MedicalResearch.com: Medical Research Exclusive Interviews July 9 2015

MedicalResearch.comExclusive Interviews with Medical Research and

Health Care Researchers from Major and Specialty Medical Research Journals and Meetings

Editor: Marie Benz, MD [email protected]

July 9 2015

For Informational Purposes Only: Not for Specific Medical Advice.

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Low Testosterone Linked To Obesity and Depression In MenMedicalResearch.com Interview with:Michael S. Irwig MDDivision of Endocrinology Medical Faculty AssociatesGeorge Washington University

• Medical Research: What is the background for this study? What are the main findings?

Response: Many factors are associated with lower testosterone levels and many men who have their testosterone levels checked have non-specific depressive symptoms. The main finding is a remarkably high rate of depression and depressive symptoms (56%) in men who are referred for borderline testosterone levels. Other significant findings include a prevalence of overweight and obesity higher than the general population

• .• Medical Research: What should clinicians and patients take away from your report?• Response: Symptoms of low testosterone overlap with many other conditions such as

depression. It is very important to assess for depression in men referred for borderline testosterone levels.

Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.

http://medicalresearch.com/mental-health-research/depression/low-testosterone-linked-to-obesity-and-depression-in-men/15481/









http://medicalresearch.com/author-interviews/testosterone-therapy-lowered-mortality-in-hypogonadal-men/14044/

http://medicalresearch.com/author-interviews/low-testosterone-may-affect-more-than-25-of-us-males/14212/





http://medicalresearch.com/menopause/should-the-ovaries-be-removed-at-time-of-hysterectomy-for-benign-disease/1236/

Low Testosterone Linked To Obesity and Depression In MenMedicalResearch.com Interview with:Michael S. Irwig MDDivision of Endocrinology Medical Faculty AssociatesGeorge Washington University

• Medical Research: What recommendations do you have for future research as a result of this study?

• Response: I recommend more research on how different mental health conditions can impact testosterone levels.

• Citation:• Westley, C. J., Amdur, R. L. and Irwig, M. S. (2015), High Rates of Depression and Depressive S

ymptoms among Men Referred for Borderline Testosterone Levels. Journal of Sexual Medicine. doi: 10.1111/jsm.12937











http://medicalresearch.com/mental-health-research/depression/testosterone-may-protect-against-mood-related-disorders/13353/

http://onlinelibrary.wiley.com/doi/10.1111/jsm.12937/abstract








Diabetes Medication Reduced Weight and Improved Metabolic Parameters in Obese PatientsMedicalResearch.com Interview with:Dr. F. Xavier Pi–Sunyer MDDivision of Endocrinology and Obesity Research CenterColumbia University, New York


Dr. Pi-Sunye: In a large randomized trial, the drug Liraglutide was compared to placebo in overweight and obese non-diabetic volunteers. Over 52 weeks, in combination with diet and increased physical activity, Liraglutide lowered body weight by 8.4 kg as compared to 2.8 kg in placebo. 63% vs 27% lost at least 5% of baseline weight, 33% vs 10% lost more than 10% of baseline weight.

Medical Research: What are the implications of this report?• Dr. Pi-Sunye: This medication adds to the armamentarium physicians will have in helping

overweight and obese patients lose weight and maintain it off.


http://medicalresearch.com/diabetes/diabetes-medication-reduced-weight-and-improved-metabolic-parameters-in-obese-patients/15485/














Diabetes Medication Reduced Weight and Improved Metabolic Parameters in Obese PatientsMedicalResearch.com Interview with:Dr. F. Xavier Pi–Sunyer MDDivision of Endocrinology and Obesity Research CenterColumbia University, New York

• Medical Research: What is the take home message?• Dr. Pi-Sunye: Liraglutide can lower weight, improve cardiovascular risk factors and improve

quality of life. It can also reduce the progression to type 2 diabetes from prediabetes.• Medical Research: What recommendations do you have for future research as a result of

this study?• Dr. Pi-Sunye: I think it would be an advance if an oral analogue to this medication could be

developed.• Citation:• A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management• Xavier Pi-Sunyer, M.D., Arne Astrup, M.D., D.M.Sc., Ken Fujioka, M.D., Frank Greenway, M.D.,

Alfredo Halpern, M.D., Michel Krempf, M.D., Ph.D., David C.W. Lau, M.D., Ph.D., Carel W. le Roux, F.R.C.P., Ph.D., Rafael Violante Ortiz, M.D., Christine Bjørn Jensen, M.D., Ph.D., and John P.H. Wilding, D.M. for the SCALE Obesity and Prediabetes NN8022-1839 Study Group

• N Engl J Med 2015; 373:11-22July 2, 2015 DOI: 10.1056/NEJMoa1411892











http://www.nejm.org/doi/full/10.1056/NEJMoa1411892












Warming Climate May Not Reduce Winter MortalityMedicalResearch.com Interview with:Prof. Patrick L Kinney Ph.D.Professor of Environmental Health Sciences andDirector, Columbia Climate and Health Program Mailman School of Public Health

Columbia University, New York, NY

• Medical Research: What is the background for this study?

Dr. Kinney: Many previous assessments have concluded that climate change will lead to large reductions in winter mortality.

• Medical Research: What are the main findings?

Dr. Kinney: We carried out analyses that contradict this conclusion. We argue that climate change won’t have much impact one way or the other on winter mortality.


http://medicalresearch.com/author-interviews/warming-climate-may-not-reduce-winter-mortality/15490/
















Warming Climate May Not Reduce Winter MortalityMedicalResearch.com Interview with:Prof. Patrick L Kinney Ph.D.Professor of Environmental Health Sciences andDirector, Columbia Climate and Health Program Mailman School of Public Health

Columbia University, New York, NY

• Medical Research: What should clinicians and patients take away from your report?

• Dr. Kinney: I don’t think we can expect marked changes in the current annual cycle of disease and deaths (higher in winter, lower in other seasons).


• Response: Most useful would be analyses of data over long time periods in multiple locations.

• Citation:• Winter season mortality: will climate warming bring benefits?• Patrick L Kinney et al 2015 Environ. Res. Lett. 10 064016

doi:10.1088/1748-9326/10/6/064016













http://dx.doi.org/10.1088/1748-9326/10/6/064016






Celiac Disease Implies Higher Risk of Other Autoimmune DiseasesMedicalResearch.com Interview with:Louise Emilsson, MD PhD, PostdocPrimary Care Research unitVårdcentralen Värmlands Nysäter and Institute of Health and Society

University of Oslo

• MedicalResearch: What is the background for this study? • Dr. Emilsson: Genetics is considered an important factor in the development of celiac disease

and other autoimmune diseases. For e.g. the prevalence of celiac disease is about 10% in first-degree relatives of celiac patients compared to about 1% in the general population. Several earlier genome-wide association study (GWAS) studies have established shared genetic features also in-between different autoimmune diseases, however, very little is known about the risk of developing other autoimmune diseases in relatives of celiac patients. Therefore we assessed the risk of several other non-celiac autoimmune diseases (Crohn’s disease, type 1 diabetes mellitus, hypothyroidism, hyperthyroidism, psoriasis, rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus or ulcerative colitis) in all first degree relatives and spouses of Swedish celiac patients.


http://medicalresearch.com/author-interviews/celiac-disease-implies-higher-risk-of-other-autoimmune-diseases/15478/















http://medicalresearch.com/pediatrics/celiac-disease-gluten-introduced-infants/2140/







University of Oslo

• MedicalResearch: What should clinicians and patients take away from your report?• Dr. Emilsson: Clinicians could benefit from knowing that the genetic predisposition for celiac

disease in celiac first-degree relative also implies a higher risk of other autoimmune diseases. For the patients the most important message is that it seems that both genetic and environmental factors contribute to development of autoimmune diseases.























University of Oslo

• MedicalResearch: What are the main findings?• Dr. Emilsson: The main finding is that both first-degree relatives (+28%) and spouses (+20%)

are at increased risk of other autoimmune diseases. There are several plausible explanations for these findings. One is of course that individuals with celiac disease and their first-degree relatives share a genetic autoimmune predisposition, another potential explanation involves shared environment (relevant for both first-degree relatives and spouses) but finally we cannot rule out that a certain degree of increased awareness of signs and symptoms in both first-degree relatives and spouses might lead to more examinations and thereby diagnoses (so-called ascertainment bias). Probably all these mechanisms contributed to the finding.

















http://medicalresearch.com/pediatrics/growth-screening-facilitates-early-diagnosis-of-celiac-disease-in-children/12169/







University of Oslo

• MedicalResearch: What recommendations do you have for future research as a result of this study?

• Dr. Emilsson: The findings open up for future research on which shared environmental factors confer an increased risk of autoimmune diseases. Such knowledge would of course be of high clinical importance if they also mean that prevention is possible. It would also be interesting to see if future GWAS studies on shared genetics in-between celiac disease and systemic lupus erythematosus would yield some new loci of shared genetic traits.

• Citation:• Louise Emilsson, Cisca Wijmenga, Joseph A. Murray, Jonas F. Ludvigsson. Autoimmune

Disease in First-Degree Relatives and Spouses of Individuals With Celiac Disease. Clinical Gastroenterology and Hepatology, 2015; 13 (7): 1271 DOI: 10.1016/j.cgh.2015.01.026

















http://dx.doi.org/10.1016/j.cgh.2015.01.026






Evidence of Value of Orphan Drugs InconsistentMedicalResearch.com Interview with:Igho Onakpoya MD MSc Clarendon ScholarUniversity of OxfordCentre for Evidence-Based MedicineNuffield Department of Primary Care Health SciencesOxford UK

• MedicalResearch: What is the background for this study? What are the main findings?• Dr. Onakpoya: Several orphan drugs have been approved for use in Europe. However, the

drugs are costly, and evidence for their clinical effectiveness are often sparse at the time of their approval.

• We found inconsistencies in the quality of the evidence for approved orphan drugs. We could not identify a clear mechanism through which their prices drugs are determined. In addition, the costs of the branded drugs are much higher than their generic or unlicensed versions.


http://medicalresearch.com/medication-research/evidence-of-value-of-orphan-drugs-inconsistent/15498/





















• MedicalResearch: What should clinicians and patients take away from your report?• Dr. Onakpoya: Because of inconsistencies in the evidence regarding the benefit-to-harm

balance of orphan medicines, coupled with their high prices, clinicians and patients should assess whether the orphan drugs provide real value for money before making a decision about their use for a medical condition.
























• Dr. Onakpoya: We need more clinical trials to assess the benefits and harms of orphan drugs, especially for those which currently have low levels of evidence. Systematic reviews of some orphan medicines are outdated, and these need to be updated since further clinical trial results have become available. Furthermore, research aimed at providing a standard, transparent and robust mechanism for determining the prices of orphan drugs is imperative.

• Citation:• Effectiveness, safety and costs of orphan drugs: an evidence-based review

Igho J Onakpoya, Elizabeth A Spencer, Matthew J Thompson, Carl J Heneghan• BMJ Open 2015;5:6 e007199 doi:10.1136/bmjopen-2014-007199

















http://bmjopen.bmj.com/citmgr?gca=bmjopen;5/6/e007199









Omega-3 fatty Acid Supplementation May Benefit Mild Cognitive ImpairmentMedicalResearch.com Interview with:Milan Fiala, M.D.Research Professor, UCLA Department of SurgeryLos Angeles, CA

Medical Research: What is the background for this study? What are the main findings?

Dr. Fiala: Omega-3 fatty acid supplementation is well-known to public for its health benefits in cardiovascular diseases and putative benefits against “Minor Cognitive Impairment” reported in other studies . This study shows that omega-3 protected against oxidation and resveratrol improves the immune system against amyloid-beta in the brain, probably by increasing its clearance from the brain by the immune system. Overall the patients taking the drink seemed to preserve their memory better for up to 2 years than expected based on previous studies. However, our study was small and not controlled by a placebo, which may present a bias.


http://medicalresearch.com/author-interviews/omega-3-fatty-acid-supplementation-may-benefit-mild-cognitive-impairment/15446/















• Medical Research: What should clinicians and patients take away from your report?• Dr. Fiala: Omega-3 supplementation with the Smartfish drink used in the study has objective

beneficial effect on the immune system important in prevention of Minor Cognitive Impairment. However, personal problems may interfere with the immune system response including infections, surgeries, GI intolerance, non-compliance, and personal issues like being unable to travel with omega-3 drink ( 200 ml per day). The best responses were in ApoE3/E3 patients. Some ApoE4/E3 genotype patients have good response to the drink, whereas other ApoE4 do not respond.











http://medicalresearch.com/diabetes/omega-3-fatty-acids-mi-risk-diabetic-non-diabetic-patients-cad/2323/








• Dr. Fiala: Omega-3 fatty acid supplementation has benefits in Minor Cognitive Impairment patients but not in patients with Alzheimer dementia, thus must be started early. Our flow cytometric test of amyloid-beta phagocytosis can identify the patients who have defective immunity against amyloid-beta and need omega-3 supplementation.

• Minor Cognitive Impairment is a human disease related to defective immune system against amyloid-beta. Minor Cognitive Impairment must be investigated in human immune system of human patients, which have specific biochemical defects not observed in animal models. Therapy of Minor Cognitive Impairment needs to be individually applied and immunologically monitored.

• This study was supported in part by Smartfish, Oslo, Norway.• Citation:• Fiala, R. C. Halder, B. Sagong, O. Ross, J. Sayre, V. Porter, D. E. Bredesen. –3 Supplementation

increases amyloid- phagocytosis and resolvin D1 in patients with minor cognitive impairment. The FASEB Journal, 2015; DOI: 10.1096/fj.14-264218











http://medicalresearch.com/addiction/alcohol/omega-3-fatty-acid-may-protect-brain-alcohol-binges/6667/

http://dx.doi.org/10.1096/fj.14-264218






No Definitive Biomarker Predicts Cancer Response To Radiation TherapyMedicalResearch.com Interview with:Dr Ananya ChoudhuryConsultant and Honorary Senior Clinical Lecturer, Clinical OncologyThe Christie NHS Foundation Trust, Wilmslow Road

Withington, Manchester, UK


Response: Although more than half of newly diagnosed cancer patients are treated with radiotherapy, it is still not possible to select patients who will respond and tolerate radiotherapy compared to those who do not. There has been a lot of work done to try and isolate intrinsic biomarkers which will identify either radio-responsive or radio-resistant disease. We have undertaken a systematic view summarising the evidence for biomarkers as predictors of radiotherapy.

• Despite identifying more than 500 references during a systematic literature search, we found only twelve studies which fulfilled our inclusion criteria. Important exclusion criteria included pre-clinical studies, studies with no control population and a sample size of less than 100 patients.

• Only 10 biomarkers were identified as having been evaluated for their radiotherapy-specific predictive value in over 100 patients in a clinical setting, highlighting that despite a rich literature there were few high quality studies suitable for inclusion. The most extensively studied radiotherapy predictive biomarkers were the radiosensitivity index and MRE11; however, neither has been evaluated in a randomised controlled trial.


http://medicalresearch.com/author-interviews/no-definitive-biomarker-predicts-cancer-response-to-radiation-therapy/15506/

















http://medicalresearch.com/cancer-_-oncology/breast-cancer/breast-cancer-intraoperative-vs-whole-breast-radiotherapy/2652/








• Medical Research: What should clinicians and patients take away from your report?• Response: Although these biomarkers show promise there is not enough evidence to justify

their use in routine practice. Further validation is needed before biomarkers can fulfil their potential and predict treatment outcomes for large numbers of patients.



























• Response: Robust research following the REMARK guidelines such as the importance of including a detailed assay method should be undertaken using where possible tissue collected from large clinical trials. The biomarker should be validated in multiple independent cohorts before being tested in a biomarker-driven phase III study.

• Citation:• Biomarkers of Tumour Radiosensitivity and Predicting Benefit from Radiotherapy

Forker LJ, Choudhury A, Kiltie AE.• Clin Oncol (R Coll Radiol). 2015 Jun 25. pii: S0936-6555(15)00235-6. doi: 10.1016/j.clon.2015.

06.002.

[Epub ahead of print



















http://www.ncbi.nlm.nih.gov/pubmed/26119726










Medicare’s Inconsistent Drug Coverage Policies Can Impede Access To New TechnologiesMedicalResearch.com Interview with:Joshua P. Cohen Ph.DResearch Associate ProfessorTufts Center for the Study of Drug DevelopmentBoston, Massachusetts


Dr. Cohen: Florbetapir 18F was the first radioactive diagnostic agent approved by the US Food and Drug Administration for positron emission tomography imaging of the brain to evaluate amyloid â neuritic plaque density.

• Medical Research: What are the main findings?• Dr. Cohen: Medicare has restricted coverage of florbetapir in the US, whereas conspicuously

the UK NHS decided to reimburse the radiopharmaceutical. Note, the British NHS is generally more restrictive with regard to coverage of new technologies than the Centers for Medicare and Medicaid Services. Historically Medicare has rejected coverage of 25% of diagnostics approved by the FDA, but covers all FDA approved drugs administered in the physicians �office. Furthermore, Medicare has subjected labeled use of diagnostics, including a half-dozen Alzheimer’s diagnostics, to its coverage with evidence development program while not subjecting any labeled uses of drugs to coverage with evidence development. In sum, diagnostics are subject to a level of scrutiny by Medicare that is rarely given Medicare Part B drugs (physician-administered).


http://medicalresearch.com/author-interviews/medicares-inconsistent-drug-coverage-policies-can-impede-access-to-new-technologies/15519/














Medicare’s Inconsistent Drug Coverage Policies Can Impede Access To New TechnologiesMedicalResearch.com Interview with:Joshua P. Cohen Ph.DResearch Associate ProfessorTufts Center for the Study of Drug DevelopmentBoston, Massachusetts

• Medical Research: What should clinicians and patients take away from your report?• Dr. Cohen: From a clinical and policymaker perspective, Medicare’s inconsistency can impede

patient access to important new technologies, such as florbetapir. Medicare should be more consistent in terms of the level of scrutiny given diagnostics and drugs. In addition, measurement of benefits of diagnostics such as florbetapir should be broader than patient outcomes. In the absence of Alzheimer’s treatments that confer significant benefits, florbetapir’s impact will be measured with respect to its ability to rule out Alzheimer’s, which in turn will influence a patient’s treatment pathways.


• Response: A prudent approach would be for the Centers of Medicare and Medicaid Services to provide all Medicare beneficiaries with access to florbetapir.

• Citation:• Cohen Joshua P, Dong Jinghui, Lu Christine Y, Chakravarthy Ranjana. Restricting access to florb

etapir: Medicare coverage criteria for diagnostics and drugs are inconsistent 2015; 351 :h3333











http://medicalresearch.com/mental-health-research/alzheimers-dementia/long_term_benzodiazepines_may_increase_alzheimers_disease_risk/7440/

http://www.bmj.com/content/351/bmj.h3333








Women With Epilepsy At Much High Risk Of Death During DeliveryMedicalResearch.com Interview with:Sarah C. MacDonald, BSHarvard T. H. Chan School of Public Health

MedicalResearch: What is the background for this study? What are the main findings?Response: Approximately 0.3-0.5% of all pregnancies are in women with epilepsy. While individual studies have suggested that women with epilepsy may be at increased risk for certain adverse outcomes in pregnancy, the risks have not been well quantified in large population based samples. We addressed this issue using a large retrospective sample of delivery hospitalizations from across the United States.The main findings were that women with epilepsy had a more than 10 fold increased risk of death during their delivery hospitalization as compared to the risk in women without epilepsy (80 deaths per 100,000 women with epilepsy vs. 6 deaths per 100,000 in women without epilepsy). We also found that women with epilepsy were at increased risk for a cesarean delivery, prolonged hospital stay, preeclampsia, preterm labor, stillbirth and other adverse outcomes.


http://medicalresearch.com/neurological-disorders/women-with-epilepsy-at-much-high-risk-of-death-during-delivery/15494/






http://medicalresearch.com/sleep-disorders/sleeping-on-stomach-may-increase-risk-of-death-in-epilepsy/10889/







• MedicalResearch: What should clinicians and patients take away from your report?• Response: The findings from our work suggest that women with epilepsy are at a higher risk

for many adverse outcomes during their delivery admission in hospital. While this is only one study, our work suggests that pregnancies in women with epilepsy may be high risk and that these patients may be best treated by physicians who are comfortable caring for these complex patients. While the relative risk of death in women with epilepsy was quite high, it is important to note that maternal death during delivery is still very rare, with only approximately 80 deaths for every 100,000 women with epilepsy.















• Response: Our study was not designed to determine particular causes for the increased risks in women with epilepsy. Therefore further research is needed to understand why women with epilepsy are at a higher risk for adverse outcomes during delivery. Future research is also needed to determine the benefits of particular interventions. One possible route of improvement could be in triaging women with epilepsy to higher risk centers and following them closely throughout gestation and post-delivery.

• Citation:• MacDonald SC, et al “Mortality and morbidity during delivery hospitalization among pregnant

women with epilepsy in the United States” JAMA Neurology 2015; DOI: 10.1001/jamaneurol.2015.1017








http://archneur.jamanetwork.com/article.aspx?articleid=2368725









Rosacea May Be Linked To Skin and Thyroid CancerMedicalResearch.com Interview with:Wen-Qing Li Ph.DDepartment of Dermatology Warren Alpert Medical SchoolDepartment of Epidemiology, School of Public Health,

Brown University, Providence, RI


Response: Rosacea is a chronic inflammatory cutaneous disorder and may be an end-organ response in a systemic disorder. We systemically examined the association between personal history of rosacea and risk of cancer based on 75088 whites in the Nurses’ Health Study II, during a follow-up of 20 years.


Response: We suggest possible associations between personal history of rosacea and an increased risk of thyroid cancer and Basal Cell Cancer. Analyses did not find significant associations for other individual cancer types.


http://medicalresearch.com/cancer-_-oncology/rosacea-may-be-linked-to-skin-and-thyroid-cancer/15539/









http://medicalresearch.com/author-interviews/rosacea-metronidazole-plus-modified-release-40-mg-doxycycline-improved-moderate-to-severe-disease/14231/






Rosacea May Be Linked To Skin and Thyroid CancerMedicalResearch.com Interview with:Wen-Qing Li Ph.DDepartment of Dermatology Warren Alpert Medical SchoolDepartment of Epidemiology, School of Public Health,

Brown University, Providence, RI

• Medical Research: What should clinicians and patients take away from your report?• Response: We provide evidence demonstrating that rosacea may represent a systemic

disorder beyond a skin condition. Pending further replication of our findings from other studies, clinicians would be suggested to closely follow up their Rosacea cases for potential malignant outcomes. Frequent physical examinations would also be suggested for patients.


• Response: Further studies are required to replicate our findings in other populations, particularly those of women and non-Caucasians. It would be critical to explore the potential heterogeneities for the association with cancer in different subtypes of rosacea. Studies are warranted to explore the underlying mechanisms for our findings.

• Citation:• Personal history of rosacea and risk of incident cancer among women in the US• W-Q Li, M Zhang, F W Danby, J Han and A A QureshiBritish Journal of Cancer

advance online publication 23 June 2015; doi: 10.1038/bjc.2015.217











http://medicalresearch.com/author-interviews/rosacea-improved-with-modified-release-doxycycline-40-mg-plus-topical-metronidazole/13861/

http://www.nature.com/bjc/journal/vaop/ncurrent/abs/bjc2015217a.html









Key Study Shifts Focus To Smooth Muscle Cells In Atherosclerotic Heart DiseaseMedicalResearch.com Interview with:Dr. Gary K Owens Ph.DRobert M. Berne Cardiovascular Research CenterUniversity of Virginia, Charlottesville, Virginia

Medical Research: What is the background for this study?

Dr. Owens: The leading cause of death in the USA and worldwide is cardiovascular disease with many of the clinical consequences including heart attacks (myocardial infarctions) and strokes being secondary consequences of atherosclerosis, commonly referred to as hardening of the arteries. Importantly, a heart attack is not caused by gradual narrowing of a large coronary artery by the atherosclerotic plaque, but rather is caused by acute rupture of a plaque that results in a catastrophic thrombotic event that can completely occlude a major coronary artery shutting off blood supply to a major heart region. Similarly, rupture of a plaque can result in formation of a thrombus that breaks off and circulates to a cerebral vessel where it can occlude blood flow to a brain region leading to a stroke. As such, it is critical to understand the mechanisms that regulate the stability of plaques, and the likelihood of plaque rupture.


http://medicalresearch.com/heart-disease/key-study-shifts-focus-to-smooth-muscle-cells-in-atherosclerotic-heart-disease/15548/








http://medicalresearch.com/author-interviews/dvts_clot_busing_procedure_gaining_in_safety_and_utilization/6489/







The general dogma among clinicians and cardiovascular researchers has been that atherosclerotic plaques that have an abundance of macrophages and macrophage-derived foam cells relative to smooth muscle cells (SMC), the cells that normally line all of your blood vessels, are less stable and more prone to rupture with subsequent clinical consequences. However, the evidence for this is based on use of methods that are unreliable in identifying which cells within the plaque are truly derived from macrophages versus SMC, and even more importantly, what mechanisms regulate phenotypic transitions of these cells that are critical in the pathogenesis of this disease. Indeed, results of studies in cultured smooth muscle cells and macrophages have shown that each cell can express markers of the other cell type in response to stimuli likely to be present within advanced atherosclerotic lesions while down-regulating expression of their typical cell selective markers. As such, previous studies in the field have likely mis-identified which cell is which in many cases.
















The goals of our studies were to clearly identify which cells within advanced atherosclerotic lesions are derived from SMC, to determine the various phenotypes exhibited by these cells and their functional role in lesion pathogenesis, and to determine what regulates these phenotypic transitions.
















Medical Research: What are the main findings?

Dr. Owens: Using a rigorous SMC-specific lineage tracing mouse developed by our lab, we determined that >80% of SMC within advanced atherosclerotic lesions of ApoE knockout hyperlipidemic mice cannot be identified using typical SMC markers such as SM alpha-actin (SMaA), the marker used in virtually all previous studies in the field. Moreover, we observed that approximately 1/3 of cells within lesions that express macrophage markers are of SMC not myeloid origin and that SMC-derived lesion cells that are negative for SMaA also express markers of mesenchymal stem cells and/or myofibroblasts. Importantly, using a novel single cell epigenetic SMC lineage tracing method previously developed by our lab, we also showed that transition of smooth muscle cells to macrophage-like cells also is highly prevalent within advanced human coronary artery atherosclerotic lesions comprising about 20% of cells previously thought to be macrophages.
















Finally, we show that SMC specific knockout of the stem cell pluripotency gene Klf4 did not result in a change in the number of smooth muscle cells within lesions but resulted in these cells undergoing transition to a phenotype that was atheroprotective as evidenced by lesions that were much smaller in size, that contained far fewer SMC-derived macrophage-like cells, and which exhibited multiple indices of increased plaque stability including a thickened fibrous cap. As such, loss of one gene, Klf4, in one cell type, SMC, had a rather profound positive impact on the pathogenesis of atherosclerosis.
















• Medical Research: What should clinicians and patients take away from your report?• Dr. Owens: Taken together, results of our studies indicate that smooth muscle cells-derived

cells play a much more important role in atherosclerosis pathogenesis than has generally been appreciated but that SMC-derived lesion cells can exhibit detrimental as well as beneficial properties depending on the nature of their phenotypic transitions. Results also clearly establish that most previous studies of atherosclerosis have mis-identified many of the SMC and macrophages within lesions of both man and animal models, as well as the extent to which these cells contribute to formation of foam cells and plaque stability.

















• Dr. Owens: Our results clearly establish that use of conventional markers of smooth muscle cells and macrophages are insufficient for identifying these cell types within lesions. Future studies need to be much more careful in interpreting results if the experimental approach does not include rigorous lineage tracing.

• However, of greatest significance, studies are the first to our knowledge to demonstrate that therapeutic targeting of smooth muscle cells within lesions represents a viable means of enhancing plaque stability to reduce the probability of plaque rupture with possible myocardial infarction or stroke. That is, can we identify therapeutic agents that induce SMC to undergo changes in phenotype that are beneficial in promoting stability of advanced atherosclerosis plaques?
















• This represents a paradigm shift for the atherosclerosis field since therapies to date have largely been focused on drugs such as statins that control blood lipids which do modestly reduce disease prevalence and/or anti-inflammatory strategies targeting macrophages and other immune cells which have largely failed, including a number of recent $500M+ clinical trials that showed either no significant benefit or detrimental effects. A key goal for the future is to identify the factors and mechanisms that can promote beneficial changes in smooth muscle cells phenotype that can either augment or replace these more conventional anti-atherosclerotic therapies.

• Citation:• KLF4-dependent phenotypic modulation of smooth muscle cells has a key role in atherosclero

tic plaque pathogenesis• Nature Medicine 21,628–637(2015) doi:10.1038/nm.3866Received• 05 February 2015 Accepted 22 April 2015 Published online18 May 2015• Laura S Shankman, Delphine Gomez,Olga A Cherepanova Morgan Salmon,• Gabriel F Alencar,Ryan M Haskins,Pamela Swiatlowska,Alexandra A C Newman,• Elizabeth S Greene,Adam C Straub,Brant Isakson,Gwendalyn J Randolph• & Gary K Owens










http://medicalresearch.com/heart-disease/nanoparticle-exposure-may-increase-atherosclerosis-and-heart-disease-risk/10671/

http://www.nature.com/nm/journal/v21/n6/full/nm.3866.html













Cognitive Behavioral Therapy May Help Many Patients With InsomniaMedicalResearch.com Interview with:Jason Ong, Ph.D., CBSMAssociate Professor, Department of Behavioral SciencesDirector, Behavioral Sleep Medicine Training Program

Rush University Medical Center


Response: Insomnia is a very common sleep problem that was previously thought to be related to another medical or psychiatric condition. Evidence now supports the notion that insomnia can emerge as a disorder distinct from the comorbid condition. In this study, we evaluated the effectiveness of cognitive behavioral therapy for insomnia (CBT-I), the most widely used nonpharmacologic treatment for insomnia, in the context of medical and psychiatric comorbidities.

• We conducted a systematic review and meta-analysis of 37 studies and found that 36% of patients who received cognitive behavioral therapy for insomnia were in remission at post-treatment compared to 17% who received a control or comparison condition. CBT-I had medium to large effects for improving sleep quality and reducing the amount of time awake in bed. Positive findings were also found on the comorbid condition, with greater improvements in psychiatric conditions compared to medical conditions.


http://medicalresearch.com/mental-health-research/cognitive-behavioral-therapy-may-help-many-patients-with-insomnia/15545/










http://medicalresearch.com/mental-health-research/study-highlights-benefits-of-cognitive-behavioral-therapy-for-childhood-anxiety/12354/








• Medical Research: What should clinicians and patients take away from your report?• Response: Patients who experience sleep disturbances should discuss their sleep problems

with their doctors. Clinicians should regularly assess for sleep disturbances in the context of comorbid medical and psychiatric conditions and they should be aware that cognitive behavioral therapy for insomnia is an effective treatment option.




















• Response: Future studies should examined more precisely the impact of treating sleep disturbances on the comorbid condition. This would help improve the understanding of the relationship between sleep and overall health. In addition, research on dissemination and implementation of cognitive behavioral therapy for insomnia is needed to find more efficient and effective ways to deliver cognitive behavioral therapy for insomnia to patients with insomnia. Currently, there is an insufficient number of CBT-I providers to meet the demands of the numerous people with insomnia.

• Citation:• Wu JQ, Appleman ER, Salazar RD, Ong JC. Cognitive Behavioral Therapy for Insomnia Comorbi

d With Psychiatric and Medical Conditions: A Meta-analysis. JAMA Intern Med. Published online July 06, 2015. doi:10.1001/jamainternmed.2015.3006.












http://medicalresearch.com/author-interviews/cognitive-therapy-may-be-safe-and-effective-for-chronic-insomnia/14729/

http://archinte.jamanetwork.com/article.aspx?articleid=2363024








Benzoyl Peroxide May Reduce Risk of P.acnes Infection After SurgeryMedicalResearch.com Interview with:Paul M. Sethi, MDOrthopaedic & Neurosurgery SpecialistsGreenwich, CT

• MedicalResearch: What is the background for this study?• Dr. Sethi: Propionibacterium acnes is one of the most significant pathogens in shoulder

surgery; the cost of a single infection after shoulder arthroplasty may be upwards $50,000. Residual P. acnes may be found on the skin 29% of the time immediately after surgical skin preparation and in 70% of dermal biopsy specimens. Identifying more ideal skin preparation may help reduce the risk of infection.

• MedicalResearch: What is the purpose of this study?• Dr. Sethi: The purpose of this study was to evaluate the ability of topical benzoyl peroxide

(BPO) cream, along with chlorhexidine skin preparation, to reduce the chance of identifying residual bacteria after skin preparation. Our hypothesis was that adding topical benzoyl peroxide to our skin preparation would reduce the number of positive P. acnes cultures identified during surgery.


http://medicalresearch.com/infections/benzoyl-peroxide-may-reduce-risk-of-p-acnes-infection-after-surgery/15555/












http://medicalresearch.com/author-interviews/vitamin_d_may_not_have_a_causal_link_to_diabetes/7973/







• MedicalResearch: What are the main findings?• Dr. Sethi: This study demonstrates that adding topical benzoyl peroxide (BPO) cream to

current skin preparation reduces the rate at which residual P. acnes is identified. When topical BPO cream is used 48 hours before shoulder surgery, there was no significant detectable difference in the rate of positive cultures between a control air swab and surgically obtained samples. Our findings are important as recent studies have demonstrated a 36% to 70% increased risk above controls for having a positive P. acnes culture.














http://medicalresearch.com/author-interviews/nonsurgical-treatments-may-equal-surgery-for-many-broken-shoulders/12585/







• MedicalResearch: What should clinicians and patients take away from your report?• Dr. Sethi: Benzoyl Peroxide (BPO) along with current surgical preparation reduced the risk of

P. acnes. Application of BPO is an effective way to reduce P. acnes on skin at the beginning and, importantly at the end of surgical procedure. This may result in a lower risk for postoperative infection. This is a safe and effective adjunct to help decrease the risk for post-operative infection after shoulder surgery.





















• Dr. Sethi: We plan on a multi-center longitudinal study to determine if this new skin preparation will reduce the actual rate of infection in shoulder arthroplasty across a broad group of patients. This is very exciting as this is a simple, safe and in expensive way to reduce post-operative infection, a potentially devastating problem.

• Citation:• Efficacy of topical benzoyl peroxide on the reduction of Propionibacterium acnes during shoul

der surgery• James R. Sabetta, MD Vishal P. Rana, BS Katherine B. Vadasdi, MD R. Timothy Greene, MD Ja

mes G. Cunningham, MD Seth R. Miller, MD, Paul M. Sethi, MD• Journal of Shoulder and Elbow Surgery• Volume 24, Issue 7, July 2015, Pages 995–1004














http://www.sciencedirect.com/science/article/pii/S1058274615001986











Modest Lifestyle Changes May Markedly Reduce Heart Failure RiskMedicalResearch.com Interview with:Liana C. Del Gobbo, PhDPostdoctoral Research FellowFriedman School of Nutrition Science & PolicyTufts University Boston MA


Dr. Del Gobbo: Heart failure most commonly develops in adults over 65 years old- the most rapidly growing portion of the US population. The condition greatly reduces the quality of life of older adults. Heart failure is the leading cause of hospitalizations in the US among those on Medicare, and is associated with large health care costs. Prevention is key for reducing the burden of this disease.

• A detailed analysis of factors that might help prevent heart failure, such as a person’s pattern of eating (as well as individual foods), in addition to other lifestyle factors (eg. smoking, physical activity, etc), had not been previously examined all together, in the same study.

• To get a fuller picture of how to prevent this condition, this study examined the relative importance of dietary habits and other lifestyle factors for development of heart failure.

• Our paper shows that older adults can cut their risk in half by adhering to a few healthy lifestyle factors, including moderate physical activity, modest alcohol consumption (eg. more than one drink/week, but not more than 1-2 drinks/day), not smoking, and maintaining a healthy weight.


http://medicalresearch.com/heart-disease/modest-lifestyle-changes-may-markedly-reduce-heart-failure-risk/15559/










http://medicalresearch.com/heart-disease/emergency-room-coding-of-heart-failure-diagnosis-validated/13910/







• Medical Research: What should clinicians and patients take away from your report?• Dr. Del Gobbo: The take-home message is encouraging- older adults can make simple

changes to reduce their heart failure risk, such as not smoking, engaging in moderate physical activity, and maintaining a healthy weight.

• Our findings hold true for adults of both sexes, for older and younger seniors, and whether or not adults have pre-existing cardiovascular disease, diabetes, or are on hypertensive medications. For adults with chronic diseases, check with your doctor before starting or changing your exercise program.



















• Dr. Del Gobbo: We need to look into specific dietary determinants, such as sodium, and physical activity type, duration, and frequency in future studies and trials for heart failure prevention among older adults.

• We need to better understand and integrate the determinants and relative contribution of lifestyle and other risk factors for heart failure beyond the scope of this work, including congenital defects, cardiomyopathies, drugs and/or toxins, renal dysfunction, and genetic risk predictors.

• Citation:• Del Gobbo LC, Kalantarian S, Imamura F, et al. Contribution of Major Lifestyle Risk Factors for I

ncident Heart Failure in Older Adults: The Cardiovascular Health Study. JCHF. 2015;3(7):520-528. doi:10.1016/j.jchf.2015.02.009.












http://heartfailure.onlinejacc.org/article.aspx?articleid=2375099








Autoimmune Antibodies Can Lead To EKG Abnormalities and Ventricular ArrhythmiasMedicalResearch.com Interview with:Mohamed Boutjdir, PhD, FAHADirector of the Cardiovascular Research Program VA New York Harbor Healthcare System

Professor, Depts of Medicine, Cell Biology and Pharmacology, State University of New York Downstate Medical Center andNYU School of Medicine, New York, NY


Dr. Boutjdir: Patients with autoimmune diseases including Sjogren’s syndrome, systemic lupus erythematosus and other connective tissue diseases who are seropositive for anti-SSA/Ro antibodies may present with corrected QTc prolongation on the surface ECG. This QTc prolongation can be arrhythmogenic and lead to Torsades de Pointes fatal arrhythmia.

• In our study, we established for the first time an animal model for this autoimmune associated QTc prolongation that is reminiscent of the clinical long QT2 syndrome. We also demonstrated the functional and molecular mechanisms by which the presence of the anti-SSA/Ro antibodies causes QTc prolongation by a direct cross-reactivity and then block of the hERG channel (Human ether-a-go-go-related gene). This hERG channel is responsible for cardiac repolarization and its inhibition causes QTc prolongation. We were able to pinpoint to the target epitope at the extracellular pore forming loop between segment 5 and segment 6 of the hERG channel.


http://medicalresearch.com/heart-disease/autoimmune-antibodies-can-lead-to-ekg-abnormalities-and-ventricular-arrhythmias/15563/





















• Medical Research: What should clinicians and patients take away from your report?• Dr. Boutjdir: QT prolongation has been attributed to either a congenital origin resulting from

ion channel mutations or an acquired origin generally resulting from QT-prolonging drugs. Patients with QTc prolongation are prone to complex ventricular arrhythmias, including Torsade de Pointes, syncope, and sudden death. Here, we propose a novel form of acquired QT prolongation of autoimmune origin induced by anti-SSA/Ro antibodies. QTc prolongation associated with anti-SSA/Ro antibodies per se may confer an increased risk for developing ventricular arrhythmias and represents an additional risk factor for patients with drug-induced or congenital QTc prolongation.

• The finding from the present study supports the recommendations that adult patients with anti-Ro antibodies may benefit from routine ECG screening for QTc prolongation and that those already identified with anti-Ro antibodies associated QTc prolongation should receive counseling, including education about avoiding drugs and other conditions known to prolong the QT interval.
















http://medicalresearch.com/heart-disease/antibiotics-increased-risk-cardiac-arrhythmias/10184/









• Dr. Boutjdir: Large multicenter clinical trials with thousands of patients with autoimmune diseases are warranted to confirm or infirm whether the anti-SSA/Ro antibodies are associated with QTc prolongation and under which circumstances. Similarly, the molecular mechanisms underlying the absence of QTc prolongation in certain cohorts of patients despite the presence of anti-SSA/Ro antibodies need be elucidated.

• Citation:• Yue, M. Castrichini, U. Srivastava, F. Fabris, K. Shah, Z. Li, Y. Qu, N. El-Sherif, Z. Zhou, C.

January, M. M. Hussain, X.-C. Jiang, E. A. Sobie, M. Wahren-Herlenius, M. Chahine, P.-L. Capecchi, F. Laghi-Pasini, P.-E. Lazzerini, M. Boutjdir. Pathogenesis of the Novel Autoimmune-Associated Long QT Syndrome. Circulation, 2015; DOI: 10.1161/CIRCULATIONAHA.115.009800
















http://dx.doi.org/10.1161/CIRCULATIONAHA.115.009800






Brown Fat Transplants May One Day Cure Type I DiabetesMedicalResearch.com Interview with:Subhadra Gunawardana DVM, Ph.DResearch Associate ProfessorDepartment of Molecular Physiology & Biophysics Vanderbilt University Medical Center

Nashville, TN 37232


Response: For many years the general consensus has been that insulin replacement is essential for treating type 1 diabetes. Recent studies increasingly show that extra-pancreatic hormones, particularly those arising from adipose tissue, can compensate for insulin, or entirely replace the function of insulin under appropriate circumstances. Our work on mouse models show that type 1 diabetes can be effectively reversed without insulin, through subcutaneous transplantation of embryonic brown adipose tissue (BAT). BAT transplantation leads to replenishment of recipients’ white adipose tissue; dramatic decrease of inflammation; secretion of a number of beneficial adipokines; and fast and long-lasting euglycemia. Insulin-independent glucose homeostasis is established physiologically, through a combination of endogenously generated hormones arising from the transplant and/or newly-replenished white adipose tissue.


http://medicalresearch.com/diabetes/brown-fat-transplants-may-one-day-cure-type-i-diabetes/15512/














http://medicalresearch.com/cancer-_-oncology/breast-cancer/links_between_breast_cancer_and_obesity_studied/6193/







Nashville, TN 37232

• Medical Research: What should clinicians and patients take away from your report?• Response: If translated to human patients, this approach could provide a cure for

type 1 diabetes that does not require regular exogenous administration of insulin or any other compound, and would thus avoid the many inherent difficulties with such therapies.
















http://medicalresearch.com/diabetes/type-1-diabetes_new_model_predicts_major_outcomes/7224/







Nashville, TN 37232


• Response: The ability to reverse diabetes without insulin is unique to embryonic/fetal brown adipose tissue. Transplantation of adult adipose tissue has failed to achieve the same results so far. Identifying the specific embryonic factors mediating these functions would help mimic the results with adult adipose tissue, which would greatly improve the practicality of this approach.

• Citation:• Insulin-independent reversal of type 1 diabetes in nonobese diabetic mice with brown adipos

e tissue transplant• Subhadra C. Gunawardana , David W. Piston • American Journal of Physiology – Endocrinology and Metabolism Published 15 June 2015 Vol.

308 no. 12, E1043-E1055 DOI: 10.1152/ajpendo.00570.2014
















http://medicalresearch.com/weight-research/white_fat_may_be_converted_into_energy_burning_brown_fat/9767/

http://ajpendo.physiology.org/content/308/12/E1043










Endocrine Therapies for Young Breast Cancer Patients Can Cause Abrupt Menopause SymptomsMedicalResearch.com Interview with:Dr. Jürg Bernhard Ph.D.

International Breast Cancer Study Group Coordinating Center and Bern University Hospital, Inselspital, Bern, Switzerland


Response: In the combined analysis of the SOFT and TEXT trials, the aromatase inhibitor exemestane was more effective than tamoxifen in preventing breast cancer recurrence in young women (premenopausal) who also receive ovarian function suppression (OFS) as adjuvant (post-surgery) treatment for hormone-sensitive early breast cancer, providing a new treatment option for these women. These trials were conducted by the International Breast Cancer Study Group (IBCSG) and involved more than 4700 patients of over 500 centers in 27 countries. Now we present patient-reported quality of life outcomes from these trials.

• In the TEXT and SOFT trials, patients assigned exemestane+OFS reported more detrimental effects of bone or joint pain, vaginal dryness, greater loss of sexual interest and difficulties becoming aroused, while patients assigned tamoxifen+OFS were more affected by hot flushes and sweats. Global quality of life domains (mood, ability to cope and physical well-being) were similar between the randomized treatment groups.


http://medicalresearch.com/cancer-_-oncology/breast-cancer/endocrine-therapies-for-young-breast-cancer-patients-can-cause-abrupt-menopause-symptoms/15514/

















• Medical Research: What should clinicians and patients take away from your report?• Response: From a quality of life perspective, there is no strong indication favoring either

exemestane+OFS or tamoxifen+OFS. The different side effects of the two treatments should be considered with each patient, to determine how these symptoms might affect her individually, especially considering the better disease control for one of the treatments.












http://medicalresearch.com/cancer-_-oncology/breast-cancer/premenopausal_breast_cancer_ovarian_suppression_with_exemestane/5651/









• Response: Endocrine treatments for premenopausal women can cause menopausal symptoms earlier in their lives than natural menopause, and often more abruptly. These two treatments both cause treatment-induced menopausal symptoms. An early recognition of the impact these symptoms is essential for patient care. Some of the menopausal symptoms can be lessened by a multidisciplinary approach, but there is also a need to develop more safe and effective treatments for menopausal symptoms.

• Citation:• Patient-reported outcomes with adjuvant exemestane versus tamoxifen in premenopausal wo

men with early breast cancer undergoing ovarian suppression (TEXT and SOFT): a combined analysis of two phase 3 randomised trials

• Dr Jürg Bernhard, PhD,Weixiu Luo, MD,Karin Ribi, PhD,Marco Colleoni, MD,Harold J Burstein, MD,Carlo Tondini, MD,Graziella Pinotti, MD,Simon Spazzapan, MD,Thomas Ruhstaller, MD,Fabio Puglisi, MD,Lorenzo Pavesi, MD,Vani Parmar, MBBS,Meredith M Regan, ScD,Olivia Pagani, MD,Gini F Fleming, MD,Prudence A Francis, MD,Karen N Price, BS Alan S Coates, MD,Richard D Gelber, PhD,Aron Goldhirsch, MD Barbara A Walley, MD

• Lancet Oncology Volume 16, No. 7, p848–858, July 2015• DOI: http://dx.doi.org/10.1016/S1470-2045(15)00049-2












http://medicalresearch.com/cancer-_-oncology/breast-cancer/premenopausal-breast-cancer-exemestane-found-superior-tamoxifen-estrogen-positive-disease/6283/

http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00049-2/abstract















Hormonal and Reproductive Factors Influence Uterine Cancer Risk in Lynch SyndromeMedicalResearch.com Interview with:Aung Ko Win, MBBS MPH PhD Research FellowNHMRC Early Career Clinical Research FellowCentre for Epidemiology and BiostatisticsMelbourne School of Population and Global Health


Response: About 2-5% of uterine cancer are associated with an underlying genetic condition mainly Lynch syndrome. Lynch syndrome is caused by a mutation in one of the mismatch repair genes. At least 1 in 1000 people in the population have a mutation that causes Lynch syndrome and these people have a very high risk of cancers mainly bowel and uterine cancers. One in three women with a mutation in one of the mismatch repair genes are likely to develop a uterine cancer in their lifetime. The only way to reduce the risk of uterine cancer for these women is to remove the uterus. There is no current recommendation for screening method to detect uterine cancer early. Almost nothing is known about if and how lifestyle factors and hormonal factors can modify their risk of uterine cancer.

• By studying 1128 women with a mutation that causes Lynch syndrome who were recruited from Australia, New Zealand, Canada and the USA, we found that later age at first menstrual cycle, having one or more live births, and using hormonal contraceptive use for one year or longer were associated with a lower risk of uterine cancer.


http://medicalresearch.com/cancer-_-oncology/hormonal-and-reproductive-factors-influence-uterine-cancer-risk-in-lynch-syndrome/15508/














http://medicalresearch.com/author-interviews/statins-may-impede-growth-uterine-fibroids/8985/







• Medical Research: What should clinicians and patients take away from your report?• Response: For women with a Lynch syndrome mutation, some reproductive and hormonal

factors are associated with a lower risk of uterine cancer. The directions and strengths of associations are similar to those for women from the general population. If replicated, women with a Lynch syndrome mutation may be counseled like the general population in regard to hormonal influences on uterine cancer risk.
















http://medicalresearch.com/cancer-_-oncology/tubal-ligation-may-limit-spread-of-endometrial-cancer/15442/








• Response: It is important to conduct further research on the role of lifestyle and hormonal factors in the development of uterine cancer in women with a Lynch syndrome mutation. Identifying modifiers of cancer risks for people with a Lynch syndrome mutation is important for them to reduce their cancer risks.

• Citation:• Seyedeh Ghazaleh Dashti, Rowena Chau, Driss Ait Ouakrim, Daniel D. Buchanan, Mark

Clendenning, Joanne P. Young, Ingrid M. Winship, Julie Arnold, Dennis J. Ahnen, Robert W. Haile, Graham Casey, Steven Gallinger, Stephen N. Thibodeau, Noralane M. Lindor, Loïc Le Marchand, Polly A. Newcomb, John D. Potter, John A. Baron, John L. Hopper, Mark A. Jenkins, Aung Ko Win. Female Hormonal Factors and the Risk of Endometrial Cancer in Lynch Syndrome. JAMA, 2015; 314 (1): 61 DOI: 10.1001/jama.2015.6789
















http://medicalresearch.com/cancer-_-oncology/bariatric_surgery_may_reduce_risk_of_uterine_cancer/4419/

http://dx.doi.org/10.1001/jama.2015.6789






Aspirin and Ibuprofen May Reduce Bowel Cancer Risk in Lynch SyndromeMedicalResearch.com Interview with:Aung Ko Win, MBBS MPH PhDResearch FellowNHMRC Early Career Clinical Research Fellow


Response: At least 1 in 1,000 people in the population have a mutation in one of the mismatch repair genes that causes Lynch syndrome. These people have a very high risk of bowel cancer (colorectal cancer): if nothing is done, about half would develop the disease. The main risk reduction method for these people is to have regular colonoscopy screening every year. Almost nothing is known whether or not lifestyle factors and medications can modify the risk of bowel cancer for people with Lynch syndrome.

• A study was conducted to investigate the associations between aspirin and ibuprofen intake and the risk of bowel cancer, by studying 1,858 people with Lynch syndrome who were recruited into the Colon Cancer Family Registry from Australia, New Zealand, Canada and the USA. This is the largest study to date investigating the associations between aspirin, ibuprofen and bowel cancer risk for people with Lynch syndrome.


http://medicalresearch.com/cancer-_-oncology/aspirin-and-ibuprofen-may-reduce-bowel-cancer-risk-in-lynch-syndrome/15578/










http://medicalresearch.com/cancer-_-oncology/aspirin_may_reduce_cancer_incidence_and_mortality/7012/







• Medical Research: What are the main findings?• Response: People with Lynch syndrome who took aspirin regularly have half the risk of

developing bowel cancer compared with people who did not take aspirin. People with Lynch syndrome who took ibuprofen regularly, another nonsteroidal anti-inflammatory drug, were about 60% less likely to develop bowel cancer compared with people who did not take ibuprofen. These associations were seen in both men and women.


















• Medical Research: What should clinicians and patients take away from your report?• Response: For people with Lynch syndrome, chemoprevention by taking aspirin and

ibuprofen might be effective in reducing their risk of bowel cancer.• Medical Research: What recommendations do you have for future research as a result of

this study?• Response: Further studies are needed to help determine the optimal dose, duration and

timing of taking aspirin and ibuprofen to recommend for people with Lynch syndrome.• Citation:• Driss Ait Ouakrim, Seyedeh Ghazaleh Dashti, Rowena Chau, Daniel D. Buchanan, Mark Clende

nning, Christophe Rosty, Ingrid M. Winship, Joanne P. Young, Graham G. Giles, Barbara Leggett, Finlay A. Macrae, Dennis J. Ahnen, Graham Casey, Steven Gallinger, Robert W. Haile, Loïc Le Marchand, Stephen N. Thibodeau, Noralane M. Lindor, Polly A. Newcomb, John D. Potter, John A. Baron, John L. Hopper, Mark A. Jenkins, and Aung Ko Win

• Aspirin, Ibuprofen, and the Risk of Colorectal Cancer in Lynch Syndrome JNCI J Natl Cancer Inst (2015) 107 (9): djv170 doi:10.1093/jnci/djv170 First published online June 24, 2015 (11 pages)













http://jnci.oxfordjournals.org/citmgr?gca=jnci;107/9/djv170













Residents Participation In Neurosurgery Did Not 30-Day OutcomesMedicalResearch.com Interview with:Judy Huang, M.D. Professor of NeurosurgeryProgram Director, Neurosurgery Residency ProgramFellowship Director, Cerebrovascular Neurosurgery

Johns Hopkins Hospital


Dr. Huang: Residents are medical school graduates who are in training programs working alongside and under supervision of more senior physicians, known as attendings. Patients are sometimes wary of having residents assist in their operations, but an analysis of 16,098 brain and spine surgeries performed across the United States finds that resident participation does not raise patient risks for postoperative complications or death.


http://medicalresearch.com/author-interviews/residents-participation-in-neurosurgery-did-not-30-day-outcomes/15580/


















• Medical Research: What should clinicians and patients take away from your report?• Dr. Huang: An analysis of the data from 16,098 patients in American College of Surgeons National

Surgical Quality Improvement Program database who had undergone elective or emergent neurosurgical procedures between 2006 and 2012 suggests that contributions of residents had no effect on patients’ risks of postoperative complications or death within 30 days of the surgery.

• Overall, 15.8% of all patients had at least one postoperative complication. A complication rate of 20.12% was found in the attending+resident group, while patients with an attending-only surgeon had a statistically significantly lower complication rate at 11.70% (p < 0.001). In the entire study population, 263 patients (1.63%) died within 30 days of surgery. Stratified by operating surgeon status, 162 patients (2.07%) in the attending+resident group died versus 101 (1.22%) in the attending only group (p < 0.001). Regression analyses compared patients who had resident participation to those with only attending surgeons, the referent group. After adjustment for preoperative patient characteristics and comorbidities, multivariate regression analysis demonstrated that patients with resident participation in their surgery had the same odds of 30-day morbidity (OR = 1.05, 95% CI 0.94–1.17) and mortality (OR = 0.92, 95% CI 0.66–1.28) as their attending only counterparts.

• Cases with resident participation had higher rates of mortality and morbidity; however, these cases also involved patients with more comorbidities initially. On multivariate analysis, resident participation was not an independent risk factor for postoperative 30-day morbidity or mortality following elective or emergent neurosurgical procedures.













http://medicalresearch.com/author-interviews/costs-health-care-teaching-medical-residents-provide-cost-conscious-care/3132/









• Dr. Huang: Further examination of the effect of resident participation in specific neurosurgical procedures as well as in other surgical subspecialty fields would be of potential interest to patients.

• Citation:• Mohamad Bydon, Nicholas B. Abt, Rafael De la Garza-Ramos, Mohamed Macki, Timothy F.

Witham, Ziya L. Gokaslan, Ali Bydon, Judy Huang. Impact of resident participation on morbidity and mortality in neurosurgical procedures: an analysis of 16,098 patients. Journal of Neurosurgery, 2015; 122 (4): 955 DOI: 10.3171/2014.11.JNS14890













http://medicalresearch.com/stroke/july-effect-no-adverse-stroke-outcomes/10124/

http://dx.doi.org/10.3171/2014.11.JNS14890






IVF: Single Cell Analysis Allows Extremely Early Prediction Of Embryo AbnormalitiesMedicalResearch.com Interview with:Shawn L. Chavez, Ph.DAssistant Scientist/ProfessorOregon National Primate Research Center

OHSU | Oregon Health & Science University


Dr. Chavez: This study builds upon a previous study also published in Nature Communications in 2012, which demonstrated that chromosomally normal and abnormal 4-cell human embryos can be largely distinguished by combining the timing intervals of the first three cell divisions with the presence or absence of a dynamic process called cellular fragmentation. The current study further combines time-lapse imaging of embryo development and full chromosome analysis with high throughout single-cell gene expression profiling to assess the chromosomal status of human embryos up to the 8-cell stage.


http://medicalresearch.com/author-interviews/ivf-single-cell-analysis-allows-extremely-early-prediction-of-embryo-abnormalities/15588/
















Medical Research: What are the main findings?

Dr. Chavez: The key findings of this research were that by measuring the duration of the first cell division, one can identify which embryos are chromosomally normal versus abnormal even earlier in development. By examining gene expression at a single-cell level, we were able to correlate the chromosomal make-up of an embryo to a subset of 12 genes that are activated prior to the first cell division. These genes likely came from either the egg or sperm and can be used to predict whether an embryo will be chromosomally normal or abnormal within the first 30 hours of development.


















• Medical Research: What should clinicians and patients take away from your report?• Dr. Chavez: A big debate in the in vitro fertilization (IVF) community right now is whether

time-lapse imaging is actually beneficial and can replace pre-implantation screening (PGS). Personally, I think that by combining these two techniques and now potentially extending this to gene expression profiling, will provide the most comprehensive information for both clinicians and patients in the decision of which embryo(s) to transfer. The main goal of the prediction model was not to predict chromosomal abnormalities by itself, but to identify cellular pathways and related molecules indicative of embryo viability in culture medium or via other methods.











http://medicalresearch.com/genetic-research/ivf_preimplantation_genetic_screening_improved_with_ngs/5616/









• Dr. Chavez: Although the predictive model has been tested on embryos from several different patients and IVF clinics, it will likely be necessary to test the model on other embryo cohorts in order to further substantiate our findings. Additional studies should also focus on the 1-cell embryo as a potential source of biomarkers that can prospectively predict embryo chromosomal status and obviously, this needs to be non-invasive at this stage of development.

• Citation:• Maria Vera-Rodriguez, Shawn L. Chavez, Carmen Rubio, Renee A. Reijo Pera, Carlos Simon.

Prediction model for aneuploidy in early human embryo development revealed by single-cell analysis. Nature Communications, 2015; 6: 7601 DOI: 10.1038/ncomms8601











http://medicalresearch.com/cancer-_-oncology/ivf-increased-risk-cancer-children-vitro-fertilization/2628/

http://dx.doi.org/10.1038/ncomms8601






New Molecular Device Can Quickly Detect Dangerous SuperbugsMedicalResearch.com Interview with:Yingfu Li, PhDProfessor, Dept of Biochemistry and Biomedical Sciences andDept of Chemistry and Chemical Biology

McMaster University, Hamilton, Canada


Dr. Li: Simple, accurate and sensitive diagnostic tests are highly sought-after in modern medicine. Take bacterial infection as an example. Many microbial pathogens pose serious threats to public health and are responsible for many annual outbreaks that result in numerous human illnesses and deaths. Early and accurate detection of specific pathogens has long been recognized as a crucial strategy in the control of infectious diseases because such a measure can provide timely care of patients, prevent potential outbreaks, and minimize the impact of on-going epidemics. To detect the infection early, we need highly sensitive tests.

• We have developed a molecular device made of DNA that can be turned on by a molecule of choice, such as a biomarker for a disease. When it gets switched on, the system will undergo massive signal amplification allowing for extremely sensitive detection of the target molecule. The test has the best sensitivity ever reported for a detection system of this kind – it is as much as 10,000 times more sensitive than other detection systems. The scientific report can be found at http://onlinelibrary.wiley.com/doi/10.1002/anie.201503182/abstract


http://medicalresearch.com/infections/new-molecular-device-can-quickly-detect-dangerous-superbugs/15567/












http://onlinelibrary.wiley.com/doi/10.1002/anie.201503182/abstract








• Medical Research: What should clinicians and patients take away from your report?• Dr. Li: he test we have developed is very versatile and can be applied for various diseases. We

are in the process of developing several clinically useful tests that can be used to easily and quickly identify dangerous superbugs including C. difficile and MRSA.






















• Dr. Li: We wish to adapt this assay on paper, so as to create litmus paper-like sensors. These simple devices would completely eliminate the need for lab instruments, allowing users—family physicians, for example—to run the test.

• Citation:• Meng Liu, Wenqing Zhang, Qiang Zhang, John D. Brennan, Yingfu Li. Biosensing by Tandem

Reactions of Structure Switching, Nucleolytic Digestion, and DNA Amplification of a DNA Assembly. Angewandte Chemie International Edition, 2015; DOI: 10.1002/anie.201503182














http://dx.doi.org/10.1002/anie.201503182






PD-L1 and TILS Predict Resistance in BRAF-Treated Melanoma PatientsMedicalResearch.com Interview with:Mario Mandalà, MDDepartment of Oncology and HaematologyPapa Giovanni XXIII HospitalBergamo, Italy


Dr. Mandalà: In addition to their established molecular mechanism of action, growing evidence suggests that the therapeutic efficacy of BRAFi relies on additional factors that affect the tumor–host interactions, including the enhancement of melanoma antigen expression and the increase in immune response against tumor cells. Preclinical data show that oncogenic BRAF contributes to immune evasion, and that targeting this mutation may increase the melanoma immunogenicity. Data in vitro or from animal models propose PD-L1 as a potential mechanism that favors BRAFi resistance through the modulation of host immune responses. However, demonstration of this hypothesis in the clinical setting is lacking.


http://medicalresearch.com/author-interviews/pd-l1-and-tils-predict-resistance-in-braf-treated-melanoma-patients/15529/

















• Medical Research: What are the main findings?• Dr. Mandalà: In the present study, we have evaluated, in a homogeneous series of MMP

treated with BRAFi, the association of tumoral PD-L1 IHC expression and the density of TIMC with RR, PFS and OS. Results provide the first proof-of-principle clinical evidence of the predictive and prognostic relevance of PD-L1 IHC expression and density of immune cell infiltration in BRAFV600 mutated MMP receiving BRAFi.



















• Medical Research: What should clinicians and patients take away from your report?• Dr. Mandalà: The most striking finding of this study is that IHC PD-L1 overexpression,

together with the lack of TIMC in metastatic melanoma samples, are associated with resistance and poor prognosis in MMP receiving BRAFi. A limitation of our study is that in our patient cohort, no patient received BRAF and MEK inhibitors, which are now known to improve RR, PFS and OS, as compared to BRAFi alone. Furthermore we did not evaluate the immunophenotype of immune cell infiltration, and the absence of CD8 staining that has been widely used in previous studies in association with PD-L1 expression and could give more quantitative and reliable results regarding the immune infiltrate.




















• Dr. Mandalà: Since PD-L1 overexpressing melanoma patients are at higher risk of developing early progression and worse outcome than those who are PD-L1 negative, a different strategy should probably be pursued in these patients. Whether starting with anti PD-1 antibodies may result in a better outcome should be evaluated in ad hoc designed studies, since PD-L1 positive melanomas with immune cell infiltration seem to benefit particularly from anti PD-1 antibodies

• Citation:• Massi, D. Brusa, B. Merelli, C. Falcone, G. Xue, A. Carobbio, R. Nassini, G. Baroni, E. Tamborini,

L. Cattaneo, V. Audrito, S. Deaglio, and M. Mandalà• The status of PD-L1 and tumor-infiltrating immune cells predict resistance and poor prognosis

in BRAFi-treated melanoma patients harboring mutant BRAFV600 Ann Oncol first published online June 2, 2015 doi:10.1093/annonc/mdv255













http://annonc.oxfordjournals.org/citmgr?gca=annonc;mdv255v1












Simultaneous Risk Factors Markedly Increase Heart Disease Death RatesMedicalResearch.com Interview with:Dr Emanuele Di Angelantonio FESC FAHAUniversity Lecturer | University of CambridgeDirector | MPhil in Public Health


Response: Previous research as mainly focused on individual with one cardiometabolic condition alone and, despite it could be expected that having more than one condition poses a greater risk, this is the first study that is able to precisely quantify how much is worst. Furthermore, given that the conditions we study (diabetes, heart attack, and stroke) share several risk factors, it could be expected that the combination of these will not be multiplicative. We were somewhat surprised to find that participants who had 1 condition had about twice the rate of death; 2 conditions, about 4 times the rate of death; and all 3 conditions, about 8 times the rate of death. We estimated that at the age of 60 years, men with any two of the cardiometabolic conditions studied would on average have 12 years of reduced life expectancy, and men with all three conditions would have 14 years of reduced life expectancy. For women at the age of 60 years, the corresponding estimates were 13 years and 16 years. The figures were even more dramatic for patients at a younger age. At the age of 40 years, men with all three cardiometabolic conditions would on average have 23 years of reduced life expectancy; for women at the same age, the corresponding estimate was 20 years.


http://medicalresearch.com/heart-disease/simultaneous-risk-factors-markedly-increase-heart-disease-death-rates/15510/



















• Medical Research: What should clinicians and patients take away from your report?• Response: These results are of main use for clinicians and policy makers, and emphasize for

example the importance of measures to prevent cardiovascular disease in people who already have diabetes, and, conversely, to avert diabetes in people who already have cardiovascular disease. However, at the same time, we must not lose sight of tackling these serious conditions within the wider population.






















• Response: Future research should focused on the wider issues of co-morbidities in an aging population.

• Citation:• The Emerging Risk Factors Collaboration. Association of Cardiometabolic Multimorbidity With

Mortality. JAMA. 2015;314(1):52-60. doi:10.1001/jama.2015.7008.

• Dr Emanuele Di Angelantonio FESC FAHA, & University Lecturer | University of Cambridge (2015). Simultaneous Risk Factors Markedly Increase Heart Disease Death Rates















http://jama.jamanetwork.com/article.aspx?articleid=2382980









New Generation Biologic Markedly Improved PsoriasisMedicalResearch.com Interview with:Prof. Dr. med. Kristian ReichDERMATOLOGIKUM HAMBURGHamburg


Prof. Reich: The Phase 2b X-PLORE study compared a new generation biologic therapy, guselkumab – an inhibitor of IL–23, with the anti–tumor necrosis factor (TNF)–alpha agent adalimumab (Humira®) and placebo in the treatment of moderate-to-severe plaque-type psoriasis. It showed that up to 86 percent of patients treated with guselkumab achieved a Physician’s Global Assessment (PGA) score of cleared psoriasis or minimal psoriasis at week 16, the study’s primary endpoint. Interestingly, levels of efficacy were higher for several guselkumab doses through week 16 when compared to adalimumab. Improvements with guselkumab continued through week 40 with every eight- or twelve-week maintenance treatment.


http://medicalresearch.com/author-interviews/new-generation-biologic-markedly-improved-psoriasis/15571/









http://medicalresearch.com/author-interviews/not-all-biologics-for-psoriasis-carry-same-risk-of-serious-infections/14428/







• Medical Research: What should clinicians and patients take away from your report?• Prof. Reich: The Phase 2b guselkumab study shows that blockade of IL-23 resulted in

significant skin clearance, and provides important insights into the role of IL-23 in the pathogenesis of psoriasis and the potential therapeutic benefit of guselkumab. IL-23 appears to be a particularly attractive therapeutic target in psoriasis given the emerging profile of guselkumab, in particular the combination of high levels of response with a very favorable safety profile and an extremely convenient injection scheme. This is the desirable profile of a new generation biologic therapy.


















• Prof. Reich: As a dermatologist, I am particularly excited about the potential of guselkumab and what this investigational therapy may mean for patients and the treatment of moderate to severe plaque psoriasis in the future. Findings from the ongoing Phase 3 guselkumab studies will provide even greater insights into the efficacy and safety profile of this novel biologic.

• Citation:• A Phase 2 Trial of Guselkumab versus Adalimumab for Plaque Psoriasis• Kenneth B. Gordon, M.D., Kristina Callis Duffin, M.D., Robert Bissonnette, M.D., Jörg C. Prinz,

M.D., Yasmine Wasfi, M.D., Ph.D., Shu Li, Ph.D., Yaung-Kaung Shen, Ph.D., Philippe Szapary, M.D., M.S.C.E., Bruce Randazzo, M.D., Ph.D., and Kristian Reich, M.D., Ph.D.

• N Engl J Med 2015; 373:136-144• July 9, 2015 • DOI: 10.1056/NEJMoa1501646























Duration of Anticoagulation After Primary Pulmonary Embolism ClarifiedMedicalResearch.com Interview with:Professor Francis Couturaud, MD, PhDDepartment of Internal Medicine and Chest DiseasesUniversity Hospital Center of Brest

Brest, France


Dr. Couturaud: Patients who have completed 3 to 6 months of anticoagulation for a first episode of pulmonary embolism that was not provoked by a major transient risk factor, such as surgery or prolonged immobilization, have a high risk of recurrent venous thromboembolism after stopping anticoagulation. In this high-risk population, extending anticoagulation beyond 3 to 6 months is associated with a major reduction in recurrences as long as the treatment is continued. However, whether this benefit is maintained thereafter remains uncertain, as in most previous studies, patients were not followed after treatment discontinuation. In addition, while extending anticoagulation is very effective in preventing recurrent venous thromboembolism, anticoagulation is also associated with an increased risk of bleeding. Therefore, in patients with a first episode of unprovoked pulmonary embolism, the optimal duration of anticoagulation remains uncertain.


http://medicalresearch.com/author-interviews/duration-of-anticoagulation-after-primary-pulmonary-embolism-clarified/15517/
















Brest, France

• In the PADIS-PE multicenter, double-blind, randomized trial that included 371 patients with a first episode of unprovoked pulmonary embolism initially treated during 6 months, we aimed to evaluate the benefit and risk of an additional 18 months of warfarin therapy versus placebo during the 18-month study treatment period and during an additional 2 years of follow-up after study treatment discontinuation.

• The main findings are the followings: during the study treatment period, we found a 80% reduction in the relative risk of recurrent venous thromboembolism or major bleeding, mainly driven by the 90% risk reduction of recurrences; however, during the post-treatment follow-up period of two years, the benefit was lost, and the risks of recurrent venous thromboembolism and major bleeding were not different between the 2 groups. In addition, recurrent venous thromboembolism occurred as pulmonary embolism in 80% of cases (8% were fatal) and were unprovoked in 90% of cases.


















Brest, France

• Medical Research: What should clinicians and patients take away from your report?• Dr. Couturaud: Our study provides convincing result that extended but limited duration of

anticoagulation does not improve the long-term prognosis of a first episode of unprovoked pulmonary.

• The consequences for clinicians are the followings:

First, only two options of management should be discussed: either a conventional duration of 3 to 6 months or an indefinite duration of anticoagulation.

• Second, more than ever, the individual risk factors of recurrent VTE if anticoagulation is stopped and risk factors of bleeding if anticoagulation is continued should be carefully identified and weighted in order to propose the most adequate long-term secondary prevention (long-term anticoagulation or specific prophylactic counseling in high-risk situations). This evaluation should also included patient’s preference.

• Third, the benefit risk ratio of indefinite anticoagulation should be serially evaluated in these patients not only if indefinite anticoagulation is decided but also if anticoagulation is stopped as patient’s profile will change over the time (age, additional comorbidities, etc.) and in order to determine if anticoagulation should be stopped or started again.












http://medicalresearch.com/author-interviews/anticoagulation-bridge-therapy-may-be-unnecessary-for-low-risk-venous-thromboembolism-patients/14484/







Brest, France

For the patients, once the first episode of unprovoked pulmonary embolism, they should be informed about their high risk of recurrent venous thromboembolism if anticoagulation is stopped and their risk of bleeding if anticoagulation is continued. They also should be informed that recurrent venous thromboembolism occurs more often as pulmonary embolism; in this setting, patients should be informed about clinical symptoms of pulmonary embolism but also of deep vein thrombosis and the links between these two entities. This will help people to express their preferences.


















Brest, France


• Dr. Couturaud: : The first issue is to identify, among patients with unprovoked venous thromboembolism, those who have a lower risk of recurrence that may not justify indefinite anticoagulation. Several predictive scores, combining clinical variables such at gender, age, and tests such as D-dimer have been derived but prospective validation is not yet available.The second issue is to explore long-term secondary thrombo-prophylaxis strategies with a lower risk of bleeding and a similar efficacy. This is currently the case with aspirin and low dose of Direct Oral Anticoagulants. However, additional studies are needed to determine if such strategies have a better benefit risk ratio than conventional anticoagulation.

• Citation:• Couturaud F, Sanchez O, Pernod G, et al. Six Months vs Extended Oral Anticoagulation After a

First Episode of Pulmonary Embolism: The PADIS-PE Randomized Clinical Trial. JAMA. 2015;314(1):31-40. doi:10.1001/jama.2015.7046.












http://medicalresearch.com/heart-disease/study-confirms-anticoagulation-choice-after-myocardial-infarction/11785/










CDC Study Finds Variable Risk of Antidepressants During Pregnancy and Birth DefectsMedicalResearch.com Interview with:Jennita Reefhuis, PhDEpidemiologist with CDCNational Center on Birth Defects and Developmental Disabilities


Dr. Reefhuis: There are previous reports on the link between birth defects and SSRIs. However, the results across some of these studies conflicted. It is not clear whether one SSRI might be safer than other SSRIs.


Dr. Reefhuis: Reassuringly, we found that the five earlier reported links between specific birth defects and sertraline were not found again. We did find that some birth defects occur two to three times more frequently among babies born to mothers who took paroxetine and fluoxetine in early pregnancy.


http://medicalresearch.com/author-interviews/cdc-study-finds-variable-risk-of-antidepressants-during-pregnancy-and-birth-defects/15593/















CDC Study Finds Variable Risk of Antidepressants During Pregnancy and Birth DefectsMedicalResearch.com Interview with:Jennita Reefhuis, PhDEpidemiologist with CDCNational Center on Birth Defects and Developmental Disabilities

• Medical Research: What should clinicians and patients take away from your report?• Dr. Reefhuis: Depression can be very serious and women should not suddenly stop taking

their medications. Women should talk to their health care providers about available options, ideally before planning a pregnancy, since early pregnancy is a critical time for the development of a baby’s organs.


• Dr. Reefhuis: Research needs to continue to focus on individual SSRIs and specific birth defects, so that we can hopefully provide the safest options to women who need treatment for depression before and during pregnancy.

• Citation:• Reefhuis Jennita, Devine Owen, Friedman Jan M, Louik Carol, Honein Margaret A. Specific SSR

Is and birth defects: bayesian analysis to interpret new data in the context of previous reports 2015; 351 :h3190

• Jennita Reefhuis, PhD, & Epidemiologist with CDC (2015). CDC Study Finds Variable Risk of Antidepressants During Pregnancy and Birth Defects












http://medicalresearch.com/menopause/menopausal-ssris-increases-risk-of-bone-fractures/15318/









Not All Dengue Viruses Have Have Same Potential For Disease OutbreaksMedicalResearch.com Interview with:Dr. Eng Eong Ooi BMBS PhD FRCPathAssociate Professor & Deputy DirectorProgram in Emerging Infectious Diseases

Duke-NUS Graduate Medical SchoolSingapore


Response: Dengue prevention continues to rely exclusively on vector control guided by disease and virologic surveillance. The latter has focused on detecting changes in the prevalence of the four antigenically distinct viral serotypes as, in general terms, herd immunity depends on long-lived serotype-specific antibodies. However, epidemiological observations have indicated that a small number of changes within the viral genome have also been associated with several major outbreaks, without any change in viral serotype. Identifying the genetic changes that alter viral fitness epidemiologically would thus be important to differentiate strains that have a greater potential of causing epidemics and targeted for control.


http://medicalresearch.com/author-interviews/not-all-dengue-viruses-have-have-same-potential-for-disease-outbreaks/15595/























Using the 1994 outbreak in Puerto Rico as a case in point, we identified nucleotide substitutions in the 3’ untranslated region (3’UTR) of the viral genome as critical determinants of dengue virus’ epidemiological fitness. Mechanistically, mutations in the 3’UTR altered secondary viral RNA structures and changed the relative proportion of genomic to subgenomic RNA of the virus in infected cells. The epidemiologically fitter viruses produced larger amounts of subgenomic to genomic RNA. This subgenomic RNA then binds a host protein, TRIM25, which is a E3 ubiquitin ligase that polyubiquitylates RIG-I to amplify and sustain signalling for type-I interferon expression. By binding to TRIM25, the subgenomic RNA of dengue virus inhibits the activation and thus enzymatic function of TRIM25. We suggest that with reduced interferon expression, the virus was thus able to spread more effectively from cell to cell within the infected individuals to reach viremia levels for further subsequent mosquito-borne transmission


















http://medicalresearch.com/author-interviews/disposable-device-can-detect-dengue-antibodies-in-saliva-in-20-minutes/11204/








• Medical Research: What should clinicians and patients take away from your report?• Response: Our work indicates that not all dengue viruses have the same potential for causing

outbreaks. Identifying the genetic signatures that give rise to epidemiologically fitter viruses could enable us to refine our virologic surveillance from a serotype level information to one based on molecular evidence. Public health response to dengue could thus be triaged based on risk of epidemic emergence rather than the number of cases within specific locales. The latter often represents a response that is too little too late to stem an epidemic.


























• Response: Besides identifying a determinant of epidemiological fitness, our work has also now provided a framework to investigate past outbreaks. Cataloging the genetic changes that affects dengue virus fitness in its epidemiological setting and how these changes are mediated mechanistically would be important if we are to bring virologic surveillance to a new level of accuracy in the future.

• Citation:• Manokaran, E. Finol, C. Wang, J. Gunaratne, J. Bahl, E. Z. Ong, H. C. Tan, O. M. Sessions, A. M.

Ward, D. J. Gubler, E. Harris, M. A. Garcia-Blanco, E. E. Ooi. Dengue subgenomic RNA binds TRIM25 to inhibit interferon expression for epidemiological fitness. Science, 2015; DOI: 10.1126/science.aab3369


















http://dx.doi.org/10.1126/science.aab3369






Retrievable Inferior Vena Cava Filters May Be Removed Despite Long Dwell TimeMedicalResearch.com Interview with:Robert J. Lewandowski, MD FSIRAssociate Professor of RadiologyDirector of Interventional Oncology Department of Radiology

Northwestern University Feinberg School of Medicine


Response: Retrievable inferior vena cava filters (rIVCF) were designed to provide temporary prevention from pulmonary embolism and then be removed when no longer needed. With permanent United States Food and Drug Administration (FDA) indication, these devices now account for the majority of IVC filters placed. Most rIVCFs placed are never removed because of poor clinical follow up, failed retrieval procedures, or patients not being offered the opportunity for filter removal secondary to prolonged dwell time; the latter has previously been correlated with retrieval failure.

• Retrievable IVCFs appear to be subject to greater device related complications (e.g., filter penetration of the IVC, filter migration, filter fracture) relative to permanent devices; furthermore, the rates of these complications appear to increase with filter dwell time. This prompted the FDA to issue a 2010 safety alert urging removal of rIVCFs once they are deemed no longer necessary.


http://medicalresearch.com/author-interviews/retrievable-inferior-vena-cava-filters-may-be-removed-despite-long-dwell-time/15626/

















In the present study, we sought to determine whether rIVCF dwell time affects technical success of the retrieval procedure. Over a six-year period, 648 retrieval procedures were performed at our institution, with filter dwell times ranging from 0-108 months. We found that filter dwell time did not negatively impact IVC filter retrieval success nor did it increase our adverse events from the retrieval procedure. With advanced, adjunctive IVC filter retrieval techniques, rIVCFs can be safely and reliably removed despite long dwell times.



















• Medical Research: What should clinicians and patients take away from your report?• Response: Retrievable IVCFs can be safely removed with a high rate of technical success,

regardless of filter dwell time. When weighed against the risks of leaving a device in place when no longer necessary, patients and their managing clinicians should seek consultation to have these devices removed. Since prolonged filter dwell time is associated with increased use of advanced filter retrieval techniques (including forceps and laser sheath-assisted photo-thermal fibrin ablation), clinicians should consider referral to a center with expertise in these advanced IVC filter removal procedures.




















• Response: It is important to recognize that there remains a paucity of prospective data in the utilization of IVC filters. The initiation of the PRESERVE trial, a multi-center prospective clinical research trial jointly organized between the Society of Interventional Radiology and the Society of Vascular Surgery, will add significant device-specific knowledge. The goal of this trial is to obtain a real-world view of the safety and effectiveness of most IVC filters placed in the United States.

• Acknowledging the fact that not all medical centers have the expertise to perform advanced IVC filter retrievals, we believe that a next research step from our current work in optimizing the care of patients with IVC filters is to determine a more precise definition of prolonged dwell time. This information would help promote earlier IVC filter removal while also facilitating referral to centers with retrieval expertise for those patients with high likelihood of requiring advanced removal techniques.

• Citation:• Desai KR, Lewandowski RJ, Salem R, et al. Retrieval of Inferior Vena Cava Filters With Prolonge

d Dwell Time: A Single-Center Experience in 648 Retrieval Procedures. JAMA Intern Med. Published online June 22, 2015. doi:10.1001/jamainternmed.2015.2561.












http://archinte.jamanetwork.com/article.aspx?articleID=2323412








Surgeons Need To Document Why Patient Care May Fall Outside Standard GuidelinesMedicalResearch.com Interview with:Judy A. Tjoe, MD, FACSBreast Oncology SurgeonAurora Health CareMilwaukee, WI

• Medical Research: What is the background for this study? What are the main findings?• Dr. Tjoe: Numerous national health organizations have confirmed minimally invasive breast

biopsy (MIBB), which uses a percutaneous core needle as opposed to open surgical techniques, as the biopsy procedure of choice when a patient’s diagnostic test reveals a breast lesion suggestive of malignancy. Unfortunately, despite the overwhelming evidence supporting use of MIBB, open breast biopsy rates in the United States remain as high as 24-39%. Our study was designed to determine if measuring individual practice patterns and providing subsequent feedback to surgeons across a large, multihospital healthcare system would improve their adherence to the quality metric of using minimally invasive breast biopsy to diagnose indeterminate breast lesions.


http://medicalresearch.com/author-interviews/surgeons-need-to-document-why-patient-care-may-fall-outside-standard-guidelines/15602/










http://medicalresearch.com/cancer-_-oncology/breast-cancer/breast-cancer-black-patients-fewer-sentinel-lymph-node-biopsies/5986/







We found that the proportion of studied surgeons (n=46) appropriately adhering to the MIBB quality metric in every instance (i.e. those who achieved 100% adherence) significantly improved from 80.4% to 95.7% (p=0.0196) after receiving feedback on not only their own practice patterns, but those of their blinded peers. As might be expected, the handful of breast-dedicated surgeons (n=4) who cared for nearly half of the analyzed patient population achieved perfect adherence throughout the study, but interestingly, the gains made in total adherence were driven by the general surgeons (n=42), showing that the study’s direct educational efforts were effective in changing practice patterns for the better. These efforts included sending letters describing adherence to the quality metric to individual surgeons and organizational leadership.


















• Medical Research: What should clinicians and patients take away from your report?• Dr. Tjoe: Research on quality metrics can be used for quality improvement, accountability,

payment incentives/penalties, patient steerage and public transparency. However, poorly designed studies that inappropriately measure quality metric adherence and then use the results for accountability have the potential to create risk for surgeons and healthcare systems if substandard outcomes are attributed to the surgeon rather than, for example, radiographic or patient anatomic limitations, patient comorbidities or compliance, or the actions taken by a prior surgeon before transfer of care to the accepting accountable surgeon. For every defined quality metric, there are “nonquality” and “quality” reasons for physician adherence/compliance, and responsible reporting of this influential data should take both into consideration. It is absolutely critical to define and record these appropriate exceptions, and herein lies the strength of our institutional review compared to those of national databases: our granular data distinguishes appropriateness of nonadherence by abstracting from each patient chart the surgeon’s reason for not performing minimally invasive breast biopsy. While doing this is resource-intensive and time-consuming, it nevertheless is essential to responsible and fair reporting of quality metric adherence data.












http://medicalresearch.com/cancer-_-oncology/breast-cancer/choice_to_use_needle_biopsy_influenced_by_surgeon/5806/







As healthcare institutions move toward the growing trend of mining databases to identify practice trends, it is in surgeons’ best interests to personally review data accredited to them to determine proper interpretation and attribution of quality metrics. Surgeons themselves should take the important and necessary step of documenting their reasons for why an individual patient’s care may fall outside standard guidelines, as recommended by the Commission on Cancer. Such instances do not demonstrate willful defiance, but rather exemplify sound judgment and understanding that every particular patient is an individual with a unique set of circumstances influencing his/her disease. Surgeons and/or their institutions should not be penalized for selecting treatment options outside of standard guidelines if it is necessary or appropriate in a particular situation.



















• Dr. Tjoe: While our study did not find significant differences between male and female surgeons in quality metric adherence following internal performance feedback, there was a notable difference between surgeons under age 55 compared to those 55 and older, even after accounting for acceptable scenarios for nonadherence to minimally invasive breast biopsy. It would be interesting to determine if external motivating factors (e.g., financial incentives or disincentives) versus internal motivating factors (e.g., innate perfectionism or intense sense of responsibility that often characterizes the surgeon personality) affect younger and older generations of surgeons’ responses to performance feedback differently.

• Citation:• Quality Metric Adherence in a Multihospital Health System: Educating Surgeons on Minimally

Invasive Breast BiopsyTjoe, Judy A. et al.

• Journal of the American College of SurgeonsAbstract presented at the American College of Surgeons Clinical Congress, San Francisco, CA, October 2014.

• DOI: http://dx.doi.org/10.1016/j.jamcollsurg.2015.06.003












http://dx.doi.org/10.1016/j.jamcollsurg.2015.06.003








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MedicalResearch.com: Medical Research Exclusive Interviews July 9 2015

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