Author Interviews, Breast Cancer, Genetic Research, JAMA / 25.02.2016

MedicalResearch.com Interview with: [caption id="attachment_22015" align="alignleft" width="175"]Dr. Shoshana Rosenberg ScD, MPH Department of Medical Oncology Dana-Farber Cancer Institute Boston, Massachusetts Dr. Shoshana Rosenberg[/caption] Dr. Shoshana Rosenberg ScD, MPH Department of Medical Oncology Dana-Farber Cancer Institute Boston, Massachusetts Medical Research: Why would BRCA testing rates have increased among younger women with cancer?   Dr. Rosenberg: There has been increasing awareness surrounding genetic testing for breast cancer in more recent years, likely contributing to the trend that we saw over time  in our cohort. This has included more media attention, most notably Angelina Jolie’s sharing her story in 2013. Medical Research: Is this increase in testing a good thing? Dr. Rosenberg: Young women who are diagnosed with breast cancer should be getting tested so the fact that an increasing proportion of women have been undergoing BRCA testing in recent years indicates patients (and the physicians who treat them) are following recommendations.
Author Interviews, Heart Disease, NEJM, Pharmacology / 25.02.2016

MedicalResearch.com Interview with: [caption id="attachment_22006" align="alignleft" width="120"]Professor Paul Myles MBBS, MPH, MD, FCARCSI, FANZCA, FRCA Director, Dept of Anaesthesia and Perioperative Medicine Alfred Hospital and Monash University, Melbourne, Australia Prof. Paul Myles[/caption] Professor Paul Myles MBBS, MPH, MD, FCARCSI, FANZCA, FRCA Director, Dept of Anaesthesia and Perioperative Medicine Alfred Hospital and Monash University, Melbourne, Australia Medical Research: What is the background for this study? What are the main findings? Dr. Myles: When we set up this study 10 years ago there was marked variation in practice for  people taking aspirin waiting for coronary artery bypass surgery.  About half were being told that they must stop their aspirin 5-7 days before surgery, and the other half were told that they should stay on their aspirin. This variation existed across different countries, different cities, and even within a single hospital. Doctors had varied opinions because reliable medical research was sparse; the evidence was contradictory. We thus designed a definitive clinical trial in which half the patients were randomly assigned to receive aspirin and the other half received a placebo. Our study has shown that aspirin is safe (i.e. it does not increase the bleeding risk). We also found that there does not appear to be a benefit during and after surgery, but in view of the clear benefits that exist in daily life, including the preoperative waiting period, we recommend that people should stay on their aspirin if they are having coronary artery surgery.
Asthma, Author Interviews, Education, Pediatrics / 25.02.2016

MedicalResearch.com Interview with: [caption id="attachment_22192" align="alignleft" width="130"]Joy Hsu, MD, MS Air Pollution and Respiratory Health Branch Division of Environmental Hazards and Health Effects National Center for Environmental Health CDC Atlanta GA 30341 Dr. Joy Hsu[/caption] Joy Hsu, MD, MS Air Pollution and Respiratory Health Branch Division of Environmental Hazards and Health Effects National Center for Environmental Health CDC Atlanta GA 30341 Medical Research: What is the background for this study? Dr. Hsu: Asthma is a leading cause of missed school days related to chronic illness. This study is based on survey data from 2006 to 2010 on children aged 17 years and younger with asthma from 35 states and the District of Columbia. 
Author Interviews, Critical Care - Intensive Care - ICUs, Infections, JAMA / 24.02.2016

MedicalResearch.com Interview with: [caption id="attachment_22018" align="alignleft" width="200"]Dr-Manu-Shankar-Hari.jpg Dr. Manu Shankar-Hari[/caption] Dr. Manu Shankar-Hari MB BS MD FRCA EDIC FFICM MSc[Epi] Consultant, Intensive Care Medicine; Guy’s and St Thomas’ NHS Foundation Trust Clinical Research Associate, Intensive Care National Audit and Research Centre Honorary Senior Lecturer in Intensive Care Medicine Division of Asthma Allergy and Lung Biology King’s College London, UK  Medical Research: What is the background for this study? What are the main findings? Dr. Shankar-Hari: Septic shock is a complex illness.  The previous Consensus Definitions (1991 and 2001) place emphasis on the circulatory abnormalities as the core concept and neither definitions provide data driven clinical criteria. In addition, last ten years of basic science research has established the concept that septic shock is associated with plethora of cellular and metabolic abnormalities (often referred to as cellular stress), alongside circulatory dysfunction. In this background, the paper published in JAMA provides an updated illness concept (definitions) and data driven clinical criteria for diagnosing septic shock at the bedside.

The updated illness concept: 'Septic shock is defined as a subset of sepsis in which underlying circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than sepsis alone.’

The clinical criteria: 'Adult patients with septic shock can be identified using the clinical criteria of hypotension requiring vasopressor therapy to maintain mean arterial blood pressure 65 mm Hg or greater and having a serum lactate level greater than 2 mmol/L after adequate fluid resuscitation.'
Author Interviews, BMJ, Cancer Research, OBGYNE / 24.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21992" align="alignleft" width="150"]Jiangrong Wang PhD Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm, Sweden Dr. Jianrong Wang[/caption] Jiangrong Wang PhD Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm, Sweden Medical Research: What is the background for this study? What are the main findings? Dr. Wang: Cervical screening has been proved to effectively suppress the occurrence of cervical cancer, since it detects not only cervical cancer at early stages, but also precursor lesions that can be treated before progressing to invasive cancers. However, cervical screening has mainly reduced the occurrence of squamous cell cervical cancer, the most common type of invasive cervical cancer, but not adenocarcinoma of the cervix which originates from glandular cells. Although there is a well-known connection between adenocarcinoma in situ and invasive adenocarcinoma, questions remain on the magnitude of the cancer risk after detection of the glandular intraepithelial lesion-atypical glandular cells (AGC). We also wanted to study whether the current clinical management after detection of glandular abnormalities reduced the cancer risk as much as the standard management for squamous intraepithelial lesions does. Our findings show that 2.6% of women with  intraepithelial lesion-atypical glandular cells as the first abnormality developed invasive cervical cancer after 15 years of follow up and 74% of the cancers were adenocarcinoma. A moderately high proportion of women with AGC had prevalent cancer (diagnosed within 6 months from AGC), while there was considerably high incidence of cervical cancer within 0.5-6.5 years after a detection of AGC. The incidence of cervical cancer following AGC was significantly higher than for high-grade squamous intraepithelial lesions, and this increased risk remained even after having histology assessment in the initial half year.

The high risk of cervical cancer associated with AGC implies that the current clinical management following AGC does not prevent cervical cancer as sufficiently as the management for squamous intraepithelial lesions does.

 

Author Interviews, Hospital Acquired, Infections, Nature / 24.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21986" align="alignleft" width="200"]Ashootosh Tripathi, PhD Postdoctoral Research Fellow Life Sciences Institute I Sherman lab University of Michigan Ann Arbor, MI, USA Dr. Ashootosh Tripathi[/caption] Ashootosh Tripathi, PhD Postdoctoral Research Fellow Life Sciences Institute I Sherman lab University of Michigan Ann Arbor, MI, USA MedicalResearch: What is the background for this study? What are the main findings? Dr. Tripathi: Acinetobacter baumannii is a nosocomial opportunistic and resistant pathogen that can spread epidemically among patients causing ventilator-associated pneumonia and bacteremia. The mortality rates associated with it can be as high as 60%, representing a paradigm of pathogenesis, transmission and resistance. In addition, numerous reports have shown the startling emergence of multidrug-resistant A. baumannii in hospitals as well as the identification of pan-drug-resistant strains at some locations. Among the  various reasons for the antibiotic resistance of this pathogenic microbe, perhaps the most significant is mediated by its tendency to form biofilms (a highly structured extracellular polymeric matrix), which provide the microbe with the alarming ability to colonize medical devices. Interestingly, despite the well-understood role of bacterial biofilm behind aggravating antimicrobial resistance, there are currently no drugs specifically targeting biofilms in clinical trials to date. The study sought to solve this problem through the development of a biofilm inhibitor as a precision medicine, directed towards vulnerable patients, to avoid potential life-threatening infections. A crystal-violet based high throughput in vitro screen was developed to identify inhibitors of A. baumannii biofilms against our natural products extract (NPE) library. The vast NPE library of ~42,000 extracts has been under constant development in Prof David H. Sherman laboratory at University of Michigan, Ann Arbor, for over the past decade, from a relatively underexplored marine microbiome collected from different part of world viz., Costa Rica, Panama, Papua New Guinea, etc., and is available for any research group with a robust high-throughput screening (HTS) assay (http://www.lsi.umich.edu/centers/center-for-chemical-genomics). The HTS assay that was queried against a library of 9,831 NPEs aimed to identify extracts inhibiting biofilm formation as a primary screening. Further secondary  screening and   activity  threshold optimization revealed the extract from Streptomyces gandocaensis (collected from Costa Rica) to be of particular interest due to its ability to inhibit biofilm formation and had a limited effect on A. baumannii growth. Activity based chromatographic separation and analysis of extracts derived from S. gandocaensis resulted in the discovery of three peptidic metabolites (cahuitamycins A–C),   with cahuitamycin  C  being   the   most effective biofilm inhibitor (IC50 =14.5 µM)   with  negligible A.  baumannii growth inhibition (an important trait for ideal biofilm inhibitor). Following up on the exciting discovery, we also completely characterized the biosynthetic machinery involved in making the active molecules by S. gandocaensis, using sophisticated bioinformatics and molecular biology techniques. The knock out analysis revealed that the biosynthesis of cahuitamycin C proceeds via a convergent biosynthetic pathway, with one of the steps apparently being catalyzed by an unlinked gene encoding a 6-methylsalicylate synthase. Efforts to assess starter unit diversification through selective mutasynthesis led to production of unnatural analogues cahuitamycins D and E with increased potency (IC50=8.4 and 10.5 µM) against A. baumannii biofilm.
Author Interviews, OBGYNE, Pediatrics, Pulmonary Disease, Tobacco Research / 24.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21974" align="alignleft" width="135"]Dr. med. Julia Dratva, MD MPH Medical Specialist Prevention and Public Health - FMH Scientific project leader MAS Versicherungsmedizin/Studienkoordinationleitung Dr. Julia Dratva[/caption] Dr. med. Julia Dratva, MD MPH          Medical Specialist Prevention and Public Health FMH  Scientific project leader MAS Versicherungsmedizin/Studienkoordinationleitung Dept. Epidemiology and Public Health Swiss Tropical and Public Health Institute Socinstrasse 57, P.O. Box, 4002 Basel, Switzerland Medical Research: What is the background for this study? What are the main findings? Dr. Dratva: Early childhood is a critical time window for subsequent health. Early life environment is known to be important for lung development and respiratory health. Little is known on the potential impact on lung ageing and the potential mechanisms responsible for the long-term impact. We investigated early childhood factors and their association with lung function decline, a common marker of lung aging, in two long-standing adult cohorts, SAPALDIA and ECRHS. As recently published in scientific journal PlosONE, maternal smoking, early respiratory infections or season of birth are associated with a faster decline in lung function decline, while less rapid decline was found in persons who had attended daycare. The early exposures may not only have an independent adverse effect on lung aging but also increase the respiratory vulnerability to other adult risk factors. Stronger effects were observed in in smokers exposed to the aforementioned adverse factors.
Author Interviews, Heart Disease, JAMA, Kidney Disease, Pharmacology / 24.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21970" align="alignleft" width="158"]Frederic T. Billings Dr. Frederic T.Billings[/caption] Frederic T. Billings IV, MD, MSc Assistant Professor of Anesthesiology and Medicine Additional Specialty: Cardiothoracic Anesthesiology Vanderbilt University Medical Research: What is the background for this study? What are the main findings? Dr. Billings: Acute kidney injury (AKI) affects up to 30% of patients following cardiac surgery and is associated with long-term kidney function decline as well as a 5-fold increase in death during hospitalization following surgery. Statins affect several mechanisms of AKI following cardiac surgery including improvement of endothelial function and attenuation of oxidative stress, so we performed a clinical trial to test the hypothesis that high-dose atorvastatin (brand name Lipitor) use prior to and following surgery reduces AKI following cardiac surgery. In 615 patients who completed the study high-dose atorvastatin treatment, compared to placebo administration, did not reduce the risk of AKI overall, among patients naïve to statins, or patients already using a statin. In fact, among patients naïve to statins with baseline chronic kidney disease we found some evidence that atorvastatin may increase risk for kidney injury, although the number of patients was small in this subgroup.
Author Interviews, Brigham & Women's - Harvard / 24.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21963" align="alignleft" width="160"]Dr. Michelle Dossett Dr. Michelle Dossett[/caption] Michelle Dossett, MD, PhD, MPH Benson-Henry Institute for Mind Body Medicine Massachusetts General Hospital  Medical Research: What is the background for this study? What are the main findings? Dr. Dossett: In 2015 the FDA and FTC held public hearings on the regulation and advertising, respectively, of homeopathic drug products.  Among their questions, they were curious about the use and public perceptions of these products.  However, there is little data available to answer these questions.  Every 5 years, the National Center for Health Statistics at the CDC and the National Center for Complementary and Integrative Health (NCCIH) at the NIH team up to survey Americans about their use of complementary and integrative medicine (CIM) modalities.  We analyzed data from the 2012 survey to address some of the questions raised by the FDA and FTC. We found that 2.1% of U.S. adults had used homeopathic products within the past year, however, only 19% had seen a practitioner for homeopathic therapy.  The most common health complaints that homeopathic products were used to address included head and chest colds and other respiratory and otorhinolaryngology (ear, nose, and throat) complaints. The second most common category of conditions these products were used for was musculoskeletal pain such as muscle and joint pain.  Intriguingly, people who used homeopathic products were more likely to find them helpful for a health condition than supplement users found their use of supplements.  Moreover, homeopathy users who saw a practitioner were more likely to find that it helped their health problem “a great deal” than those who did not.
Author Interviews, Pain Research, Race/Ethnic Diversity / 24.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21957" align="alignleft" width="178"]Adam T. Hirsh PhD Assistant Professor, Psychology Indiana University Indianapolis, IN Dr. Adam T. Hirsh[/caption] Adam T. Hirsh PhD Assistant Professor, Psychology Indiana University Indianapolis, IN  Medical Research: What is the background for this study? What are the main findings? Dr. Hirsh: Pain is highly prevalent and is a major cause of disability. How patients cope with pain affects how much pain they feel and how much that pain interferes with their lives. Compared to White individuals, Black individuals experience greater pain across a number of clinical conditions, as well as in response to experimentally-delivered stimuli. These race differences may be due to differences in pain-related coping. We conducted a meta-analysis of clinical and experimental studies (including 2,719 Black and 3,770 White adults) to quantify race differences in the overall use of pain coping strategies as well as specific coping strategies. The results indicated that, compared to White individuals, Black individuals used pain coping strategies more frequently overall. In particular, Black individuals more frequently used strategies that involved praying and catastrophizing, whereas White individuals more frequently used strategies that involved task persistence. These results suggest that Black individuals use coping strategies more frequently, specifically strategies associated with poorer pain outcomes.
Abuse and Neglect, BMJ, Imperial College, Microbiome, OBGYNE / 23.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21901" align="alignleft" width="214"]Dr. Aubrey Cunnington Faculty of Medicine, Department of Medicine Clinical Senior Lecturer Imperial College, London Dr. Aubrey Cunnington[/caption] Dr. Aubrey Cunnington Faculty of Medicine, Department of Medicine Clinical Senior Lecturer Imperial College, London Medical Research: What is the background for this study? What are the main findings? Dr. Cunnington: We noticed that increasing numbers of women who were having Caesarean section deliveries at our hospitals were requesting for their vaginal fluid to be swabbed onto their babies after birth – a process often termed “vaginal seeding”. The idea behind this, is that it transfers all the natural bacteria (microbiota) from the mother’s vagina to the baby. We know that early on in life, babies born by Caesarean section have different bacteria living on their bodies and in their guts to those of babies born by vaginal delivery. Some people think these differences in the microbiota may be responsible for differences in long-term health, although a causal link is unproven. The hope is that vaginal seeding might reduce the risk of the baby developing some diseases like obesity and asthma in the future. Unfortunately we are a long way from having the evidence to show that this is possible, and we do not know whether vaginal seeding is really safe. Babies born by elective Caesarean section are at lower risk of transfer of some potentially harmful bacteria and viruses from the birth canal, but these harmful bacteria and viruses could be transferred to the baby on a swab and potentially cause a devastating infection. MedicalResearch.com Editor's note:  'Vaginal Seeding' is also known as "microbirthing",   
Author Interviews, Compliance, Neurological Disorders, Stroke / 23.02.2016

MedicalResearch.com Interview with: Dr-William-Patrick-Neil William P. Neil, MD Vascular Neurologist SCPMG Regional Stroke Champion Neurology    Medical Research: What is the background for this study? Dr. Neil: Stroke survivors are less likely to have a recurrent stroke, or other complications if they take their medications as prescribed by their doctor. Mail order pharmacies are increasingly being used to deliver medications for a variety of diseases, and their use is associated with better medication adherence.  We wanted to see whether stroke patients who use mail-order pharmacies were more likely to have good medication adherence than those who used  local pharmacies. Medical Research: What are the main findings? Dr. Neil: We looked through a large electronic medical database in California, and found a total of 48,746 people discharged from the hospital with a stroke, and who also filled either a cholesterol medication or an anticoagulant (blood thinner). Of these, 136,722 refills were from a local pharmacy and 68,363 were by mail. Overall, patients were adherent to the medications 46.5% of the time if they picked up the medication from the pharmacy and 74% of the time if they had prescriptions mailed to them.
Author Interviews, Clots - Coagulation, Genetic Research, Heart Disease, JACC / 23.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21677" align="alignleft" width="150"]Professor Keith AA Fox Duke of Edinburgh Professor of Cardiology University of Edinburgh Prof. Keith Fox[/caption] Professor Keith AA Fox Duke of Edinburgh Professor of Cardiology University of Edinburgh Medical Research: What is the background for this study? Prof. Fox: From previous reports, certain alleles of CYP2C19 are associated with reduced enzymatic function and reduced conversion of clopidogrel to the active metabolite. Patients carrying these reduced function alleles (reduced metabolizers) exhibit higher platelet reactivity when treated with clopidogrel, compared with patients without reduced-function alleles (extensive metabolizers). However, the relationship of CYP2C19 genotype and outcomes in medically managed patients with acute coronary syndromes (ACS) is not known. Medical Research: What are the main findings? Prof. Fox: There was no association between CYP2C19 metabolizer status (EM vs. RM) and the primary composite endpoint of cardiovascular death, myocardial infarction (MI), or stroke (hazard ratio [HR]: 0.86). EM and RM patients had similar rates of the primary endpoint whether treated with prasugrel (HR: 0.82) or clopidogrel (HR: 0.91; p for interaction non significant).
Author Interviews, Depression, Eating Disorders, Mental Health Research, Nutrition, OBGYNE, Pediatrics / 23.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21832" align="alignleft" width="200"]Lisanne de Barse Department of Epidemiology Erasmus Medical Center Rotterdam Dr. Lisanne De Barse[/caption] Lisanne de Barse PhD Department of Epidemiology Erasmus Medical Center Rotterdam MedicalResearch: What is the background for this study? Dr. de Barse: Fussy (or “picky”) eating behaviour, which is characterised by consistent rejection of particular foods, is common in childhood and a source of concern for parents. It is not well understood what affects fussy eating. It is, however, well known that internalizing psychiatric problems of parents (i.e. anxiety and depression) have an impact on children’s health and development. Studies have also shown that mothers’ internalizing problems during the child’s preschool period was linked to child fussy eating. It was not clear whether the child’s eating problems causes stress and psychiatric symptoms in mothers or whether mothers’ symptoms predict child eating behaviour. Nor was it known what potential impact the dads’ state of mind have. The purpose of this study was to examine whether mothers’ and fathers’ internalizing problems during pregnancy and during the child’s life predicts child fussy eating. MedicalResearch: What are the main findings? Dr. de Barse: Our main findings indicate that mothers’ anxiety and depressive symptoms during pregnancy could have an influence on children’s fussy eating. This was irrespective of mothers’ internalizing symptoms at the child’s preschool period. We also found indications that fathers’ anxiety and depressive symptoms might influence children’s fussy eating behaviour. This was studied in Generation R, a study that has been tracking the health and wellbeing of children from conception onwards, conducted by the Erasmus Medical Centre, in Rotterdam, the Netherlands.
Annals Internal Medicine, Author Interviews, Emergency Care, Gout, Pharmacology / 23.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21670" align="alignleft" width="120"]Professor Timothy H Rainer MD MBBCh Director, Accident & Emergency Medicine Academic Unit The Chinese University of Hong Kong Prof. Timothy Rainer[/caption] Professor Timothy H Rainer  MD MBBCh Director, Accident & Emergency Medicine Academic Unit The Chinese University of Hong Kong  Medical Research: What is the background for this study? What are the main findings? Prof. Rainer: Gout is a type of arthritis characterised by periodic attacks of acute joint swelling and severe pain, and  often treated with colchicine or nonsteroidal anti-inflammatory drugs (NSAIDs).  Two recent randomized, controlled trials showed that oral prednisolone, a corticosteroid, was as effective as NSAIDs in the treatment of acute gout, but these studies involved small numbers of patients.  The researchers investigatedwhether oral prednisolone was as effective and safe as indomethacin (a NSAID) in a larger sample of patients who had acute gout symptoms and who were seen in the emergency department (ED) setting. Patients in both the prednisolone and indomethacin groups had clinically meaningful decreases in their pain levels during the 2 hours they were observed in the ED as well as during the 14-day follow-up period. Both groups had a similar decrease in pain levels. No major adverse events were reported in either group although there were more minor adverse events in the indomethacin group.
Author Interviews, Imperial College, Pulmonary Disease, Toxin Research / 23.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21406" align="alignleft" width="149"]Dr Rebecca Ghosh, Research Associate Small Area Health Statistics Unit (SAHSU) MRC-PHE Centre for Environment and Health Imperial College London St Mary's Campus, Norfolk Place, Londo Dr. Rebecca Ghosh[/caption] Dr Rebecca Ghosh, Research Associate  Small Area Health Statistics Unit (SAHSU) MRC-PHE Centre for Environment and Health Imperial College London St Mary's Campus, Norfolk Place, London  Medical Research: What is the background for this study? What are the main findings? Dr. Ghosh: Since the 1950s a lot of evidence has accumulated that high levels of air pollution cause harmful effects on health.  However there is limited evidence on the very long term (>25 years) effects of air pollution.  Our study is one of the longest running to date looking at air pollution and mortality, following 368,000 people in England and Wales for 38 years.  We estimated air pollution exposures throughout England & Wales for 1971, 1981, 1991 and 2001 using data from historic air pollution monitoring networks, the first time this has been done. We found that air pollution exposure in 1971 was still associated with a small increased risk of death in 2002-9, over 30 years later, suggesting that harmful effects of air pollution are extremely long-lasting.  However, risks from an individual’s past exposures waned over time and their more recent exposures gave the highest mortality risks.
Author Interviews, Autism, Genetic Research / 23.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21940" align="alignleft" width="213"]Li ZENG, Ph.D. Principal Investigator Neural Stem Cell Research Lab National Neuroscience Institute Singapore Dr. Li Zeng[/caption] Li ZENG, Ph.D. Principal Investigator Neural Stem Cell Research Lab National Neuroscience Institute Singapore Medical Research: What is the background for this study? What are the main findings? Dr. Zeng: Autism Spectrum Disorders (ASDs) are a group of highly inheritable behavioural disorders that pose major personal and public health concerns. Patients with ASDs have mild to severe communication difficulties, repetitive behaviour and social challenges. Such disorders significantly challenge an individual’s ability to conduct daily activities and function normally in society. Currently there are very few medication options that effectively treat ASDs. Therefore, there is a need to better understand the biology of that produces Autism Spectrum Disorder symptoms. In the study, we found how one brain-specific microRNA (miR-128) plays a key role in causing abnormal brain development. MicroRNAs are small molecules that regulate gene expression in the human body to ensure proper cellular functions. Although it was known that miR-128 is misregulated in some patients with autism, what that meant and how it functioned was not known. We showed that miR-128 targets a protein called PCM1 that is critical to the cell division of neural precursor cells (NPCs). NPCs during early brain development have two fates - they either stay as NPCs and undergo self-renewal or become neurons through differentiation. The dysfunctional regulation of PCM1 by misregulated miR-128 impairs brain development, which may underlie brain size changes in people with Autism Spectrum Disorders.
Author Interviews, Global Health, HIV, NEJM, OBGYNE / 22.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21920" align="alignleft" width="200"]Jared Baeten, MD PhD Vice Chair, Department of Global Health Professor, Departments of Global Health, Medicine, and Epidemiology Co-Director, International Clinical Research Center University of Washington Dr. Jaret Baeten[/caption] Jared Baeten, MD PhD Vice Chair, Department of Global Health Professor, Departments of Global Health, Medicine, and Epidemiology Co-Director, International Clinical Research Center University of Washington MedicalResearch.com: What is the background for this studies? Dr. Baeten: Women account for nearly 60 percent of adults with HIV in sub-Saharan Africa, where unprotected heterosexual sex is the primary driver of the epidemic. While several studies have shown that antiretroviral medications (ARVs) are highly effective in preventing HIV, other studies – such as VOICE and FACTS 001 – suggest that for young, at-risk women in Africa, ARVs delivered as a vaginal gel or as a tablet may not be acceptable. Products must be used to be effective, and that was not the case for most of the participants in previous studies. Medical Research: What was the aim of ASPIRE and The Ring Study? Dr. Baeten: As Phase III clinical trials, ASPIRE and The Ring Study were designed to determine whether a vaginal ring containing an antiretroviral (ARV) drug called dapivirine is safe and effective in protecting women against HIV when used for a month at a time. These trials also sought to determine whether women find the vaginal ring practical and easy to use. As sister studies, ASPIRE and The Ring Study were designed as the centerpiece of a broader licensure program to provide the strength of evidence to support potential licensure of the dapivirine vaginal ring for preventing HIV in women. Because at least two Phase III efficacy trials are usually needed for a product to be considered for regulatory approval, ASPIRE and The Ring Study were conducted in parallel to accelerate the timeline to the ring’s potential approval.
Anesthesiology, Author Interviews, Critical Care - Intensive Care - ICUs, JAMA, Pulmonary Disease / 22.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21841" align="alignleft" width="180"]John G. Laffey MD Chief, Department of Anesthesia; Co-Director, Critical illness and Injury Research Centre; Scientist, Keenan Research Centre for Biomedical Science ‑ St. Michael's Hospital Professor, Anesthesia, Critical Care, and Physiology ‑ University of Toronto Dr. John Laffey[/caption] John G. Laffey MD Chief, Department of Anesthesia; Co-Director, Critical illness and Injury Research Centre; Scientist, Keenan Research Centre for Biomedical Science ‑ St. Michael's Hospital Professor, Anesthesia, Critical Care, and Physiology ‑ University of Toronto Medical Research: What is the background for this study? Dr. Laffey: Acute respiratory distress syndrome is the commonest cause of severe acute respiratory failure in the critically ill. ARDS is a major cause of death and disability in the critically ill worldwide. Second, there is no treatment for ARDS, and our present management approaches are limited to supporting organ function while treating the underlying causes We performed the LUNG SAFE study to address several clinically important questions regarding ARDS. First, the current incidence in a large international cohort was not known. Large regional differences had been suggested: for example, the incidence of ARDS in the US was reported to be ten times greater of that in Europe_ENREF_4. Second, we wanted to understand how we manage patients with  Acute respiratory distress syndrome in the ‘real world’ situation. Specifically, it was not clear to what extent newer approaches to artificial ventilation, such as reducing the size of the breaths (lower tidal volumes) and keeping the lung pressure positive at all times to minimize collapse (PEEP) were used. The impact of studies showing promise for other measures to improve gas exchange such as turning patients prone during mechanical ventilation, or using neuromuscular blockade, on routine clinical practice in the broader international context was not known. Third, there were some concerns over the extent of clinician recognition of ARDS. This was an important issue because implementation of the effective therapies may be limited by lack of recognition of ARDS by clinicians. A better understanding the factors associated with ARDS recognition and how this recognition influenced patient management could lead to effective interventions to improve care. Lastly we wanted to determine the outcome from  Acute respiratory distress syndrome in a global cohort of patients. Medical Research: What are the main findings? Dr. Laffey: We found that ARDS continues to represent an important public health problem globally, with 10% of ICU patients meeting clinical criteria for ARDS. While there appeared to be some geographic variation, this did not seem as great as previously thought. An important finding was the under-recognition of  Acute respiratory distress syndrome by clinicians, with 40% of all cases not being recognized. In addition, over one third of patients did not receive protective lung ventilation strategies. The use of other measures to aid gas exchange during artificial ventilation, such as turning the patient into the prone position, or the use of neuromuscular blockade was also quite low. Of most concern, ARDS continues to have a very high mortality of approximately 40% of patients dying in hospital.
Anemia, Author Interviews, Kidney Disease, Pharmacology / 22.02.2016

MedicalResearch.com Interview with: Dr. Navdeep Tangri Attending physician and Assistant Professor in the Division of Nephrology Department of Medicine and the Department of Community Health Sciences University of Manitoba and Dr. David Collister  Seven Oaks General Hospital Renal Program Winnipeg, Manitoba Canada.  Medical Research: What is the background for this study? What are the main findings? Response: Anemia is common in chronic kidney disease (CKD) including dialysis and its treatment with erythopoetin stimulating agents (ESAs) reduces the need for blood transfusions and has varying effects on morbidity and mortality. The optimal hemoglobin (HGB) targets for treating anemia in CKD are controversial with safety concerns around the normalization of hemoglobin levels due to an increase in cardiovascular (CV) events. The effects of ESAs on health related quality of life (HRQOL) are unclear with individualization o fhemoglobin targets being controversial as clinicians and patients attempt to balance perceived HRQOL benefits with cardiovascular risk. We performed an updated meta-analysis of randomized controlled trials (RCTs) that evaluated the treatment of anemia in CKD with ESAs that targeted higher versus lower hemoglobin targets using validated HRQOL metrics including SF-36 and KDQ. We included 17 studies and found that higher hemoglobin targets compared to lower HGB targets did result in a statistically significant difference in HRQOL and thus did not improve HRQOL beyond a clinically meaningful threshold. Any change in HRQOL was further attenuated in dialysis subgroups.
Author Interviews, Gender Differences, Health Care Systems, Women's Heart Health / 22.02.2016

MedicalResearch.com Interview with: Professor Robyn Norton Principal Director of The George Institute for Global Health Board Member, The George Institute for Global Health Professor of Public Health at the University of Sydney Professor of Global Health at the University of OxfordProfessor Robyn Norton Principal Director of The George Institute for Global Health Board Member, The George Institute for Global Health Professor of Public Health at the University of Sydney Professor of Global Health at the University of Oxford Medical Research: What is the background for this study? What are the main findings? Prof. Norton: The impetus to focus on women’s health, stems from the knowledge that, while noncommunicable diseases (NCDs) are the leading cause of death and disability for women worldwide, this is not sufficiently recognized nor sufficiently resourced. Equally, while there is increasing evidence that we can learn so much more about how to address the burden of disease for women, by collecting and analyzing data on women, separately to that for men, this is not happening. We are calling for a refocus of the women’s health agenda on NCDs – given that globally and in many countries the focus of women’s health almost exclusively is still on women’s sexual and reproductive health. The fact is that in all but the poorest countries, the greatest health burden, for women, is  noncommunicable diseases and so that if we are to make significant gains in improving women’s health then we must focus on addressing NCDs. The current global burden of disease for women reflects both the significant gains that have been made as a result of addressing maternal mortality and changes that have affected both women and men equally – namely, that populations are living longer, as a consequence of reductions in both infant mortality and communicable diseases, as well as the fact that populations are becoming wealthier and, as a result, are engaging in behaviors that increase the risk of noncommunicable diseases.
Author Interviews, Cost of Health Care, Pediatrics / 22.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21916" align="alignleft" width="200"]Joanna Thomson MD MPH Assistant Professor Division of Hospital Medicine Cincinnati Children’s Hospital Medical Center Dr. Joanna Thomson[/caption] Joanna Thomson MD MPH Assistant Professor Division of Hospital Medicine Cincinnati Children’s Hospital Medical Center Medical Research: What is the background for this study? What are the main findings? Response: Children with medical complexity have lifelong and complex illnesses. These children account for a disproportionate amount of pediatric health care use.  The lives of families are affected – both financially and socially.  We sought to characterize the challenges these families face through examination of financial and social hardships. In a cohort of families with children who receive care at Cincinnati Children’s Complex Care Center, four out of five families reported experiencing at least one hardship. The striking frequencies observed, despite relatively high measures of household socioeconomic status, suggest that these families face great challenges.  For example, families frequently experienced the need to borrow money and expected little to no help from family or friends. In order to benchmark the hardships experienced by families of children with medical complexity, we compared the hardships they experienced to those faced by the families of children with asthma in the Greater Cincinnati Asthma Risks Study. After accounting for key demographic and socio-economic differences between the two groups, families of children with medical complexity experienced similar to higher levels of financial and social hardship.  For instance, families of children with medical complexity were over two times as likely to report the inability to pay their rent or mortgage than families of children with asthma.
Author Interviews, Heart Disease, Stroke / 22.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21909" align="alignleft" width="140"]Dr. Rolf Wachter Head Senior physician University of Goettingen Göttingen, Germany Dr. Rolf Wachter[/caption] Dr. Rolf Wachter Head Senior physician University of Goettingen Göttingen, Germany Medical Research: What is the background for this study? What are the main findings? Dr. Wachter: Atrial Fibrillation is a known risk factor for stroke, and in stroke patients, it is a strong predictor of adverse outcome, if it is not adequately treated (e.g. by anticoagulation). However, in its paroxysmal form, Atrial Fibrillation (AF) may escape routine diagnostics. We aimed to show that we can increase the number of patients with detected AF if we do more monitoring for atrial fibrillation. As a unique feature of our study, we did not focus on a certain stroke subtype (i.e. cryptogenic stroke), but we aimed to consider all patients >= 60 years in whom the detection of  Atrial Fibrillation has a clinical relevance. The main finding of our study was that enhanced and prolonged Holter ECG monitoring (3x10 days of monitoring, analysed in a dedicated core lab) tripled the number of detected AF cases (from 4.5 to 13.5 %). 11 patients had to undergo enhanced and prolonged monitoring to find one additional case of Atrial Fibrillation.
Author Interviews, Diabetes, OBGYNE, Pediatrics / 22.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21895" align="alignleft" width="200"]Laurie A. Nommsen-Rivers, PhD, RD, IBCLC Assistant Professor, UC Department of Pediatrics Cincinnati Children's Hospital Medical Center Dr. Laurie Nommsen-Rivers[/caption] Laurie A. Nommsen-Rivers, PhD, RD, IBCLC Assistant Professor, UC Department of Pediatrics Cincinnati Children's Hospital Medical Center  Medical Research: What is the background for this study? Dr. Nommsen-Rivers: Breastfeeding provides important benefits for mother and infant. Exclusive breastfeeding—that is, without any other food or fluids provided to the infant—is recommended for the first six months of life by multiple public health organizations. Some mothers, despite their best efforts, have difficulty establishing and sustaining sufficient milk production to support exclusive breastfeeding. Our previous research suggested that mothers with less optimal glucose tolerance are at risk for prolonged delays in time between birth and the establishment of copious milk production. We wanted to extend this finding by probing if mothers who had diabetes in pregnancy, as a sign of less optimal glucose tolerance, are at greater risk of sustained low milk production. “Glucose tolerance” refers to the body’s ability to metabolize glucose and maintain a healthy blood sugar level, which is orchestrated by the hormone insulin. For a long time, we did not consider insulin to play a role in milk production, but we are now learning that insulin plays an essential role in milk production.
Author Interviews, Epilepsy / 21.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21891" align="alignleft" width="153"]Dr. Samba Reddy, PhD, RPh, FAAPS Professor Neuroscience and Experimental Therapeutics College of Medicine Texas A&M University Health Science Center Bryan, TX Dr. Samba Reddy[/caption] Dr. Samba Reddy, PhD, RPh, FAAPS Professor Neuroscience and Experimental Therapeutics College of Medicine Texas A&M University Health Science Center Bryan, TX Medical Research: What is the background for this study? What are the main findings? Dr. Reddy: Neurosteroids are a group of neuroactive compounds present in the brain. They are known to modulate ionotropic post-synaptic GABA-A receptors, which are the primary mediators of fast inhibitory neurotransmission in the brain. Hence, the neurosteroid—GABA-A receptor system is a critical axis for controlling neuronal excitability in certain brain disorders, such as anxiety and epilepsy. There is new evidence that such neurosteroids can strongly activate extrasynaptic GABA-A receptors, which are located outside of the synapses mainly on soma, dendrites and axons. However, the neurosteroid structure requirement for functional activation of extrasynaptic receptors remains largely unexplored.  In this study, we identified a consensus neurosteroid pharmacophore model at extrasynaptic GABA-A receptors for activation of tonic current and seizure protection.
Author Interviews, Clots - Coagulation, Stroke / 21.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21887" align="alignleft" width="90"]Thorsten Steiner, MD, PhD Klinikum Frankfurt Hoechst and Heidelberg University Hospital Germany Dr. Thorsten Steiner[/caption] Thorsten Steiner, MD, PhD Klinikum Frankfurt Hoechst and Heidelberg University Hospital Germany Medical Research: What is the background for this study? What are the main findings? Dr. Steiner: Background of the study is intracranial hemorrhage (ICH) related to vitamin-K antagonists. The mortality rate is about 60%. Main reason for the high mortality rate is hematoma expansion which occurs in about 50% during the acute phase right after the start of symptoms. We performed an investigator initiated randomized controlled trial (RCT) and found that a 4-factor prothrombin complex (PCC) is superior to fresh frozen plasma (FFP) in normalizing the international normalized ratio (INR) and prevents hematoma expansion. This let to more deaths within 48 hours in the FFP-group but had no clinical impact at 3 months - but our study was powered to detect INR normalization and not a clinical endpoint.
Author Interviews, CDC, HIV / 21.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21878" align="alignleft" width="158"]Martin Hoenigl, MD Postdoctoral Fellow AntiViral Research Center, Department of Medicine University of California, San Diego Dr. Martin Hoenigl[/caption] Martin Hoenigl, MD Postdoctoral Fellow AntiViral Research Center, Department of Medicine University of California, San Diego Medical Research: What is the background for this study? Response: The detection of acute HIV infection (AHI) is critical to HIV prevention and treatment strategies. Many field-based testing programs rely on point-of-care HIV antibody testing, which will reliably identify persons with established infection, but fail to detect persons with AHI. In many of these programs additional tests for AHI are only performed / recommended in persons presenting with signs and symptoms consistent with an acute retroviral syndrome (ARS). These signs and symptoms are unspecific and include fatigue, headache, pharyngitis, skin rash, GI symptoms, night sweats and others. However, the proportion of persons with acute HIV infection presenting symptomatic for their diagnostic test remains unknown. The objective of our study was therefore to determine the proportion of persons with acute HIV infection presenting with signs and symptoms consistent with ARS for HIV screening. Medical Research: What are the main findings? Response: We analyzed signs and symptoms in 90 patients diagnosed with acute HIV infection in a community-based program in San Diego that offered universal HIV-1 nucleic acid amplification testing, independent of signs and symptoms. Forty-seven (52%) patients reported ongoing signs or symptoms consistent with ARS on the day of NAT screening. Another 25 (28%) reported signs or symptoms that had occurred during the 14 days before testing, but had resolved by the testing date. Another 12 (13%) reported signs and symptoms that started after the diagnostic test. Only 6/90 (7%) reported no signs and symptoms consistent with ARS. As a secondary finding, viral loads were significantly higher (p=0.001) in the 72 individuals reporting signs and symptoms consistent with ARS before or at the time of NAT screening compared to the 18 participants who did not report signs and symptoms at their diagnostic test. Most frequently reported ARS signs and symptoms included fever, myalgia, fatigue and headache.
Author Interviews, Genetic Research, JNCI, Melanoma / 21.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21873" align="alignleft" width="140"]Nancy E. Thomas, MD PhD Department of Dermatology, University of North Carolina Chapel Hill, NC 27599 Dr. Nancy E. Thomas[/caption] Nancy E. Thomas, MD PhD Department of Dermatology, University of North Carolina Chapel Hill, NC 27599 Medical Research: What is the background for this study? Dr. Thomas: Melanoma had been thought for some time to arise from at least two causal pathways, a ‘chronic sun exposure pathway’ and a ‘nevus pathway’. However, the role of inherited genetic variation in development of melanoma along these pathways had not previously been studied. Thus, we chose to examine the association of SNPs in putative low-penetrance melanoma susceptibility loci with histologic markers of divergent pathways. Medical Research: What are the main findings? Dr. Thomas: Within the large Genes, Environment and Melanoma Study, we investigated the relationship of germline variants in newly identified low-penetrance melanoma risk loci to histologic markers of divergent causal pathways in melanoma. We present strong evidence that the IRF4 rs12203592*T genotype is positively associated with chronic sun exposure-related melanoma and inversely associated with nevus-related melanoma. We also found that the IRF4 rs12203592 genotype is linked to the bi-model age distribution known to occur in melanoma and which is related to the divergent pathways. IRF4 rs12203592 is a functional variant known to affect IRF4 expression in human skin and melanoma cell lines. We conclude that IRF4rs12203592 is likely, at least in part, to determine pathway-specific risk for melanoma development.
Author Interviews, Gender Differences, Race/Ethnic Diversity, Stroke, Wake Forest / 20.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21869" align="alignleft" width="117"]Cheryl Bushnell, MD, MHS Professor of Neurology Director, Wake Forest Baptist Stroke Center Wake Forest Baptist Health Medical Center Boulevard Winston Salem, NC 27157 Dr. Cheryl Bushnell[/caption] Cheryl Bushnell, MD, MHS Professor of Neurology Director, Wake Forest Baptist Stroke Center Wake Forest Baptist Health Medical Center Boulevard Winston Salem, NC  27157  Medical Research: What is the background for this study? What are the main findings? Dr. Bushnell: The catalyst for the study was to see if comorbidities and the management of them might influence functional status.  But, we pre-specified gender and race because we knew these could be important predictors of outcome.  As it turns out, the results of our analysis did, in fact, show that gender and race were the most significant predictors of poor functional outcome. Medical Research: What should clinicians and patients take away from your report? Dr. Bushnell: The take-home message is that women and minorities have poorer functional outcome after stroke, but the reasons for this outcome need to be further explored.  Our model showed that we only explained 31% of the variance in SIS-16 with gender, race/ethnicity, and stroke severity, so unmeasured factors are extremely important.  We could speculate from this dataset and other published data that women may be more likely to have functional deficits prior to stroke, be unmarried/widowed, live alone, or institutionalized after stroke.  Non-white stroke survivors may have poorer access to care, have multiple strokes, and more comorbidities.