Author Interviews, Genetic Research, Schizophrenia, UCSD / 12.06.2018

MedicalResearch.com Interview with: Marcelo Pablo Coba PhD Assistant Professor of Psychiatry Zilkha Neurogenetic Institute Keck School of Medicine of USC MedicalResearch.com: What is the background for this study? What are the main findings? Response: Psychiatric diseases such as schizophrenia (SCZ) are complex brain disorders where a multitude or risk factors have been implicated in contributing to the disease, with a low number of genes that have been strongly implicated in a very low number of cases. One of these genes is Disrupted in schizophrenia 1 (DISC1), which was first described in 2000 as a balanced translocation that segregates with schizophrenia and related psychiatric disorders in a large Scottish family. Because DISC1 does not have an identified protein function such as enzymatic, channel, transporter, etc… the field moved to try to understand what proteins are associated (physically connected) to DISC1 and to try to explain DISC1 function through the function of its protein interactors. This means that if DISC1 binds proteins X, Y and Z, then mutations in the DISC1 gene should affect the functions of   these proteins. Therefore, there has been much effort in trying to identify DISC1 protein interactors. However this task has not been straightforward. (more…)
Asthma, Author Interviews, Biomarkers / 12.06.2018

MedicalResearch.com Interview with: Dr. Supinda Bunyavanich MD Pediatric Allergy and Immunology Physician and researcher at the Icahn School of Medicine. MedicalResearch.com: What is the background for this study? What are the main findings?  Response: In this study, we report on an accurate asthma biomarker we have developed based on a simple nasal brush. Nasal Brush-based Classifier of Asthma Asthma is a chronic respiratory disease that affects 10% of children and adults in the U.S. Mild to moderate asthma can be difficult to diagnose because symptoms change over time and can be complicated by other respiratory conditions. Given the high prevalence of asthma, there is high potential impact of improved diagnostic tools on reducing morbidity and mortality from asthma. Current diagnostic tools for asthma, including spirometry and bronchoscopy, require specialized equipment and expertise to operate properly. Many individuals, particularly young children, have difficulty with pulmonary function testing because it requires, coordinated, forced breaths into a device. Spirometry results are unreliable when done with poor technique. Bronchoscopy is not practical for mild to moderate symptoms. For these reasons, asthma is often diagnosed and managed based on self-reporting of symptoms  This can be unreliable, resulting in repeated doctor visits and even trips to the ER. Thus, a biomarker test for asthma that is easy to implement and interpret is highly desirable for the diagnosis and management of asthma. (more…)
Author Interviews, Brigham & Women's - Harvard, JAMA, OBGYNE / 12.06.2018

MedicalResearch.com Interview with: Sheryl L. Rifas-Shiman, MPH Lead Research Analyst Department of Population Medicine Harvard Medical School and Harvard Pilgrim Health Care Institute Landmark Center Boston, MA 02215  MedicalResearch.com: What is the background for this study? Response: Caesarean delivery rates remain high and variable across hospitals, regions, and countries. Caesarean delivery may be a risk factor for childhood obesity, possibly because delivery route can influence the intestinal microbiomes, which may influence energy regulation. Previously reported associations of caesarean delivery with childhood obesity may be confounded by maternal BMI and sociocultural factors. To address this possibility, we studied sibling pairs from the Linked CENTURY Study, a longitudinal clinical database of well-child visits in Massachusetts linked to each child’s birth certificate, to isolate the effect of caesarean delivery from most other factors. (more…)
Annals Internal Medicine, Author Interviews, Cancer Research, HIV, Infections / 12.06.2018

MedicalResearch.com Interview with: Lesley S. Park, PhD, MPH Instructor, Medicine- Primary Care and Population Health BioStanford Center for Population Health Sciences (PHS) Associate Director, Research and Data Strategy; Director, PHS Postdoctoral Fellowship Veterans Aging Cohort Study (VACS) Cancer Core Co-Director MedicalResearch.com: What is the background for this study? What are the main findings?  Response: As the population of persons living with HIV/AIDS is aging, the overall burden of cancer is substantial and increasing; however, we have much to learn about the potential cancer prevention benefits of antiretroviral treatment (ART). Our study is the first to examine the effects of prolonged periods of viral suppression and potential cancer prevention benefits. While prior randomized clinical trials (RCTs) and observational studies have examined viral suppression and cancer risk, they mostly were limited to small numbers of cancer outcomes or were only focused on few specific cancer types. Our study demonstrated a benefit of the prevention of cancer development in AIDS-defining cancers (non-Hodgkin lymphoma, Kaposi sarcoma), which was expected, but also in some non-AIDS-defining cancer types (lung, larynx, melanoma, leukemia).  (more…)
Annals Internal Medicine, Author Interviews, Diabetes, Education, Outcomes & Safety / 12.06.2018

MedicalResearch.com Interview with: Bradley Gray, PhD Senior Health Services Researcher American Board of Internal Medicine MedicalResearch.com: What is the background for this study? Response: This study is part of an ongoing effort to improve and validate ABIM’s MOC process through the use of real data that is ongoing here at ABIM. MedicalResearch.com: What are the main findings?  Response: The paper examines the association between MOC status and a set of HEDIS process quality measures for internists twenty years past the time they initially certified. An example of one HEDIS performance measure we looked at was percentage of patients with diabetes that had twice annual HbA1c testing. The key findings of the paper are that physicians who maintained their certification had better scores on 5 of 6 HEDIS performance measures than similar physicians who did not maintain their certification. (more…)
Author Interviews, CMAJ, Cost of Health Care, Health Care Systems, Hip Fractures, Surgical Research / 12.06.2018

MedicalResearch.com Interview with: Daniel Pincus MD Department of Surgery Institute for Clinical Evaluative Sciences University of Toronto MedicalResearch.com: What is the background for this study? What are the main findings? Response: We chose to look at hip fractures because is the most common reason for urgent surgery complications have be tied to wait times (and in particular wait times greater than 24 hours). (more…)
Alzheimer's - Dementia, Author Interviews, JAMA, Medical Imaging, Memory / 12.06.2018

MedicalResearch.com Interview with: Arno de Wilde, MD / PhD candidate Department of Neurology & Alzheimer Center Amsterdam Neuroscience VU University Medical Center Amsterdam, the Netherlands MedicalResearch.com: What is the background for this study? What are the main findings? Response: Previous studies assessing the clinical utility of amyloid imaging used very selected research populations, limiting the translatability to clinical practice. In contrast, we used an unselected memory clinic cohort, offering amyloid PET to ALL patients visiting our memory clinic, and for the purpose of this study, we implemented amyloid PET in our routine diagnostic work-up. Our results demonstrate that amyloid PET has important consequences, in terms of diagnosis and treatment changes, for a significant number of patients within a situation that closely resembles clinical practice. I think that these results are an important step in 'bridging the gap' between using amyloid PET in a research setting versus daily clinical practice. (more…)
Author Interviews, HIV, Infections, OBGYNE / 12.06.2018

MedicalResearch.com Interview with: Manish Sagar, MD Infectious Disease Physician at Boston Medical Center Boston MA  MedicalResearch.com: What is the background for this study? Response: Women compromise the majority of new infections in the world and most of them acquire the virus after sexual exposure.  The goal of the study was to understand how HIV establishes initial infection in the female genital tract. We obtained discarded vaginal tissue and isolated cells present in the outermost layer that contact the virus during exposure. (more…)
Addiction, Author Interviews / 11.06.2018

MedicalResearch.com Interview with: Professor, Rita Z. Goldstein, PhD Department of Psychiatry (primary) and Department of Neuroscience, Friedman Brain Institute (secondary) Chief, Neuropsychoimaging of Addiction and Related Conditions (NARC) Research Program Anna Zilverstand PhD Assistant Professor, Psychiatry Icahn School of Medicine at Mount Sinai The Leon and Norma Hess Center for Science and Medicine New York, NY 10029  MedicalResearch.com: What is the background for this study? What are the main findings? Response: In comparison to previous reviews that often focused on investigating select brain circuits, such as the reward network, our review is the first to systematically discuss all brain networks implicated in human drug addiction. Based on more than 100 neuroimaging studies published since 2010, we found that six major brain networks showed altered brain function in individuals with addiction. These brain circuits are involved in a person’s ability to select their actions (executive network), in directing someone’s attention (salience network), in adaptive learning of new behaviors (memory network), in the automatization of behaviors (habit network), in self-reflection (self-directed network) and the valuation of different options (reward network). When individuals with addiction are confronted with pictures of drug taking, all of these networks become very highly engaged; however, when the same individuals are confronted with scenes depicting other people, their brains show a reduced reaction as compared to healthy individuals, indicating less involvement. Similarly, the brain of an addicted individual is less engaged when making decisions (that are not relevant to their drug taking) or when trying to inhibit impulsive actions. We further found that some impairments of brain functions, such as alterations underlying the difficulty to inhibit impulsive actions, seem to precede drug addiction, as we observe similar impairments in adolescents that later go on to abuse drugs. However, particularly the impairments in the executive network (involved in the ability to inhibit impulsive actions), the valuation network (which computes the value of an option) and the salience network (that directs attention towards events) seem to be getting worse with more severe drug use and also predict if someone is likely to relapse or not. The good news is that we also found that it is possible to (partially) recover and normalize brain function in these networks through treatment. Importantly, the widespread alterations of brain function were independent of what drug an individual was addicted to (marijuana, alcohol, cigarettes, cocaine, methamphetamine, heroin, amongst others). (more…)
Author Interviews, Heart Disease, OBGYNE / 11.06.2018

MedicalResearch.com Interview with: Sandra T. Davidge, PhD, FCAHS Executive Director, Women and Children's Health Research Institute Canada Research Chair in Maternal and Perinatal Cardiovascular Health Professor, Depts. of Ob/Gyn and Physiology University of Alberta Edmonton, Alberta Canada MedicalResearch.com: What is the background for this study? Response: This research contributes to the growing body of literature that developmental programming of adult onset cardiovascular disease originates in the womb. Our study is among the first to discover that maternal age may be considered a ‘prenatal stress’ in certain circumstances. (more…)
Author Interviews, JAMA, MRI, Prostate Cancer / 11.06.2018

MedicalResearch.com Interview with: Dr. Lars Boesen MD PhD Department of Urology Herlev Hospital MedicalResearch.com: What is the background for this study? What are the main findings?  Response: The current standard of care in prostate cancer diagnosis includes untargeted transrectal ultrasound-guided biopsies for all biopsy-naïve men with clinically suspicion of prostate cancer. However, this strategy that practically has remained unchanged for decades has limited diagnostic accuracy as significant cancers are missed or under-graded and insignificant cancers are unintendedly detected by the random sampling leading to possible overtreatment. Multiparametric MRI in the diagnosis of prostate cancer has been studied extensively in recent years and has improved detection, localization, staging and risk stratification. It has been suggested that if multiparametric MRIs were used as a triage test prior to biopsies, a significant proportion of men might safely avoid prostate biopsies and the diagnostic ratio of significant vs. insignificant cancer could be improved compared to performing standard biopsies in all men. However, multiparametric MRIs are generally time-consuming (~40 min scan time), expensive and include intravenous contrast media. This reduces its feasibility for widespread clinical implementation in larger patient populations in the western community with its high PCa prevalence. The development of a simpler and faster (~15 min) biparametric MRI protocol using less scan sequences and circumvents intravenous contrast-media seems to preserve adequate diagnostic accuracy in a detection setting and could facilitate dissemination of prostate MRI as a triage test before any biopsy. Here we present a large prospective study that assesses the diagnostic accuracy of a novel biparametric MRI to rule out significant prostate cancer in N=1020 biopsy-naive men with clinically suspicion of prostate cancer. We found that a low suspicion biparametric MRI had a very high negative predictive value (97%) for ruling out significant cancer on confirmatory biopsies. Furthermore, bpMRI suspicion scores were strongly associated with prostate cancer detection rates and restricting biopsies (targeted plus standard) to men with suspicious biparametric MRIs meant 30% could avoid prostate biopsies, improved significant prostate cancer diagnosis by 11%, and reduced insignificant prostate cancer diagnosis by 40% compared to our current diagnostic approach – standard biopsies for all men with clinically suspicion of prostate cancer.  (more…)
AHA Journals, Author Interviews, Blood Pressure - Hypertension, Stroke / 10.06.2018

MedicalResearch.com Interview with: Dr. Alain Lekoubou Looti, MD Msc Clinical Neurophysiology Department of Neurosciences College of Medicine Medical University of South Carolina MedicalResearch.com: What is the background for this study? What are the main findings? Response: Hypertension is strongly associated with stroke. Individuals who suffer a stroke are more likely to have another stroke. They also die at a rate twice as high as those who experience a first event. We have evidence that treating hypertension reduces the risk of recurrence stroke among stroke survivors. Prior hypertension guidelines defined hypertension for a systolic blood pressure (top number) equal or greater than 140 and a diastolic blood pressure (lower number) equal or greater than 90. The American college of cardiology/American heart association have published a new guideline to help healthcare providers identify and treat blood pressure including among stroke survivors. The threshold to define blood pressure has been lowered to 130 for the top number and 80 for the lower number for everyone. Unlike the general population, pharmacological treatment for stroke survivors is now recommended for systolic blood pressure greater than or equal than 130 and diastolic blood pressure greater than or equal to 80. In the same line achieving a blood pressure of less than 130/80 mmHg in stroke survivors is now recommended. In the stroke community, there has been mounting evidence to suggest that achieving lower blood pressure goal was desirable. When the new guidelines were published, we could not wait any longer to see the impact of the new guidelines on the proportion of stroke survivors with hypertension, recommended pharmacological treatment, and above blood pressure target. We were also curious to see how the new guidelines would potentially affect mortality among stroke survivors.  We have found that the new guidelines would result in a nearly 67% (from 29.9% to 49.8%) to relative increase in the proportion of U.S. stroke survivors diagnosed with hypertension and 54% (from 36.3% to 56%) relative increase in those not within the recommended BP target.  We have also found that if the new guidelines were applied, this would result in a 33% relative drop in mortality.  (more…)
Allergies, Author Interviews, Autism, JAMA, Pediatrics / 10.06.2018

MedicalResearch.com Interview with: Wei Bao, MD, PhD Assistant Professor, Epidemiology College of Public Health University of Iowa MedicalResearch.com: What is the background for this study? What are the main findings? Response: Previous studies indicated a possible link between immunologic dysfunction and autism. The current study, based on nationally representative large-scale surveys, showed that food allergy, respiratory allergy, and skin allergy, all relevant to immunological dysfunction, were associated with autism spectrum disorder among US children. (more…)
Author Interviews, Fertility, Nature / 09.06.2018

MedicalResearch.com Interview with: Tomer Avidor-Reiss, Ph.D.  Professor, College of Natural Sciences and Mathematics Department of Biological Sciences University of Toledo Toledo, OH 43606 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Most dividing cells in the body need exactly two centrioles for normal cell division and development. Abnormalities in centriole number can cause cancer and devastating developmental defects. Because of this importance of centriole number and because all cells originate from the zygote – the product of the sperm and egg – it makes sense that the zygote should possess two centrioles, as well. However, the egg does not contain any centrioles, so the sperm is the sole contributor of the centrioles; and yet, it is currently thought that the sperm contains only one centriole. This is problematic because supposedly that leaves the zygote with only one centriole, even though it must propagate cells with two centrioles. In the past, we found that insect sperm have an atypical centriole that escaped discovery because it is so different. We therefore hypothesized that humans may also have an atypical sperm centriole. Our new paper shows that in human sperm there exists, in addition to the known centriole, a second centriole that deviates from the typical structural and composition that is expected from a centriole. Although it looks very different from any centriole ever described, we found that it functions in an in vitro functional assay. Furthermore, during fertilization, it performs the functions traditionally associated with centrioles. Together, this resolves a 50-year-long debate regarding the centrioles of human sperm; the sperm contains two functional centrioles, despite that one is atypical.  (more…)
Author Interviews, Genetic Research / 09.06.2018

MedicalResearch.com Interview with: “The human Brain” by Kristian Mollenborg is licensed under CC BY 2.0David Haussler PhD Investigator, Howard Hughes Medical Institute Distinguished Professor, Biomolecular Engineering Scientific Director, UC Santa Cruz Genomics Institute Scientific Co-Director, California Institute for Quantitative Biosciences  and Sofie Salama, PhD Research Scientist in BIomolecular Engineering Howard Hughes Medical Institute Senior Scientist MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Haussler:  Researchers specializing in this area are interested understanding which evolutionary changes in our genome underlie human-specific brain features including our large (3X greater than chimpanzee) brain. It has been my personal dream to peer into human evolution at the level of individual genes and gene functions.  (more…)
Author Interviews, Ophthalmology / 09.06.2018

MedicalResearch.com Interview with: “pplkpr phone” by Kyle McDonald is licensed under CC BY 2.0Michelle Nguyen Senior Director, Consumer Marketing Lead Shire Ophthalmics MedicalResearch.com: What is the background for this initiative? How does screen time affect eye health?  Response: Screen responsibly is an educational initiative about the intersection between our screen use and eye health. This initiative is underscored by new national survey data and aimed at increasing our dialogue about how to love both our screens and our eyes. Screen responsibly is an extension of the eyelove campaign, which Shire launched in 2016 to elevate the importance of eye health and raise awareness of the signs and symptoms of Chronic Dry Eye, commonly referred to as Dry Eye. Since being glued to your screen can trigger Dry Eye symptoms, it is important that people are aware of ways to screen responsibly.  MedicalResearch.com:  How common is the problem of Dry Eye? How is it related to excessive screen time? Response: In the United States, nearly 30 million adults report symptoms consistent with Dry Eye. Dry Eye symptoms include a burning, itchy, stinging or gritty feeling in the eyes, episodes of blurred vision, eye redness and watery eyes. Shire is committed to addressing unmet needs within the Dry Eye patient community, and to do so, we sought to better understand their current behaviors, perceptions and knowledge around a common trigger of Dry Eye symptoms – intense screen usage. (more…)
Abuse and Neglect, Author Interviews, Breast Cancer, JAMA, MD Anderson / 08.06.2018

MedicalResearch.com Interview with: Naoto Tada Ueno, M.D., Ph.D., F.A.C.P. Executive Director, Morgan Welch Inflammatory Breast Cancer Research Program and Clinic Section Chief, Section of Translational Breast Cancer Research, Department of Breast Medical Oncology Division of Cancer Medicine The University of Texas MD Anderson Cancer Center Houston, TXNaoto Tada Ueno, M.D., Ph.D., F.A.C.P. Executive Director, Morgan Welch Inflammatory Breast Cancer Research Program and Clinic Section Chief, Section of Translational Breast Cancer Research, Department of Breast Medical Oncology Division of Cancer Medicine The University of Texas MD Anderson Cancer Center Houston, TX   MedicalResearch.com: What is the background for this study? What are the main findings? Response: The best outcome of inflammatory breast cancer (IBC) is dependent on achieving a pathological completed response after neoadjuvant chemotherapy for primary inflammatory breast cancer, which is the most aggressive type of breast cancer. We have conducted extensive preclinical work, which showed that EGFR is a potential therapeutic targets of IBC. Based on this preclinical data, we have conducted a phase II study to determine the pathological complete response rate of panitumumab plus neoadjuvant chemotherapy for HER2 negative primary inflammatory breast cancer.  (more…)
Author Interviews, Heart Disease, Occupational Health / 08.06.2018

MedicalResearch.com Interview with: Eleonor Fransson, PhD Associate Professor in Epidemiology Department of Natural Sciences and Biomedicine School of Health and Welfare JÖNKÖPING UNIVERSITY MedicalResearch.com: What is the background for this study? Response: Atrial fibrillation is a very common heart rhythm disorder affecting a large number of people in the population, but there is limited knowledge about risk factors for the disease. This is especially true when it comes to the role of occupational factors. MedicalResearch.com: What are the main findings? Response: We found that work stress measured as job strain, that is, a combination of having high psychological job demands and low control over the work situation, was associated with almost 50% increased risk of atrial fibrillation. When we combined the results from our study with two previously published studies on the same topic, we found that work stress was associated with 37% increased risk. (more…)
Author Interviews, Autism, Blood Pressure - Hypertension, JAMA, OBGYNE, Pediatrics / 08.06.2018

MedicalResearch.com Interview with: “Blood Pressure” by Bernard Goldbach is licensed under CC BY 2.0Ali Khashan, PhD Senior Lecturer in Epidemiology School of Public Health & INFANT Centre University College Cork Cork, Ireland MedicalResearch.com: What is the background for this study? What are the main findings? Response: There is some evidence to suggest an increased likelihood of neurodevelopmental disorders in relation to hypertensive disorders in pregnancy, however consensus is lacking. Considering hypertensive disorders in pregnancy are among the most common prenatal complication, we decided to synthesise the published literature on this topic by conducting a comprehensive systematic review and meta-analysis. Our main findings suggest that hypertensive disorders in pregnancy are associated with about 30% increase in the likelihood of autism spectrum disorders (ASD) and ADHD in the offspring, compared to offspring not exposed to hypertensive disorders in pregnancy. (more…)
Author Interviews, Brigham & Women's - Harvard, Dermatology, Environmental Risks, Melanoma, Transplantation / 08.06.2018

MedicalResearch.com Interview with: “Sunscreen” by Tom Newby is licensed under CC BY 2.0Rebecca Ivy Hartman, M.D Instructor in Dermatology Brigham and Women's Hospital Boston MA 02115 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Organ transplant recipients (OTR) are at 100-fold higher risk to develop certain skin cancers compared to the general population due to immunosuppression, and thus preventing skin cancer in this population is critical. Our study found that in a high-risk Australian OTR population, only half of patients practiced multiple measures of sun protection regularly. However, after participating in a research study that required dermatology visits, patients were over 4-times more likely to report using multiple measures of sun protection regularly. Patients were more likely to have a positive behavioral change if they did not already undergo annual skin cancer screening prior to study participation. (more…)
Addiction, Alcohol, Author Interviews, Opiods / 07.06.2018

MedicalResearch.com Interview with: Dr. Katie Witkiewitz PhD Professor, Department of Psychology University of New Mexico MedicalResearch.com: What are the main findings? Response: The main findings from our study indicate that individuals with alcohol dependence who misused opioids (e.g., used without a prescription or not as prescribed) had a significantly higher likelihood of relapse to heavy drinking during alcohol treatment and were drinking more alcohol during and following alcohol treatment. (more…)
Amgen, Author Interviews, Gastrointestinal Disease, Gluten / 07.06.2018

MedicalResearch.com Interview with: Markku Mäki, MD, PhD Professor (emeritus) at the University of Tampere and Presently research director at the Tampere University Hospital Tampere, Finland MedicalResearch.com: What is the background for this study? Response: The only treatment for this life-long gluten-induced autoimmune systemic disease is a strict avoidance of wheat, rye and barley, the food cereals which contain gluten, the environmental trigger and driving force in celiac disease.  Gluten causes intestinal inflammation, usually with (but sometimes without) gastrointestinal or nutritional symptoms or signs, and with frequent extra-intestinal diseases. However, it is impossible for celiac disease patients to avoid gluten entirely and indefinitely and a third of patients report symptoms on a strict gluten-free diet. Gut mucosal healing is not optimal in half of the patients, and inflammation and injury is detected for years after starting the diet, presumably due to contamination with gluten in the diet. This is why patients are requesting, and academia and industry are looking for novel adjunct therapies for celiac disease. Initially, these therapies are tested to prevent the consequences of hidden gluten; the ultimate goal being that also celiacs could one day eat safely wheat, barley and rye products. Some 20 novel experimental therapies are at present actively being investigated (modifying wheat or different drugs, devices and vaccines/immunotherapy). The present study investigated whether blocking interleukin 15, an important mediator of celiac disease, reduces or prevents gluten-driven ill health, both the inflammation and injury at the small intestinal mucosal level and gluten-induced symptoms. The experimental drug used was Amgen’s AMG 714, a human monoclonal antibody, used at a low and high dose, in the presence or absence of a high-dose gluten challenge. (more…)
Author Interviews, Dermatology, Hepatitis - Liver Disease, NEJM / 07.06.2018

MedicalResearch.com Interview with: Dr Christophe Corpechot Centre de Référence Maladie Rares: Maladies Inflammatoires des Voies Biliaires et Hépatites Auto-immunes (MIVB-H) Filière Maladies Rares: Maladies Rares du Foie de l’Adulte et de l’Enfant Hôpital Saint-Antoine (APHP) et Sorbonne Universités Paris MedicalResearch.com: What is the background for this study? Response: Primary biliary cholangitis (PBC, previously known as "primary biliary cirrhosis") is a rare, chronic, slowly progressive liver disease of unknown cause, mainly affecting women of middle age. It is characterized by serum marks of autoimmunity (specific auto-antibodies), chronic inflammation and destruction of small intra-hepatic bile ducts, and consequent bile secretion impairment (chronic cholestasis) leading to the progressive development of cirrhosis and liver failure. Ursodeoxycholic acid (UDCA) is the only first-line approved treatment for PBC. It improves the biochemical measures of cholestasis and prolongs survival without liver transplantation. However, 30% to 40% of UDCA-treated patients continue to have clinically significant abnormalities of their biochemical liver tests and those patients remain at high risk of developing end-stage liver disease complications. Recently (2016), obeticholic acid (OCA) in association with UDCA has been conditionally approved in patients with an inadequate response to UDCA. This approval (FDA, EMA) was based one the results of a 1-year randomized, double-blind, placebo-controlled trial of OCA in patients with an incomplete response or intolerance to UDCA (POISE trial). In this trial, OCA was shown to improve the biochemical features of cholestasis (alkaline phosphatase (ALP) level < 1.67 times the upper limit of the normal range and a reduction of at least 15% from baseline) but was associated with a significant increase of pruritus, a characteristic, potentially debilitating symptom of PBC. BEZURSO is the first ever placebo-controlled phase 3 trial of a fibrate (a class of drugs known to be agonists of the peroxisome proliferator-activated receptors alpha) in PBC. In this 2-year randomized double-blind trial, 100 patients with an incomplete response to UDCA were assigned to bezafibrate 400 mg/day (n=50) or placebo (n=50), all in association with continued UDCA therapy. (more…)
ASCO, Author Interviews, Cancer Research / 07.06.2018

MedicalResearch.com Interview with: Axel Le Cesne, MD Institute de Cancerologie Gustave-Roussy Villejuif, France MedicalResearch.com: What is the background for this study? What are the main findings? Response: With the exception of a study in translocation-related sarcomas (TRS) (Kawai, TLO 2015), trabectedin was never compared to best supportive care (BSC) in a randomized study in patients with all STS histotypes. This trial required by French Health Authorities in 2014. The tumor control rate after 6 cycles of trabectedin is similar (30%) to previous study in French referral centers (T-DIS trial, Le Cesne, Lancet Oncol 2015) evaluating trabectedin in all subtypes of STS. As already reported, trabectedin was well tolerated with no cumulative toxicities This study met its first endpoint as a preplanned PFS analysis showed a significant improvement in median PFS with trabectedin  over BSC in patients with pretreated ASTS including multiple histologies (HR: 0.39). A major impact of trabectedin was observed in the L-STS cohort (liposarcomas and leiomyosarcomas) with a median PFS of 1.4 months in the BSC arm and 5.13 m (HR: 0.29, p<0.0001) in the trabectedin arm. respectively). The benefit observed with trabectedin in the L-STS cohort of patients is similar to those observed in the US trial in the same population (4.2 vs 1.5m for DTIC) (Demetri, JCO 2016) and in the Japanese trial mentioned above (5.8 vs 0.9m for BSC) (Kawai, TLO 2015) After the crossing over allowed by the protocol (trabectedin for patients progressing in the BSC arm), safety and efficacy profiles of trabectedin remains similar. We did not observe a difference in terms of OS between the two arms, probably due to the cross-over planned by the protocol.  (more…)
Author Interviews, Biomarkers, Orthopedics / 06.06.2018

MedicalResearch.com Interview with: Rick Sumner, PhD, FAAA The Mary Lou Bell McGrew Presidential Professor for Medical Research Chair, Department of Cell & Molecular Medicine (formerly, Anatomy and Cell Biology) Rush University Medical Center Chicago, IL  60612   MedicalResearch.com: What is the background for this study? What are the main findings? Response: The main cause of failure for total hip replacements is implant loosening which is often a consequence of particle-induced peri-implant osteolysis. Unfortunately, this condition is usually not diagnosed until it has progressed to the point of needing a revision surgery. We discovered two biomarkers that may be useful for identifying at risk patients much earlier than is currently possible. (more…)
ASCO, Author Interviews, Breast Cancer, Brigham & Women's - Harvard / 06.06.2018

MedicalResearch.com Interview with: Dr. Aditya Bardia  MD, MPH Assistant Professor, Medicine Harvard Medical School Attending Physician, Medical Oncology Massachusetts General Hospital MedicalResearch.com: What is the background for this study? What are the main findings? Response: Hormone receptor-positive (HR+)/ and human epidermal growth factor receptor 2-negative (HER2-) breast cancer is the most common sub-type of breast cancer. While metastatic HR+/HER2- breast cancer is initially treated with endocrine therapy-based combinations, including CDK 4/6 inhibitors, patients eventually have disease progression, but the response rate to standard chemotherapy is low (~10-15 percent, post-taxane setting). In particular, patients with visceral disease have a poor prognosis. In this trial, we evaluated the efficacy of sacituzumab govitecan in patients with metastatic HR+/HER2- breast cancer, who had measurable disease and had received prior therapies for metastatic breast cancer. We observed an overall response rate of 31 percent in a heavily pre-treated population (prior number of therapies for metastatic breast cancer = 5; number of patients with prior CDK 4/6 inhibitor use = 69 percent). The responses were durable (median duration of response = 7.4 months). Neutropenia was the main adverse event noted (grade 3 neutropenia = 42 percent), and two patients (3.7 percent) discontinued the clinical trial due to adverse events. The response rate in patients with visceral metastaseswas 27 percent.  (more…)
Author Interviews, Colon Cancer, Gastrointestinal Disease / 06.06.2018

MedicalResearch.com Interview with: Anas Raed, MD Section of General Internal Medicine Augusta University MedicalResearch.com: What is the background for this study? Response: Colorectal cancer (CRC) incidence and mortality rates have been decreasing in the US since mid 1980s, however, recent evidence shows that incidence and mortality rates of CRC in patients younger than 50 years have been increasing significantly. In spite of the increasing trend of colorectal cancer, routine screening of this population has not been addressed due to lack of evidence and cost-effectiveness. Administering screening colonoscopy for all individuals younger than 50 years might not be feasible and, therefore routine screening colonoscopy for specific age groups might reduce the disparity of the incidence in this disease. (more…)
Addiction, Author Interviews, JAMA, Race/Ethnic Diversity / 06.06.2018

MedicalResearch.com Interview with: Randall C. Swaim, Ph.D. Senior Research Scientist and Director Linda R. Stanley, Ph.D. Senior Research Scientist Tri-Ethnic Center for Prevention Research Department of Psychology Colorado State University                           MedicalResearch.com: What is the background for this study? Response: American Indian adolescents consistently report the highest levels of substance use compared with other US racial/ethnic groups. The harm associated with these high rates of use include higher risk of developing a substance use disorder, more alcohol-related problems, including alcohol-attributable death, and other negative outcomes such as school failure. These findings point to the importance of continuing to monitor this group, particularly given changing trends in perceived harmfulness of illicit substances as new statutes alter access to medical and recreational use of cannabis. (more…)
Author Interviews, Kidney Disease, Neurological Disorders, Pain Research, UCSF / 06.06.2018

MedicalResearch.com Interview with: Dr. Julie H. Ishida MD Department of Medicine, Division of Nephrology University of California, San Francisco and San Francisco Veterans Affairs Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: Gabapentin and pregabalin are used for the management of symptoms such as neuropathic pain, itching, and restless leg syndrome in patients receiving hemodialysis. However, hemodialysis patients may be particularly vulnerable to adverse events related to these agents, which are cleared by the kidney, but there is limited data evaluating their risk in this population. Gabapentin and pregabalin use were associated with risk for altered mental status, fall, and fracture, and in some cases, even at doses that would be considered safe for use in this population.  (more…)
Author Interviews, Mental Health Research, Pediatrics / 06.06.2018

MedicalResearch.com Interview with: Alfio Maggiolini, MD Minotauro, Milan MedicalResearch.com: What is the background for this study? What are the main findings? Response: Antisocial behaviour is common during adolescence and it incurs significant costs both for society and for the young people themselves. Persistent antisocial behaviour places a heavy burden on the community, the justice system and the public health system. Responses to juvenile crime have always seen a tension between a focus on the understanding and the rehabilitation of the youth and the need to enforce discipline and public safety through punishment and threat. The treatment of young offenders was traditionally deemed particularly difficult, and often ineffective. In recent years, therapeutic nihilism has given way to cautious optimism. While punitive-based approaches, at all levels, are hardly ever effective in the long term, the most popular and effective programs tend to focus on behaviour control. Common core elements of such programs include positive reinforcement, problem solving skills training and role playing, as behavioral problems are often assumed somewhat inherently wrong, or a “lack of something”, the programs aims at improving or changing. The study presents a developmental approach that understands behavioral problems as the result of intentions, values and goals that need to be taken in full consideration and that are usually legitimate, even though carried out in ways that prove dysfunctional for both the young person and society. In other words, we consider antisocial behaviors as maladaptive responses to legitimate developmental tasks, a deviant way of meeting positive goals and taking control of one’s life. In the program we describe, a developmental understanding is combined with a psychoanalytically informed perspective on treatment and delivered in multi-modal terms. It has been carried out in Italy for the past 20 years, with positive outcomes, both in private practice and within the juvenile justice services.  (more…)