Prednisolone and Mycobacterium indicus pranii in Tuberculous Pericarditis (IMPI) was a randomized controlled trial that investigated whether adjunctive prednisolone or M. indicus pranii injections improved outcomes in 1,400 patients with tuberculous pericarditis, many of whom also had HIV. The trial found no significant difference in the primary outcome but prednisolone reduced the risk of constrictive pericarditis and hospitalization. However, prednisolone and M. indicus pranii both significantly increased the risk of cancer in these immunosuppressed patients.
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
All manuscripts are subject to rapid peer review. Those of high quality (not previously published and not under consideration for publication in another journal) will be published without delay.
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
All manuscripts are subject to rapid peer review. Those of high quality (not previously published and not under consideration for publication in another journal) will be published without delay.
Origin of virus??
Transmission of virus??
First case in Wuhan?
Aerosol transmission? Fomites? Re- infection/ reactivation
Vaccine/ safety & efficacy/ antibody test/ community transmission?
Case definition?
Pathophysiology/ pathology
Cardiovascular manifestations/ risk?
ACS
Role of aspirin
Low platelet in covid-19
Anti-coagulants
ACEI/ARB/ARNI
Diuretics
Clinical features
High risk groups
Antibiotics
HCQ& Lopinavir, Ritonavir
Anti viral drugs- remdisivir/ favipiravir
Biological therapy- tocilizumab
Convalescent plasma therapy
Systemic steroids
Ivermectin
NSAIDs
Respiratory failure
Other management in covid 19- fluid/ nebulization
Chemoprophylaxis
Bronchial asthma
Anti diabetics
Origin of virus??
Transmission of virus??
First case in Wuhan?
Aerosol transmission? Fomites? Re- infection/ reactivation
Vaccine/ safety & efficacy/ antibody test/ community transmission?
Case definition?
Pathophysiology/ pathology
Cardiovascular manifestations/ risk?
ACS
Role of aspirin
Low platelet in covid-19
Anti-coagulants
ACEI/ARB/ARNI
Diuretics
Clinical features
High risk groups
Antibiotics
HCQ& Lopinavir, Ritonavir
Anti viral drugs- remdisivir/ favipiravir
Biological therapy- tocilizumab
Convalescent plasma therapy
Systemic steroids
Ivermectin
NSAIDs
Respiratory failure
Other management in covid 19- fluid/ nebulization
Chemoprophylaxis
Bronchial asthma
Anti diabetics
Luca Richeldi, MD, PhD, prepared useful Practice Aids pertaining to interstitial lung disease for this CME activity titled "Improving Care in ILD: Accurate Interpretation of HRCT and Advancing Therapies for Treatment." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2MyDprs. CME credit will be available until August 20, 2019.
Critical Illness Polyneuromyopathy (CIPNM) is frequently present in critically ill as a certain degree of symmetric extremity paresis and respiratory muscle weakness. The consequences of this complication may last for months or years after severe illness. It prolongs the stay in ICU and dependence onmechanical ventilation, increases long-term disability and care costs. We report a 58-year old female patient admitted to our Intensive Care Unit for acute respiratory insuffi ciency due to infl uenza pneumonia and acute respiratory distress syndrome. Thirty-three days of mechanical ventilation and 11 days of extracorporal membrane oxygenation were complicated by severe CIPNM, tetraparesis, mental disorders, and diffi culties in weaning off mechanical ventilation. No specifi c therapy is available for treatment of CIPNM. Preventive, supportive and rehabilitation measures are discussed in the article.
Invasive Aspergillosis in Post Kidney Transplant Patient A Case Reportijtsrd
Invasive aspergillosis IA is a rapidly progressive, often fatal infection that occurs in patients who are severely immunocompromised. Though IA remains rare, new reports shows that the illness is becoming more prevalent. Faster detection of infectious agent and use of right antifungal is very necessary to prevent further complications. In this case, a forty four year old male with k c o CKD s p renal allograft recipient complained of left sided facial and ear pain during follow up. This case report study has been presented for the consideration of the growing prevalence of this condition in renal transplant patients. Teena Thomas | Femi Liz Babu | Alisha Maria Shaji ""Invasive Aspergillosis in Post Kidney Transplant Patient: A Case Report"" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-3 | Issue-4 , June 2019, URL: https://www.ijtsrd.com/papers/ijtsrd23932.pdf
Paper URL: https://www.ijtsrd.com/medicine/other/23932/invasive-aspergillosis-in-post-kidney-transplant-patient-a-case-report/teena-thomas
Austin Journal of Clinical Cardiology is an open access, peer reviewed, scholarly journal dedicated to publish articles in all areas of cardiology and angiology. The aim of the journal is to provide a forum for cardiologists, researchers, physicians, and other health professionals to find most recent advances in the areas of cardiology and cardiovascular diseases.
Austin Journal of Clinical Cardiology accepts original research articles, review articles, case reports, clinical images and rapid communication on all the aspects of cardiology and circulatory system.
Austin Journal of Clinical Cardiology strongly supports the scientific upgradation and fortification in related scientific research community by enhancing access to peer reviewed scientific literary works. Austin Publishing Group also brings universally peer reviewed journals under one roof thereby promoting knowledge sharing, mutual promotion of multidisciplinary science.
Austin Journal of Clinical Cardiology is an open access, peer reviewed, scholarly journal dedicated to publish articles in all areas of cardiology and angiology
A cardiologists perspective to current scenario in light of corona pandemic in india and world wide. cardiac procedures , heart disease , aceinhibitors , arni , heart failure , troponin, nt probnp
Population-based resistance of Mycobacterium tuberculosis
isolates to pyrazinamide and fl uoroquinolones: results from
a multicountry surveillance project
4. ¡ What is pericarditis?
§ Pericarditis is an inflammation of the pericardium that surrounds the
heart.
¡ How does it present acutely?
§ Pain that typically presents with precordial chest pain with radiation
which may be relieved by sitting up and bending forward and is often
worsened by lying or inspiration.
§ The pain resembles angina or a heart attack acutely.
§ Colchicine 0.5 mg BID added to NSAID or as mono-therapy appears to
be effective for for the initial attack and prevention.
§ Systemic corticosteroid therapy is reserved for connective tissue diseases,
auto-reactive or uremic pericarditis.
PERICARDITIS BACKGROUND
5. ¡ How is Tuberculous Pericarditis different?
§ Primarily seen in AIDS patients with a mortality rate of untreated
acute effusive TB pericarditis that approaches 85%.
§ Clinical presentation:
§ Variable
§ Acute pericarditis w/ or w/out effusions
§ Cardiac tamponade
§ Acute constriction pericarditis or chronic pericarditis
§ Pericardial constriction occurs in 30-50% of the patients.
§ Chronic inflammation of the pericardium leading to impaired filling of
ventricles and reduced ventricular function.
§ Pericardium has effusions and sometimes calcification of the fibers that
constrict upon the heart.
§ Pericardiectomy is the only treatment for permanent constriction.
TUBERCULOUS PERICARDITIS
BACKGROUND
6. ¡ Tuberculous Pericarditis
§ Diagnosis:
§ Identification of Mycobacterium tuberculosis in the pericardial fluid or
tissue; ELISPOT tests for M. tuberculosis antigen as well are useful.
§ Tuberculin tests may be positive or negative
§ Peri/epicardial biopsy with caseous granuloma
§ Granulocytes and macrophages > 40 U/mL
§ Treatment:
§ Pericarditomy and pericardiectomy rarely needed, use only if constriction
develops after antituberculous drugs + prednisone
§ Various antituberculous drug combinations of different lengths
§ Prednisone at 1-2mg/kg per day for 5-7 days may be associated with
fewer deaths; controversial with limited data
§ High doses of prednisone (1-2 mg/kg per day) should be used since rifampin induces its
metabolism
TUBERCULOUS PERICARDITIS
EUROPEAN SOCIETY OF CARDIOLOGY GUIDELINES
7. ¡ Current therapy to treat TB pericarditis consists of medical
treatment for 6 months with:
§ rifampicin (rifampin)
§ isoniazid
§ pyrazinamide
§ ethambutol
¡ Treatment also includes:
§ Pericardial drainage for cardiac tamponade
§ Pericardiectomy for pericardial constriction
TUBERCULOUS PERICARDITIS
9. ¡ Despite antituberculosis therapy, pericardial drainage, or
pericardiectomy morbidity and mortality remain high in
patients with tuberculous pericarditis.
§ 26% mortality within 6 months
§ 40% mortality in AIDS patients
¡ “Glucocorticoid therapy in patients with TB pericarditis to
attenuate the inflammation may improve outcomes and
decrease risk of death by reducing cardiac tamponade and
pericardial constriction.”
§ “A meta-analysis of all trials of adjunctive glucocorticoid therapy for
all forms of tuberculosis also suggested reduced mortality.”
¡ IMPI hypothesis: Adjunctive prednisolone would benefit
tuberculous pericarditis patients overall.
IMPI TRIAL
10. ¡ Furthermore, preliminary evidence suggests that repeated
doses of intradermal heat-killed Mycobacterium indicus pranii
may reduce inflammation and increase the CD4+ and T-cell
count in HIV patients
§ Mycobacterium indicus pranii is a nonpathogenic, saprophytic, rapid
growing atypical mycobacterium species.
§ Shown clinical benefit with pulmonary tuberculosis patients and HIV in
leprosy patients.
¡ IMPI hypothesis: Intradermal M. indicus pranii could be
effective in suppressing inflammation in patients with
tuberculous pericarditis.
IMPI TRIAL
11. ¡ What was IMPI?
§ IMPI was a randomized, double-blind, placebo controlled, intention to
treat, multi-center/national, 2-2 factorial trial.
¡ Who were the patients in IMPI?
§ 1,400 adult patients in Africa with definite or probable tuberculous
pericarditis were enrolled in the study.
§ Approximately 66% of the patients had co-morbid HIV infections
§ All patients received treatment for TB and HIV according to WHO
guidelines.
IMPI TRIAL
13. ¡ Study design primary objective: To assess the effectiveness
and safety of prednisolone and M. indicus pranii
§ Published in the American Heart Journal in February 2013
¡ Primary outcome in published IMPI trial: Efficacy outcome was
a composite of death or first occurrence of cardiac tamponade
requiring pericariocentesis or constrictive pericarditis
§ Secondary efficacy outcomes were individual components of primary
outcome with the addition of hospitalization.
¡ Safety outcome: Occurrence of opportunistic infections and
cancer, as well as the effect of interventions on the CD4+ T-
cell count and the incidence of immune reconstitution
inflammatory syndrome.
IMPI TRIAL
15. ¡ How did they conduct IMPI?
§ Prednisolone or placebo was administered for 6 weeks
§ Week 1 dose: 120 mg daily
§ Week 2 dose: 90 mg daily
§ Week 3 dose: 60 mg daily
§ Week 4 dose: 30 mg daily
§ Week 5 dose: 15 mg daily
§ Week 6 dose: 5 mg daily
§ Prednisolone median follow up time: 636.5 days (1.7 years)
§ This 6 week duration came from an effective adjunctive
dexamethasone regimen withTuberculous Meningitis (31% RRR).
§ M. indicus pranii injections were given ID at time of enrollment, then
again at 2 weeks, 4 weeks, 6 weeks, and then at 3 months.
§ M indicus pranii median follow up time: 720.5 days (1.9 years)
IMPI TRIAL
16. ¡ How did they conduct IMPI?
§ Needed to recruit 1,400 patients for the study to have 90% power to
detect a 22.9% reduction in the hazard ratio.
§ Met power analysis
§ Two sided type I error rate of 5%, alpha = 0.05
§ Conducted seven interim analyses without adjustment of alpha
§ Increases the likelihood that any difference found may be due to chance alone and may not
be true.
§ Trial was conducted from January 2009 to February 2014,
approximately 5 years.
IMPI TRIAL
17. IMPI RESULTS
PRIMARY EFFICACY OUTCOME
¡ No statistically significant difference with either prednisolone
or M. indicus pranii for the primary endpoint.
19. IMPI RESULTS
SAFETY OUTCOMES
¡ Cancer: Placebo vs. prednisolone; 0.6% vs. 1.8%, 227% relative risk increase,
p=0.03
§ Absolute risk increase: 1.2%; NNH: 84
§ Similar data with M. indicus pranii
¡ HIV-related cancer: Placebo vs. prednisolone; 0.1% vs. 1.3%, 804% relative risk
increase, p=0.04
§ Absolute risk increase: 1.2%; NNH: 84
§ Similar data with M indicus pranii
20. ¡ Reduction in the incidence of hospitalization could be attributed
to the reduction in constrictive pericarditis.
§ Pericardiectomy is the definitive treatment for chronic pericardial
constriction, but it itself is associated with high perioperative morbidity
and mortality
§ However, cardiac surgery isn’t widely available in Africa making the finding of
a reduction in constrictive pericarditis more relevant.
¡ The increase in HIV-related cancer with prednisolone is
consistent with two other studies of HIV-associated tuberculosis
§ Possible that glucocorticoids and M. indicus pranii act synergistically to
increase the risk of cancer in immunosuppressed patients.
¡ IMPI investigators point out that a definite diagnosis of
tuberculosis in the pericardium or elsewhere in the body was
made in only 25% of the patients.
§ Interventions may have not been effective because few patients actually
had tuberculous pericarditis.
§ However, the results were consistent between patients with definite and
probable diagnoses as well.
IMPI TRIAL
DISCUSSION
21. ¡ Mayosi B.M., eta al. Prednisolone and Mycobacterium indicus pranii in
Tuberculous Pericarditis. New England Journal of Medicine. 2014 Sep
18;371(12):1121-30.
¡ Mayosi B.M., PhilD, et al. Rationale and design of the Investigation of the
Management of Pericarditis (IMPI) trial: A 2X2 factorial randomized double-
blind multicenter trial of adjunctive prednisolone and Mycobacterium w
immunotherapy in tuberculous pericarditis. American Heart Journal. 2013
Feb;165:109-115.
¡ Maisch B, et al. Guidelines on the Diagnosis and Management of
Pericardial Diseases: The Task Force on the Diagnosis and Management of
Pericardial Diseases of the European Society of Cardiology. European Heart
Journal. 2004;25:587-610.
¡ Mayosi BM, Burgess LJ, et al. Tuberculous pericarditis. Circulation.
2005;112:3608-16.
¡ Trautner BW and Darouiche RO. Tuberculous Pericarditis: Optimal Diagnosis
and Management. Clinical Infectious Diseases. 2001;33:954-61.
¡ Thwaites GE, Nguyen DB, eta al. Dexamethasone for the treatment of
tuberculous meningitis in adolescents and adults. New England Journal of
Medicine. 2004;35:1741-51.
IMPI TRIAL
REFERENCES