MedicalResearch.com - Medical Research Week in Review

MedicalResearch.com
Hemodialysis research, author interviews, dialysis updates and information on chronic
kidney disease and end stage renal failure.
Editor: Marie Benz, MD
info@medicalresearch.com
July 26 2013
For Informational Purposes Only: Not for Specific Medical Advice.

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Read more interviews on Hemodialysis.com

Should the Ovaries be Removed at Time of Hysterectomy for Benign Disease?
MedicalResearch.com Interview with:
Catherine A. Matthews, MD
Associate Professor and Division Chief
Urogynecology and Reconstructive Pelvic Surgery
University of North Carolina, Chapel Hill
MedicalResearch.com: What are the main findings of the study?
• Dr. Matthews: Women under 50 should try and preserve their ovaries at the time of hysterectomy for benign disease;
however, women over 50 should consider elective ovarian removal as a way to reduce ovarian cancer. There is no adverse
impact on cardiovascular, bone or sexual health in women over 50 who elect ovarian removal.
• MedicalResearch.com: Were any of the findings unexpected?
• Dr. Matthews: Based on a prior decision analysis, some have recommended ovarian preservation until age 65. Based on a
critical review of the literature, we believe that 50 is a more appropriate discriminatory age.
• MedicalResearch.com: What should clinicians take away from this report?
• Dr. Matthews: The beneficial effects of postmenopausal ovarian function have been overstated and there is no robust
evidence that ovarian preservation after age 50 significantly benefits cardiovascular health. In women who elect ovarian
preservation, removal of the fallopian tubes can reduce the rate of ovarian cancer.
• Citation:
• A Critical Evaluation of the Evidence for Ovarian Conservation Versus Removal at the Time of Hysterectomy for Benign
Disease.
• Matthews CA.
• Department of Obstetrics and Gynecology, University of North Carolina , Chapel Hill, North Carolina.
J Womens Health (Larchmt). 2013 Jul 18.
[Epub ahead of print]
Read the rest of the interview on MedicalResearch.com

Stroke Risk and Physical Activity Frequency
Michelle N. McDonnell, PhD
Division of Health Sciences International Centre for Allied Health Evidence
University of South Australia
Adelaide, SA 5001 Australia
• .
• MedicalResearch.com: What are the main findings of the study?
• Dr. McDonnell: In this study, we asked people how many times a week they engaged in intense physical activity, enough to work up a sweat. People
responded that they were physically active 0, 1-3 or 4 or more times a week. When we followed up these people for several years, those who did not
do any vigorous exercise were 20% more likely to have a stroke, compared to those who exercised four or more times a week. However, when we
adjusted these results for other risk factors, this attenuated the effect down to 14% which was not statistically significant. We also noticed that
people who exercised four or more times a week had less hypertension (high blood pressure), were less likely to be obese and less likely to have
diabetes. Each of these things on their own reduces your risk of stroke, so when we adjust for that the association between physical activity and
stroke is weaker (20% to 14%). So physical activity seems to have an effect on stroke risk by improving these other risk factors.
MedicalResearch.com: Were any of the findings unexpected?
• Dr. McDonnell: As we expected, those who were more physically active were less likely to have hypertension (high blood pressure), a high body mass
index and less likely to have diabetes. The unexpected finding was that this group was also more likely to report heavy alcohol use, which was
defined as ≥7 drinks/wk for women and ≥14 drinks/wk for men.
• MedicalResearch.com: What should clinicians and patients take away from your report?
• Dr. McDonnell: I think the big message here is that you can control your destiny with regards to stroke. It is largely preventable, and many people
don’t know that they can change their risk of stroke by adhering to some healthy lifestyle choices. A combination of healthy diet, healthy body
weight, regular exercise along with a moderate alcohol consumption and not smoking can reduce your risk of stroke by 80%.
• Here we show that regular physical activity is an important aspect of that, and should be encouraged. And it is quite a simple message for clinicians:
Ask your patients whether they are physically active four or more times a week at an intensity to work up a sweat. Let them know that this level of
physical activity is good for their health for many reasons, but particularly to reduce their risk of stroke.
• MedicalResearch.com: What recommendations do you have for future research as a result of this study?
• Dr. McDonnell: Much more research needs to be done to quantify just how much of a benefit you receive from exercise to reduce stroke risk
according to how much exercise you do. Just like we know the dose of medication you need to take to reduce blood pressure, we would like to clarify
the effect of precise amounts of exercise on improving your health outcomes.
• Citation:
• Physical Activity Frequency and Risk of Incident Stroke in a National US Study of Blacks and Whites
• Michelle N. McDonnell, Susan L. Hillier, Steven P. Hooker, Anh Le, Suzanne E. Judd, and Virginia J. Howard
Stroke. 2013;STROKEAHA.113.001538published online before print July 18 2013, doi:10.1161/STROKEAHA.113.001538

TAp73, a molecular relative of p53 Tumor Suppressor Protein, gives tumor cells a growth advantage
Xiaolu Yang, Ph.D.
Professor of Cancer Biology at the Perelman School of Medicine
University of Pennsylvania
and the Abramson Family Cancer Research Institute,
• Dr. Yang: TAp73 is a structural homologue of the preeminent tumor suppressor p53, but its role in tumorigenesis has been unclear. In
this study, we show that TAp73 supports the proliferation of tumor cells. Mechanistically, TAp73 activates the expression of glucose-6-
phosphate dehydrogenase (G6PD), a rate-limiting enzyme in the pentose phosphate pathway. This function of TAp73 is required for
maintaining a robust biosynthesis and anti-oxidant defense in tumor cells. These finding connects TAp73 to oncogenic growth and
suggest that G6PD may be a valuable target for tumor therapy.
•
• Dr. Yang: No. Previous studies suggested that TAp73, like p53, may be a tumor suppressor.
• Dr. Yang: Tumor cells rely on re-programmed metabolic pathways to rapidly generate biomass and to defense against oxidative stress.
TAp73-medidated G6PD activation may be an important part of this metabolic reprogramming that enables tumor growth.
• Dr. Yang: There are many questions that remain to be addressed about the regulation of G6PD and its role in tumor cells. For
example, we previously show that p53 has an effect on G6PD that is totally opposite of TAp73, raising the question as to how these two
p53 family proteins together may fine tune the metabolic flux through G6PD under various conditions, for normal and malignant cell
growth. The pentose phosphate pathway has two branches, which generate overlapping but also different metabolites. It is still not
clear how these two branches may be differentially regulated by TAp73 (and p53) to suit the metabolic needs of cells. For a cancer
therapy point of view, it would be very interesting to test whether the reduction of G6PD, either along or in combination with other
therapeutic approaches, decreases tumor growth.
• Citation:
• TAp73 enhances the pentose phosphate pathway and supports cell proliferation.
• Du W, Jiang P, Mancuso A, Stonestrom A, Brewer MD, Minn AJ, Mak TW,
Wu M, Yang X.
• Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of
China, Hefei, Anhui, 230027, ChinaAbramson Family Cancer Research Instituteand Department of Cancer Biology, University of
Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Nat Cell Biol. 2013 Jun 30. doi: 10.1038/ncb2789. [Epub ahead of print]

High Coffee Consumption: Small Decrease Bone Density, No Increase Fracture Risk
Helena Hallström Ph.D., M.Sc. (Toxicology)
Department of Surgical Sciences, Section of Orthopedics
Uppsala University, Uppsala, Sweden and
Risk and Benefit Assessment Department National Food Agency, Uppsala, Sweden.
• Answer: The aim of the study was to investigate whether high consumption of coffee is associated with osteoporosis and development of osteoporotic
fractures, since results from previous fracture studies regarding potential associations between coffee drinking and fracture risk are inconsistent. The longitudinal
population-based Swedish Mammography Cohort, including 61,433 women born between 1914 and 1948, was followed from 1987 through 2008. Coffee
consumption was assessed with repeated food frequency questionnaires. During follow-up, 14,738 women experienced any type of fracture and of these 3,871 had a
hip fracture. In a sub-cohort (n=5,022), bone density was measured and osteoporosis was determined (n=1,012). There was no evidence of a higher rate of any
fracture or hip fracture with increasing coffee consumption. However, a high coffee intake (≥4 cups) in comparison with a low intake (<1 cup) was associated with a 2-
4% reduction in bone mineral density (BMD), depending on site (p<0.001), but the odds ratio of osteoporosis was only 1.28 (95% confidence interval: 0.88, 1.87).
Thus, high coffee consumption was associated with a small reduction in bone density that did not translate into an increased risk of fracture.
• Answer: Previous studies in women on consumption of coffee or intake of caffeine and fracture risk have shown discrepant results. Some studies have demonstrated
increased risk of fractures with high intakes of coffee/caffeine, whereas others were unable to demonstrate such an association. In contrast to the present results, we
have earlier observed an increased rate of osteoporotic fractures in women consuming at least four cups of coffee per day in a subset of the present cohort.
Limitations in our previous analysis, some also shared with other studies, were a shorter maximum follow-up time, a lower number of fracture cases, and most
importantly we had incomplete case ascertainment since we were only able to identify fractures occurring in the county where the study was performed. Further, we
were previously not able to adequately control for lifestyle habits and comorbidity, which could potentially influence the association, although adjustments in our
study did not confer major changes in estimates. In this subset of the present cohort, we found that the higher risk of fracture with high coffee intake was
concentrated to women with a modest calcium intake. This effect modification was not confirmed in the present analysis.
• In the majority of previously performed studies in women investigating associations between coffee/caffeine consumption or intake and BMD no association could
be demonstrated, whereas some studies have observed such association. Several explanations for the lack of association in these studies are possible, including small
study size, low consumption of coffee or not assessing tea and coffee consumption separately.
•
• Answer: The small differences in BMD observed in the present study associated with coffee consumption do not seem to impact the risk of osteoporosis or incident
fractures.
• Answer: Since this study, to our knowledge, is one of largest studies performed in this research area, with a long follow-up, a large number of fractures, BMD as a
secondary outcome in a large sub-cohort and the use of repeated measurements of coffee consumption, we believe that this study ends a long running debate about
coffee as a potential risk factor for osteoporotic fractures, at least in women. An interesting issue for future research would however be to clarify possible
mechanisms of coffee and tea on bone mineral density.
• Citation:
• Long-term Coffee Consumption in Relation to Fracture Risk and Bone Mineral Density in Women
American Journal of Epidemiology(ISSN 0002-9262)(EISSN 1476-6256)
2013

Controlling Health Care Costs : US Physicians Views
Jon C. Tilburt, MD, MPH
Division of General Internal Medicine, Mayo Clinic, Rochester, Minnesota
Biomedical Ethics Program, Mayo Clinic
Knowledge & Evaluation Research Unit, Mayo Clinic
• What did you set out to find, what was your objective in this study?
• We wanted to know physicians perceived roles and responsibilities in addressing health care costs as well as their enthusiasm for proposed strategies
to contain health care spending.
• Who did you study and what did you look at?
• Practicing US physicians under age 65, we randomly selected 3900 physicians representing all specialties and mailed them an 8-page survey entitled
“Physicians, Health Care Costs, and Society.” We received 2,556 completed surveys (65% response rate).
• What were the results of the study?
• 85% agreed that “trying to contain costs is the responsibility of every physician.”
• Most (76%) reported being aware of the costs of tests or treatments they recommend
• Strongly endorsed prioritizing patients’ best interests over issues of cost (78%).
• 85% of physicians disagreed that they should “sometimes deny beneficial but costly services” for others.
• Most ascribed “major responsibility” for reducing health care costs to entities like trial lawyers, health insurance companies, and pharmaceutical and
device manufacturers
• A minority (36%) reported individual practicing physicians have “major responsibility” while most (59%) thought physicians had “some responsibility”
(4% “no responsibility”)
• Most expressed enthusiasm for cost-containment initiatives aimed at improving the quality and efficiency of care, and favored improving conditions
for evidence-based decision making.
– Improving quality/efficiency of care: 75% very enthusiastic about “promoting continuity of care”; 70% very enthusiastic about “rooting out fraud and abuse”;
69% very enthusiastic about “promoting chronic disease care coordination”.
– Improving conditions for evidence-based decision making: 63% very enthusiastic about “limiting corporate influence on physician behavior”; 51% very
enthusiastic about “expanding access to quality and safety data”.
– Strategies for changing how care gets paid for received mixed enthusiasm, and payment cuts were viewed least favorably.
• 51% very enthusiastic about “limiting access to expensive treatments with little net benefit”;
• 65% not enthusiastic about “paying a network of practices a fixed, bundled price for managing all care for a defined population”;
• “allowing Medicare payment cuts to doctors to take effect” (94% not enthusiastic); “eliminating fee-for-service payment models” 70% not enthusiastic.
• Physicians’ degree of enthusiasm for various cost-containment strategies were associated with practice setting and compensation structure.

Controlling Health Care Costs : US Physicians Views
Jon C. Tilburt, MD, MPH
Division of General Internal Medicine, Mayo Clinic, Rochester, Minnesota
Biomedical Ethics Program, Mayo Clinic
Knowledge & Evaluation Research Unit, Mayo Clinic
(cont)
• What did you conclude from this study?
• Physicians struggle to navigate their responsibilities not only to address health care costs but also to fulfill their primary obligation to
provide the best possible quality of care to individual patients.
• What do we know now that we didn’t know before the study?
• Most physicians agree they do have obligations to address healthcare cost
• Even though they endorse this obligation, most say it will not get in the way of doing their best for individual patients
• Addressing cost might improving the quality and opportunities for getting evidence into practice
• What’s the bottom line take-home message of this study?
• Physicians feel stuck in a difficult position. Despite their sense of responsibility to address healthcare costs, physicians consistently
express a commitment to the best interests of patients even when it is expensive. They have little appetite for rationing healthcare.
• What’s important for patients to know about the results of the study?
• The profession still wants to do the right thing for individual patients. They want to find the win-win strategies for making healthcare
leaner.
• Was there anything you found surprising from this study?
• Physicians have no problem endorsing a strong commitment to address healthcare costs and at the same time saying they are willing to
go to bat for their patients even if it is expensive.
• They see no contradiction between “Limiting access to expensive treatments with little net benefit” and I “being solely devoted to
my individual patients’ best interests, even if that is expensive.”
• Policy Implications:
• Physicians will likely support cost-savings strategies that are a “win-win” for improving quality of care (informed speculation: these
might be worth trying first)
• Mandatory initiatives designed to redesign payment will likely meet some resistance
• Payment reform (including incentive programs) should not create a “moral stress test” (Sulmasy) that strongly encourage individual
physicians to make cost-saving choices that violate the best interests of individual patients
• Citation:
• Tilburt JC, Wynia MK, Sheeler RD, et al. Views of US Physicians About Controlling Health Care Costs. JAMA. 2013;310(4):380-388.
doi:10.1001/jama.2013.8278.

Antibiotic Prophylaxis: What is the Quality of Reporting of Studies of Interventions to Increase Compliance?
MedicalResearch.com Interview with: Lillian S. Kao, MD, MS
Associate Professor, Department of Surgery
The University of Texas School of Medicine at Houston
Houston, Texas 77030
• MedicalResearch.com Interview with: Lillian S. Kao, MD, MS
Associate Professor, Department of Surgery
The University of Texas School of Medicine at Houston
Houston, Texas 77030
• Dr. Kao:
• -The internal validity (methodological rigor) and external validity (generalizability) of quality improvement (QI) studies of implementation of surgical antibiotic
prophylaxis measures are poor.
• -Studies demonstrating large positive effect on compliance were often performed in settings where the baseline compliance was extremely low (i.e., less than
20%), thus further limiting their generalizability.
• -Very few studies evaluated the effect of the QI interventions to increase appropriate antibiotic prophylaxis use on surgical site infections (SSIs). Moreover, those
studies that included SSI as an outcome measures were usually underpowered to identify a significant effect.
• -The majority of studies failed to report metrics relating to the quality of the implementation of the interventions to increase antibiotic prophylaxis compliance.
Effectiveness of evidence-based measures is dependent upon their implementation. For example, did all of the targeted groups adopt the intervention? Or were the
QI interventions sustained beyond the initial measurement or study period?
• Dr. Kao:
• -Clinicians seeking to implement interventions to improve surgical antibiotic prophylaxis should measure not only compliance with the prophylaxis measures but also
implementation of the intervention. Despite the poor methodological quality of the studies, most showed an improvement in compliance. However, no single
intervention or combination of interventions was universally effective; thus, the intervention should be tailored to the local context.
• -Patients should be aware that the findings should not discourage clinicians to engage in QI efforts to improve compliance with surgical antibiotic prophylaxis. Even if
compliance or SSIs do not appear to be altered, QI interventions such as checklists may result in improved safety culture or other positive changes that are not
currently measured in these studies.
• Dr. Kao:
• -Future research should focus on understanding what contextual factors improve uptake of interventions to increase compliance with evidence-based measures.
Citation:
• What is the Quality of Reporting of Studies of Interventions to Increase Compliance with Antibiotic Prophylaxis?
• Shauna M. Levy, Uma R. Phatak, KuoJen Tsao, Curtis J. Wray, Stefanos G. Millas, Kevin P. Lally, Lillian S. Kao
• Journal of the American College of Surgeons – 08 July 2013 (10.1016/j.jamcollsurg.2013.06.018)

Transthoracic Echocardiograms: Most Lead to No Appreciable Change in Patient Care
Susan Matulevicius, MD, MSCS
Department of Medicine, The University of Texas Southwestern Medical Center, Dallas
• . MedicalResearch.com: What are the main findings of the study?
• Dr. Matulevicius: In our cohort of 535 transthoracic echocardiograms performed at a single academic medical center, we found that
the majority (92%) of echocardiograms were appropriate by the 2011 Appropriate Use Criteria; however, only 1 in 3 echocardiograms
lead to an active change in patient care while 1 in 5 resulted in no appreciable change in patient care.
• Dr. Matulevicius: The low rate of active change in care (31.8%) in echocardiograms mostly classified as appropriate (91.8%) is surprising
and highlights the need for a better method to optimize echocardiography’s utilization of limited health care resources efficiently in the
deliver of high value care.
• Dr. Matulevicius: A diagnostic test, unlike a therapeutic test, may be appropriate in its ability to diagnose a certain disease process but
not necessary because the clinical history, physical, and laboratory data may be enough to provide high value care. Clinicians and
patients should consider what information will be gained from any diagnostic test, including echocardiograms, and ask how this
additional information will add to their clinical care. If the answer, it will do nothing, then potentially the study should not be ordered
and care should proceed without investing additional time and resources into diagnostic testing. This should prompt physicians and
patients to engage in open conversations about the likely etiology of the patient’s symptoms, the potential treatments for that
condition, and the expected results of testing and treatment.
• Dr. Matulevicius: Diagnostic testing has always been evaluated on its ability to detect disease (sensitivity and specificity) but not on its
ability to impact patient care. Hopefully this study will inspire the imaging community to develop standardized patient-centered
definitions against which the value of a diagnostic test to patient care can be compared between testing modalities as well as with and
without testing. Similarly, future studies that examine the patient, physician, and environmental factors associated with clinically
impactful diagnostic tests may help inform when additional testing may be most beneficial.
• Citation:
• Appropriate Use and Clinical Impact of Transthoracic Echocardiography
• Matulevicius SA, Rohatgi A, Das SR, Price AL, deLuna A, Reimold SC. Appropriate Use and Clinical Impact of Transthoracic
Echocardiography. JAMA Intern Med. 2013;():-. doi:10.1001/jamainternmed.2013.8972.

Weight Loss, Satiety Improved by Healthy Snacking
MedicalResearch.com Interview with: Roberta Re, Ph.D.
Nutrition research manager at Leatherhead Food Research in Surrey, England.
• MedicalResearch.com Interview with: Roberta Re, Ph.D.
Nutrition research manager at Leatherhead Food Research in Surrey, England.
• Dr. Re: The main finding of the study on snacking is that consumption of nuts (almonds and peanuts in particular) can help
to a reduced subjective perception of appetite and reduce energy intake at the next meal.
• Dr. Re: No. Although nuts are considered highly in calories the calories due to the fat content, the bioavailability of some of
the macronutrients is somehow limited due to digestibility. Nuts are also high in protein and the effect of nuts on satiety has
been extensively investigated.
• Dr. Re: Snacking has often had a negative connotation, however the choice of a healthy snack (and by snack I mean a small
meal!) may help reduce the energy intake at the main mean and be a positive approach to weight management. The choice
of a healthy snack, like Almonds, that are also high in vitamins and micronutrients can be a positive addition to a healthy
diet.
• Dr. Re: We need to look at the long-term impact of snacking and in particular understanding the mechanistic beyond it.
• It is also very important to be able to communicate these finding to consumers and to ensure that the key messages
resonate with them
• Citation:
• Institute of Food Technologists (IFT) (2013, July 16). The right snack may aid satiety, weight loss

Pregnancy-Related Hospitalizations – Venous Thromboembolism Rates
Sheree Boulet, DrPH, MPH
Assisted Reproductive Technology Surveillance and Research Team
Women’s Health and Fertility Branch Division of Reproductive Health
Centers for Disease Control and Prevention
• MedicalResearch.com Interview with:
Sheree Boulet, DrPH, MPH
Assisted Reproductive Technology Surveillance and Research Team
Women’s Health and Fertility Branch
Division of Reproductive Health
Centers for Disease Control and Prevention
• Dr. Boulet: Between 1994-2009, the rate of pregnancy-related hospitalizations with venous thromboembolism (VTE) increased by 14%. We also
found that the prevalence of hypertension, obesity, diabetes, and heart disease increased over the same time period for pregnancy hospitalizations
with VTE.
• Dr. Boulet: We evaluated temporal trends according to type of pregnancy hospitalization (e.g., antepartum, delivery, postpartum) and found
that, after adjusting for maternal socio-demographic and medical characteristics, a temporal increase in the likelihood of VTE diagnosis during
pregnancy was only observed for antepartum hospitalizations. This may indicate that co-morbid conditions confer varying degrees of risk for VTE
across the different periods of pregnancy.
• Dr. Boulet: VTE is a serious concern and an important cause of pregnancy-related complications in the U.S. Clinicians who care for pregnant women
should be aware of these risks and should have a low threshold to evaluate anyone with symptoms.
• Dr. Boulet: Our study used hospital discharge data to identify VTE-associated pregnancy hospitalizations. Future studies with clinically validated VTE
diagnoses observed in inpatient and outpatient settings are needed to confirm our findings and further explore the potential interaction between
comorbid conditions and varying VTE risk during the antepartum and postpartum periods.
• Citation:
• Trends in Venous Thromboembolism among Pregnancy-Related Hospitalizations, United States, 1994–2009
• Am J Obstet Gynecol. 2013 Jun 26. pii: S0002-9378(13)00655-8. doi: 10.1016/j.ajog.2013.06.039. [Epub ahead of print]
• Ghaji N, Boulet SL, Tepper N, Hooper WC.
• Division of Blood Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA.
.

Neuraminidase 1 and Regulation of Insulin Signaling
Alexey V. Pshezhetsky, Ph.D Professor
Departments of Pediatrics and Biochemistry University of Montreal Division of Medical Genetics
Sainte-Justine University Hospital Research Center
Montréal, PQ, Canada, H3T 1C5.
• Dr. Pshezhetsky: Our laboratory found that the presence of sugar known as sialic acid on the insulin receptor can determine whether
cells react normally to insulin or are resistant. Sialic acid modifies molecules like the insulin receptor, and reduces their
activity. We studied the enzyme that removes sialic acid, known as neuraminidase 1 or Neu1. Cells that lacked Neu1 had more sialic
acid on the insulin receptor and were resistant to insulin. Genetically-modified mice with ~10% of the normal Neu1 activity exposed to
a high-fat diet develop hyperglycemia and insulin resistance twice as fast as their wild type counterparts. Together, these studies
identify Neu1 and sialic acid as novel components of the signaling pathways of energy metabolism and glucose uptake.
• Dr. Pshezhetsky: Yes, you can say so. Neuraminidase 1 (Neu1) has a well-characterized catabolic function in the lysosome, where it
removes the terminal sialic acid residues of oligosaccharides and glycoproteins so its genetic deficiency cases rare inherited diseases of
children that affect bones, vision and brain. We showed that in addition to its catabolic role in lysosomes, Neu1 can also found on the
cell surface where it plays unexpected role as a structural and functional modulator of cellular receptors, proteins that sit on the surface
of the cells and and turn on or of different signals including those for inflammation, immune reaction, and cell growth. In the current
study, we showed that Neu1 action on insulin receptor is physiologically important to regulate glucose metabolism.
• Dr. Pshezhetsky: Activating the insulin receptor by manipulating the level of neuraminidase might give doctors an opportunity to treat
diabetes type 2. Also by measuring levels of Neu1 in human population we may detect a group that is at additional risk of having
diabetes.
• Dr. Pshezhetsky: Our lab continues to study how Neu1 regulates insulin sensitivity and whether changing neuraminidase activity this
might help to restore normal insulin response in type 2 diabetes.
• Citation:
• Positive regulation of insulin signaling by neuraminidase 1.
• Dridi L, Seyrantepe V, Fougerat A, Pan X, Bonneil E, Thibault P, Moreau A, Mitchell GA, Heveker N, Cairo CW, Issad T, Hinek
A, Pshezhetsky AV.
• Division of Medical Genetics, Sainte-Justine University Hospital Research Center, University of Montréal, Montréal, Québec, Canada.
• Diabetes. 2013 Jul;62(7):2338-46. doi: 10.2337/db12-1825. Epub 2013 Mar 21.

MS Progression: Cannabis Active Ingredient Ineffective
Professor John Zajicek
Professor of Clinical Neuroscience, Centre for Clinical Trials & Health Research –
Translational & Stratified Medicine (Peninsula Schools of Medicine and Dentistry)
• Prof. Zajicek: Our study investigated whether dronabinol (one of the major active ingredients of cannabis) may slow the progression of multiple
sclerosis. We currently have no treatments that are effective in modifying the disease course in people with either primary or secondary MS. We did
a clinical trial across the UK involving nearly 500 patients, who were randomly allocated to dronabinol or placebo, and followed them up for three
years to look at progression on rates. Overall we failed to find an effect of dronabinol on disease progression, either clinically (using a variety of
clinical measures) or using magnetic resonance imaging (MRI). There was a suggestion of an effect in people with the least disability (who didn’t need
a stick to help them walk), and there were no major problems with serious side effects. However, over all the population that took part in the study
also progressed less than we expected, which reduced our chances of finding an effect of treatment. The study was not designed to investigate an
effect on MS-related symptoms (such as pain and muscle stiffness), which have been investigated before.
• MedicalResearch.com: Where any of the findings unexpected?
• Prof. Zajicek: It was disappointing that we did not get an overall effect, but encouraging that there may be an effect in people with less disability.
One of the surprising findings was the relative lack of progression in the overall group of patients who took part. Side effects of active treatment also
meant that people stopped taking active treatment, also reducing the chance of a positive result. We will use this study to plan future studies to
ensure we can design trials that are most likely to have a chance of finding an effect i f one is present.
• MedicalResearch.com: What should patients and providers take away from this study?
• Prof. Zajicek: This is essentially another negative study looking for treatment in a neurodegenerative disorder. We desperately need treatments not
only for progressive MS, but also Parkinson’s and Alzheimer‘s diseases. Our results do not detract from the established symptomatic benefit that has
been identified in previous shorter-term studies of cannabinoids.
• MedicalResearch.com: What further research do you recommend as a result of your report?
• Prof. Zajicek: The relative absence of treatments for neurological degeneration, means that we should take every opportunity to follow each
lead, however slender. Future studies in MS should focus on people most likely to progress over the course of a trial, and further studies of
cannabinoid treatments should occur, using lower doses to encourage greater retention on treatment.
• Citation:
• Effect of dronabinol on progression in progressive multiple sclerosis (CUPID): a randomised, placebo-controlled trial
• Prof John Zajicek PhD,Susan Ball MSc,Prof David Wright PhD,Jane Vickery MSc,Prof Andrew Nunn MSc,Prof David Miller FMedSci,Mayam Gomez
Cano PhD,David McManus MSc,Sharukh Mallik MSc,Prof Jeremy Hobart PhD,on behalf of the CUPID investigator group
The Lancet Neurology – 13 July 2013
DOI: 10.1016/S1474-4422(13)70159-5

Obesity and the Disabled Population in New York City
Abigail Franklin
Vice President for Development & Communications
The New York Academy of Medicine
• Answer: The New York State Department of Health (NYSDOH) Overweight and Obesity Brief was derived from information gathered for
the NYS Behavioral Risk Factor Surveillance System (BRFSS). The BRFSS is an annual statewide telephone survey of adults administered
by the provide information on behaviors, risk factors, and utilization of preventive services. The survey conducted in 2011 found that
nearly 25% of adults in NYS are obese and another 36% overweight. It also found that obesity rates are higher among adults who are
Black (32.5%), earn an annual household income less than $25,000 (26.8%), have less than a college education (27.1%), or are currently
living with a disability (34.9%). These findings bring to light that social and economic factors in our communities can be a major
contributor to health disparities, like greater risk of obesity among people of color, low income individuals, and people who are
disabled.
• Answer: It is very disappointing to see the continuing disparity for communities of color and alarming to see that people with disabilities
have such high rates of obesity. This can be particularly problematic for people with disabilities that reside in institutional settings, live
in a food desert, or rely on supplemental food programs. The data from this kind of research helps to guide and support the approach
of DASH-NY (www.dashny.org), which is to address the policy, systems, and environmental changes that will result in more equitable
health status for all communities.
• Answer: People with disabilities in every instance deserve attention to their whole health, not just their disability. Obesity is a
preventable condition; its disproportionate prevalence among people with disabilities can be addressed though a combination of
supports in the community and the health care system. Health professionals have an opportunity to think about ways that they can get
involved within their own practices and at the community, state, and federal policy levels to help their disabled patients attain healthier
lifestyles. We are seeing more and more physicians using their experience and position of influence to advocate for healthy public
policy changes like Complete Streets laws and healthy food procurement policies which make it easier for everyone to access healthy
food and take advantage of daily opportunities to be active.
• Answer: More research and attention is needed on the prevention interventions that particularly work to address obesity disparities
among disabled populations. A glaring gap in current obesity prevention research is the dearth of validated obesity prevention
interventions for people with disabilities. Researchers should focus on very high risk populations, like communities of color and people
with disabilities, to better identify replicable models that will meet their needs. Research is also needed to identify the best system-
changes and financing mechanisms that will orient health care providers toward promoting prevention for all their patients, including
those living with disabilities.

Study finds Current Medical Practices often Not Re-Evaluated, Many offer little Net Benefit
MedicalResearch.com Interview with Dr. Vinay Prasad, MD
Medical Oncology Branch, National Cancer Institute
National Institutes of Health, 10 Center Dr 10/12N226, Bethesda, MD20892.
• Dr. Prasad: We reviewed all original articles in the New England Journal of Medicine over ten years. 1344 articles tested
some medical practice– which is a screening or diagnostic test, medication, procedure or surgery. Only 27% or 363 articles
tested current medical practice. And of these articles 146 (40%) contradicted current standard of care, constituting a
medical reversal.
• Dr. Prasad: Yes, we were surprised that such a large fraction (40%) of established standard of care is incorrect.
• Dr. Prasad: Clinicians and patients should realize that if a medical practice is not supported by a large well done RCT
powered for hard endpoints (like morbidity or mortality), then there is the chance it could be a medical reversal. Medical
practices that are unsupported should be systematically appraised by non-conflicted bodies.
• Dr. Prasad: Researchers should be brave in designing and conducting clinical trials. Much of medicine is unproven, and
unquestioned. Like the 146 examples we detailed, brave investigators have the ability to lend clarity to major medical
practices
• Citation:
• A Decade of Reversal: An Analysis of 146 Contradicted Medical Practices
• Vinay Prasad, Andrae Vandross, Caitlin Toomey, Michael Cheung, Jason Rho, Steven Quinn, Satish Jacob Chacko, Durga
Borkar, Victor Gall, Senthil Selvaraj, Nancy Ho,
Adam Cifu
• Mayo Clinic Proceedings – 22 July 2013 (10.1016/j.mayocp.2013.05.012)

Catestatin Molecular Mimics May Lead to New Anti-Hypertension Medications
Igor F. Tsigelny, Ph.D.
Department of Neurosciences, University of California at San Diego
San Diego Supercomputer Center, University of California at San Diego
Moores Cancer Center, University of California at San Diego La Jolla, California 92093
• Dr. Tsigelny: We find a new set of possible very effective drug-candidates for cure of hypertension. According to our
preliminary testing these molecules are not toxic and can start a new series of drugs.
• Dr. Tsigelny: I have not expected such efficacy of the selected candidates. Usually the way of drug design is a painful road.
You start from the barely active compounds and with a lot of modifications come to the reasonable inhibiting properties. In
our case we had the nice results very quickly. Moreover, recently we synthesized a new compound that had shown
nanomolar inhibiting properties and can be used as a lead candidate. This is a new development that is based on the result
published.
• Dr. Tsigelny: A new drug for cure of hypertension with much less of side effects than many of the current drugs.
• Dr. Tsigelny: We currently work on the design of new molecules based on these studies and (as I said above) we have a good
results.
Development of a pharmacophore model for the catecholamine release-inhibitory peptide catestatin: Virtual screening and
functional testing identify novel small molecule therapeutics of hypertension

Experimental Fish Oil DHA Extract Prevented Injury Induced Neuropathic Pain
Ru-Rong Ji, PhD Professor, Chief of Pain Research
Department of Anesthesiology and Neurobiology
Duke University Medical Center
Durham, NC 27710
• Answer: We found the pro-resolution lipid mediator protectin D1 (PD1), derived from the fish oil DHA, can effectively
prevent nerve injury-induced neuropathic pain. This treatment can also prevent nerve injury-induced neuroinflammation in
the spinal cord (such as glial activation and expression of cytokines and chemokines, e.g., IL-1b, CCL2). These cytokines and
chemokines are known to elicit pain.
• MedicalResearch.com Were any of the findings unexpected?
• Answer: Yes. We found peri-surgical treatment of PD1 can completely prevent nerve injury-induced neuropathic pain. To my
knowledge, this is the most effective prevention in animal models of chronic pain.
• Answer: The pro-resolution lipid mediators such as PD1 may be used to prevent surgery-induced chronic neuropathic pain.
Certain surgeries, such as amputation and chest surgeries have high incidence (30-80%) of chronic neuropathic pain, due to
surgery-induced nerve damage.
• Answer: Clinical trial could start when the pharmaceutical grade of PD1 is ready and safe. Otherwise, direct treatment with
DHA (precursor of PD1) or increasing DHA uptake from the diet may reduce the incidence of surgery-indued chronic pain.
CITATION: “Neuroprotectin/Protectin D1 protects neuropathic pain in mice after nerve trauma,” Zhen-Zhong Xu, Xing-Jun
Liu, Temugin Berta, Chul-Kyu Park, Ning Lü, Charles N. Serhan and Ru-Rong Ji. Annals of Neurology, online May 18, 2013.
DOI: 10.1002/ana.23928

Threatened Preterm Labor : Cost of Hospital Admissions
MedicalResearch.com Interview with: Robert E. Garfield, PhD
Department of Perinatology, Division of Obstetrics and Gynecology
University Medical Centre Ljubljana, Slovenia
• MedicalResearch.com :What are the main findings of the study?
• Dr. Garfield: Unnecessary admissions and treatments for “threatened preterm labor” are still part of everyday clinical practice and
contribute to exploding healthcare costs. This happens despite substantial evidence that measuring CL by trans-vaginal ultrasound can
help to avoid needless interventions due to the high negative predictive values of this test.
• Were any of the findings unexpected?
• Dr. Garfield: The U.S. spends more per capita on publicly funded health care than just about every other developed country, including
spending more than those countries with universal publicly funded health care systems. The high expenses associated with admissions
and treatments were, therefore, expected. What was surprising, however, was how much unnecessary tests, admissions, and
treatments, not supported by evidence, contribute to the economic burden of preterm labor hospitalizations.
• What should clinicians and patients take away from your report?
• Dr. Garfield: The potential of reducing costs in everyday clinical practice without jeopardizing outcome is enormous. There is no
question that health care costs must be reduced, and clinicians have a major responsibility in this regard. But if providers are not willing
to embrace evidence-based medicine to reduce costs, then someone else will find a different way to reduce them. And in that
case, physicians will no longer be the ones deciding how their patients are treated.
• What recommendations do you have for future research as a result of this study?
• Dr. Garfield: While it is clear that TOCO has low positive predictive value for preterm labor, and that CL and FFN test have high negative
predictive utility, there is as yet no test for early preterm labor that has a high positive predictive value. Uterine electromyography
(EMG), as studied in our center, may prove to be such a test (Lucovnik M, Maner WL, Chambliss LR, et al. Noninvasive uterine
electromyography for prediction of preterm delivery. Am J Obstet Gynecol 2011;204:228.e1-10.). Studies that compare the
specificity, sensitivity, and predictive value of EMG to TOCO, CL, and fetal fibronectin should be performed in women who present with
signs and symptoms of preterm labor.
• Citation:
• Costs of Unnecessary Admissions and Treatments for “Threatened Preterm Labor”
• Lucovnik M, Chambliss LR, Garfield RE.
• Department of Obstetrics and Gynecology, St. Joseph’s Hospital and Medical Center, Phoenix, Arizona, United States, 85013;
Department of Perinatology, Division of Obstetrics and Gynecology, University Medical Centre Ljubljana, Slovenia.

Pre-Term Deliveries Associated with Future Risk of Cardiovascular Events
MedicalResearch.com Interview with
Prof. Eyal Sheiner MD PhD
Senior Obstetrician
Soroka Medical Center, Israel
• Dr. Sheiner: The study was aimed to investigate whether a history of preterm delivery (PTD) poses a risk for subsequent maternal long-term
cardiovascular morbidity.
• During the study period 47,908 women met the inclusion criteria; 12.5% (n=5992) patients delivered preterm. During a follow-up period of more
than ten years, patients with PTD had higher rates of simple as well as complex cardiovascular events and higher rate of total cardiovascular related
hospitalizations. A linear association was found between the number of previous PTD and future risk for cardiovascular hospitalizations (5.5% for two
or more PTD, 5.0% for one PTD vs. 3.5% in the comparison group; P<0.001). The association remained significant for spontaneous vs. induced PTD
and for early (<34 weeks) as well as late (34-36+6 weeks) PTD. In a Cox proportional hazards model that adjusted for pregnancy confounders such as
labor induction, diabetes mellitus, preeclampsia and obesity, PTD was independently associated with cardiovascular hospitalizations (adjusted HR
1.4, 95% CI 1.2-1.6).
•
• Dr. Sheiner: The link between pregnancy complications and future risk for cardiovascular disease (CVD) has been previously studied with a specific
focus on preeclampsia and gestational diabetes mellitus. This evidence led to recent recommendations published by the American heart
association, including preeclampsia and gestational diabetes mellitus in the guidelines for the preliminary risk evaluation for CVD in women. The
association between PTD and subsequent cardiovascular complication was not established previously and PTD was not part of the recommended
risk-assessment.
Dr. Sheiner: In assessing a patient’s risk for cardiovascular disease, the clinician may consider pregnancy with an adverse outcome to represent the
equivalent of a physiologic stress test for the purpose of future risk assessment.
• Women who previously have experienced preterm delivery might benefit from cardiovascular risk screening that could lead to early detection and
perhaps secondary prevention of cardiovascular disease.
• Dr. Sheiner: Further large population based studies are needed to verify PTD as a risk for long term cardiovascular morbidity, and accordingly PTD
should also be suggested to be part in the guidelines for the preliminary risk evaluation for CVD in women.
• Citation:
• An association between preterm delivery and long-term maternal cardiovascular morbidity
• Kessous R, Shoham-Vardi I, Pariente G, Holcberg G, Sheiner E.
Department of Obstetrics and Gynecology, Faculty of Health Sciences, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-
Sheva, Israel.

PCI – Angioplasty: Monitoring Risk Using CK-MB
Interview with: Dr Nicholas D Gollop BSc (Hons) MB BCh
Norfolk and Norwich University Hospital,
Norwich, NR4 7UY
Norfolk, United Kingdom
• We completed a best evidence topic in interventional cardiac surgery to investigate the significance of elevated markers of cardiac damage following percutaneous
coronary intervention (PCI).
• We compared the clinical and prognostic relevance of the elevation of creatinine kinase-myocardial band (CK-MB) and cardiac troponin (cTn) levels during peri-
procedural period and post-procedural period, respectively, following an emergency or elective PCI.
• We found in excess of 390 papers after a systematic literature search, of which 10 represented the best evidence to answer the clinical question. From the best
evidence available we showed that the monitoring of cardiac biomarkers following PCI can provide important clinical information about the health of the
myocardium, as well as prognostic information on short to mid-term outcomes of mortality up to 3 years.
• The narrow evidence base advocates the use of peri-procedural CK-MB monitoring; recommending that an elevation in CK-MB is a significant predictor of adverse
events. Troponins remain a precise and reliable marker of cardiac damage; however current evidence argues that cTn holds little prognostic relevance until the
degree of elevation is almost 5 times the upper limit of normal (ULN).
• Thus, the best evidence recommends the use of peri-procedural CK-MB routinely during and following PCI to provide clinical and prognostic information about the
degree of myocardial injury and risk of post-procedural morbidity and mortality.
• It was surprising that, despite current practice, most of the evidence advocates the use of CK-MB as opposed to cTn to predict morbidity and mortality following
emergency and elective PCI. It was also unexpected to show that there is a limited evidence base surrounding this topic – as it would seem – improved understanding
of complications following PCI is of vital importance, both clinically to enable clinicians to instigate step-up care/step down care and for the delivery of an effective
and co-ordinated health service (management of patient flow, length of hospital stay, in-patient mortality etc.)
• Monitoring of cardiac biomarkers following emergency and elective PCI can provide important clinical information about the health of the myocardium and can
provide prognostic information on short to mid-term outcomes of mortality.
• The best evidence recommends the use of peri-procedural CK-MB routinely during and following emergency and elective PCI to provide clinical and prognostic
information about the degree of myocardial injury and risk of post-procedural morbidity and mortality.
• MedicalResearch.com:What recommendations do you have for future research as a result of this study?
• Our findings are in contrast to clinical practice in most centres, in which cardiac troponins are most frequently monitored to assess for cardiac damage and to predict
morbidity and mortality during and following emergency and elective PCI.
• We have shown by review of the current evidence that cardiac troponins hold little prognostic relevance until the degree of elevation is almost 5 times the ULN.
Future prospective studies assessing the sensitivity and specificity of CK-MB in predicting morbidity and mortality in various settings should be attempted to
corroborate our findings for potential future clinical use.
• Citation:
• Gollop ND, Dhullipala A, Nagrath N, Myint PK. Is periprocedural CK-MB a better indicator of prognosis after emergency and elective percutaneous coronary
intervention compared with post-procedural cardiac troponins? Interact Cardiovasc Thorac Surg. 2013 Jul 9. [Epub ahead of print] PMID: 23842761 [PubMed - as
supplied by publisher]

Aortic Dissection Repair: Does the Lunar Cycle Affect Outcomes?
MedicalResearch.com Interview with Dr. Frank Sellke, MD
Chief of cardiothoracic surgery and co-director of the Cardiovascular Institute at Rhode Island,
The Miriam and Newport hospitals
• Dr. Sellke: The main findings of the study are that outcomes of repair of an ascending aortic dissection are improved under a
full moon compared to other phases of the moon. This was with regard to both mortality and length of hospital stay.
Interestingly, there was no correlation with season of the year.
• Dr. Sellke: We were unsure what the findings would be, so we were surprised. We do not have a good
explanation, however, many biologic processes are dependent on gravitation forces, etc, which may be different under a full
moon. But we cannot say with any certainly or event scientific evidence that this is the case.
• Dr. Sellke: It is more of a curiosity that anything else, but having major surgery, such as repair of an aortic dissection may be
associated with improved outcome under a full moon.
• Dr. Sellke: Repeating the study in other centers would be the first step. If it is repeatable in other centers, determining the
reason would be interesting. If it only occurs in our center, it may just be a statistical fluke.
• Citation:
• The influence of seasons and lunar cycle on hospital outcomes following ascending aortic dissection repaiR
• Jeffrey H. Shuhaiber, Joseph L. Fava, Tai Shin, Nikola Dobrilovic, Afshin Ehsan, Arthur Bert, and Frank Sellke
Interact CardioVasc Thorac Surg f
irst published online July 9, 2013 doi:10.1093/icvts/ivt299

Childhood High Blood Pressure Rates Increasing
MedicalResearch.com Interview with: Dr. Bernard Rosner
Harvard School of Public Health
Professor in the Department of Biostatistics Department of Biostatistics
Channing Laboratory 180 Longwood Avenue Boston, Massachusetts 02115
• MedicalResearch.com: What are the Main Findings of this study?
• Dr. Rosner: The risk of elevated blood pressure (BP) among children has increased 27% over a 13-year period based on a study among
11,636 children ages 8-17 seen in the NHANES study from 1988-2008. In NHANES III (1988-1994) the risk was 15.8% among boys and
8.2% among girls. In NHANES 1999-2008 (1999-2008) the risk was 19.2% among boys and 12.6% among girls.
• Important risk factors for elevated BP were BMI, waist-circumference and sodium intake.
• Risk approximately doubled for children in the highest age-sex-specific quartile of BMI vs. children in the lowest quartile
• Risk approximately doubled for children in the highest age-sex-specific quartile of waist circumference vs. children in the lowest quartile
• Risk increased 36% among children with dietary Na intake > 3450 mg/day vs. children with intake <2300 mg/day. Na intake was
normalized per 2000 calories.
• There were large increases in both mean BMI and mean waist circumference over the 13-year period, especially for girls.
• MedicalResearch.com: Where any of the findings unexpected?
• Dr. Rosner: Over 80% of children were above the RDI for Na of 2300 mg per 2000 calories in both studies. However, there was a slight
decrease in % of children > 1.5 * RDI (> 3450 mg/2000 calories) for both boys and girls (boys 38% vs. 31%; girls 40% vs. 31%).
• About 70-80% of children were above the RDI for total and saturated fat intake in both studies, with a slight decline over time for boys.
• MedicalResearch.com: What is the Take-Home Message for Clinicians and Patients?
• Dr. Rosner: It is important to monitor blood pressure in children, since elevated bp in childhood is associated with elevated bp in
adulthood, and elevated bp in adulthood is associated with increased risk of heart disease and stroke.
• Important blood pressure risk factors to monitor are BMI, waist circumference and Na intake.
• MedicalResearch.com: What Recommendations for Future Research do you have as a result of this study?
• Dr. Rosner: An important issue would be to relate short-term changes or levels of blood pressure in children to echocardiographic
findings (e.g. elevated left ventricular mass) in a large study representative of the U.S. pediatric population.
• Citation:
• Childhood Blood Pressure Trends and Risk Factors for High Blood Pressure: The NHANES Experience 1988–2008
• Bernard Rosner, Nancy R. Cook, Stephen Daniels, and Bonita Falkner
Hypertension. 2013;HYPERTENSIONAHA.111.00831published online before print July 15
2013, doi:10.1161/HYPERTENSIONAHA.111.00831

Visual Impairment Among U.S. Adults and Age-Related Eye Diseases
MedicalResearch.com Interview with: Chiu-Fang Chou DrPH
Division of Diabetes Translation National Center for Chronic Disease Prevention and Health Promotion CDC,
4770 Buford Hwy, NE (K-10)
Atlanta GA 30341-3727
• A: We estimated nearly 9 million people aged 40 years and older are visually impaired using the National Health and
Nutrition Examination Survey. Three out of every four people aged 40 years and older with VI have uncorrected refractive
error that could be easily corrected with simple glasses or contact lenses. The ocular disease most associated with visual
impairment in our study sample was age-related macular degeneration. Finally, increasing age and low educational
attainment were significant predictors of visual impairment.
•
MedicalResearch.com: What should clinicians and patients take away from your report?
• A: Early detection and timely treatment can prevent or delay visual impairment. The clinicians need to remind their patients
of the importance of recommended eye examination. In addition, screening of the elderly may identify adults at increased
risk of VI due to eye diseases. Increasing public awareness of vision and eye health, and the availability of affordable eye
care services might help to reduce avoidable visual impairment.
• MedicalResearch.com:: What recommendations do you have for future research as a result of this study?
• A: More effort is needed to collect national and local data in order to monitor the nation’s eye health and eye care
utilization. There is a need for innovative interventions to reduce unnecessary vision impairment.
• Citation:
• Chou CF, Cotch MF, Vitale S, Zhang X, Klein R, Friedman DS, Klein BEK, Saaddine JB. Age-related eye diseases and visual
impairment among U.S. Adults.
Am J Prev Med. 2013 Jul;45(1):29-35. doi: 10.1016/j.amepre.2013.02.018.

Diet Sodas: Adverse Effects of Altered Metabolism, Weight Gain
Susan E. Swithers PhD
Professor, Behavioral Neuroscience
Department of Psychological Sciences and Ingestive Behavior Research Center
Purdue University, 703 Third Street West Lafayette, IN 47907, USA
• Dr. Swithers: The paper examined the last 5 years of studies that looked at risks associated with consuming artificially sweetened beverages like diet
soda. These studies indicated that those who consume diet soda were at significantly greater risk for a variety of negative health outcomes like type
2 diabetes, coronary heart disease, hypertension and stroke, along with being more likely to gain excess weight. These effects might be due to a
disruption of basic learned response. The idea is that normally things when things that taste sweet are consumed, the body receives calories and
sugar. Our bodies can learn to prepare to deal with these calories and this sugar by starting up our digestive processes as soon as the sweet taste hits
our mouth, for example by releasing hormones that not only help us regulate blood sugar, but also can contribute to feelings of fullness. When we
consume diet sodas, the mouth gets the sweet taste, but the body doesn’t get the calories or the sugar. The body may then learn that a sweet taste
in the mouth doesn’t always predict sugar and calories, so it makes adjustments in how many hormones it releases. So when we actually consume
real sugar, the body doesn’t produce the same kinds of physiological responses, which can lead to overeating, higher blood sugar, and over the long
term could contribute to diseases like diabetes and stroke.
• Dr. Swithers: The paper also looked at the risks associated with drinking regular sodas when they were reported along with the diet soda data, and it
was somewhat unexpected that the increase in risk for diet soda drinkers was often quite similar to that seen with regular soda drinkers.
• Dr. Swithers: Frequent consumption, as little as one every day, of sweetened drinks, whether they regular sodas or diet sodas, is linked to serious
health risks. Diabetes, heart disease, metabolic syndrome and stroke all occur at higher rates in people who drink these beverages. This means that
people need to be much more mindful when they drink sweetened beverages. They should be viewed as occasional treats, not as normal
accompaniments to meals or regular snacks. And people need to pay attention to how much sugar and other sweeteners they are consuming in their
overall diet as well, especially if they drink sodas.
• Dr. Swithers:We still need to understand what mechanisms are responsible for these observed links between soda intake and negative health
outcome. Research looking at whether people who are given unsweetened beverages to consume compared to sweetened beverages have better
outcomes is clearly needed, and more research into the basic physiological processes that could connect diet sodas to diseases like diabetes and
heart disease might help us come with strategies to potentially prevent or reverse these outcomes.
• Citation:
• Trends in Endocrinology & Metabolism
Susan E. Swithers
10.1016/j.tem.2013.05.005
11 July 2013

High Risk Abdominal Wounds: Does Delayed Primary Closure Reduce Infection Risk?
Aneel Bhangu, MBChB, MRCS and Douglas M. Bowley, FRCS
Royal Centre for Defense Medicine, Birmingham, England
• Answer: Our study was a meta-analysis, which combined the findings from 8 randomized controlled trials that included a total of 623 patients. The key finding was
that delayed primary skin closure (DPC) for contaminated and dirty abdominal incisions may reduce the rate of surgical site infection. However, due to high risk of
bias from the included studies, including flaws in study design, definitive evidence is lacking.
• We believe that this meta-analysis represents an exciting development in biomedical publishing; this was a true collaboration between US and UK military surgeons
to examine an area of major concern and interest to surgeons everywhere. This work uses experience hard-won on the battlefields of Iraq and Afghanistan, combined
with published surgical trials, to inform both future research activity as well as military and civilian surgical practice. This cross-fertilization of ideas is one positive
consequence of all the sacrifice and suffering of recent conflicts.
• Answer: In our study, a fixed effect model showed that DPC significantly reduced wound infection, but the random effect model did not. The decision about whether
to use a fixed or random effect meta-analysis remains hotly debated. Since the data were heterogeneous, the traditional statistical approach is to take the result from
the random effects model: that there is no difference between groups. However, as clinicians we can interpret the two different results as indicating uncertainty in
the effect. We believe this means that the technique should certainly not be dismissed, as it is a cheap and potentially useful intervention.
• Answer: Our message for the practicing surgeon is that due to the potential [but not convincingly proven] benefit, DPC has a role for surgical site infection
prophylaxis for the high-risk patient. The patient group most likely to benefit are those whose operation can be classed as ‘dirty’. Patient-related factors that would
contribute include: presence of shock/requirement for inotropes, pre-existing patient co-morbidity [high ASA grade, immunosuppression, diabetes, steroid use and
the obese or a combination of these. Currently, for ‘contaminated’ cases we do not advocate using DPC and suggest that surgeons should continue to follow their
own choice of closure.
• We are now extending the paradigm of ‘damage control surgery’ beyond the trauma setting into emergency general surgery. Surgeons should be considering the
patient’s physiological status and planning their surgical approach appropriately. Think of DPC of the laparotomy wound as a technique of ‘damage control’ for the
general surgical patient. So for the midline laparotomy for perforated sigmoid diverticulitis, in the presence of fecal contamination and particularly if there are
patient related risk factors, we recommend [and also practice] delayed primary closure of the wound.
• Answer: The findings of our study, in particular a borderline effect when considering the random versus fixed effect models, adds fuel to clinical equipoise and
demonstrate that this is a particularly good time for a randomized trial. Clinical equipoise means that enough surgeons must believe this to be a significant
problem, and to be unsure of the correct way to treat it. Recent evidence shows an increasing culture of randomized, controlled trials [RCTs], and although there has
been a recent slight decrease in North American RCTs, the United States remains the country with the highest number of published RCTs. Thus, if there is equipoise
and an improving culture towards trials, we put out a call for a multicenter, and hopefully transatlantic, randomized trial.
• Citation:
• Systemic Review and Meta-analysis of Randomized Clinical Trials Comparing Primary vs. Delayed Primary Skin Closure in Contaminated and Dirty Abdominal Incisions
• Bhangu A, Singh P, Lundy J, Bowley DM. Systemic Review and Meta-analysis of Randomized Clinical Trials Comparing Primary vs. Delayed Primary Skin Closure in
Contaminated and Dirty Abdominal Incisions. JAMA Surg. 2013;():1-8. doi:10.1001/jamasurg.2013.2336.

Poor Sleep and Poor Behavior in Children
MedicalResearch.com Interview with: Rebecca J. Scharf MD MPH
Developmental and Behavioral Pediatrics
Kluge Children’s Rehabilitation Center
Center for Global Health
• Dr. Scharf: This study examined data from approximately 8,500 children, born in 2001, who were 4 years old at the time of
the study. These children are representative of the population of the United States. The main findings of our study were
that children with shorter nighttime sleep duration had higher odds of parent-reported externalizing behaviors such as
aggression, tantrums, overactivity and anger.
• Dr. Scharf: What was unexpected to us was how consistent the results were. When run categorically to look for odds of
worse behaviors, as well as linearly, children in the shortest sleep categories had higher odds of all the behaviors we
examined and as sleep increased, externalizing behaviors decreased.
• Dr. Scharf: This study showed an association between nighttime sleep duration and
tantrums, aggression, anger, overactivity, and annoying behaviors in preschool age children. When presented with a child in
the office who is struggling with behavior, it may be helpful for clinicians to remember to ask about nighttime sleep habits
and encourage parents to facilitate healthy sleep patterns for their young children.
• Dr. Scharf: We are interested in examining this relationship over time, as the children get older. We would also be interested
in examining teacher report of externalizing behaviors.
• Citation:
• Nighttime Sleep Duration and Externalizing Behaviors of Preschool Children
Scharf, Rebecca J.; Demmer, Ryan T.; Silver, Ellen J.; Stein, Ruth E.K.
• Journal of Developmental & Behavioral Pediatrics. 34(6):384-391, July/August 2013.
doi: 10.1097/DBP.0b013e31829a7a0d

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