Author Interviews, JAMA / 07.01.2015

Sakthivel Sadayappan, PhD, MBA Associate Professor Department of Cell and Molecular Physiology Loyola University Chicago Health Sciences Division Maywood, IL 60153-5500, USA.MedicalResearch.com Interview with: Sakthivel Sadayappan, PhD, MBA Associate Professor Department of Cell and Molecular Physiology Loyola University Chicago Health Sciences Division Maywood, IL  60153-5500, USA. MedicalResearch: What is the background for this study? What are the main findings? Dr. Sadayappan: Hypertrophic cardiomyopathy (HCM) is the most common form of genetic heart defect, affecting 1 in 500 people in the general population. HCM results in excessive thickening of heart muscle without an obvious cause, such as hypertension or exercise stress. Often, HCM results in sudden cardiac arrest as a result of cardiac arrhythmia. Electrocardiogram, echocardiogram and cardiac magnetic resonance imaging are commonly used to diagnose HCM. However, genetic defects in more than 10 genes could also cause HCM, and standard screening for these genes is readily available. Notwithstanding our ability to diagnose the disease, a major challenge arises from its heterogeneity. That is, individuals with the same genetic defect often present with different symptoms, ranging from no symptoms at all to severe heart enlargement. Therefore, treatment options vary from person to person, and, at present, no permanent cure is available for HCM. Beta-blockers, calcium antagonists and anti-arrhythmic drugs are currently being used to manage the disease. However, scientists must discover the reasons that explain why some people experience more severe symptoms than others. In today’s modern world, people are afflicted with stresses including, for example, diabetes, hypertension, hyperlipidemia (high cholesterol), and alcoholism. Therefore, we have hypothesized that additional cardiac stresses can aggravate the onset of Hypertrophic cardiomyopathy. To prove our hypothesis, we used a mouse model having a genetic defect known to affect cardiac muscle contractility. We subjected these mice to severe cardiac stress over a period of 12 weeks. Compared with normal mice, we found that the mutant mice showed significant cardiac abnormalities, including those associated with HCM. Thus, this demonstrated, for the first time, that additional cardiac stress applied in the presence of known genetic defects exacerbates the onset of HCM. (more…)
Author Interviews, Diabetes, Lancet / 07.01.2015

Ahmad Haidar PhD Institut de Recherches Cliniques de Montreal Montreal, QC, CanadaMedicalResearch.com Interview with: Ahmad Haidar PhD Institut de Recherches Cliniques de Montreal Montreal, QC, Canada Medical Research: What is the background for this study? What are the main findings? Response: We published a study in 2013 (Canadian Medical Association Journal 185.4 (2013): 297-305) where we did the first randomized trial comparing dual-hormone artificial pancreas against conventional pump therapy. We showed spectacular reduction in hypoglycemia (8-fold) with the artificial pancreas, but the first question people asked: Out of the improvement you showed, how much is due to simply closing the loop between the glucose sensor and the insulin pump, and how much is due to adding glucagon? In other words: if you just close the loop with insulin alone and use an advanced dosing algorithm, you may get a very high reduction of hypoglycemia that glucagon may not be needed (glucagon is associated with increased cost and device complexity). We were not able to answer this question with our study design. Since then, there have been other studies by other groups either comparing single-hormone artificial pancreas vs conventional pump therapy, or comparing dual-hormone artificial pancreas vs conventional pump therapy, and most of these studies showed improvement of both artificial pancreas systems compared to conventional pump therapy. However, there has been no study comparing the three interventions to allow us to quantify the relative benefits of simply closing the loop between glucose sensor and insulin pump versus adding glucagon to the system. Quantifying the relative benefits of glucagon is important given the increased cost and device complexity of the dual-hormone artificial pancreas. So our study compared the three interventions, and is the first study to do so. (more…)
Author Interviews, Brigham & Women's - Harvard, Nursing, Occupational Health / 07.01.2015

Eva Schernhammer, MD, DrPH Associate Professor of Medicine Brigham and Women's Hospital and Harvard Medical School Associate Professor of Epidemiology Harvard School of Public Health Channing Division of Network MedicineMedicalResearch.com Interview with: Eva Schernhammer, MD, DrPH Associate Professor of Medicine Brigham and Women's Hospital and Harvard Medical School Associate Professor of Epidemiology Harvard School of Public Health Channing Division of Network Medicine Medical Research: What is the background for this study? What are the main findings? Prof. Schernhammer: The study is an observational cohort study of over 70,000 registered nurses from within the US who reported the total number of years they had worked rotating night work and were followed for several decades. We examined overall mortality in these women, and observed significantly higher overall mortality, as well as higher mortality from cardiovascular disease in women with several years of rotating night shift work, compared to nurses who had never worked night shifts. There was also some suggestion for modest and non-significant increases in mortality from a few cancers. The study is unique due to its size, the fact that all participants were nurses (eliminating potential biases arising from differing occupational exposures), the long follow-up, and the possibility to take into account most known risk factors for chronic diseases that we currently know of (all of this information has been collected regularly and repeatedly).  (more…)
Author Interviews, Heart Disease / 07.01.2015

Dr. Kongkiat Chaikriangkrai MD Department of Medicine, Houston Methodist Hospital Houston, TX 77030 MedicalResearch.com Interview with: Dr. Kongkiat Chaikriangkrai MD Department of Medicine, Houston Methodist Hospital Houston, TX 77030 Medical Research: What is the background for this study? Dr. Chaikriangkrai: Coronary computed tomography angiography (CCTA) and coronary artery calcium score are well known to be useful tools for patients suspected for coronary artery disease.  Although both imaging studies are similar in many ways (e.g. CT-based studies, anatomical evaluation of coronary artery disease, etc.), they are completely independent tests that measure different aspects of coronary artery. Furthermore, each test also requires its own separate scan. In earlier times, calcium score testing was routinely performed prior to CCTA since high calcium score can affect diagnostic accuracy of CCTA. Therefore, CCTA may not be the best option for patients who are known to have high calcium score and other tests along the line can be further considered. However; there have been debates over the need for calcium score scan in this setting alone without enough evidence of additive prognostic benefit of measuring calcium score on top of CCTA due to concerns of extra radiation exposure from performing CT scanning twice. From this very clinical question, our study was designed to examine whether there was any additional benefit of measuring calcium score over CCTA alone (i.e. Does a patient with high calcium score have worse prognosis than a patient with lower calcium score given that both have similar CCTA results?) Medical Research: What are the main findings? Dr. Chaikriangkrai: Our study found that both CCTA and calcium score testing carried its own prognostic value which was independent from each other. Furthermore, measuring calcium score also gave extra ability to predict bad clinical outcomes on top of the information obtained from CCTA alone in patients suspected for coronary artery disease (i.e. A patient with high calcium score did have worse prognosis than a patient with lower calcium score given that both have similar CCTA results). (more…)
Author Interviews, CDC, Smoking / 07.01.2015

dr-mary-puckettMedicalResearch.com Interview with: Mary Puckett, PhD CDC Division of Cancer Prevention and Control. Medical Research: What is the background for this study? What are the main findings? Dr. Puckett: Smoking causes 480,000 deaths per year in the United States. Quitline services are offered by all 50 states. In addition to telephone quitlines, 96% of states also offer some form of web-based cessation service. Seven months after enrollment in the study, participants from four state quitlines were asked if they had smoked in the past 30 days as a measure of their smoking cessation success. Participants who used quitlines and web-based services in combination had higher rates of smoking cessation than participants who used only one of these services. (more…)
Author Interviews, Breast Cancer, Geriatrics / 07.01.2015

MedicalResearch.com Interview with: Pamela Vacek, PhD Research Assistant Professor Department of Pathology Medical Biostatistics Unit, College of Medicine University of Vermont,  Burlingon, Vermont Medical Research: What is the background for this study? What are the main findings? Dr. Vacek: Clinical trials to evaluate the effectiveness of screening mammography have focused primarily on women under age 70 and, consequently, its benefit for older women is uncertain. However, many believe that the benefit of screening mammography diminishes as women age and acquire other health problems, because they are less likely to live long enough for any detected breast cancer to have a clinical impact. To gain insight into this, we followed approximately 20,000 women aged 70 and older for an average of 10 years to examine their mammography use, cancer detection and survival. We found that screening mammography use declined steadily (9% per year) after age 70, but this was not accompanied by decline in the incidence of invasive breast cancer. Hence, as the women aged breast cancer was more likely to be detected clinically than by screening. The clinically detected tumors were significantly larger and of more advance stage and were associated with poorer overall survival, for all but the oldest and most infirm women. We also found that the use of breast conserving surgery as the only treatment for early stage cancer increased markedly with age and was associated with shorter survival compared to women receiving radiation or mastectomy. (more…)
Author Interviews, Colon Cancer, Compliance / 07.01.2015

Dr Siu Hing Lo Research Associate in Health Psychology UCL Research Department of Epidemiology and PublicMedicalResearch.com Interview with: Dr Siu Hing Lo Research Associate in Health Psychology UCL Research Department of Epidemiology and Public Medical Research: What is the background for this study? What are the main findings? Dr. Lo: Most types of population-based cancer screening – such as the Faecal Occult Blood (FOB) test – require repeat participation to be effective. The Faecal Occult Blood test is a stool test that typically needs to be self-completed every two years. This study investigated predictors of repeat participation in the NHS Bowel Cancer Screening Programme (BCSP). Late kit return, a definitive abnormal [FOB test] result and failure to comply with a follow-up colonoscopy in a previous screening episode were consistently and independently associated with lower repeat uptake. (more…)
Author Interviews, Heart Disease, JAMA, University of Pittsburgh / 07.01.2015

Inmaculada Hernandez, PharmD PhD Student, Health Services Research and Policy Deparment of Health Policy and Management Graduate School of Public Health University of Pittsburgh Pittsburgh, PA 15261MedicalResearch.com Interview with: Inmaculada Hernandez, PharmD PhD Student, Health Services Research and Policy Deparment of Health Policy and Management Graduate School of Public Health University of Pittsburgh Pittsburgh, PA 15261 Medical Research: What is the background for this study? What are the main findings? Response: The approval of dabigatran was considered a major contribution to the therapeutic arsenal of anticoagulants since warfarin, whose therapeutic management is complicated, was the only oral anticoagulant approved before 2011. Clinicians therefore considered dabigatran a very promising drug; however, the safety warnings released by the regulatory agencies and the reports of bleeding published in 2011 raised concerns about the safety profile of dabigatran. By the time we initiated our study, the FDA had concluded that dabigatran was associated with similar rates of bleeding than warfarin. However, the results of this observational study were not adjusted by patient characteristics. We therefore compared the risks of bleeding with dabigatran and warfarin adjusting for patient characteristics and using propensity score methods to mitigate selection biases, which observational studies are sensitive to. We found that dabigatran was associated with a higher risk of major bleeding and gastrointestinal bleeding than warfarin. However, the risk of intracranial bleeding was lower with dabigatran. In addition, we found that the increased risk of bleeding with dabigatran was specially higher for African Americans and for patients with chronic kidney disease. (more…)
Author Interviews, Toxin Research / 06.01.2015

Rick Vetter (retired) Department of Entomology Univ. Calif. Riverside Riverside, CA 92521MedicalResearch.com Interview with: Rick Vetter   (retired) Department of Entomology Univ. Calif. Riverside Riverside, CA  92521 Medical Research: What is the background for this study? What are the main findings? Response: Regarding the spider toxinology field, many misconceptions have been voiced over the years with statements being made in the medical literature which are tenable sounding explanations offered by well-meaning physicians, however, when given further scrutiny, are not supported by the data.  An example of this is the platitude from years ago (and sometimes still today) that brown recluse spider bites are feasible diagnoses anywhere in North America because the spiders CAN get transported around.  However, these authors never actually show that brown recluse spiders ARE frequently transported around in sufficient numbers such that they are tenable culprits in necrotic skin lesions. The evidence developed in the last decade regarding this situation shows that brown recluses DO NOT get transported often, DO NOT establish extra-indigenous populations often and they are not likely etiologies for necrotic skin lesions outside of their indigenous range.  Similarly, a commonly heard statement over the decades is that spiders are likely vectors of bacterial skin lesions.  Several studies have swabbed the fangs and mouthparts of spiders, found bacteria and proudly proclaim the association between spider bites and bacterial infections.  However, these same authors never actually prove that verified spider bites result in bacterial transfer to humans. This current study was instigated in part due to statements made in the 1990s by the late Dr. Philip Anderson, Missouri dermatologist and brown recluse spider bite expert, that recluse spider bites are never infected even in non-medicated patients.  So if spiders actually can vector bacteria, then a data-mining of the vast literature on spider bites worldwide should show significant bacteria association in the form of infected skin lesions as signs of envenomation.  In contrast, there is almost a complete absence of reports of infection when one examines the thousands of spider bites that include a vast array of medically important spiders including the widows, recluses, armed or wandering spiders of South America, Sydney funnel web spiders, wolf spiders, yellow sac spiders, as well as studies involving a random conglomeration of species.  A mechanism to explain this lack of bacterial vectoring may lie in the fact that the venom of spiders (as well as other venomous animals) has antibacterial and antimicrobial capabilities which may function evolutionarily to prevent bacterial transfer from prey to spider in bites. (more…)
Author Interviews, PNAS / 06.01.2015

Akiko Iwasaki PhD Departments of Immunobiology and Laboratory Medicine, Yale University School of Medicine New Haven, CT 06520 MedicalResearch.com Interview with: Akiko Iwasaki PhD Departments of Immunobiology and Laboratory Medicine, Yale University School of Medicine New Haven, CT 06520 Medical Research: What is the background for this study? What are the main findings? Dr. Iwasaki: Since the 1960's, scientists have known that the rhinovirus, the common cold virus, replicates preferably at the cooler temperature found in the nose (33C) but not at the core body temperature found in the lungs (37C). However, the underlying mechanisms were not known. We focused on the host immune response as a possible factor that enables rhinovirus to replicate in the cooler temperature. Indeed, we found that by incubating airway cells isolated from mice at the cooler temperature, immune response to the virus was impaired. By using airway cells from knockout mice from which key innate sensor pathway or interferon receptor is deleted, we found that the virus now replicates even at the core body temperature of 37C. These experiments showed us that the rhinovirus replication is blocked at the higher temperature because of a more efficient immune defense at the core body temperature. (more…)
Author Interviews, JAMA, Mental Health Research, University of Pittsburgh / 06.01.2015

Dr. Brent David MD Academic Chief, Child and Adolescent Psychiatry at Western Psychiatric Institute and Clinic Professor of Psychiatry, Pediatrics & Epidemiology University of Pittsburgh School of Medicine MedicalResearch.com Interview with: Dr. Brent David MD Academic Chief, Child and Adolescent Psychiatry at Western Psychiatric Institute and Clinic Professor of Psychiatry, Pediatrics & Epidemiology University of Pittsburgh School of Medicine Medical Research: What is the background for this study? Dr. David: There are now many studies that show that suicide and suicidal behavior run in families. A family history of suicide increases the risk for suicide attempt and vice versa, so that we believe that the trait that is being passed from parent to child is a tendency to act on suicidal thoughts, resulting in either an attempt or an actual suicide. However, what was not not known was the mechanism by which parents transmitted the risk of suicidal behavior to their children, and what the precursors of suicidal behavior looked like in individuals who were at risk for suicidal behavior, but had not yet engaged in a suicide attempt. Therefore, we conducted a high-risk family study, in which studied the children of parents with mood disorders, about half of whom also had a history of a suicide attempt. Medical Research: What are the main findings? Dr. David: We followed 701 offspring for an average of 5.6 years, and found that those offspring whose parents had made a suicide attempt were almost 5 times more likely to make a suicide attempt themselves, even after accounting for mood disorder in parent and child and past suicidal behavior in the offspring. We found three main pathways by which suicidal behavior was passed from parent to child:
  • Parental mood disorder was transmitted to children, and that was a precursor of a suicide attempt.
  • Parent attempt was related to offspring impulsive aggression, which in turn increased the risk for mood disorder, which then increased the likelihood of a suicide attempt. (We define impulsive aggression as a tendency to response with hostility or aggression to provocation or frustration.
  • Finally, there is a direct path from parent attempt to child attempt, with no precursors or intervening variables.
Implications for clinicians and patients:
  • First, these findings highlight that a parental history of a suicide attempt increases the risk of an attempt in the parent's children. Clinicians who take care of adults who have attempted suicide should make sure that children are assessed as they are at increased risk and that parents know what to look for in the future in order to get their children into needed treatment.
  • Second, the transmission of suicidal behavior from parent to child can be attenuated by preventing the transmission of mood disorder, and of impulsive aggression. There are now evidence based interventions that reduce the likelihood of a child of a depressed parent from developing depression; these treatment involve cognitive behavioral principles and may also involve family interventions. There are now good family-based interventions for impulsive aggression that can attenuate the risk that the child or adolescent will go on to develop a mood disorder, which in turn greatly increases the risk for suicidal behavior.
(more…)
Author Interviews, JAMA, Schizophrenia / 06.01.2015

MedicalResearch.com Interview with: Toshiaki A. Furukawa, MD, PhD Professor and Chair, Department of Health Promotion and Human Behavior Professor, Department of Clinical Epidemiology Kyoto University Graduate School of Medicine / School of Public Health, Yoshida Konoe-cho, Sakyo-ku, Kyoto Japan Medical Research: What is the background for this study? What are the main findings? Dr. Furukawa: The efficacy of antidepressants in the treatment of depressive disorders has recently been called into question as some studies suggested they may have less efficacy for the milder spectrum of the disorder. It is not known if the same would apply to antipsychotics, which constitute the mainstay in the treatment of schizophrenia. We found that, in patients with schizophrenia with acute treatment as well as with predominant negative symptoms, the severer the baseline severity, the greater the magnitude of the benefit from the active treatment in comparison with placebo. (more…)
Author Interviews, JAMA, OBGYNE / 06.01.2015

Dr. Jennifer Kawwass MD Assistant Professor Emory UniversityMedicalResearch.com Interview with: Dr. Jennifer Kawwass MD Assistant Professor Emory University Medical Research: What should clinicians and patients take away from your report? Dr. Kawwass: This study affirms that Assisted Reproductive Technology treatment is relatively safe and that reported complications remain rare.  In the US from 2000-2011, autologous and donor ART procedures were associated with low reported stimulation and surgical complication risks; no concerning trends or patterns were identified. Ovarian hyperstimulation syndrome (OHSS) was the most frequently reported complication among autologous and donor cycles, though less frequent in donor cycles.  Obstetric mortality which may or may not be related to Assisted Reproductive Technology was rare. (more…)
Author Interviews, JAMA, Pediatrics, UCSF / 06.01.2015

Yvonne Wu MD Professor of Clinical Neurology and Pediatrics UCSF School of MedicineMedicalResearch.com Interview with: Yvonne Wu MD Professor of Clinical Neurology and Pediatrics UCSF School of Medicine   Medical Research: What is the background for this study? What are the main findings? Dr. Wu: Newborn infants commonly have elevated bilirubin levels, manifested as jaundice, because the body's mechanisms for breaking down bilirubin have not yet fully matured.  Although high bilirubin levels are almost always well tolerated, extremely high bilirubin levels may lead to brain injury, or kernicterus, which in turn can cause a very severe form of cerebral palsy.  When bilirubin levels are extremely high, or when bilirubin levels remain high despite phototherapy, it is recommended that an exchange transfusion be performed to prevent brain injury and cerebral palsy.  The American Academy of Pediatrics (AAP) has published recommendations on when an exchange transfusion should be performed, based on bilirubin level, age of infant and other clinical factors.  However, no previous study had examined the actual risk of cerebral palsy in infants whose bilirubin levels exceeded the exchange transfusion thresholds. Among 500,000 newborns born at Kaiser Permanente Northern California over a 17-year period, we found 1833 who had at least one bilirubin level above the AAP exchange transfusion level.  There were only 3 cases of cerebral palsy due to kernicterus in this group, even though only 42 (2.3%) of them had received exchange transfusions.  All 3 infants had bilirubin levels at least 5 mg/dL above the AAP exchange transfusion threshold and all 3 infants had 2 or more other risk factors for brain damage, including prematurity, sepsis, hypoxia and the hereditary blood disorder G6PD deficiency.  We did not identify any cases of kernicterus among otherwise well term babies, even at bilirubin levels that exceeded the AAP exchange transfusion threshold. (more…)
Author Interviews, JAMA, Mental Health Research, UCSF / 06.01.2015

Dr. Georges Naasan MD Neurologist, Clinical Instructor UCSF Memory and Aging CenterMedicalResearch.com Interview with: Dr. Georges Naasan MD Neurologist, Clinical Instructor UCSF Memory and Aging Center Medical Research: What is the background for this study? What are the main findings? Dr. Naasan: Degenerative diseases of the brain can lead to dysfunction in judgment, emotional processing, social decorum and self-awareness. In turn, such dysfunctions may result in criminal behavior that appears for the first time in middle-aged adults or even later in life. We studied 2397 patients from the Memory and Aging Center at UCSF and found 204 (8.5%) that had a criminal behavior as part of their illness. The large majority of these patients were patients with a specific type of neurodegenerative disease called behavioral variant of frontotemporal dementia, followed by a group of people with a disease called semantic variant of primary progressive aphasia. People with Alzheimer's disease, a disease that does not usually interrupt the functions mentioned above, were the least likely to exhibit criminal behavior. The common manifestation of criminal behaviors in people with the behavioral variant frontotemporal dementia included theft, sexual advances trespassing and public urination in contrast to people with Alzheimer's disease who, when such behaviors were present, primarily committed traffic violations often secondary to cognitive impairment. (more…)
Author Interviews, JACC, Weight Research / 06.01.2015

MedicalResearch.com Interview with: Dr. Joshua Bell PhD Candidate Epidemiology & Public Health University College London, UK Medical Research: What is the background for this study? What are the main findings? Dr. Bell: When viewed at single points in time, about one-third of obese adults show normal metabolic profiles, that is, they have normal blood pressure, cholesterol and blood sugar levels. These adults have been labeled as 'healthy', but until now we have lacked evidence on the long-term stability of this state over time. By viewing theDr. Joshua Bell PhD Candidate Epidemiology & Public Health University College London, UK natural course of healthy obesity over two decades we found that about half of healthy obese adults become unhealthy obese after 20 years, with a clear trend for increasing progression to ill-health over time. Healthy obese adults are also much more likely to become unhealthy obese than healthy or unhealthy non-obese adults, indicating that healthy obesity is often just a phase. (more…)
Author Interviews, Inflammation, Pediatrics, Pediatrics / 06.01.2015

MedicalResearch.com Interview with: Professor of Pediatrics Hans Bisgaard, MD, DMSc Copenhagen Prospective Studies on Asthma in Childhood Herlev and Gentofte Hospital, University of Copenhagen, Denmark Medical Research: What is the background for this study? What are the main findings? Prof. Bisgaard: The purpose of this study was to look for a shared risk factor for immunological diseases which make its debut in childhood. During the recent decades a parallel increase in prevalence of immune diseases such as asthma, allergy, inflammatory bowel disease, and type 1 diabetes have been observed in westernized countries. The rate of cesarean delivery has increased in the same period and has previously been associated with the development of some of these diseases. This study takes advantage of the unique and valuable nationwide registry data in Denmark to establish a large population based cohort (2 million term children) with 35 years of follow up (in the period 1977-2012). We found cesarean delivery to be a common risk factor for a range of childhood immunological diseases: asthma, juvenile arthritis, inflammatory bowel diseases, connective tissue disorders, immune deficiencies and leukemia, but with no association to psoriasis, celiac disease, and diabetes type 1. (more…)
Author Interviews, HIV, Johns Hopkins, Kidney Disease / 06.01.2015

Alison G Abraham PhD Associate Scientist Department of Epidemiology Johns Hopkins Bloomberg School of Public HealthMedicalResearch.com Interview with: Alison G Abraham PhD Associate Scientist Department of Epidemiology Johns Hopkins Bloomberg School of Public Health Medical Research: What was the motivation for this study? Dr. Abraham: HIV-infected individuals are at higher risk for kidney dysfunction compared to the general population.  Prior to effective antiretroviral therapy, very aggressive forms of kidney disease were described primarily among black HIV-infected individuals.  While effective therapy and increasing viral suppression rates have made HIV-associated nephropathy rare, some of these same drugs have nephrotoxic effects.  In addition, the reduction in AIDS and mortality has led to HIV-infected individuals living long enough to experience age-related chronic diseases, which are also risk factors for kidney disease and end-stage renal disease.  Thus we wanted to know how these competing forces were affecting end-stage renal disease risk in the well-treated HIV-infected North American population over time.  Are we seeing more ESRD as a result of nephrotoxic drugs and chronic disease, or less ESRD as a result of better viral suppression and large reductions in HIV-associated nephropathy? Medical Research: What are the main findings? Dr. Abraham: We found that end stage renal disease rates have been steadily falling over the past 10 years coincident with notable improvements in viral suppression prevalence.  However a large racial discrepancy in ESRD risk has persisted even though HIV-associated nephropathy cases are now rare.  While ESRD cases among blacks in our study tended to have higher viral loads and lower CD4 counts compared to non-black ESRD cases, suggesting less effective HIV treatment, we found that the racial discrepancy in ESRD risk persisted even among the well-suppressed subset, i.e. those who had undetectable viral loads for 90% of their follow-up time. (more…)
Author Interviews, JAMA, Surgical Research, Weight Research / 06.01.2015

David Arterburn, MD, MPH, FACP Associate Investigator Group Health Research Institute Seattle, WA 9810MedicalResearch.com Interview with: David Arterburn, MD, MPH, FACP Associate Investigator Group Health Research Institute Seattle, WA 98101   and David L. Maciejewski PhD Center for Health Services Research in Primary Care Durham VA Medical Center, Durham, North CarolinaDavid L. Maciejewski PhD Center for Health Services Research in Primary Care Durham VA Medical Center, Durham, North Carolina MedicalResearch.com: Why was this study needed? Response: There were several reasons to conduct this study.  First, although complications and death during and soon after bariatric surgery have progressively declined over the past several decades, there is simply very little long-term evidence on the survival benefits of bariatric surgery in Americans having surgical procedures that are being used today in routine practice. Second, we felt that it was important to look at the impact of bariatric surgery among veterans because they represent an older male cohort often with multiple medical comorbidities, which is different from the typical bariatric patient in the United States, who is often younger and female. MedicalResearch.com: How was your study conducted? Response: We conducted a retrospective observational study using high-quality data from national Department of Veterans Affairs electronic databases and the VA Surgical Quality Improvement Program. We identified veterans who underwent bariatric surgery in VA medical centers from 2000 to 2011. Three quarters of them were men. We matched them to control patients using an algorithm that included age, sex, VA geographic region, body mass index (BMI), diabetes, and Diagnostic Cost Group. We then compared survival across bariatric patients and matched controls using Kaplan-Meier estimators and stratified, adjusted Cox proportional hazards analyses.  MedicalResearch.com: What were the main findings of your study? Response: This study had three important results: 1)      Our analysis showed no significant association between bariatric surgery and death from all causes in the first year of follow-up. In other words, having bariatric surgery was not significantly related to a veteran’s chance of dying in the first year compared to not having surgery. 2)      We had an average follow-up of 6.9 years in the surgical group and 6.6 years in the matched control group. After one to five years, adjusted analyses showed significantly lower mortality in the patients who had surgery: 55% lower, with a hazard ratio of 0.45. The finding was similar at 5 or more years, with a hazard ratio of 0.47. This means that bariatric surgery was associated with lower long-term mortality – that is, better long-term survival among veterans, which is consistent with limited non-VA research that has addressed this same question. 3)      Finally, we also found that the relationship between surgery and survival were similar comparing men and women, patients with and without diagnosed diabetes, and patients who had bariatric surgery before versus after year 2006. (more…)
Author Interviews, Dermatology, Infections, Pediatrics / 06.01.2015

Jonathan Olsen Institute of Primary Care and Public Health Cardiff University Heath Park CardiffMedicalResearch.com Interview with: Jonathan Olsen Institute of Primary Care and Public Health Cardiff University Heath Park Cardiff MedicalResearch: What is the background for this study? What are the main findings? Response: Molluscum Contagiosum is a common skin condition in children which has a prevalence of between 5.1% to 8% in children aged 14 years and under. Strikingly however, there is little epidemiological evidence describing the natural history, transmission between family members and impact upon quality of life of molluscum contagiosum. Our research aimed to address this gap in evidence by conducting a prospective cohort study of UK children recruited by clinical and self-referral using the validated Molluscum Contagiosum Diagnostic Tool for Parents (MCDTP). We recruited 306 children during 2013 and showed that on average lesions will last for 12 months, however 30% still had lesions at 18 months and 13% still had lesions at 24 months. Most children experienced only a small effect on their quality of life from the condition, however 1 in 10 experienced a large or very large impact on their quality of life. The condition was shown to be highly contagious with further transmission between children living in the same household as an index case shown in 40%. (more…)
Author Interviews, Gastrointestinal Disease, Pediatrics / 06.01.2015

Miranda van Tilburg, PhD Associate Professor of Medicine University of North CarolinaMedicalResearch.com Interview with: Miranda van Tilburg, PhD Associate Professor of Medicine University of North Carolina Medical Research: What is the background for this study? What are the main findings? Dr. van Tilburg: Functional gastrointestinal disorders are common in children, adolescents and adults but little is known about the prevalence in infants and toddlers.  Functional gastrointestinal disorders in infancy include disorders such as regurgitation, colic, and dyschezia, while functional gastrointestinal disorders in toddlers include functional constipation, functional diarrhea, functional dyspepsia, cyclic vomiting, and rumination. Of these disorders only colic and regurgitation have received much research attention. Prevalence, cause and consequences of most functional gastrointestinal disorders in infants and toddlers are largely unknown. We set out to determine the prevalence in the US by asking a representative sample of mothers to report on their child’s symptoms. Our study found that 27% of infants and toddlers may suffer from a functional gastrointestinal disorder. Among infants, regurgitation was the most common disorder and among toddlers constipation. Despite functional gastrointestinal disorders generally being more prevalent in older girls and adult women, no sex differences were found in this age group. Toddlers who suffer from a functional gastrointestinal disorders had lower quality of life and made more health care visits. (more…)
Author Interviews, HPV, JAMA, Vaccine Studies / 05.01.2015

Anders Hviid, M.Sc., Dr.Med.Sci. Senior Investigator, Statens Serum InstitutMedicalResearch.com Interview with: Anders Hviid, M.Sc., Dr.Med.Sci. Senior Investigator, Statens Serum Institut Medical Research: What is the background for this study? Response: After the widespread introduction of HPV vaccination of adolescent girls, a number of safety concerns have emerged. In this case, demyelinating diseases, including multiple sclerosis, occurring after HPV vaccination has been reported in social media, news media and medical journals. Medical Research: What are the main findings? Response: In a study of almost 4 million Danish and Swedish women, we found no support for an increased risk of multiple sclerosis or other demyelinating diseases following HPV vaccination. (more…)
Author Interviews, Brigham & Women's - Harvard, JAMA, Nutrition / 05.01.2015

Qi Sun, MD ScD Assistant Professor of Medicine Channing Division of Network Medicine Brigham and Women's Hospital and Harvard Medical School Assistant Professor Department of Nutrition, Harvard School of Public Health 665 Huntington Avenue, Boston, MA 02115MedicalResearch.com Interview with: Qi Sun, MD ScD Assistant Professor of Medicine Channing Division of Network Medicine Brigham and Women’s Hospital and Harvard Medical School, Assistant Professor, Department of Nutrition Harvard School of Public Health Boston, MA 02115 Medical Research: What is the background for this study? What are the main findings? Dr. Sun: While we know whole grains are beneficial for reducing the risk of some major chronic diseases, such as heart disease and diabetes, evidence regarding whether whole grains are also able to lower mortality is sparse. We therefore want to answer this important research question in the current analysis. Using data collected from two prospective cohort studies consisted of more than 100 thousand US men and women, we found that whole grain intake was significantly associated with lower total mortality and lower cardiovascular mortality, but not cancer mortality. For every serving (28 grams) of whole grain intake per day, the total mortality is reduced by 5% and cardiovascular mortality by 9%. (more…)
Author Interviews, Case Western, Genetic Research / 05.01.2015

Michael A. Weiss, MD, PhD The Cowan-Blum Professor and Chairman of the Department of Biochemistry Distinguished Research Professor andMedicalResearch.com Interview with: Michael A. Weiss, MD, PhD The Cowan-Blum Professor and Chairman of the Department of Biochemistry Distinguished Research Professor and Professor of Medicine in the Endocrine Division at the Case Western Reserve School of Medicine in Cleveland, Ohio. Joseph Racca Researcher and graduate student Department of BiochemistryJoseph Racca Researcher and graduate student Department of Biochemistry Case Western Reserve School of Medicine in Cleveland, Ohio. Medical Research: What is the background for this study? What are the main findings? Response: The function of the gene responsible for male differentiation, sex-determining region of the Y chromosome (SRY), was first demonstrated in transgenic mouse models by P. Koopman, R. Lovell-Badge and colleagues in the early 1990s. These findings were corroborated by identification of mutations in human SRY that are associated with human sex reversal: XY, 46 gonadal dysgenesis leading to somatic sex reversal (Swyer’s Syndrome). Such mutations may occur spontaneously in spermatogenesis or be inherited. The characterization of the molecular defects associated with these mutations has unmasked novel biological and biochemical activities of SRY. More broadly, such studies have also increased our understanding of an entire family of related transcription factors (Sry-box related; SOX), which broadly function in metazoan development (from worms, fish and flies to mammals). Within human SRY, the majority of clinical mutations occur in the region of the protein responsible for specific DNA binding and DNA bending, the primary molecular actions of SRY at target genes. Our study bridges structure (i.e., protein folding and stability) and function (i.e., transcriptional activation of target genes and related cell-biological processes such as trafficking and proteosomal degradation). In our current study, we highlighted the importance of a structural scaffold in human SRY, specifically a key single amino acid that buttresses the unique L-shape structure of this domain. The mutation of interest represents a “perfect storm” leading to deleterious effects on multiple activities, including specific DNA binding, cellular localization, and both protein and cellular stability (lifetime), among other properties, together leading to sex reversal and cancer (gonadoblastoma) in the proband patient. Our integrated multi-disciplinary approach allowed us to characterize these various facets of SRY in the context of its biological site of action: the pre-Sertoli cell in an embryonic gonadal ridge just prior to its morphological differentiation into a testis. We are grateful to Prof. Patricia K. Donahoe (Harvard Medical School and the Massachusetts General Hospital), who generously provided this micro-dissected pre-Sertoli cell line. (more…)
Author Interviews, Depression, Heart Disease / 05.01.2015

Nancy L. Sin, Ph.D. Postdoctoral Fellow Center for Healthy Aging & Department of Biobehavioral Health The Pennsylvania State University University Park, PA 16802MedicalResearch.com Interview with: Nancy L. Sin, Ph.D. Postdoctoral Fellow Center for Healthy Aging & Department of Biobehavioral Health The Pennsylvania State University University Park, PA 16802 Medical Research: What is the background for this study? What are the main findings? Dr. Sin: Older patients with coronary heart disease often experience declines in functional status, which is the ability to perform daily activities such as bathing, walking, and doing housework. The key factors that contribute to functional status among cardiac patients are not well-understood. Previous studies have found only weak or no associations between cardiovascular disease severity and functional status. Psychological factors—such as depression—are known to increase the risk of functional impairment, but this has not been studied long-term in patients with coronary heart disease. It is unclear the extent to which long-term functional status is determined by psychological factors versus cardiovascular disease severity. The purpose of our study was to compare the contributions of depressive symptoms with those of cardiovascular disease severity (specifically, left ventricular ejection fraction, exercise capacity, and angina frequency) for predicting subsequent functional decline in 960 older adults with stable coronary heart disease. Across a 5-year period, people who had more severe depressive symptoms were at greater risk of functional decline, independent of cardiovascular disease severity, demographics, health behaviors, cognitive function, and other factors.  Low exercise capacity was also strongly related to future functional decline, but ejection fraction and angina frequency were not. These findings underscore the importance of considering both mental and physical health in determining long-term functional status. (more…)
Author Interviews, Lung Cancer, Medical Imaging / 05.01.2015

Joao R. Inacio, MD Cardiothoracic Radiologist Director Visiting Professor Program Assistant Professor of Radiology, University of Ottawa Medical Imaging, The Ottawa Hospital Ottawa, ONMedicalResearch.com Interview with: Joao R. Inacio, MD Cardiothoracic Radiologist Director Visiting Professor Program Assistant Professor of Radiology, University of Ottawa Medical Imaging, The Ottawa Hospital Ottawa, ON Medical Research: What is the background for this study? What are the main findings? Dr. Inacio: Lung cancer is the most common and most lethal cancer worldwide. Its prognosis remains poor with a 5-year survival rate of 6–18%. Adenocarcinoma has surpassed squamous cell carcinoma as the leading histologic type. The presence of metastases carries the worst prognosis in lung cancer and is the most important in determining staging and management. Hematogenous spread (i.e., carried by blood) is the most common mechanism of intrapulmonary metastasis. Cumulative evidence suggests that intrapulmonary aerogenous spread may exist and is under recognized. Deriving from our clinical experience, we performed a literature review that supports the hypothesis that lung cancer, particularly adenocarcinoma, may spread through the airways. With aerogenous metastases, it has been postulated that cancer cells growing along the alveolar septa at the primary site detach from the basal membrane, spread through the airways and re-attach and grow along alveolar septa away from the primary focus. Radiology-pathology correlation studies, using Chest Computed Tomography (CT), have documented the radiological evolution from focal adenocarcinoma to multifocal airspace disease and demonstrated cytologic and histologic findings supportive of aerogenous spread. (more…)
Antibiotic Resistance, Author Interviews, Infections, Science / 04.01.2015

Melanie Blokesch PhD Assistant Professor (tenure-track) Laboratory of Molecular Microbiology Global Health Institute, School of Life Sciences Swiss Federal Institute of Technology Lausanne (EPFL) Lausanne SwitzerlandMedicalResearch.com Interview with: Melanie Blokesch PhD Assistant Professor (tenure-track) Laboratory of Molecular Microbiology Global Health Institute, School of Life Sciences Swiss Federal Institute of Technology Lausanne (EPFL) Lausanne Switzerland Medical Research: What is the background for this study? What are the main findings? Dr. Blokesch: We have been studying the cholera-causing bacterium Vibrio cholerae for many years in my laboratory. Our main focus has always been on elucidating how this pathogen acquires new genetic material that allows it to evolve. This is often accomplished through a mechanism known as horizontal gene transfer (HGT). There are three main modes of horizontal gene transfer in bacteria and the one we are primarily interested in is called natural competence for transformation. When the bacterium enters the state of natural competence it can take up free genetic material from its surrounding and in case it recombines this new material into its own genome the bacterium is considered to be naturally transformed. Notably, natural competence/transformation was first described in 1928 by Fred Griffith, who showed that transformation can render harmless bacteria pathogenic. These early experiments can be considered a milestone in molecular biology as it later led to the discovery of DNA as the carrier of genetic information. Medical Research: What are the main findings? Dr. Blokesch: The main finding of our study is that the pathogen V. cholerae does not solely rely on free DNA floating around but that it actively kills neighbouring bacteria followed by the uptake of their DNA. Indeed, we were able to show that the two processes - killing of other bacteria and DNA uptake - are co-regulated by the same proteins within the bacterial cell. We also used imaging techniques to visualize the killing of other bacteria by V. cholerae, followed by the release of their genetic material, which the predator then pulled into its own cell. We further quantified these HGT events by following the transfer of an antibiotic resistance gene from the killed bacterium to the predatory V. cholerae cell. Notably, the spread of antibiotic resistances is a major health concern and HGT is a major driver of it. (more…)
Author Interviews, CHEST, Hospital Readmissions, Pulmonary Disease / 03.01.2015

Tina Shah, MD University of Chicago Medicine Department of Pulmonary and Critical Care University of ChicagoMedicalResearch.com Interview with: Tina Shah, MD University of Chicago Medicine Department of Pulmonary and Critical Care University of Chicago Medical Research: What is the background for this study? What are the main findings? Dr. Shah: The reason why we undertook this study is to better understand the Medicare COPD population that falls under the purview of the CMS Hospital Readmissions Reduction Program (HRRP). This program places up to a 3% penalty on all Medicare revenues for hospitals that take care of beneficiaries should a hospital exceed its “expected readmission rate.” Previously 30 day readmissions after index admissions for congestive heart failure, acute myocardial infarction and pneumonia fell subject to the HRRP. As of October 2014, COPD has been added to the list, despite minimal evidence to guide hospitals in how to curb COPD readmissions. The goal of this research was to provide an epidemiological background for this population and identify trends as a hypothesis generating first step to predict who is most likely to be readmitted and to identify targets for successful future interventions on this group. Our study population is unique in that we longitudinally look at about 1/2 of all Medicare admissions for COPD exacerbations, using the CMS guideline definition which is based on discharge ICD-9 codes. As described in previous literature, there is a large discrepancy between identification of COPD by provider versus coding algorithm, however since the Hospital Readmissions Reduction Program is based on discharge coding it is important to examine this particular group. (more…)
Author Interviews, Breast Cancer, Mayo Clinic, NEJM / 03.01.2015

MedicalResearch.com Interview with: Dr. Lynn C. Hartmann MD Professor of Oncology, Mayo Clinic Associate Director for Education of the Mayo Clinic Cancer Center. Medical Research: What is the background for this study? What are the main findings? Dr. Hartmann: Women with atypical hyperplasia of the breast – which is defined via breast biopsy that was done to evaluate findings on a mammogram or a palpable concern – have been considered a “high risk” group of women, but the extent of their risk has not been clearly defined. As a consequence, practice guidelines for high-risk women (eg for screening MRI) do not include them. Mayo Clinic has developed a cohort of women with atypical hyperplasia who have been followed long-term for later breast cancers and we show that their risk of developing breast cancer is about 30% at 25 years of follow-up. This same level of risk was confirmed in the other large cohort of women with atypical hyperplasia, based at Vanderbilt University (Nashville Breast Cohort). This level of risk meets the current criterion for screening MRI and should also encourage the use of anti-estrogen drugs, such as tamoxifen, which have already been shown to be efficacious in this population of women. Medical Research: What should clinicians and patients take away from your report? Dr. Hartmann: There are about 100,000 US women each year diagnosed with atypical hyperplasia via breast biopsy. Although strictly speaking, atypical hyperplasia is a benign finding, it is associated with a sizable risk of a later breast cancer. Physicians from numerous disciplines care for women with high-risk benign breast issues, including gynecologists, family physicians, internists, surgeons and oncologists. These practitioners, and the patients themselves, need information about the absolute risk of breast cancer occurring over time after a diagnosis of atypical hyperplasia. This information is provided in the NEJM report. Also, current guidelines should be updated to include this high-risk population and specifics about their absolute risk, and that the risk level qualifies these patients for screening MRI. Moreover, from the standpoint of risk reduction, four previously conducted breast cancer prevention trials included women with atypical hyperplasia. These trials used hormonal therapies (anti-estrogens) and showed that, in women with atypical hyperplasia, the use of such medications could lower the risk of a later breast cancer by 50% or more. Yet, other research has shown that women are quite reluctant to take such medications, primarily because of fear of side effects. In the NEJM report, we detail specific numbers of side effects that actually occurred in women who used these anti-estrogens (as opposed to the number of side effects seen in women taking placebo) and show that most of the side effects occurred quite uncommonly. Thus, we hope that the combination of information provided in this report on (i) actual risks of breast cancer and (ii) actual risks of side effects will help patients and practitioners make informed decisions on the best treatment approaches for women with atypical hyperplasia. Medical Research: What recommendations do you have for future research as a result of this study? Dr. Hartmann: First, women with atypical hyperplasia should be included in future prospective trials of novel imaging strategies (they were not included in trials of MRI, which had been limited to women with hereditary risk). Second, efforts should continue to predict which women with atypical hyperplasia are at highest risk, especially in the first 5-10 years after their biopsy, so they can be cared for optimally. Our research team, and others, continue to study the underlying molecular pathways that drive the progression from atypical hyperplasia to cancer; identifying such processes would not only aid in risk prediction but also identify driving pathways that could be blocked pharmaceutically. Citation: upcoming NEJM publication discussing: Women with Atypical Hyperplasia are at Higher Risk of Breast Cancer MedicalResearch.com Interview with: Dr. Lynn C. Hartmann MD Professor of Oncology, Mayo Clinic Associate Director for Education of the Mayo Clinic Cancer Center. Medical Research: What is the background for this study? What are the main findings? Dr. Hartmann: Women with atypical hyperplasia of the breast – which is defined via breast biopsy that was done to evaluate findings on a mammogram or a palpable concern  – have been considered a “high risk” group of women, but the extent of their risk has not been clearly defined.  As a consequence, practice guidelines for high-risk women (eg for screening MRI) do not include them.  Mayo Clinic has developed a cohort of women with atypical hyperplasia who have been followed long-term for later breast cancers and we show that their risk of developing breast cancer is about 30% at 25 years of follow-up.  This same level of risk was confirmed in the other large cohort of women with atypical hyperplasia, based at Vanderbilt University (Nashville Breast Cohort).  This level of risk meets the current criterion for screening MRI and should also encourage the use of anti-estrogen drugs, such as tamoxifen, which have already been shown to be efficacious in this population of women. (more…)