diagnostic Evaluation The diagnosis of genital ulcer disease is based on the presence of one or more mucocutaneous ulcers involving the genitalia, perineum, or anus.5 Diagnosing the specific cause of genital ulcers is based on history, physical examination, and laboratory findings. History and Physical Examination Risk factors for infectious causes of genital ulcers are similar to those for STIs, whereas risk factors for noninfectious causes vary (Table 21-3,5,6). For instance, patients with psoriasis are at greater risk of genital ulcers after exposure to trauma or medications such as 508 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 nonsteroidal anti-inflammatory drugs, antimalarials, angiotensin-converting enzyme inhibitors, beta blockers, lithium, salicylates, or corticosteroids.1 Behçet syndrome is associated with the human leukocyte antigen-B51/B5 allele (57.2 percent of patients with the allele have the condition).11 History and physical examination findings associated with genital ulcers are summarized in Table 3.1,3,5,12-16 Genital HSV infection usually begins as multiple vesicular lesions, sometimes painless, that are located inside the foreskin, labia, vagina, or rectum. Vesicles may rupture spontaneously, becoming painful, shallow ulcers (Figure 1).17 Prodromal symptoms may occur in 20 percent of HSV cases before ulceration. The prodrome may include a mild tingling sensation up to 48 hours before ulceration, or shooting pain in the buttocks, legs, or hips up to five days before.12 Asymptomatic viral shedding may occur in more than 60 percent of patients with HSV infection.18 First-time infections may also feature constitutional symptoms and regional lymphadenopathy.3 Primary syphilis usually begins with a single, painless, well-demarcated ulcer (chancre) with a clean base and indurated border19 (Figure 2). When the patient seeks treatment for signs or symptoms, the solitary chancre of primary infection may still be visible, or it may have progressed to secondary infection (e.g., rash, lymphadenopathy) or tertiary infection (e.g., gummatous lesions). Chancroid ulcers are usually nonindurated and painful with a serpiginous border and friable base (Figure 3). The ulcers occur on the prepuce and frenulum of the penis in men or on the vulva or cervix in women. Perineal lesions are common in women or in men who have sex with men. Painful, unilateral, inguinal adenitis occurs in one-half of patients with chancroid and may develop into buboes.19,20 Fluctuant buboes may rupture spontaneously if not aspirated or incised and drained. Complications of chancroid include phimosis in men and further ulceration caused by secondary bacterial infection.20 Extragenital lesions on the inner thighs and fingers have been reported but are relatively rare.20 Lymphogranuloma venereum infection is characterized by a small, shallow, painless genital or rectal papule that may ulcerate at the site of infection after an incubation period of three to 30 days. These ulcers may be selflimited and remain primarily undetected within the urethra, vagina, or rectum. However, if left untreated, the condition may be complicated by secondary
- 9. American Family Physician Table3. Summary of the Diagnosis and Treatment of Genital Ulcers Etiology Clinical presentation Diagnosis Treatment options Usually multiple vesicular lesions that rupture and become painful, shallow ulcers (Figure 1) Definitive: herpes simplex virus identified on culture or polymerase chain reaction testing of ulcer scraping or vesicle fluid aspirate First episode Constitutional symptoms, lymphadenopathy in firsttime infections Presumptive: typical lesions and any of the following factors Infectious* Herpes simplex virus infection Previously known outbreak Positive Tzanck smear of ulcer scraping Exclusion of other causes of ulcers Fourfold increase in acute and convalescent antibody titer results (in a first-time infection) Acyclovir, 400 mg orally three times daily for seven to 10 days, or 200 mg orally five times daily for seven to 10 days Famciclovir, 250 mg orally three times daily for seven to 10 days Valacyclovir, 1,000 mg orally twice daily for seven to 10 days Recurrent episode Acyclovir, 400 mg orally three times daily for five days, 800 mg orally twice daily for five days, 800 mg orally three times daily for two days, or 200 mg orally five times daily for five days Famciclovir, 1,000 mg twice daily for one day, 500 mg orally once then 250 mg twice daily for two days, or 125 mg orally twice daily for five days Valacyclovir, 500 mg orally twice daily for three days or 1,000 mg orally once daily for five days Suppressive therapy Acyclovir, 400 mg orally twice daily or 200 mg orally three to five times daily Famciclovir, 250 mg orally twice daily Valacyclovir, 1,000 mg orally once daily Valacyclovir, 500 mg orally once daily, if fewer than 10 outbreaks per year Syphilis (primary) Single, painless, welldemarcated ulcer (chancre) with a clean base and indurated border (Figure 2) Treponema pallidum identified on darkfield Penicillin G benzathine, 2.4 million microscopy or direct fluorescent antibody units intramuscularly in a single dose testing of a chancre or lymph node aspirate or Mild or minimally tender Positive result on serologic nontreponemal inguinal lymphadenopathy testing (i.e., Venereal Disease Research Laboratories or rapid plasma reagin) that is confirmed with a positive result on serologic treponemal testing (i.e., fluorescent treponemal antibody absorption or T. pallidum passive agglutination) Chancroid Nonindurated, painful with serpiginous border and friable base; covered with a necrotic, often purulent exudate (Figure 3) Tender, suppurative, unilateral inguinal lymphadenopathy or adenitis Gram stain suggestive of Haemophilus Needle aspiration of fluctuant buboes ducreyi (gram-negative, slender rod or Azithromycin, 1 g orally in a single dose coccobacillus in a “school of fish” pattern) Ceftriaxone, 250 mg intramuscularly in Definitive: H. ducreyi identified on culture a single dose Presumptive: painful genital ulcer or ulcers Ciprofloxacin, 500 mg orally twice daily with regional lymphadenopathy and no for three days† evidence of T. pallidum infection at least seven days after ulcer onset, and testing Erythromycin, 500 mg orally four times daily for seven days negative for herpes simplex virus continued... Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 509
- 10. American Family Physician Table3. Summary of the Diagnosis and Treatment of Genital Ulcers (continued) Etiology Clinical presentation Diagnosis Lymphogranuloma Small, shallow, painless, Definitive: venereum genital or rectal papule or Chlamydia trachomatis serotype L1, L2, or L3 ulcer; no induration culture, identified from clinical specimen Unilateral, tender or inguinal or femoral Immunofluorescence demonstrating inclusion lymphadenopathy bodies in leukocytes of an inguinal lymph node Rectal bleeding, pain, (bubo) aspirate or discharge; ulcerative or proctitis; constipation or Microimmunofluorescence positive for tenesmus lymphogranuloma venereum strain of C. trachomatis Treatment options Doxycycline, 100 mg orally twice daily for 21 days Erythromycin base, 500 mg orally four times daily for 21 days Pregnant or lactating women: erythromycin, 500 mg orally four times daily for 21 days Presumptive: Clinical suspicion Community prevalence Exclusion of other causes of proctocolitis, inguinal lymphadenopathy, or genital ulcers Granuloma inguinale (donovanosis) Persistent, painless, beefy-red (highly vascular) papules or ulcers (Figure 4) May be hypertrophic, necrotic, or sclerotic No lymphadenopathy Definitive: Treatment should continue until Intracytoplasmic Donovan bodies on Wright lesions have healed Doxycycline, 100 mg orally twice daily stain for at least 21 days or Positive result with Giemsa stain or biopsy of Azithromycin, 1 g orally once weekly for at least 21 days granulation tissue Ciprofloxacin, 750 mg orally twice daily for at least 21 days May have subcutaneous granulomas Erythromycin base, 500 mg orally four times daily for 21 days Trimethoprim/sulfamethoxazole double strength, 160/800 mg orally twice daily for at least 21 days Noninfectious Behçet syndrome Aphthous oral ulcers (100 percent of cases); genital ulcers (70 to 90 percent of cases) Consider rheumatoid factor, antinuclear antibody Spontaneous regression is possible testing Pegylated interferon alfa-2a, 6 May have positive antibodies to carboxy-terminal million units subcutaneously three times weekly for three months for subunit of SIP1 Biopsy may show diffuse arteritis with venulitis mucocutaneous involvement Diagnostic criteria: recurrent aphthous oral ulcers (more than three per year) and any two of the following Recurrent genital ulcers Eye lesions (e.g., uveitis) Cutaneous lesions (e.g., erythema nodosum) Positive pathergy test (2 mm erythema appears 24 to 48 hours after skin prick test) Biopsy may show diffuse arteritis with venulitis continued... 510 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013
- 11. American Family Physician Table3. Summary of the Diagnosis and Treatment of Genital Ulcers (continued) Etiology Clinical presentation Diagnosis Treatment options Fixed drug eruptions Varied ulcerations that Diagnosis of exclusion when ulcers resolve Self-limited resolve with withdrawal of after drug withdrawals Topical analgesics or anti-inflammatory offending agent agents, as needed Consider treating exacerbation of underlying inflammatory disease if applicable *Listed in order of frequency. †Contraindicated in pregnant or lactating women and in patients younger than 18 years. Information from references 1, 3, 5, and 12 through 16. bacterial infections or lymphatic obstruction, which may progress to genital elephantiasis.10 In persons who have receptive anal intercourse, lymphogranuloma venereum may result in tenesmus; constipation; rectal bleeding; pain or discharge; proctitis; anogenital ulcerations; and unilateral, tender inguinal or femoral lymphadenopathy.13,20,21 Granuloma inguinale, or donovanosis, is characterized by persistent, painless, beefy-red papules or ulcers, which may be hypertrophic, necrotic, or sclerotic with an incubation period of eight to 12 weeks (Figure 4).22 Patients with Behcet syndrome usually have intermittent arthritis, recurrent oral and genital ulcers, and possibly a family history of inflammatory disorders.23 Up to 60 percent of genital ulcers associated with Behçet syndrome lead to significant scarring.24 Laboratory Evaluation Laboratory evaluation of an initial genital ulcer outbreak should include culture or polymerase chain reaction testing for HSV infection, HSV type-specific serology, serologic testing for syphilis, and culture for H. ducreyi in settings with a high prevalence of chancroid. For the diagnosis of HSV infection, polymerase chain reaction testing is 96 to 100 percent sensitive and 97 to 98 percent specific (positive likelihood ratio = 49, negative likelihood ratio = 0.02), much more sensitive than culture.25,26 Among adults who report that they have never had genital herpes, the seroprevalence of HSV type 2 antibodies is 21.6 percent, suggesting the disease is underdiagnosed.27 Darkfield microscopy and direct fluorescent antibody tests of exudate or tissue material are the definitive methods for diagnosing primary syphilis.3,4,28 However, in patients presenting with genital ulcers, a presumptive diagnosis of syphilis can be made with a serologic nontreponemal test (i.e., Venereal Disease Research Laboratories or rapid plasma reagin). But, because of possible false-positive results, positive nontreponemal test results should be confirmed with serologic treponemal testing (i.e., fluorescent treponemal antibody absorption or T. pallidum passive agglutination).3,4,28 Nontreponemal titers typically decline and may become nonreactive after treatment, but most positive treponemal test results tend to remain persistently active. If primary syphilis is treated, up to 25 percent of patients may have nonreactive treponemal results in two to three years; however, treponemal titers are not recommended to evaluate response to treatment.3 Although a definitive diagnosis of chancroid requires identification of H. ducreyi, testing with special culture media is less than 80 percent sensitive and polymerase chain reaction testing for H. ducreyi is not available in the United States.4 A presumptive diagnosis is possible with a painful genital ulcer, regional lymphadenopathy, no evidence of T. pallidum infection, and negative HSV test results.3 To diagnose lymphogranuloma venereum, genital swabs or bubo aspirate may be tested for C. trachomatis serotypes L1, L2, and L3 by culture, direct immunofluorescence, or nucleic acid amplification.3 Nucleic acid amplification tests for lymphogranuloma venereum are not approved by the U.S. Food and Drug Administration for rectal specimens. Health care professionals may collect and send rectal specimens to state health departments for referral to the Centers for Disease Control and Prevention for testing and validating diagnostic methods for lymphogranuloma venereum.3 Even with appropriate laboratory testing, no pathogen is identified in up to 25 percent of patients with genital ulcers.4 Biopsy is rarely needed to diagnose the cause of genital ulcers, but it may be considered if an ulcer persists after treatment.3 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 511
- 12. American Family Physician Treatment The2010 Centers for Disease Control and Prevention guidelines for managing STIs provide treatment options for patients with genital ulcer disease.3 Treatment of HSV infection should be initiated before test results are available because early treatment decreases transmission and duration of ulcers. Patients should be instructed to abstain from sexual activity during the prodrome stage, while lesions are present, and for the duration of treatment. Treatments for common causes of genital ulcers are outlined in Table 3.1,3,5,12-16 The first episode of genital HSV infection may be treated with acyclovir, 400 mg orally three times daily for seven to 10 days (five days for recurrent episodes). Alternative therapies include famciclovir or valacyclovir.3,29 Topical antivirals are of limited benefit in the treatment of HSV infection and are not recommended.3 Primary syphilis may be treated with intramuscular penicillin G benzathine, 2.4 million units in a single dose. The Centers for Disease Control and Prevention guidelines recommend that patients allergic to penicillin undergo desensitization.3 Treatment options for chancroid include intramuscular ceftriaxone, 250 mg in a single dose, or oral azithromycin, ciprofloxacin, or erythromycin. Treatment is less effective for uncircumcised males and patients coinfected with human immunodeficiency virus (HIV). Sex partners should be treated for chancroid, regardless of symptoms, if they have had sexual contact with the patient within the previous 10 days.3 Patients with lymphogranuloma venereum or donovanosis are treated with oral doxycycline, 100 mg twice daily for 21 days, and followed clinically. Donovanosis may require continued antibiotics until resolution of symptoms. Erythromycin is an alternative therapy for lymphogranuloma venereum.3 Treatment of mucocutaneous ulcers in Behçet syndrome is based on associated symptoms because ulcerations may regress spontaneously. In a randomized trial, subcutaneous pegylated interferon alfa-2a, 6 million units three times weekly for three months, improved duration and pain of oral ulcers and frequency of genital ulcers.14 A Cochrane review of randomized controlled trials found insufficient evidence for the use of oral acyclovir, oral colchicine, or topical interferon to treat ulcers caused by Behçet syndrome.30 In patients with Behçet syndrome, topical or vaginal sucralfate (not available in the United States) decreases the pain of oral ulcers, but does not significantly decrease the average frequency, healing time, or pain of genital ulcers.31 512 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 Treatment of extensive genital ulcers, regardless of etiology, has traditionally included wound cleansing and dressing. Although clinical trials are lacking, local treatment may include topical or oral analgesics, perineal baths, topical or oral anti-inflammatory agents, or cool compresses with Burow solution.15 Topical antimicrobials, such as benzoyl peroxide, dimethyl sulfoxide, gentamicin, oxyquinoline (not available in the United States), and silver sulfadiazine, may be beneficial for extragenital ulcers, but evidence of effectiveness is limited.16 Promptly treating genital ulcers is particularly important for patients with HIV to reduce HIV shedding and transmission. Genital ulcers increase HIV viral load in semen, increasing the likelihood of transmission to sex partners. Conversely, a patient with genital ulcers is more likely to acquire HIV infection with unprotected sexual contact.28,32,33 Prevention and Screening The U.S. Preventive Services Task Force recommends screening for syphilis in persons at increased risk,34 and recommends against routinely screening for HSV in asymptomatic patients.35 There are no current screening recommendations for chancroid, lymphogranuloma venereum, or donovanosis. Patients with genital ulcers should be counseled on reducing risk factors for STIs, including limiting the number of sex partners, using a condom with each sexual encounter, and regularly being screened for STIs if recommended by evidence-based guidelines. HIV testing should be performed in all patients with previously negative HIV test results who have genital ulcers caused by T. pallidum or H. ducreyi infection, and should be strongly considered for those who have genital ulcers caused by HSV infection.3 Avoiding sexual intercourse during outbreaks does not prevent HSV transmission.36 Although condom use can effectively prevent transmission, the infection can be spread through skin-to-skin contact in genital areas unprotected by a condom.37,38 The American College of Obstetricians and Gynecologists recommends that women who have partners with HSV infection be offered type-specific serologic testing to assess their risk, and these couples should be advised on condom and dental dam use, including a warning about incomplete protection.39 Chemoprophylaxis is available for severe or recurrent outbreaks of genital HSV infection in the form of daily suppressive medication. Suppressive therapy
- 13. American Family Physician Figure3. Chancroid ulcers are usually nonindurated with serpiginous borders and friable base, often covered with purulent exudate. Figure 1. Genital herpes simplex virus. Painful, shallow ulcers may manifest from ruptured vesicular lesions. Figure 4. Genital ulcer with hypertrophic borders, caused by donovanosis. Figure 2. Primary syphilis begins as a single, well-demarcated ulcer (chancre) with a clean base and indurated border. reduces the frequency and severity of outbreaks, reduces asymptomatic viral shedding by 90 percent, and reduces the risk of transmission to a seronegative partner.40 Options for suppressive therapy include acyclovir, 400 mg twice daily; famciclovir, 250 mg twice daily; or valacyclovir, 1,000 mg daily.29,41,42 If a patient has fewer than 10 outbreaks per year, 500 mg of oral valacyclovir daily is an appropriate option.3 Famciclovir is equally effective for suppression but less effective for the prevention of viral shedding and transmission to sex partners.43 The American College of Obstetricians and Gynecologists recommends that pregnant patients with HSV infection begin suppressive therapy at 34 to 36 weeks’ gestation to reduce the likelihood of lesions Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 513
- 14. American Family Physician duringlabor.44 Suppressive therapy reduces the risk of recurrence by 75 percent and the rate of cesarean delivery because of HSV lesions by 40 percent.45 REFERENCES 1. Augenbraun MH. Diseases of the reproductive organs and sexually transmitted diseases: genital skin and mucous membrane lesions. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, Pa.: Churchill Livingstone; 2009:1475-1484. 2. Louden BA, Jorizzo JL. Behcet’s disease. In: Firestein GS, Budd RC, Harris ED, McInnes IB, Ruddy S, Sergent JS, eds. Kelley’s Textbook of Rheumatology. 8th ed. Philadelphia, Pa.: Elsevier, Inc.; 2009:1475-1480. 3. Workowski KA, Berman S; Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2010 [published correction appears in MMWR Recomm Rep. 2011;60(1):18]. MMWR Recomm Rep. 2010;59(RR-12):1-110. 4. Low N, Broutet N, Adu-Sarkodie Y, Barton P, Hossain M, Hawkes S. Global control of sexually transmitted infections. Lancet. 2006;368(9551):2001-2016. 5. Cohen DE, Mayer K. Genital ulcer disease. In: Klausner JD, Hook EW III, eds. Current Diagnosis & Treatment of Sexually Transmitted Diseases. New York, NY: McGrawHill Medical; 2007:19-26. 6. Centers for Disease Control and Prevention. CDC fact sheet. Genital herpes. http://www.cdc.gov/std/herpes/ herpes-fact-sheet-lowres-2010.pdf. Accessed September 27, 2010. 7. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Sexually transmitted disease surveillance 2009. http://www.cdc.gov/std/ stats09/surv2009-Complete.pdf. Accessed May 8, 2011. 8. Centers for Disease Control and Prevention. CDC fact sheet. Syphilis. http://www.cdc.gov/std/syphilis/syphilisfact-sheet-press.pdf. Accessed September 27, 2010. 9. Centers for Disease Control and Prevention. Chancroid: tracking the hidden epidemics. Trends in STDs in the United States. 2000. http://www.cdc.gov/std/Trends2000/ chancroid.htm. Accessed September 14, 2011. 10. Centers for Disease Control and Prevention. CDC fact sheet. LGV. http://www.cdc.gov/std/lgv/LGV-Fact-Sheet. pdf. Accessed September 27, 2011. 11. de Menthon M, Lavalley MP, Maldini C, Guillevin L, Mahr A. HLA-B51/B5 and the risk of Behçet’s disease: a systematic review and meta-analysis of casecontrol genetic association studies. Arthritis Rheum. 2009;61(10):1287-1296. 12. Schiffer JT, Corey L. Herpes simplex virus. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, Pa.: Churchill Livingstone; 2009:1943-1962. 514 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 13. Burstein GR. Sexually transmitted infections. In: Kliegman R, Nelson WE, eds. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, Pa.: Saunders; 2011:705-714. 14. Alpsoy E, Durusoy C, Yilmaz E, et al. Interferon alfa-2a in the treatment of Behçet disease: a randomized placebocontrolled and double-blind study. Arch Dermatol. 2002;138(4):467-471. 15. Warts, herpes simplex and other viral infections. In: Clinical Dermatology: A Color Guide to Diagnosis and Therapy. Habif TP, ed. 5th ed. Edinburgh, Scotland: Mosby; 2010:454-490. 16. O’Meara SM, Cullum NA, Majid M, Sheldon TA. Systematic review of antimicrobial agents used for chronic wounds. Br J Surg. 2001;88(1):4-21. 17. Sharma R, Dronen SC. Herpes simplex in emergency medicine. Medscape Reference. http://emedicine.medscape. com/article/783113-overview. Accessed September 13, 2011. 18. Wald A, Zeh J, Selke S, et al. Reactivation of genital herpes simplex virus type 2 infection in asymptomatic seropositive persons. N Engl J Med. 2000;342(12):844-850. 19. Kimberlin DW, Rouse DJ. Clinical practice. Genital herpes. N Engl J Med. 2004;350(19):1970-1977. 20. Lewis DA. Chancroid: clinical manifestations, diagnosis, and management. Sex Transm Infect. 2003;79(1):68-71. 21. Sethi G, Allason-Jones E, Richens J, et al. Lymphogranuloma venereum presenting as genital ulceration and inguinal syndrome in men who have sex with men in London, UK [published correction appears in Sex Transm Infect. 2009;85(5):406]. Sex Transm Infect. 2009;85(3):165-170. 22. Velho PE, Souza EM, Belda Junior W. Donovanosis. Braz J Infect Dis. 2008;12(6):521-525. 23. Klippel JH, Weyand CM. Wortmann R, eds. Primer on the Rheumatic Diseases. 11th ed. Atlanta, Ga.: Arthritis Foundation; 1997:89. 24. Mat MC, Goksugur N, Engin B, Yurdakul S, Yazici H. The frequency of scarring after genital ulcers in Behçet’s syndrome: a prospective study. Int J Dermatol. 2006;45(5):554-556. 25. Ashley RL. Sorting out the new HSV type specific antibody tests. Sex Transm Infect. 2001;77(4):232-237. 26. Wald A, Huang ML, Carrell D, Selke S, Corey L. Polymerase chain reaction for detection of herpes simplex virus (HSV) DNA on mucosal surfaces: comparison with HSV isolation in cell culture. J Infect Dis. 2003;188(9): 1345-1351. 27. Fleming DT, McQuillan GM, Johnson RE, et al. Herpes simplex virus type 2 in the United States, 1976 to 1994. N Engl J Med. 1997;337:1105-1111. 28. Bruisten SM, Cairo I, Fennema H, et al. Diagnosing genital ulcer disease in a clinic for sexually transmitted diseases in Amsterdam, The Netherlands. J Clin Microbiol. 2001;39(2):601-605. 29. Fife KH, Barbarash RA, Rudolph T, Degregorio B, Roth R. Valaciclovir versus acyclovir in the treatment of first-
- 15. American Family Physician episodegenital herpes infection. Results of an international, multicenter, double-blind, randomized clinical trial. The Valaciclovir International Herpes Simplex Virus Study Group. Sex Transm Dis. 1997;24(8):481-486. 30. Saenz A, Ausejo M, Shea B, Wells G, Welch V, Tugwell P. Pharmacotherapy for Behcet’s syndrome. Cochrane Database Syst Rev. 2000;(2):CD001084. 31. Alpsoy E, Er H, Durusoy C, Yilmaz E. The use of sucralfate suspension in the treatment of oral and genital ulceration of Behçet disease: a randomized, placebo-controlled, double-blind study. Arch Dermatol. 1999;135(5):529-532. 32. Powers KA, Poole C, Pettifor AE, Cohen MS. Rethinking the heterosexual infectivity of HIV-1: a systematic review and meta-analysis. Lancet Infect Dis. 2008;8(9):553-563. 33. Krieger JN. Prostatitis, epididymitis, and orchitis: semen as a vector for human immunodeficiency virus. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, Pa.: Churchill Livingstone; 2009:1521-1527. 34. U.S. Preventive Services Task Force. Screening for syphilis infection. July 2004. http://www. uspreventiveservicestaskforce.org/uspstf/uspssyph.htm. Accessed September 13, 2011. 35. U.S. Preventive Services Task Force. Screening for genital herpes. March 2005. http://www. uspreventiveservicestaskforce.org/uspstf05/herpes/ herpesrs.htm. Accessed September 13, 2011. 36. Kim HN, Wald A, Harris J, Almekinder J, Heitman C, Corey L. Does frequency of genital herpes recurrences predict risk of transmission? Further analysis of the valacyclovir transmission study. Sex Transm Dis. 2008;35(2):124-128. 37. Martin ET, Krantz E, Gottlieb SL, et al. A pooled analysis of the effect of condoms in preventing HSV-2 acquisition [published correction appears in Arch Intern Med. 2010;170(11):929]. Arch Intern Med. 2009;169(13):12331240. 38. Wald A, Langenberg AG, Link K, et al. Effect of condoms on reducing the transmission of herpes simplex virus type 2 from men to women. JAMA. 2001;285(24):3100-3106. 39. American College of Obstetricians and Gynecologists. Gynecologic herpes simplex virus infections. ACOG Practice Bulletin no. 57. Washington, DC: American College of Obstetricians and Gynecologists; 2004. 40. Corey L, Wald A, Patel R, et al.; Valacyclovir HSV Transmission Study Group. Once-daily valacyclovir to reduce the risk of transmission of genital herpes. N Engl J Med. 2004;350(1):11-20. 41. Diaz-Mitoma F, Sibbald RG, Shafran SD, Boon R, Saltzman RL. Oral famciclovir for the suppression of recurrent genital herpes: a randomized controlled trial. Collaborative Famciclovir Genital Herpes Research Group. JAMA. 1998;280(10):887-892. 42. Bodsworth NJ, Crooks RJ, Borelli S, et al. Valaciclovir versus aciclovir in patient initiated treatment of recurrent genital herpes: a randomised, double blind clinical trial. International Valaciclovir HSV Study Group. Genitourin Med. 1997;73(2):110-116. 43. Wald A, Selke S, Warren T, et al. Comparative efficacy of famciclovir and valacyclovir for suppression of recurrent genital herpes and viral shedding. Sex Transm Dis. 2006;33:529-533. 44. Randolph AG, Hartshorn RM, Washington AE. Acyclovir prophylaxis in late pregnancy to prevent neonatal herpes: a cost-effectiveness analysis. Obstet Gynecol. 1996;88(4 pt 1):603-610. 45. Sheffield JS, Hollier LM, Hill JB, Stuart GS, Wendel GD. Acyclovir prophylaxis to prevent herpes simplex virus recurrence at delivery: a systematic review. Obstet Gynecol. 2003;102(6):1396-1403. ■■■■ Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 515
- 16. American Family Physician PracticeGuidelines ACIP Releases Influenza Vaccination Updates for 2013-2014 The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) has updated its annual guidelines for routine influenza vaccination in 2013-2014. Vaccination is recommended for all persons six months or older who do not have contraindications. No specific vaccine product is preferable to another if more than one product is appropriate for an individual patient. This year’s updates include changes to the U.S. trivalent influenza vaccine and the quadrivalent influenza vaccine, the availability of new recently licensed vaccine alternatives for specific populations, and a new vaccine option for adults with egg allergy. Table 1 lists the influenza vaccines available for 2013-2014; contraindications and precautions to the influenza vaccine are presented in Table 2. This season, the U.S. trivalent influenza vaccines include an A/California/7/2009 (H1N1)–like virus, an H3N2 virus antigenically like the cell-propagated prototype virus A/Victoria/361/2011, and a B/Massachusetts/2/2012–like virus. The quadrivalent vaccines include an additional virus strain, which is a B/Brisbane/60/2008–like virus. There are several newly licensed vaccine alternatives expected to be available. A quadrivalent live attenuated influenza vaccine (Flumist) is anticipated to replace the trivalent formulation; it is appropriate for healthy, nonpregnant persons two to 49 years of age. Three quadrivalent inactivated influenza vaccines are available in addition to their previous trivalent formulations; Fluarix and Flulaval are indicated for persons three years or older, and Fluzone is indicated for persons six months or older. Finally, a trivalent cell culture–based inactivated influenza vaccine (Flucelvax) is indicated for persons 18 years or older, and a recombinant hemagglutinin vaccine (Flublok) is available for persons 18 to 49 years of age. Although this is the first season both the trivalent and quadrivalent inactivated influenza vaccines are available, the quantity of quadrivalent doses may be limited. The quadrivalent dose provides broader protection against circulating influenza B viruses during seasons when the B virus in the trivalent vaccine is not an optimal match. There is no preference between the trivalent and quadrivalent inactivated vaccines; therefore, if only the trivalent vaccine is available, it should be used so as not to delay vaccination. Additionally, the high-dose trivalent inactivated influenza vaccine (Fluzone High- Table 1. Vaccines for the 2013-2014 Influenza Season Vaccine Dispensing method Mercury content (mcg per 0.5-mL dose) Ovalbumin Approved content (mcg ages per 0.5-mL dose) Route of administration 0.5-mL single-dose prefilled syringe 0 ≤ 1.0 ≥ 9 years* Intramuscular† 5.0-mL multidose vial 24.5 ≤ 1.0 ≥ 9 years* Intramuscular† Fluarix 0.5-mL single-dose prefilled syringe 0 ≤ 0.05 ≥ 3 years Intramuscular† Flucelvax 0.5-mL single-dose prefilled syringe 0 Not included‡ ≥ 18 years Intramuscular† Flulaval 5.0-mL multidose vial < 25.0 ≤ 0.3 ≥ 3 years Intramuscular† Fluvirin 0.5-mL single-dose prefilled syringe ≤ 1.0 ≤ 1.0 ≥ 4 years Intramuscular† 5.0-mL multidose vial 25.0 ≤ 1.0 ≥ 4 years Intramuscular† 0.25-mL single-dose prefilled syringe 0 —§ 6 to 35 months Intramuscular† 0.5-mL single-dose prefilled syringe 0 — ≥ 36 months Intramuscular† 0.5-mL single-dose vial 0 — ≥ 36 months Intramuscular† 5.0-mL multidose vial 25.0 — ≥ 6 months Intramuscular† 0.1-mL prefilled microinjection system 0 — 18 to 64 years Inactivated influenza vaccine, trivalent, standard dose Afluria Fluzone Fluzone intradermal|| Intradermal¶ continued... 516 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013
- 17. American Family Physician Table1. Vaccines for the 2013-2014 Influenza Season (continued) Vaccine Dispensing method Mercury content (mcg per 0.5-mL dose) Ovalbumin content (mcg per 0.5-mL dose) Approved ages Route of administration 0 — ≥ 65 years Intramuscular† Inactivated influenza vaccine, trivalent, high dose Fluzone High-Dose** 0.5-mL single-dose prefilled syringe Inactivated influenza vaccine, quadrivalent, standard dose Fluarix quadrivalent 0.5-mL single-dose prefilled syringe 0 ≤ 0.05 ≥ 3 years Intramuscular† Flulaval quadrivalent 5.0-mL multidose vial < 25.0 ≤ 0.3 ≥ 3 years Intramuscular† 0 — 6 to 35 months Intramuscular† 0.5-mL single-dose prefilled syringe 0 — ≥ 36 months Intramuscular† 0.5-mL single-dose vial 0 — ≥ 36 months Intramuscular† 0 0 18 to 49 years Intramuscular† 0 (per 0.2-mL dose) < 0.24 (per 0.2mL dose) 2 to 49 years‡‡ Intranasal Fluzone quadrivalent 0.25-mL single-dose prefilled syringe Recombinant influenza vaccine, trivalent Flublok 0.5-mL single-dose vial Live attenuated influenza vaccine, quadrivalent Flumist quadrivalent†† 0.2-mL single-dose prefilled intranasal sprayer Note: Immunization providers should check U.S. Food and Drug Administration–approved prescribing information for 2013-2014 influenza vaccines for the most complete and updated information, including (but not limited to) indications, contraindications, and precautions. Package inserts for U.S.licensed vaccines are available at http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm093833.htm. *Age indication per package insert is 5 years or older; however, the Advisory Committee on Immunization Practices recommends that Afluria not be used in children 6 months to 8 years of age because of increased risk of febrile reactions noted in this age group with 2010 Southern Hemisphere trivalent inactivated vaccine. If no other age-appropriate, licensed inactivated seasonal influenza vaccine is available for a child 5 to 8 years of age who has a medical condition that increases the child’s risk of influenza complications, Afluria can be used; however, health care professionals should discuss with the parents or caregivers the benefits and risks of influenza vaccination with Afluria before administering this vaccine. Afluria may be used in persons 9 years or older. †For adults and older children, the recommended site of vaccination is the deltoid muscle. The preferred site for infants and young children is the anterolateral aspect of the thigh. Specific guidance regarding site and needle length for intramuscular administration may be found in the Advisory Committee on Immunization Practices General Recommendations on Immunization (Centers for Disease Control and Prevention. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices, 2011. MMWR. 2011;60[RR-2].). ‡Information not included in package insert. The total egg protein is estimated to be less than 50 femtograms (5 × 1014 g) total egg protein (of which a fraction is ovalbumin) per 0.5-mL dose of Flucelvax. §Available on request from Sanofi Pasteur (1-800-822-2463 or MIS.Emails@sanofipasteur.com). ||Inactivated influenza vaccine, intradermal: a 0.1-mL dose contains 9 mcg of each vaccine antigen (27 mcg total). ¶The preferred site is over the deltoid muscle. Fluzone intradermal is administered using the delivery system included with the vaccine. **Inactivated influenza vaccine, high dose: a 0.5-mL dose contains 60 mcg of each vaccine antigen (180 mcg total). ††It is anticipated that the quadrivalent formulation of Flumist will replace the trivalent formulation for the 2013-2014 season. Flumist is shipped refrigerated and stored in the refrigerator at 35°F to 46°F (2°C to 8°C) after arrival in the vaccination clinic. The dose is 0.2 mL divided equally between each nostril. Health care professionals should consult the medical record, when available, to identify children 2 to 4 years of age with asthma or recurrent wheezing that might indicate asthma. In addition, to identify children who might be at greater risk of asthma and possibly at increased risk of wheezing after receiving live attenuated influenza vaccine, parents or caregivers of children 2 to 4 years of age should be asked, “In the past 12 months, has a health care professional ever told you that your child had wheezing or asthma?” Children whose parents or caregivers answer “yes” to this question and children who have asthma or who had a wheezing episode noted in the medical record within the past 12 months should not receive Flumist. ‡‡Flumist is indicated for healthy, nonpregnant persons 2 to 49 years of age. Persons who care for severely immunosuppressed persons who require a protective environment should not receive Flumist given the theoretical risk of transmission of the live attenuated vaccine virus. Dose) is approved for persons 65 years or older. Three prelicensure studies among persons in this age group showed that, compared with the standard dose, the high-dose vaccine elicited higher hemagglutination inhibition antibody titers against the three virus strains included in the seasonal influenza vaccine during the study period. However, there is no recommendation for using the high-dose vaccine vs. the standard-dose vaccine in this population. Persons 18 to 49 years of age who have an egg allergy of any severity now have the option of receiving trivalent recombinant influenza vaccine, an egg-free vaccine. In persons who have no known history of egg exposure but who have received allergy test results suggestive of an egg allergy, consultation with a physician who has expertise in allergy management is recommended before vaccination. Figure 1 provides an algorithm for influenza vaccination in persons who report an allergy to eggs. Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 517
- 18. American Family Physician Table2. Contraindications and Precautions* to the Use of 2013-2014 Influenza Vaccines Inactivated, including trivalent, quadrivalent, and cell culture–based History of severe allergic reaction to any component of the vaccine, including egg protein, or after previous dose of any influenza vaccine Recombinant History of severe allergic reaction to any component of the vaccine Live attenuated History of severe allergic reaction to any component of the vaccine, including egg protein, gentamicin, gelatin, and arginine, or after a previous dose of any influenza vaccine Concomitant aspirin therapy in children and adolescents In addition, the Advisory Committee on Immunization Practices recommends against use in the following groups: Children < 2 years Persons with asthma Persons with egg allergy Adults ≥ 50 years Children and adults who have chronic pulmonary, cardiovascular (except isolated hypertension), renal, hepatic, neurologic/ neuromuscular, hematologic, or metabolic disorders Close contacts and caregivers of severely immunosuppressed persons who require a protected environment Children 2 to 4 years of age whose parents or caregivers report that a health care professional has told them during the past 12 months that their child had wheezing or asthma, or whose medical record indicates Children and adults who have a wheezing episode has occurred during the immunosuppression (including past 12 months (Table 1) immunosuppression caused by medications or by human immunodeficiency virus infection) Pregnant women Note: Immunization providers should check U.S. Food and Drug Administration–approved prescribing information for 2013-2014 influenza vaccines for the most complete and updated information, including (but not limited to) indications, contraindications, and precautions. Package inserts for U.S.licensed vaccines are available at http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm093833.htm. *Precautions should be taken in persons with moderate to severe illness with or without fever, and in persons with a history of Guillain-Barré syndrome within six weeks of receipt of influenza vaccine. Influenza Vaccination in Patients with Egg Allergy Can the person eat lightly cooked egg (e.g., scrambled egg) without reaction?* No After eating eggs or egg-containing foods, does the person experience only hives? Yes Yes No Yes After eating eggs or egg-containing foods, does the individual experience other symptoms such as: Cardiovascular changes (e.g., hypotension) Respiratory distress (e.g., wheezing) Gastrointestinal symptoms (e.g., nausea, vomiting) Reaction requiring epinephrine Reaction requiring emergency medical attention Administer vaccine per usual protocol Administer recombinant influenza vaccine, trivalent, if patient is 18 to 49 years of age or Administer inactivated influenza vaccine Observe for reaction for at least 30 minutes following vaccination Administer recombinant influenza vaccine, trivalent, if patient is 18 to 49 years of age or Refer to a physician with expertise in management of allergic conditions for further evaluation *Persons with egg allergy might tolerate egg in baked products (e.g., bread or cake). Tolerance to egg-containing foods does not exclude the possibility of egg allergy. For persons who have no known history of exposure to egg but who are suspected of being egg-allergic on the basis of previously performed allergy testing, consultation with a physician who has expertise in the management of allergic conditions should be obtained before vaccination. Alternatively, recombinant influenza vaccine, trivalent, may be administered if the recipient is 18 to 49 years of age. Figure 1. Algorithm for influenza vaccination in persons who report egg allergy. Source: Adapted from Am Fam Physician. 2013;88(8):543-550. 518 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013
- 19. American Family Physician PhotoQuiz Acute Foot Rash in a Healthy Child During Travel During a trip to Brazil, a two-year-old girl presented with sudden foot pain while playing in the dirt near a tree. Her mother saw no glass, nails, or insects on the ground where the child was playing. The sole of the child’s left foot initially turned white in a linear pattern. Three hours later, the foot was erythematous with multiple petechiae (Figure 1). Swelling progressed from the sole to the rest of the foot, and then to the ankle with linear streaks. The child could not put weight on the foot. Four hours after the injury, she developed a fever of 103° F (39.4° C) and was difficult to console. Oral and topical antibiotics and acetaminophen were ineffective. Question Based on the patient’s history and physical examination, which one of the following is the most likely diagnosis? Figure 1. A. Acute dermatitis. B. Cellulitis. C. Contusion. D. Foreign body injury. E. Insect bites. SEE THE FOLLOWING PAGE FOR DISCUSSION. Source: Adapted from Am Fam Physician. 2011;83(2):201-202. Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 519
- 20. American Family Physician SummaryTable Condition Characteristics Acute dermatitis A transient but sometimes painful inflammatory reaction of the skin; reactions vary from mild, localized itching to more severe pain, swelling, and inflammation; more severe systemic reactions are rare but possible Cellulitis Diffuse inflammation of subcutaneous and loose connective tissue caused by bacterial infection; may lead to localized pain, erythema, swelling, and warmth Contusion Mechanical injury resulting in hemorrhage beneath unbroken skin; often associated with blunt trauma; injury may evolve with time Foreign body injury Localized trauma causing a wound; traumatic injuries can range from minor to life threatening Insect bite Inflammation at the site of punctured skin; usually appears within minutes to a few hours after the bite Discussion The answer is A: Acute dermatitis from a caterpillar sting. Further investigation found lime green caterpillars feeding on the leaves of the tree near where the child was playing (Figure 2). Caterpillars usually camouflage themselves on tree leaves. The family returned to the United States nine days after the injury, and the mother took the child to their family physician. Physical examination revealed swelling, purulent pockets, and multiple black caterpillar hairs/spines on the bottom of the foot. The physician discontinued the antibiotics and cleaned the area with soapstone (localized debridement). The child was able to walk on the foot after two days, and her fever subsided. Stinging caterpillars have specialized spines that contain poison glands. If the spines penetrate the skin, toxins spread on the surface of the skin, causing dermatitis.1,2 Reactions vary from mild, localized itching to more severe pain, swelling, and inflammation. Occasionally, a systemic response with diarrhea occurs. There have been reports from around the world of reactions from caterpillar stings, including dermatologic, pulmonary, and other systemic reactions.2,3 Removal of the caterpillar spines through debridement is the most effective means to counteract the toxic process and clear the localized reaction. Stings from some species of caterpillars can cause hemorrhagic reactions and arthritis.4,5 520 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 Figure 2. Cellulitis is a diffuse inflammation of subcutaneous and loose connective tissue caused by bacterial infection. It can lead to localized pain, erythema, swelling, and warmth. Typical treatment involves appropriate antibiotic therapy.6 Contusions are usually caused by mechanical injury resulting in hemorrhage beneath unbroken skin. They are often associated with blunt trauma, and the injury may evolve over time. Foreign body injuries are associated with localized trauma that causes a wound. Traumatic injuries can range from minor to life threatening. A typical reaction to an insect bite is an inflammatory response at the site of the punctured skin. It usually appears within minutes to a few hours after the bite. Insects that commonly bite humans include fleas, mosquitoes, ticks, bedbugs, blackflies, and sand flies.6,7 REFERENCES 1. Stanton G. Stinging caterpillars out in late summer and fall. http:// ipmnet.umd.edu/landscape/docs/ StingingCaterpillars-UMD.pdf. Accessed July 5, 2009. 2. Diaz JH. The evolving global epidemiology, syndromic classification, management, and prevention of caterpillar envenoming. Am J Trop Med Hyg. 2005;72(3):347-357. 3. Bessin R. Stinging caterpillars. http://www.ca.uky.edu/ entomology/entfacts/ef003.asp. Accessed July 5, 2009. 4. Secretaria de Estado da Saude do Parana. (Lonomia) acidentes II. http://www.saude.pr.gov.br/modules/conteudo/ conteudo.php?conteudo= 389. Accessed July 5, 2009. 5. Lima C. Largatas que queimam. January 31, 2008. http://www. olharvital. ufrj.br/2006/index.php?id_edicao=114&codigo=10. Accessed July 5, 2009. 6. Ectoparasite infestations and arthropod and stings: caterpillar stings and dermatitis. In: Kasper DL, Harrison TR, eds. Harrison’s Principles of Internal Medicine. 16th ed. New York, NY: McGraw-Hill; 2005:2607. 7. Lepidoptera: arthropods and leeches. In: Cecil RL, Goldman L, Ausiello DA, eds. Cecil Textbook of Medicine. 22nd ed. Philadelphia, Pa.: Saunders; 2004:2128-2129.
- 21. CARDIOLOGY Systolic and DiastolicRatio and Rate Pressure Product in Anemia K Singh Abstract Anemia, a common clinical entity is associated with hyperdynamic circulation and may be involved in etiopathology of heart failure. So, the current study was carried out in 30 patients in the age group 20-40 years with hemoglobin level < 6 g/dl and of at least three month duration of anemia (using WHO definition) and compared with 30 age- and sex-matched healthy subjects. Duration of systole and diastole was estimated by recording of electrocardiogram, apex-cardiogram and phonocardiogram on polyrite with the paper speed of 50 mm/sec. Duration of cardiac cycle was reduced (18.22%) and heart rate was increased (p < 0.001) in anemia compared to controls. On comparison of duration of systole and diastole, there was more decrement in diastole (26.76%, p < 0.001) compare to systole (6.45%, p < 0.01) in anemia versus healthy subjects. Similarly, when fraction occupied by systole and diastole in cardiac cycle were compared, the systolic fraction was increased, diastolic fraction in cardiac cycle was reduced and systole/diastole ratio was increased (p < 0.001) in anemics compared to controls. Rate pressure product and double product were elevated (p < 0.001) in anemia versus controls, imposing mechanical load on heart. So, it is concluded that patients of severe anemia are at the brink of heart failure and should be treated promptly. Keywords: Systole, diastole, cardiac cycle, anemia S ystole and diastole are the fundamental periods of cardiac cycle. Intervals of cardiac cycle as measured by echocardiography, apex-cardiography, i.e., isovolumic contraction time, isovolumic relaxation time are used to assess ventricular function.1 Recently, importance of duration of systole and diastole is emphasized and it is advocated that they can be used to assess cardiac functions as prognosis of patients suffering from diastolic heart failure (DHF) is as ominous as prognosis of patients suffering from systolic heart failure (SHF).2 Anemia, a frequently encountered clinical entity, said to be a risk factor for functional and cognitive disease3 imposes mechanical load on heart and may be involved in pathogenesis and progression of heart failure,4 chronic angina5 and acute coronary syndrome.6 Moreover, it is associated with ventricular hypertrophy, ischemia and increased heart rate.6 So, the current study is planned to evaluate the duration of cardiac Professor Dept. of Physiology Pt. BD Sharma, Postgraduate Institute of Medical Sciences (PGIMS), University of Health Sciences Rohtak (UHSR), Rohtak, Haryana Address for correspondence Dr K Singh 6J-11, Medical Campus, Rohtak - 124 001, Haryana E-mail: dr_rb_singh@rediffmail.com cycle, ratio of systole/diastole (S/D ratio), rate pressure product (RPP - since, it is an easy measurable index of myocardial oxygen consumption and load on heart)7 and double product (DoP) in patients of anemia. Methods The study was carried out in 30 patients of anemia (hemoglobin level was >6 g/dl for at least 3-month duration)8 using World Health Organization (WHO) definition of anemia - hemoglobin <13 g/dl for men and <12 g/dl in women9 in the age group of 20-40 years (mean age 32.65 ± 1.62) with body mass index (BMI) 22.9 ± 0.33 without clinical evidence of cardiac decompensation, and 30 age- (mean 31.49 ± 3.34 years) and sex-matched healthy subjects (hemoglobin level 11-14.02 g/dl) having BMI 22.2 ± 0.36. Electrocardiogram (ECG), apex-cardiogram (ACG) and phonocardiogram (PCG) were recorded with the paper speed of 50 mm/sec on polyrite (INCO). Systole was measured from onset of ventricular depolarization to first high frequency vibration of aortic sound. Diastole was measured from beginning of first high frequency of second heart sound to the beginning of sudden upstroke of ACG (Fig. 1). Duration of cardiac cycle, proportion of cardiac cycle occupied by systole and diastole, and S/D ratio were evaluated. Heart rate (HR) was assessed from ECG (lead II). Blood pressure (BP) was recorded manually by using sphygmomanometer. Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 521
- 22. CARDIOLOGY RPP was calculatedas SP × HR × 10-2, where SP is systolic pressure and value obtained was expressed as mmHg beats/min.7 Similarly, DoP was calculated as MP x HR, where MP is mean pressure and it was expressed in mmHg beats/min.10 Statistical analysis was done by unpaired ‘t’ test. Values were expressed as mean ± SD. A p value of < 0.05 was accepted as significant. Result Duration of cardiac cycle was 884.76 ± 87.54 msec. in normal healthy controls at the HR of 75.4 ± 12.5 beats/min in contrast to 723.5 ± 55.02 msec at the HR of 92.08 ± 18.19 beats/min in anemia. This reduction in duration of cardiac cycle (18.22%) was significant (p < 0.001). Duration of systole and diastole was 372.06 ± 29.41 versus 512.70 ± 110.14 msec, respectively in controls compared to duration of systole and diastole 348.04 ± 39.46 versus 375.46 ± 107.40 msec, respectively Electrocardiogram Apex-cardiogram Phonocardiogram Systole Diastole Figure 1. Simultaneous recording of ECG, ACG and PCG in controls. Electrocardiogram Apex-cardiogram Phonocardiogram Figure 2. Simultaneous recording of ECG, ACG and PCG in anemia. 522 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 in anemic patients. On comparison of systole and diastole, there was more decrement in diastole (26.76%, p < 0.001) compared to systole (6.45%, p < 0.001) in anemic patients versus healthy controls (Fig. 2). In healthy subjects systole and diastole constitute 42.05% and 57.94% fraction of cardiac cycle, respectively. While in anemia systole and diastole constitute 48.1% and 51.89% fraction of cardiac cycle, respectively, indicating fraction of systole was increased and diastole was reduced in anemia (Table 1). S/D ratio was lengthened (p < 0.001) in anemia, i.e., 1.04 ± 0.23 versus 0.71 ± 0.06 in controls (Fig. 2). RPP and DoP were significantly (p < 0.001) elevated in anemia compared to controls (Table 1). Discussion Anemia is said to be involved in the pathogenesis of heart failure (HF).4 It is hypothesized that relative duration of systole and diastole are altered and S/D ratio increases in HF.1 Duration of cardiac cycle in present study is about 0.88 second at normal HR in controls, which is in agreement with other authors.11 But in anemia, duration of cardiac cycle is shortened, which may be explained by hyperkinetic circulation. Reduction in duration of diastole is more (26%) than systole (6.4%), may be due to tachycardia. Tachycardia adversely affects the diastolic function by several mechanisms, as it diminishes the left ventricular filling, coronary perfusion time, increases myocardial oxygen demand, raises myocardial oxygen consumption and causes incomplete relaxation.12 It has to be noted that although duration of systole as such is reduced, proportion of cardiac cycle occupied by systole is lengthened from 42.05% in controls to 48% in anemics. In contrast proportion of cardiac cycle occupied by diastole is more reduced in anemia, from 57.9% to 51% in controls and anemics, respectively. All these changes result in enhanced S/D ratio in anemia in current study, which is consistent with the findings described by other authors in patients of HF. Myocardial perfusion occurs primarily in diastole. Myocardial blood flow in patients of left ventricular hypertrophy (LVH) (anemia can be associated with LVH) may depend upon diastolic perfusion time and perfusion pressure. Myocardial remodeling induced by renin-angiotensin system activated due to decreased renal perfusion and increased catecholamine secretion in anemia predisposes the ischemic damage.13 Reduced oxygen carrying capacity of blood, increase in circulation time and HR with reduction in diastolic time may further complicate coronary perfusion and still worsen the cardiac function.1
- 23. CARDIOLOGY Table 1. Comparisonof Parameters in Control and in Anemia (Mean ± SD) Parameters Heart rate (beats/ min) Systolic Diastolic BP BP (mmHg) (mmHg) Cardiac cycle length (msec) Duration of systole (msec) Duration of diastole (msec) Proportion of systole and diastole (%) in cardiac cycle S/D ratio RPP mmHg, beats/ min DoP mmHg, beats/ min Controls 75.4 ± 12.5 120.80 ± 8.90 71.10 ± 9.20 884.76 ± 87.54 372.06 ± 29.41 512.70 ± 110.14 42.05 and 57.94 0.71 ± 0.06 91.06 ± 12.32 7609.56 ± 190.5 Anemia 92.08** ± 18.19 111.04** ± 10.21 70.80 ± 9.27 723.5** ± 55.02 348.04* ± 39.46 375.46** ± 107.40 48.1 and 51.89 1.04** ± 0.23 Difference or p value <0.001 <0.001 NS 18.22% 6.45% 26.76% <0.001 102.24** 9029.37** ± 15.21 ± 260.1 0.001 <0.001 P value * = <0.01, ** = <0.001. BP = Blood pressure; S/D ratio = Systolic/Diastolic ratio; RPP = Rate pressure product; DoP = Double product. But clinical signs and symptoms pointing to HF were not evident in these patients.14 They were not taking treatment of it inspite of enhanced RPP and DoP in anemia indicating increase in O2 consumption and load on the heart. Enhanced O2 consumption of cardiac muscles in severe anemia is demonstrated by other authors also.15 But it is difficult to explain the reason for absence of features of HF, may be at this HR filling of LV is adequate enough to maintain cardiac output.11 As it is also stated that DHF is referred to as HF with normal left ventricular ejection fraction (LVEF), i.e. HFNLVEF.12 Moreover, onsets of symptoms also depend on the rapidity with which the anemia develops as well as physical activity of patient. So, our findings as lengthened systole, enhanced systolic and diastolic ratio and reduction in duration of diastole pointed out that patients of anemia are at the brink of HF. So, while treating the patient of HF and coronary artery disease, we should also have a look for anemia as treatment of systole and diastole failure is different. References 1. Friedberg MK, Silverman NH. Cardiac ventricular diastolic and systolic duration in children with heart failure secondary to idiopathic dilated cardiomyopathy. Am J Cardiol 2006;97(1):101-5. 2. Aurigemma GP. Diastolic heart failure: a common and lethal condition by any name. N Engl J Med 2006;355(3):308-10. 3. Denny SD, Kuchibhatla MN, Cohen HJ. Impact of anemia on mortality, cognition, and function in communitydwelling elderly. Am J Med 2006;119(4):327-34. 4. de Silva R, Rigby AS, Witte KK, Nikitin NP, Tin L, Goode K, et al. Anemia, renal dysfunction, and their interaction in patients with chronic heart failure. Am J Cardiol 2006;98(3):391-8. 5. Sharma S, Gage BF, Deych E, Rich MW. Anemia: an independent predictor of death and hospitalizations among elderly patients with atrial fibrillation. Am Heart J 2009;157(6):1057-63. 6. Meneveau N, Schiele F, Seronde MF, Descotes-Genon V, Oettinger J, Chopard R, et al; Reseau de Cardiologie de Franche Comte. Anemia for risk assessment of patients with acute coronary syndromes. Am J Cardiol 2009;103(4):442-7. 7. Gobel FL, Norstrom LA, Nelson RR, Jorgensen CR, Wang Y. The rate-pressure product as an index of myocardial oxygen consumption during exercise in patients with angina pectoris. Circulation 1978;57(3): 549-56. 8. Agarwal V, Sachdev A, Lehl S, Basu S. Unusual haematological alterations in rheumatoid arthritis. J Postgrad Med 2004;50(1):60-1. 9. Felker GM, Gattis WA, Leimberger JD, Adams KF, Cuffe MS, Gheorghiade M, et al. Usefulness of anemia as a predictor of death and rehospitalization in patients with decompensated heart failure. Am J Cardiol 2003;92(5):625-8. 10. Madanmohan, Udupa K, Bhavanani AB, Vijayalakshmi P, Surendiran A. Effect of slow and fast pranayams on reaction time and cardiorespiratory variables. Indian J Physiol Pharmacol 2005;49(3):313-8. 11. Ganong WF. Heart as a pump. Chapter 29. In: Review of Medical Physiology. 21st edition, A Lange Medical Book: McGraw-Hill, New Delhi 2010;Chap. 31, Sec.VI, p.570. 12. Chopra HK. Diastolic heart failure: a clinical challenge early recognition and timely intervention is the need of the hour. Indian Heart J 2009;61(2):138-45. 13. Schrier RW, Abraham WT. Mechanism of disease: Hormones and haemodynamics in heart failure. N Engl J Med 1999;341:577-85. 14. Braunwald E. Heart failure and corpulmonale. Chapter 216. In: Harrison’s Principle of Internal Medicine. Vol. II, 6th edition, McGraw-Hill: New York 2005:p.1370. 15. Levy PS, Quigley RL, Gould SA. Acute dilutional anemia and critical left anterior descending coronary artery stenosis impairs end organ oxygen delivery. J Trauma 1996;41(3):416-23. Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 523
- 24. DENTISTRY Probiotics: How Promisingare they in Promoting Periodontal Health? R Hemalatha*, A Sivachandran** Abstract With the widespread emergence of bacterial resistance to antibiotics, the concept of probiotic therapy has been considered for application in oral health. Dental caries, periodontal disease and halitosis are among the oral disorders that have been targeted. More than 700 species of oral microbiota have been detected in the human mouth and the resident microbiota of an individual may consist of 30-100 species. Studies suggest that lactobacilli as members of resident oral microflora could play an important role in the microecological balance in the oral cavity. Keywords: Probiotic therapy, dental caries, periodontal disease, halitosis, lactobacilli T he term ‘probiotics’, the antonym of the term ‘antibiotics’, was introduced in 1965 by Lilly and Stillwell as substances produced by microorganisms that promote the growth of other microorganisms. First probiotic species to be introduced in research was Lactobacillus acidophilus by Hull et al in 1984, followed by Bifidobacterium bifidum by Holcombh et al in 1991.1,2 Probiotics most commonly belong to the genera Lactobacillus and Bifidobacterium. The term ‘probiotic’ is derived from the Greek word, meaning ‘for life’.3 As defined by the Food Agricultural Organization/World Health Organization (FAO/WHO) probiotics are living organisms, principally bacteria, that are safe for human consumption and, when ingested in sufficient quantities, have beneficial effects on human health, beyond the basic nutrition.4 Such nonpathogenic organisms (yeasts or bacteria, particularly lactic acid bacteria) are present in food and can have a favorable impact on host health. Common Probiotic Strains Essential Conditions for Microorganisms to Exert Probiotic Properties To exert probiotic properties in the oral cavity, it is essential for the microorganisms that they:6 ÂÂ Should resist the oral environmental conditions and defense mechanisms ÂÂ Should adhere to the saliva-coated surfaces ÂÂ Should colonize and grow in the mouth ÂÂ Should inhibit oral pathogens ÂÂ Should be also safe for the host. Periodontal pathogens The main pathogenic periodontitis are: agents associated ÂÂ Porphyromonas gingivalis ÂÂ Treponema denticola ÂÂ Tannerella forsythia ÂÂ with Aggregatibacter actinomycetemcomitans.7 Lactobacillus species from which probiotic strains have been isolated include L. acidophilus, L. johnsonii, L. casei, L. rhamnosus, L. gasseri and L. reuteri. Bifidobacterium strains include B. bifidum, B. longum and B. infantis.5 These bacteria have a variety of virulent characteristics allowing them to colonize the subgingival sites, escape the host’s defense system and cause tissue damage.7 *Reader Karpaga Vinayaga Institute of Dental Sciences, Kanchipuram, Tamil Nadu **Senior Lecturer SRM Kattankulathur Dental College, Kanchipuram, Tamil Nadu Address for correspondence Dr A Sivachandran, Senior Lecturer SRM Kattankulathur Dental College, Kanchipuram, Tamil Nadu The treatment strategies conferred by probiotics against periodontal diseases are mainly anticipated to be either by inhibition of specificx pathogens or by altering the host immune response through the following multiple factors:6,8,9 524 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 Probiotics: Proposed Mechanism of Action Against Periodontal Pathogens
- 25. DENTISTRY ÂÂ Inhibition of specificorganisms Inhibition of pathogen adhesion, colonization and biofilm formation Inhibition of pathogen growth by various substances such as organic acids, hydrogen peroxide and bacteriocins against oral pathogens Effects on host response Inhibition of collagenases and reduction of inflammation-associated molecules Induction of expression of cytoprotective proteins on host cell surfaces Modulation of proinflammatory pathways induced by pathogens Prevention of cytokine-induced apoptosis ÂÂ Modulation of host immune response ÂÂ ÂÂ ÂÂ ÂÂ ÂÂ ÂÂ ÂÂ Probiotics: Role in prevention of periodontal disease Various studies have reported the capacity of lactobacilli to inhibit the growth of periodontopathogens, including P. gingivalis, Prevotella intermedia and A. actinomycetemcomitans.10,11 Krasse and colleagues12 assessed the beneficial effect of L. reuteri against gingivitis. First, L. reuteri is known for its secretion of two bacteriocins, reuterin and reutericyclin, that inhibit the growth of a wide variety of pathogens;13,14 second, L. reuteri has a strong capacity to adhere to host tissues, thereby competing with pathogenic bacteria.15 periodontitis.19 Hojo et al suggested that Bifidobacterium inhibited some black-pigmented anaerobes by competing for an essential growth factor vitamin K.20 Shimauchi et al demonstrated that the oral administration of a tablet containing L. salivarius WB21 decreased plaque index significantly and pocket probing depth markedly in smokers and reduced salivary lactoferrin at the end of 8-week trial.21 Twetman et al used L. reuteri-containing chewing gum in 42 healthy patients and assessed its effects on crevicular fluid volume, cytokine (interleukin-1β, interleukin-6, interleukin-10 and tumor necrosis factor-α [TNF-α]) levels and bleeding on probing. Crevicular fluid volume, as well as TNF-α and interleukin-8 levels and bleeding were significantly reduced.22 When the probiotic Streptococcus salivarius K12 was added to this bacterial model, the amount of cytokine release was greatly reduced after eight hours. This strongly suggests that S. salivarius K12 was able to dramatically downregulate the cytokine release from the pathogenic bacteria.23 Probiotics and Halitosis Kang and colleagues24 reported the capacity of various strains of W. cibaria to inhibit the production of volatile sulfur compounds by F. nucleatum. They concluded that this beneficial effect resulted from the production of hydrogen peroxide by W. cibaria, which inhibited the proliferation of F. nucleatum.24 Staab et al observed reduction in activity of matrix metalloprotein-3 (MMP-3) and elastase enzymes in subjects with plaque-induced gingivitis after consuming probiotic milk containing Lactobacillus casei species for a period of eight weeks.16 Currently Available Probiotic Agents in Periodontal Disease Management Riccia et al studied the anti-inflammatory effects of Lactobacillus brevis in a group of patients with chronic periodontitis. Anti-inflammatory effects of L. brevis could be attributed to its capacity to prevent the production of nitric oxide and consequently the release of prostaglandin E2(PGE2) and the activation of MMPs induced by nitric oxide.17 ÂÂ Probiotics in the form of tablets, lozenges, chewing gums or toothpastes are available: Another probiotic lozenge is avaliable, which is a blend of two L. reuteri strains containing a minimum of 1 × 108 colony forming units (CFU) for each of the strains DSM 17938 and ATCC PTA 5289.26 Ishikawa et al observed in vitro inhibition of P. gingivalis, P. intermedia and P. nigrescens by daily ingestion of L. salivarius in tablet form.18 Van Essche et al have reported that B. bacteriovorus attack, prey on and kill A. actinomycetemcomitans, thus suggesting a potential scope for the role of B. bacteriovorus in the prevention and treatment of Lozenges: One of the first probiotic specifically formulated to fight periodontal disease, contained a patented combination of two strains of L. reuteri selected for their synergistic properties in fighting cariogenic bacteria and periodontopathogens. Each dose of lozenge contained at least 2 × 108 living cells of L. reuteri Prodentis.25 ÂÂ Toothpastes: Toothpastes containing Dental-Lac, a functional Lactobacillus paracasei probiotic are available.25 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 525
- 26. DENTISTRY ÂÂ Tablets: A probioticpreparation, which is a complex of five live lyophilized lactic acid bacteria is available and is claimed to improve both clinical and microbiologic parameters in gingivitis and mild periodontitis patients. Conclusion Various studies have shown that the use of oral probiotics is associated with improvement in periodontal health. More research and clinical trials will facilitate identification of the probiotics that are best suited to oral use, as well as the most appropriate vehicles: Food products (cheese, milk, yogourt) or supplements (chewing gum, lozenges). The existence of probiotics in the indigenous oral microflora of humans needs exploration because these bacteria offer the advantage of being perfectly adapted to the human oral ecosystem. References 1. Tanboga I, Caglar E, Kargul B. Campaign of probiotic food consumption in Turkish children, oral perspectives “Probiotics for your child”. Int J Pediatr Dent 2003;13:59-64. 2. Flichy-Fernández AJ, Alegre-Domingo T, PeñarrochaOltra D, Peñarrocha-Diago M. Probiotic treatment in the oral cavity: an update. Med Oral Patol Oral Cir Bucal 2010;15(5):e677-80. 3. Hamilton-Miller JM, Gibson GR, Bruck W. Some insights into the derivation and early uses of the word ‘probiotic’. Br J Nutr 2003;90(4):845. 4. Report of a Joint FAO/WHO Expert consultation on evaluation of health and nutritional properties of probiotics in food including powder milk with live lactic acid bacteria. FAO/WHO, October 2001. 5. Suvarna VC, Boby VU. Probiotics in human health: a current assessment. Curr Science 2005;88:1744-88. 6. Stamatova I, Meurman JH. Probiotics and periodontal disease. Periodontol 2000 2009;51:141-51. 7. Houle MA, Grenier D. Maladies parodontales: connaissances actuelles. Current concepts in periodontal diseases. Médecine et Maladies Infectieuses 2003;33(7): 331-40. 8. Mackay AD, Taylor MB, Kibbler CC, Hamilton-Miller JM. Lactobacillus endocarditis caused by a probiotic organism. Clin Microbiol Infect 1999;5(5):290-2. 9. Reid G, Jass J, Sebulsky MT, McCormick JK. Potential uses of probiotics in clinical practice. Clin Microbiol Rev 2003;16(4):658-72. 10. Sookkhee S, Chulasiri M, Prachyabrued W. Lactic acid bacteria from healthy oral cavity of Thai volunteers: inhibition of oral pathogens. J Appl Microbiol 2001;90(2):172-9. 11. Kõll-Klais P, Mändar R, Leibur E, Marcotte H, Hammarström L, Mikelsaar M. Oral lactobacilli in chronic periodontitis and periodontal health: species composition and antimicrobial activity. Oral Microbiol Immunol 2005;20(6):354-61. 526 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 12. Krasse P, Carlsson B, Dahl C, Paulsson A, Nilsson A, Sinkiewicz G. Decreased gum bleeding and reduced gingivitis by the probiotic Lactobacillus reuteri. Swed Dent J 2006;30(2):55-60. 13. Gänzle MG, Höltzel A, Walter J, Jung G, Hammes WP. Characterization of reutericyclin produced by Lactobacillus reuteri LTH2584. Appl Environ Microbiol 2000;66(10):4325-33. 14. Talarico TL, Casas IA, Chung TC, Dobrogosz WJ. Production and isolation of reuterin, a growth inhibitor produced by Lactobacillus reuteri. Antimicrob Agents Chemother 1988;32(12):1854-8. 15. Mukai T, Asasaka T, Sato E, Mori K, Matsumoto M, Ohori H. Inhibition of binding of Helicobacter pylori to the glycolipid receptors by probiotic Lactobacillus reuteri. FEMS Immunol Med Microbiol 2002;32(2):105-10. 16. Staab B, Eick S, Knöfler G, Jentsch H. The influence of a probiotic milk drink on the development of gingivitis: a pilot study. J Clin Periodontol 2009;36(10):850-6. 17. Riccia DN, Bizzini F, Perilli MG, Polimeni A, Trinchieri V, Amicosante G, et al. Anti-inflammatory effects of Lactobacillus brevis (CD2) on periodontal disease. Oral Dis 2007;13(4):376-85. 18. Ishikawa H, AibaY, Nakanishi M, Oh-Hashi Y, Koga Y. Suppression of periodontal pathogenic bacteria by the administration of Lactobacillus salivarius T12711. J Jap Soc Periodontol 2003;45:105-12. 19. Van Essche M, Quirynen M, Sliepen I, Van Eldere J, Teughels W. Bdellovibrio bacteriovorus attacks Aggregatibacter actinomycetemcomitans. J Dent Res 2009;88(2):182-6. 20. Hojo K, Mizoguchi C, Taketomo N, Ohshima T, Gomi K, Arai T, et al. Distribution of salivary Lactobacillus and Bifidobacterium species in periodontal health and disease. Biosci Biotechnol Biochem 2007;71(1):152-7. 21. Shimauchi H, Mayanagi G, Nakaya S, Minamibuchi M, Ito Y, Yamaki K, et al. Improvement of periodontal condition by probiotics with Lactobacillus salivarius WB21: a randomized, double-blind, placebo-controlled study. J Clin Periodontol 2008;35(10):897-905. 22. Twetman S, Derawi B, Keller M, Ekstrand K, YucelLindberg T, Stecksen-Blicks C. Short-term effect of chewing gums containing probiotic Lactobacillus reuteri on the levels of inflammatory mediators in gingival crevicular fluid. Acta Odontol Scand 2009;67(1):19-24. 23. Streptococcus salivarius K12 and M18 Probiotics reduce Periodontal Pathogen-induced inflammation. 24. Kang MS, Kim BG, Chung J, Lee HC, Oh JS. Inhibitory effect of Weissella cibaria isolates on the production of volatile sulphur compounds. J Clin Periodontol 2006;33(3):226-32. 25. Wilson M. Manipulation of the indigenous microbiota. In: Microbial Inhabitants of Humans. Wilson M (Eds.), Cambridge University Press: New York 2005:p.395 -416. 26. Vivekananda MR, Vandana KL, Bhat KG. Effect of the probiotic Lactobacilli reuteri (Prodentis) in the management of periodontal disease: a preliminary randomized clinical trial. J Oral Microbiol 2010;2.
- 27. DERMATOLOGY Herpes Zoster: MultiplePresentations in a Single Patient SONIA JAIN Abstract Herpes zoster is a common viral opportunistic infection in human immunodeficiency virus (HIV)-infected patients with low CD4 count and high viral load. This is consistent with previous observations that HIV-infected individuals on highly active antiretroviral therapy (HAART) may not fully recover from the varicella zoster virus-specific cell-mediated immune (CMI) responses. Herpes zoster is an acute posterior ganglion radiculitis and results from reactivation of the varicella zoster virus that remains quiescent in the neurons. It can occur in any age, irrespective of the immune status. Here we report the case of an elderly male who was seropositive for HIV and had an atypical presentation with disseminated and multidermatomal herpes zoster. Keywords: Multidermatomal, herpes zoster, human immunodeficiency virus D espite three decades of concerted effort, human immunodeficiency virus (HIV) epidemic poses a tremendous public health challenge in developed and developing countries.1,2 Varicella zoster virus (VZV) is a neurotropic virus belonging to alpha herpesvirus group. Primary infection occurs as varicella (chicken pox) after which the virus remains latent in ganglionic neurons along the entire neuraxis. Factors like increasing age, immunosuppression, organ transplant, malignancy or acquired immunodeficiency syndrome (AIDS) cause reactivation of VZV to produce herpes zoster.3 There is high incidence of zoster in HIVpositive adults4,5 and children,6 where it follows a more protracted course. VZV reactivation produces multiple ocular and neural disorders, estimated to occur in upto 11% of HIV-positive cases.7 Multidermatomal and disseminated herpes zoster frequently occurs in patients with lymphoreticular malignancy or HIV infection.8 Case Report We report a case of a 65-year-old married man who presented to us with multiple vesiculobullous, hemorrhagic lesions associated with burning sensation over his left upper back of arm, forearm and medial three fingers of hand (Figs. 1-3). He also had large eschar (gangrenous) with hyperpigmentation and Professor Dept. of Skin and VD Mahatma Gandhi Institute of Medical Sciences Sewagram, Wardha, Maharashtra Figure 1. Multiple vesiculobullous hemorrhagic lesions over left arm and medial three fingers of hand. hemorrhagic crust over the back (periscapular area) (Fig. 4). The lesions were distributed along C 6, 7, 8 and T 1, 2, 3 dermatomes. Within three four days he developed multiple fluid-filled lesions over face, abdomen, back and upper and lower extremities, suggestive of disseminated herpes zoster (Fig. 5). He was found to be reactive for both HIV-1 and HIV-2 antibodies by Comb AIDS and Triline diagnostic kits. The tests are based on the principles of immunodot and immunochromatographic assays, respectively. Blood, and urine tests along with a chest X-ray were normal. Tzanck smear showed presence of acantholytic cells. He was treated with oral acyclovir and analgesics and he responded well. He was referred to the government hospital for further management. Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 527
- 30. DERMATOLOGY Figure 2. Multiplevesiculobullous hemorrhagic lesions over left forearm. Figure 3. Multiple vesiculobullous hemorrhagic lesions over left upper back of the arm. Figure 4. Large eschar with hyperpigmentation and hemorrhagic crust over the back. Figure 5. Multiple fluid-filled lesions over abdominal area. Discussion Conclusion The presentation of HIV has changed over the past 15 years. Cutaneous markers like extensive seborrheic dermatitis, psoriasis, multidermatomal herpes zoster, oral hairy leukoplakia and molluscum contagiosum are all pointers toward immunosuppression. Such patients should be thoroughly screened for the primary infection leading to immunosuppression, especially HIV. Disseminated cutaneous zoster is defined as having more than 20 vesicles in other than the area of primary and adjacent dermatomes. In a study by Abdul Latheef et al, 90% HIV patients had localized lesions as in normal patients and only 10% had dissemination, bulla formation and necrosis. Disseminated herpes zoster can occur in the immunocompromised elderly patient and HIV may sometimes be overlooked. HIV-infected patients with low CD4 cell counts have impaired VZVspecific cell-mediated immunity and thus they remain at a higher risk for developing multidermatomal herpes zoster.9,10 Intravenous acyclovir administered for three days is an effective treatment for cutaneous herpes zoster in patients with HIV infection.11 We report this case because of its rarity and multiple clinical presentations in one patient having multidermatomal, disseminated, hemorrhagic and gangrenous pattern of herpes zoster in an immunocompromised host. Timely diagnosis, adequate therapy and prevention of untoward complications should be our primary aim of treatment. 530 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 REFERENCES 1. Hall HI, Song R, Rhodes P, Prejean J, An Q, Lee LM, et al; HIV Incidence Surveillance Group. Estimation of HIV incidence in the United States. JAMA 2008;300(5): 520-29. 2. Coenen T, Lundgren J, Lazarus JV, Matic S. Optimal HIV testing and earlier care: the way forward in Europe. HIV Med 2008;9 Suppl 2:1-5. 3. Birlea M, Arendt G, Orhan E, Schmid DS, Bellini WJ, Schmidt C, et al. Subclinical reactivation of varicella zoster virus in all stages of HIV infection. J Neurol Sci 2011;304(1-2):22-4. Cont’d on page 534...
- 31. DERMATOLOGY Lichen Sclerosus etAtrophicus in a Young Girl YS Marfatia*, SoNIA JAIN** Abstract Lichen sclerosus et atrophicus is a chronic inflammatory dermatosis that results in white plaques and epidermal atrophy. The condition has both genital and extragenital presentations. Here we describe the case of a 12-year-old girl who presented to us with white plaques over her genitals and no manifestation of extragenital disease. Keywords: Lichen sclerosus et atrophicus, lichen albus, white spot disease L ichen sclerosus is a chronic inflammatory dermatosis that most commonly affects the anogenital region and leads to intractable pruritus and soreness. The condition is more common in females1 as in the present case also the patient is a young girl who presented with complaints of white plaques with itching over the genitals since her prepubertal years. The condition involves the risk of malignant transformation more so over the genital lesions but the precise incidence has not been defined. Pathophysiologically, the condition is associated with the presence of autoantibodies to glycoprotein extracellular matrix protein 1 (ECM-1).2 Several risk factors have also been proposed including autoimmune diseases, infections and genetic predisposition.3 There is evidence of its association with thyroid disease.4 Figure 1. Photograph showing labial atrophy. CASE SUMMARY A 12-year-old young girl presented to us with depigmented patches over the genitals, which had an insidious onset and were gradually progressive over a period of one year (Fig. 1). She had moderate itching over the site and she had seen many doctors for her complaints but had no relief. On dermatological examination, labia majora showed atrophy along with depigmentation of the labia minora (Fig. 2). The *Professor and Head Dept. of Skin and VD, Baroda Medical College SSG Hospital, Raopura, Vadodara, Gujarat **Professor Dept. of Skin and VD MGIMS, Sewagram, Wardha, Maharashtra Address for correspondence Dr Sonia Jain A-14, Dhanvantri Nagar MGIMS, Sewagram, Wardha, Maharashtra E-mail: soniapjain@rediffmail.com Figure 2. Photograph showing depigmented patch over the labia. depigmented patches extended from the fourchette to the vestibule and she had no oral or cutaneous lesions elsewhere. There was no history of sexual abuse or any high-risk behavior and none of the family members Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 531
- 34. DERMATOLOGY abuse associated witha higher incidence of LSA in pediatric population. Besides, they also described the association of LSA with infection, autoimmunity and trauma. There has been a case on the records wherein Virdi and Kanwar reported the co-existence of localized cutaneous morphea with LSA and submucosal fibrosis in a middle-aged man in his late-thirties.5 Another citation of a similar association between the aforesaid conditions has been mentioned by Prasad and Padmavathy et al, wherein they reported a case of a young male in his mid-twenties who presented with generalized morphea and LSA along with osteolytic bone changes.6 However, our patient showed no signs of morphea or any other systemic disease. Figure 3. Histology showing homogenization of the collagen and inflammatory infiltrate in the dermis. had a similar clinical picture. She had no urinary or bowel complaints. We performed a labial biopsy from the depigmented patch after taking a written informed consent and the histopathological findings were consistent with Lichen sclerosus et atrophicus (LSA) showing homogenization of the collagen and inflammatory infiltrate in the dermis (Fig. 3). DISCUSSION Lichen sclerosus is also known as LSA, balanitis xerotica obliterans (BXO) in men, Csillag’s disease, White spot disease, Lichen albus and Krauosis vulvae. LSA was first described in 1887 by Dr Hallopeau. A case series of 42 children (all females) suffering from LSA has been reported by Shirley A Warrington and Camille de San Lazaro where they found a high incidence of sexual REFERENCES 1. Tasker GL, Wojnarowska F. Lichen sclerosus. Clin Exp Dermatol 2003;28(2):128-33. 2. Chan I, Oyama N, Neill SM, Wojnarowska F, Black MM, McGrath JA. Characterization of IgG autoantibodies to extracellular matrix protein 1 in lichen sclerosus. Clin Exp Dermatol 2004;29(5):499-504. 3. Yesudian PD, Sugunendran H, Bates CM, O’Mahony C. Lichen sclerosus. Int J STD AIDS 2005;16(7):465-73, test 474. 4. Birenbaum DL, Young RC. High prevalence of thyroid disease in patients with lichen sclerosus. J Reprod Med 2007;52(1):28-30. 5. Virdi SK, Kanwar AJ. Generalized morphea, lichen sclerosis et atrophicus associated with oral submucosal fibrosis in an adult male. Indian J Dermatol Venereol Leprol 2009;75(1):56-9. 6. Prasad PV, Padmavathy L, Sethurajan S, Kumar P, Rao L. Generalised morphoea with lichen sclerosus et atrophicus and unusual bone changes. Indian J Dermatol Venereol Leprol 1995;61(2):113-5. ■■■■ ...Cont’d from page 530 4. De La Blanchardiere A, Rozenberg F, Caumes E, Picard O, Lionnet F, Livartowski J, et al. Neurological complications of varicellazoster virus infection in adults with human immunodeficiency virus infection. Scand J Infect Dis 2000;32(3):263-9. 5. Vafai A, Berger M. Zoster in patients infected with HIV: a review. Am J Med Sci 2001;321(6):372-80. 6. Gershon AA, Mervish N, LaRussa P, Steinberg S, Lo SH, Hodes D, et al. Varicella-zoster virus infection in children with underlying human immunodeficiency virus infection. J Infect Dis 1997;176(6):1496-500. 7. Burke DG, Kalayjian RC, Vann VR, Madreperla SA, Shick HE, Leonard DG. Polymerase chain reaction detection and clinical significance of varicella-zoster virus in cerebrospinal fluid from human immunodeficiency virusinfected patients. J Infect Dis 1997;176(4):1080-4. 534 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 8. Friedman-Kien AE, Lafleur FL, Gendler E, Hennessey NP, Montagna R, Halbert S, et al. Herpes zoster: a possible early clinical sign for development of AIDS in high risk individual. J Am Acad Dermatol 1986;14(6):1023-8. 9. Blank LJ, Polydefkis MJ, Moore RD, Gebo KA. Herpes zoster among persons living with HIV in the current antiretroviral therapy era. J Acquir Immune Defic Syndr 2012;61(2):203-7. 10. De Castro N, Carmagnat M, Kernéis S, Scieux C, Rabian C, Molina JM. Varicella-zoster virus-specific cell-mediated immune responses in HIV-infected adults. AIDS Res Hum Retroviruses 2011;27(10):1089-97. 11. Noonan L, Gunson T, Ellis-Pegler R, Thomas M, Briggs S. Short-course intravenous aciclovir treatment for cutaneous herpes zoster in patients with HIV infection. Int J STD AIDS 2012;23(5):356-8.
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- 36. 536 Indian Journal ofClinical Practice, Vol. 24, No. 3, August 2013 EDGE India reprint/Galvus/CVM/097/11/13 GASTROENTEROLOGY
- 37. ENDOCRINOLOGY Effectiveness and Tolerabilityof Vildagliptin in Indian Patients with Type 2 Diabetes Mellitus: Results From Edge−A Real-World Observational Study Subhash K Wangnoo*, Giovanni Bader**, Apurva Gawai†, Shradhanand Singh‡ Abstract Objective: To assess the effectiveness and tolerability of vildagliptin in combination with another oral antidiabetic drug (OAD) versus any other two-agent OAD combinations in Indian patients with type 2 diabetes mellitus (T2DM) in a real-world setting. Study design: This was a post hoc analysis of a multicenter, prospective, 1-year, observational EDGE study for patients enrolled in India. The primary efficacy endpoint of the study was proportion of patients achieving glycosylated hemoglobin (HbA1C) reduction of >0.3% without peripheral edema, hypoglycemic event, discontinuation due to a gastrointestinal event or weight gain. One of the secondary efficacy endpoints was proportion of patients achieving HbA1C <7% without hypoglycemia and weight gain. Results: The mean age, body mass index, HbA1C and duration of T2DM were 51.8 years, 26.6 kg/m2, 8.6% and 4.3 years, respectively. The proportion of patients achieving the efficacy endpoints was significantly higher in the vildagliptin cohort compared with the comparator cohort (p < 0.0001). The vildagliptin cohort showed a numerically greater reduction in HbA1C than the comparator cohort (1.4 vs 1.1%; analysis not pre-specified). Adverse events were comparable in both groups (4.2% vs 4.9%). Conclusion: In India, in a real-world setting, vildagliptin showed better overall clinical benefits compared with comparator OADs in patients with T2DM. Keywords: Dipeptidyl peptidase-4 inhibitor, dual combination, India, oral antidiabetic drug, real-world, type 2 diabetes, vildagliptin T ype 2 diabetes mellitus (T2DM), a major lifestyle disorder, has transitioned from being a class disease to a mass epidemic and poses a rapidly emerging global threat to public health with a worldwide prevalence of 366 million.1 India, once known as the ‘diabetes capital of the world’2, was home to 61.3 million patients with T2DM in 2011 and this figure is expected to rise to 101.2 million by 2030.1 Various phenotypic and genotypic characteristics in Indians may lead to increased insulin resistance, lower *Senior Consultant Endocrinologist and Diabetologist Apollo Centre for Obesity, Diabetes and Endocrinology (ACODE) Indraprastha Apollo Hospital, Sarita Vihar, New Delhi **Principal Medical Scientific Expert, Global Medical Affairs - Diabetes, Novartis Pharma AG, Postfach, Switzerland †Medical Advisor Novartis Healthcare Private Limited, Worli, Mumbai ‡Clinical Research Medical Advisor Novartis Healthcare Private Limited, Worli, Mumbai Address for correspondence Dr Apurva Gawai Medical Advisor Novartis Healthcare Private Limited Sandoz House, 7th Floor, Shivsagar Estate Dr Annie Besant Road, Worli, Mumbai - 400 018 E-mail: apurva.gawai@novartis.com adiponectin, greater abdominal adiposity (higher waist circumference despite lower body mass index [BMI]) and a higher prevalence of impaired glucose tolerance; all of these factors contribute to a higher risk of developing T2DM at a comparatively young age.3 Physical inactivity, changes in dietary habits, a carbohydrate rich diet, urbanization and environmental factors also add to this risk.4 In addition, patients and healthcare professionals in India face challenges such as clinical inertia (failure to initiate or intensify the treatment) in achieving glycemic control, inadequate treatment follow-up and lack of disease awareness among patients.4 Guidelines suggest the use of combination therapies including diverse oral antidiabetic drugs (OADs), acting via multiple mechanisms, to effectively manage hyperglycemia, while dealing with the challenges of the progressive nature of T2DM and monotherapy failure.5 Vildagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor improves pancreatic α- and β-cell responsiveness to glucose, and consequently provides improved glycemic control as monotherapy, or as a component of combination therapy, without weight gain and hypoglycemia.6-8 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 537
- 38. ENDOCRINOLOGY Pragmatic real-world observationalstudies are designed to provide a closer look into routine clinical practice.9 EDGE (Effectiveness of Diabetes control with vildaGliptin and vildagliptin/mEtformin) was a prospective, 1-year, observational study conducted across 27 countries from Europe, Central and Latin America, Asia and Middle East to evaluate the efficacy, safety and tolerability of vildagliptin in combination with another OAD versus all other two-agent OAD combinations in real-world settings.10 In these post hoc analyses, we assessed the effectiveness and tolerability of vildagliptin combination versus all other two-agent OAD combinations in patients enrolled from India in the EDGE study. Subjects and Study Design Of the 45,868 patients enrolled in the EDGE study,10 11,057 were enrolled across 472 sites in India. Patients with T2DM, aged ≥18 years, who had inadequate glycemic control, while receiving OAD monotherapy with a sulfonylurea (SU), metformin, thiazolidinedione, glinide or α-glucosidase inhibitor were eligible. Patients receiving DPP-4 inhibitors other than vildagliptin, incretinmimetics/analogs or insulin, requiring three or more OADs, or who had a history of hypersensitivity to study drugs were excluded. Physicians chose antidiabetic treatment for their patients at their own discretion. To avoid physician bias for a particular choice of treatment, patients were asked for informed consent and enrolled in the study only after the treatment decision was made (Fig. 1). The term index therapy was used to represent the combination treatment initiated at enrolment. Further details of the subjects and study design are reported elsewhere.10 Materials and Methods Efficacy Endpoints The primary efficacy endpoint of the study was the proportion of patients responding to the treatment (reduction in glycosylated hemoglobin [HbA1C] >.3% from baseline to 12 months) with no intolerability findings (peripheral edema, hypoglycemic event, discontinuation due to a gastrointestinal event or weight gain ≥5%). One of the secondary efficacy endpoints was the proportion of patients with baseline HbA1C ≥7% who achieved target HbA1C <7% without hypoglycemia and weight gain ≥3%. Change in HbA1C from baseline to study endpoint was also evaluated in 538 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 these post hoc analyses (an analysis not pre-specified in the protocol). Hypoglycemia was defined as symptoms suggestive of hypoglycemia that resolved promptly on administration of oral carbohydrate (including mild and severe events). Statistical Analysis Descriptive statistics were used for these post hoc analyses. Inference is provided for primary and secondary efficacy endpoints. The per protocol (PP: Patients who completed the study without any major protocol deviation) population was used for analyses of the efficacy endpoints. Data were censored if patients changed index therapy. The probability of success was analyzed for the efficacy endpoints using a binary logistic regression model to calculate odds ratios (ORs) with 95% confidence intervals (CIs). The OR expresses odds in favor of success with vildagliptin combinations relative to odds in favor of success with comparator OADs. Patients whose outcomes could not be categorized as a success or failure (e.g., due to missing HbA1C or body weight data at the 12-month endpoint) were considered nonevaluable. These nonevaluable patient data were considered failures in calculation of the OR for success. Only unadjusted ORs were reported for the primary and secondary efficacy endpoints in these post hoc analyses. HbA1C drop was adjusted with baseline value by using an analysis of covariance (ANCOVA) model. Results Of the 11,057 patients enrolled from India in the EDGE study, 365 patients (198 in the vildagliptin and 167 in the comparator cohort) were excluded due to inadequate source documentation or problems with quality or accuracy of data entry. The remaining intention-to-treat (ITT) population received newly prescribed vildagliptin (5,621) or a nonvildagliptin OAD (5,071) added to prior monotherapy (Table 1). The PP population, a subset of the ITT population comprising 5,606 patients in the vildagliptin cohort and 5,070 patients in the comparator cohort, was used for the analyses of efficacy endpoints. The demographic and baseline characteristics of patients in the ITT population are summarized in Table 2. Overall, 61.4% patients were male. The mean values of age, BMI, HbA1C and duration of T2DM at baseline were 51.8 years, 26.6 kg/m2, 8.6% and 4.3 years, respectively. Despite the fact that this was a nonrandomized study, the baseline characteristics were comparable across the groups (Table 2).
- 39. ENDOCRINOLOGY Table 1. PatientPopulations and Flow Enrolled* 11,057 No cohort assignment 0 Vildagliptin cohort Comparator cohort 5,819 5,238 198 167 ITT** 5,621 5,071 Patients completed 5,418 4,874 203 197 7 3 5,606 5,070 Assigned No adequate source documentation at site; lack of quality and accuracy of data entry Patients discontinued Patients with ≥1 protocol deviation Per protocol † *The enrolled population includes all patients who gave documented informed consent. **The intention-to-treat (ITT) population is a subset of the enrolled population and includes all patients who were assigned to new treatment at study start. †The per protocol (PP) population is a subset of the ITT population, who completed the study without any major protocol deviation; it was used for the analyses of effectiveness endpoints. Table 2. Demographic and Patient Baseline Characteristics (ITT Population) Characteristic Vildagliptin (n = 5,621) Comparator (n = 5,071) Total (n = 10,692) 51.7 ± 9.94 52.0 ± 9.95 51.8 ± 9.95 Male 3,459 (61.5) 3,102 (61.2) 6,561 (61.4) Female 2,162 (38.5) 1,969 (38.8) 4,131 (38.6) Age (years) Gender, n (%) (kg/m2) 26.8 ± 4.16 26.4 ± 3.93 26.6 ± 4.06 Baseline HbA1C (%) 8.6 ± 1.12 8.5 ± 1.09 8.6 ± 1.11 Duration of T2DM (years) 4.4 ± 4.29 4.1 ± 3.89 4.3 ± 4.11 BMI Data are mean ± standard deviation unless specified otherwise. BMI = Body mass index; ITT = Intention-to-treat; SD = Standard deviation; T2DM = Type 2 diabetes mellitus. Table 3. Index Medication (ITT Population) Vildagliptin cohort* (n = 5,621) Treatments Comparator cohort* (n = 5,071) No. of patients (%) Treatments No. of patients (%) TZDs-vildagliptin 131 (2.3) SUs-TZDs 253 (5.0) SUs-vildagliptin 1,252 (22.3) Metformin-TZDs 482 (9.5) Metformin-vildagliptin 4,176 (74.4) Metformin-SUs 3,946 (77.8) Glinides-vildagliptin 10 (0.2) Metformin-insulin 0 (0) AGI-vildagliptin 47 (0.8) Glinides-TZDs 3 (0.1) Glinides-SUs 30 (0.6) Glinides-metformin 38 (0.7) AGIs-TZDs 10 (0.2) AGIs-SUs 83 (1.6) AGIs-metformin 223 (4.4) AGIs-glinides 3 (0.1) AGI = α-glucosidase inhibitor; ITT = Intention-to-treat; SU = Sulfonylurea; TZD = Thiazolidinedione. Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 539
- 40. ENDOCRINOLOGY Vildagliptin as add-onor vildagliptin/metformin (fixed-dose)* Monotherapy failure Comparator dual therapy OADs** Month 0 1 2 3 4 5 6 7 8 9 10 11 12 BL Demography HbA1C HbA1C HbA1C Weight Weight Weight T2DM Meds T2DM Meds T2DM Meds AEs, SAEs Required AEs, SAEs Optional Required Data Collection Opportunities Figure 1. Study design. *Vildagliptin cohort: T2DM patients newly initiating vildagliptin as add-on, or newly initiating vildagliptin-metformin (fixed-dose) from nonvildagliptin monotherapy. **Comparator OAD cohort: T2DM patients newly initiating dual therapy with antidiabetic therapies other than vildagliptin (defined as SU, metformin, TZDs, metiglinides, a-glucosidase inhibitors as add-on dual therapy) except as add-on to vildagliptin, other DPP-4 inhibitors or GLP-1 mimetics/analogs. AEs = Adverse events; AGI = a-glucosidase inhibitor; BL = Baseline; DPP-4 = Dipeptidyl peptidase-4; GLP-1 = Glucagon-like peptide-1; OAD = Oral antidiabetic drugs; SAEs = Serious AEs; SU = Sulfonylurea; T2DM = Type 2 diabetes mellitus; TZD = Thiazolidinedione. At study entry, most patients were receiving metformin monotherapy. Table 3 reports index therapies in the ITT population for both cohorts. The percentage of patients achieving the primary efficacy endpoint was 68.5% in the vildagliptin cohort compared with 56.8% in the comparator cohort (Fig. 2A), with an unadjusted OR of 1.65 (95% CI: 1.53, 1.79; p < 0.0001) in favor of vildagliptin. For the secondary efficacy endpoint, the numbers were 25.7% patients in the vildagliptin cohort compared with 14.6% patients in the comparator cohort (Fig. 2A), resulting in an unadjusted OR of 2.03 (95% CI: 1.83, 2.25; p < 0.0001) in favor of vildagliptin. who experienced myocardial infarction died during the study; he reported a medical history of hypertension, renal impairment, transient ischemic attack, diabetic retinopathy, dyslipidemia and hyperlipidemia. The death was not suspected to be due to the study drug. After 12 months of treatment, vildagliptin resulted in a numerically greater adjusted mean change in HbA1C than the comparator cohort with a mean treatment difference of 0.3% in favor of vildagliptin (Fig. 2B). Discussion Overall, 234 patients (4.2%) in the vildagliptin cohort and 248 patients (4.9%) in the comparator cohort reported adverse events (AEs). Three cases of serious AEs (SAEs), namely myocardial infarction, foot abscess and uncontrolled hyperglycemia, were reported in the vildagliptin cohort versus none in the comparator cohort. However, none of the SAEs were suspected to be treatment-related. The patient 540 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 A total of 19 patients (0.3%) reported hypoglycemia in the vildagliptin cohort versus 66 patients (1.3%) in the comparator cohort. Most of the hypoglycemic events in the comparator group were reported by patients who were receiving a metformin and SU combination (54 patients, 1.1%). Real-world studies are valuable for a country like India, which has a population with high prevalence of T2DM patients with poor glycemic control.4 Various studies have reported that Indian patients with T2DM have higher mean HbA1C11,12 than the recommended treatment goal,5,13 indicating poor glycemic control among Indians. In addition, our post hoc analyses indicated that patients enrolled in India had a numerically higher baseline HbA1C (8.6% ± 1.1%) than that reported for the overall population in the EDGE study (8.2% ± 1.3%).10
- 41. ENDOCRINOLOGY A Patients achieved studyendpoints (%) 80 70 60 Vildagliptin 68.5 Comparator 56.8 50 40 30 25.7 20 14.6 10 0 B Primary efficacy endpoint Secondary efficacy endpoint 0.0 Change in HbA1C from baseline (%) −0.2 −0.4 −0.6 −0.8 −1.0 −1.1 −1.2 −1.4 −1.4 −1.6 Figure 2. (A) Primary and secondary efficacy endpoints (PP population); (B) Change in HbA1C after 12 months of treatment (ITT population). (A) Percentage of patients achieving study endpoints in PP population; unadjusted odds ratios (95% CI): 1.65 (1.53, 1.79) for primary endpoint and 2.03 (1.83, 2.25) for secondary endpoint; both p <0.0001. (B) Mean HbA1C change (± standard error) from baseline to study endpoint in ITT population using an ANCOVA model. These post hoc analyses demonstrated that vildagliptin in combination with another OAD provides better glycemic control than any other two-agent OAD combination. After 12 months of treatment, the vildagliptin cohort exhibited a greater proportion of patients (unadjusted OR 1.65 [95% CI: 1.53, 1.79]) achieving the primary efficacy endpoint (reduction in HbA1C >0.3% without peripheral edema, hypoglycemic event, discontinuation due to a gastrointestinal event or weight gain ≥5%) and the secondary efficacy endpoint of HbA1C<7% without hypoglycemia and weight gain ≥3% from a baseline HbA1C of ≥7% (unadjusted OR 2.03 [95% CI: 1.83, 2.25]) versus all other two-agent OAD combinations. The results for this secondary efficacy endpoint confirm results from other studies, which consistently showed better responder rates with vildagliptin versus comparators, although such comparisons have limitations.14,15 The reduction in HbA1C was numerically greater with vildagliptin combinations versus other two-agent OAD combinations, as in the overall EDGE study population.10 However, the vildagliptin cohort in the Indian population showed a numerically greater reduction (1.4%) when compared with the vildagliptin cohort in the overall EDGE study population (1.2%).10 This larger reduction in HbA1C in Indian patients may be partly explained by the higher baseline HbA1C in the Indian patients. The vildagliptin cohort showed a good safety and tolerability profile without any clinically relevant trends, which further corroborates the good safety profile of vildagliptin.16,17 The study revealed that fewer patients in the vildagliptin cohort reported hypoglycemia than in the comparator cohort; the majority of patients reporting hypoglycemia were using a metformin and SU combination. This is consistent with results from a previously reported large pooled analysis of safety data, which showed that vildagliptin, as monotherapy or in combination with metformin, thiazolidinedione or an SU, is associated with significantly fewer hypoglycemic events than comparators.17 There were some limitations to our study. Because physicians were required to select any drug-based on their clinical judgment, the open study design resulted in a possible imbalance favoring the vildagliptin arm in the overall EDGE study population, although this did not seem to be the case in the Indian patients. Moreover, the patients were recruited both in specialty and routine care centers, which may have had an impact on the overall results because of poor quality and missing data that needed to be excluded from the effectiveness analyses. In addition, unlike in randomized controlled trials, reporting of AEs was based on a voluntary reporting scheme, which might have led to unnoticed or under-reported events. conclusion These post hoc analyses of the EDGE study confirmed that vildagliptin in combination with another OAD showed better overall clinical benefit versus any other two-agent OAD combination, as measured by a composite endpoint assessing effectiveness (HbA1C reduction) and tolerability (peripheral edema, Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 541
- 42. ENDOCRINOLOGY gastrointestinal events, hypoglycemiaand weight gain) in Indian patients with T2DM in a real-world setting. Contributors All authors had full access to all data, and take responsibility for the integrity of the data and accuracy of analyses. SKW and GB were involved with study design, data collection and data interpretation. SS was involved in data interpretation and drafting of the manuscript. AG was involved with data interpretation. All authors actively participated in the preparation of the manuscript and provided critical review at each step. Acknowledgments This study was funded by Novartis Pharma AG. The authors acknowledge Arvind Semwal (M. Pharm., Ph.D.), Novartis Healthcare Private Limited, Hyderabad, India, for providing writing assistance and editorial support towards the development of the manuscript. Conflicts of Interest SKW does not have any conflict of interest regarding the financial aids/disclosures nor is he on a company board as a paid member. GB is an employee of Novartis Pharma AG, and AG and SS are employees of Novartis Healthcare Private Limited. References 1. Whiting DR, Guariguata L, Weil C, Shaw J. IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract 2011;94(3):311-21. 2. Mohan V, Madan Z, Jha R, Deepa R, Pradeepa R. Diabetessocial and economic perspectives in the new Millennium. Int J Diab Dev Countries 2004;24:29-35. 3. Radha V, Mohan V. Genetic predisposition to type 2 diabetes among Asian Indians. Indian J Med Res 2007;125(3):259-74. 4. Joshi SR, Das AK, Vijay VJ, Mohan V. Challenges in diabetes care in India: sheer numbers, lack of awareness and inadequate control. J Assoc Physicians India 2008;56:443-50. 5. nzucchi SE, Bergenstal RM, Buse JB, Diamant M, I Ferrannini E, Nauck M, et al; American Diabetes Association (ADA); European Association for the Study of Diabetes (EASD). Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2012;35(6):1364-79. 6. Bosi E, Camisasca RP, Collober C, Rochotte E, Garber AJ. Effects of vildagliptin on glucose control over 24 weeks in patients with type 2 diabetes inadequately controlled with metformin. Diabetes Care 2007;30(4):890-5. 7. Garber AJ, Schweizer A, Baron MA, Rochotte E, Dejager S. Vildagliptin in combination with pioglitazone improves glycaemic control in patients with type 2 diabetes failing thiazolidinedione monotherapy: a randomized, placebocontrolled study. Diabetes Obes Metab 2007;9(2):166-74. 8. Dejager S, Schweizer A, Foley JE. Evidence to support the use of vildagliptin monotherapy in the treatment of type 2 diabetes mellitus. Vasc Health Risk Manag 2012;8:339-48. 9. Ware JH, Hamel MB. Pragmatic trials - guides to better patient care? N Engl J Med 2011;364(18):1685-7. 10. Mathieu C, Barnett AH, Brath H, Conget I, de Castro JJ, Göke R, et al. Effectiveness and tolerability of secondline therapy with vildagliptin vs. other oral agents in type 2 diabetes: a real-life worldwide observational study (EDGE). Int J Clin Pract 2013;67(10):947-56. 11. Raheja BS, Kapur A, Bhoraskar A, Sathe SR, Jorgensen LN, Moorthi SR, et al. DiabCare Asia - India Study: diabetes care in India - current status. J Assoc Physicians India 2001;49:717-22. 12. Moses CR, Seshiah V, Sahay BK, Kumar A, Asirvatham AJ, Balaji V, et al. Baseline results indicate poor glycemic control and delay in initiation and optimization of insulin therapy: results from the improving management practices and clinical outcomes in type 2 diabetes study. Indian J Endocrinol Metab 2012;16(Suppl 2):S432-3. 13. ndian Council of Medical Research. Guidelines for I Management of Type 2 Diabetes. 2005. Available at: http:// icmr.nic.in/guidelines_diabetes/guide_diabetes.htm 14. Bader G, Geransar P, Schweizer A. Vildagliptin more effectively achieves a composite endpoint of HbA1C < 7.0% without hypoglycaemia and weight gain compared with glimepiride after 2 years of treatment. Diabetes Res Clin Pract 2013;100(3):e78-81. 15. Ahrén B, Foley JE, Bosi E. Clinical evidence and mechanistic basis for vildagliptin’s action when added to metformin. Diabetes Obes Metab 2011;13(3):193-203. 16. Ligueros-Saylan M, Foley JE, Schweizer A, Couturier A, Kothny W. An assessment of adverse effects of vildagliptin versus comparators on the liver, the pancreas, the immune system, the skin and in patients with impaired renal function from a large pooled database of Phase II and III clinical trials. Diabetes Obes Metab 2010;12(6):495-509. 17. chweizer A, Dejager S, Foley JE, Kothny W. Assessing S the general safety and tolerability of vildagliptin: value of pooled analyses from a large safety database versus evaluation of individual studies. Vasc Health Risk Manag 2011;7:49-57. ■■■■ 542 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013
- 43. ENT Impact of Tonsillectomyon Quality-of-life in Children: Our Experience Neelima Gupta*, Lakshmi Vaid**, PP Singh† Abstract An important requirement of contemporary medicine is the assessment of patient benefit or change in health status resulting from medical or surgical intervention. Tonsillectomy is a commonly performed surgery in children. Its indications and benefits have been documented in the literature but to the best of our knowledge, there have been no Indian studies to measure the quality-of-life (QOL), post-tonsillectomy, in children. Objective: To assess QOL of children after tonsillectomy, with or without adenoidectomy. Study design and setting: Retrospective study in a tertiary referral center. Methodology: The sample consisted of 136 children who had undergone tonsillectomy with or without adenoidectomy over a period of two years. The parents of these children were sent a questionnaire to assess their QOL six months after the surgery. The questionnaire used was a modified version of Glasgow Children’s Benefit Inventory (GCBI), a post-intervention, health-related benefit measure. Results: Forty-four questionnaires were returned (32.2% response rate). Four questionnaires were declared invalid. Two parents reported worsening of a few symptoms, resulting in a negative score. In the remainder, the total score ranged from 2.08 to 91.6. Conclusions: Sixty-eight percent of the parents were extremely satisfied after the surgery. Overall, the parents reported change for the better in various observed aspects of the life of their children as reflected in the positive scores after intervention. Most of them reported decreased number of visits to the doctor and decreased need for antibiotic prescription, that is, there was an improvement in the ‘physical health’ aspect of the life of children. But there was no change observed in the ‘emotional and psychosocial’ aspect of behavior in children. Keywords: Quality-of-life, tonsillectomy, children T onsillectomy and adenotonsillectomy are common surgical procedures performed in children. But their indications are still variable and differ from center to center. In the past, the most frequent indication for surgery was recurrent tonsillitis. There has been a rise in obstructive sleep apnea (OSA) as a significant indication from 0% in 1978 to 19% in 1986.1 Various studies have evaluated the effect of tonsillectomy in children suffering from upper airway obstruction. This study was designed to evaluate the effect of tonsillectomy on the quality-of-life (QOL) of children, with the idea that the beneficial effects of tonsillectomy could be ascertained and more pertinent recommendations for surgery may be formulated. *Associate Professor **Professor †Professor and Head Dept. of ENT University College of Medical Sciences and GTB Hospital, Delhi Address for correspondence Dr Neelima Gupta A-304, Abhyant Apartments, 2, Vasundhara Enclave, Delhi - 96 E-mail: write2drneelima@yahoo.com As far as our knowledge goes, there are very few Indian studies that have studied the effect of tonsillectomy on the QOL of children. Methodology Study design: Retrospective study. Study area: Children operated for tonsillectomy or adenotonsillectomy in a hospital setting. Case selection: One hundred and thirty-six children consecutively operated over a period of two years were selected from records. Twelve years was taken as the upper age limit. Questionnaires were mailed to all of them with a self-addressed envelope. Only 44 parents returned questionnaires (response rate of 32%). Out of the respondents, the age group of children ranged from 4 to 12 years with the mean being 8.45 years. The malefemale ratio was 1.2:1. We adapted the questionnaire from the Glasgow Children’s Benefit Inventory (GCBI), which has 24 questions on the consequences of a specified intervention on various aspects of the child’s day-to-day life, without reference to any specific symptoms.2 The questionnaire was modified and translated into Hindi Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 543
- 44. ENT (mother tongue) andwas pretested among a group of parents prior to its administration. It was also tested for its consistency and internal validity. We also added one question (Question number 25), which asked for the parents, overall satisfaction with the intervention. The questionnaire was self-administered and was filled up by either parent of the operated child. The questions were worded to apply to child of any age. The pattern of responses assesses the child’s QOL in terms of emotion, physical health, learning and vitality. For each question, a response was given on a 5-point Likert-type rating scale, with the central point being ‘no change’ and the extremes representing ‘much better’ and ‘much worse’. Assigning the individual responses, a numerical value from –2 to +2, adding the total score and dividing by 24, calculated a summary score for the questionnaire. The score was multiplied by 50 to produce a result on a scale from –100 (maximum harm) to +100 (maximum benefit). Observation and Results Forty-four questionnaires were returned out of 136. Four were declared invalid since a few questions were unanswered in these forms. On calculating the scores, two questionnaires had a negative score of –8.33 and –20.83. The rest had positive scores ranging from 2.08 to 91.6. Responses related to questions pertaining to self-consciousness, embarrassment, easy distraction, self-esteem, confidence and self-care addressing the factor of ‘emotion’ were mostly responded to as ‘no change’. Similarly, the questions assessing change in learning, concentration, liveliness, fun with friends and leisure activities addressing the factors of ‘learning’ and ‘vitality’ were responded to as ‘no change’. Questions relating to overall life, absences from school, colds, visit to the doctor and need for antibiotic prescriptions, addressing the factor of ‘physical health’ were uniformly answered with ‘much better’ as shown in Table 1 that shows the number of parents who gave a particular response. The figures in bold indicate that this is the response ticked by the maximum number of parents. No statistically significant difference was observed in responses regarding change in food habits, sleep pattern, learning and progress of the child, as they were either answered with ‘little better’ or ‘no change’. Limitations of the study: Ideally, a pre post comparison on QOL of the patients should have been done, but due to logistic constraints a comparative study could not be undertaken. Similarly, no matched control group of 544 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 unoperated children was available. The attrition rate was very high, as only 32% respondents returned the filled up questionnaire, may be because of the socioeconomic background, lack of permanent addresses and literacy level constraints of our population. But considering that there are few Indian studies in this area, our findings add substantively to the existing knowledge regarding impact of tonsillectomy on the QOL of the children. Discussion As decisions concerning resource allocation become increasingly stringent, it is important to understand the personal impact of diseases and their treatment beyond the standard medical morbidity or functional limitations so that this can be incorporated into the decision-making process. This has led to studies pertaining to outcome measures and effect of disease and management on QOL. On review of literature, we encountered various studies that assessed the QOL before and after an intervention. We used a retrospective measure of assessment of QOL after tonsillectomy. The advantages of the retrospective approach are that it halves the burden of questionnaires for the parents, it is much more sensitive to change and it can be used in conditions for which a sizeable cohort of patients can take years to build up.2 It has been shown in a few studies that trials commonly use serial measurements by the patients at two points in time, while clinicians use the patient’s retrospective assessment of change made at one point in time. Retrospective measures were found to be more sensitive to change than serial measures and correlated more strongly with patient’s satisfaction with change.3 Therefore, we chose to use a retrospective measure. Paradise et al4 studied the efficacy of tonsillectomy for recurrent throat infection in 187 children in randomized as well as nonrandomized trials. They found that tonsillectomy with or without adenoidectomy was unequivocally effective for two years and probably for one more year in reducing the frequency and severity of episodes of throat infection. Differences between the treatment groups in regard to secondary outcome measures such as number of visits on which isolated cervical lymphadenopathy was found, number of parent reported sore-throat days and school absent days due to sore-throat, were less clear cut and of uncertain clinical importance. In our study, majority of parents reported decrease in visits to the doctor, improvement in school attendance and decrease in episodes of cold. Our study has a follow-up of only six months, so we have not studied infection rate following tonsillectomy.
- 45. ENT Table 1. Numberof Responses to the Questions Assessing Various Aspects of QOL S. No. Question Much better Little better No change Little worse Much worse 1 Overall life 8 17 14 1 0 2 Things they do 5 12 23 0 0 3 Behavior 7 12 20 1 0 4 Progress and development 8 15 16 1 0 5 Liveliness 2 19 15 3 1 6 Sleep 8 17 11 3 1 7 Food 10 14 16 0 0 8 Self-consciousness 4 4 29 2 1 9 Family harmony 7 4 27 2 0 10 Fun with friends 5 7 27 1 0 11 Embarrassment 4 5 31 0 0 12 Distractibility 3 3 31 2 1 13 Learning 6 14 17 3 0 14 Absences from school 18 8 13 0 1 15 Concentration 2 6 27 5 0 16 Irritability 5 6 24 3 2 17 Self-esteem 8 10 22 0 0 18 Happiness 4 16 19 0 1 19 Confidence 6 9 24 0 0 20 Self-care 5 7 28 0 0 21 Leisure 6 12 22 0 0 22 Colds 20 15 4 0 1 23 Visits to doctor 26 10 2 2 0 24 Need for medication 29 7 2 2 0 25 Overall satisfaction 27 9 1 2 1 The figures in bold indicate the response given by maximum number of parents. In a study comprising of 138 children, compared with children who had not undergone adenotonsillectomy, parents of the adenotonsillectomy group more frequently reported improvement in breathing, snoring, excessive daytime sleepiness and QOL, postoperatively. Parental reporting of asthma, bedwetting, concentration, school performance and intellectual or developmental progress were not statistically different between the two groups.5 In our analysis, 67.5% of the parents observed ‘no change’ in level of concentration or intellectual progress of the child after intervention. Ali and his group6 concluded from their study on 33 children, that following surgery relief of mildto-moderate sleep-disordered breathing improves behavior and functioning. In our study, 50% of the parents said they had observed no change in behavior of the child after surgery, while 30% said that the behavior had changed for the better. Pediatricians and otolaryngologists should advice parents that adenotonsillectomy most likely results in improvement in breathing, sleep and QOL but should be guarded in promising improvement in behavior and development. Some studies have shown improvement in all aspects of the life of children. Goldstein,7 in a pilot study, demonstrated a high prevalence (28%) of abnormal behavior in children undergoing tonsillectomy and adenoidectomy (T&A) for chronic upper airway obstruction. The Child Behavior Checklist (CBCL) scores significantly improved following T&A. Subclasses that showed improvement were withdrawn behavior, somatic complaints, attention problems and thought problems. Similarly, De Serres et al,8 in their study of 101 children found large, moderate and small improvements in QOL in 74.5%, 6.1% and 7.1% Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 545
- 46. ENT of children, respectively.Sleep disturbance, caregiver concern and physical suffering were the most improved domains, although significant changes also occurred for speech and swallowing problems, emotional disturbance and activity limitations. However, in our study, 57.5% and 67.5% parents observed no change in the child’s activities and his interaction with friends, respectively as shown in Table 1. In their study on 64 children who underwent tonsillectomy, Goldstein et al9 found that behavioral and emotional difficulties were found in children with sleep-disordered breathing before treatment and improved after intervention. They used the CBCL total problem T scores as their outcome measure. Flanary10 studied both short-term and long-term effect of adenotonsillectomy on general and disease specific QOL in children suffering from upper airway obstruction secondary to adenotonsillar hypertrophy. This study used both Children’s Health Questionnaire Parent Form-28 and OSA-18 QOL measures and found that CHQPF-28 psychosocial summary scores did not show significant improvement in the short-term or long-term results. Mitchell11 also confirmed that caregiver concerns were reduced after tonsillectomy and the domain with the most significant improvement was sleep disturbance, while least improvement was seen in emotional distress. We observed in our study that 42.5% parents reported ‘a little better’ sleep pattern in their children, while 27.5% parents observed no change in sleep pattern. Conclusion Tonsillectomy definitely leads to an improvement in the QOL in children and 68% of parents were extremely satisfied with the surgical outcome. Almost all the parents reported decrease in visits to the doctor and in antibiotic prescription but there were no significant changes observed in the emotional aspects and personality of the children. The low response rate led to a small sample size so we could not apply any tests of statistical significance. A control group of children who are followed up with no surgical intervention will help in concluding that improvement is because of the surgical intervention. Also our results can only give insight into short-term QOL improvements because we thought that if we send the questionnaires any later it will lead to further reduction in response rate. However, these limitations notwithstanding we conclude that tonsillectomy has a positive impact on QOL of children. What we know: There are studies available about the effects of tonsillectomy on child behavior and QOL, in western literature. What this study adds: Tonsillectomy is a frequently performed surgery in India, but very few outcome evaluation studies are available. Our study adds to the knowledge that tonsillectomy has a positive impact on the physical health of the child, while there are none or little changes observed in the emotional and behavioral aspects of the child’s life. References 1. Rosenfeld RM, Green RP. Tonsillectomy and adenoidectomy: changing trends. Ann Otol Rhinol Laryngol 1990;90(3 Pt 1):187-91. 2. Kubba H, Swan IR, Gatehouse S. The Glasgow Children’s Benefit Inventory: a new instrument for assessing healthrelated benefit after an intervention. Ann Otol Rhinol Laryngol 2004;113(12):980-6. 3. Fischer D, Stewart AL, Bloch DA, Lorig K, Laurent D, Holman H. Capturing the patients view of change as a clinical outcome measure. JAMA 1999;282(12):1157-62. 4. Paradise JL, Bluestone CD, Bachman RZ, Colborn DK, Bernard BS, Taylor FH, et al. Efficacy of tonsillectomy for recurrent throat infection in severely affected children. N Engl J Med 1984;310(11):674-83. 5. Constantin E, Kermack A, Nixon GM, Tidmarsh L, Ducharme FM, Brouillette RT. Adenotonsillectomy improves sleep, breathing and quality of life but not behavior. J Pediatr 2007;150(5):540-6, 546.e1. 6. Ali NJ, Pitson D, Stradling JR. Sleep disordered breathing: effects of adenotonsillectomy on behaviour and psychological functioning. Eur J Pediatr 1996;155(1):56-62. 7. Goldstein NA, Post JC, Rosenfeld RM, Campbell TF. Impact of tonsillectomy and adenoidectomy on child behavior. Arch Otolaryngol Head Neck Surg 2000;126(4):494-8. 8. De Serres LM, Derkay C, Sie K, Biavati M, Jones J, Tunkel D, et al. Impact of adenotonsillectomy on quality of life in children with obstructive sleep disorders. Arch Otolaryngol Head Neck Surg 2002;128(5):489-96. 9. Goldstein NA, Fatima M, Campbell TF, Rosenfield RM. Child behavior and Quality of life before and after tonsillectomy and adenoidectomy. Arch Otolaryngol Head Neck Surg 2002;128(7):770-5. 10. Flanary VA. Long-term effect of adenotonsillectomy on quality of life in pediatric patients. Laryngoscope 2003;113(10):1639-44. 11. Mitchell RB, Kelly J, Call E, Yao N. Quality of life after adenotonsillectomy for obstructive sleep apnea in children. Arch Otolaryngol Head Neck Surg 2004;130(2):190-4. ■■■■ 546 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013
- 47. infectious diseases A RareCase of Angioimmunoblastic Lymphoma: A Report Ramesh B*, Mohammed Moinuddin Nawazi**, Shyamala K† Abstract Angioimmunoblastic lymphoma is a rare type of T-cell lymphoma. A 60-year-old male presented with complaints of cough with expectoration and chest pain associated with exertional dyspnea since two months. There was history of significant loss of weight. Chest X-ray showed large opacity suggestive of mass with ill-defined margins seen in left posterosuperior aspect overlapping the posterior aspect of aortic arch and proximal descending aorta. CT guided biopsy showed angioimmunoblastic T-cell lymphoma. This case is presented for its rarity. Keywords: Angioimmunoblastic lymphoma, non-Hodgkins lymphoma A ngioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is a type of peripheral T-cell lymphoma that is clinically characterized by high fever and generalized lymphadenopathy. Approximately 40-50% of patients also have cutaneous involvement. As the disorder progresses, hepatosplenomegaly, hemolytic anemia and polyclonal hypergammaglobulinemia may develop. a history of significant loss of weight and he is a chronic smoker consuming 24 beedies/day since last 20 years. There was history of hemoptysis. Patient not a known diabetic or hypertensive or has history of hypothyroidism or tuberculosis in the past. No history of high-risk behavior. The exact incidence of AILD is not known. In the United States, approximately 1-2% of non-Hodgkin lymphomas are associated with AILD. In one case series in Korea, one of 78 cases of lymphoma was diagnosed as AILD. In a series of 3,194 cases of lymphoma in Japan, 2.35% were diagnosed as AILD. Moderately built and poorly nourished, no pallor, no icterus, no cyanosis, no lymphadenopathy, no pedal edema, clubbing+ Grade ΙΙ, prominent dilated veins over the anterior chest wall B/L+, no thyroid enlargement blood pressure (BP): 126/88 mmHg, pulse: 82 bpm, respiratory rate: 26 bpm, temperature: 97.8°F; FSpO2: 94% on room air; jugular venous pressure (JVP) is not raised. Biopsies of the bone marrow, lymph node and skin are key in diagnosing AILD. Many agents have been used to treat AILD, but none has proved universally or consistently effective. CASE REPORT A 60-year-old male unmarried fruit vendor presented to OPD with complaints of cough with expectoration and chest pain since two months which had increased since last one week. Chest pain was associated with exertional dyspnea since two months. Patient has *Associate Professor **Junior Resident †Assistant Professor Dept. of Medicine Dr BR Ambedkar Medical College, Bangalore On Examination Respiratory System Inspection Trachea appeared to be in midline. Respiratory movements were decreased in left interscapular, infrascapular and infra-axillary areas. Apical impulse was located in the 5th intercostal space half an inch medial to the mid clavicular line. Engorged veins were present over the anterior chest wall. Crowding of the ribs was noted over the left side. Palpation Decreased chest movements in left infrascapular, interscapular and infra-axillary areas. Vocal fremitus was decreased in these areas. Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 547
- 48. infectious diseases Percussion USG Chest Impairednote was present in left infrascapular, interscapular and infra-axillary areas. Hyperresonant note was present in right infraclavicular and mammary areas. Cardiac dullness was normal. Liver dullness was located in the right 6th intercostal space (ICS). Sternum was resonant on percussion. Left lower lobe collapse, elevated left lobe of diaphragm secondary to the left lower lobe collapse; no pleural effusion (Fig. 1). Auscultation Decreased breath sounds were heard in left infrascapular, interscapular and infra-axillary areas. Normal vesicular breath sounds were heard in all areas. No added sounds, vocal resonance was decreased in left infrascapular, interscapular and infra-axillary areas. Cardiovascular system (CVS): Apical impulse was located in the normal position. S1, S2 were heard. Per abdomen: Soft and no organomegaly central nervous system (CNS): No abnormality was detected. X-ray Chest-Pa View Large homogenous opacity with irregular peripheral border was seen in the left upper/mid zone. Left lower zone hazy ? Effusion ? Large left hilar mass lesion. X-ray Chest Lateral View Large opacity suggestive of mass with ill-defined margins seen in left posterosuperior aspect overlapping the posterior aspect of aortic arch and proximal descending aorta. Inferiorly there was a opacity with sharp and mildly convex anterior margins, s/o left lower lobe collapse- likely due to compression of left lower lobe bronchus by above mentioned mass. Complete Blood Picture Hemoglobin (Hb)-14.6 g/dl, total leukocyte count (TLC)-23,400 cells/mm3, platelets-7.46 lac/mm3, erythrocyte sedimentation rate (ESR)-74 mm/1st hour, N78L24M05E03. Renal Function Tests Blood urea: 14 mg/dl, serum creatinine: 0.7 mg/dl, serum electrolytes: Na+ 130 mEq/l, K+-3.3 mEq/l, Cl--96 mEq/l. a b Figure 1. USG chest showing left lower lobe collapse with elevated left lobe of diaphragm. 548 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 Figure 2. Histopathalogy: USG-guided FNAC (a) and CT-guided biopsy (b).
- 49. infectious diseases Routine urineexamination: No albumin/no sugar/no pus cells or epithelial cells. Retroviral status: Negative, thyroid profile: Normal. Liver Function Tests Total serum bilirubin: 0.2 mg/dl, indirect bilirubin: 0.2 mg/dl, total protein: 5.8 g/dl, serum albumin: 3.3 g/dl, serum globulin: 2.5 g/dl, serum glutamic oxaloacetic transaminase (SGOT): 25 IU/l, serum glutamic pyruvic transaminase (SGPT): 56 IU/l, alkaline phosphatase (ALP): 47 IU/l. Sputum for Examination Acid-fast bacilli (AFB) was negative, malignant cells was negative, Gram’s stain was negative. ECG: Incomplete RBBB USG abdomen: Left dome of diaphragm was elevated. No other sonological abnormalities. USG-guided FNAC Inconclusive because of the paucicellularity. Possibility of a neoplasm of germ cell origin only could be suggested. Histopathology Angioimmunoblastic T-cell lymphoma. Angioinvasive carcinoma. Poorly differentiated carcinoma. DIFFERENTIAL DIAGNOSIS ÂÂ Neurogenic tumors ÂÂ Paraspinal abscess ÂÂ Multiple myelomas ÂÂ Disseminated lymphoma and metastatic carcinoma ÂÂ Extramedullary hemopoietic tissue ÂÂ Anterior thoracic meningocele ÂÂ Traumatic wedge compression fracture of a vertebral body with hematoma formation ÂÂ Dilated esophagus ÂÂ Aorta unfolded, dilated or aneurysmal ÂÂ Neuroenteric cyst ÂÂ Enteric cyst ÂÂ Hiatus hernia ÂÂ Bochdalek hernia ÂÂ Pseudopancreatic cyst ÂÂ Extramedullary hemopoietic system ÂÂ Angioimmunoblastic lymphoma DISCUSSION In 1974, Frizzera et al1 described AILD. AILD may represent a spectrum of disease ranging from a hyperplastic but still benign immune reaction to frank malignant lymphoma. Because clonal expansion of T cells has been demonstrated in most but not all cases of AILD, the following three subclassifications have been introduced: ÂÂ AILD with no evidence of clonal lymphoid proliferation ÂÂ AILD-type dysplasia with inconsistent findings regarding the clonality of the proliferating cells ÂÂ AILD-type lymphoma with strong evidence of clonality by immunohistochemical tests, rearrangement analysis and cytogenetic studies. Krenacs et al have suggested that the phenotype of neoplastic cells in angioimmunoblastic T-cell lymphoma appears consistent with the phenotype of activated follicular B-helper T cells.2 It has become clear that AILD is a clonal T-cell disorder involving deregulation of B-cells and endothelial cells against a background involving a unique malignant microenvironment. Evidence exists that AILD develops in a serial fashion. The initial reaction may be an unbalanced immune response to an unknown antigen. This stage is followed by an oligoclonal phase that is driven by persistence and ineffective handling of the primary and initial stimulus. In AILD, the factors that result in the serial evolution into malignant lymphoma have yet to be defined. Patients frequently pass through a phase of atypical immune reactions, such as an allergic drug reaction or an allergic reaction to an arthropod bite. Latent viral infection may also be involved. AILD, specifically angioimmunoblastic T-cell lymphoma, is mainly derived from CD2+ CD3+ CD4+ CD5+ CD7- mature T-helper cells with varying expression and partial loss of detectable CD4. Dunleavy et al noted that over expression of the chemokine CXCL13 and vascular endothelial growth factor-A in angioimmunoblastic T-cell lymphoma suggests that it may be derived from follicular helper T cells.3 Murakami et al reported that the oncogene c-Maf was expressed in the majority of angioimmunoblastic T-cell lymphomas studied.4 Tripodo et al have suggested that mast cells have a role in the proinflammatory microenvironment of AILD.5 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 549
- 50. infectious diseases They observedthat mast cells, which preferentially occurred in AILD cases, directly synthesized interleukin-6 and correlated with the presence of interleukin-17-producing T cells. Patients with Sjögren syndrome are at increased risk for developing lymphoma. Although, most lymphomas in these patients are of the B-cell variety, AILD constitutes the majority of T-cell lymphomas associated with Sjögren syndrome.6 The female-to-male ratio in AILD remains uncertain. In 2000, in a series of 10 patients, Martel et al reported seven women and three men.7 In 1995, Siegert et al reported a female-to-male ratio of 1:1.4 in a series of 62 patients.8 Although, AILD has been reported in children, most patients are middle-aged or elderly. Siegert et al reported a median patient age of 64 years (range, 21-87 years) in a series of 62 patients.8 Medications linked to the induction of AILD include salazosulfapyridine, azithromycin and doxycycline. The exact incidence of AILD is not known. In the United States, approximately 1-2% of non-Hodgkin lymphomas are associated with AILD. In one case series in Korea, one of 78 cases of lymphoma was diagnosed as AILD. In a series of 3,194 cases of lymphoma in Japan, 2.35% were diagnosed as AILD. AILD usually starts in a nonspecific fashion. Clinical manifestations are typical of lymphoma and may include the following: All organ systems can be affected by AILD. Typical findings at presentation include the following: ÂÂ Skin rash (50% of cases) ÂÂ Pruritus (30%) ÂÂ Edema (40%) ÂÂ Pleural effusion (40%) ÂÂ Arthritis (20%) ÂÂ Ascites (25%) Skin involvement in AILD manifests as a vascular reaction pattern rash that can resemble a viral exanthem, a toxic-mediated erythema, or a drug reaction. It can manifest as erythroderma or with pruritus that is intense and dermatitis herpetiformislike lesions. Ferran et al suggested that the ‘deck-chair sign’ (i.e., rash with sparing of skin creases) is specific for cutaneous involvement by angioimmunoblastic T-cell lymphoma.11 AILD with scleromyxedemalike lesions and serum monoclonal protein has been reported,12 as have subcorneal pustules and deep dermal-hypodermal nodules13 and toxic epidermal necrolysis.14 Pulmonary findings are varied and include hypoxemia. Some patients have interstitial pneumonia or bronchopneumonia. Patients with bronchopneumonia can have opportunistic infections, such as Pneumocystis jiroveci pneumonia; a case of cytomegalovirus infection has also been reported. Jarrett et al reported a case of shortness of breath and peripheral edema.15 Goenka et al described a case of angioimmunoblastic lymphadenopathy with multiple polyps of the gastrointestinal tract. The patient presented with fever, abdominal mass, ascites, diarrhea, generalized lymphadenopathy, anemia and marked peripheral eosinophilia.16 ÂÂ Maculopapular rashes (these can resemble a viral rash) ÂÂ Seropositive polyarthritis ÂÂ Fever ÂÂ Pruritus ÂÂ Lymphadenopathy ÂÂ Night sweats ÂÂ Weight loss Patients with AILD may exhibit laboratory findings characteristic of autoimmune disease, such as the following: ÂÂ Edema ÂÂ Circulating immune complexes Patients can present with unusual infections. ÂÂ Antismooth muscle antibodies AILD can mimic tuberculosis. Singh et al reported a case of AILD with pulmonary involvement that was initially mistaken for tuberculosis based on fine-needle aspiration cytology (FNAC) and was treated with antituberculous therapy for three months.9 ÂÂ Rheumatoid factor ÂÂ Autoimmune hemolysis ÂÂ Cold agglutinins ÂÂ Paraproteinemia ÂÂ Anticardiolipin antibodies ÂÂ Rheumatoid factor (less common) ÂÂ Cryoglobulins (less common). Hosoki et al described angioimmunoblastic T-cell lymphoma developing with lymphocytic pleural effusion.10 550 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013
- 51. infectious diseases Other bloodchemistry values that can be abnormal include the following: ÂÂ FSR (almost all cases) ÂÂ Lactate dehydrogenase (LDH) level (commonly increased) ÂÂ Polyclonal gammaglobulins (common). Radiographs and CT scans can demonstrate lymphadenopathy. They may also demonstrate pulmonary abnormalities, such as pleural effusions and multiple opacities, predominantly basal, of variable size. Radiographic findings include bilateral mediastinal and hilar lymphadenopathy, pleural effusion, interstitial shadow, alveolar shadow and atelectasis. Diffuse CT contrast enhancement of cervical lymph nodes can aid in diagnosing angioimmunoblastic lymphadenopathy. Magnetic resonance imaging (MRI) of bone marrow can demonstrate angioimmunoblastic lymphadenopathy. Biopsies of the bone marrow, lymph node and skin are key in diagnosing AILD. AILD is diagnosed by a positive biopsy result obtained from an affected lymph node, although sometimes, biopsy results are only suggestive of AILD, not diagnostic. In patients with ascites (25% of cases), paracentesis with cytologic examination of ascitic fluid is indicated. The Ann Arbor staging system uses both the number of sites of involvement and the presence of disease above or below the diaphragm. It defines the following 4 stages of disease: ÂÂ Stage I: Involvement of a single lymph node region (I) or a single extranodal site (IE). ÂÂ Stage II: Involvement of two or more lymph node regions on the same side of the diaphragm (II) or localized involvement of an extralymphatic site (IIE). ÂÂ Stage III: Involvement of lymph node regions on both sides of the diaphragm (III) and localized involvement of an extralymphatic site (IIIE) or spleen (IIIs) or both (IIIEs). ÂÂ Stage IV: Diffuse or disseminated involvement of one or more extralymphatic organs with or without associated lymph node involvement; localized involvement of liver or bone marrow is also considered Stage IV. Patients are divided into two subsets according to the absence (subset A) or presence (B) of systemic symptoms. Fever of no evident cause, night sweats, and weight loss of more than 10% of the patient’s body weight are considered systemic symptoms. Even though itching is frequently present, it should not be considered a systemic symptom. Bulky disease (e.g., a lesion of 10 cm or more in the longest diameter) is designated by appending ‘X’ to the stage designation. Extranodal involvement is identified by the following modifiers: ÂÂ O - Bone ÂÂ L - Lung ÂÂ D - Skin Corticosteroids are first-line agents for angioimmunoblastic lymphoma.17 Prednisone may be used alone or in combination with cyclophosphamide, vincristine or both. The combination of cyclophosphamide, hydroxydaunorubicin, oncovin (vincristine) and prednisone (CHOP) has been used before or after prednisone and with or without interferon-a as consolidation. In retrospective analyses, CHOP and CHOP-based regimens have produced complete remission rates of about 60%.18,19 High-dose chemotherapy followed by autologous bone marrow transplantation represents a promising new treatment modality for patients with advanced lymphoma and may conceivably be useful in AILD. Rodríguez et al described prolonged survival for patients with angioimmunoblastic T-cell lymphoma after high-dose chemotherapy and autologous stem cell transplantation.20 Shinohara et al reported durable remission after the administration of rituximab for Epstein–Barr virus (EBV)-negative, diffuse large B-cell lymphoma that developed after autologous peripheral blood stem cell transplantation for angioimmunoblastic T-cell lymphoma.21 Dunleavy et al have suggested that novel therapeutic strategies that include immunomodulation with agents such as cyclosporine and angiogenesis inhibition with drugs such as bevacizumab may prove helpful.3 There are reports of sustained remission from angioimmunoblastic T-cell lymphoma induced by alemtuzumab.22,23 In a few cases, the removal of the spleen has improved the symptoms of AILD or induced remission. Nakashima et al reported successful coil embolization of a ruptured hepatic aneurysm in a patient with polyarteritis nodosa accompanied by angioimmunoblastic T-cell lymphoma.24 Patients must be monitored for infections and must be educated about the importance of seeking medical care if they develop a fever or other constitutional symptoms. Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 551
- 52. infectious diseases Overall, AILDhas a moderately aggressive course, with occasional spontaneous remissions or protracted responses to therapy. The median survival is 24 months. AILD can evolve into high-grade lymphomas of T- or B-cell type, EBV-positive B-cell lymphomas and chronic lymphatic leukemia, among other kinds of lymphoma and leukemia. Most patients eventually die of infections due to immunologic compromise. REFERENCES 1. Frizzera G, Moran EM, Rappaport H. Angioimmunoblastic lymphadenopathy with dysproteinaemia. Lancet 1974;1(7866):1070-3. 2. Krenacs L, Schaerli P, Kis G, Bagdi E. Phenotype of neoplastic cells in angioimmunoblastic T-cell lymphoma is consistent with activated follicular B helper T cells. Blood 2006;108(3):1110-1. 3. Dunleavy K, Wilson WH, Jaffe ES. Angioimmunoblastic T cell lymphoma: pathobiological insights and clinical implications. Curr Opin Hematol 2007;14(4):348-53. 4. Murakami YI, Yatabe Y, Sakaguchi T, Sasaki E, Yamashita Y, Morito N, et al. c-Maf expression in angioimmunoblastic T-cell lymphoma. Am J Surg Pathol 2007;31(11):1695-702. 5. Tripodo C, Gri G, Piccaluga PP, Frossi B, Guarnotta C, Piconese S, et al. Mast cells and Th17 cells contribute to the lymphoma-associated pro-inflammatory microenvironment of angioimmunoblastic T-cell lymphoma. Am J Pathol 2010;177(2):792-802. 6. Saito M, Fukuda T, Shiohara T, Homori M. Angioimmunoblastic T-cell lymphoma: a relatively common type of T-cell lymphoma in Sjögren’s syndrome. Clin Exp Rheumatol 2005;23(6):888-90. 12. Rahmani R, Brenner S, Krakowski A, Lipitz R, Ilie B, Behar AJ. Angioimmunoblastic lymphadenopathy with scleromyxedema-like lesions and serum monoclonal protein. Isr J Med Sci 1983;19(3):235-9. 13. Sellier S, Levesque H, Courville P, Joly P. [Cyclophosphamide-induced neutrophilic disease in a patient with angioimmunoblastic lymphadenopathy and myelodysplastic syndrome]. Ann Dermatol Venereol 2006;133(5 Pt 1):459-62. 14. Jones B, Vun Y, Sabah M, Egan CA. Toxic epidermal necrolysis secondary to angioimmunoblastic T-cell lymphoma. Australas J Dermatol 2005;46(3):187-91. 15. Jarrett R, Walk N, Castellano-Sanchez AA, Kreisel FH. A 68-year-old man with shortness of breath and peripheral edema. Angioimmunoblastic T-cell lymphoma. Arch Pathol Lab Med 2006;130(2):219-22. 16. Goenka MK, Vaiphei K, Nagi B, Sriram PV, Joshi K, Kochhar R. Angioimmunoblastic lymphadenopathy: an etiology for gastrointestinal lymphomatous polyposis. Am J Gastroenterol 1996;91(6):1236-8. 17. Matsumiya H, Arai A, Nagai A. [A case of angioimmunoblastic T-cell lymphoma with interstitial shadow which disappeared after injection of hydrocortisone]. Nihon Kokyuki Gakkai Zasshi 2006;44(7):537-40. 18. Alizadeh AA, Advani RH. Evaluation and management of angioimmunoblastic T-cell lymphoma: a review of current approaches and future strategies. Clin Adv Hematol Oncol 2008;6(12):899-909. 19. Pautier P, Devidas A, Delmer A, Dombret H, Sutton L, Zini JM, et al. Angioimmunoblastic-like T-cell non Hodgkin’s lymphoma: outcome after chemotherapy in 33 patients and review of the literature. Leuk Lymphoma 1999;32 (5-6):545-52. 7. Martel P, Laroche L, Courville P, Larroche C, Wechsler J, Lenormand B, et al. Cutaneous involvement in patients with angioimmunoblastic lymphadenopathy with dysproteinemia: a clinical, immunohistological, and molecular analysis. Arch Dermatol 2000;136(7):881-6. 20. Rodríguez J, Conde E, Gutiérrez A, Arranz R, Gandarillas M, Leon A, et al. Prolonged survival of patients with angioimmunoblastic T-cell lymphoma after high-dose chemotherapy and autologous stem cell transplantation: the GELTAMO experience. Eur J Haematol 2007;78(4):290-6. 8. Siegert W, Nerl C, Agthe A, Engelhard M, Brittinger G, Tiemann M, et al. Angioimmunoblastic lymphadenopathy (AILD)-type T-cell lymphoma: prognostic impact of clinical observations and laboratory findings at presentation. The Kiel Lymphoma Study Group. Ann Oncol 1995;6(7):659-64. 21. Shinohara A, Asai T, Izutsu K, Ota Y, Takeuchi K, Hangaishi A, et al. Durable remission after the administration of rituximab for EBV-negative, diffuse large B-cell lymphoma following autologous peripheral blood stem cell transplantation for angioimmunoblastic T-cell lymphoma. Leuk Lymphoma 2007;48(2):418-20. 9. Singh MK, Solanki RN, Shah NJ, Tanna D, Patel DR, Desai IM. Angioimmunoblastic lymphadenopathy with dysproteinemia: thoracic involvement. Indian J Chest Dis Allied Sci 2004;46(2):125-8. 22. Halene S, Zieske A, Berliner N. Sustained remission from angioimmunoblastic T-cell lymphoma induced by alemtuzumab. Nat Clin Pract Oncol 2006;3(3):165-8; quiz 169. 10. Hosoki K, Okada S, Ichinohasama R, Yamaguchi M, Uchiyama B, Maeyama T. Angioimmunoblastic T-cell lymphoma developed with lymphocytic pleural effusion. Intern Med 2007;46(11):739-42. 23. Amengual JE, Raphael BG. Sustained, durable responses with alemtuzumab in refractory angioimmunoblastic T-cell lymphoma. Leuk Lymphoma 2010;51(7):1347-50. 11. Ferran M, Gallardo F, Baena V, Ferrer A, Florensa L, Pujol RM. The ‘deck chair sign’ in specific cutaneous involvement by angioimmunoblastic T cell lymphoma. Dermatology 2006;213(1):50-2. 552 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 24. Nakashima M, Suzuki K, Okada M, Takada K, Kobayashi H, Hama Y. Successful coil embolization of a ruptured hepatic aneurysm in a patient with polyarteritis nodosa accompanied by angioimmunoblastic T cell lymphoma. Clin Rheumatol 2007;26(8):1362-4.
- 53. INTERNAL MEDICINE Cerebral VenousThrombosis Due to Abrin Toxicity: A Case Report KV Rajalakshmi*, G Shivkumar**, S Karthikeyan, V Punitha, K Sangeetha Abstract Abrus precatorius (jequirity bean) is a common cause of accidental or intentional poisoning in the tropics. The data on exact incidence of abrus poisoning is largely insufficient in our country, due to lack of reporting. The estimated lethal dose for humans is 0.1-1 µg/kg. The toxic component is the protein abrin that causes widespread endothelial damage. Abrin causes a variety of manifestations like hemorrhagic gastroenteritis with erosions, hemolysis, acute renal damage, dyselectrolytemia, hepatotoxicity with elevated liver enzymes and seizures. Apart from the common manifestation of hemorrhagic gastroenteritis, patients experiencing mental status perturbations have been identified and documented earlier. There have been previous reports of elevated intracranial tension (ICT) in abrus poisoning, however, the exact cause for this phenomenon had not been elucidated. We herein report a case of intentional A. precatorius poisoning in a young girl that caused cerebral venous thrombosis (CVT). Keywords: Abrus precatorius poisoning, abrin poisoning, cerebral venous thrombosis, increased intracranial tension A brus precatorius seeds are often ingested with suicidal intent in India, however, data on exact incidence is lacking. Abrin is a potentially fatal toxalbumin obtained from the seeds of A. precatorius (jequirity bean, gundumani [Tamil]), which is similar in structure and properties to ricin.1 We herein report a case of A. precatorius poisoning with cerebral venous sinus thrombosis and intracerebral bleed that has never been documented earlier. CASE REPORT An 18-year-old girl, a school dropout, was brought with an alleged history of consumption of approximately 10-15 crushed abrus seeds on July 31, 2013 at 22:00 hours, following a family dispute. She was given local indigenous treatment and taken to Taluk HQ Hospital, Ulundurpet at 08:50 hours on August 1, 2013. There she was instituted emergency care and subsequently transferred to the Govt. Villupuram Medical College, at 19:35 hours, the same day. Upon arrival, the patient was *Associate Professor **Assistant Professor Dept. of Internal Medicine Govt. Villupuram Medical College, Villupuram,Tamil Nadu Address for correspondence Dr (Major) G Shivkumar Assistant Professor Dept. of Internal Medicine Govt. Villupuram Medical College, Villupuram, Tamil Nadu - 605 601 E-mail: majorshivk@yahoo.com dehydrated and had recurrent diarrhea and vomiting. She was actively resuscitated with oral and intravenous fluid replacement. Her hydration status improved and vital parameters were stabilized. Her blood counts, biochemical analysis and liver function tests (LFTs) were within normal limits. Serum Na+ 158 mEq/l, K+ 2.3 mEq/l, Cl- 126 mEq/l, HCO3- 26 mEq/l. Patient’s vomit improved but diarrhea persisted despite supportive treatment. On Day 4, patient developed bloody diarrhea for which 1 unit of compatible group blood was transfused. Biochemical analysis revealed serum creatinine of 1.1 mg%, Na+ 143 mEq/l, K+ 2.4 mEq/l, Cl- 110 mEq/l and HCO3- 23 mEq/l. Repeat LFTs including prothrombin time/INR (international normalized ratio) were within normal limits. Her blood pressure was 120/86 mmHg and urine output was 2,100 ml/24 hours. On Day 6, the patient experienced one episode of generalized tonic-clonic seizures. She was managed with intravenous loading and maintenance dose of phenytoin. She became progressively drowsy thereafter with persistent depressed mentation. Fundus examination revealed bilateral papilledema. A noncontrast computed tomography (CT) scan of brain revealed a hyperdense lesion with perilesional edema in left occipital region with hyperdense appearance of sagittal sinus (filled delta sign). The features were suggestive of superior sagittal sinus thrombosis with hemorrhage in left occipital lobe. CT contrast study was advised. Anti-edema and anticoagulant treatment with unfractionated heparin commenced. Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 553
- 54. INTERNAL MEDICINE On furtherfollow-up, despite adequately titrated doses of more than two anticonvulsants, the patient had recurrent seizures on Days 7 through 12. She also developed right-sided hemiparesis with left gaze preference. Patient’s blood glucose and renal values were not much altered. On Day 13, she showed signs of recovery and seizures stopped. ECG revealed a normal sinus rhythm and was within normal limits. Her platelet counts were consistently >2,00,000/mm3 and coagulation profile showed a normal value for prothrombin time and INR, however, activated partial thromboplastin time (aPTT) was prolonged (Control 24.9 test -29.5). D-dimer was 1,270 ng/ml (elevated), familial defective apolipoprotein B-100 (FDB) was within normal limits. Lupus anticoagulant was negative, aticardiolipin titer was normal. On Day 14, a magnetic resonance imaging (MRI) scan of the brain with magnetic resonance venography (MRV) and magnetic resonance arteriography (MRA) were done, which revealed superior sagittal sinus thrombosis and left occipital hemorrhagic infarct (Figs. 1 and 2). On Day 15, neurosurgical consult was obtained, wherein she was advised decompressive surgery for the hematoma and increased intracranial tension (ICT). Patient was referred to a superspecialty surgical center on the same day. On further follow-up, she was admitted to a tertiary care center on the same date. The patient underwent a decompressive left hemicraniectomy for elevated ICT and was placed on supported ventilation in intermediate care unit (IMCU). Patient presently has residual right hemiparesis and aphasia and is on follow-up. DISCUSSION Figure 1. Gradient sequence MR showing hemorrhagic blood products along left parieto-occipital region. Figure 2. MRV sequence showing absent flow signal intensity in superior sagittal sinus. 554 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 Poisoning from A. precatorius is attributed to the protein abrin that acts by inhibiting protein synthesis intracellularly, thereby causing cell death.1 The estimated human lethal dose is 0.1-1 mg/kg. Many of the features observed in abrin poisoning can be explained by abrin-induced endothelial cell damage, which causes an increase in capillary permeability with consequent fluid and protein leakage and tissue edema (the so-called vascular leak syndrome).1 Abrus poisoning results in a variety of clinical manifestations like hemorrhagic gastroenteritis with erosions, hemolysis, acute renal damage, dyselectrolytemia, hepatotoxicity with elevated liver enzymes and seizures.2 Previous literature also document rare manifestations like increased ICT with papilledema and autoimmune demyelination.2,3 Subrahmanyam et al have recommended routine fundus examination in such patients to detect the same.2 We herein stress the need for brain imaging in such situations. In a series of 131 patients who presented with papilledema and clinically suspected idiopathic intracranial hypertension, 10% had cerebral venous thrombosis (CVT) when MRI/MRV was
- 55. INTERNAL MEDICINE performed.4 Imagingof the cerebral venous system has been recommended for all patients with the clinical picture of idiopathic intracranial hypertension, because the distinction between CVT and idiopathic intracranial hypertension has important prognostic and treatment implications, and the yield of imaging is significant.4,5 However, abrin poisoning resulting in CVT has never been documented earlier. We performed a literature review using search terms in PubMed: (‘Abrin toxicity’ OR ‘abrin poisoning’ OR ‘Abrus precatorius poisoning’) and randomized trial: (‘Abrin poisoning’ OR ‘Abrus precatorius poisoning’) and could not find a previous reporting of CVT in abrus poisoning. Considering this fact and the frequent occurrence of increased ICT in these patients, we hypothesize that undetected CVT is probably the cause for this phenomenon. The mechanism by which abrus causes CVT is still a matter of speculation and requires indepth chemoanalysis of its components and further histopathologic or immunologic research to elucidate the bioprocess. A possible explanation could be due to widespread vascular endothelial cell damage and a procoagulant state like dehydration. In our case, although dehydration could be implicated as a potential cause, patient was well-hydrated with adequate urine output. Furthermore, it cannot account for occurrence of increased ICT in other patients documented previously.2 The management is purely supportive since there is no specific antidote.6 If early first aid is instituted by way of gastric lavage and absorbents (activated charcoal), the outcome is favorable. Adequate hydration and maintenance of optimal urine output is desirable to avoid acute kidney injury. Delay in institution of treatment worsens prognosis. Also such patients should be ideally placed under close observation for a minimum period of 72 hours, since the toxic features of abrin can manifest late.6 CONCLUSION A. precatorius poisoning is a common occurrence in the Indian subcontinent. The toxic component is abrin that causes cell lysis by inhibiting protein synthesis. Cerebral venous sinus thrombosis has never been reported in abrus poisoning, although the occurrence of increased ICT has been documented. The objective of this case report is to create awareness about this complication and to anticipate it when dealing with such patients. REFERENCES 1. Dickers KJ, Bradberry SM, Rice P, Griffiths GD, Vale GA. Abrin poisoning. Toxicol Rev 2003;22(3):137-42. 2. Subrahmanyam D, Mathew J, Raj M. An unusual manifestation of Abrus precatorius poisoning: a report of two cases. Clin Toxicol (Phila) 2008;46(2):173-5. 3. Sahoo R, Hamide A, Amalnath SD, Narayana BS. Acute demyelinating encephalitis due to Abrus precatorius poisoning - complete recovery after steroid therapy. Clin Toxicol (Phila) 2008;46(10):1071-3. 4. Lin A, Foroozan R, Danesh-Meyer HV, De Saivo G, Savino PJ, Sergott RC. Occurrence of cerebral venous sinus thrombosis in patients with presumed idiopathic intracranial hypertension. Ophthalmology 2006;113(12):2281-4. 5. Biousse V, Ameri A, Bousser MG. Isolated intracranial hypertension as the only sign of cerebral venous thrombosis. Neurology 1999;53(7):1537-42. 6. Arena JM, Thomas CC. Abrus poisoning – toxicology, symptoms and treatments. Springfield, IL 1986:p.496. ■■■■ A new observational study published online October 15 in the International Journal of Clinical Practice that followed men with hypogonadism taking testosterone for five years-the longest treatment duration to date-showed improvements in lipids, blood pressure and blood glucose levels, thereby ameliorating a number of components of the metabolic syndrome. Physicians and nurses on an acute pain service increased compliance rates with their hospital’s hand-disinfection policy by nearly 30% by wearing a personal container of antibacterial hand rub. Wearing the individual handdecontamination product improved overall application of the hand gel from a mean of 34% before the intervention to 63% after the intervention. Findings were presented at the American Society of Anesthesiologists (ASA) 2013 Annual Meeting. Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 555
- 56. NEUROLOGY Encephalopathy: An UnusualNeurological Manifestation Following Snakebite Shubha Laxmi Margekar*, Rakesh Gaharwar*, Satyam Singh Jayant*, Om Prakash Jatav**, Ashish Singhal†, Venu Gopal Margekar† Abstract Encephalopathy following snakebite is infrequent. Neurotoxicity due to snakebite is well-known with varied presentation and fatality. We report a case of young male presenting with respiratory failure and neuromuscular paralysis, who later developed diffuse encephalopathy, convulsions and right-sided hemiparesis. Toxic effect of venom can be a possible cause for this rare presentation. Keywords: Encephalopathy, neurotoxicity, snakebite S nakebite is one of the common life-threatening medical emergencies encountered in Indian population particularly in rural and farming areas. South Asia is the world’s most affected region by snakebite, due to its high population density, widespread agricultural activities, numerous venomous snake species and lack of appropriate information regarding primary treatment (first aid) in general population.1 India has the highest number of deaths (35,000-50,000 people dying per year) due to snakebites.1 Common cases of snakebites are of saw-scaled viper (Echis carinatus), Russell’s viper (a viperidae), krait (Bungarus caeruleus), common cobra (Naja naja) king cobra (Ophiophagus hannah).2 Snake venoms contain more than 20 different constituents, mainly proteins, including enzymes, nonenzymatic polypeptide toxins and nontoxic proteins.1 The clinical features reflect the effects of these venom components that are categorized into hematotoxic, neurotoxic and myotoxic. These include local tissue damage ranging from pain, swelling of the bitten limb *Assistant Professor **Professor and Head †Postgraduate Student Dept. of Medicine GR Medical College, Gwalior, Madhya Pradesh Address for correspondence Dr Shubha Laxmi Margekar Room No. 41, Senior Girls Hostel, Near Kamla Raja Hospital JA Hospital Campus, GR Medical College, Gwalior, Madhya Pradesh - 474 009 E-mail: dr_shubhalaxmi@rediffmail.com 556 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 to skin and muscle necrosis, abnormal blood clotting, spontaneous systemic bleeding, neurotoxicity leading to ptosis, ophthalmoplegia and paralysis of respiratory muscles, cardiac involvement causing arrhythmias, hypotension and shock, skeletal muscle breakdown and renal toxicity.1,2 Case Report A 16-year-old male was brought to the intensive care unit (ICU) with history of rapidly developing breathlessness, ptosis, difficulty in swallowing and body ache following snakebite in the dorsum of his left foot (near great toe) five hours prior to admission. He developed altered consciousness half an hour before presentation. At presentation, he was comatose and had no motor response to deep painful stimuli, generalized hypotonia in all four limbs, areflexic, nonelicitable plantar reflex, pupils mid-dilated and sluggishly reacting to light. His pulse was feeble, blood pressure was 60 systolic, minimal respiratory effort and saturation of peripheral oxyzen (SpO2 was 48%. There was cellulitis of the left foot. Other systems were normal. Endotracheal intubation was immediately performed and the patient was mechanically ventilated. He was given antisnake venom after sensitivity testing, tetanus toxoid in addition to antibiotics, neostigmine, atropine and supportives. SpO2 gradually improved and was near normal after ventilation. Laboratory investigations including hemoglobin, total leukocyte count, platelet count, blood glucose, blood urea, serum creatinine, serum bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), prothrombin time, bleeding time and clotting time were unremarkable with
- 57. NEUROLOGY venom toxins affectingthe coagulation cascade, the neuromuscular transmission or both. Figure 1. Diffusion-weighted MRI of the brain showing poorly defined areas of altered signal intensity involving bilateral fronto-parieto-occipital lobes and bilateral basal ganglia suggestive of cytotoxic edema-toxic/inflammatory. no hyponatremia or hypokalemia. Electrocardiogram showed sinus tachycardia. On Day 3, he developed deviation of gaze toward right with no improvement in neuromuscular involvement. This prompted us to go for diffusion-weighted magnetic resonance imaging (MRI) of the brain that revealed poorly defined areas of altered signal intensity involving bilateral frontoparieto-occipital lobes and bilateral basal ganglia suggestive of cytotoxic edema-toxic/inflammatory (Fig. 1). On Day 4, he started moving his limbs (left limbs more than the right) in response to deep painful stimuli, along with neck flexors weakness and extensor right plantar reflex with focal seizures that started in left half of face and left upper limb and then became generalized, which were controlled by intravenous phenytoin. In postictal phase, he was having flaccid quadriparesis but once the postictal phase was over, right-sided hemiparesis was noticed along with aphasia and middilated pupils reacting to light. He was weaned off the ventilator and extubated after six days of ventilation. He regained swallowing reflex and his conscious level gradually improved but aphasia persisted. The local reaction in the left foot was settled. He was discharged on Day 18 with an advise to follow-up with repeat MRI brain. Discussion Snakebite is an important cause of mortality and morbidity in India. Common neurotoxic snakes in India include cobra (Naja naja) and krait (Bungarus caeruelus). Various neurological complications are related to Venom of viper contains metalloproteinases, serine proteases and C-type lentins having anticoagulant or procoagulant activity, may be either agonists or antagonists of platelet aggregation, which may lead to ischemic or hemorrhagic strokes. Phospholipase A2, β-bungarotoxin and three-finger proteins (common in elapids) are potent neurotoxins affecting the neuromuscular transmission at either presynaptic or postsynaptic levels to inhibit peripheral nerve impulse causing muscle weakness. Presynaptic-acting β-neurotoxins inhibit the release of acetylcholine, and postsynaptic-acting a-neurotoxins cause a reversible blockage of acetylcholine receptors. Most snake venoms have multisystem effects on their victims.3 The common neurological manifestations are alteration in level of consciousness, paresthesiae, abnormalities of taste and smell, ptosis, ophthalmoplegia, limb weakness, respiratory failure, palatal weakness, difficulty in swallowing secretions, neck muscle weakness, generalized flaccid paralysis and delayed sensory neuropathy and most of the neurological symptoms are noticed usually within six hours after the bite.1,4 Our patient also presented within five hours of bite with difficulty in swallowing secretions, ptosis, respiratory paralysis and altered sensorium. Other less common complications includes stroke (ischemic or hemorrhagic) hypoxic effect on the brain, GBS and cortical blindness.5,6 Only few reports are available showing features of diffuse encephalopathy or widespread cerebral hypoxia following snakebite and focal neurological deficit was the frequent manifestation associated with cerebral hypoxia on recovery.5,6 According to Dhaliwal et al, hypoxic effect on brain is likely to be related to prolonged respiratory paralysis and cardiac arrest that occurs following neurotoxic envenomation.4 Our patient had finding of diffuse encephalopathy as documented in the diffusionweighted MRI of brain and he also developed hemiparesis during his recovery period but this cannot be fully explained by prolonged respiratory paralysis or cardiac arrest as our patient presented very early after onset of symptoms and was managed immediately with life supportive measures. In cases of neurotoxic envenomation with respiratory failure and neuromuscular paralysis, antisnake venom, anticholinestrase therapy and cardio respiratory support remains the mainstay of treatment. Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 557
- 58. NEUROLOGY MRI with diffusionand perfusion imaging provides information regarding brain lesions induced by the various toxic agents. These include vasogenic edema, cytotoxic edema, infarction, hemorrhage and demyelination.7 Imaging study in our patient was also suggestive of cytotoxic edema, which goes in favor of toxin induce brain damage. Direct effect of snake venom toxin on brain can be a possible cause resulting in diffuse encephalopathy in our patient which has been reported infrequently. Conclusion Being an unusual manifestation, encephalopathy may be masked or superadded by hypoxia or metabolic cause. Imaging studies should be done in all cases of altered sensorium following snakebite with deviation of gaze and minimal improvement in neuromuscular weakness, so that more and more cases of diffuse encephalopathy can be diagnosed early and management for cerebral edema in addition to conventional management can be started timely i.e., before development of irreversible hypoxic insult, for better outcome. References 1. Warrell DA. The clinical management of snake bites in the Southeast Asian region. Southeast Asian J Trop Med Public Health 1999;30:1-84. 2. Bawaskar HS, Bawaskar PH, Punde DP, Inamdar MK, Dongare RB, Bhoite RR. Profile of snakebite envenoming in rural Maharashtra, India. J Assoc Physicians India 2008;56:88-95. 3. Del Brutto OH, Del Brutto VJ. Neurological complications of venomous snake bites: a review. Acta Neurol Scand 2012;125(6):363-72. 4. Seneviratne U, Dissanayake S. Neurological manifestations of snake bite in Sri Lanka. J Postgrad Med 2002;48(4): 275-8; discussion 278-9. 5. Dhaliwal U. Cortical blindness: an unusual sequela of snake bite. Indian J Ophthalmol 1999;47(3):191-2. 6. Murthy JM, Kishore LT, Naidu KS. Cerebral infarction after envenomation by viper. J Comput Assist Tomogr 1997;21(1):35-7. 7. Dietemann JL, Botelho C, Nogueira T, Vargas MI, Audibert C, Abu Eid M, et al. Imaging in acute toxic encephalopathy. J Neuroradiol 2004;31(4):313-26. ■■■■ Stroke patients treated at hospitals with neurology residency programs are significantly more likely to get lifesaving clot-busting drugs than those seen at other teaching or nonteaching hospitals, new Johns Hopkins-led research suggests. The findings, described online last week in the journal Neurology, suggest that patients at academic medical centers with neurology residency programs likely benefit from having stroke specialists on hand 24 hours a day, seven days a week. These physicians have more experience with the use of tissue plasminogen activator (tPA) and are likely more confident in using the stroke treatment, which can be deadly if used in the wrong situations, the researchers say. “The use of tPA within three hours of stroke symptom onset increases the chances of a better outcome by 30% and has revolutionized stroke treatment,” says study leader Yogesh Moradiya, MD, a neuro-critical care fellow in the Dept. of Neurology at the Johns Hopkins University School of Medicine. “But the data show there is a massive underutilization of this drug, which is considered the gold standard of treatment for patients with the most common type of stroke. And our research finds that where you are treated seems to determine whether or not you receive it.” Moradiya conducted the research with colleagues at SUNY Downstate Medical Center in Brooklyn, NY, when he was a neurology resident there. The drug tPA is used only for patients with ischemic stroke, the most common type of stroke, which occurs as a result of an obstruction in a blood vessel supplying blood to the brain. It should not be used in cases of hemorrhagic stroke, marked by bleeding in the brain as the result of a broken blood vessel. Roughly 7,00,000 Americans each year suffer strokes, which may cause death or serious disability in the form of weakness, loss of sensation and difficulty with speaking, seeing or walking. 558 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013
- 59. Obstetrics and Gynecology Evaluationof Perinatal Outcome by Antenatal CTG and Umbilical Artery Doppler in Pre-eclamptic Mothers Barunoday Chakraborty*, Tamal Kumar Mondal**, Sannyasi Charan Barman†, Biswa Pratim Rudra‡, Ramkrishna Sahana¶, Prabhat Chandra Mondal¶ Abstract This was a well-controlled hospital-based longitudinal prospective randomized study with a sole focus on pre-eclampsia cases, where cardiotocography (CTG) and colored Doppler were the two special investigative tools applied to examine the perinatal outcome. The study concluded with a note that antenatal CTG is a useful objective test to know the intrauterine fetal status but it cannot forecast the fetal behavior during labor, neither does it provide a guide to optimize the timing of induction of labor (IOL) or termination by cesarean section. Color Doppler indices done after 34 weeks definitely give a qualitative assessment of fetoplacental perfusion but it cannot predict the said perfusion during labor - when there occurs a degree of compromise with the uterus contracting repetitively. Ultrasonography (USG) for fetal biometry and liquor volume is a good test to determine small for gestational age or intrauterine growth restriction (IUGR) as the case may be taking cognizance of other factors e.g., preeclampsia, fetal congenital anomaly, etc. Every mother with pre-eclampsia needs to be evaluated both clinically, biochemically and ultrasonologically. Understanding the limitation of antenatal CTG and color Doppler indices, these should be applied in a few selected cases e.g., increased fetal movement, IUGR, which is reassuring to both the patient and the doctor who can wait till a reasonable degree of fetal maturity occurs before one goes for IOL or a cesarean section. Patients with a suspicious CTG should undergo continuous CTG during labor - otherwise there is always a tendency to go for an early lower-segment cesarean section (LSCS). For a pre-eclamptic mother with a pathological CTG the decision is an elective LSCS; whereas, cases with pathological CTG but normal Doppler indices the judgment is too difficult. The answer then would lie on factors like whether the pre-eclampsia is controlled and whether the biochemical and hematological parameters are within normal limits. Of course thanks to the presence of a special newborn care unit (SNCU) nearby. Keywords: CTG, Doppler, pre-eclampsia Introduction, Review of Literature and Objectives Pre-eclampsia is a multisystem, highly variable disorder, unique to pregnancy and a leading cause of maternal and perinatal mortality and morbidity.1,2 It is *Associate Professor Dept. of Obstetrics and Gynecology BS Medical College, Bankura, West Bengal **Resident Dept. of Obstetrics and Gynecology RG Kar Medical College, Kolkata †RMO-cum Clinical Tutor ‡Senior Resident ¶Assistant Professor Dept. of Obstetrics and Gynecology BS Medical College, Bankura, West Bengal Address for correspondence Dr Barunoday Chakraborty G5/26, College Quarter, BS Medical College, Gobindanagar Bankura, West Bengal -722 102 E-mail: asmp80@rediffmail.com a syndrome defined by hypertension and proteinuria that also may be associated with a myriad of other signs and symptoms such as edema, visual disturbances, headache and epigastric pain.3 The increased incidence of perinatal morbidity and mortality seen in pregnancies complicated by pre-eclampsia is primarily due to the need for premature delivery and uteroplacental insufficiency resulting in a compromised blood flow to the fetus.4 The primary adoptive response of the fetus to placental insufficiency is a decrease in growth. Persistent placental insufficiency will result in decreased fetal movement to conserve energy, hemodynamic redistribution to favor the oxygenation of organs critical to the economy such as the brain, heart, suprarenal and attempt to improve the efficiency of the placental gas exchange by increasing the heart rate and the synthesis of red cells. Progressive decompensation like this will lead to a metabolic and respiratory acidosis, increased impedance to fetoplacental circulation, renal Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 559
- 60. Obstetrics and Gynecology insufficiencywith decreased amniotic fluid volume; myocardial compromise, absent or reversed atrial flow in ductus venosus, late deceleration in the fetal heart rate (FHR) tracing and fetal death. It would be ideal that this sequence of pathological changes elicited by placental insufficiency and fetal hypoxia could be identified in each of its different stages by a single test, which has not been achieved so far. In an attempt to stratify risk, a variety of antepartum screening tests are performed, which include few laboratory tests and sonographic assessments, besides history taking and clinical examination including serial symphysiofundal height measurement. Antenatal cardiotocography (CTG) is a special test for evaluation of fetal status. Prof. Essar GS Dows and Prof. C Redman of United Kingdom were two pioneers in the eighties who devised the computer program to evaluate CTG. The basic objective of CTG is to assess co-ordination between fetal central nervous system (CNS) and the cardiovascular system based on the fact that a welloxygenated healthy fetus with functionally intact CNScardiac axis will show accelerations (rise of FHR 15 beats/minutes for 15 seconds above baseline) with fetal movements - the so called reactive CTG. In addition, good FHR variability (≥5 bpm) suggest normal balance of sympathetic-parasympathetic activity, an indirect evidence of adequate oxygenation of fetal regulatory centers; indeed, a normal FHR variability is the hallmark of fetal well-being. Accepted normal parameters for term fetus are: ÂÂ Baseline FHR 110-160 beats/minute ÂÂ Baseline variability should be > 5 beats/minute ÂÂ Presence of two or more accelerations of FHR exceeding 15 beats/minute, sustained for at least 15 seconds in a 20-minute period. This pattern is termed as ‘Reactive.’ ÂÂ Absence of deceleration. However, the Cochrane meta-analysis of randomized controlled trials (RCTs) involving 1,558 high/ intermediate risk pregnancies suggests antepartum CTG alone has no significant impact on perinatal outcome.5 Though, initial studies have shown a strong correlation between abnormal CTG and poor perinatal outcome,6 when CTG is used alone significant interobserver variations, poor specificity and high false-positive rates causing increased number of lowersegment cesarean section (LSCS) are other problems. The change in behavior of ultrasound waveform reflecting from a moving object - the Doppler effect was introduced in the assessment of umbilical artery 560 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 flow at Dubling in 1977. Longitudinal Doppler studies of the umbilical artery show that the systolic/diastolic (S/D) ratio decreases as gestation progresses. This is an indirect evidence of decreasing placental resistance with advancing gestation.7 However, there is no definite agreement as to what constitutes an abnormal Doppler study. Most authors have accepted as S/D ratio >3.0 as the cut-off beyond 30 weeks gestation. Gradual increase in umbilical artery resistance leads to absent and subsequently reversed end-diastolic flow, which is associated with progressively worse perinatal outcome. The Doppler indices are calculated as ratios between peak systolic velocity (A), end-diastolic peak velocity (B) and mean velocity (mean). The indices most common in clinical practice, are pulsatility index (PI) = (A-B)/mean, and resistant index (RI) = (A-B)/A. With normal placental perfusion, the umbilical artery waveform has a pattern compatible with a lowresistance system displaying forward blood flow throughout the cardiac cycle.8 Inadequate placental perfusion causes progressive changes in the Doppler flow pattern of umbilical artery starting from absent or reversed end-diastolic flow, increase in resistance index, which correlate well with fetal acidosis.9 The first meta-analysis of umbilical artery Doppler in high-risk pregnancies published in 1995 demonstrated significant reduction in perinatal death.10 Two large RCTs- one from South Africa and other from Canada, and one Cochrane review of routine Doppler studies of umbilical artery in high-risk pregnancies have shown conflicting reports of benefit regarding perinatal outcome. However, evidence from small RCTs does indicate less requirement of emergency cesarean section for fetal distress if Doppler velocity was used (NICE Guideline, 2010). The ongoing TRUFFLE study has been designed to compare reduced short-term variations on CTG and Doppler velocimetry of ductus venosus to determine optimum timing of delivery of growth restricted fetus.11 In this study, spanning six months we tried to evaluate perinatal outcome in pre-eclampsia in term of mode of delivery (vaginal/instrumental/LSCS), need for induction of labor (IOL), neonatal status according to specific parameters by means of antenatal CTG and umbilical artery Doppler in late third trimester at our institution, which is a tertiary maternity care center with an annual delivery rate of >20,000, delivering optimal care free of cost to a large population from three districts namely Bankura, Purulia and Paschim Medinipur in West Bengal. Our objective was to ascertain an optimum and cost-effective way
- 61. Obstetrics and Gynecology totreat pre-eclamptic mothers and to obviate special investigations like CTG and umbilical artery Doppler in each and every case and thereby save some cost as well as manpower. Material and Methods This was a prospective longitudinal study carried out in our department during six months period from April 2012 to September 2012. All pre-eclamptic mothers of >34 weeks of gestation with a single intrauterine fetus presenting cephalic presentation without any congenital anomaly were included in the study. Patients with prelabor rupture of membrane, antepartum hemorrhage (APH), bad obstetric history, elderly primi (>35 years), multifetal pregnancy, malpresentation, history of systemic illness e.g., antiphospholipid syndrome, chronic renal disease, heart diseases, psychiatric illness were excluded. Known cases of pre-eclampsia were evaluated with history, examination and laboratory investigations including urine albumin, serum uric acid, platelet count, clotting time, renal and liver function tests. The cases were then randomized and allocated in the study group and control group. The study group had undergone an antenatal CTG for 40 minutes and umbilical artery Doppler study. Categorization of FHR traces was done following Royal College of Obstetricians and Gynecologist (RCOG) criteria 2001 as normal, suspicious and pathological. Normal implied a fetal well-being and as such a conservative approach; whereas, suspicious implied continued observation and additional test e.g., vibroacoustic stimulation (VAS) and pathological indicated an urgent delivery. Our CTG equipment was Schiller, Argus AFM, SN = SA07020009; manufacturer: Biostos Co. Ltd. Korea: 2005. The study group had also undergone assessment of fetoplacental profile and a Doppler assessment of umbilical artery. S/D ≤3 and RI ≤0.6 were considered normal; raised indices, absent or reversed enddiastolic flows were taken as signs of fetal distress. The decision to deliver the baby at an optimum time through an appropriate route (vaginal/LSCS) was taken considering the gestational age and the results of CTG and umbilical artery Doppler indices. The control group was followed up by daily clinical monitoring and routine USG for fetoplacental profile and liquor volume. They were delivered by appropriate route at an optimum gestational age according to these findings and consultant decision. Study group, where a conservative approach was taken till maturity (37 weeks) were followed up by twice in a week CTG and another Doppler study after two weeks. Control group, in similar situation had another routine USG for FPP after two weeks. The neonatal outcomes of both groups were recorded in predesigned proforma and compared using Chi-square test and Student’s t-test and statistical software Medcalc 12.3.0. Ethical clearance was obtained from College Ethical Committee and due consent was taken from patients and their husbands or a near relative. Table 1. No. of Patient Showing Reactive or Nonreactive CTG in the Study Population CTG Mode of delivery Apgar score at 1 min Normal Reactive (n = 24) Nonreactive (n = 11) Total (n = 35) LSCS Forceps ≥7 <7 22 (91.6%) 1 (4.2%) 1 18 (75%) 6 (25%) 5 (45.5%) 6 (54.5%) - 3 (27.3%) 8 (72.8%) 27 (77.14%) 7 (20%) 1 21 (60%) 14 (40%) P = 0.002 P = 0.003 Table 2. Umbilical Artery Doppler Indices of the Study Population Umbilical artery Doppler indices Mode of delivery Apgar score at 1 min Normal LSCS Forceps ≥7 <7 Normal (n = 10) 8 (80%) 1 (10%) 1 9 (90%) 1 (10%) Raised (n = 25) 19 (76%) 6 (24%) - 12 (48%) 13 (52%) 27 (77.14%) 7 (20%) 1 21 (60%) 14 (40%) Total (n = 35) P = 0.2004 P = 0.01 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 561
- 62. Obstetrics and Gynecology Table3. Perinatal Outcome in the Study and Control Group Parameters Study group Control group P value 38.6, 1.77 38.92, 1.88 t-test p = 0.792 Gestational age at birth (weeks) Mean; SD 34-37 2 6 >37 33 29 Labor events IOL 9 11 Chi-sq. t-test SOL 26 24 p = 0.298 ND 27 24 Chi-sq. t-test LSCS 7 8 p = 0.537 Forceps 1 3 Mean; SD 6.51, 1.90 6.69, 1.683 Chi-sq. t-test ≥7 at 1 min 21 19 p = 0.147 <7 at 1 min 14 16 Mean, SD 7.46, 0.99 7.86, 1.29 Chi-sq. t-test ≥7 at 5 min 33 32 p = 0.125 <7 at 5 min 2 3 2691, 392 2670, 356 Chi-sq. t-test 1,500-2,500 6 11 p = 0.816 >2,500 29 24 Yes with Bag Mask (BM) 14 16 Chi-sq. t-test No 21 19 p = 0.404 Yes 7 9 Chi-sq. t-test No 28 26 p = 0.285 Mode of delivery Apgar score Apgar score Birth weight (g) Mean, SD Need for resuscitation SNCU admission IOL = Induction of labor; SOL = Spontaneous of labor; ND = Normal delivery; LSCS = Lower-segment cesarean section; SD = Standard deviation; SNCU = Special newborn care unit. Observation and Discussion Two-third of our study population (n = 35) had a reactive CTG and one-third showed a nonreactive type (Table 1). Nearly, 92 patients of reactive CTG against 45% of those with nonreactive type had a normal delivery and 56% with nonreactive CTG had a cesarean delivery against only 3% of reactive type – the difference of picture is definitely significant (p < 0.05). Random application of CTG has increased the number of LSCS whenever CTG tracing gets abnormal has been supported by other authors in the 562 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 past: Khursheed et al showed a 72% LSCS rate when CTG was of pathological pattern.12 Overall, the incidence of vaginal delivery (normal and instrumental) among the study group was 80% (28 out of 35) and LSCS was 20%. In a tertiary care center 20% LSCS rate among pre-eclampsia cases was quite acceptable against World Health Organization (WHO) standard of 15%. So, CTG in this study has favored decision towards cesarean section but it has not pushed the number to an unacceptably high rate, which needed an audit. The message here is that
- 63. Obstetrics and Gynecology 100% Apgar≥7 90% Apgar ≤7 80% 70% 60% 50% 40% 30% 20% 10% 0% Reactive CTG Non reactive CTG Normal Doppler indices Raised Doppler indices Figure 1. Association of low Apgar score with raised Doppler indices. CTG in pre-eclampsia is an useful investigation that allows judicious decision making and does not cause unnecessary panic among obstetricians to take hasty decisions of LSCS which is obvious from the fact that 44% (5 out of 11) of nonreactive CTG cases were allowed a normal delivery. Though, a significantly higher incidence (p = 0.003) of low Apgar score was noted among nonreactive CTG, there was no perinatal death. Similar findings of increased neonatal hypoxia were noted by Khursheed and Chew et al in 2009.13 So, CTG can predict a low Apgar neonate but not enough to predict a perinatal death. More than two-third (25 out of 35, Table 2) of the study group had high umbilical artery Doppler indices (Table 2) but incidence of LSCS was not significantly higher (p = 0.24). However, among the neonates the low Apgar score was significantly associated with raised Doppler indices, 52% against 10% (p = 0.01): (Fig. 1). This finding validates the fact that umbilical artery Doppler shows the extent of fetoplacental perfusion during fetal diastole and is a recognized tool to show intrauterine fetal status. Sharma et al got almost similar findings in their study in 2010.14 The mean gestational age at birth of the study group and control group were not statistically different (p = 0.792). The labor events; the incidence of IOL versus spontaneous onset labor, incidence of vaginal delivery versus LSCS; Apgar score at one minute and five minutes; mean neonatal birth weight, number of hypoxic neonates requiring Bag Mask (BM) resuscitation and special newborn care unit (SNCU) admission when compared vis-a-vis with the control group had shown quite similar results with p value ranging from 0.125 to 0.816 (Table 3). A range of well-defined studies including one evidence-based meta-analysis from 1992 to 2001 could find no significant difference in neonatal outcome and LSCS rate with Doppler velocimetry.15 In 2010, Alfirevic et al in a Cochrane review on “Fetal and umbilical Doppler ultrasound in high-risk pregnancies” could not identify a difference in the requirement of intubation and assisted ventilation among neonates between Doppler velocimetry group and control group without Doppler velocimetry.16 Conclusion Therefore, universal application of antenatal CTG and umbilical artery Doppler does not do anything better than a routine USG among mature fetuses to forecast perinatal outcome. It is the labor monitoring and 24 hours cesarean section facility that matters when emergency arises in the form of prolonged labor, meconium staining and fetal bradycardia. Over the years, scientists have explored this area to determine the postnatal events with antenatal CTG and Doppler, which has remained a grey area even today because beyond 34-36 weeks of gestation, it is uncommon to find absent or reversed EDF in the umbilical arteries caused by uteroplacental insufficiency. Abnormal umbilical artery Doppler after 35 weeks should prompt consideration of other causes specially aneuploidy (Trisomies 18, 21). In absence of aneuploidy assessment of intrauterine growth restriction (IUGR) in late pregnancy is challenging because umbilical artery Doppler has a limited value in this setting. The timing of delivery is contentions because a favorable perinatal outcome is expected even with early delivery once diagnosis of IUGR has been made by fetal ultrasound biometry, amniotic fluid index, umbilical and middle cerebral artery Doppler indices. Elective induction of labor with continuous FHR monitoring may result in successful vaginal delivery although fetal distress and meconium staining in labor are common complications. No study exist to provide recommendation in these circumstances regarding early delivery versus antepartum monitoring and delayed delivery.17 The current study though conducted on a small sample can be considered as a pamphlet that speaks the need of careful clinical monitoring along with a routine USG after 34 weeks thanks to the presence of SNCU attached to the maternity ward. Control of blood Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 563
- 64. Obstetrics and Gynecology BaselineFHR 130 bpm Variability >5 4 accelerations No deceleration Normal CTG; Crying Boy BW - 2.8 kg (LSCS) Baseline FHR 140 bpm Variability >5 3 acceleration No deceleration Normal CTG; Crying Girl BW - 2.8 kg (ND) Baseline FHR 155 bpm Variability >5 No acceleration 2 late deceleration Suspicious CTG; Asphyxiated Boy BW - 1.75 kg (LSCS) Baseline FHR 130 bpm Variability <5 No acceleration No deceleration Suspicious CTG; Asphyxiated Girl BW - 2.7 kg (LSCS) Baseline FHR 145 bpm Variability >5 First 2 mts <5 rest of tracing No acceleration 1 deceleration Pathological CTG; Asphyxiated Girl BW - 2.9 kg (LSCS) Figure 2. CTG findings of the study population. 564 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013
- 65. Obstetrics and Gynecology pressureby labetalol or nifedipine (both the drugs are freely available at our ward); sending blood samples for Hb%, hematocrit, platelet count, serum urate, liver enzymes and 24 hours urine for protein; with or without the presence of IUGR on USG provide valuable clue to choose between immediate delivery by LSCS; IOL followed by fetal monitoring and trial of labor for at least six hours and/or prophylactic MgSO4 injection followed by emergency LSCS. 8. Neilson JP. Doppler ultrasound. Br J Obstet Gynaecol 1987;94(10):929-32. 9. Bilardo CM, Nicolaides KH, Campbell S. Doppler measurements of fetal and uteroplacental circulations: relationship with umbilical venous blood gases measured at cordocentesis. Am J Obstet Gynecol 1990;162(1): 115-20. References 10. Neilson JP, Alfirevic Z. Doppler ultrasound for fetal assessment in high risk pregnancies. Cochrane Database Syst Rev 2000;(2):CD000073. Update in: Cochrane Database Syst Rev 2010;(1):CD000073. 1. Ness RB, Roberts JM. Heterogeneous causes constituting the single syndrome of preeclampsia: a hypothesis and its implications. Am J Obstet Gynecol 1996;175(5):1365-70. 11. Cambridge Consortium. Trial of Umbilical and Fetal Flow in Europe (TRUFLE). Ultrasound Obstet Gynecol 2005;25:105-7. 2. Douglas KA, Redman CW. Eclampsia in the United Kingdom. BMJ 1994;309(6966):1395-400. 12. Khursheed F, Das CM, Jatoi N. Cardiotocography: obstetric and neonatal outcome. J Rawalpindi Med Coll 2009;13(2):86-8. 3. ACOG Committee on Obstetric Practice. ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet 2002;77(1):67-75. 4. Dekker GA, Sibai BM. Etiology and pathogenesis of preeclampsia: current concepts. Am J Obstet Gynecol 1998;179(5):1359-75. 5. Pattison N, McCowan L. Cardiotocography for antepartum fetal assessment. Cochrane Database Syst Rev 2000;(2):CD001068. Update in: Cochrane Database Syst Rev 2010;(2):CD001068. 6. Freeman RK, Anderson G, Dorchester W. A prospective multi-institutional study of antepartum fetal heart rate monitoring. I. Risk of perinatal mortality and morbidity according to antepartum fetal heart rate test results. Am J Obstet Gynecol 1982;143(7):771-7. 7. Divon MY, Ferber A. Doppler evaluation of the fetus. Clin Obstet Gynecol 2002;45(4):1015-25. 13. hew FT, Drew JH, Oats JN, Riley SF, Beischer NA. C Nonstressed antepartum cardiotocography in patients undergoing elective cesarean section - fetal outcome. Am J Obstet Gynecol 1985;151(3):318-21. 14. Sharma U, Bhatnagar B. Triple vessel wave pattern by Doppler studies in normal and high risk pregnancies and perinatal outcome. J Obstet Gynaecol India 2010; 60(4):312-6. 15. Pattinson RC, Norman K, Odendaal HJ. The role of Doppler velocimetry in the management of high risk pregnancies. Br J Obstet Gynaecol 1994;101(2):114-20. 16. Alfirevic Z, Stampalija T, Gyte GM. Fetal and umbilical Doppler ultrasound in high-risk pregnancies. Cochrane Database Syst Rev 2010;(1):CD007529. 17. Rumack CM, Wilson SR, Charbonean JW, Jo-Ann M, Johnson. Diagnostic ultrasound. Elsevier: Mosby 2005;3e(2):1542. ■■■■ Endometriosis Risk Linked to Two Pesticides A Fred Hutchinson Cancer Research Center-led study has found that two organochlorine pesticides are associated with an increased risk of endometriosis, a condition that affects upto 10% of reproductive-age women. Specifically, researchers observed that women with higher exposures to two such pesticides, betahexachlorocyclohexane and mirex, had a 30- to 70% increase in endometriosis risk. The findings are published online ahead of the print issue of Environmental Health Perspectives, a journal of the National Institute of Environmental Health Sciences, part of the National Institutes of Health. Endometriosis is a noncancerous condition that occurs when the tissue that lines the inside of the uterus, or womb, grows outside of the organ and attaches to other structures or organs. The condition most often affects the ovaries, fallopian tubes and lining of the pelvic cavity. The most common symptoms include chronic pelvic pain, painful menstrual periods and infertility. Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 565
- 66. Obstetrics and Gynecology ARare Case of Prolapse Uterus S Sampathkumari*, Mohanambal**, Rajamaheswari†, Meena Umachander† Abstract Prolapse is the commonest complaint in elderly females. We present herein a case of procidentia with more than 200 stones in bladder of varying size, treated with vaginal hysterectomy and vesical calculi removal through bladder (abdominally). Keywords: Procidentia, vesical calculi Case History Investigations Mrs. K, a 57-year-old lady, presented to us with history of mass descending per vagina since 18 years and urinary incontinence since six months along with dysuria, constipation since one month. She was admitted in the institute on April 16, 2011. Routine blood count, renal function tests, liver function tests, chest X-ray, ECG, serum electrolytes were all normal. X-ray KUB (kidneys, ureters and bladder) revealed two bladder stones and intravenous pyelography (IVP) showed nonfunctioning right kidney and left kidney with decreased excretion. USG revealed bilateral hydroureteronephrosis and colposcopy showed normal findings except for mild inflammatory features. Her previous history of menstruation was normal. The patient had been married for 32 years and had attained menopause 17 years ago. She was multiparous, with the last childbirth 20 years ago. A diabetic, she had been under oral treatment since 10 years. She did not report history of any sexual exposure since 17 years, after the mass descending per vagina. She had not consulted any doctor for this but came to the OPD because she had developed some disturbance in micturition. On examination, she had mild pallor. Other parameters of pulse, BP, thyroid were within normal limits. Pelvic examination revealed atrophic external genitalia, decreased pubic hair and pad of fat on the labia minora and majora. A pink globular mass measuring approximately 17 × 10 cm was seen protruding outside the vaginal introitus. On palpation, the inspection findings were confirmed with mass being irreducible per rectal examination. Enterocele and rectocele were present. A probable diagnosis of Stage IV pelvic organ prolapse with complete eventration of the vagina was made. *Assistant Professor **Director †Professor Dept. of Obstetrics and Gynecology Institute of Social Obstetrics and Govt. Kasturba Gandhi Hospital for Women and Children, Chennai, Tamil Nadu Address for correspondence Dr Meena Umachander Institute of Social Obstetrics and Govt. Kasturba Gandhi Hospital for Women and Children, Chennai, Tamil Nadu 566 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 Diagnosis Procidentia with vesical calculi. Treatment The rise in blood sugar was treated with insulin. After controlling sugar with insulin, the patient was posted for surgery on May 6, 2011. On opening the abdomen by a midline incision, uterus was found to be normal on palpation. The gastroenterologist revealed a normal intestine. Hence, we proceeded to do a vaginal hysterectomy. Next, the urologist removed about 200 stones with varying sizes from the bladder by an incision over the fundus of the bladder (cystotomy) (Fig. 1 a and b). After achieving perfect hemostasis with suprapubic catheter and drain, the abdomen was closed in layers. Continuous bladder drain was advised for six weeks. Postoperative sugar was controlled and fever was treated with antibiotics. Sutures were removed on 12th day. Catheter was removed when the patient reported for follow-up after six weeks. Discussion Prolapse is a common complaint of elderly women. The most important etiological factor is atonicity
- 67. Obstetrics and Gynecology a b Figure1 a and b. Showing more than 200 stones of varying sizes, which were removed. and asthenia that follow menopause. Procidentia is IV degree of prolapse with the entire uterus lying outside the introitus. Pelvic organ prolapse in general and uterine prolapse, in particular, are known to be associated with hydronephrosis. The prevalence of hydronephrosis with uterine prolapse is 7-17%. Klempner found ureteric dilatation and hydronephrosis to be 5% in I degree prolapse; 26% in II degree prolapse and 40% in III degree prolapse. Surgical treatment is the best mode of treatment. Vaginal hysterectomy with anterior colporrhaphy and posterior colpoperineorrhaphy is the complete treatment. The number of prolapse cases reported at our institute from July 2010 to June 2011 was 284. Of these, 253 were operated and only one case presented with vesical calculi. Conclusion Though prolapse is a common complaint, patients should consult a doctor without any hesitation at early stage. The true incidence of urological problem related to prolapse remains underestimated and its prevalence in asymptomatic patients in the community cannot be clearly defined because they present with unrelated and vague symptoms at a later stage. This case is presented for its rarity. Suggested Reading 1. Klempner E. Gynecological lesions and ureterohydronephrosis. Am J Obstet Gynecol 1952;64(6):1232-41. 2. Young JB, Selby PL, Peacock M, Brownjohn AM. Uterine prolapse and urinary tract obstruction. Br Med J (Clin Res Ed) 1984;289(6436):41-2. ■■■■ Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 567
- 68. Obstetrics and Gynecology ComparativeStudy of Obstetrics Outcome Between Scarred and Unscarred Uterus in Placenta Previa Cases Gayatri Mathuriya*, Pallavi Lokhande** Abstract Objective(s): To compare the incidence of placenta previa, associated factors, complications, placental position, mode of delivery and fetal and maternal outcome in scarred (Group A) and unscarred uterus (Group B) in 20 months of hospital-based study. Material and methods: In a prospective study, 140 cases of pregnancies beyond 28 weeks of gestation complicated by placenta previa were identified. These cases were divided into two groups, scarred uterus (Group A, n = 34) and unscarred uterus (Group B, n = 106). Total number of deliveries were 16,784 out of which 2,354 patients had cesarean section and 140 patients had placenta previa. Results: The incidence of placenta previa in scarred cases is significantly higher (1.2%) than overall incidence (0.6%). Majority of scarred cases had anterior placenta (85.2%) and majority of unscarred cases had posterior placenta (63.2%) (p value -0.00, HS). The number of unbooked cases in both Groups A and B was high (P value-0.404, NS). A significant association of placenta previa following curretage in Group B was observed (p value-0.002, S). There was only one maternal mortality in Group B and none in Group A. Results showed a favorable fetal outcome in both groups. (Group A-70.6%, Group B-64.2%, p value-0.08, NS). Conclusion(s): An increase in the incidence of prior cesarean section and advanced maternal age probably contribute to a rise in the number of pregnancies complicated with placenta previa and its association with adverse maternal and perinatal outcome. Keywords: Placenta previa, incidence, maternal outcome, fetal outcome P lacenta previa is an obstetric complication in which the placenta is inserted partially or wholly in lower uterine segment.1 It can sometimes occur in later part of the first trimester, but usually occurs during the second or third. It is a leading cause of antepartum hemorrhage (vaginal bleeding). It affects approximately 0.4-0.5% of all labors.2 Exact etiology of placenta previa is unknown. It is hypothesized to be related to abnormal vascularization of the endometrium caused by scarring or atrophy from previous trauma, surgery or infection. These factors may reduce differential growth of lower segment, resulting in less upward shift in placental position as pregnancy advances.3 *Assistant Professor Dept. of Obstetrics and Gynecology MGM Medical College and MY Hospital, Indore, Madhya Pradesh **Resident Dept. of Obstetrics and Gynecology MGM Medical College, Indore, Madhya Pradesh Address for correspondence Dr Gayatri Mathuriya 48, Kalindi Kunj, Indore - 452 001, Madhya Pradesh E-mail: drgayatrimathuriya@gmail.com 568 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 The traditional classification of placenta previa describes the degree to which the placenta encroaches upon the cervix in labor and is divided into low lying, marginal, partial or complete placenta previa.4 In recent years due to the increased value of transvaginal ultrasound in diagnosis of placenta previa, the traditional classification is rendered obsolete.4 Diagnosis is made on history, clinical examination and few investigations that include ultrasound (transabdominal, transvaginal) and megnetic resonance imaging (MRI).5 Although the etiology the placenta previa remains speculative, several risk factors associated with this condition have been established. These include advanced maternal age, multiparity, multiple gestation, previous abortion, previous cesarean section and placenta previa in previous pregnancy.6 Myometrial damage due to cesarean section and dilation curettage are main predisposing factors.7 Also, risk factors are previous cesarean section, history of abortion and complete previa.8 Most obstetricians have concerns about massive hemorrhage not only when complete previa exists but also when placenta is located on the anterior position of the uterus, beneath the cesarean incision site.9,10
- 69. Obstetrics and Gynecology Patientswith placenta previa are at increased risk of spontaneous abortion, fetal malpresentation, cesarean section, increased loss of blood, peripartum hysterectomy and prolonged hospitalization. The infants of these patients are also at increased risk of premature deliveries, increased perinatal mortality than in general population. The frequency of this condition may be on the rise so we need to identify and target preventive interventions among women at increased risk of placenta previa. The association of placenta previa with fetal malpresentation, abruptio placenta, postpartum hemorrhage and maternal fetal outcome were also evaluated in both the groups and compared. Chi-square test and chi-square test with Yate’s correction was used to compare different quantitative data variable. RESULTS MATERIAL AND METHODS This study was conducted in the Dept. of Obstetrics and Gynecology, MGM Medical and MY Hospital, Indore, from May 2011 to December 2012. A total number of 140 patients beyond 28 weeks gestation, complicated by placenta previa alone or with previous myomectomy, cesarean section and uterine repair were identified. All types of placenta previa were included. The subjects were divided into two groups: Group A in which placenta previa occurred in scarred uterus and Group B in which placenta previa occurred in unscarred uterus. Transabdominal sonography was done for obstetrical reasons as well as for exact location of placenta. The following potential risk factors such as maternal age, parity, previous abortion, prior cesarean section Table 1. Maternal Characteristics Scarred uterus (Group A) and multiple pregnancies were examined in both the groups and were compared. Unscarred uterus (Group B) No. % No. % 20-25 8 23.6 69 65.0 26-30 23 67.6 24 22.6 >30 3 8.8 13 P value 12.4 Age in years 0.00 (HS) Maternal characteristics of the two groups are given in Table 1. Majority of the patients in the study were between the age range of 26-30 years in Group A (67.6%) and 20-25 years in Group B (65%) (p value 0.00, HS). Primipara with placenta previa were 0 in Group A and 31 (29.2%) in Group B (p value 0.002, S). A definite association of placenta previa following curretage was observed (Group A-20.58%, Group B-3.8%, p value 0.002, S). Table 2 shows that majority of cases had Grade I or low lying placenta, which is 47.2% in unscarred and 67.8% in scarred cases (p = 0.17, NS). Majority of patients with scarred uterus had anterior placenta, that is 85.3% and majority of patients with unscarred cases had posterior placenta, that is 63.2% (p = 0.00, HS). Table 3 compares the related complications between the two groups. There was only one maternal mortality in Group B and none in Group A (p value - 0.001, S). Results showed a favorable fetal outcome in both groups (Group A-70.6%, Group B-64.2%, p value-0.08, NS) (Table 4). Both Groups A and B had a high number of unbooked patients (A-94.11%, B-97.2%, p value 0.404, NS) (Table 5). Table 2. Relative Frequency Scarred uterus (Group A) Parity 0 0 0 33 31 1 15 44 33 31 2 16 47 23 21.6 3 2 5.8 7 6.6 ≥4 1 3 8 7.6 History of curettage 7 4 3.8 0.002 (S) 20.58 Unscarred uterus (Group B) No. % No. % I 23 67.8 50 47.2 II 6 17.6 35 33.0 III 2 5.8 12 11.4 IV 3 8.8 9 8.4 Anterior 29 85.3% 39 36.8% Posterior 6 17.7 67 P value 63.2 Grading 0.002 (S) Gestational age (weeks) 0.17 (NS) Type <37 20 58 50 47 >37 14 42 56 53 0.23 (NS) Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 0.00 (HS) 569
- 70. Obstetrics and Gynecology Table3. Related Complication Complications Scarred uterus (Group A) Table 6. Relative Incidence Unscarred uterus (Group B) No. % No. % Fetal malpresentation 4 11 9 8.4 16 47.05 76 71.6 (S) Cesarean section with uterine artery ligation 7 20.5 6 5.6 Cesarean section with internal iliac artery ligation 0 0 1 0.94 Cesarean hysterectomy 3 Incidence in scarred cases Incidence in unscarred cases 1.2% 0.47% 0.001 Postpartum hemorrhage Overall incidence of placenta previa 0.6% P value 8.8 0 Our study shows increasing parity increases with risk of placenta previa, Para 3 in scarred uterus, which is 45% and in unscarred cases increased incidence is found in Para 2 cases, which is 30%. The results are consistent with Reddy et al12 in which 69% were multiparous. In our study, we found 7.8% association of placenta previa with previous history of curettage, comparable to study of Taylor et al14 who found that women with one or more spontaneous abortion or induced abortion are 30% more likely to have placenta previa in subsequent pregnancy. 0 Placenta accreta 1 2.9 0 0 Placenta percreta 1 2.9 0 0 Maternal mortality 0 0 1 0.94 Blood transfusion 29 85 76 71.6 Table 4. Fetal Outcome Scarred uterus (Group A) Unscarred uterus (Group B) P value No. % No. % Alive 24 70.6 68 64.2 0.08 Stillbirth 3 9 26 24.4 (NS) Neonatal death 7 20.4 12 11.4 Table 5. Booking Status Status Scarred uterus (Group A) Unscarred uterus (Group B) P value No. % No. % Booked 2 5.88 3 2.8 0.404 Emergency 32 94.11 103 97.2 (NS) DISCUSSION The incidence of placenta previa in present study is 0.62%, which is comparable to study of Hemmadi et al11 and Reddy et al,12 which is 0.4% and 0.5%, respectively. Incidence of placenta previa is significantly higher in patients with previous cesarean section (1.2%) than overall incidence of 0.6%. 570 Placenta previa is more common among increasing age group, which is 68% in 26-30 years in scarred cases and in unscarred cases 65% in the age group 20-25 years, as comparable to Reddy et al.12 who reported 73% incidence in 20-29 years age group and also comparable to Rasmussen13 who showed increase incidence with increasing maternal age (20-29 years). Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 Incidence of placenta accreta is greater in patients with prior cesarean section than in unscarred uterus. In our study, 5.8% out of the scarred uterus constitute placenta accreta and percreta, which is consistent with the study of Clark et al15 who concluded that probability of placenta accreta is greater in patients with prior cesarean section. In evaluation of the related complications, we found that women with placenta previa were more likely to have postpartum hemorrhage, cesarean hysterectomy as diminished muscle content in lower uterine segment causes less effective contraction to control bleeding. The associated malpresentation with placenta previa increases the number of cesarean section, deliveries even in cases where placenta previa is marginal. Anterior previa is more common in patients with prior cesarean section compared to no prior cesarean section and it is more dangerous than posterior previa in view of increasing maternal morbidity such as excessive blood loss, massive transfusion, placenta accreta and hysterectomy.16 In our study, also 85.3% cases have anterior previa in scarred uterus and only 36.8% cases in unscarred uterus (p value = 0.00 HS). Prematurity due to placenta previa accounts for 60% of perinatal morbidity.17 In our study, 50% of cases delivered premature babies.
- 71. Obstetrics and Gynecology CONCLUSION Thisstudy concludes that efforts should be made to reduce the rates of operative deliveries because there is greater likelihood of placenta previa in scarred uterus in subsequent pregnancies. Sonographic detection of anterior placenta is very important to predict maternal outcome in placenta previa and in such cases obstetricians should be aware of maternal massive hemorrhage. The family planning services should be further improved to attain a decline in the number of women of high parity. The morbidity associated with placenta previa can be reduced by detecting the condition in the antenatal period by ultrasound, before it becomes symptomatic. This calls for educating our patients and making them aware of the importance of antenatal care and its availability. REFERENCES 1. Kumaran A, Warren R, Sabaratnam. Best Practice in Labour and Delivery. 1st edition, 3rd printing edition, Cambridge University Press: Cambridge 2009:p.142-6. 2. Faiz AS, Ananth CV. Etiology and risk factors for placenta previa: an overview and meta-analysis of observational studies. J Matern Fetal Neonatal Med 2003;13(3):175-90. 3. Dashe JS, McIntire DD, Ramus RM, Santos-Ramos R, Twickler DM. Persistence of placenta previa according to gestational age at ultrasound detection. Obstet Gynecol 2002;99(5 Pt 1):692-7. 4. Oppenheimer L; Society of Obstetricians and Gynaecologists of Canada. Diagnosis and management of placenta previa. J Obstet Gynaecol Can 2007;29(3):261-73. 5. Razia A, Alyia B, Asma G, Rabia N, Chohan A. Frequency of placenta praevia with previous caesarean section. Ann King Edward Med Coll 2005;1:299-300. 6. Hung TH, Hsieh CC, Hsu JJ, Chiu TH, Lo LM, Hsieh TT. Risk factors for placenta previa in an Asian population. Int J Gynaecol Obstet 2007;97(1):26-30. 7. Palacios-Jaraquemada JM. Diagnosis and management of placenta accreta. Best Pract Res Clin Obstet Gynaecol 2008;22(6):1133-48. 8. Choi SJ, Song SE, Jung KL, Oh SY, Kim JH, Roh CR. Antepartum risk factors associated with peripartum cesarean hysterectomy in women with placenta previa. Am J Perinatol 2008;25(1):37-41. 9. Ogawa M, Sato A, Yasuda K, Shimizu D, Hosoya N, Tanaka T. Cesarean section by transfundal approach for placenta previa percreta attached to anterior uterine wall in a woman with a previous repeat cesarean section: case report. Acta Obstet Gynecol Scand 2004;83(1):115-6. 10. Boehm FH, Fleischer AC, Barrett JM. Sonographic placental localization in the determination of the site of uterine incision for placenta previa. J Ultrasound Med 1982;1(8):311-4. 11. Hemmadi SS, Shenyar NK Walvekar. J Obstet Gynecol India 1995,4:365. 12. Reddy R, Latha C. Placenta previa: an analysis of 4 year experience. J Obstet Gynecol India 1999;53-56. 13. Rasmussen S, Albrechtsen S, Dalaker K. Obstetric history and the risk of placenta previa. Acta Obstet Gynecol Scand 2000;79(6):502-7. 14. Taylor VM, Kramer MD, Vaughan TL, Peacock S. Placental previa in relation to induced and spontaneous abortion: a population-based study. Obstet Gynecol 1993;82(1):88-91. 15. Clark SL, Koonings PP, Phelan JP. Placenta previa/accreta and prior cesarean section. Obstet Gynecol 1985;66(1): 89-92. 16. Jang DG, We JS, Shin JU, Choi YJ, Ko HS, Park IY, et al. Maternal outcomes according to placental position in placental previa. Int J Med Sci 2011;8(5):439-44. 17. Decherney AH, Pernoll ML. Current Obstetrics and Gynecology. Diagnosis and Treatment Third Trimester Hemorrhage. 8th edition, 1994:p.404-9. ■■■■ Early imbalances in angiogenic factors predict poor pregnancy outcomes in women with systemic lupus erythematosus or antiphospholipid syndrome (APL), a new research presented at the American College of Rheumatology (ACR) 2013 Annual Meeting. According to the authors, these findings could lead to a test to predict poor pregnancy outcomes as early as 16 weeks of gestation. Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 571
- 72. ONCOLOGY Lytic Skeletal Metastasisfrom Lung Cancer Amit Agrawal Abstract We discuss imaging findings in a case of skull and pelvic metastasis from a lung cancer, in a 40-year-old man, who presented with painless parietal scalp swelling. Keywords: Adenocarcinoma, metastasis, lung, skull, skeletal metastases P atients with skull metastases are characterized by higher age, shorter duration of symptoms, local swelling that is usually painless and less frequently present with neurological deficit, when compared to primary skull tumors and benign tumorlike lesions.1-4 Possibility of skull metastasis must be kept in mind when considering the differential diagnosis of a lytic skull lesion.2-4 Case report A 40-year-old gentleman, a chronic smoker (>30 years) presented with productive cough and hemoptysis since two months, right parietal scalp swelling of one month, and severe pain in left hip region of three days duration associated with loss of weight and appetite. On examination, he was emaciated, pallor was present and he had Grade III clubbing. Chest examination revealed bronchial breath sounds and crepitations in left mammary area. There was no hepatosplenomegaly or lymphadenopathy. Local examination showed 2 × 2 cm firm, nontender, nonpulsatile scalp swelling over right parietal region fixed to bone and skin over it was healthy. There were no focal neurological deficits. His hemoglobin was 9.2 g% and erythrocyte sedimentation rate (ESR) was 110 mm in 1st hour. Other blood investigations were normal. X-ray pelvis showed Associate Professor (Neurosurgery) Dept. of Surgery Datta Meghe Institute of Medical Sciences Sawangi (Meghe), Wardha, Maharashtra Address for correspondence Dr Amit Agrawal Associate Professor (Neurosurgery) Clinical and Administrative Head Division of Neurosurgery Datta Meghe Institute of Medical Sciences, Sawangi, (Meghe) Wardha- 442 004, Maharashtra E-mail: dramitagrawal@gmail.com 572 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 a b Figure 1. CT scan of the head shows a lytic skull lesion (a); X-ray chest showing well-defined lesion in left lower lobe of lung (b).
- 73. ONCOLOGY lytic lesion insuperior aspect of left acetabulum. X-ray skull showed lytic lesion in right parietal bone. Computed tomography (CT) revealed an irregular osteolytic lesion in right parietal bone that invaded and expanded through both inner and outer tables of the skull in full thickness with normal brain parenchyma (Fig. 1a). X-ray chest showed consolidation in left lower zone (Fig. 1b). Ultrasound abdomen was normal. He underwent gross total removal of the lesion to establish the diagnosis. Histological examination of the tumor revealed a metastatic adenocarcinoma. initial treatment, modified follow-up or reconsideration of surgical therapy for the primary tumor.9,11 Discussion 3. Wong GK, Boet R, Poon WS, Ng HK. Lytic skull metastasis secondary to thyroid carcinoma in an adolescent. Hong Kong Med J 2002;8(2):149-51. Lung cancer is the most common cancer in the world and accounts for 12.3% of all new cancer cases with millions of deaths per year.5 According to reports by the American Lung Association, the vast majority of patients with lung cancer (85%) have metastatic disease at the time of presentation.6 Patients with metastatic lung cancer have a 5-year survival rate of 2.1%, compared to those who have disease limited to the lungs at 48.5%.7 Hematogenous skull metastases can be caused by nearly all types of tumors including breast, lung, prostate, thyroid carcinoma, malignant melanoma).1,3,8 However, the most common sites for metastases from lung cancer are the upper abdomen followed by lung and pleura and lastly bone.2 Metastases from lung cancer involve spine and hip but skull involvement is uncommon.9 X-ray and CT is a keystone in the diagnostic evaluation of suspected lung cancer, because it provides the most detailed anatomical images.10 Multiplicity, irregular edges and absence of peripheral sclerosis should arouse suspicion of malignancy and a biopsy is warranted in these cases.3 Preoperative contrast-enhanced Magnetic resonance imaging of the brain and skeleton is recommended for the detection of parenchymal and osseous lesions in patients with large pulmonary lesions (>3 cm diameter or higher than T1 stage).9,11 The correct staging of patients with lung cancer is essential for appropriate care and cost containment as patients with nonresectable metastatic disease may need additional therapy at the time of References 1. Stark AM, Eichmann T, Mehdorn HM. Skull metastases: clinical features, differential diagnosis, and review of the literature. Surg Neurol 2003;60(3):219-25; discussion 225-6. 2. Aquino SL, Fischman AJ. Does whole-body 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography have an advantage over thoracic positron emission tomography for staging patients with lung cancer? Chest 2004;126(3):755-60. 4. Kim SH, Kosnik E, Madden C, Morran S, Rusin J, Gordon T, et al. Lytic skull metastasis from a follicular thyroid carcinoma in a child. Pediatr Neurosurg 1998;28(2):84-8. 5. Tyczynski JE, Bray F, Parkin DM. Lung cancer in Europe in 2000: epidemiology, prevention, and early detection. Lancet Oncol 2003;4(1):45-55. 6. Pretreatment evaluation of non-small-cell lung cancer. The American Thoracic Society and The European Respiratory Society. Am J Respir Crit Care Med 1997;156(1):320-32. 7. Trends in lung cancer morbidity and mortality. American Lung Association Epidemiology and Statistics Unit, Research and Scientific Affairs, June 2003. Available at: http://www. lungusa.org/atf/cf/. Accessed March 12, 2008. 8. Bontoux D, Plazanet F, Azais I. Distribution of bone metastases of cancers. A scintigraphic study of 376 cases. Bull Acad Natl Med 1998;182(5):997-1008; discussion 1008-9. 9. Earnest F 4th, Ryu JH, Miller GM, Luetmer PH, Forstrom LA, Burnett OL, et al. Suspected non-small cell lung cancer: incidence of occult brain and skeletal metastases and effectiveness of imaging for detection - pilot study. Radiology 1999;211(1):137-45. 10. Verschakelen JA, Bogaert J, De Wever W. Computed tomography in staging for lung cancer. Eur Respir J Suppl 2002;35:40s-48s. 11. Akeson P, Larsson EM, Kristoffersen DT, Jonsson E, Holtås S. Brain metastases--comparison of gadodiamide injection-enhanced MR imaging at standard and high dose, contrast-enhanced CT and non-contrast-enhanced MR imaging. Acta Radiol 1995;36(3):300-6. ■■■■ For HIV-infected patients with cancer undergoing chemotherapy, the integrase strand-transfer inhibitor raltegravir is the best choice for viral suppression, according to a new study presented at the 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy. The efficacy of raltegravir is similar to that of nonnucleoside reversetranscriptase inhibitors, but the rate of adverse events is lower. Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 573
- 74. ORTHOPEDICS Study of OrthopedicMorbidities Among Postmenopausal Women in a Medical College Hospital in Rural Area of Western Maharashtra, India Shubhada SUNIL Avachat*, Shrikant Balkrishna Deshpande**, Mrinal Balbhim Zambare†, DEEPAK BABURAO PHALKE‡ Abstract Introduction: It is estimated that a total of 130 million Indian women are expected to live beyond menopause by 2015. Health of postmenopausal women is of growing concern because of increased longevity and various morbidities associated with old age. Objectives: 1) To assess various orthopedic problems among postmenopausal women in rural area. 2) To estimate magnitude of common orthopedic problems and associated sociodemographic factors. Methodology: A cross-sectional study was conducted at the medical college hospital in rural area of Western Maharashtra on 500 postmenopausal women availing healthcare in a medical college hospital. Data was collected with the help of predesigned questionnaire by interview technique and with the help of case records available from orthopedic department. Results: Backache (62%) and osteoarthritis (51.6%) were common orthopedic problems. Osteoarthritis was significantly associated with obesity. Keywords: Postmenopausal women, orthopedic problems M enopausal and postmenopausal health has emerged as an important concern owing to increased longevity and changing lifestyle of Indian women. It is estimated that a total of 130 million Indian women are expected to live beyond menopause by 2015.1 The focus of women’s health researchers and health policy planners has also shifted toward postmenopausal women since recent trends suggest an increase in their numbers and life expectancy. Long-term consequences of changes in ovarian hormonal levels include morbidities associated with *Assistant Professor Dept. of PSM Padmashree Dr Vithalrao Vikhe Patil Foundation’s Medical College, Ahmednagar, Maharashtra **Associate Professor Bharati Vidyapeeth Deemed University Medical College and Hospital, Sangli, Maharashtra †Professor and Head Dept. of PSM Padmashree Dr Vithalrao Vikhe Patil Foundation’s Medical College, Ahmednagar, Maharashtra ‡Professor and Head Dept. of PSM Rural Medical College, Loni, Maharashtra Address for correspondence Dr (Mrs) Shubhada Sunil Avachat 5, Samartha Colony, Bhutkarwadi Savedi Road, Ahmednagar - 414 003, Maharashtra E-mail: shubhadasunuil@gmail.com 574 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 aging such as cardiovascular diseases, osteoporosis, problems related to memorization, urinary incontinence, skin aging and others.3,4 Postmenopausal women are generally affected by osteoporosis and fracture rates among them are approximately twice as high as men. The cause of osteoporosis is very complex but it is clear that hormonal changes after menopause increase the rate of bone resorption, leading to greater risk of osteoporosis. This silently progressing metabolic bone disease is widely prevalent in India and is a common cause of morbidity and mortality in women.5 The occurrence of osteoporosis in postmenopausal women is a very common problem especially in India, as Indian women are exposed to many risk factors like low calcium diet, lack of exercise, family history and in general, lack of health awareness. The prevalence of osteoporosis increases with age and it is estimated that 70% of women over the age 80 years have osteoporosis.6 The problem of backache becomes more pronounced in postmenopausal women.7 During this period of women’s life, the likelihood of weight gain and manifestation of low back pain increases due to the changes of the muscles and skeleton structures as a result of aging, occupational or other factors. Osteoarthritis is also one of the common health problem among elderly women.
- 75. ORTHOPEDICS Osteoarthritis strikes womenmore often than men and it increases in prevalence, incidence and severity after menopause.8,9 postmenopausal age who visited orthopedic department during study period were ready to participate, making the sample size 500. There is a growing recognition that various morbidities occur in postmenopausal age group, yet information on the levels and patterns of these health problems experienced by women in India is sparse. Only a few studies have been undertaken to understand the effects of menopausal transition in relation to aging process on general health profile of women in postmenopausal life. Since, a large proportion of women suffer morbidity silently and are reluctant to seek care or to visit clinics and hospitals, it is difficult to assess the true magnitude of the problem or the patterns of morbidity from which women suffer. Yet the small amount of data available suggest startlingly high levels of morbidity, for which treatment is rarely sought. Data Collection Because of inadequate medical facilities in rural areas and poor resources to obtain treatment from private medical practitioners, women in villages often become a victim of a number of health problems. Hence, studies are needed in rural areas to investigate physical, physiological and social changes experienced during the menopausal transitions along with the nature and magnitude of health problems during postmenopausal life. Orthopedic problems are very common after menopause and significantly affect the health of Indian women. Therefore, present study was conducted among postmenopausal women attending medical college hospital in a rural area to assess morbidity pattern with special reference to orthopedic morbidity. Data was tabulated and appropriate statistical analysis was done with the help of percentages and proportions. Test of significance was applied wherever required. Methodology Study Design A cross-sectional study. Study Setting Study was conducted in the Dept. of Orthopedics, Rural Medical College and Hospital during January 2010 to December 2010. Sampling and Sample Size All the women in postmenopausal age group attending orthopedic outpatient department (OPD) during study period and who were ready to participate were included in the study. Women who had not achieved menopause and who were not ready to participate were excluded from the study. Five hundred women of After explaining purpose of the study and obtaining verbal consent, data was collected from them by interview technique. A predesigned, structured questionnaire was used to collect necessary information. Questions were mainly pertaining to their complaints related to orthopedic problems. The clinical findings and X-ray findings were obtained from individual case records prepared by resident doctors and other faculty members of orthopedic department. Modified BG Prasad’s classification was used for determining economic status.10 Statistical Analysis RESULTS Our study was conducted among 500 women of postmenopausal age who visited orthopedic OPD during the study period. Majority of the women were from the age group of 55-65 years. Sixty-four percent women were married, 68.6% were illiterate and most of them were from low socioeconomic status (Table 1). Majority of women seeking healthcare from orthopedic department had either joint pain (predominantly knee) or backache. Some of the women had backache as well as knee pain. Only few women in postmenopausal age group had other orthopedic complaints like fracture, sprain and ligament problems (Table 2). Out of 500 women, 310 (62%) were suffering from backache. Degenerative disease (osteoporosis) was the most common cause of backache observed in our study. Common X-ray findings observed among our study subjects were osteoporotic changes in spine, osteophytes in vertebrae or wedge compression (Table 3). Joint pain with predominant involvement of knee joint was another common symptom observed in our study participants. Out of 500 women having orthopedic problems, 258 (51.6%) were suffering from osteoarthritis. Reduction of medial joint space and reduction of bone trabeculae with increase in lucency were the X-ray findings observed in our study among patients suffering from knee joint pain. Body mass index of patients Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 575
- 76. ORTHOPEDICS Table 1. SociodemographicProfile of Study Participants Age in years Table 4. Association of Osteoarthritis and Obesity 9 (1.8%) 50-55 74 (14.8%) 55-60 111 (22.2%) 60-65 248 (49.6%) 65-70 47 (9.4%) >70 11 (2.2%) Total 500 Married 324 (64.8%) Widow 159 (31.8%) Unmarried 017 (3.4%) 500 Educational status Illiterate 343 (68.6%) Primary 118 (23.6%) Secondary and higher secondary 37 (7%) Graduate and above 2 (0.4%) Total 500 Economical status Upper (I, II, III of BG Prasad) 186 (37.2%) Lower (IV and V of BG Prasad) 314 (62.8%) Total 500 Table 2. Symptom-wise Distribution of Patients (Multiple Response) Symptoms No. of patients Backache 310 Joint pain 274 Others 053 Table 3. Distribution of Backache Patients According to Etiology (n = 310) Age group (in years) Degenerative disc disease (osteoporosis) Facet joint arthopathy Spondylolisthesis 50-55 22 16 1 55-60 46 18 4 61-65 98 43 8 65-70 40 6 2 >70 5 0 1 Total 211 83 16 576 Total 147 (63.6%) 84 (36.4%) 231 (100%) 111 158 269 258 242 500 χ2 = 24.2; d.f. = 1; p < 0.001; Highly significant. suffering from osteoarthritis was also calculated and it was observed that osteoarthritis was significantly associated with obesity in our study (Table 4). Marital status Total No. of nonobese women Total < 50 No. of obese women Absent Age Osteoarthritis Present No. of women Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 Discussion The abrupt endocrine changes during menopausal transition have important impacts on the physiology of female body that exacerbate risks for many diseases and disabilities during postmenopausal life. Present study was conducted among 500 postmenopausal women to assess various orthopedic problems among them; majority of women in our study population were in the age group of 60-70 years (59%), illiterate (68.6%), and belonged to low economic status. Similar finding was observed by Mandal et al in their study, 58.6% women were in the age group between 60-70 years, 61% were illiterate and majority of them belonged to low economic status.11 Backache and joint pain as a manifestation of osteoporosis and osteoarthritis, respectively, were the most common problems among our study subjects. Similar finding was observed by Scharla et al in their study, 85.1% postmenopausal women had back pain and 41.8% had joint pain.12 Many studies showed that the prevalence of osteoarthritis increases in old age and more so in women than men. Females are found to have more severe osteoarthritis and involvement of knee joint is more common.13-15 In our study, osteoarthritis was present among 51.6% women. Obesity is a well-known risk factor for osteoarthritis and in our study also it was significantly common among obese women. Similar to our finding, the prevalence of osteoarthritis was 49% in the study conducted by Mandal et al and 57% in the study conducted by Lena et al.16 Conclusion Orthopedic morbidities are very common in postmenopausal women. Osteoporosis and osteoarthritis
- 77. ORTHOPEDICS are the commonorthopedic problems and large number of these health problems can be prevented and managed by simple measures like exercise, diet and proper healthcare. Acknowledgment 7. Popkess-Vawter S, Patzel B. Compounded problem: chronic low back pain and overweight in adult females. Orthop Nurs 1992;11(6):31-5, 43. 8. Felson DT. The epidemiology of knee osteoarthritis: results from the Framingham Osteoarthritis Study. Semin Arthritis Rheum 1990;20(3 Suppl 1):42-50. We are thankful to the management of Pravara Medical Trust, Dept. of Orthopedic, Pravara Rural Hospital, for allowing the study and the interns Miss Bajpayee and Sharmin Bala for their help. 9. Kellgren JH, Lawrence JS, Bier F. Genetic factors in generalized osteoarthrosis. Ann Rheum Dis 1963;22: 237-55. References 11. Mandal PK, Chakrabarty D, Manna N, Mallik S. Disability among geriatric females: an uncared agenda in rural India. Sudanese J Pub Health 2009;4(4):377-82. 1. Sengupta A. The emergence of the menopause in India. Climacteric 2003;6(2):92-5. 2. World Health Organization. Women Aging and Health. WHO: Geneva, 2000. Fact sheet No. 252. 3. Genazzani AR, Gambacciani M, Schneider HP, Christiansen C. International Menopause Society Expert Workshop. Postmenopausal osteoporosis: therapeutic options. Climacteric 2005;8(2):99-109. 4. Isles CG, Hole DJ, Hawthorne VM, Lever AF. Relation between coronary risk and coronary mortality in women of the Renfrew and Paisley survey: comparison with men. Lancet 1992;339(8795):702-6. 5. Gupta A. Osteoporosis in India - the nutritional hypothesis. Natl Med J India 1996;9(6):268-74. 6. Osteoporosis in Postmenopausal Women: Diagnosis and Monitoring. Summary, Evidence Report/Technology Assessment: No.28. Agency for Healthcare Research and Quality Publication No. 01-E031, Feb 2001. Available at: http://www.ahrq.gov/clinic/epcsums/osteosum.htm 10. Kumar P. Social classification - need for constant updating. IJCM 1993;18(2):60-1. 12. Scharla S, Oertel H, Helsberg, et al. Skeletal pain in postmenopausal women with osteoporosis. J Bone Miner Res 2005;20(Suppl 1):318-98. 13. Felson DT. The epidemiology of knee osteoarthritis: results from the Framingham Osteoarthritis Study. Semin Arthritis Rheum 1990;20(3 Suppl 1):42-50. 14. Slemenda CW. The epidemiology of osteoarthritis of the knee. Curr Opin Rheumatol 1992;4(4):546-51. 15. Eti E, Kouakou HB, Daboiko JC, Ouali B, Ouattara B, Gabla KA, et al. Epidemiology and features of knee osteoarthritis in the Ivory Coast. Rev Rhum Engl Ed 1998;65(12): 766-70. 16. Lena A, Ashok K, Padma M, Kamath V, Kamath A. Health and social problems of the elderly: a cross-sectional study in Udupi Taluk, Karnataka. Indian J Community Med 2009;34(2):131-4. Diet Combined with Exercise Relieves Arthritic Knee Pain Osteoarthritis (OA) is a common trouble in old age. Symptoms of OA may include joint pain, tenderness, stiffness, locking and sometimes an effusion. Generally, doctors advise the patients to reduce weight to help reduce knee pain. A study was published recently that aimed to assess the clinical and functional outcome in knee pain in arthritic patients by modifying diet alone (Group A), modifying diet and combining it with exercise (Group B), and by exercise only (Group C). It was single-blind, randomized clinical trial, which was done for 18 months to study the outcome of pain on 454 overweight and obese people aged >55 years with positive radiographic knee OA findings. It was observed that slightly changing the lifestyle by doing some amount of exercise along with diet control were more effective in reducing weight, inflammation and pain. Their quality-of-life improved as they had less pain and more mobility. On the contrary, the group that performed only diet modifications or only exercised did not experience such positive results. In diet modifications, two meals consisted of only nutritional shakes while the third meal had very less fats but was rich in vegetables. Average weight loss was greater in the diet and exercise group (−10.6 kg; 95% confidence interval [CI], −14.1 to −7.1 kg) and the diet group (−8.9 kg; 95% CI, −12.4 to −5.3 kg) compared with the exercise group (−1.8 kg; 95% CI, −5.7 to 1.8 kg) at the 18-month follow-up. On 6-month follow-up, all the three groups had similar amount of pain reduction, but on 18-month follow-up it was noticed that the group with diet modifications combined with exercises provided more relief in pain and better mobility. So, it was concluded that diet or exercise alone would be less effective than diet clubbed with exercise in knee OA. (Source: JAMA 2013;310:1263-73.) Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 577
- 78. Preventive and socialmedicine A Quantitative Assessment of RNTCP in Meerut District of Uttar Pradesh SANJAY GUPTA Abstract Objective: The study has been conducted to study the various operational and performance indicators of RNTCP quantitatively in the urban and rural area of Meerut District, Uttar Pradesh. It is a cross-sectional study with a multistage random sampling from tuberculosis unit, microscopy centers and directly observed treatment, short-score (DOTS) centers to cover one-eighth of the district. Four hundred tuberculosis patients taking DOTS in Meerut District were the participants. The methodology developed to conduct the study was a modified form of rapid survey methods, for monitoring and evaluation of district tuberculosis center (DTC), tuberculosis units, microscopic centers and DOTS center. The data was collected, coded manually, tabulated and has been presented in the form of simple frequency tables and bivariate table as and where required. The proportion of the sputum smear-positive among symptomatic was found to be 17.1%, the proportion of the sputum smear-positive put on DOTS 90.9% and three months sputum conversion rate was found to be 94.9. The cure rate was found to be 80.5%, treatment completed 7.5%, treatment failure 1.5%, death rate 2.2%, ratio of nonseriously ill smear-negative to seriously ill smear-negative was found to be 11.5:1 and the ratio of nonseriously ill extrapulmonary to seriously ill extrapulmonary was found to be 10:1. Keywords: Tuberculosis, performance, efficiency T uberculosis, the word evokes feelings of fear, anxiety, stigma and despair, known for centuries to afflict, debilitate, impoverish large section of the population and even kill, continues to ravage the world. It is a worldwide health problem. For the control of tuberculosis, in 1962, Government of India launched National Tuberculosis Control Program,1 but the program did not achieve the desired results. In 1992 Government of India, World Health Organization (WHO) and World Bank, Revised National Tuberculosis Control Program (RNTCP) with direct observation of swallowing of drugs by the patients and the objectives of achieving at least 85% cure rate through directly observed treatment, short-course (DOTS) and case finding 70% of the estimated cases.2 This revised strategy was introduced in the country as a pilot project since 1992 in a phased manner and proposed to be expanded throughout the country by the year 2005.3 Studies have shown that treatment success under RNTCP has increased for all types of patients between 1995 and 1998.4 RNTCP being a switch-over program from the previous NTCP, more and more Associate Professor Dept. of Community Medicine Guru Gobind Singh Medical College, Faridkot, Punjab E-mail: sanjayguptacmc@rediffmail.com 578 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 operational researches are needed at this juncture when it is moving from one phase to another to know whether it is heading toward the right direction as far as pace and quality of implementation are concerned. DOTS is the strategy and heart of the program5 and the DOTS providers have equal importance. The performance of any program is judged by certain performance indicators related with it, results achieved and the patient satisfaction. Performance indicators may be of qualitative or quantitative type. WHO has defined certain performance indicators at various levels of implementations in the program. The present study that has been conducted in Meerut District is an attempt to access the efficiency of the program in comparison to the standard performance indicators of WHO of RNTCP. Material and MethodS The study was conducted in the Meerut District of Uttar Pradesh. For the program implementation, the entire district was divided into six tuberculosis units. The tuberculosis units were further divided into microscopic centers and DOTS centers. The material for the study was obtained by multistage random sampling. One-eighth portion of the district has been covered that comprises three treatment units, seven microscopic centers, 60 DOTS centers and 431 patients.
- 79. Preventive and socialmedicine The methodology developed to conduct the study is a modified form of rapid survey methods for monitoring and evaluation of district tuberculosis centers (DTC), tuberculosis units, microscopic centers and DOTS centers. An interview and salient observation were made at various levels on the DOTS day of the weeks, that is Monday, Wednesday and Friday. Minimum 4-5 visits have been given to each center of study. The unavailable patients on the respective centers were contacted at their home. At the end of the prescribed duration of treatment, all the patients were again contacted at their home to see the final outcome of the patients. Out of the 431 registered patients on the selected centers, only 400 (92.8%) could be covered, rest 31 (7.2%) could not be covered due to nonavailability or uncooperative behavior. The data was collected, coded manually, tabulated and has been presented in the form of simple frequency tables and bivariate tables as and where required. The data was analyzed and statistically evaluated wherever applicable by appropriate tests of significance. Results and Discussion It is evident from the Table 1 that majority of the patients 220 (55.0%) are in the age group 20-29 years followed by 58 (14.5%) patients who were in the age group 40-44 and 53 (13.2%) who were in 30-34 years. In a longitudinal study by National Tuberculosis Institute, Bangalore5 (1961-1968), prevalence of tuberculosis increases with age was found to be maximum (62.1%) in the age group 55 and above followed by 45-54 (60.7%), 35-44 (55.8%), 25-34 (47.3%) and in 15-24, it was 31.9%. In the present study, this age-wise difference in the sex proportion of the cases was not found to be statistically significant (p > 0.05). In the present study, 181 (41.2%) were males and 219 (54.8%) were females. In Bijnor District6 of Table 1. Age and Sex-wise Distribution of Tuberculosis Cases Age group 15-19 20-24 25-29 30-34 35-39 40-44 45+ Total Male N % 12 6.6 52 28.7 46 25.4 28 15.5 7 3.9 28 15.5 8 4.4 181 45.2 Female N % 10 4.5 53 24.2 69 31.5 25 11.5 19 8.7 30 13.7 13 5.9 219 54.8 Total N % 22 5.5 105 26.2 115 28.8 53 13.2 26 6.5 58 14.5 21 5.3 400 100 Table 2. Religion-wise Distribution of Tuberculosis Cases Religion Male Female Total N % N % N % Hindu 119 49.1 123 50.9 242 60.5 Muslim 62 39.2 96 60.8 158 39.5 Total 181 45.2 219 54.8 400 100 Table 3. Education-wise Distribution of Tuberculosis Cases Literacy level Ιlliterate Just literate Primary Middle Higher secondary Intermediate Graduate and above Total N 46 44 30 23 15 Male % 25.4 24.3 16.6 12.7 8.3 Female N % 79 36 24 11 55 25.1 31 14.2 17 7.7 Total N % 125 31.3 68 17 85 21.2 54 13.5 32 8 19 4 10.5 2.2 12 1 5.5 0.5 31 5 7.8 1.2 181 45.2 219 54.8 400 100 Table 4. Breakdown Ratio of Tuberculosis Cases Ratio New smear-positive: New smear-negative New smear-positive: Retreatment smear-positive New smear-positive: Extrapulmonary Non seriously ill smear-negative: Seriously ill smear-negative Nonseriously ill extrapulmonary: Seriously ill extrapulmonary Study Expected population 1.40:1 1:1 1.65:1 2:1 4.79:1 11.5:1 5:1 4:1 10.0:1 4:1 Uttar Pradesh, this ratio was 56% and 44% for male, and female, respectively. Ahmed (1981), in a study of prevalence of tuberculosis in Meerut District also found male dominancy in tuberculosis patients, that is, 62%.7 According to the National Sample Survey8 the prevalence of disease in males was 3-5 times more than in the females. As we can see from Table 3, 125 (31.3%) were illiterate, 68 (17.0%) were just literate and 85 (21.2%) were literate, only upto primary. One hundred ninety-three (48.3%) were either illiterate or just literate. In contrast to 70% being illiterate as reported by Ahmed (1981)7 this may Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 579
- 80. Preventive and socialmedicine be due to overall uplift of literacy level of the population. For the program efficiency, during a specific three months period all the patient whose sputum was examined in all the selected tuberculosis unit were assessed. The proportion of the sputum smear-positive was found to be 17.1% that was more than the expected (8-12%) indicating either high prevalence of tuberculosis in the area or the awareness was more in the population regarding the symptoms of tuberculosis. The proportion of the sputum smear-positive put on DOTS was found to be 90.9% (expected >90%) and three months sputum conversion rate was found to be 94.9% that is more than the expected (85%) indicating either good compliance or good quality work of the DOT providers. The ratio of the new sputum smear-positive to new sputum smear-negative was found to be 1.4:1, which is higher than the expected value of the program that is, 1:1 and never be higher than 1:1.2, indicating that more of the infectious cases are present in the community in comparison to expected cases according to WHO or over diagnosis of pulmonary cases. The ratio of the nonseriously ill smear-negative was found 11.5:1, which is much higher than the expected of the program that is, 4:1 indicating the seriously ill cases are either under reporting or patients were presenting early before reaching the seriously ill stage. The ratio of nonseriously ill extrapulmonary to seriously ill extrapulmonary cases was found to be 10:1, which is also much higher than the expected value of 4:1. It shows again either the seriously ill cases are under reporting or patients were presenting early before reaching the seriously ill stage. Out of these 400, 322 were cured, 30 had completed their treatment, 33 defaulted, six were treatment failure and nine died. The cure rate 80.5% was found to be less than of expected 85% of Meerut District 91% of Uttar Pradesh9 86% and of India10 as a whole 83%. Defaulter rate 8.3% was also found to be also higher than the expected of 5%. Failure rate was found to be 1.5%, which is much Table 5. Outcome of the Patients Outcome of the patients No. % Expected Cured 322 80.5 85.00% Completed treatment 30 7.5 3.00% Default 33 8.3 < 5% Treatment failure 6 15 < 4% Death 9 2.2 < 4% 580 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 less than the expected, which is upto 4%. Similarly, death rate (2.2%) was also lesser than the expected which is upto 4%. Conclusion Efficiency is a measure how well resources (money, manpower, material and time) are utilized to achieve a given effectiveness. This simply means whether the outcome of the activity/program are or not within the accepted norms as compared to the desired standard. The studies recommend that there should be periodic re-orientation training of Medical Officers and DOTS providers, ensuing proper supervision from tuberculosis unit and district level, reviewing of performance and timely feedback regarding performance of each health unit can be undertaken at the present moment for improvement of performance for better implementation and sustenance of the program in the area. REFERENCES 1. Park K. Textbook of Preventive and Social Medicine. 6th edition, Banarasi Das Bhanot: Jabalpur 1997:p.120-40. 2. World Health Organization. Stopping Tuberculosis. WHO Regional office for South East Asia, New Delhi, 2000. 3. Central TB Division. Managing the Revised National Tuberculosis Control Programme in your Area. A Training Course: Modules 1-4. Directorate General of Health Services, Ministry of Health and Family Welfare, New Delhi, 1998. 4. World Health Organization. Joint Tuberculosis Programme Review of India. WHO Regional Office for South East Asia, New Delhi. 2000. 5. National Tuberculosis Institute: Facts & Figures on Tuberculosis and National Tuberculosis Programme Second. Bangalore. 6. Bhatnagar S. Distribution pattern of tuberculosis patients attending district tuberculosis centres, Bijnore, Uttar Pradesh, NTI Bulletin 2000;36(1&2):11-2. 7. Ahmed S. A retrospective study of epidemiology of pulmonary tuberculosis in a rural community of Meerut District. A thesis for M.D (SPM), Meerut University1981:p.6-40. 8. Chadha VK. National sample of different parts of India. NTI Bulletin 2000;XXXVI (1&2):12-6. 9. Central TB Division. TB India 2001. RNTCP Status Report, Directorate General of Health Services Ministry of Health and Family Welfare, New Delhi, 2001. 10. Khatri GR. The Revised National Tuberculosis, Control Programme: a status report on first 1,00,000 patients. NTI Bulletin 2000;XXXVI(1&2):18-26.
- 81. UROLOGY Nephrotic Syndrome: ARare Presentation of AIDS Prabhat Agrawal*, Ashish Gautam*, Manish Kumar Bansal**, Ayush Agrawal† Abstract The clinical presentation of HIV-associated nephropathy (HIVAN) include proteinuria, typically in nephrotic range (often massive) and renal insufficiency. HIVAN can be an early manifestation of HIV infection. The term HIVAN is reserved for focal segmental glomerulosclerosis (FSGS) but other glomerular lesions may be there. We are reporting a case of nephrotic syndrome (MPGN) in an otherwise asymptomatic HIV-infected patient. Keywords: HIVAN, nephrotic syndrome, MPGN H uman immunodeficiency virus (HIV) disease usually presents with the classical features of acquired immunodeficiency syndrome (AIDS) and opportunistic infections. According to available literature, presentation of anasarca is rare. HIV-associated nephropathy (HIVAN) is one of the leading causes of end-stage renal disease (ESRD) among HIV-infected patients. HIVAN is characterized by heavy proteinuria and impairment of renal function. HIVAN could be an early manifestation of HIV infection. The term HIVAN is reserved for the characteristic light microscopic pattern of focal segmental glomerulosclerosis (FSGS) with collapsing feature and related mesangiopathies.1 Here, we are reporting a case who presented with anasarca, an uncommon feature of HIV-associated nephropathy. On examination, the blood pressure reported was 170/100 mmHg and pulse rate was 88 per minute. The patient was having pallor and generalized swelling (pitting type), without lymphadenopathy or icterus. Chest, cardiovascular and neurological examination was normal. On abdominal examination, distended abdomen and mild hepatosplenomegaly was present. His investigations revealed hemoglobin (Hb) was 8.8 g/dl, total leukocyte count was 6,900/mm3 (P-40, L-46, E-12, M-2), platelet count was 1.78 lakh/mm3, blood urea was 75 mg/dl and serum creatinine was 2.2 mg/dl. On urine examination, albumin was 4+, RBCs: 20-30 per high power field, 2-3 pus cells/HPF and granular and hyaline casts were present. A 24-year-old male came to the outdoor department (OPD) with complaints of progressive generalized swelling for 20-25 days. There was no history of fever, decreased urinary output, jaundice, rash, oral ulcers, sore throat, arthralgia, hematuria, blood transfusion or recent vaccination. Total serum proteins reported were 4.2 g/dl with both albumin and globulin being 2.1 mg/dl each. Serum cholesterol was 310 mg/dl. Antistreptolysin O (ASO) titer was negative at the time of admission and after one week. Liver function tests (LFTs), thyroid function tests and serum electrolytes and blood sugar levels were found to be normal. Chest X-ray was normal. Ultrasonography (USG) abdomen showed bilaterally enlarged kidneys with the right kidney being 151 × 67 mm and left kidney being 155 × 75 mm, hepatosplenomegaly and mild ascites. *Assistant Professor **Associate Professor †Junior Resident PG Dept. of Medicine Sarojini Naidu Medical College, Agra, Uttar Pradesh Address for correspondence Dr Prabhat Agrawal Assistant Professor PG Dept. of Medicine Sarojini Naidu Medical College, Agra, Uttar Pradesh E-mail: prabhatagrawal123@rediffmail.com On further investigations, C3 complement levels were low (< 0.30 g/dl) and C4 was normal. Twenty-four hours urinary protein was found to be 17.8 g. The patient was found to be HIV-1 positive by enzyme-linked immunosorbent assay (ELISA) and his absolute CD4 count was 301. Hepatitis B surface antigen (HBsAg) and anti-HCV (hepatitis C virus) were negative. Renal biopsy was done with universal precautions and on light microscopy membranoproliferative glomerulonephritis (MPGN) was diagnosed. CASE REPORT Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 581
- 82. UROLOGY The working diagnosiswas kept as an immunocompromised state that presented with anasarca, the cause being nephrotic syndrome (MPGN). renal disease with heavier proteinuria and higher incidence of nephrotic syndrome and associated renal insufficiency. The patient was treated conservatively with salt and fluid restriction along with antihypertensives, diuretics and angiotensin-converting enzyme (ACE) inhibitors. The patient was put on corticosteroids (prednisolone 1 mg/kg daily) and antiretroviral therapy (ART) after the biopsy report. On follow-up after one month, his anasarca had subsided and the patient was asymptomatic. His 24-hour urine protein had decreased to 7.5 g/dl. Now the patient is on ART and tapering dose of steroids over 2-3 months, and is in regular follow-up after every 15 days. Racial factors are also important as they are involved in the mutation of HIV receptors, which may in part, explain some differences in the racial predisposition of HIV infection to HIVAN. Although intravenous drug use has been the most common risk factor for HIVAN, the disease has been seen in all groups at risk for AIDS including homosexuals, those with perinatally acquired disease, heterosexual transmission and exposure to contaminated blood products. HIVAN usually occurs in patients with a low CD4 count, but full blown AIDS is not a pre-requisite for the disease. In one New York study, the onset of HIVAN was most common in otherwise asymptomatic HIV-infected patients (12 out of the 26 were asymptomatic patients). There is no relationship between the development of HIVAN and the patient age, duration of HIV infection or the presence or absence of other opportunistic infections. DISCUSSION Renal involvement in a patient infected with HIV may include glomerulonephritis, tubule interstitial disease, acute tubular necrosis, drug-related interstitial nephritis, pyelonephritis, nephrocalcinosis, electrolyte abnormalities, neoplasms (Kaposi’s sarcoma and lymphoma) and opportunistic infections (such as aspergillosis, mucormycosis and adenovirus infections).2 The classic and the most common HIV-associated glomerulopathy is an aggressive form of FSGS, an entity that is termed as HIVAN. This disease may be the first manifestation of infection in an otherwise asymptomatic patient.3 Renal biopsy typically reveals visceral epithelial cell swelling, collapse of the glomerular capillary tuft, severe tubule-interstitial inflammation and microcystic dilatation of renal tubules. The presence of tubuloreticular inclusions and the aggressive clinical course distinguish HIVAN from idiopathic FSGS. The mechanisms of renal cell injury are still being defined. Viral DNA has been demonstrated in the renal epithelia of HIV-infected patients with or without nephropathy, suggesting that pathogenic factors, other than the infection of cells, are required for the induction of disease. In HIV-infection, about 73% are FSGS (HIVAN), about 10% are MPGN, 6% are minimal change disease and 5% are membranous nephropathy. Immunoglobulin A nephropathy and mesangioproliferative nephropathy make up the remaining fraction.1 There is strong predilection for HIVAN among black HIV-infected patients. The black:white ratio among patients with HIVAN is 12:1.4 Blacks are also more likely to have more severe clinical 582 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 The clinical features of HIVAN include the presenting features of proteinuria (typically in the nephrotic range) and renal insufficiency. Other manifestations of the nephrotic syndrome including edema, hypoalbuminemia and hypercholesterolemia have been common. The sonographic evaluation may reveal enlarged kidneys. The clinical course in most patients is marked by progression to ESRD within weeks to months. MPGN may be the most common pattern of immune complex-mediated glomerulonephritis seen in HIVinfected patients.5 MPGN is a pathologic term characterized by thickening of the glomerular basement membrane, proliferation of mesangial cells and influx of mononuclear inflammatory cells. This disease is often the result of immune complexes. Immune complex disease associated with HCV coinfection is the most common cause of MPGN in HIV-1 infection. Renal function in some patients has been reported to improve dramatically in response to treatment with corticosteroids, but this is not predictable and carries significant risk.6 At present, the therapy of HIVAN should include the same ART as the patients without nephropathy. ACE inhibitors have been shown to decrease the proteinura in HIVAN and to slow the progression to renal failure. Renal transplantation is a viable option in selected patients.7 Our patient of nephrotic syndrome was diagnosed to be a case of MPGN, which can be the initial manifestation
- 83. UROLOGY of HIV infection.Therefore, we suggest that in an unexplained case of nephrotic syndrome in an adult, the HIV status should be checked. 4. Bourgoigine JJ, Ortiz-Interian C, Green DF. The human immunodeficiency virus epidemic and HIV associated nephropathy. In: Nephrology. Hatano M (Ed.), SpringerVerlag: Tokyo 1990:p.484-92. REFERENCES 5. Appel, Radha Krishnan, D’Agati. Secondary glomerular disease. In: Brenner and Rector’s: The Kidney. 7th edition, Brenner BM (Ed.), Saunders 2004:p.1381-447. 1. D’Agati V, Appel GB. Renal pathology of human immunodeficiency virus infection. Semin Nephrol 1998; 18(4):406-21. 2. Rao TK, Freidman EA, Nicastri AD. The types of renal disease in acquired immunodeficiency syndrome. N Engl J Med 1987;316(17):1062-8. 6. Smith MC, Pawar R, Carey JT, Graham RC Jr, Jacobs GH, Menon A, et al. Effect of corticosteroid therapy on human immunodeficiency virus associated nephropathy. Am J Med 1994;97(2):145-51. 3. Brady HR, Yvonne M, Meara O’, Barry M, Brenner. Glomerular disease. In: Harrison’s Principles of Internal Medicine. 18th edition. Kasper DL (Ed.), 7. Winston JA, Klotman PE. Renal disease. In: AIDS Therapy. 2nd edition, Dolin R, Masur H, Sarg MS (Eds.), Churchill Livingstone 1999:p.853-9. ■■■■ A patient’s immune response may provide better and more rapid insights into the cause, severity and prognosis of certain bacterial infections than conventional tests, according to a study appearing in an upcoming issue of the Journal of the American Society of Nephrology (JASN). Such an “immune fingerprint” could lead to more accurate diagnoses and more appropriate antibiotic treatment. Approximately 11% of kidney failure patients on dialysis receive peritoneal dialysis, which is home-based. Peritoneal dialysis is generally perceived as less burdensome and as effective as clinic-based hemodialysis, but infections can cause treatment failure and even patient death if not detected early. Unfortunately, current tests for infections - which use microbiological culture methods - are slow and inefficient. Fear of infection is the major reason for patients and their doctors to opt against peritoneal dialysis despite its otherwise potential clinical benefit. “To our knowledge, this is the first study in acutely infected patients exploiting the notion that microorganisms display distinct sets of pathogen-associated patterns and interact with the immune system in a unique and specific manner for diagnostic purposes,” said Professor Topley. In addition to potentially improving the diagnosis and treatment of peritonitis in peritoneal dialysis patients, the findings may also be applicable to other local and systemic infections. Dr. Eberl added that “the data suggest that it may be possible to develop a simple fingerprintbased point-of-care test that can be used by a general practitioner - at the bed-side or at home - to ensure that the right treatment is given to each patient.” In an accompanying editorial, Marien Fieren, PhD (Erasmus Medical Center, in The Netherlands) noted that the study “deepens our understanding of the complex, local pathogen-host interactions. Such patient-based studies are important not only from a theoretical perspective but also for the prospect of future developments that could improve diagnosis and management of the various forms of peritonitis.” Customizing Treatments for Deadly Prostate Cancer with Tumor Genomics. A new study at Mayo Clinic is using genomic sequencing to develop customized treatments for men with castration-resistant prostate cancer, a progressive and incurable stage of prostate cancer, which no longer responds to hormone therapies that stop or slow testosterone production. Several new therapies have recently been approved by the FDA for use in treating castration-resistant prostate cancer, offering new hope for men with this disease. However, many questions remain over which medications to use in individual cases. In the PROMOTE study, researchers and doctors are using exome sequencing and RNA profiling to identify molecular fingerprints within prostate cancers that can be used to identify the optimal drug for the individual patient. Prostate cancer is the most commonly diagnosed solid organ malignancy in the US with more than 2,38,000 new diagnoses annually and an estimated 29,720 deaths. It is the second leading cause of cancer deaths among American men, according to the Surveillance Epidemiology and End Results Program of the National Cancer Institute. Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 583
- 84. mediLAW Judges have toFollow the Laws of the Country KK Aggarwal Q. I am greatly perturbed by the gang rape and brutal injuries to a 23-year-old physiotherapy student in Delhi on 16-12-2012. During my eight years stay in Zanjan (Iran) not a single case of theft of any kind or adultery was seen or heard of. The law there is Tit for Tat (Hand/s amputation for theft and killing by stoning for adultery). Punishment should be given in such a way that criminals are afraid of committing the crime. I know that judiciary does not follow common sense. I am not sure I am for or against such law. But, human laws cannot be applied to those rapists who not only gangraped the helpless girl but hurt her genitals and other body parts with sharp objects. What are your comments? Ans. My comments are as follows: 1. Ref: I know that judiciary does not follow common sense. It is obvious that your knowledge is deficient. The basics are as follows: a. Law reflects the will of the people b. Law is based on common sense. c. The judiciary is bound by law. It has to follow law. If the law makers (legislators) have made a law that appears to be against common sense, the judge does not have the freedom to substitute the express provision of law by his common sense or intelligence, however intelligent he may be. The judiciary does use common sense along with its legal sense, as it should be. 2. Every judge has to follow the law of the country concerned. Iranian laws cannot be used in India. 3. Law may frighten people but does not change them. Ask people in other countries (where Sharia law does not operate) as to whether Iranians, Arabs, etc. commit less or more theft and adultery compared to local population. There answer will surprise you. As a matter of fact, every two years or so you read in the newspapers that some prince or princess from the Arabian Sheikhdoms is caught shop-lifting in Europe or USA. Their Sharia does not make them more virtuous or pious. 4. As per principles of criminology, the punishment is supposed to have three main aims—Retributory; Deterrent; and Reformative. Scholarly studies have shown that the deterrent effect of the most severe punishment (capital punishment) is minimal. 5. Ref: Human rights laws cannot be applied to those rapists. Rapists are humans and have human rights. Those rights have even been partially extended to animals, particularly apes, in some countries. In India too, there is the Prevention of Cruelty to Animals Act, 1960. Cruelty cannot be applied to humans when denied by law to animals. ■■■■ Senior Physician and Cardiologist Moolchand Medcity, New Delhi 584 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013
- 85. Medifinance Bonds, Shares andGold: Capital Loss Offset Strategy Developing an Investment Portfolio One of the most difficult tasks that doctors and the financial advisors who advise them, face is choosing investments with characteristics that will help the individual meet his or her near and long-term goals. While many courses are available that teach portfolio design, none can teach instinct and common sense. These two elements are frequently important factors in developing an investment strategy. There are five basic asset categories in an investment portfolio. These are: ÂÂ Liquid assets (cash and equivalents) ÂÂ Bonds ÂÂ Stocks ÂÂ Real estate (residential and investment property) ÂÂ Gold Before allocating funds to each of these investment categories, it is important to look first at the balance of the existing portfolio. Then, the actual percentage allocated to each category will depend on the doctor and his or her circumstances. In assessing an individual doctor’s circumstances, it is necessary to keep in mind certain asset characteristics. Assets are generally held for either personal use or production of current or future income. Since assets held for personal use are a matter of individual discretion, the focus is on those assets held for the production of current income or for potential appreciation. The asset characteristics which matter are: ÂÂ Taxability upon deposit, on income and at withdrawal ÂÂ Safety ÂÂ Growth and inflation protection ÂÂ Yield ÂÂ Liquidity Each of the asset categories listed earlier can be evaluated according to these characteristics in order to decide what role each should play in the final investment portfolio. There is no single investment that possesses all of the above characteristics. We therefore, need to have a balanced investment portfolio which will include a number of investment vehicles that together will contribute the needed characteristics. By spreading capital over many investments, an investor may be able to reduce the overall risk of the portfolio. Investment capital should be spread proportionally over several different investments and among several vehicles within an asset category. The result will hopefully be a portfolio that produces the sought-after investment results and helps the individual to achieve his or her goals and objectives. A related decision that must be made is how a particular asset will be held. Stocks for example can be held individually or by investing in a mutual fund. Individually held stocks can be managed by the investor or by a professional portfolio manager. Real estate can be in the form of a limited partnership or individual properties. Many of these decisions depend on the degree of management and control the investor wishes to have. Similar options are available for bonds and precious metals like gold. Sometimes the choice of investment vehicle will depend on the amount of funds available. Coordination with Retirement Plans Many doctors have over time developed substantial amounts of retirement assets. In developing an investment portfolio, these assets must be an integral part of the overall design. Current assets and retirement assets need to be considered together. Sometimes assets that are considered suitable for the overall portfolio are better if held in a retirement vehicle. When considering real estate limited partnerships, many investors object to their long-term, illiquid nature. Given the long-term nature of retirement plans, a doctor with 10 or more years to retirement could afford to hold the partnership for the period necessary to get the full economic benefits. Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 585
- 86. Medifinance Responsibility of Doctorsas Clients ÂÂ Understand the basic nature of investments. ÂÂ Have the discipline to maintain basic policies. ÂÂ Client should define his or her emotional reactions to the inevitable short-term volatility of the financial markets. ÂÂ Client should define his or her need for long-term policies to achieve long-term objectives or shortterm policies to cope with short-term needs. ÂÂ How to take advantage of the strongest lever an investor can have-time. ÂÂ Determine timeframe against which an investor should measure the worth of his investment policy and what rate of return should be expected. ÂÂ Do not get caught up in the bullishness or bearishness of the moment, as the basis for making decisions. Understand their own interests and objectives. ÂÂ ÂÂ Stay focused on the long-term objectives. Responsibility of Financial Advisors ÂÂ Understand the client’s needs and listen to what the client states, relative to what the client means. ÂÂ Define realistic investment objectives that can meet the client’s needs - based on agreed upon definitions. ÂÂ Establish the right mixture of assets. ÂÂ Develop well-reasoned, sensible investment policies designed to achieve the client’s realistic and specified long-term investment objectives. ÂÂ Revise the portfolio to respond to changes in the marketplace and in the securities within the portfolio. ÂÂ Coordinate tax and cash flow planning, estate planning and risk/reward planning. ÂÂ Revise the portfolio in response to changes in the client’s objectives or financial circumstances. Establish Investment Attributes and Understand Asset Performance in Different Economic Scenarios ÂÂ Safety of principal ÂÂ Safety of income ÂÂ Safety of purchasing power ÂÂ Appreciation potential ÂÂ Consider the risk of portfolio depreciation ÂÂ What to Look for in an Investment? ÂÂ Cost sharing arrangement. ÂÂ Structure of investment and what flexibility is offered. ÂÂ Substance, not pretty pictures, promises or endorsements. ÂÂ How the investment will react to economic changes over time? ÂÂ How it will be valued in the future? Make a specific model and implement it to the client’s satisfaction based on all the above. monitor the Effects of Ongoing Results, to the Client’s Goals Tax avoidance or deferral ÂÂ Establish an office procedure for inputting data. ÂÂ Understand the reports. ÂÂ Coordinate the portfolio with other software to project tax, cash flow and financial statement growth. Avoid Investment Mismatch by Establishing Investment Policies and Procedures ÂÂ Compare performance to original expectations. ÂÂ Compare performance to standard indices. ÂÂ Evaluating an investment manager’s policies ÂÂ ÂÂ Market timer Evaluate the portfolio in light of client’s current needs and objectives. ÂÂ Has special knowledge or expertise ÂÂ ÂÂ Plays specific stocks or groups Evaluate investments in light of the future outlook for the economy and the investment. ÂÂ Undertakes variable strategies ÂÂ Has an insightful long-term philosophy ÂÂ Real target: What is right for client, not ‘beat the market’. 586 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 Changes, Repositioning and Reinforcing Return ÂÂ Maintain investment flexibility. ÂÂ Evaluate client’s needs and objectives periodically.
- 87. Medifinance Capital Loss OffsetStrategy Capital Gains are Divided into Short-term and Long-term Indian Tax payers can use CII (cost inflation index) to reduce taxes. CII helps in inflating the cost of the acquired asset and thus help tax payers to show lower gains. This CII data for every year is published by GOI. Investors in India should learn to use this table effectively. Long-term capital gain (LTCG) on stocks and stock mutual funds - exempted from Taxes u/s 10(38). This law was made only in Financial Year 2004. Before that, LTCG was taxed in India. This is important to know. Because law can change in future. Also since the gains are exempted, the losses are lost and not available for adjustment. Please note long-term losses arising from other asset classes like real estate, gold, foreign assets can be adjusted with other long-term gains and if the net is still loss, this can be carry forward. Only the long-term loss from equity is lost for ever, that too only if STT is paid. Short-term capital gain (STCG) on stocks and stock mutual funds are taxed at 15% u/s 111A and 115AD. Few years back it was 10%. So, remember law can change. A doctor needs to keep up with current laws and regulations. LTCG on stocks/stock mutual funds will be tax exempted only if STT is paid. If STT is not paid, for example, if stocks are traded using off-market trades, LTCG tax is payable and not exempted. Not only tax on gains are payable, even losses can be used. This can be used as an effective tool in tax minimization. Indian tax laws do not recognize wash sales. So, an individual can have two brokerage accounts and sell in one and buy in another simultaneously and thus realize short-term losses for tax management and continue to hold it for future appreciation. Even though there is no Indian regulation preventing this practice for tax minimization, there are other clean methods that can be employed as well. ÂÂ Husband and wife both have two demat accounts. Husband sells from his account and wife buys in her account simultaneously. ÂÂ Individual sells from his account and buy it on the next day back. ÂÂ Individual buys in his account and sells old lot next day. What won’t Work? Some try to play it aggressively by selling the old lot and buying new lot back on the same day in the same account. Some time, they may escape audit but this method has inherent accounting issues unique to Indian brokerage system. Same day, trades are settled in exchange as intraday trades and they don’t hit your demat account. So, it is not possible for the tax payer to prove he sold the old lot. Because old lot still stays in his demat account and never sent for delivery. If the old lot is not delivered, the cost basis still stays with that lot. First in First Out Indian tax laws do not allow the investors to use any other method than first in first out (FIFO) in demat account. So, it is tax payer’s responsibility to keep the cost basis of all the lots they bought and sold in chronological order and use it for tax computation. FIFO is applied on per account basis and not across the accounts for the individual. This opens up some possibilities for tax minimization. If the tax payer maintains 2-3 demat accounts, he has option to choose the lot by selecting the right demat account and sell. Also keeping the shares in material form (paper certificates) also can help in specific lot accounting. Even though technically this is possible, one will find it very cumbersome to work with paper certificates. But, if the specific lot size is running into crores, it is worth attempting it. Losses Carry Forward Both short-term and long-term losses can be carried forward and adjusted in eight years time. The Income tax return has a chart to enter tax losses for the preceding eight years only. They are not combined into one number. In USA, all short-term losses of all preceding years are combined into one number and all long-term losses are combined into one number and thus one can lose year to year breakup. This is ok, because US allows the tax payer to carry the tax loss till their death. Since India allows only eight years limit, this distinction is necessary. Classification of Assets for Determination of Long-term Capital Gain/Loss In a particular year, an investor may have gains and losses arising out of following accounts: ÂÂ Stocks/Stock Mutual funds Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 587
- 88. Medifinance Class A Class B ClassC Instruments Stocks/Stock mutual funds Bonds, zero coupon bonds, debentures and other Indian mutual funds, gold ETF, e-gold Real estate, gold bullion, foreign assets, commodities Minimum holding period to enjoy long-term capital gain tax benefits 1 Year 1 Year 3 Years Short-term gains 15% Slab rate Slab rate Short-term losses Can be carried forward Can be carried forward Can be carried forward Long-term gains Exempted 10%, or 20% with indexation 10%, or 20% with indexation Long-term losses Can’t be carried forward Can be carried forward Can be carried forward ÂÂ Debt/Liquid funds • Take lesser of the two in each item. ÂÂ Bonds • Total up losses and gains for each class. ÂÂ Real estate property ÂÂ Gold/Commodities ÂÂ Foreign assets Income Heads and Special Set-off Conditions Income is classified into following five types. Computation of Gains ÂÂ For every capital asset item, get buy date and sale date; compute holding period. If that item is eligible for long-term taxation benefits as per the above table, one can include other costs incurred at the time of purchase and costs incurred at the time of disposal of the assets. This may include taxes, brokerages, statutory and other costs. By inclusion of these costs, the taxable gain reduces. ÂÂ Separate each item into short-term and long-term tax groups. ÂÂ Compute loss/gain for each item in short-term tax group. • For long-term tax group, compute taxes individually on each item using both methods - with indexation and without indexation. • • 588 For calculating indexed cost, use cost inflation index table published by GOI. Without indexation the tax rate is 10%. With indexation, the tax rate is 20%. Please note an item with capital gain may end up as capital loss after the application of indexation, which not only eliminate tax for that item but also end up reducing tax from another item that has gains. Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 ÂÂ Salaries ÂÂ Income from house property ÂÂ Profits and gains from business or profession ÂÂ Further all these transactions can be split into shortterm and long-term-based on the holding period. Let us group these asset types into following categories. Capital gains ÂÂ Income from other sources Section 70 allows set-off of loss from one head to be adjusted with income from same head. Section 71 allows set-off of loss from one head to be adjusted with income from another head. The excess losses can be carried forward to eight years. Loss incurred during a particular financial year can be adjusted against any other head but carried forward losses can be adjusted only against income from the same head in future. If there is a failure to adjust carried forward loss in a subsequent year(s) with income, it can’t be set-off at a later date. POINTS TO REMEMBER ÂÂ Business loss can be set-off against capital gains; but not against salary income. ÂÂ Losses from gambling, race horses or speculation can be adjusted only against income from the same business. This loss can be carried forward only for four years and not for eight years like other losses. ÂÂ Capital loss can be set-off only against capital gains and not under any other head. Further any long-term loss can’t be set-off against shortterm gains.
- 89. eMedi Quiz Quiz Time Q1. Which of the following statements regarding tamoxifen is correct? A. Compared with aromatase inhibitors (AI’s), tamoxifen has been associated with a decreased risk of venous thromboembolic events. B. Similar to AI’s in postmenopausal women tamoxifen increases the risk of bone loss and osteoporosis. C. In postmenopausal women tamoxifen has shown better efficacy than AIs. D. Tamoxifen may be associated with an increased risk of ischemic cerebrovascular complications. Q2. All of the following statement regarding management of side effects of hormonal therapy are correct except? A. Vaginal bleeding is a warning sign for possible endometrial cancer or pathology in postmenopausal women on tamoxifen. B. Fluoxetine is the ‘selective serotonin reuptake inhibitors (SSRI)’ of choice for the management of hot flushes in women taking tamoxifen. C. D. Estrogen replacement therapy is contraindicated in women with ER/PR positive breast cancer for managing hot flushes and bone loss. Gabapentin is an active agent for the management of tamoxifen related hot flushes. Q3. Over a 4-day period, five men, four women, and six children are admitted to Philadelphia Metropolitan Hospitals with fever, prostration, hypotension and various degrees of mucosal bleeding. All patients have thrombocytopenia, leukopenia and elevated liver and renal function tests. None of the patients have traveled outside the mid-Atlantic area in the past three months. A viral hemorrhagic fever is suspected. Which one of the following epidemiological clues most strongly suggests that the outbreak is the result of a deliberate epidemic? A. Multiple simultaneous epidemics of different diseases. B. Unusual age distribution of a common disease. C. Unusual antibiotic resistance pattern. D. Unusual geographic clustering of disease. E. Unusual route of exposure. Q4. During rapid sequence induction of anesthesia: A. Slick’s maneuver is not required. B. Pre-oxygenation is mandatory. C. Suxamethonium is contraindicated. D. Patient is mechanically ventilated before end tracheal incubation. Answers to eMedi Quiz Published in October 2013 Issue Q1. (a) Babinski’s Q2. (b) 1 week to 1 year, peaking at 2-4 months Q3. (b) The presence of a boggy mass Q4. (b) The client keeps the drainage bag below the bladder at all times. Q5. (a) Hematuria Send your answers to the Editor-Indian Journal of Clinical Practice. E-mail: editorial@ijcp.com The correct answers will be published in the next issue of IJCP. Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 589
- 90. emedinews inspiration The LastCab Ride T wenty years ago, I drove a cab for a living. One time I arrived in the middle of the night for a pick up at a building that was dark except for a single light in a ground floor window. Under these circumstances, many drivers would just honk once or twice, wait a minute and then drive away. But I had seen too many impoverished people who depended on taxis as their only means of transportation. Unless a situation smelled of danger, I always went to the door. This passenger might be someone who needs my assistance, I reasoned to myself. So I walked to the door and knocked. ‘Just a minute,’ answered a frail, elderly voice. I could hear something being dragged across the floor. After a long pause, the door opened. A small woman in her 80s stood before me. She was wearing a print dress and a pillbox hat with a veil pinned on it, like somebody out of a 1940s movie. By her side was a small nylon suitcase. The apartment looked as if no one had lived in it for years. All the furniture was covered with sheets. There were no clocks on the walls, no knick knacks or utensils on the counters. In the corner was a cardboard box filled with photos and glassware. ‘Would you carry my bag out to the car?’ she said. I took the suitcase to the cab and then returned to assist the woman. She took my arm and we walked slowly toward the curb. She kept thanking me for my kindness. ‘It’s nothing,’ I told her. “I just try to treat my passengers the way I would want my mother treated.” ‘Oh, you’re such a good boy,’ she said. When we got in the cab, she gave me an address, and then asked, ‘Could you drive through downtown?’ ‘It’s not the shortest way,’ I answered quickly. ‘Oh, I don’t mind,’ she said. “I’m in no hurry. I’m on my way to a hospice.” I looked in the rear view mirror. Her eyes were glistening. ‘I don’t have any family left,’ she continued. “The doctor says I don’t have very long.” I quietly reached over and shut off the meter. ‘What route would you like me to take?’ I asked. For the next two hours, we drove through the city. She showed me the building where she had once worked as an elevator operator. We drove through the neighborhood where she and her husband had lived when they were newlyweds. She had me pull up in front of a furniture warehouse that had once been a ballroom where she had gone dancing as a girl. Sometimes she’d ask me to slow in front of a particular building or corner and would sit staring into the darkness, saying nothing. As the first hint of sun was creasing the horizon, she suddenly said, “I’m tired. Let’s go now.” We drove in silence to the address she had given me. It was a low building, like a small convalescent home, with a driveway that passed under a portico. Two orderlies came out to the cab as soon as we pulled up. They were solicitous and intent, watching her every move. They must have been expecting her. I opened the trunk and took the small suitcase to the door. The woman was already seated in a wheelchair. ‘How much do I owe you?’ she asked, reaching into her purse. ‘Nothing,’ I said. ‘You have to make a living,’ she answered. ‘There are other passengers.’ Almost without thinking, I bent and gave her a hug. She held onto me tightly. ‘You gave an old woman a little moment of joy,’ she said. ‘Thank you.’ I squeezed her hand, then walked into the dim morning light. Behind me, a door shut. It was the sound of the closing of a life. I didn’t pick up any more passengers that shift. I drove aimlessly, lost in thought. For the rest of that day, I could hardly talk. What if that woman had gotten an angry driver, or one who was impatient to end his shift? What if I had refused to take the run, or had honked once, then driven away? On a quick review, I don’t think that I have done anything more important in my life. We’re conditioned to think that our lives revolve around great moments. But great moments often catch us unaware—beautifully wrapped in what others may consider a small one. ■■■■ 590 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013
- 92. Around the Globe Newsand Views ÂÂ Red and processed meat consumption was significantly associated with colorectal cancer risk in patients who had a common gene mutation. ÂÂ Death rates are as high in individuals who develop autoimmune diabetes as adults as they are in those with type 2 diabetes, despite a more favorable baseline metabolic risk profile among the former, according to a new population-based study published online October 15 in Diabetes Care from Norway. ÂÂ An FDA panel has unanimously recommended simeprevir (Janssen) for the treatment of chronic hepatitis C virus (HCV) genotype 1 (GT1) infection, combined with peginterferon alfa and ribavirin in adults with compensated liver disease (including cirrhosis) who are treatment naïve or who have failed previous interferon therapy with or without ribavirin. ÂÂ The US FDA has approved the expanded use of the mu-opioid receptor antagonist alvimopan (entereg, cubist pharmaceuticals). The supplemental new drug application (sNDA) expands the indication to accelerate the time to upper and lower GI recovery following surgeries that include partial bowel resection with primary anastomosis. The FDA originally approved alvimopan in 2008 to accelerate the time to upper and lower gastrointestinal (GI) recovery following partial large- or small-bowel resection with primary anastomosis. ÂÂ Weekly azithromycin reduces pulmonary exacerbations of noncystic fibrosis bronchiectasis and chronic suppurative lung disease in indigenous children, researchers from Australia and New Zealand report. ÂÂ The findings of a first-ever study to compare the use of antibiotics with surgery for the treatment of diabetic foot osteomyelitis point to antibiotic therapy being the logical first choice for the patient population in this trial, those with diabetic foot osteomyelitis and ulcers in the forefoot. If a person has a soft-tissue infection associated with osteomyelitis, a good vascular supply and you cannot see the bone, then the best option is 90 days of antibiotics. After this period, if things don’t improve, you can consider surgery as a second option, said lead author José Luis Lázaro-Marinez, PhD, from Unidad de Pie Diabético, Madrid, Spain. 592 Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 ÂÂ The so-called ‘Mississippi baby’ might be the forerunner of a new approach to treating infants born with HIV. As reported in the New England Journal Medicine, the child, whose mother was HIV-positive, was started on triple-drug therapy 30 hours after birth. After about 18 months of therapy, she was lost to follow-up for several months, during which time she did not get antiretroviral therapy. When care resumed at 23 months, there was little or no sign of HIV and there has been no viral rebound up to the age of 30 months. As per the authors, this case suggests that very early therapy might “interfere with either the quantities or qualities of persistent reservoirs of replicationcompetent virus. ÂÂ Provisional guidelines from the CDC describe FDA-approved and off-label uses of bedaquiline fumarate (sirturo, janssen therapeutics) in populations with multidrug-resistant tuberculosis (MDR TB) that were not included in clinical trials. The new recommendations regarding use of this oral diarylquinoline in children, pregnant women, or persons with extrapulmonary MDR TB were published in the October 25 issue of the morbidity and mortality weekly report. Bedaquiline is in the first new class of TB drugs to be approved to treat TB in more than 4 decades. ÂÂ Hospital patients who are excessively anxious about their health may benefit from brief, modified cognitive behavioral therapy (CBT). In a clinical trial, adapted CBT for health anxiety (CBT-HA) delivered by nonspecialists with minimal training proved substantially more effective than standard care at reducing symptoms of health anxiety, the researchers report. The study was published online October 18 in the Lancet. ÂÂ A novel inhaled drug appeared safe as a dual bronchodilator and anti-inflammatory in asthma and chronic obstructive pulmonary disease (COPD), a series of proof-of-concept studies showed. In COPD patients, nebulized RPL554 boosted forced expiratory volume in one second (FEV1) by 17% versus placebo, with peak effects comparable to inhaled beta-2 agonists. ÂÂ The American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM) in a joint opinion
- 93. Around the Globe publishedin the November issue of Obstetrics and Gynecology. As per the authors, after the physician has provided information and careful counseling, the patient and physician will often reach a mutually acceptable decision. If the patient and physician cannot reach an agreement, then referral or second opinion may be appropriate. published in the November issue of obstetrics and gynecology have discouraged the use of the general label ‘term pregnancy’ and replacing it with these categories: zz early-term: 37 weeks to 38 weeks, 6 days; zz full-term: 39 weeks to 40 weeks, 6 days; zz late-term: 41 weeks to 41 weeks, 6 days; and zz post-term: 42 weeks and beyond. ÂÂ Of the nine million cases of tuberculosis (TB) across the world annually, children below 15 years of age account for about one million as reported in the Hindu, October 24, 2013. As per India’s Revised National TB Control Programme (RNTCP), pediatric cases account for about 12% of the total TB caseload in the country. According to a March 2013 paper in the Indian pediatrics journal, the number of pediatric (below 14 years) cases in India has been on the rise-nearly 60,000 (5.6%) in 2005 and about 84,000 (7%) in 2011. Many studies have pointed out that pediatric TB case detection is way down in the priority list of RNTCP and hence many cases go undetected. ÂÂ A new study published in Rheumatology has suggested that women who walk with flat feet are 50% more likely than those with normal or high arches to have low back pain. ÂÂ Bacterial communities isolated from the urine of women with urinary incontinence differ depending on the type of incontinence, according to a study that, for the first time, suggests that bladder microbiota could play a role in this condition. ÂÂ Updated opinion statement of the American College of Obstetricians and Gynecologists (ACOG) states that physicians should carefully counsel women who are considering elective surgery that is not traditionally recommended and, ideally, jointly make the decision with them. The statement is ÂÂ A large number of HIV-infected men with early syphilis may have neurosyphilis, despite low serum titers and no symptoms, according to a new study presented at the 14th European AIDS conference. In the study, 92% of the patients in the study showed positive for neurosyphilis by cerebrospinal fluid examination. ÂÂ Adults without symptoms or risk factors should not be screened for chronic kidney disease (CKD), according to new guidelines from the American College of Physicians (ACP). The new evidencebased recommendations, published online October 21 in the annals of internal medicine, address screening, monitoring and treatment of adults with stage 1 to 3 CKD. ÂÂ Over 9.3 lakh Indians with the world’s most dangerous air borne disease – tuberculosis, are currently going undetected and being ’missed’ by the country’s health system as reported in TOI, October 23, 2013. Around 3 million people-equal to one in three people falling ill with TB are not being detected globally. What is bad news for India is that 31% of those are in India. India is presently home to around 26% of the world TB patients - 1 in 4 globally. According to the World TB report 2013 released on Wednesday, 75% of the estimated missed cases – people who were either not diagnosed or diagnosed but not reported were in 12 countries. In order of total numbers, India led the list followed by South Africa, Bangladesh, Pakistan, Indonesia, China, Congo, Mozambique, Nigeria, Ethiopia, Philippines and Myanmar. ■■■■ Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 593
- 96. lighter reading Lighter Sideof Medicine “Money is not the most important thing in the world. Love is. Fortunately, I love money.” Make Sure Quote During Medical Practice A patient after sublingual nitrate developed fainting attack —Jackie Mason “I don’t try to describe the future. I try to prevent it. —Ray Bradbury Oh my God! Why was the systolic murmur missed on auscultation? Mind Trivia 1. If folk is spelled Folk how do you spell the white of an egg? ©IJCP Academy 2. Take off my skin -- I won’t cry, but you will! What am I? Make sure that patient with left ventricular outflow tract (LVOT) obstruction are not given sublingual nitrates. Ans. (1) White (2) An onion (3) Silence or a promise (4) Washington DC (5) Nine ILLUSION Dr. Good and Dr. Bad Situation: An obese patient came with BMI of >40. ©IJCP Academy First try diet, exercise and drug therapy. Lesson: Obesity surgery is indicated in patient with BMI >40 who have failed diet and exercise with or without drugs. KK Aggarwal 596 4. If the red house is on the right side and if the blue house is on the left side where’s the white house? 5. If two’s company, and three’s a crowd, what are four and five? KK Aggarwal Go for surgery 3. No sooner spoken than broken. What is it? Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013
- 97. Information for Authors Manuscriptsshould be prepared in accordance with the ‘Uniform requirements for manuscripts submitted to biomedical journals’ compiled by the International Committee of Medical Journal Editors (Ann. Intern. Med. 1992;96: 766-767). Indian Journal of Clinical Practice strongly disapproves of the submission of the same articles simultaneously to different journals for consideration as well as duplicate publication and will decline to accept fresh manuscripts submitted by authors who have done so. The boxed checklist will help authors in preparing their manuscript according to our requirements. Improperly prepared manuscripts may be returned to the author without review. The checklist should accompany each manuscript. Authors may provide on the checklist, the names and addresses of experts from Asia and from other parts of the World who, in the authors’ opinion, are best qualified to review the paper. Covering letter – – – The covering letter should explain if there is any deviation from the standard IMRAD format (Introduction, Methods, Results and Discussion) and should outline the importance of the paper. Principal/Senior author must sign the covering letter indicating full responsibility for the paper submitted, preferably with signatures of all the authors. Articles must be accompanied by a declaration by all authors stating that the article has not been published in any other Journal/Book. Authors should mentioned complete designation and departments, etc. on the manuscript. Manuscript – Three complete sets of the manuscript should be submitted and preferably with a CD; typed double spaced throughout (including references, tables and legends to figures). – The manuscript should be arranged as follow: Covering letter, Checklist, Title page, Abstract, Keywords (for indexing, if required), Introduction, Methods, Results, Discussion, References, Tables, Legends to Figures and Figures. – All pages should be numbered consecutively beginning with the title page. Note: Please keep a copy of your manuscript as we are not responsible for its loss in the mail. Manuscripts will not be returned to authors. Title page Should contain the title, short title, names of all the authors (without degrees or diplomas), names and full location of the departments and institutions where the work was performed, name of the corresponding authors, acknowledgment of financial support and abbreviations used. – The title should be of no more than 80 characters and should represent the major theme of the manuscript. A subtitle can be added if necessary. – A short title of not more than 50 characters (including inter-word spaces) for use as a running head should be included. – The name, telephone and fax numbers, e-mail and postal addresses of the author to whom communications are to be sent should be typed in the lower right corner of the title page. – A list of abbreviations used in the paper should be included. In general, the use of abbreviations is discouraged unless they are essential for improving the readability of the text. Summary – The summary of not more than 200 words. It must convey the essential features of the paper. – It should not contain abbreviations, footnotes or references. Introduction – The introduction should state why the study was carried out and what were its specific aims/objectives. Methods – These should be described in sufficient detail to permit evaluation and duplication of the work by others. – Ethical guidelines followed by the investigations should be described. Statistics The following information should be given: – The statistical universe i.e., the population from which the sample for the study is selected. – Method of selecting the sample (cases, subjects, etc. from the statistical universe). – Method of allocating the subjects into different groups. – Statistical methods used for presentation and analysis of data i.e., in terms of mean and standard deviation values or percentages and statistical tests such as Student’s ‘t’ test, Chi-square test and analysis of variance or non-parametric tests and multivariate techniques. – Confidence intervals for the measurements should be provided wherever appropriate. Results – These should be concise and include only the tables and figures necessary to enhance the understanding of the text. Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 597
- 98. Discussion – This should consistof a review of the literature and relate the major findings of the article to other publications on the subject. The particular relevance of the results to healthcare in India should be stressed, e.g., practicality and cost. References These should conform to the Vancouver style. References should be numbered in the order in which they appear in the texts and these numbers should be inserted above the lines on each occasion the author is cited (Sinha12 confirmed other reports13,14...). References cited only in tables or in legends to figures should be numbered in the text of the particular table or illustration. Include among the references papers accepted but not yet published; designate the journal and add ‘in press’ (in parentheses). Information from manuscripts submitted but not yet accepted should be cited in the text as ‘unpublished observations’ (in parentheses). At the end of the article the full list of references should include the names of all authors if there are fewer than seven or if there are more, the first six followed by et al., the full title of the journal article or book chapters; the title of journals abbreviated according to the style of the Index Medicus and the first and final page numbers of the article or chapter. The authors should check that the references are accurate. If they are not this may result in the rejection of an otherwise adequate contribution. Examples of common forms of references are: Articles Paintal AS. Impulses in vagal afferent fibres from specific pulmonary deflation receptors. The response of those receptors to phenylguanide, potato S-hydroxytryptamine and their role in respiratory and cardiovascular reflexes. Q. J. Expt. Physiol. 1955;40:89-111. Figures – Two complete sets of glossy prints of high quality should be submitted. The labelling must be clear and neat. – All photomicrographs should indicate the magnification of the print. – Special features should be indicated by arrows or letters which contrast with the background. – The back of each illustration should bear the first author’s last name, figure number and an arrow indicating the top. This should be written lightly in pencil only. Please do not use a hard pencil, ball point or felt pen. – Color illustrations will be accepted if they make a contribution to the understanding of the article. – Do not use clips/staples on photographs and artwork. – Illustrations must be drawn neatly by an artist and photographs must be sent on glossy paper. No captions should be written directly on the photographs or illustration. Legends to all photographs and illustrations should be typed on a separate sheet of paper. All illustrations and figures must be referred to in the text and abbreviated as “Fig.”. Please complete the following checklist and attach to the manuscript: 1. Classification (e.g. original article, review, selected summary, etc.)_______________________________ 2. Total number of pages ________________________ 3. Number of tables ____________________________ 4. Number of figures ___________________________ Books 5. Special requests _____________________________ Stansfield AG. Lymph Node Biopsy Interpretation Churchill Livingstone, New York 1985. 6. Suggestions for reviewers (name and postal address) Articles in Books 2.____________ 2.________________ Strong MS. Recurrent respiratory papillomatosis. In: Scott Brown’s Otolaryngology. Paediatric Otolaryngology Evans JNG (Ed.), Butterworths, London 1987;6:466-470. 3.____________ 3.________________ 4.____________ 4.________________ Tables – These should be typed double spaced on separate sheets with the table number (in Roman Arabic numerals) and title above the table and explanatory notes below the table. Legends – These should be typed double spaces on a separate sheet and figure numbers (in Arabic numerals) corresponding with the order in which the figures are presented in the text. – 598 The legend must include enough information to permit interpretation of the figure without reference to the text. Indian Journal of Clinical Practice, Vol. 24, No. 6, November 2013 Indian 1.____________Foreign 1.________________ 7. All authors’ signatures________________________ 8. Corresponding author’s name, current postal and e-mail address and telephone and fax numbers __________________________________________ Online Submission Also e- Issue @ www.ijcpgroup.com For Editorial Correspondence Dr KK Aggarwal Group Editor-in-Chief Indian Journal of Clinical Practice E-219, Greater Kailash, Part-1 New Delhi - 110 048. Tel: 40587513 E-mail: editorial@ijcp.com Website: www.ijcpgroup.com
- 100. R.N.I. No. 50798/90 Dateof Publication 13th of Same Month Date of Posting 13-14 Same Month DL (S)-01/3200/2012-2014 Posted in N.D. PSO New Delhi