Alcohol, Author Interviews, Brigham & Women's - Harvard, Cancer Research, Dermatology / 26.10.2015

[caption id="attachment_18787" align="alignleft" width="200"]Shaowei Wu, MD, PhD Department of Dermatology, Warren Alpert Medical School Brown University, Providence, Rhode Island Department of Dermatology Brigham and Women’s Hospital and Harvard Medical School Boston, Massachusetts Dr. Shaowei Wu[/caption] MedicalResearch.com Interview with: Shaowei Wu, MD, PhD Department of Dermatology, Warren Alpert Medical School Brown University, Providence, Rhode Island Department of Dermatology Brigham and Women’s Hospital and Harvard Medical School Boston, Massachusetts Medical Research: What is the background for this study? What are the main findings? Response: Basal cell carcinoma (BCC) of the skin is the most prevalent cancer in the US, and is responsible for substantial morbidity and billions of dollars of health care expenditures. Knowledge on the modifiable risk factors of BCC is required for targeted prevention of cancer incidence. Alcohol consumption is a well-known risk factor for human cancer and has been linked to a number of cancers, including breast, prostate, pancreatic, and colon cancers. Interestingly, a large epidemiological study has reported a positive association between alcohol consumption and increased prevalence of severe sunburn, an established skin cancer risk factor. It is hypothesized that metabolites of alcohol (e.g., acetaldehyde) can serve as photosensitizers and promote skin carcinogenicity in the presence of UV radiation. However, epidemiological evidence for the association between alcohol consumption and BCC risk has been limited and a few previous studies on this topic have yielded conflicting results. Therefore we conducted a comprehensive prospective study to investigate this question using data from three large cohorts including the Nurses’ Health Study (1984-2010), Nurses’ Health Study II (1989-2011), and Health Professionals Follow-up Study (1986-2010). We documented a total of 28,951 incident Basal cell carcinoma cases over the study follow-up. We found that increasing alcohol intake was associated with an increased Basal cell carcinoma risk in both women and men. In the combined analysis with all 3 cohorts, those who consumed 30 grams or more alcohol per day had a 22% higher risk of developing BCC when compared to nondrinkers. This increased risk was consistent in people with different levels of sun exposure. We also found that BCC risk was associated with alcohol intake levels more than a decade ago, suggesting that alcohol may have a lagged effect that can persist for a long-term period. Among the individual alcoholic beverages, white wine and liquor were positively associated with Basal cell carcinoma risk whereas red wine and beer were not associated with BCC risk. This difference may be due to some other chemicals accompanying alcohol in the specific beverages. For example, red wine contains higher amounts of phenolic compounds compared to white wine, and these compounds have antioxidant activities which may be beneficial for counteracting the potential carcinogenic properties of alcohol and its metabolites.
Author Interviews, FDA, Immunotherapy, Lung Cancer / 24.10.2015

MedicalResearch.com Interview with: Dickran Kazandjian, MD Office of Hematology and Oncology Products Center for Drug Evaluation and Research US Food and Drug Administration Silver Spring, Maryland Medical Research: What is the background for this study? What are the main findings? Dr. Kazandjian: Nivolumab is the first approved immunotherapy, for the treatment of metastatic squamous non–small-cell lung cancer (NSCLC) after platinum-based chemotherapy.  FDA initiated an expedited review after obtaining the data monitoring committee report of a planned interim analysis of a second-line squamous NSCLC trial demonstrating a large overall survival benefit (CheckMate 017). Nivolumab efficacy in metastatic Squamous (SQ) NSCLC has been previously reported in two studies.  CheckMate 063 was a single-arm trial in 117 patients with metastatic SQ NSCLC who had progressed after previous treatment with 2 systemic regimens including platinum-based doublet chemotherapy (Rizvi et al)  CheckMate 017 was a randomized study of nivolumab compared to docetaxel in 272 patients with metastatic SQ NSCLC who had progressed after prior platinum-based doublet chemotherapy (Brahmer et al).  The median survival of patients randomized to nivolumab was 9.2 months vs 6.0 months for docetaxel (hazard ratio, 0.59; 95%CI, 0.44-0.79; P < .001) a 41% improvement in the risk of death. Approval was supported by the single-arm study which demonstrated an objective response rate of 15% and at the time of analysis, 10 of the 17 responding patients (59%) had response  durations of 6 months or longer. The FDA approved nivolumab on March 4, 2015, saving 6 months by not waiting for formal preparation of data by the sponsor and 2.5 months by expediting review.
Author Interviews, Cancer Research, MD Anderson, Nature / 23.10.2015

[caption id="attachment_18717" align="alignleft" width="114"]Dihua Yu, M.D., Ph.D. Professor and Deputy Chair Dept. of Molecular and Cellular Oncology Hubert L. and Olive Stringer Distinguished Chair in Basic Science University Distinguished Teaching Professor Co-Director, Center of Biological Pathways Univ. of TX MD Anderson Cancer Center Houston, TX 77030 Dr. Dihua Yu[/caption] MedicalResearch.com Interview with: Dihua Yu, M.D., Ph.D. Professor and Deputy Chair Dept.  of Molecular and Cellular Oncology Hubert L. and Olive Stringer Distinguished Chair in Basic Science University Distinguished Teaching Professor Co-Director, Center of Biological Pathways Univ. of TX MD Anderson Cancer Center Houston, TX 77030 Medical Research: What is the background for this study? What are the main findings? Dr. Yu: Metastasis is the number one cause of cancer-related mortality. Despite the continuous advancement of modern medicine in better controlling primary cancer progress, brain metastasis incidence constantly and steadily increases. Major neoplastic diseases such as melanoma, lung, breast, and colon cancers have high incidences of brain metastases. One-year survival after diagnosis of brain metastasis is less than 20%. Cancer cells dynamically interacts with specific organ microenvironments to establish metastasis as depicted by the “seed and soil” hypothesis. Many research have focused on how tumor cells modulate the metastatic microenvironment, but the reciprocal effect of the organ microenvironment on tumor cells has been overlooked. The brain tissue is very distinct from primary tumor environment for metastatic cancer cells. Brain metastasis frequently manifests in the late stages of cancer, and a long period of dormancy often precedes relapse. This implies that additional regulations imposed by the brain microenvironment are essential for metastatic colonization and outgrowth. Yet it is unclear when and how disseminated tumor cells acquire the essential traits from the brain microenvironment that primes their subsequent metastatic outgrowth.
Author Interviews, Beth Israel Deaconess, CHEST, Education, Pulmonary Disease / 23.10.2015

[caption id="attachment_18711" align="alignleft" width="116"]Dr. George Cheng MD Beth Israel Deaconess Medical Center Dr. George Cheng[/caption] MedicalResearch.com Interview with: Dr. George Cheng MD Beth Israel Deaconess Medical Center  Medical Research: What is the background for this study? What are the main findings? Dr. Cheng: Since the introduction of flexible bronchoscope in late 1960s, flexible bronchoscopy has gained wide popularity and with over 500,000 procedures being performed in the USA annually.  Bronchoscopy training has been undergoing rapid advancement in recent years.  Virtual bronchoscopy, either web-based training or VR bronchoscopic simulators, were used to teach and to improve performance in bronchoscopy.  However, virtual reality simulators often cost over $100,000 dollars.  Given the prohibitive high cost, recent CHEST expert panel recommended that high fidelity simulators be offered only in regional simulation centers.  Therefore, low cost realistic bronchoscopy training models are an area of need. Recent development in 3D printing and 3D medical modeling has allowed clinicians to utilize CT scans to create physical models.  This approach can be used to create affordable 3D printed, anatomically accurate bronchoscopy training models.  However, the 3D printed tracheobronchial model has never been evaluated as a bronchoscopy simulation tool.  We aimed to address this question with our study. The 3D printed bronchoscopy model was generated from flexible nylon material and stained to match the airway mucosa coloration.  Participants of varies training levels performed bronchoscopy on both standard and 3D printed bronchoscopy model, graded each on a sliding scale from 0-100.  Overall, clinicians preferred the 3D printed model regardless of their level of training.
Author Interviews, Brigham & Women's - Harvard, JAMA, Prostate Cancer, Race/Ethnic Diversity, Surgical Research / 23.10.2015

[caption id="attachment_18619" align="alignleft" width="120"]Dr. Quoc-Dien Trinh MD Assistant Professor of Surgery Harvard Medical School Brigham and Women's Hospital Boston, MA 02115 Dr. Quoc-Dien Trinh[/caption] MedicalResearch.com Interview with: Dr. Quoc-Dien Trinh MD Assistant Professor of Surgery Harvard Medical School  Brigham and Women's Hospital Boston, MA 02115 Medical Research: What is the background for this study? What are the main findings? Dr. Trinh:  Blacks who undergo radical prostatectomy, e.g. surgical removal of the prostate for cancer, are more likely to experience complications, emergency room visits, readmissions compared to their non-hispanic White counterparts. As a result, the 1-year costs of care for Blacks is significantly higher than non-hispanic Whites. Interestingly, despite these quality of care concerns, the survival of elderly Blacks and Whites undergoing prostatectomy is the same. Medical Research: What should clinicians and patients take away from your report? Dr. Trinh: A possible interpretation of our findings is that the biological differences in tumor aggressiveness among Blacks  (e.g. Blacks have more aggressive prostate cancer than Whites) may have been exaggerated, and that the perceived gap in survival is a result of lack of access or cultural perceptions with regard to surgical care for prostate cancer or other factors that differentiate who makes it to the operating table.
Author Interviews, C. difficile, Gastrointestinal Disease, Mayo Clinic, Microbiome, Transplantation / 22.10.2015

[caption id="attachment_18565" align="alignleft" width="125"]Dr. Sahil Khanna MBBS Assistant Professor of Medicine Mayo Clinic Dr. Sahil Khanna[/caption] MedicalResearch.com Interview with: Dr. Sahil Khanna MBBS Assistant Professor of Medicine Mayo Clinic Medical Research: What is the background for this study? What are the main findings? Response: C. difficile infection patients are at a high risk of complications such as treatment failure. Gut microbiota signatures associated with CDI have been described but it is unclear if differences in gut microbiota play a role in response to therapy. No studies have identified predictors of treatment failure and we aimed to identified gut microbiota signatures to predict response to treatment for primary C. difficile . While there were no clinical predictors of treatment response, there were increases in certain genera in patients with successful treatment response in the fecal samples at initial diagnosis compared to non-responders. A risk index built from this panel of microbes highly differentiated between patients based on response and ROC curve analysis showed that this risk index was a strong predictor of treatment response, with a high area under the curve of 0.83..
Author Interviews, Brigham & Women's - Harvard, Gastrointestinal Disease / 22.10.2015

[caption id="attachment_18654" align="alignleft" width="150"]Kyle Staller, MD, MPH Massachusetts General Hospital Harvard Medical School Dr. Kyle Staller[/caption] MedicalResearch.com Interview with: Kyle Staller, MD, MPH Massachusetts General Hospital Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Dr. Staller: Constipation is exceedingly common and exerts a considerable economic effect.  Although many clinicians assume that the severity of constipation symptoms is the primary driver of obligation absenteeism, our data from over 100 patients undergoing physiologic evaluation for chronic constipation demonstrates that comorbid depression was a bigger predictor or work and school absenteeism than symptom severity and quality of life.
ADHD, Author Interviews, Mental Health Research, Nature, NYU/NYMC / 22.10.2015

[caption id="attachment_18640" align="alignleft" width="300"]Michael M. Halassa, MD, PhD, Assistant professor Departments of Psychiatry and Neuroscience and Physiology The Neuroscience Institute Depts. of Psychitatry Langone Medical Center New York, NY 10016 Dr. Michael Halassa[/caption] MedicalResearch.com Interview with: Michael M. Halassa, MD, PhD, Assistant professor Departments of Psychiatry and Neuroscience and Physiology The Neuroscience Institute Depts. of Psychitatry Langone Medical Center New York, NY 10016 Medical Research: What is the background for this study? What are the main findings? Dr. Halassa:  Attention is a vital aspect of our daily life and our minds are not merely a reflection of the outside world, but rather a result of careful selection of inputs that are relevant. In fact, if we indiscriminately open up our senses to what’s out there, we would be totally overwhelmed. Selecting relevant inputs and suppressing distractors is what we call attention, and as humans we are able to attend in a highly intentional manner. Meaning, we choose what to pay attention to, and we do so based on context. If you’re driving and getting directions from your GPS, you’ll be intentionally splitting your attention between your vision and hearing. Now, in one context, you might have just updated the GPS software, so you know it’s reliable; this would allow you to intentionally pay attention more to the voice coming from the GPS. In another context, the GPS software may be outdated making voice instructions unreliable. This context would prompt you to direct your attention more towards using visual navigation cues and less to the GPS voice. How the brain intentionally and dynamically directs attention based context is unknown. The main strength of our study is that we were able to study context-dependent attention in mice. Mice are unique models because they provide genetic tools to study brain circuits. Meaning, we can turn circuits on and off very precisely in the mouse, and in a way we cannot do in other experimental animals. The inability to do these types of manipulations has been the major roadblock for progress in understanding what brain circuits mediate attention and its intentional allocation. Because we couldn’t train mice to drive and listen to the GPS, we decided to do something much simpler. Based on context (the type of background noise in the experimental enclosure), a mouse had to select between conflicting visual and auditory stimuli in order to retrieve a milk reward. Mice love milk; it turns out, and will work tirelessly to do well on getting it. Each trial, the mouse is told ‘you need to pick the light flash’ or ‘you need to pick the auditory sweep’; these stimuli appeared on either side of the mouse randomly so the animal really had to pay attention in order to get its reward. It also had to take the context into account. We found that mice did this task, and as humans would do, they were reliant on the prefrontal cortex for determining the appropriate context. The major finding was that the prefrontal cortex changed the sensitivity of the brain to incoming stimuli (meaning, made the visual stimulus brighter when the mouse cared about vision and made the auditory stimulus louder when the mouse cared about hearing), by influencing activity in the thalamus. The thalamus is the major early relay station in the brain. The prefrontal cortex does that by instructing the brain’s switchboard, known as the thalamic reticular nucleus (TRN) to control how much visual or auditory information the thalamus was letting through. So in a sense, we discovered that executive function, represented by the prefrontal cortex, can talk to ‘attentional filters’ in the thalamus to determine what ultimately is selected from the outside environment to build our internal world.
Author Interviews, Cannabis, Columbia, JAMA / 21.10.2015

Deborah S. Hasin, Ph.D. Professor of Epidemiology Columbia University New York, New York 10032MedicalResearch.com Interview with: Deborah S. Hasin, Ph.D. Professor of Epidemiology Columbia University New York, New York 10032 Medical Research: What is the background for this study? What are the main findings? Dr. Hasin: This study is based on data from two large-scale national surveys conducted over an eleven-year period that are designed to provide information on many health-related conditions in U.S. adults, including use of marijuana and other substances, changes over time in the prevalence of marijuana users, changes over time in the prevalence of disorders such as marijuana abuse and dependence, and the correlates and predictors of those disorders. The main findings of the study are that between 2001-2002 and 2012-2013, the prevalence of marijuana users in the United States adult general population more than doubled, from 4.1% to 9.5%, while the prevalence of adults with marijuana use disorder (abuse or dependence) also increased substantially, from 1.5% to 2.9% of American adults. About three in ten adult marijuana users met criteria for a marijuana use disorder. The findings are consistent with other studies showing increases in rates of marijuana-related harms over the same general time period. This may be to do with how accessible marijuana has become, for example you can even find a purple lotus menu on various websites. This is perfectly safe and fun, but can develop into an addiction later in life.
Anemia, Author Interviews, Infections, Kidney Disease, UCSF / 21.10.2015

Dr. Julie H. Ishida MD San Francisco Veterans Affairs Medical Center Nephrology Section San Francisco, CAMedicalResearch.com Interview with: Dr. Julie H. Ishida MD San Francisco Veterans Affairs Medical Center Nephrology Section San Francisco, CA Medical Research: What is the background for this study? What are the main findings? Dr. Ishida: Intravenous iron is important in the treatment of anemia of end-stage renal disease, but it is biologically plausible that iron may increase infection risk. While results from epidemiologic studies evaluating the association between intravenous iron and infection in hemodialysis patients have been conflicting, guidelines for the treatment of anemia of chronic kidney disease have recommended caution in prescribing, avoidance and withholding of intravenous iron in the setting of active infection. However, no data specifically support the recommendation to withhold intravenous iron during active infection. Our study observed that among hemodialysis patients hospitalized for bacterial infection who had been receiving intravenous iron as an outpatient, continued receipt of intravenous iron was not associated with higher all-cause mortality, readmission for infection, or longer hospital stay.
Author Interviews, Breast Cancer, JAMA, Mammograms, UC Davis / 21.10.2015

[caption id="attachment_18491" align="alignleft" width="75"]Diana Miglioretti, PhD Diana Miglioretti, PhD[/caption] MedicalResearch.com Interview with: Diana L. Miglioretti, PhD Dean's Professor in Biostatistics Department of Public Health Sciences UC Davis School of Medicine Davis, CA  95616 Medical Research: What is the background for this study? What are the main findings? Dr. Miglioretti: Screening mammography intervals remain under debate in the United States. The US Preventive Services Task Force recommends biennial (every other year) screening, whereas other organizations recommend annual screening. To help inform their updated screening guidelines, the American Cancer Society guideline development group requested that the US Breast Cancer Surveillance Consortium conduct a study comparing cancer outcomes among women screened annually vs. biennially. Prior studies conducted by the consortium used wide intervals for defining annual and biennial mammograms. We wanted to evaluate cancer outcomes for women who more closely adhere to screening intervals. Our goal was to determine if women diagnosed with cancer following biennial screening have tumors with less favorable prognostic characteristics compared to women diagnosed after annual screening. We evaluated outcomes separately by age and by menopausal status because evidence suggests that younger women and premenopausal women may have more aggressive tumors and thus may benefit from more frequent screening. We found from this study that premenopausal women diagnosed with invasive breast cancer following biennial versus annual screening mammography were more likely to have tumors with less-favorable prognostic characteristics (e.g., later stage, larger size). For example, women with an invasive breast cancer diagnosed after a biennial screen had a 28% increased risk of a stage IIB or higher tumor, a 21% increased risk of being diagnosed with a tumor >15 mm, and an 11% higher risk of being diagnosed with a tumor with any less-favorable prognostic characteristic compared women diagnosed with breast cancer following an annual mammogram. In contrast, we found postmenopausal women not using hormone therapy and women 50 years of age or older had similar proportions of tumors with less-favorable prognostic characteristics regardless of screening interval. Relative risk estimates were close to one with no significant differences between biennial and annual screeners. Among postmenopausal women using hormone therapy at the time of the mammogram and women age 40-49, results were less clear. Relative risk estimates for biennial versus annual screeners were consistently above one, but were not as large as for premenopausal women and were not statistically significant.
Author Interviews, Brigham & Women's - Harvard, Cost of Health Care, Health Care Systems, JAMA / 20.10.2015

MedicalResearch.com Interview with: Hannah Neprash PhD student Health Policy program Harvard University. Medical Research: What is the background for this study? Response: Hospitals are increasingly employing or purchasing physician practices. This trend started before the Affordable Care Act, as our study documents, but there is a concern that these trends may accelerate as providers reorganize to meet the challenges of new payment models that hold providers accountable for the entire spectrum of patient care, spanning inpatient and outpatient settings. It’s not clear how this change in provider market structure should affect spending. It could lead to lower spending, if care is better coordinated, reducing waste and unnecessary utilization. But, it could also lead to higher spending if larger provider groups have more market power and can negotiate higher prices with insurers. Medical Research: What are the main findings? Response: We used Medicare claims to quantify the share of physicians in major metropolitan markets that were owned or employed by a hospital. Most markets saw an increase in physician-hospital integration from 2008 to 2012. The average market saw a 3% increase in physician-hospital integration; the 75th percentile market saw a 5% increase; and the 95th percentile market saw a 15% increase. An increase in physician-hospital integration equivalent to the 75th percentile was associated with a $75 per person (or 3%) increase in annual outpatient spending among a non-elderly commercially insured population. This was driven by price increases – as we found no change in utilization. We did not find a similar association between physician-hospital integration and inpatient hospital spending. This is likely because hospital markets were already less competitive than physician markets at the beginning of our study period. When a hospital system buys a physician practice, the hospitals might not gain much bargaining power against an insurer in negotiating prices for inpatient care, but the hospital’s bargaining power could be used to negotiate higher fees for the outpatient physician practice.  That is, an insurer may not be persuaded by the threat of excluding the physician practice from its network, but the threat of excluding the entire hospital system from the insurer’s network is likely to carry more weight.
Author Interviews, Baylor University Medical Center Dallas, Biomarkers, BMJ, Cancer Research / 20.10.2015

Ajay Goel, Ph.D. Investigator/Professor Director, Center for Gastrointestinal Research Director, Center for Epigenetics, Cancer Prevention and Cancer Genomics Baylor Research Institute and Charles A. Sammons Cancer Center Baylor University Medical Center Dallas, TX 75246MedicalResearch.com Interview with: Ajay Goel, Ph.D. Investigator/Professor Director, Center for Gastrointestinal Research Director, Center for Epigenetics, Cancer Prevention and Cancer Genomics Baylor Research Institute and Charles A. Sammons Cancer Center Baylor University Medical Center Dallas, TX 75246 Medical Research: What is the background for this study? What are the main findings? Dr. Goel: Colorectal cancer (CRC) remains one of the most common and lethal malignancies worldwide, and is the second leading cause of cancer-related deaths in the United States. Although there are some improvements in cancer treatments, such as development of novel chemotherapeutic drugs and technical advances in invasive treatment for metastatic lesion, there is a clear need for prognostic biomarkers that can identify high-risk patients, who can benefit from intensive post-treatment surveillance protocols for early detection of recurrence. Small nucleolar RNAs (snoRNAs) are one of the largest groups of single-stranded small ncRNAs, and in the past, snoRNAs were recognized for housekeeping functions due to their roles in rRNA maturation, while causing a relatively low impact on cellular homeostasis. However, recent evidence has revealed a new and previously unrecognized role of snoRNAs in the control of cell fate and oncogenesis in various cancers. The main finding of this study is to firstly demonstrate the clinical impact of snoRNA expression as a predictive biomarker of recurrence and poor prognosis in patients with Colorectal cancer. This study for the first time showed that higher levels of SNORA42 were associated with overall and disease-free survival, and emerged as a risk factor for the return of cancer in another part of the body. It was also correlated with high risk of recurrence and shorter survival in a smaller sample of bowel cancer patients in early stages of their disease.
Author Interviews, Medical Imaging, NYU/NYMC, Surgical Research / 19.10.2015

[caption id="attachment_18550" align="alignleft" width="200"]Nolan S. Karp, MD Associate Professor, Hansjorg Wyss Department of Plastic Surgery NYU Langone Dr. Nolan S. Karp[/caption] MedicalResearch.com Interview with: Nolan S. Karp, MD  Associate Professor, Hansjorg Wyss Department of Plastic Surgery NYU Langone Medical Research: What is the background for Three-dimensional imaging? Dr. Karp: This was really developed for industry in product engineering.  We and others applied this to medicine. Medical Research: What kind of technology is required? Dr. Karp: This is a fancy picture.  We obtain a 3D surface scan of the person or an object, which corresponds to a digital data set. Medical Research: How does Three-dimensional imaging help the physician and patient plan for better surgical outcomes? Dr. Karp: It lets you simulate the surgery.  For the surgeon, we can plan the surgery better.  For the patient, they can see the expected outcome better, before surgery.
Author Interviews, Brigham & Women's - Harvard, Heart Disease, JACC, Pediatrics / 18.10.2015

[caption id="attachment_18531" align="alignleft" width="300"]Ashley Winning, ScD, MPH Postdoctoral Research Fellow Department of Social and Behavioral Sciences Harvard T.H. Chan School of Public Health Dr. Ashley Winning[/caption] MedicalResearch.com Interview with: Ashley Winning, ScD, MPH Postdoctoral Research Fellow Department of Social and Behavioral Sciences Harvard T.H. Chan School of Public Health Medical Research: What is the background for this study?  Dr. Winning: Several studies have found associations between psychological distress and heart disease and diabetes; however, much of the research has measured distress and disease risk in adulthood and we can’t tell how long people have been distressed or how far-reaching the effects of distress are. Some work has shown that childhood distress is associated with adult health, indicating that distress may start to affect health even earlier in life than we thought. However most of the research has measured distress at a single point in time so we have not been able to answer questions regarding effects of persistent distress or if effects on health are less bad if people become less distressed over time. Medical Research: What are the main findings? Dr. Winning: Distress at any period in the life course was associated with increased cardiovascular and metabolic disease risk in adulthood (age 45). Not surprisingly, those with high levels of distress in both childhood and adulthood had the greatest cardiometabolic risk. The most striking finding is that high levels of childhood distress (measured in childhood) predicted heightened adult disease risk, even when there was no evidence that these high levels of distress persisted into adulthood.
Author Interviews, Case Western, Hand Washing, Infections / 17.10.2015

[caption id="attachment_18519" align="alignleft" width="150"]Curtis J. Donskey, MD Professor of Medicine Case Western Reserve University Staff Physician, Infectious Diseases Section, Louis Stokes Cleveland VA Medical Center Dr. Curtis Donskey[/caption] MedicalResearch.com Interview with: Curtis J. Donskey, MD Professor of Medicine Case Western Reserve University Staff Physician, Infectious Diseases Section, Louis Stokes Cleveland VA Medical Center Medical Research: What is the background for this study? Dr. Donskey: Personal protective equipment (PPE) is intended to protect healthcare personnel by preventing them from acquiring an infection and to protect patients by preventing pathogen transmission. This study focused on gloves and gowns which are designed to reduce contamination of the skin and clothing of personnel. There are several concerns about the effectiveness of gloves and gowns.
  • First, several studies have demonstrated that personnel may acquire pathogens such as Clostridium difficile and methicillin-resistant Staphylococcus aureus (MRSA) on their hands and clothing during patient care activities despite wearing gloves and gowns.
  • Second, some studies involving simulations have suggested that contamination of the skin and clothing occurs frequently during removal of gloves and gowns.
  • Finally, lapses in technique for PPE removal may contribute to acquisition of potentially fatal pathogens such as Ebola virus. These concerns highlight the urgent need for improved strategies to prevent contamination of personnel during PPE removal.
We had 3 goals in the study.
  • First, we wanted to determine if contamination with a fluorescent lotion during glove and gown removal would correlate well with contamination with a benign virus. We did this because the fluorescent lotion method could potentially be very useful for training personnel because you can easily visualize contamination with a black light and provide immediate feedback.
  • Second, we used the fluorescent lotion method to evaluate contamination of the skin and clothing of personnel from 4 hospitals during removal of contaminated gloves or gowns.
  • Finally, we tested whether an intervention would reduce contamination in one of the 4 hospitals. The intervention included practice in removal of contaminated gloves and gowns with immediate visual feedback based on fluorescent lotion contamination of skin and clothing.
Medical Research: What are the main findings? Dr. Donskey: Our first key finding was that contamination with the fluorescent lotion correlated well with contamination with the benign virus. This was an important finding because it suggests that the fluorescent lotion method is a useful surrogate method to assess pathogen contamination during Personal protective equipment removal. Our second key finding was that contamination of the skin and clothing of personnel occurred frequently during removal of contaminated gloves or gowns. For 435 total simulations, contamination occurred 46% of the time, with similar results for each the 4 study hospitals (43%-50%). Incorrect donning or doffing technique was common and was associated with an increase in contamination (70% of the time with incorrect technique versus 30% with correct technique). Our final key finding was that the intervention was very effective in reducing contamination during PPE removal. Immediately after the training session, the frequency of contamination decreased from 60% to 20% and then was 12% at 1 and 3 months after the intervention.
Author Interviews, Smoking, University of Pennsylvania, Weight Research / 16.10.2015

[caption id="attachment_18458" align="alignleft" width="150"]Dr. Samuel H. Preston Ph.D Professor, Department of Sociology and Population Studies Center University of Pennsylvania Philadelphia, Pennsylvania Dr. Samuel Preston[/caption] MedicalResearch.com Interview with: Dr. Samuel H. Preston Ph.D Professor, Department of Sociology and Population Studies Center University of Pennsylvania Philadelphia, Pennsylvania  Medical Research: What is meant by the Obesity Paradox? Is it reported more in some groups? Dr. Preston: The obesity paradox is a term that is used when a study finds that obese people have lower mortality than non-obese people. The finding is considered paradoxical because the obese do not have lower mortality in cross-sections of the general population. The paradox is, however, commonly observed among people who suffer from a particular illness such as heart disease or diabetes.  Medical Research: What are the main findings of your study? What is reverse causation and how does it affect obesity studies? Dr. Preston: We find in a nationally representative sample that, among people suffering from cardiovascular disease, mortality is indeed lower for people who are overweight or obese than for people of normal weight. So the paradox appears among this group. However, when we study people's mortality according to their maximum lifetime weight, the paradox disappears. We attribute its disappearance primarily to the fact that many  people who have lost weight from their maximum are doing so because they are ill. This phenomenon is referred to as "reverse causation" because illness is affecting weight rather than weight affecting illness and mortality.
Anemia, Author Interviews, Cancer Research, University Texas / 16.10.2015

[caption id="attachment_18447" align="alignleft" width="114"]Anil K. Sood, M.D Dr. Anil Sood[/caption] MedicalResearch.com Interview with: Anil K. Sood, M.D. Professor of Gynecologic Oncology and Reproductive Medicine The University of Texas MD Anderson Cancer Center Medical Research: What is the background for this study? What are the main findings? Dr. Sood: Erythropoietin is an important drug for managing anemia, but concerns have surfaced that it might promote cancer growth. The data with the conventional epo-receptor were not convincing with regard to an explanation for why tumor growth might increase. Therefore, we considered whether there could be an alternative receptor to explain these findings. We carried out a systematic search and identified EphB4 as the alternative receptor that explained the increased tumor growth in response to epo.
Author Interviews, Brigham & Women's - Harvard, Clots - Coagulation, Heart Disease, JACC / 16.10.2015

Laura Mauri, MD, MSc Division of Cardiovascular Medicine, Department of Medicine Brigham and Women’s Hospital Boston, MA 02115MedicalResearch.com Interview with: Laura Mauri, MD, MSc Division of Cardiovascular Medicine, Department of Medicine Brigham and Women’s Hospital Boston, MA 02115  Medical Research: What is the background for this study? What are the main findings? Dr. Mauri: The Dual Antiplatelet Therapy (DAPT) Study, the largest randomized controlled trial to date comparing different durations of dual antiplatelet therapy (thienopyridine plus aspirin) after coronary stenting, found that patients who were free from major ischemic or bleeding events at 1 year after coronary stenting (either drug-eluting [DES] or bare metal [BMS]), and who were compliant with their antiplatelet therapy, experienced significant reductions in stent thrombosis and myocardial infarction (MI) but increases in moderate or severe bleeding when treated with 30 months of thienopyridine plus aspirin, as compared with 12 months. We analyzed these outcomes in a post hoc analysis of the subset of patients who received everolimus-eluting stents (EES) in the DAPT Study, because EES were the most frequently used stent in the study, and because data suggest that EES may have lower rates of stent thrombosis when compared with paclitaxel-eluting stents. We found that 30 months of dual antiplatelet therapy after coronary stenting (compared to 12 months) was associated with reduced rates of stent thrombosis and MI, no difference in a composite outcome of death, MI and stroke, and increased rates of moderate or severe bleeding. As found in the primary analysis of the DAPT Study, 30 months of dual antiplatelet therapy was associated with increased all-cause mortality, largely due to increased non-cardiovascular mortality. Bleeding-related deaths accounted for a minority of these deaths, where as cancer-related deaths in patients with pre-existing cancer diagnoses accounted for the majority of the mortality difference.
Author Interviews, Autism, Radiology, UCLA / 16.10.2015

MedicalResearch.com Interview with: Kay Jann, PhD, Department of Neurology Danny JJ Wang, Prof., Department of Neurology Laboratory of Functional MRI Technology Ahmanson-Lovelace Brain Mapping Center Department of Neurology University of California Los Angeles Los Angeles  Medical Research: What is the background for this study? What are the main findings? Response: The brain controls most of our behavior and thus changes in how brain areas function and communicate with each other can alter this behavior and lead to impairments associated with mental disorders. Higher cognitive functions are controlled by brain areas that form complex interconnected networks and alterations in these networks can lead to cognitive impairments. In autism, one such network is the so called default mode network. This network controls self-referential thoughts, reasoning past and future and is involved in understanding mental states of others (i.e. Theory of Mind). Functional MRI based functional connectivity is a research tool to understand the interrelations between brain areas and how separate, distributed areas can be organized into brain networks that serve specific cognitive functions. In autism, local hyperconnectivity along with hypoconnectivity in long range connections between anterior and posterior cingulate cortices has been discussed to be one of the physiological underpinnings of the behavioral symptoms in social interaction and cognition observed in austism. It is hypothesized to be due to a developmental delay and disbalance of the balance between neuronal excitation/inhibition in brain areas that lead to oversynchronized strong short-range (local) networks while long-range connections that develop later in neurodevelopment are less well established. In our study, we used a non-invasive MRI technique called arterial spin labeling (ASL) perfusion MRI for the first time in autism research. Similarly to Positron Emission Tomography (PET) this technique allows measuring cerebral blood flow (CBF), however without the need to inject radioactive tracers. ASL MRI uses magnetically labeled blood water as an endogenous tracer to quantify CBF. Accordingly, our approach enabled us to combine information about how brain areas are functionally connected, as well as their associated metabolic energy consumption in autism spectrum disorder.  We found that in typically developing children, the known relation between how strongly an area is connected to other areas in a brain network, the more energy it requires holds. In children with autism spectrum disorder this relation, however, was disrupted in a major brain area (the dorsal anterior cingulate cortex) that is relevant to social interactions and in Theory of Mind. Both are cognitive processes that are to some extent impaired in persons with autism spectrum disorders.
Author Interviews, Brigham & Women's - Harvard, Cost of Health Care, PLoS / 14.10.2015

[caption id="attachment_18390" align="alignleft" width="150"]James E. Stahl, MD Senior Scientist Assistant Professor of Medicine, Harvard Medical School MGH Institute for Technology Assessment Dr. James E. Stahl[/caption] MedicalResearch.com Interview with: James E. Stahl, MD Senior Scientist Assistant Professor of Medicine, Harvard Medical School MGH Institute for Technology Assessment Medical Research: What is the background for this study? What are the main findings? Dr. Stahl: Poor psychological and physical resilience in response to stress drives a great deal of health care utilization. Mind-body interventions can reduce stress and build resiliency. Over the last few decades we have seen substantial evidence that evoking the relaxation response helps the heart, blood pressure, reduces inflammation and creates changes all the way down to the epigenetic level. We have not until now had a broad look at the effect at the health systems level. The rationale for this study is therefore to estimate the effect of mind-body interventions on healthcare utilization. The main findings are that looking at a broad population these tools, and specifically the relaxation response and resiliency training offered at the BHI, results in real world reductions in health care utilization.
Author Interviews, Baylor College of Medicine Houston, Health Care Systems, Heart Disease, JACC / 14.10.2015

[caption id="attachment_18369" align="alignleft" width="120"]Salim S. Virani, M.D., Ph.D Investigator, Health Policy, Quality & Informatics Program, Center for Innovations in Quality, Effectiveness and Safety, Staff Cardiologist, Michael E. DeBakey VA Medical Center Associate Director for Research, Cardiology Fellowship Training Program Associate Professor (tenured), Section of Cardiovascular Research Baylor College of Medicine Houston Salim S. Virani, M.D., Ph.D[/caption] MedicalResearch.com Interview with: Salim S. Virani, M.D., Ph.D Investigator, Health Policy, Quality & Informatics Program, Center for Innovations in Quality, Effectiveness and Safety, Staff Cardiologist, Michael E. DeBakey VA Medical Center Associate Director for Research, Cardiology Fellowship Training Program Associate Professor (tenured), Section of Cardiovascular Research Baylor College of Medicine  Houston Medical Research: What is the background for this study? What are the main findings? Dr. Virani: The increase in Americans securing health care coverage under the Affordable Care Act, in combination with a projected shortage of specialty and non-specialty physicians, has led to a growing pressure on the existing physician workforce in America.  One proposed solution is to increase the scope of practice for advanced practice providers (APPs) (nurse practitioners [NPs] and physician assistants [PAs].  An important aspect of this discussion is whether the quality of care provided by APPs is comparable to that provided by physicians. The study utilized data from the American College of Cardiology’s (ACC) National Cardiovascular Data Registry PINNACLE Registry® to examine whether there were clinically meaningful differences in the quality of coronary artery disease (CAD), heart failure (HF), and atrial fibrillation (AF) care delivered by advanced practice providers  versus physicians in a national sample of cardiology practices. The primary analyses included 883 providers (716 physicians and 167 APPs) in 41 practices who cared for 459,669 patients. The mean number of patients seen by APPs (260.7) was lower compared to that seen by physicians (581.2). Compliance with most CAD, HF, and AF measures was comparable, except for a higher rate of smoking cessation screening and intervention (adjusted rate ratio [RR] 1.14, 95% CI 1.03-1.26) and cardiac rehabilitation referral (RR 1.40, 95% CI 1.16-1.70) among CAD patients receiving care from APPs. Compliance with all eligible CAD measures was low for both (12.1% and 12.2% for APPs and physicians, respectively) with no significant difference. Results were consistent when comparing practices with both physicians and APPs (n = 41) and physician-only practices (n = 49).
Author Interviews, Cleveland Clinic, JAMA, Multiple Sclerosis / 13.10.2015

Dr. Jeffrey Cohen MD Director Mellen Center for Multiple Sclerosis Treatment and Research Director of the Experimental Therapeutics Program Cleveland Clinic Main CampusMedicalResearch.com Interview with: Dr. Jeffrey Cohen MD Director Mellen Center for Multiple Sclerosis Treatment and Research Director of the Experimental Therapeutics Program Cleveland Clinic Main Campus MedicalResearch: What is the background for this study? What are the main findings? Dr. Cohen: Medications are a major contributor to the high cost of Multiple Sclerosis (MS) care.  As medications go off patent, there is the opportunity to develop generic versions with lower cost.  This trial was conducted after extensive in vitro and animal studies supported the equivalence of a generic glatiramer acetate to the brand drug Copaxone. The trial showed that generic and brand glatiramer acetate have equivalent efficacy as measured by MRI and clinical endpoints, safety, and tolerability.
Author Interviews, Cleveland Clinic, Heart Disease, JACC, Kidney Disease, Transplantation / 13.10.2015

W.H. Wilson Tang, MD, FACC Assistant Professor in Medicine, Cleveland Clinic Lerner College of Medicine Staff, Section of Heart Failure & Cardiac Transplant Medicine Assistant Program Director, General Clinical Research Center (GCRC) The Cleveland Clinic Cleveland, OHMedicalResearch.com Interview with: W.H. Wilson Tang, MD, FACC  Assistant Professor in Medicine, Cleveland Clinic Lerner College of Medicine Staff, Section of Heart Failure & Cardiac Transplant Medicine Assistant Program Director, General Clinical Research Center The Cleveland Clinic  Cleveland, OH Medical Research: What is the background for this study? What are the main findings? Dr. Tang: Cardiac function is a key determinant of outcomes after surgery, especially transplantation. End-stage renal disease (ESRD) poses a unique scenario, as the metabolic and uremic derangements that result from this condition lead to adverse cardiac remodeling, and kidney transplantation offers a potential for reverse remodeling. We studied patients who underwent kidney transplantation and found that echocardiogram following transplantation demonstrated consistent and significant improvement in cardiac structure and function. Post-transplant improvement in anemia was a vital factor that independently predicted such positive changes, whereas post-transplant changes in blood pressure, renal function at 12 months, and dialysis duration duration did not. Moreover, patients that demonstrated reverse remodeling had outcomes comparable to those with normal baseline cardiac function.
Author Interviews, Brigham & Women's - Harvard, Frailty, Geriatrics, Infections / 12.10.2015

Farrin A. Manian, MD, MPH, FACP, FIDSA, FSHEA Inpatient Clinician Educator, Department of Medicine, Massachusetts General Hospital Visiting Associate Professor, Harvard Medical School, Boston, MA 02114MedicalResearch.com Interview with: Farrin A. Manian, MD, MPH, FACP, FIDSA, FSHEA Inpatient Clinician Educator, Department of Medicine, Massachusetts General Hospital Visiting Associate Professor, Harvard Medical School Boston, MA 02114 Medical Research: What is the background for this study? What are the main findings? Dr. Manian:  Falls are a leading cause of injury and death, afflicting about one-third of adults over 65 years of age annually.  Although there are many potential causes for falls, infections have received very little attention, with previous published reports primarily revolving around institutionalized elderly with dementia and urinary tract infection. We found that the spectrum of patients at risk for falls precipitated by infections goes far beyond the institutionalized elderly with dementia and urinary tract infection.  In fact, the majority of our patients fell at home and did not have a diagnosis of dementia.  In addition, besides urinary tract infections which accounted for 44.1% of cases, bloodstream (40.0%) and lower respiratory tract infections (23.0%) were also frequently represented.  Although the mean age of our patients was 76 years, 18% were younger than 65 years.  We also found that the signs and symptoms of these infections at the time of the presentation for the fall were often non-specific (e.g. weakness or mental status changes) or absent, with only 44% of patients meeting the criteria for systemic inflammatory response syndrome and only 20% having fever or abnormal temperature possibly related in part to advanced age.  These factors may make it difficult for the patient, family members and healthcare providers to readily consider infections contributing to the fall.  In fact a coexisting systemic infection was not initially suspected by providing clinicians in 40% of our patients and 31% of those who were later diagnosed with a bloodstream infection.
AHA Journals, Author Interviews, Dermatology, Heart Disease, NIH / 12.10.2015

Nehal Mehta, M.D., M.S.C.E., F.A.H.A. Lasker Clinical Research Scholar Section of Inflammation and Cardiometabolic Diseases NIHMedicalResearch.com Interview with: Nehal Mehta, M.D., M.S.C.E., F.A.H.A. Lasker Clinical Research Scholar Section of Inflammation and Cardiometabolic Diseases NIH Medical Research: What is the background for this study? What are the main findings? Dr. Mehta: Psoriasis increases cardiovascular disease (CVD), and this study shows for the first time that the amount of psoriasis on the skin is mirrored in the blood vessels by increasing blood vessel inflammation. Medical Research: What should clinicians and patients take away from your report? Dr. Mehta: Even one plaque may be too many if we are seeing a relationship between skin disease severity and vascular inflammation.
Author Interviews, Biomarkers, Cleveland Clinic, Heart Disease, JACC, Kidney Disease / 12.10.2015

Dr. Wilson Tang MD Professor of Medicine Cleveland Clinic Lerner College of Medicine Case Western Reserve University Director of the Center for Clinical Genomics Cleveland ClinicMedicalResearch.com Interview with: Dr. Wilson Tang MD Professor of Medicine Cleveland Clinic Lerner College of Medicine Case Western Reserve University Director of the Center for Clinical Genomics Cleveland Clinic  Medical Research: What is the background for this study? What are the main findings? Dr. Tang: Renal impairment has long been associated with worse outcomes in acute heart failure. Administration of diuretic therapy often obscures accurate assessment of renal function by urine output.  Despite extensive literature suggesting the poor outcomes in those with a rise in creatinine following treatment, recent data has suggested that in the presence of effective diuresis, this phenomenon likely represents hemoconcentration and azotemia rather than acute kidney injury.  We observed that using a novel and sensitive biomarker that identified acute kidney injury, specific to tubular injury, we can identify those at higher risk of adverse outcomes in patents admitted for acute heart failure.   However, after adjusting for standard risk factors, the prognostic value was clearly attenuated.
Author Interviews, Infections, Respiratory, Vaccine Studies, Vanderbilt / 11.10.2015

Annabelle de St. Maurice MD, MPH Pediatric Infectious Disease Fellow Vanderbilt Children's HospitaMedicalResearch.com Interview with: Annabelle de St. Maurice MD, MPH Pediatric Infectious Disease Fellow Vanderbilt Children's Hospital  Medical Research: What is the background for this study? What are the main findings? Dr. de St. Maurice: Susceptibility to certain infectious diseases appears to vary by gender. For example, males may be at increased risk of certain infections in childhood, including lower respiratory tract infections such as RSV, however females may have more severe infections, such as influenza, during pregnancy. Some early studies have suggested that males may be at increased risk of pneumococcal infections but this has not been confirmed. Furthermore, whether those potential gender differences remain after introduction of pneumococcal conjugate vaccines is unknown. Invasive pneumococcal disease, which includes meningitis, bacteremic pneumonia and bacteremia/septicemia, is a significant cause of morbidity and mortality in the United States in children and adults. The 7-valent pneumococcal conjugate vaccine (PCV7) and the 13-valent pneumococcal conjugate vaccine (PCV13) led to declines in invasive pneumococcal disease rates as well as eliminated racial disparities in regards to invasive pneumococcal disease rates. Our study sought to identify potential gender differences in the incidence of invasive pneumococcal disease, and to determine the impact of vaccines on gender differences in the susceptibility to these diseases. We conducted a large study that used data from a population-based surveillance system of invasive pneumococcal diseases in Tennessee. This is part of a large CDC funded network of surveillance sites for these diseases. For our study, we identified patients with laboratory-confirmed invasive pneumococcal disease, and calculated the incidence of invasive pneumococcal diseases from 1998-2013 by gender. We also stratified the calculations by age groups and race, both well-known factors that affect the occurrence of invasive pneumococcal disease. Our study found that males had generally higher rates of invasive pneumococcal disease than females across age groups, regardless of race. Although introduction of the pneumococcal conjugate vaccines led to a significant decrease in invasive pneumococcal disease rates, males continued to have higher rates than females in several age groups.
Author Interviews, Chemotherapy, Lung Cancer, NEJM, UT Southwestern / 11.10.2015

David E. Gerber, MD Associate Professor Division of Hematology-Oncology Associate Director for Clinical Research Co-Leader, Experimental Therapeutics Program Co-Director, Lung Disease Oriented Team Harold C. Simmons Cancer Center University of Texas Southwestern Medical Center Dallas, TXMedicalResearch.com Interview with: David E. Gerber, MD Associate Professor Division of Hematology-Oncology Associate Director for Clinical Research Co-Leader, Experimental Therapeutics Program Co-Director, Lung Disease Oriented Team Harold C. Simmons Cancer Center University of Texas Southwestern Medical Center Dallas, TX Medical Research: What is the background for this study? What are the main findings? Dr. Gerber: In this trial, we compared an immunotherapy and a chemotherapy drug in patients with non-squamous non-small cell lung cancer (NSCLC) whose disease continued to progress after first-line chemotherapy. We found that nivolumab immunotherapy improved overall survival compared to docetaxel chemotherapy and was generally well tolerated. These results are significant because options for patients whose lung cancer progresses after initial treatment are limited. Nivolumab is an immunotherapy drug that works by inhibiting the cellular pathway known as PD-1 protein on cells that block the body’s immune system from attacking cancerous cells.  The idea behind nivolumab and other immunotherapy drugs is to kick-start the body’s natural immune response to a cancer. Cancer develops and grows in part because it has put the brakes on the immune response. These drugs take the foot off the brake, allowing the immune system to accelerate and attack the cancer. The phase 3 clinical trial followed more than 500 patients who had non-squamous non-small cell lung cancer (NSCLC): 287 received nivolumab and 268 received the chemotherapy drug docetaxel. The one-year survival rate was 51 percent in the nivolumab arm versus 39 percent in the docetaxel arm. The most common reported side effects with nivolumab were fatigue, nausea, decreased appetite, and weakness, and they were less severe than with docetaxel treatment. In a minority of cases, patients treated with nivolumab also developed autoimmune toxicities affecting various organs. In addition to studying safety and efficacy, the trial examined the protein biomarker PD-L1, which is believed to play a role in suppressing the immune system. The study results suggested that patients with a higher level of PD-L1 in their cancers may experience the greatest benefit from nivolumab, which targets the related molecule PD1. Using a biomarker helps oncologists predict which patients will do best on which treatment, and plan their treatment accordingly. Other promising predictive biomarkers for cancer immunotherapies include the degree of immune cell infiltration within a tumor and the number of mutations a tumor has. Specifically, the more mutations a cancer has, the more foreign it appears to the body, thus marking it for immune attack. With lung cancer, we see the greatest number of tumor mutations – and perhaps the greatest benefit from immunotherapy – among individuals with the heaviest smoking history.