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. (more…)
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. (more…)
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. (more…)
Author Interviews, Cancer Research, JAMA, NYU, Surgical Research / 03.06.2015

Wiliam C. Huang, MD FACSAssociate Professor of Urology Division of Urologic Oncology NYU Langone Medical Center/Perlmutter Cancer InstituteMedicalResearch.com Interview with: Wiliam C. Huang, MD FACS Associate Professor of Urology Division of Urologic Oncology NYU Langone Medical Center/Perlmutter Cancer Center Medical Research: What is the background for this study? What are the main findings? Dr. Huang: The presentation of kidney cancers has dramatically evolved over the past two decades with most kidney cancers being incidentally diagnosed at an early stage. We have begun to recognize that at this small size (< 4 cm), the tumors are frequently indolent in nature and some are completely benign. Consequently, the management options for these small cancers have expanded and evolved.  Whereas the entire removal of the kidney was the treatment of choice in the past, alternative options including removal or ablation of the tumor-bearing portion of the kidney has become increasingly utilized. Similar to other early stage cancers, watchful waiting or observation is also becoming a reasonable treatment option. We used the most recent SEER-Medicare Data (2001 – 2009) to evaluate the management trends and outcomes of small kidney cancers in the new millennium.  We believe that this is an important study as it provides important and practical findings, which are useful to both clinical researches as well as practicing physicians. (more…)
Author Interviews, JAMA, Kaiser Permanente, Pain Research / 03.06.2015

Harley Goldberg, DO Physical Medicine and Rehabilitation Kaiser PermanenteMedicalResearch.com Interview with: Harley Goldberg, DO Physical Medicine and Rehabilitation Kaiser Permanente Medical Research: What is the background for this study? What are the main findings? Dr. Goldberg: This is the first large-scale randomized, double-blind, placebo-controlled clinical trial of oral steroids for acute radiculopathy, commonly called sciatica, associated with a herniated lumbar disk. Lumbar radiculopathy (or pain down the leg in a lumbar nerve root distribution) is a common source of pain and disability for many adults. It is thought that inflammation from a disk herniation is responsible for many of the symptoms, so giving a powerful anti-inflammatory, such as steroid medication, might help relieve sciatica symptoms quickly. Prior research has shown that lumbar diskectomy does not affect the one year outcome for most patients, and epidural steroid injections do not have strong support by clinical trials. If the use of epidural steroids injections is based on application of steroid anti-inflammatory to the affected nerve root(s), perhaps an oral steroid can have affect. Although oral steroids are used by many physicians and have been included in some clinical guidelines, no large-scale clinical trials of oral steroids for sciatica have been conducted before. Our study found that among patients with acute radiculopathy associated with a herniated lumbar disk, a short course of oral steroids resulted in only modest improvement in function and no significant improvement in pain. (more…)
Author Interviews, Dermatology, JAMA, Melanoma / 03.06.2015

Catherine M. Olsen, PhD Population Health Department QIMR Berghofer Medical Research Institute Queensland, Australia MedicalResearch.com Interview with: Catherine M. Olsen, PhD Population Health Department QIMR Berghofer Medical Research Institute Queensland, Australia MedicalResearch: What is the background for this study? Dr. Olsen: Effective skin cancer control requires two strategies: regular sun protection to prevent new cancers from occurring and early detection assisted by periodic skin examinations. The aim of our study was to describe the prevalence and predictive factors for sun protection and skin examination practices of adults in Queensland, Australia, a region that experiences the highest rates of skin cancer in the world. We were particularly interested in whether sun protection and skin examination practices differed between those with and without a previously confirmed melanoma and/or treatment for other skin lesions. MedicalResearch: What are the main findings? Dr. Olsen: The prevalence of both sun protection and skin examination practices was generally high in this large cohort of people who experience high levels of ambient sun exposure. People who had been diagnosed with a melanoma or other skin lesion were more likely than those without to report sun protection practices including regular use of sunscreen and wearing hats. The strongest predictor of sun protection practices was having a sun-sensitive skin type, and the strongest predictor of skin examination practices was having many moles and/or a family history of melanoma. (more…)
Author Interviews, Breast Cancer, JAMA, Leukemia / 03.06.2015

Efrat Amitay, PhD, MPH School of Public Health University of Haifa Mount Carmel, Haifa, IsraelMedicalResearch.com Interview with: Efrat Amitay, PhD, MPH School of Public Health University of Haifa Mount Carmel, Haifa, Israel Medical Research: What is the background for this study? Dr. Amitay: Although childhood cancer is still rare, we are seeing an increase of around 0.9% annually in the incidence rate in the western world. In spite of advancements in treatment technologies, childhood cancer is a leading cause of death among children and adolescents in the western world – accounting for about 12.3% of all deaths among children age 1-14 years in the US. Childhood cancer is also emerging as a major cause of death in other parts of the world where death rates from communicable diseases are declining. Leukemia is the most common type of childhood cancer and accounts for about 30% of all childhood and adolescent cancers. Medical Research: What are the main findings? Dr. Amitay: The meta-analysis of all 18 studies indicated that compared with no or shorter duration of breastfeeding, breastfeeding for 6 months or longer was associated with a 19% lower risk for childhood leukemia (OR=0.81, 95% CI, 0.73-0.89). A separate analysis of 15 of those studies indicated that ever being breastfed compared with never being breastfed was associated with an 11% lower risk for childhood leukemia (OR=0.89, 95% CI, 0.84-0.94). All meta-analyses of other sub groups of studies have shown similar associations, indicating that 14%-19% of all childhood leukemia cases may be prevented by breastfeeding for 6 months or more. (more…)
Author Interviews, Brigham & Women's - Harvard, JAMA, Transplantation / 03.06.2015

Paula Chatterjee, MD, MPH Department of Medicine, Brigham and Women’s Hospital Harvard Medical School Boston, MassachusettsMedicalResearch.com Interview with: Paula Chatterjee, MD, MPH Department of Medicine, Brigham and Women’s Hospital Harvard Medical School Boston, Massachusetts Medical Research: What is the background for this study? What are the main findings? Dr. Chatterjee: Thousands of patients die every year due to organ shortages. Finding ways to address this public health issue is critical. States have designed a variety of strategies to promote organ donation and transplantation, however we don’t know if any of these strategies have been successful. The goal of our study was to try to figure out which strategies have been most successful in terms of increasing organ donation and transplantation. We found that states have implemented a wide and creative set of strategies, but unfortunately, it seems that these strategies have had almost no effect on increasing organ donation and transplantation. In states that adopted these strategies compared to those that did not, the rates of donation and transplantation increased at nearly the same rate over the past two decades. The only strategy that seemed to have a small effect was when states created revenue pools dedicated toward organ donation activities. (more…)
Author Interviews, JAMA, Ophthalmology, Technology / 02.06.2015

Andrew Bastawrous, MRCOphth International Centre for Eye Health, Clinical Research Department London School of Hygiene and Tropical Medicine (LSHTM), London, EnglandMedicalResearch.com Interview with: Andrew Bastawrous, MRCOphth International Centre for Eye Health, Clinical Research Department London School of Hygiene and Tropical Medicine (LSHTM), London, England Medical Research: What is the background for this study? What are the main findings? Dr. Bastawrous: As part of my PhD with the International Centre for Eye Health at the London School of Hygiene & Tropical Medicine, I led the follow-up of a major cohort study of eye disease [http://www.biomedcentral.com/1471-2415/14/60] following up 5,000 people in 100 different locations across the Great Rift Valley in Kenya. It was really challenging, two-thirds of the locations had no road access or electricity and we were carrying over £100,000 worth of fragile eye equipment and a team of 15 people in two vans to be able to carry out high quality measures of eye disease and answer some important questions for planning eye services. What we found was that in the most difficult to reach locations we would find lots of people waiting to see us who had been unnecessarily blind from preventable/treatable diseases. Despite the locations having no roads, electricity and often no water, nearly all the locations had good phone signal. Together with a brilliant team of developers, engineers and ophthalmologists we developed a suite of smartphone based tests to see if we could replace some of the standard equipment being used, in the hope that we could make it more portable and easier for non-specialists to perform so that ultimately the most high-risk individuals could be reached and treated. This paper describes one of those tests, the visual acuity test - Peek Acuity. Our field workers tested patients in their own homes using a standard card based Snellen chart (the type of vision test most non-ophthalmic healthcare workers are familiar with and has been the most commonly used acuity test for several decades now) and Peek Acuity. The same tests were repeated by the same healthcare worker in the clinic the following day as well as a reference standard vision test (LogMAR ETDRS) performed by an eye trained clinical officer. This allowed us to perform "test re-test", a measure of a tests repeatability. i.e. if you have the same test at two separate time points we would expect the the measures to be very close. We found that for both Peek Acuity and Snellen they were highly repeatable. An advantage of Snellen is the speed of the test, Peek Acuity came out slightly quicker overall. We also found when compared to the reference standard test, Peek Acuity was highly comparable and within a clinically acceptable limit of difference. (more…)
Author Interviews, Heart Disease, JAMA, Surgical Research / 02.06.2015

Mark L. Friedell, MD, FACS Chairman Department of Surgery University of Missouri Kansas City School of Medicine Kansas City, MO 64108MedicalResearch.com Interview with: Mark L. Friedell, MD, FACS Chairman Department of Surgery University of Missouri Kansas City School of Medicine Kansas City, MO 64108 Medical Research: What is the background for this study? What are the main findings? Response: The controversial practice of administering pre-surgery beta-blockers to patients having noncardiac surgery was associated with an increased risk of death in patients with no cardiac risk factors but it was beneficial for patients with three to four risk factors, according to a report published online by JAMA Surgery. Pre-surgery β-blockade is a widely accepted practice in patients having cardiac surgery. But its use in patients at low risk of heart-related events having noncardiac surgery is controversial because of the increased risk of stroke and hypotension (low blood pressure). Because of the persistent controversy, researcher Mark L. Friedell, M.D., of the University of Missouri-Kansas City School of Medicine, and coauthors analyzed data from the Veterans Health Administration to examine the effect of perioperative β-blockade on patients having noncardiac surgery by measuring 30-day surgical mortality. The analysis included 326,489 patients: 314,114 (96.2 percent) had noncardiac surgery and 12,375 (3.8 percent) had cardiac surgery. Overall, 141,185 patients (43.2 percent) received a β-blocker. Of the patients having cardiac surgery, 8,571 (69.3 percent) received a β-blocker and 132,614 (42.2 percent) of the patients having noncardiac surgery got one. The unadjusted 30-day mortality rates among patients having noncardiac surgery for those not receiving β-blockers were 0.5 percent for patients with no cardiac risk factors, 1.4 percent for patients with one to two risk factors and 6.7 percent for patients with three to four risk factors. For those patients having noncardiac surgery who did receive β-blockers, the unadjusted 30-day mortality rates for patients with no cardiac risk factors, one to two risk factors and three to four risk factors were 1 percent, 1.7 percent and 3.5 percent, respectively, according to the results. The results suggest that among patients with no cardiac risk factors having noncardiac surgery, those patients receiving β-blockers were 1.2 times more likely to die than those not receiving β-blockers. The risk of death decreased for those patients with one to two risk factors but the reduction was not significant. However, for patients having noncardiac surgery with three to four cardiac risk factors, those receiving β-blockers were significantly less likely to die than those not receiving β-blockers, the authors found. The authors did not observe similar results in patients having cardiac surgery. “β-blockade is beneficial perioperatively for patients with three to four cardiac risk factors undergoing NCS [noncardiac surgery] but not in patients with one to two cardiac risk factors. Most important, the use of β-blockers in patients with no cardiac risk factors appears to be associated with a higher risk of death, which has, to our knowledge, not been previously reported,” the study concludes. (more…)
Author Interviews, Depression, End of Life Care, JAMA / 28.05.2015

Katherine Ornstein, PhD MPH Assistant Professor Brookdale Department of Geriatrics and Palliative Medicine Institute for Translational Epidemiology Icahn School of Medicine at Mount Sinai One Gustave L. Levy Place, Box 1070 New York, NY 10029MedicalResearch.co Interview with: Katherine Ornstein, PhD MPH Assistant Professor Brookdale Department of Geriatrics and Palliative Medicine Institute for Translational Epidemiology Icahn School of Medicine at Mount Sinai New York, NY 10029 Medical Research: What is the background for this study? What are the main findings? Dr. Ornstein: There is an increased focus on the need to support caregivers and families, particularly at the End of Life (EOL). They play a critical role in the care process and decision making, yet this can be a very high stress role with an increased risk for negative consequences. Hospice services, which are increasing, are focused on palliative rather than curative care and include medical services, symptom management, spiritual counseling, social services and bereavement counseling delivered by an interdisciplinary team of professionals for dying patients.  An important part of the hospice service is the provision of support to families during illness and after death.  Prior research suggests that hospice (which is cost saving, has benefits to patients), may also  be beneficial to families. Yet these studies have been largely limited to patients with cancer, have failed to adequately control for differences between patients who do or do not use hospice. Overall, there was an increase in depressive symptoms after death.  However, surviving spouses of those who used hospice were more likely to have a decrease in depressive symptoms. We found that the positive benefit of hospice was much stronger when we looked at least 1 year after death. (more…)
Asthma, Author Interviews, JAMA, Nutrition / 27.05.2015

Lewis J. Smith, MD Professor of Medicine and Associate Vice President for Research Northwestern University and the Feinberg School of Medicine Chicago, IL 60611MedicalResearch.com Interview with: Lewis J. Smith, MD Professor of Medicine and Associate Vice President for Research Northwestern University and the Feinberg School of Medicine Chicago, IL 60611 Medical Research: What is the background for this study? What are the main findings? Dr. Smith: We previously observed in a survey of more than 1,000 patients with asthma that those consuming soy isoflavones in their diet had better lung functioning than their counterparts who consumed little or none.  Using a more detailed soy questionnaire, we confirmed the observation in a different group of patients with asthma, and followed that up with laboratory studies.  In cell culture studies, we saw that genistein, the major soy isoflavone, at levels that are achieved in individuals consuming a high soy diet, reduces eosinophilic inflammation, a key feature in asthma. In addition, people who consume more soy products, mostly in Japan and parts of China, generally have less asthma than in western countries.  Although these data indicate a potential beneficial effect of soy isoflavones in patients with asthma and nutritional supplements are commonly used by people to treat and prevent disease and improve their health, there was little direct data to prove that the supplement is actually effective.  As a result, we explored the effects of a soy isoflavone supplement in 386 adults and children aged 12 or older with poorly controlled asthma. All were taking medicine to treat their asthma – either corticosteroids or leukotriene modifiers – but none consumed soy more than once a week. In the randomized, double-blind study, half of the participants took a soy isoflavone supplement twice daily for six months, and the other half took a placebo. We found that the supplement, though able to increase blood levels of genistein, did not improve lung function, symptoms or measures of inflammation in these individuals. (more…)
Author Interviews, Dermatology, JAMA / 26.05.2015

MedicalResearch.com Interview with: Robert E Kalb, M.D. Clinical Professor of Dermatology State University of New York at Buffalo School of Medicine and Biomedical Sciences Buffalo Medical Group, P.C. Buffalo, NY 14221MedicalResearch.com Interview with: Robert E Kalb, M.D. Clinical Professor of Dermatology State University of New York at Buffalo School of Medicine and Biomedical Sciences Buffalo Medical Group, P.C. Buffalo, NY 14221 Medical Research: What is the background for this study? What are the main findings? Dr. Kalb: It's important to evaluate the safety of biologics in the real world post-marketing setting, and in particular with respect to serious infections. We studied patients with psoriasis in the PSOLAR registry and evaluated the risk of various biologic therapies. We found that infliximab and adalimumab were associated with increased risk of serious infections when compared with non-biologic/non-methotrexate therapies, while ustekinumab and etanercept were not associated with increased risk. (more…)
Author Interviews, Cancer Research, JAMA, Toxin Research / 26.05.2015

MedicalResearch.com Interview with: Catterina Ferreccio, MD, MPH School of Medicine Pontificia Universidad Católica de Chile Santiago, Chile Medical Research: What is the background for this study? What are the main findings? Dr. Ferreccio: In Chile, gallbladder cancer (GBC) is the 2nd highest cause of cancer death in women.  Other than gallstones no other causal factors have been identified. We conducted a pilot case-control study of gallbladder cancer to evaluate its association with aflatoxin B1 (AFB1) exposure. Aflatoxins are toxics products of the fungis Aspergillus flavus and Aspergillus parasiticus and are contaminants of food; AFB1 is carcinogenic. Usually they are found in areas closer to the Equator than Chile. Main findings were the high proportion (35%) of study subjects carrying aflatoxins adducts and the particularly high exposure among the Gallbladder cancer (GBC) cases (64%) compared with gallstones controls (18%) or with population controls (23%). Difference of gallbladder cancer vs controls were statistically significant and suggests aflatoxins may be a significant risk factor for gallbladder cancer; hypothesis never tested before. (more…)
Author Interviews, Genetic Research, JAMA / 26.05.2015

Prof. Alexandre Reymond Director, Center for Integrative Genomics University of Lausanne Lausanne SwitzerlandMedicalResearch.com Interview with : Prof. Alexandre Reymond Director, Center for Integrative Genomics University of Lausanne Lausanne Switzerland MedicalResearch : What is the background for this study? Prof. Reymond: Though a subset of recurrent DNA copy number variants (differing numbers of copies of genetic sequence at locations in the genome; CNVs) with rare population prevalence are known to have strong impact on carrier’s health, up to now their association with phenotypes such as intellectual disability has been almost exclusively evaluated in clinical context using individuals ascertained for diagnostics of developmental disorders. Thus the contribution of these genetic variants to health, cognition and life quality in the general population remains unclear. We used a population biobank, that of Estonia (Estonian Genome Center, University of Tartu), which contains samples from 52,000 adult participants (representative 5% of the country’s adult population), a British birth cohort (The Avon Longitudinal Study of Parents and Children; ALSPAC) and two more population-based cohorts from the USA and Italy to explore the consequences of CNVs in presumptively healthy populations. MedicalResearch : What are the main findings? Prof. Reymond: Rare recurrent CNVs known to be causative for specific syndromes (termed genomic disorders) have a global population prevalence of around 1%. Contrary to popular assumption that carriers of these syndromic CNVs identified in unselected, but assumed to be healthy, adult population cohorts are asymptomatic, we found that they are associated with unrecognized, but serious clinical sequelae. Additionally our results showed that individually rare (less than 1 in 2000 individuals) but collectively common (around 10% of population) intermediate-size CNVs are negatively associated with carriers’ educational attainment. Altogether our results suggest that the life quality of at least 1 of 40 people might be negatively affected by rare CNVs. (more…)
Alzheimer's - Dementia, Author Interviews, JAMA, Medical Imaging, UCSF / 20.05.2015

Rik Ossenkoppele PhD. Postdoctoral researcher UCSF Memory and Aging CenterMedicalResearch.com Interview with: Rik Ossenkoppele PhD. Postdoctoral researcher UCSF Memory and Aging Center MedicalResearch: What is the background for this study? Dr. Ossenkoppele: Since 2004, several PET tracers have been developed that measure fibrillar amyloid-β plaques, a neuropathological hallmark of Alzheimer’s disease (AD). Through visual assessment by a nuclear medicine physician or quantitative cut-points, the presence or absence of amyloid-β pathology can be determined in the living human brain. The FDA, in support of the clinical application of amyloid imaging, has recently approved three of these PET tracers. A proportion of patients with other types of dementia then Alzheimer’s disease that harbor cerebral amyloid-β pathology, however, potentially limits the clinical utility of amyloid imaging. When ordering clinical amyloid PET scans and correctly interpreting the significance of amyloid PET results, clinicians need to understand the prevalence of amyloid-positivity across different types of dementia. It is also important to be aware of the relationships of amyloid-positivity prevalence and demographic (e.g. age and sex), cognitive and genetic (e.g. presence of the AD-risk allele apolipoprotein E [APOE] ε4) factors. Most amyloid PET studies to date come from single centers with modest sample sizes. We therefore conducted a meta-analysis with individual participant data from 29 cohorts worldwide, including 1359 patients with clinically diagnosed Alzheimer’s disease and 538 patients with non-AD dementia. We also included 1849 healthy controls with amyloid PET data, and an independent sample of 1369 AD patients with autopsy data from the NACC database. MedicalResearch: What are the main findings? Dr. Ossenkoppele: In patients clinically diagnosed with Alzheimer’s disease, the prevalence of amyloid-positivity decreased from 93% at age 50 to 79% at age 90. The drop in amyloid-positivity was most prominent in older Alzheimer’s disease patients who did not carry an APOE ε4 allele (~1/3 of these patients had a negative amyloid PET scan). This most likely reflects a mix of 1) clinical misdiagnoses (i.e. non-AD pathology causing an AD phenotype), 2) false negative PET scans (i.e. abundance of cerebral amyloid pathology that is not detected by PET), and 3) possibly elder patients need less amyloid pathology (sub-threshold levels for PET) to reach the stage of dementia due to age-related reductions in cognitive resilience (“cognitive reserve theory”) or simultaneous presence of multiple pathologies (“double-hit theory”). The relatively high rate of amyloid-negative Alzheimer’s disease patients highlights the necessity of biomarker-informed patient selection for Alzheimer’s disease clinical trials. In most patients clinically diagnosed with non-AD, the prevalence of amyloid-positivity increased with aging and was ~18% higher in APOE ε4 carriers. Presence of amyloid pathology in non-AD dementia may reflect 1) clinical misdiagnosis (i.e. AD pathology is the causative pathology), or 2) comorbid pathologies, where amyloid may be secondary to other pathologies that are actually driving the clinical presentation. Interestingly, patients with a clinical diagnosis of non-AD dementia who harbored cerebral amyloid pathology showed lower Mini-Mental State Examination scores (measure of global cognition), suggesting that amyloid-β is not just an innocent bystander. (more…)
Aging, Author Interviews, JAMA, Metabolic Syndrome / 20.05.2015

Robert Wong, M.D., M.S. Attending Physician, Gastroenterology & Hepatology Director, GI Research Highland Hospital   I A member of Alameda Health System Oakland, CA 94602MedicalResearch.com Interview with: Robert Wong, M.D., M.S. Attending Physician, Gastroenterology & Hepatology Director, GI Research Highland Hospital   I A member of Alameda Health System Oakland, CA 94602 Medical Research: What is the background for this study? What are the main findings? Dr. Wong: The main findings are that despite the stabilizing prevalence of metabolic syndrome, a large proportion of U.S. adults affected with metabolic still raises concern, especially given the significant health consequences associated with this syndrome.  In additional to cardiovascular disease, metabolic syndrome also increases the risk of concurrent nonalcoholic fatty liver disease, often considered the hepatic manifestation of metabolic syndrome.  Many studies, including work that our group has completed suggests that nonalcoholic fatty liver disease will soon become the leading etiology of chronic liver disease in the U.S.  Furthermore, our finding that metabolic syndrome increases with increasing age, reflects the increased risk for metabolic syndrome associated diseases such as hypertension, diabetes, and dyslipidemia with older age.  This is important to recognize given the aging population of the U.S. (more…)
Author Interviews, Brain Injury, JAMA, UT Southwestern / 18.05.2015

C. Munro Cullum, PhD, ABPP Professor of Psychiatry and Neurology & Neurotherapeutics Pamela Blumenthal Distinguished Professor of Clinical Psychology Chief of Psychology Director of Neuropsychology Univ. of Texas Southwestern Medical Center Dallas, TX  75390-9044 MedicalResearch.com Interview with: C. Munro Cullum, PhD, ABPP Professor of Psychiatry and Neurology & Neurotherapeutics Pamela Blumenthal Distinguished Professor of Clinical Psychology Chief of Psychology , Director of Neuropsychology Univ. of Texas Southwestern Medical Center Dallas, TX Medical Research: What is the background for this study? What are the main findings? Dr. Cullum: My colleague and principal investigator of the study, Dr. John Hart and I have been interested in the acute and longer-term effects of traumatic brain injury for years, and because of my roles in the Alzheimer’s Disease Center and the Texas Institute for Brain Injury and Repair at the University of Texas Southwestern Medical Center, it seemed like a natural to begin studying older individuals with and without cognitive disorder who have a history of traumatic brain injury.  Our main findings are two-fold: First, we demonstrated that a history of concussion with loss of consciousness (which make up only about 10% of all concussions) was associated with smaller memory centers in the brain (the hippocampus) and lower memory results in our sample of retired professional football players. Concussions that did not result in loss of consciousness did not show that same strong association. Second, our data suggest that patients with a clinical diagnosis of mild cognitive impairment (ie a memory disorder that does not grossly impair overall functioning but may lead to dementia) who also have a history of concussion with loss of consciousness show worse memory results and more brain atrophy than similar individuals diagnosed with mild cognitive impairment in the absence of a history of concussion. (more…)
Author Interviews, Bipolar Disorder, Depression, JAMA / 18.05.2015

MedicalResearch.com Interview with: Maaike M. M. Rive Program for mood disorders AMC/De Meren, Department of Psychiatry PA3.221 Amsterdam  The Netherlands Medical Research: What is the background for this study? What are the main findings? Response: For clinicians, it can be difficult to distinguish whether a depressed patient suffers from major depressive disorder (characterized by depressive episodes only) or bipolar disorder (characterized by both depressive and (hypo)manic episodes). Differentiation between the two disorders is important because e.g. the treatment approaches are different. Although we know that both types of mood disorders are characterized by emotion regulation disturbances, little is known about differences in emotion regulation between the two disorders. Better insight in these differences would be helpful for differentiation between uni- and bipolar disorder. However, previous studies comparing these disorders often allowed medication use, and this may have influenced results. Furthermore, much is unknown about the effect of mood state on emotion regulation differences. We therefore investigated emotion regulation by showing happy, sad and fearful pictures to patients and healthy controls. Participants were instructed to either passively view the pictures, or to distance themselves from their feelings, by thoughts like: ‘this is only a picture’, ‘this will never happen to me’, etc. Emotion regulation success was measured by the difference between subjective ratings of emotional intensity after passive viewing versus distancing. Brain activity was measured with fMRI. The results of our study indicate that emotion regulation does indeed differ between medication-free major depressive or bipolar patients, and that specific differences depend on mood state. During remission, bipolar patients showed impaired emotion regulation across different types of emotions. In contrast, patients with major depressive disorder did not how such impairments during remission. During depression, patients differed regarding happy and sad emotion regulation: bipolar patients showed impaired sad, but unexpectedly normal happy emotion regulation, whereas in major depressive disorder, both sad and happy emotion regulation were compromised. These emotion regulation difficulties were associated with differences in brain activity in the dorsolateral prefrontal cortex (involved in effortful emotion regulation) and the rostral anterior cingulate cortex (connecting emotional and cognitive brain areas). (more…)
Author Interviews, Emergency Care, Heart Disease, JAMA / 18.05.2015

Michael B. Weinstock, MD Professor of Emergency Medicine, Adjunct Department of Emergency Medicine, The Ohio State University College of Medicine Emergency Department Chairman and Director of Medical Education, Mt. Carmel St. Ann's Dept. of Emergency Medicine Columbus, OhioMedicalResearch.com Interview with: Michael B. Weinstock, MD Professor of Emergency Medicine, Adjunct Department of Emergency Medicine, The Ohio State University College of Medicine Emergency Department Chairman and Director of Medical Education, Mt. Carmel St. Ann's Dept. of Emergency Medicine Columbus, Ohio Medical Research: What is the background for this study? Response: Patients with potential cardiac ischemia are often admitted to the hospital even after a negative evaluation in the emergency department due to concern about missed MI, unstable angina, or potential for cardiac arrhythmia. Medical Research: What are the main findings? Response: Our study was different than previous studies and clinical decision rules; instead of looking at a 30 day marker, which is important to the cardiologist, ours looked at the risk of a Clinically Relevant Adverse Cardiac Event (CRACE) occurring during hospitalization. These events included inpatient STEMI, life-threatening arrhythmia, cardiac or respiratory arrest, or death. The study found only 4 of these events out of 7266 patients studied and of the 4, two were possibly iatrogenic, suggesting that after a negative ED evaluation (including 2 negative serial cardiac enzyme tests, non-ischemic and interpretable ECG, and nonconcerning vital signs) a patient can be safely sent home for an expedited cardiac outpatient evaluation. (more…)
Author Interviews, JAMA, OBGYNE, Surgical Research / 14.05.2015

Robert A. Meguid, MD MPH FACS Assistant Professor Section of General Thoracic Surgery Division of Cardiothoracic Surgery Department of Surgery University of Colorado Denver | Anschutz Medical Campus Aurora, CO 80045MedicalResearch.com Interview with: Robert A. Meguid, MD MPH FACS Assistant Professor Section of General Thoracic Surgery Division of Cardiothoracic Surgery Department of Surgery University of Colorado Denver | Anschutz Medical Campus Aurora, CO 80045 Medical Research: What is the background for this study? What are the main findings? Dr. Meguid: The surgical literature on adverse outcomes after surgery on pregnant patients is conflicting.  We know that the majority of surgery performed on pregnant patients is not elective (and just over 50% of it in the database studied was emergency surgery).  We expected to find an increased rate of adverse outcomes in those pregnant patients.  However, when we matched the pregnant and non-pregnant women who underwent surgery in the database, with excellent matching on all available preoperative characteristics and on the actual operation performed, we found similar, low rates of 30-day postoperative death and complication.  In this study, pregnant patients had undergone a broad spectrum of different types of operations, including general, vascular, thoracic, head and neck, non-obstetric gynecologic and urologic, orthopedic, reconstructive, and neuro-surgery.  Given the concern that we as surgeons have over operating on pregnant patients, both for the well-being of the patient and her child, our findings are reassuring.  This suggests that we as a medical profession are diligent in minimizing risk to pregnant women who need surgery that cannot be delayed until after the child's birth.  Again, this study faces the limitations of being unable to assess any short term harm done to the fetus and the subsequent long term outcome of the child. (more…)
Author Interviews, Clots - Coagulation, JAMA, Radiology / 12.05.2015

MedicalResearch.com Interview with: Dott. Michelangelo Sartori U.O. di Angiologia e Malattie della Coagulazione Azienda Ospedaliera di Bologna Policlinico Sant'Orsola Malpighi Bologna Medical Research: What is the background for this study? What are the main findings? Response: The safety of withholding anticoagulation only on the basis of ultrasound imaging has not been evaluated in patients with suspected (Upper Extremity Deep Vein Thromobsis) UEDVT. The purpose of this management study was to evaluate the failure rate of ultrasound testing for UEDVT diagnosis in outpatients. Our data show that, similarly to the lower extremity, a negative complete ultrasound assessment of the upper extremity can safely exclude DVT. We found a 3-month VTE rate of 0.6% after a negative ultrasound and such figure is not different from the 3-month VTE incidence in management studies for lower limb DVT.  Thus anticoagulant therapy can be withheld for clinically suspected UEDVT after negative ultrasound examination without further testing in the ambulatory office setting. (more…)
Author Interviews, JAMA / 11.05.2015

William M. Sage MD JD James R. Dougherty Chair for Faculty Excellence School of Law The University of TexasMedicalResearch.com Interview with: William M. Sage MD JD James R. Dougherty Chair for Faculty Excellence School of Law The University of Texas Medical Research: What is the background for this study? What are the main findings? Response: We reviewed settlement agreements in malpractice claims closed by The University of Texas System as part of a larger study on incorporating patient perspectives into safety improvement funded by the Agency for Health Care Research and Quality. Over the five years studied, we found that 88.7% of the 124 settlement agreements that met our study criteria contained non-disclosure provisions, but with little standardization or consistency. Restrictions on disclosure, which selectively burdened patients and their families, seemed broader than needed to protect health care providers from disparagement or to avoid attracting additional litigation. Medical malpractice could happen to anyone at any time during your visit to your hospital. If you or a member of your family have been the victim of medical palpractice you might want to look into getting help from someone like this Tate Law Offices Ft. Worth Personal Injury Law Firm or a law firm that is local to you that might be able to help with your case. Nearly half of the agreements (46.4%) prohibited disclosure of the underlying facts, which may be inconsistent with emerging principles of patient safety and compassionate care, and 26.4% prohibited reporting to regulatory bodies, a restriction that the health system subsequently eliminated in response to our findings. Settlements reached after tort reform took full effect in Texas had stricter non-disclosure provisions than earlier settlements, suggesting greater leverage by defendants notwithstanding the reduced risk of additional litigation. (more…)
Author Interviews, C. difficile, Hospital Acquired, JAMA / 05.05.2015

Dale N. Gerding, MD Research Physician, Edward Hines, Jr., VA Hospital Professor, Department of Medicine of Loyola University Chicago Stritch School of MedicineMedicalResearch.com Interview with: Dale N. Gerding, MD Research Physician, Edward Hines, Jr., VA Hospital Professor, Department of Medicine of Loyola University Chicago Stritch School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Gerding: Naturally occurring strains of C. difficile lack the genes for production of the toxins that cause C. difficile infection (CDI) and are known as non-toxigenic C. difficile (NTCD). These strains when ingested by patients whose normal microbiota is disrupted by antibiotic treatment will harmlessly colonize the colon and remain in the gut for weeks to months. Specific strains of NTCD found in patients were shown to colonize the gut and prevent C. difficile infection when challenged with toxigenic C. difficile strains in animal models. One such NTCD strain, NTCD-M3, was shown to be safe and well tolerated in human volunteer trials and was used in the present study to determine if it would prevent recurrence of C. difficile infection in patients who had just completed treatment with vancomycin or metronidazole of either their first CDI episode or first recurrence of C. difficile infection. 168 patients were randomized to receive by mouth in a liquid form, either 10,000 spores/day of NTCD-M3 for 7 days, 10 million spores/day for 7 days, 10 million spores/day for 14 days, or an identical placebo for 14 days.  Primary outcome was safety, and secondary outcomes were the percent who colonized the gut with NTCD-M3 in the time period from end of treatment to week 6, and the rate of recurrent CDI in the patients at week 6. The results showed that NTCD-M3 was safe and well tolerated, and colonized the gut of 69% of patients who received it. The C. difficile infection recurrence rate was 30% in the placebo patients and 11% in patients who received any of the NTCD-M3 doses (P<.006). The best dose tested was 10 million spores/day for 7 days which resulted in a recurrence rate of only 5% (p<.01 vs placebo). Colonization of the gut was not permanent, but lasted a maximum of 22 weeks. The summary conclusion is that NTCD-M3 is safe, colonized the gut, and when it colonized the gut, reduced recurrence of C. difficile infection to 2% (p<.001 vs patients who were not colonized). (more…)
Author Interviews, Brain Injury, JAMA, Pediatrics / 04.05.2015

Thomas P. Dompier, PhD, ATC President and Injury Epidemiologist Datalys Center for Sports Injury Research and Prevention, Inc Indianapolis, IN 46202 Adjunct Faculty Appointments Ohio University Rocky Mountain University of Health Professions University of South CarolinaMedicalResearch.com Interview with: Thomas P. Dompier, PhD, ATC President and Injury Epidemiologist Datalys Center for Sports Injury Research and Prevention, Inc Indianapolis, IN 46202 Adjunct Faculty Appointments Ohio University Rocky Mountain University of Health Professions University of South Carolina Medical Research: What is the background for this study? D: Dompler: Per the Institute of Medicine’s recent recommendations to better describe the incidence of concussion in sport across the entire spectrum of youth sports (5-23 years), this study is the first to provide an apples-to-apples comparison using epidemiologic data provided by healthcare providers (athletic trainers) who attended all practices and games and used the same methodology to report concussions and student-athlete exposure information. Medical Research: What are the main findings? D: Dompler: a.  The main findings are that the risk (how many players out of 100 can expect to suffer at least one concussion during the season) is lowest in the youth, and increases with age. b. Game concussion rates (how many players out of 1000 exposed during a practice or game, includes multiple concussions to the same player) are highest in college but practice concussion rates are lowest in college during practice.  This suggests more can be done during high school and youth practices to reduce concussion frequency (e.g. limiting how much time can be devoted to full contact, reducing player-to-player contact by teaching proper tackling without using full contact drills such as the Oklahoma drill and others). c. While the rate is higher, there is still a substantial number of concussions that occur during practice (because there are more practices), therefore sports medicine staff should be available at both if possible (this is difficult at the youth level because of cost, however). (more…)
Author Interviews, Blood Pressure - Hypertension, JAMA, Salt-Sodium / 29.04.2015

Lynn L. Moore, DSc, MPH Department of Medicine Boston University School of Medicine Boston, Massachusetts MedicalResearch.com Interview with: Lynn L. Moore, DSc, MPH Department of Medicine Boston University School of Medicine Boston, Massachusetts Medical Research: What is the background for this study? Dr. Moore: The USDA’s current Dietary Guidelines for sodium intake have become increasingly controversial. Current recommendations include restricting sodium intake after the age of 2 years to no more than 2300 mg per day. For African-American adults and children, intakes should be restricted to no more than 1500 mg per day. Actual intake levels are much higher, with most Americans consuming about 3500 mg per day. Our goal was to estimate the effects of dietary sodium and potassium intakes on the change in blood pressure throughout adolescence. We used data from the National Growth and Health Study, a prospective study of more than 2000 girls who were 9-10 years of age at the time of enrollment. Lifestyle factors were assessed repeatedly throughout the study, and blood pressure was measured annually. Dietary sodium and potassium were assessed using multiple sets of three-day diet records. We used longitudinal modeling to estimate the effects of dietary sodium and potassium on blood pressure change over 10 years. Medical Research: What are the main findings? Dr. Moore: In this study, there was no evidence for a beneficial effect of reduced sodium intake on blood pressure change during adolescence. By 19-20 years of age, girls who consumed more than 4000 mg of sodium per day had systolic and diastolic blood pressure levels that were similar to those seen among girls with lower levels of sodium intake. Specifically, there was no beneficial effect on blood pressure associated with sodium intakes of less than 2500 mg per day. These results were similar for blacks and whites. In contrast, the repeated measures analyses showed that girls who consumed more than 2400 mg of potassium per day had lower blood pressures throughout adolescence compared with girls consuming less than 1800 mg per day of potassium. (more…)
Alzheimer's - Dementia, Author Interviews, Diabetes, JAMA / 28.04.2015

MedicalResearch.com Interview with: Dimitry S. Davydow, MD, MPH Associate Professor Department of Psychiatry and Behavioral Sciences University of Washington School of Medicine Seattle, WA 98195 Dr, Davydow wishes to acknowledge Dr. Wayne Katon, the lead investigator of the study, who passed away on March 1, 2015. Medical Research: What is the background for this study? Dr. Davydow: The medical and public health communities have known for quite a while that diabetes and depression are both potential risk factors for developing dementia later in life. Dr. Wayne Katon previously published two articles detailing the results of two studies of relatively large groups of patients (one with nearly 4,000 patients and the other with 29,000 patients) with diabetes showing that those with diabetes and co-existing depression had a greater risk of developing dementia later in life than those patients with just diabetes. These initial studies were important since patients with diabetes are 3 to 4-times more likely to suffer from depression compared to the general population. However, it remained unclear when comparing to a population without either diabetes or depression, to what extent each independently raised the risk of developing dementia, and then to what extent having both conditions increased an individual’s subsequent risk of dementia. We sought to answer these questions with this study. In addition, with the growing obesity epidemic, which carries with it higher burdens of both diabetes and depression, there is reason to be concerned that the risk of dementia could be higher at even younger ages. To address this issue, we also wanted to see if there was a differential impact of the combination of diabetes and co-existing depression on dementia risk among those younger than 65 compared to individuals 65 or older. We were fortunate to be able to examine health data from all Danish citizens 50 or older over a 6 year period, a population numbering nearly 2.5 million people to be able to answer these questions. Medical Research: What are the main findings? Dr. Davydow: We found that compared to individuals without diabetes or depression, those with diabetes alone had about a 15% greater risk of developing dementia, those with depression alone had about an 83% greater risk of developing dementia, and those with both diabetes and co-existing depression had a 107% greater risk of developing dementia compared to those without either condition. We also found that of all of the cases of dementia diagnosed in Denmark among individuals 50 or older between 2007 through 2013, 6% were potentially due to combination of having both diabetes and depression. This was also true for those 65 or older, where 6% of all diagnosed dementia was potentially attributable to the combination of both diabetes and depression. However, among individuals under age 65, we found that 25% of all cases of dementia may have been directly attributable to the combination of diabetes and co-existing depression. (more…)
Author Interviews, End of Life Care, Heart Disease, JAMA, Kidney Disease / 27.04.2015

MedicalResearch.com Interview with: Susan P. Y. Wong, M.D. Acting Instructor & Senior Research Fellow Division of Nephrology University of Washington Medical Research: What is the background for this study? What are the main findings? Dr. Wong: There is a paucity of information on the use of cardiopulmonary resuscitation (CPR) and its outcomes among patients receiving maintenance dialysis. To address this knowledge gap, we performed a retrospective study to define contemporary trends in in-hospital CPR use and its outcomes among a nationally representative sample of 663,734 patients receiving maintenance dialysis between 2000 and 2011. We found that in-hospital CPR use among this cohort of patients was very high—nearly 20 times more common than that found in the general population. The rate of in-hospital CPR use has also been increasing among patients receiving maintenance dialysis despite evidence of poor long-term survival among these patients. Median survival after hospital discharge for members of this cohort was only 5 months, and this has not change substantially in the recent decade. We also found that a large proportion  of dialysis patients who died in hospital settings had received CPR during their terminal hospitalization. This proportion has also been steadily increasing over time, and in 2011, 1 in 5 dialysis patients who died in hospital had received CPR during their terminal hospitalization. (more…)