Author Interviews, Psychological Science, Weight Research / 10.06.2015

MedicalResearch.com Interview with: Katie Becofsky Ph.D. Weight Control and Diabetes Research Center The Miriam Hospital Providence, RI Medical Research: What is the background for this study? What are the main findings? Dr. Becofsky: Previous research has provided clear evidence of a relationship between social relations (e.g., frequency of social participation, perceived social support) and mortality risk.  We investigated two specific aspects of social relations- source of social support and size of weekly social network- in more detail.  The purpose of our study was to examine the associations between different sources of social support (relative, friend, and partner support), as well as size (and source) of weekly social network, on mortality risk in a large cohort of patients from the Aerobics Center Longitudinal Study. We found that perceived support from one’s spouse/partner and relatives, as well as weekly social interaction with a network of 6-7 friends, was associated with lower long-term mortality risk.  When the sources were reversed, the effects did not stand- perceived social support from friends did not affect mortality risk, nor did the quantity of weekly familial contacts.
Author Interviews, Blood Pressure - Hypertension, JAMA, Surgical Research, UCSF / 10.06.2015

MedicalResearch.com Interview with: Susan Ming Lee, MD, FRCPC, MAS (Clinical Research) Clinical Instructor, Dept. of Anesthesia and Perioperative Care University of California, San Francisco Medical Research: What are the main findings? Dr. Lee: Angiotensin receptor blockers (often referred to as ARBs) are common medications used to treat high blood pressure, heart disease, and kidney disease.  Doctors sometimes stop these medications briefly around the time of surgery, since they are known to cause low blood pressure under general anesthesia.  Doctors may hesitate to restart ARBs after surgery because they are worried about low blood pressure or kidney function.  Prior to our research, there was little information to guide the optimal timing of restarting ARBs after surgery. Medical Research: What are the main findings? Dr. Lee: Our study of over 30,000 veterans shows that nearly one third of veterans admitted to hospital for non-cardiac surgery are not restarted on their usual ARBs within two days of their operation.  This delay in resuming ARBs is associated with increased death rates in the first month after surgery.  In fact, even accounting for factors that might contribute to why doctors would withhold ARB (such as low blood pressure, kidney dysfunction, or other comorbidities), 30-day postoperative mortality was increased approximately 50% in those without resumption of ARBs, and this effect was even greater in younger patients under age 60.  Our findings of reduced rates of infections, pneumonia, heart failure, and kidney failure in those that resumed ARBs soon after surgery suggest that early resumption may also reduce complications after surgery.
Author Interviews, CDC, Gastrointestinal Disease, JAMA, Pediatrics, Vaccine Studies / 10.06.2015

Eyal Leshem, MD Division of Viral Diseases, US Centers for Disease Control and Prevention, Atlanta, GeorgiaMedicalResearch.com Interview with: Eyal Leshem, MD Division of Viral Diseases, US Centers for Disease Control and Prevention, Atlanta, Georgia Medical Research: What is the background for this study? What are the main findings? Response: Routine vaccination of US children to protect against rotavirus began in 2006. The purpose of this study was to examine the effect of implementation of rotavirus vaccine on gastroenteritis and rotavirus hospitalizations of children younger than 5 years old. The main finding from this study is that hospitalizations for diarrhea in U.S. children younger than 5 years old decreased dramatically during 2008 to 2012 following implementation of routine rotavirus vaccination in 2006. Additionally, seasonal peaks of hospitalizations for rotavirus illness were considerably reduced after the vaccine was implemented compared to years prior to rotavirus vaccination. By 2012, rates of rotavirus hospitalization declined by approximately 90% across all settings and age groups. Factors such as increasing vaccine coverage as well as herd immunity resulting in less transmission of rotavirus may be responsible for this large decrease.
Annals Internal Medicine, Author Interviews, Insomnia, Psychological Science / 10.06.2015

MedicalResearch.com Interview with: Dr David Cunnington Sleep Physician & Director Melbourne Sleep Disorders Centre East Melbourne Australia Medical Research: What is the background for this study? What are the main findings? Response: Insomnia is a very common problem with 15-20% of adults having chronic insomnia, that is, trouble getting to sleep or staying asleep most days for  3 months or more. The most commonly used treatment is sleeping pills or hypnotics, however, they don’t address the underlying disorder, and come with potential side effects. Also, sleeping tablets just mask the symptoms, and as soon as tablets are stopped, symptoms recur. People with chronic insomnia think and behave differently around sleep, which perpetuates their symptoms. The key to improving symptoms in the long run is addressing thoughts and behaviours around sleep, which is what cognitive behaviour therapy does. Our study showed that cognitive behaviour therapy reduced the time taken to get to sleep by 20 minutes and reduced the amount of time spent awake after falling asleep by nearly 30 minutes. These effects were maintained out to 12 months after treatment. These reductions in time taken to get to sleep and time spent awake are similar to those reported in clinical trials of hypnotics. 
Author Interviews, CDC, Vaccine Studies / 10.06.2015

MedicalResearch.com Interview with: Dr. Pedro Moro, MD, MPH Immunization Safety Office Division of Healthcare Quality Promotion Centers for Disease Control and Prevention Atlanta, GA 3033 Medical Research: What is the background for this study? What are the main findings? Response: The Vaccine Adverse Event Reporting System (VAERS) is a US national vaccine safety surveillance system, co-administered by the Centers for Disease Control and Prevention (CDC) and the US Food and Drug Administration (FDA). VAERS accepts reports of adverse events (possible side effects) following vaccination. Anyone can submit a report to VAERS. The study team searched VAERS for US reports of death after any vaccination from 7/1/1997 to 12/31/2013. During that time period, VAERS received 2,149 death reports, with most (68.4%) occurring in children. Among children, the most common causes of death were: o   sudden infant death syndrome (44%) o   asphyxia, or lack of oxygen to the brain (6%) o   septicemia, or blood poisoning from a bacterial infection (5%) o   pneumonia (5%) Among adults, the most common causes of death were: o   diseases of the circulatory system (47%) o   diseases of the respiratory system (15%) o   infections and parasitic diseases (12%) o   tumors (4%) The main causes of death seen in VAERS reports were consistent with the most common causes of death in the US population. When studied separately, none of these causes of death have found to be related to vaccines. This finding is reassuring, and consistent with previous research on vaccine safety.
Author Interviews, Dermatology / 10.06.2015

MedicalResearch.com Interview with: Chante Karimkhani MD Columbia University College of Physicians and Surgeons, New York, New York, Erika Hagstrom MD Loyola University of Chicago Stritch School of Medicine, Maywood, Illinois Robert Dellavalle MD, PhD, MPH Department of Dermatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado; Dermatology Service, US Department of Veterans Affairs, Eastern Colorado Health Care System, Denver, Colorado; Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado MedicalResearch: What is the background for this study? What are the main findings? Response: Allocation of funding dollars to research is a critical and daunting task. While many factors may impact research-funding decisions, establishing a transparent priority-setting exercise is paramount. This is particularly important for the National Institutes of Health, which invests over $30 billion for medical research each year. Diseases that have the greatest impact on our population warrant increased research dollars to reduce disease burden. The Global Burden of Disease Study (GBD) is an epidemiological effort to quantify the global burden of disease in a universal metric called disability-adjusted life years (DALYs). Focusing on our particular interest of dermatology, we investigated the 2012-2013 NIH funding for 15 skin diseases and matched this to corresponding DALY metrics. Our results demonstrated that melanoma, non-melanoma skin cancer, and leprosy were over-funded by the NIH according to DALY metrics. In contrast, dermatitis, acne vulgaris, pruritus, urticaria, decubitus ulcer, fungal skin diseases, alopecia areata, cellulitis, and scabies appeared under-funded. Three skin diseases, bacterial skin diseases, viral skin diseases, and psoriasis, were well-matched in terms of NIH funding and disease burden. Disease burden is one of a myriad of factors that may impact funding priorities.
Author Interviews, BMJ, Urology / 09.06.2015

MedicalResearch.com Interview with: Bilal Chughtai, MD & Art Sedrakyan, MD, PhD Department of Urology Weill Cornell Medical College Medical Research: What is the background for this study? What are the main findings? Response: Since 2008, the U.S. Food and Drug Administration has released number of public health notifications cautioning the use of mesh in pelvic organ prolapse (POP) surgery. Despite these notifications and subsequent public scrutiny, studies have reported a large increase of mesh use in female patients with pelvic organ prolapse during the last decade. In light of the reported rise in mesh utilization, we sought to determine the use of mesh in prolapse surgery and compare short-term outcomes of prolapse surgery with or without mesh. After identifying 7,338 and 20,653 patients who underwent prolapse repair procedures with and without mesh in a 4-year period, we found that mesh use increased 44.7%. Most patients were under 65 (62.3%), and there were more patients older than 65 years in the mesh group (44.3% versus 35.4%). Overall, complications were not common. However, patients who received mesh were more likely to experience urinary retention within 90-days and had a higher chance of having re-intervention at 1 year. Mesh use was also associated with higher risk of urinary retention in older patients (≥ 65 year olds) and re-intervention within 1 year in younger patients (<65 year olds).
Author Interviews, Hospital Acquired, Infections / 08.06.2015

Stephanie Bonne, MD, FACS Assistant Professor Trauma, Acute, and Critical Care Surgery Washington University in St. LouisMedicalResearch.com Interview with: Stephanie Bonne, MD, FACS Assistant Professor Trauma, Acute, and Critical Care Surgery Washington University in St. Louis Medical Research: What is the background for this study? What are the main findings? Response: We had previously implemented education programs in our ICU in an attempt to decrease our Central Line-Associated Bloodstream Infection (CLABSI) rate.  We were, however, unable to come to zero.  We were looking for innovative ways to lower our CLABSI rate, and the use of Clorhexidine/Silver Sulfadiazine catheters was unable to move our CLABSI rate.  We decided to try Minocycline/Rifampin catheters, and monitor our Central Line-Associated Bloodstream Infection rate. Medical Research: What should clinicians and patients take away from your report? Response: The use of Minocycline/Rifampin impregnated catheters can lower Central Line-Associated Bloodstream Infection rate, particularly in ICUs who have been unable to reach a Central Line-Associated Bloodstream Infection rate of zero with other measures.
Author Interviews, Depression, Diabetes, Heart Disease, Pharmacology, Women's Heart Health / 08.06.2015

Dr. Karin Rådholm MD Ph.D. Division of Community Medicine, Primary Care, Department of Medicine and Health Sciences, Faculty of Health Sciences, Linköping University, Department of Local Care West, County Council of Östergötland, Linköping, SwedenMedicalResearch.com Interview with Dr. Karin Rådholm MD Ph.D. student Division of Community Medicine, Primary Care, Department of Medicine and Health Sciences, Faculty of Health Sciences, Linköping University Department of Local Care West, County Council of Östergötland, Linköping, Sweden MedicalResearch: What is the background for this study? Dr. Rådholm: Psychosocial risk factors and depressive disorders often co-occur with general medical comorbidities, such as myocardial infarction. Depression is more common in patients with diabetes than in patients without diabetes. About 10-30% of patients with diabetes have a comorbid depressive disorder, which is double the estimated prevalence of depression in individuals without diabetes. There is an association between comorbid depressive symptoms and diabetes complications. This is believed to be mainly due to poor adherence to treatment recommendations and diabetes self-management activities, but could also possibly be due to biological and behavioural causes that could predispose for both metabolic and affective disorders. The general risk of myocardial infarction is strongly dependent on age and sex, where men have an earlier disease onset compared to women. In the general population women are at much lower risk for ischemic heart disease mortality than men are. However, women with diabetes are at especially high risk for coronary heart disease, relatively more so than men with type 2 diabetes, meaning that the impact of diabetes on the risk of coronary death is significantly greater for women than men. The age- and gender-specific risk for myocardial infarction due to diabetes with coexistent depression has not previously been described. Data on all dispensed drug prescriptions in Sweden are available in the Swedish Prescribed Drug Register and all myocardial infarctions are registered in the Myocardial Infarction Statistics. These registers are population-based and have a total national coverage and high validity, which has been previously shown. Prescribed and dispensed antidiabetics and antidepressants were used as markers of disease. Our objective was to prospectively explore the gender- and age-specific risk of first myocardial infarction in people treated with antidiabetic and/or antidepressant drugs compared to participants with no pharmaceutical treatment for diabetes or depression in a nationwide register study.
Author Interviews, Biomarkers, Chemotherapy, JAMA, Johns Hopkins, Prostate Cancer / 08.06.2015

Emmanuel S. Antonarakis, M.B.B.CH Department of Urology and Oncology Johns Hopkins University School of Medicine Baltimore, MarylandMedicalResearch.com Interview with: Emmanuel S. Antonarakis, M.B.B.CH Department of Urology and Oncology Johns Hopkins University School of Medicine Baltimore, Maryland Medical Research: What is the background for this study? What are the main findings? Dr. Antonarakis: In a previous publication, we reported that detection of the androgen receptor splice variant 7 (AR-V7; an abnormal version of the androgen receptor) in circulating tumor cells from patients with advanced prostate cancer was associated with resistance to hormonal therapies such as abiraterone and enzalutamide. Here, we aimed to explore the role of AR-V7 in the context of chemotherapy treatment. We showed that detection of AR-V7 was not associated with resistance to the chemotherapy drugs docetaxel or cabazitaxel, and that AR-V7-positive patients could still derive benefit from these chemotherapies.
ASCO, Author Interviews, Biomarkers, Cancer Research / 06.06.2015

MedicalResearch.com Interview with: Dr. Kirsten Timms, PhD Program Director VP Biomarker Discovery at Myriad Genetics Inc Medical Research: What is the background for this study? What are the main findings? Dr. Timms: The Homologous Recombination Deficiency (HRD) score is a tumor biomarker which quantitates genomic rearrangements associated with defects in DNA damage repair. It has been shown in multiple studies that HRD score can identify tumors sensitive to DNA damaging agents such as platinum salts or PARP inhibitors. Many tumors are spatially heterogeneous: different parts of a tumor show variation at both the genomic level, and in their appearance. This tumor heterogeneity has the potential to negatively impact the accuracy of biomarker tests. This study assessed the consistency of the HRD score in multiple biopsies obtained from the same cancer to understand the impact of tumor heterogeneity on the HRD score. The main finding of this study is that the HRD score is highly conserved between different biopsies of the same tumor.
Author Interviews, JAMA, Obstructive Sleep Apnea / 06.06.2015

Marie Marklund, DDS senior lecturer Department of Odontology, Faculty of Medicine Umeå University SwedenMedicalResearch.com Interview with: Marie Marklund, DDS senior lecturer Department of Odontology, Faculty of Medicine Umeå University Sweden MedicalResearch: What is the background for this study? What are the main findings? Response: Snoring and obstructive sleep apnea are common in the population and these disorders continuously increase because of the ongoing obesity epidemic in many countries. Today, 34% of men and 17% of women in the US suffer from obstructive sleep apnea of all severities. Symptoms include daytime sleepiness, poor sleep quality, headache, insomnia and restless legs. In the longer term, a more severe sleep apnea is associated with serious consequences, such as hypertension, stroke, cancer, traffic accidents and early death. Continuous positive airway pressure is a highly effective treatment for sleep apnea patients. Adherence problems, for instance from nasal stuffiness and claustrophobia reduces its effectiveness. An oral appliance holds the lower jaw forwards during sleep in order to reduce snoring and sleep apneas. This therapy has primarily been suggested for snorers and patients with mild and moderate sleep apnea. No previous placebo-controlled study has, however, evaluated this specific group of patients. Results from more severe sleep apnea patients have shown a good effect on sleep apneas. The effect of oral appliances on daytime symptoms is unclear. Symptomatic improvement is an important outcome for milder sleep apnea patients. The primary aims of the present study were to study the effects on daytime sleepiness and quality of life of a custom-made, adjustable oral appliance in patients with daytime sleepiness and snoring or mild to moderate sleep apnea, i.e. the primary target group for this type of therapy. Secondary aims included the effects on sleep apnea, snoring and various other symptoms of sleep disordered breathing such as headaches and restless legs. We found that oral appliance therapy was effective in reducing sleep apneas, snoring and symptoms of restless legs. The apnea-hypopnea index was normal (<5) in 49% of patients using the active appliance and in 11% using placebo, with a numbers needed to treat of three. Daytime sleepiness and quality of life did not differ during active treatment and the placebo intervention. The patients experienced reduced headaches with active treatment, but the results did not differ from placebo. It was concluded, that a custom-made, adjustable oral appliance reduces obstructive sleep apneas, snoring and possibly restless legs. The efficacy on daytime sleepiness and quality of life was weak and did not differ from placebo in this group of patients.
Author Interviews, BMJ, Heart Disease / 06.06.2015

MedicalResearch.com Interview with: Prachi Bhatnagar, MPH, DPhil Researcher University of Oxford British Heart Foundation Centre on Population Approaches for Non-Communicable Disease Prevention Nuffield Department of Population Health Oxford Medical Research: What is the background for this study? What are the main findings? Response: We know that cardiovascular disease presents a large burden to the UK. We aimed to bring together all the main data on cardiovascular disease mortality, morbidity, treatment and economic costs. We found that there are regional inequalities in cardiovascular disease mortality and prevalence in the UK.
Author Interviews, Diabetes, JAMA, Ophthalmology, University of Michigan / 06.06.2015

Julia E. Richards, Ph.D. Harold F. Falls Professor of Ophthalmology and Visual Sciences Professor of Epidemiology Director, Glaucoma Research Center The University of MichiganMedicalResearch.com Interview with: Julia E. Richards, Ph.D. Harold F. Falls Professor of Ophthalmology and Visual Sciences Professor of Epidemiology Director, Glaucoma Research Center The University of Michigan Medical Research: What is the background for this study? Response: We have a special interest in how the developmental processes of aging increase the risk of late onset diseases. We wondered whether drugs that target known aging pathways might be able to reduce risk of late onset disease. In the aging field, an emerging area of interest has been the category of drugs called caloric restriction mimetic (CRM) drugs, which have been found to extend life span and to reduce risk or delay onset of some late-onset diseases. These caloric restriction mimetic drugs target a set of pathways that have come to be seen as playing roles in longevity. One of these caloric restriction mimetic drugs, metformin, happens to also be one of the most common drugs used in the treatment of type 2 diabetes. Glaucoma is a leading cause of blindness worldwide and classical open-angle glaucoma shows onset in late middle age or late age, so we hypothesized that a caloric restriction mimetic drug might be able to reduce the risk of open-angle glaucoma. We used data from a large health services database to compare the rate at which open-angle glaucoma developed in individuals with diabetes mellitus who used metformin versus those who did not use metformin. We predicted that metformin would be associated with reduced risk of open-angle glaucoma. Medical Research: What are the main findings? Response: We found that use of metformin was associated with reduced risk of open-angle glaucoma. A 2 gram per day dose of the CRM drug metformin for two years was associated with a 20.8% reduction in risk of developing open-angle glaucoma. When we looked at the highest quartile of drug prescribed (>1,100 grams over a two year period) we found a 25% reduction in risk relative to those taking no metformin. This risk reduction is seen even when we account for glycemic control in the form of glycated hemoglobin, and use of other diabetes drugs was not associated with reduced risk of open-angle glaucoma. A possible explanation for our findings might be that the mechanism of risk reduction is taking place by CRM drug mechanisms that target aging pathways rather than through glycemic control of diabetes. In the long run, the approaches to late onset diseases in general will become much more powerful if we can use parallel approaches that simultaneously target both the aging processes going on and the disease-specific pathways going on. In the literature we see caloric restriction mimetic drugs metformin, rapamycin and resveratrol all being explored for their ability to target points in aging pathways in ways that can impact the risk of a variety of late-onset diseases, so it will be important for those interested in the risk factors affecting late onset diseases to pay attention to how caloric restriction mimetic drugs might be altering risk for those late onset diseases.
AHA Journals, Author Interviews, Compliance, Duke, Heart Disease / 06.06.2015

Robin Mathews, MD Duke Clinical Research Institute Duke University Medical Center Durham, NCMedicalResearch.com Interview with: Robin Mathews, MD Duke Clinical Research Institute Duke University Medical Center Durham, NC Medical Research: What is the background for this study? What are the main findings? Dr. Mathews: Though treatment for patients with an acute myocardial infarction with evidence based therapies has increased significantly over the years, adherence to these therapies after discharge remain sub optimal. We used a validated instrument, the Morisky scale, to assess patient medication adherence.  We found that in a contemporary population of 7,425 patients across 216 hospitals, about 30% of patients were not adherent to prescribed cardiovascular medications as early as 6 weeks after discharge. Patients with low adherence were more likely to report financial hardship as well as have signs of depression. In addition, we found that patients who had follow up arranged prior to discharge and those that received explanations from the provider on the specific medications, were more often adherent to therapies. There was a non significant increase in risk of death or readmission at 2 months (HR [95% CI]: 1.35 [0.98-1.87]) among low adherence patients.
Author Interviews, Outcomes & Safety, Surgical Research / 06.06.2015

Dr. Janet Martin PharmD, PhD Director, Medical Evidence, Decision Integrity & Clinical Impact (MEDICI) Assistant Professor, Department of Anesthesia & Perioperative Medicine and Department of Epidemiology & Biostatistics Schulich School of Medicine & Dentistry, Western University London, ON Canada MedicalResearch.com Interview with: Dr. Janet Martin PharmD, PhD Director, Medical Evidence, Decision Integrity & Clinical Impact (MEDICI) Assistant Professor, Department of Anesthesia & Perioperative Medicine and Department of Epidemiology & Biostatistics Schulich School of Medicine & Dentistry, Western University London, ON Canada Medical Research: What is the background for this study? What are the main findings? Response: There remains some scepticism regarding the effectiveness of the safe surgery checklist (SSCL) to tangibly improve patient safety in the real world setting, especially with respect to relative benefits in high-income versus lower-income settings. In general, push-back has been related to surgical teams doubting the power of a simple checklist to make significant impact for surgical settings. Despite their deceptive simplicity, checklists can be powerful tools to deal with the sheer volume of information that must be addressed in sequence in order to support safe surgery. The objective of our study was to determine, through meta-analysis, whether clinically-relevant outcomes after implementation of the WHO Safe Surgery Checklist (SSCL) in the clinical trial setting and in the real world setting are improved, and whether greater benefit occurs in low-middle income countries (LMICs) than in high income countries (HICs). A total of 13 studies (262,970 patients) met the inclusion criteria, including 12 cohort studies and 1 randomized trial. For SSCL versus control, the odds of death was significantly reduced by 21% (OR 0.79, 95%CI 0.67-0.93; p=0.003). The odds of surgical site infection was reduced by 28% (OR 0.72, 95%CI 0.62-0.84; p=0.001). Similarly, overall postoperative complications were significantly reduced by 30% (OR 0.70, 95%CI 0.59-0.82; p=0.009). While HIC and LMICs both experienced reductions in death, surgical site infections, and overall complications, the magnitude of reduction was generally greater for LMICs than in HICs. Sub-analysis by study design demonstrated generalizability between the clinical trial setting and the real world setting.
Author Interviews, Colon Cancer, Genetic Research, JAMA, Johns Hopkins / 05.06.2015

MedicalResearch.com Interview with: Timothy Michael Pawlik, M.D., M.P.H., Ph.D. Chief, Division of Surgical Oncology Professor of Surgery John HopkinsMedicalResearch.com Interview with: Timothy Michael Pawlik, M.D., M.P.H., Ph.D. Chief, Division of Surgical Oncology Professor of Surgery John Hopkins Medical Research: What is the background for this study? Dr. Pawlik: The prognosis of patients operated on for colorectal liver metastasis (CRLM) is currently defined by various “traditional” clinicopathologic factors. However the insight that they provide is incomplete. KRAS is the most common oncogene of the RAS family and is reported in up to 30 to 40% of patients with colorectal liver metastasis. As a result, KRAS mutational status  recently attracted a lot of attention as a potential prognostic factor in colorectal liver metastasis. However, overall mutant KRAS status (compared to wild type) correlated with worse survival only in some studies. We hypothesized that the specific KRAS activating mutations (codon 12 and codon 13) confer different biologic behaviors to the tumor and in turn, account for different (if any) prognostic values. The different proportions of each KRAS specific mutation could determine whether the overall mutational status would be associated with worse survival. In our view, the different proportions of specific mutations in various cohorts could account for the variability of the outcomes in different studies. Medical Research: What are the main findings? Dr. Pawlik: Our results showed that only codon 12 KRAS mutations conferred a worse prognosis whereas codon 13 ones did not. Furthermore, we examined the different point mutations that constitute codon 12 mutations and we found that among G12A, G12D, G12V, G12C and G12S KRAS point mutations, only G12V and G12S were independent prognostic factors of worse survival. That confirmed our hypothesis that only some of the point mutations do have a significant prognostic role and that the relative incidence of those mutations could determine if overall KRAS mutational status would be associated with worse survival in a certain cohort.
Author Interviews, HIV, Sexual Health, UCSD / 05.06.2015

MedicalResearch.com Interview with: Dr. Martin Hoenigl Center for AIDS Research University of California, San Diego Medical Research: What is the background for this study? What are the main findings? Dr. Hoenigl: Although men who have sex with men (MSM) represent a dominant risk group for human immunodeficiency Virus, the risk of HIV infection within this population is not uniform. Characterizing and identifying the MSM at greatest risk for incident HIV infection might permit more focused delivery of both prevention resources and selection of appropriate interventions, such as intensive counseling, regular HIV screening with methods that detect acute infection (ie, nucleic acid amplification test), and antiretroviral preexposure prophylaxis (PrEP). By using data collected at a single HIV testing encounter from 8326 unique MSM were analyzed, including 200 with AEH (2.4%), we were able to create the San Diego Early Test (SDET) risk score. The SDET score consist of four risk behavior variables which were significantly associated with an AEH diagnosis (ie, incident infection) in multivariable: condomless receptive anal intercourse (CRAI) with an HIV-positive MSM (3 points), the combination of CRAI plus 5 or more male partners (3 points), 10 or more male partners (2 points), and diagnosis of bacterial sexually transmitted infection (2 points), all as reported for the prior 12 months. The SDET risk score is deployed as a freely available tool at http://sdet.ucsd.edu.
Author Interviews, Weight Research / 05.06.2015

MedicalResearch.com Interview with: Aidan Gribbon M.Sc., CSEP-CEP From the Healthy Active Living and Obesity Research Group Children’s Hospital of Eastern Ontario Research Institute Ottawa, Ontario, Canada Medical Research: What is the background for this study? Response: The background for the study is that sedentary pursuits, such as video games, are omni-present in the daily lives of adolescents. Manufacturers of active video games (AVG) have been marketing them as a ‘healthy’ alternative to seated video games, with the possibility of preventing/treating obesity in this age group. Although, active video games have been shown to acutely increase energy expenditure over their seated counterparts, no study has examined their compensatory adjustments in energy expenditure or energy intake. Medical Research: What are the main findings? Response: The main finding of this paper was that although active video games are not associated with an increased food intake, they are compensated for by a decrease in physical activity such that their benefit of a reduction in the energy gap underlying weight gain is offset within 24 hours.
Author Interviews, Weight Research / 05.06.2015

Nia S. Mitchell, MD, MPH Assistant Professor Division of General Internal Medicine Department of Medicine University of Colorado Anschutz Medical CampusMedicalResearch.com Interview with: Nia S. Mitchell, MD, MPH Assistant Professor Division of General Internal Medicine Department of Medicine University of Colorado Anschutz Medical Campus Medical Research: What is the background for this study? What are the main findings? Dr. Mitchell: Despite decades of obesity research two issues remain elusive in weight management: significant, long-term weight loss and weight loss maintenance and widely accessible programs. There are numerous weight loss programs out there, but there is little evidence of the long-term effectiveness of many programs. Furthermore, these programs may not be accessible to the general population because they are too expensive and may not be geographically available. I chose to evaluate the Take Off Pounds Sensibly (TOPS) program because I thought it had the potential to address these issues. TOPS is a nationally-available, nonprofit, low-cost, peer-led weight loss program. It costs only $92 per year--$32 is the annual fee plus local chapter dues that average about $5 per month--and any four people can start a TOPS chapter, so it can be implemented and disseminated widely. The main objective of this study was to determine the weight change for individuals who consecutively renewed their membership in TOPS. We looked at people who joined TOPS from 2005 to 2011, so they could have been followed for up to seven years. We found that people who join TOPS and consecutively renew their annual membership can lose a clinically significant amount of weight and maintain the weight loss for up to seven years. Clinically significant weight loss is defined as weight loss of at least 5% of initial weight, because with a 5% weight loss people with weight-related medical conditions, such as diabetes, can see an improvement in their conditions. Therefore, a diabetic who weighs 200 pounds may see an improvement in her blood sugar control if she loses 10 pounds. In our study, fifty percent of individuals had clinically significant weight loss in their first year in the program, and 62% of those renewed their annual membership consecutively for seven years had clinically significant weight loss at seven years. This was exciting because many people who lose weight tend to gain it back. I often say that the unfortunate natural history of weight loss tends to be weight re-gain. However, the majority of these individuals maintained a clinically significant weight loss.
AACR, Author Interviews, Breast Cancer, Cancer Research, Nutrition / 05.06.2015

MedicalResearch.com Interview with: Ying Wang, PHD | Senior Epidemiologist American Cancer Society, Inc. Atlanta, Georgia Dr. Wang: Several epidemiologic studies and a recent large pooled analysis suggest that higher blood levels of carotenoids, a group of lipid-soluble pigments that are rich in colorful fruits and vegetables, are associated with lower breast cancer risk. What remains unclear is whether or not the effect of carotenoids on breast cancer differ by estrogen receptor status, tumor stage, BMI, and smoking status. We examined plasma carotenoids and breast cancer risk overall, and by aforementioned tumor and participant characteristics in a cohort of 992 postmenopausal women. We found that higher pre-diagnosis plasma α-carotene, but not other subtypes or total carotenoids, was significantly associated with lower invasive breast cancer risk. The inverse association of α-carotene with breast cancer risk seems stronger for estrogen receptor positive tumors than for estrogen receptor negative tumors. There is a suggestive inverse association of total plasma carotenoid levels and breast cancer among ever smokers but not among never smokers.
Author Interviews, Infections, Pulmonary Disease / 05.06.2015

Dr. Nelson Lee MBBS(HK),MD(CUHK),FRCP(Lond),FRCP(Edin),FHKCP,FHKAM(Med) Daniel Yu Professor of Infectious Diseases Head, Division of Infectious Diseases, Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong. Hon. Consultant, Prince of Wales Hospital, Hong KongMedicalResearch.com Interview with: Dr. Nelson Lee BBS(HK),MD(CUHK),FRCP(Lond),FRCP(Edin),FHKCP,FHKAM(Med) Daniel Yu Professor of Infectious Diseases Head, Division of Infectious Diseases, Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong. Hon. Consultant, Prince of Wales Hospital, Hong Kong Medical Research: What is the background for this study? What are the main findings? Dr. Lee: Respiratory syncytial virus (RSV) is increasingly recognized as an important cause of severe respiratory-tract infections in older adults, resulting in excessive hospitalizations and deaths annually. At present, no established antiviral treatment is available. The slow progress in therapeutics development is limited by the poor understanding of the clinical manifestations, severity, virologic changes, and pathophysiology in adult RSV diseases. To address the knowledge gap, we conducted a prospective study to look at the lower-respiratory complications, progression to respiratory failure, and their relationships to genomic viral loads in adults hospitalized for confirmed RSV infections. We found that among 123 RSV patients, nearly 90% had lower respiratory tract complications (acute bronchitis/bronchiolitis, radiographic pneumonia, exacerbation of underlying airway diseases, or their combinations), 53% developed respiratory insufficiency requiring bronchodilators and supplemental oxygen, 16% required assisted ventilation, and 12% were admitted to ICU or died. High viral RNA concentration was detected in their respiratory samples, including in patients who had onset longer than 2 days (>7 log10copies/mL). Viral load was associated with disease severity and development of respiratory insufficiency (about 40% increase in risk per log RNA increase).
Author Interviews, Fertility, Genetic Research, NEJM, University of Pittsburgh / 04.06.2015

Alexander N Yatsenko, MD, PhD Assistant Professor, Department of OBGYN and Reproductive Science, Magee-Womens Research Institute, University of Pittsburgh, PA Pittsburgh, PA 15213MedicalResearch.com Interview with: Alexander N Yatsenko, MD, PhD Assistant Professor, Department of OBGYN and Reproductive Science, Magee-Womens Research Institute, University of Pittsburgh, PA Pittsburgh, PA 15213 Medical Research: What is the background for this study? What are the main findings? Dr. Yatsenko: The known causes of male infertility not due to physical obstruction are usually because of sex-chromosome defects, such as deletions of the Y chromosome or duplication of the entire X chromosome in Klinefelter syndrome. Eight times out of 10, conventional genetic testing doesn’t reveal a chromosomal problem and infertility is considered idiopathic. We wanted to try to find other genetic reasons for the problem. We found a deletion in part of the DNA coding of the testis-expressed gene 11 (TEX11) on the X-chromosome, which men inherit from their mothers. The alteration caused meiotic arrest, meaning the precursor cells could not properly undergo meiosis. We also found similar TEX11 gene mutations and meiotic arrest in two out of 49 men diagnosed with idiopathic azoospermia in Pittsburgh or at a Poland infertility clinic, and in five out of 240 infertile men assessed at a collaborating Andrology clinic in Muenster, Germany. These genetic findings were confirmed on protein level using patients’ testis biopsies.
Author Interviews, CDC, HIV / 04.06.2015

MedicalResearch.com Interview with: Sandra Schwarcz, MD Senior HIV epidemiologist San Francisco Department of Public Health Medical Research: What is the background for this study? What are the main findings? Dr. Schwarcz: AIDS opportunistic illnesses continue to occur despite effective antiretroviral therapy. Although previous studies examined survival following a diagnosis of an opportunistic illness, there are few recent reports that are population-based. The San Francisco Department of Public Health has the only population-level data on the occurrence of and survival following opportunistic illnesses and use of antiretroviral therapy among persons reported with HIV in the United States. By measuring survival following the occurrence of opportunistic illnesses, we were able to document that survival following opportunistic illnesses has improved with better HIV treatment. However, opportunistic illnesses continue to occur and carry substantial mortality risk. Even in this era of effective HIV therapy, we found that 35% of persons who developed an opportunistic illness died within five years of their diagnosis and some opportunistic illnesses such as brain lymphoma and  progressive multifocal leukoencephalopathy remain highly lethal.
Annals Internal Medicine, Author Interviews, Beth Israel Deaconess, Hospital Readmissions / 04.06.2015

MedicalResearch.com Interview with: Kelly L. Graham, MD, MPH Instructor in Medicine Harvard Medical School Division of General Medicine and Primary Care Beth Israel Deaconess Medical Center Medical Research: What is the background for this study? What are the main findings? Dr. Graham: 30-day readmissions have become a standard quality metric used to represent inpatient quality of care and unnecessary healthcare utilization.  Effective 10/1/2009, hospitals with excess 30-day readmissions have been faced with financial penalties.  Experts have questioned the validity of this metric, and have raised concerns about the potential unintended consequence of creating health disparities, as critical access hospitals caring for the most socioeconomically burdened patients have faced the highest penalties. We were interested to see if factors associated with readmissions in the early part of the 30 day window (0-7 days post-discharge) differed from those associated with the later window (8-30 days post-discharge), ultimately attempting to better understand the "pathophysiology" of a readmission. Our findings suggest that early readmissions are associated with many factors, including those related to the index admission (acute illness burden and suboptimal discharge timing), and factors that are not related to the index hospitalization, such as chronic illness burden and social determinants of health.  In contrast, late readmissions were only associated with chronic illness burden and social determinants of health.
Author Interviews, Diabetes, mBio, Microbiome / 04.06.2015

Patrick M. Schlievert Ph.D Professor and Chair Department of Microbiology Carver College of Medicine Iowa City Iowa 52242MedicalResearch.com Interview with: Patrick M. Schlievert Ph.D Professor and Chair Department of Microbiology Carver College of Medicine Iowa City Iowa 52242 Medical Research: What is the background for this study? Dr. Schlievert:
  1. As people become obese and enter pre-diabetes type II, there is a gut microbiome shift in bacteria from Bacteroidetes to Firmicutes. A dominant pathogenic Firmicute in humans is Staphylococcus aureus.
  2. As people become obese, their skin becomes wetter due to enhanced sweating upon exertion and the presence of more skin folds. These, plus mucous membranes have enhanced Staphylococcus aureus numbers, such that 100% of people become colonized and numbers of the bacterium rise to 1013 per person. This number of bacteria is like a cubic inch of margarine spread across the skin and mucous membranes.
  3. All pathogenic Staphylococcus aureus bacteria make and secrete a family of toxins called superantigens, including toxic shock syndrome toxin and staphylococcal enterotoxins. In high amounts (0.1 μg/human), these toxins can be lethal, causing toxic shock syndrome. At lower concentrations, the same superantigen toxins cause total body inflammation without lethality.
  4. In order to show that a microbes causes human disease, it is necessary to fulfill Koch’s postulates:
    1. Must associate human symptoms with a particular disease,
    2. Must isolate a potentially causative bacterium that is always present when the disease is present.
    3. Must produce the disease in an experimental animal.
    4. Must re-isolate the microbe from the experimental animal and re-cause the disease in another animal.
Medical Research: What are the main findings? Dr. Schlievert: We have fulfilled Koch’s postulates, showing that Staphylococcus aureus and its superantigen toxins cause type II diabetes.
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