Author Interviews, JAMA, Thyroid / 15.05.2017

MedicalResearch.com Interview with: Dr. C. Seth Landefeld MD U.S. Preventive Services Task Force and Chairman of the department of Medicine and Spencer Chair in Medical Science Leadership University of Alabama at Birmingham (UAB) School of Medicine  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Thyroid cancer is rare in the United States, and the evidence shows that screening for it leads to an increase in new diagnoses without affecting the number of people who die from it. This is because screening people without signs or symptoms for thyroid cancer often identifies small or slow-growing tumors that might never affect a person during their lifetime. After reviewing the evidence, the Task Force found little evidence on the benefits of screening for thyroid cancer and considerable evidence that treatment, which is often unnecessary, can cause significant harms. Additionally, in places where universal screening has been implemented, it hasn’t helped people live longer, healthier lives. (more…)
Author Interviews, Blood Pressure - Hypertension, Compliance / 15.05.2017

MedicalResearch.com Interview with: Dr. Gupta Pankaj Consultant Metabolic Physician/Chemical Pathologist Dr. Patel Prashanth - Consultant Metabolic Physician/Chemical Pathologist Department of Metabolic Medicine and Chemical Pathology University Hospitals of Leicester NHS Trust, UK   MedicalResearch.com: What is the background for this study? What are the main findings? Response: Non-adherence or patients not taking their medications as prescribed is known since the time of Hippocrates. It is the key reason why blood pressure is well controlled in only around 50% of patients with hypertension, despite the availability of good medicines. Non-adherence leads to poorer cardiovascular outcomes and is thought to cost $100 billion to the US health economy. A crucial reason for the lack of progress in improving adherence has been the previous lack of a clinically useful objective measure. We and others have developed a robust and reliable biochemical screening method to assess for non- adherence to antihypertensive medications in urine or blood using a technique called liquid chromatography-tandem mass spectrometry.  We have previously reported a single centre study that demonstrated high rates of non-adherence in patients attending a hypertension clinic. Since, then we have set up a National Centre for Adherence Testing (NCAT, ncat@uhl-tr.nhs.uk) in the Department of Metabolic Medicine and Chemical Pathology, University Hospitals of Leicester NHS Trust (UHL) and receive samples from around 25 hypertension clinics across UK. This study analysed data from~1400 patients consisting of samples received in UHL and also from a cohort of patients in the Czech Republic. (more…)
Author Interviews, Cancer Research, Mediterranean Diet, Nutrition / 15.05.2017

MedicalResearch.com Interview with: Antonio Giordano MD PhD Sbarro Institute for Cancer Research and Molecular Medicine and Center for Biotechnology
College of Science and Technology
Temple University, Philadelphia, Pennsylvania MedicalResearch.com: What is the background for this study? What are the main findings? Response: The Mediterranean diet is considered to be one of the healthiest nutrition patterns. Tomatoes, in particular, which are consumed worldwide, and a basic ingredient of the Mediterranean diet, have been postulated to have a cancer preventive role at least for some tumor types, although few studies analyzed the effects of tomatoes in their entirety in different stages of cancer progression. Here, we focused on an in vitro model of gastric cancer because it is still one of the most common and deadly cancers and its development is strongly influenced by certain eating habits. Our results showed a possible role of tomatoes against typical neoplastic features. The treatment with tomato extracts affected the ability of cancer cell growth both in adherence and in semisolid mediums. Moreover, tomato extracts affected key processes within the cell; they hindered migration ability, arrested cell cycle through the modulation of retinoblastoma tumor suppressor family proteins and specific cell cycle inhibitors, and induced cancer cell death through apoptosis. (more…)
Author Interviews, Genetic Research, Ophthalmology / 15.05.2017

MedicalResearch.com Interview with: Zheng-Rong Lu, Ph.D. M. Frank Rudy and Margaret Domiter Rudy Professor of Biomedical Engineering Department of Biomedical Engineering Case Western Reserve University Cleveland, OH 44106 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Genetic vision disorders are a major cause of severe vision loss and blindness, especially in children and young adults. Currently, there are no approved therapies to treat these types of disorders. This study focused on one such disease known as Leber’s congenital amaurosis type 2 (LCA2). Patients with LCA2 are born with some degree of vision loss, and are often legally blind by early adulthood. LCA2 is a recessive disease caused by a mutation in one of the genes responsible for visual processing. LCA2 is a good candidate for gene therapy, and clinical trials underway to test viral vectors that deliver a healthy copy of the mutated gene into the eye have demonstrated considerable therapeutic efficacy. These trials have validated the feasibility of gene therapy to treat this disease, however viral vectors are limited by potential safety issues, complex preparation methods, and limitations on the size of genes that can be delivered. In this study, we successfully treated LCA2 in mice for 120 days by delivering the gene responsible for LCA2 in a synthetic lipid nanoparticle instead of a viral vector. Our delivery system, called ECO, specifically targets the cells in the retinal pigmented epithelium, where the mutation behind LCA2 occurs. Our nanoparticle delivery system is easy to produce, safe, and has unlimited cargo capacity. Most important, our nanoparticle gene delivery system is a platform that can be used to deliver any gene into the retina, opening the door for safe and effective gene therapy for any genetic vision disorder. (more…)
Author Interviews, Cost of Health Care, Kidney Disease / 13.05.2017

MedicalResearch.com Interview with: Shaum Kabadi HEOR Director at AstraZeneca MedicalResearch.com: What is the background for this study? What are the main findings? Response: More than 20 million adults – roughly 1 in 10 adults – in the US are estimated to have chronic kidney disease (CKD), and this population is expected to grow as the US population ages. Patients with CKD are at high risk for progression to end-stage renal disease (ESRD), a condition requiring dialysis or kidney transplantation to maintain patients’ long-term survival. The cost of treating ESRD patients was over $40 billion in public and private funds in 2009. Prior research shows per-person annual Medicare expenses attributable to CKD were $1,700 for Stage 2, $3,500 for Stage 3, and $12,700 for Stage 4. Additional research is required to understand the economic burden of CKD by stage in a contemporary cohort of commercially insured patients with non-dialysis-dependent (NDD)-CKD. This retrospective cohort study utilized data from the HealthCore Integrated Research Environment, which contained medical and pharmacy administrative claims integrated with laboratory result values from 14 regionally dispersed Anthem health plans in the US. Of 16,030 patients identified with CKD, the mean (SD) estimated glomerular filtration rate (eGFR) (all in mL/min/1.73 m2) in 2014 was 44.3 (±18.7), and the breakdown by eGFR levels was: Stage 1 (≥90) 3%, Stage 2 (60–89) 13%, Stage 3a (45–59) 27%, Stage 3b (30–44) 35%, Stage 4 (15–29) 19%, and Stage 5 (<15) 3%. Mean age across all stages was 67.4 years, and 47% were women. Hospitalization rate (%) and number of outpatient encounters (visits per patient per year) by stage were: Stage 1 (11.6%, 19.8), Stage 2 (14.9%, 22.5), Stage 3a (16.2%, 23.6), Stage 3b (23.7%, 29.5), Stage 4 (30.7%, 36.3), and Stage 5 (30.8%, 61.7) (p-trend). (more…)
Author Interviews, Gastrointestinal Disease, Lancet, Vaccine Studies / 13.05.2017

MedicalResearch.com Interview with: Leslie Williams, BS, RN, MBA</strong> Director, Founder, President and Chief Executive Officer <strong>Dr Robert P Anderson MBChB BMedSc PhD FRACP</strong> Chief Scientific Officer ImmusanT Cambridge, MALeslie Williams, BS, RN, MBA Director, Founder, President and Chief Executive Officer and Dr Robert P Anderson MBChB BMedSc PhD FRACP Chief Scientific Officer ImmusanT, Cambridge, MA MedicalResearch.com: What is the background for this study? Response: The 2 Phase 1 trials were randomized, double-blind, placebo-controlled, multi-center studies evaluating the safety, tolerability, and relevant bioactivity of Nexvax2 in HLA-DQ2.5+ patients with celiac disease. In one study, patients received three fixed doses of Nexvax2 or placebo once per week over a three-week period. In the other study, patients received 16 fixed doses of Nexvax2 or placebo twice per week over an eight-week period. Both studies evaluated a range of fixed, intradermal dose administrations in a series of ascending dose cohorts, which included a crossover, double-blind, placebo-controlled oral gluten challenge in the screening and post-treatment periods. The primary outcome measures were the number and percentage of adverse events in the treatment period. (more…)
Author Interviews, Eating Disorders / 13.05.2017

MedicalResearch.com Interview with: Cynthia Bulik, PhD, FAED Founding director of the UNC Center of Excellence for Eating Disorders and Professor at Karolinska Institutet in Stockholm, Sweden. MedicalResearch.com: What is the background for this study? Response: Researchers and clinicians from around the world came together to create the most powerful genome-wide association study of anorexia nervosa to date. Via this global collaboration, we were able to identify the first significant locus that influences risk for anorexia nervosa. We have known that anorexia is heritable for over a decade, but now we are actually identifying which genes are implicated. This is the first one identified! (more…)
AHA Journals, Author Interviews, Baylor College of Medicine Houston, Heart Disease, Lipids / 13.05.2017

MedicalResearch.com Interview with: Julia M. Akeroyd, MPH Center for Innovations in Quality, Effectiveness, and Safety (IQuESt) Michael E. DeBakey Veteran Affairs Medical Center Salim S Virani, MBBS, Ph.D. Baylor College of Medicine MedicalResearch.com: What is the background for this study? Response: In the recently published Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) trial, treatment with evolocumab resulted in a 15% relative (1.5% absolute) risk reduction of major cardiovascular events in patients with atherosclerotic cardiovascular disease (ASCVD) at a median follow-up of 2.2 years. Given the high cost of evolocumab, there is a need to identify what proportion of ASCVD patients would qualify for evolocumab based on FOURIER entry criteria and how eligibility would change if maximal doses of evidence-based lipid lowering therapies were required. (more…)
Author Interviews, CDC, Rheumatology / 13.05.2017

MedicalResearch.com Interview with: Jin Qin, ScD, MS Epidemiologist Centers for Disease Control and Prevention Chamblee, GA 30341  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The hand is one of the sites most commonly affected by osteoarthritis (OA) but is often understudied compared with knee and hip OA. Many people with hand OA have significant symptoms, impaired hand strength and function, and disability in activities of daily living, like using a smart phone or a computer keyboard, and opening a jar. Lifetime risk is the probability of developing a condition over the course of a lifetime. In this study, we estimated that 40% of adults will develop symptomatic hand OA in their lifetimes. Nearly one in two women (47%) and one in four men (25%) will develop the condition. Whites have a 41% lifetime risk, compared with 29% for blacks. The lifetime risk among individuals with obesity is 47%, which is 11 percentage points higher than those without obesity. (more…)
Author Interviews, Gastrointestinal Disease / 13.05.2017

MedicalResearch.com Interview with: Brooks D. Cash, MD Chief, Gastroenterology Division Professor of Medicine University of South Alabama Mobile, AL 36688 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Irritable bowel syndrome (IBS) is a chronic functional disorder characterized by multiple symptoms including, but not limited to, abdominal pain or discomfort, constipation, diarrhea, urgency of bowel movement (BM), a sensation of incomplete evacuation, pain at evacuation, abdominal bloating, and passage of gas or mucus. IBS can be classified into four primary subtypes: mixed IBS (IBS-M), diarrhea-predominant IBS (IBS-D), constipation-predominant IBS (IBS-C), and unsubtyped IBS (IBS-U). Among adult patients with IBS, a sizeable proportion suffers from IBS-M, with prevalence rates among IBS patients estimated to be between 44% to 66%. Because of the variability in symptoms associated with IBS-M and the lack of effective or approved therapies, clinicians often face challenges in managing this common IBS subtype. PO and its active ingredient, l-Menthol, are kappa opioid agonists, possess smooth muscle calcium channel antagonist and serotonergic (5HT3) antagonist properties, and exert anti-inflammatory, anti-infective, and carminative effect. A recent meta-analysis of medical therapies for IBS found that PO had the lowest number needed to treat among the various options evaluated. The previously published IBS Reduction Evaluation and Safety Trial (IBSREST) showed that PO-SST, a novel formulation of PO using solid-state microspheres to target delivery to the small intestine, was an effective IBS therapy at 24 hours, with improved efficacy at 4 weeks in a combined group of IBS-M and IBS-D patients. In view of the unmet need in IBS-M, we performed a post hoc analysis of the effects of PO-SST among only the IBS-M patients from the IBSREST trial. (more…)
Author Interviews, Infections, Respiratory, Vaccine Studies / 12.05.2017

MedicalResearch.com Interview with: Nima Farzan Chief Executive Officer & President of PaxVax MedicalResearch.com: What is the background for this study? What are the main findings? Response: PaxVax is developing a new and improved version of the vaccine, known as the Modernized Production Adenovirus Vaccine (MPAV) Prototype A. The Company was chosen as the Small Business Innovation Research and Regulatory Sponsor for the development of the Modernized Production Adenovirus Vaccine (MPAV) Prototype A due to the company’s prior experience working with multiple strains of Adenovirus. An Investigational New Drug (IND) application for MPACV was submitted to the U.S. Food and Drug Administration (FDA) on January 30, 2017. The Phase I clinical trial has been initiated and will be conducted at the Larner College of Medicine at the University of Vermont and Cincinnati Children’s Hospital. PaxVax expects to see results of the Phase I clinical trial in early 2018. Complications of adenovirus 4/7 can include headache, pneumonia, sore throat and eye infections. In severe cases, adenovirus can lead to acute respiratory distress syndrome and other serious complications related to organ system damage (including GI tract and bladder) that can result in death, if left untreated. (more…)
Author Interviews, Brigham & Women's - Harvard, Endocrinology, Hearing Loss, Menopause / 11.05.2017

MedicalResearch.com Interview with: Sharon G. Curhan, MD, ScM Channing Division of Network Medicine Department of Medicine Brigham and Women's Hospital Harvard Medical School Boston, MA 02115 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Hearing loss affects approximately 48 million Americans and the number is expected to increase as the population ages. Some previous studies suggested that menopause may increase the risk for hearing loss, presumably due to the reduction in circulating estrogen levels, and that postmenopausal hormone therapy might slow hearing decline by “replacing” estrogen. To evaluate the role of menopause and postmenopausal hormone therapy as risk factors for hearing loss, we examined the independent associations between menopausal status, oral hormone therapy, and risk of self-reported hearing loss in 80,972 women who are participants in the Nurses’ Health Study II, aged 27-44 years at baseline, and were followed from 1991 to 2013. After more than 1.4 million person-years of follow-up, 18,558 cases of hearing loss were reported (~23% of the women developed hearing loss). We did not observe an overall independent association between menopausal status and risk of hearing loss. However, the risk among women who underwent natural menopause at an older age was higher. Specifically, the risk among women who underwent natural menopause at age 50 or older was 10% higher than among those who underwent natural menopause before age 50 [multivariable-adjusted relative risk (MVRR): 1.10, 95% CI 1.03, 1.17]. When we conducted an analysis restricted to women who underwent natural menopause and did not use hormone therapy (HT), the multivariable-adjusted relative risk among women who underwent natural menopause at age 50-54 years was 21% higher (MVRR: 1.12, 95% CI: 1.10, 1.34), and among women who underwent natural menopause at age 55+ years was 29% higher (MVRR: 1.29, 95% CI: 1.11, 1.50), compared with women who underwent natural menopause before age 50. Among postmenopausal women, we also found that use of oral HT was associated with higher risk of hearing loss, and the magnitude of the risk tended to increase with longer duration of use (p-trend < 0.001). Compared with women who never used any type of HT, the MVRR of hearing loss among women who used oral HT for 5-9.9 years was 15% higher (MVRR: 1.15, 95% CI: 1.06, 1.24), and for 10+ years was 21% higher (MVRR: 1.21, 95% CI: 1.07, 1.37). When specific types of oral HT were examined, longer duration of use of either oral estrogen-only or of combined estrogen plus progestogen HT were each associated with higher risk. Fewer women reported use of progestogen-only oral HT, yet among these women a higher risk was suggested, but not significant (MVRR: 1.15, 95% CI: 0.98, 1.35). Transdermal HT use was less common, but the associations observed were similar to those with oral hormone therapy. When examined separately by type of menopause, the results for HT use were similar. (more…)
ADHD, Author Interviews, JAMA, Karolinski Institute / 11.05.2017

MedicalResearch.com Interview with: Zheng Chang PhD MSc Department of Medical Epidemiology and Biostatistics (MEB) Karolinska Institutet Stockholm Sweden MedicalResearch.com: What is the background for this study? What are the main findings? Response: About 1.25 million people worldwide die annually because of motor vehicle crashes (MVCs). ADHD is a prevalent neurodevelopmental disorder with symptoms that include poor sustained attention, impaired impulse control and hyperactivity. ADHD affects 5 percent to 7 percent of children and adolescent and for many people it persists into adulthood. Prior studies have suggested people with ADHD are more likely to experience MVCs. Pharmacotherapy is a first-line treatment for the condition and rates of ADHD medication prescribing have increased over the last decade in the United States and in other countries. Among the more than 2.3 million patients with ADHD (average age 32.5), we found patients with ADHD had a higher risk of an MVC than a control group of people without ADHD. The use of medication in patients with ADHD was associated with reduced risk for motor vehicle crashes in both male and female patients. (more…)
Author Interviews, Emory, Mental Health Research, Technology / 10.05.2017

MedicalResearch.com Interview with: Jessica Maples-Keller Emory University School of Medicine. MedicalResearch.com: What is the background for this study? What are the main findings? Response:  This manuscript is a review of the use of Virtual Reality (VR) technology within psychiatric treatment. VR refers to an advanced technological communication interface in which the user is actively participated in a computer generated 3-d virtual world that includes sensory input devices used to simulate real-world interactive experiences. VR is a powerful tool for the psychiatric community, as it allows providers to create computer-generated environments in a controlled setting, which can be used to create a sense of presence and immersion in the feared environment for individuals suffering from anxiety disorders. (more…)
Author Interviews, Immunotherapy, JAMA, Melanoma / 10.05.2017

MedicalResearch.com Interview with: Yasuhiro Nakamura, M.D., Ph.D. Associate Professor Department of Skin Oncology/Dermatology Comprehensive Cancer Center Saitama Medical University International Medical Center Hidaka, Saitama MedicalResearch.com: What is the background for this study? What are the main findings? Response: Regressing nevi, which are frequently associated with halo phenomenon, occur in approximately 1% of the general population. In patients with melanoma, spontaneous or treatment-related depigmentation of the skin (vitiligo) is sometimes observed. Although humoral and cellular immune responses may play a crucial role in their development, immune reactions to benign melanocytic nevi (BMN) without a halo are extremely rare in both the general population and in patients with melanoma. This publication reports a rare case with multiple metastatic melanomas who showed a remarkable clinical response to nivolumab with a simultaneous prominent immune reaction to multiple BMN without halo phenomenon. This rare phenomenon may be associated with dramatic efficacy of nivolumab in melanoma patients. (more…)
Author Interviews, Gastrointestinal Disease, Hepatitis - Liver Disease / 10.05.2017

MedicalResearch.com Interview with: Dr. Winston Dunn, MD Assistant Professor The University of Kansas Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: It is widely believed that everyone with HCV can be cured with the medications now a day. But sadly, about 5% of the patients already have very bad damage done to the liver. We call this decompensated cirrhosis. Our medication is still very effective in curing the virus, but in decompensated cirrhosis, curing the virus is not always enough. Only about half to two-thirds of patients with decompensated cirrhosis clinically gets better, but the remaining struggles along or even gets worse after the cure. That is the problem. So, our research was to understand why that was. We used genetic factor to predict which patient would get better and which patient would not. We found that a gene previous found to be predictive of fatty liver and fibrosis is also predictive of recovery in this setting. (more…)
Author Interviews, BMJ, Heart Disease, Pain Research, Pharmacology / 10.05.2017

MedicalResearch.com Interview with: Michèle Bally, BPharm, MSc, PhD Epidemiologist, Department of Pharmacy, CHUM Researcher, Health Innovation and Evaluation Hub, CRCHUM MedicalResearch.com: What is the background for this study? Response: The objective of this study was to better understand the risk of heart attack associated with using oral prescription non-steroidal anti-inflammatory drugs or NSAIDs (ibuprofen, diclofenac, celecoxib, and naproxen) the way people usually do to treat pain and inflammation in real life circumstances. A lot of people take medication, but they do not understand that some can be more harmful than beneficial, especially with consistent use. Unfortunately, something like a heart attack can happen anywhere. You could be at work and show signs of an attack. If this does happen, hopefully you have someone who is first aid trained to at least help you deal with these symptoms, until you get to the hospital. This is why having someone who knows that they are doing is beneficial in any environment. If it wasn't for companies like Coast2Coast in Ottawa, the chances of someone who was suffering from a heart attack may not have made it to the hospital if it wasn't for the assistance of someone who was first aid trained. In clinical trials, NSAIDs were typically taken on a continuous basis in high standardized doses, as assigned by the trial protocol. However, the dosages and the treatment durations studied in trials may not represent the reality of many patients who use NSAIDs in low or varying doses, use these drugs on and off, or switch between NSAID medications. We were particularly interested in determining the onset of the risk, that is how soon does the risk of heart attack start increasing? Also, we wanted to investigate the effect of dose and duration of treatment. To do this, we studied the use of a low or high dose level of NSAIDs over certain set periods of time, including taking these medications only for 1 to 7 days. (more…)
Accidents & Violence, Author Interviews, Pediatrics / 10.05.2017

MedicalResearch.com Interview with: Kris Jatana, MD FAAP Pediatric Otolaryngologist Nationwide Children’s Hospital MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study looked at a 21-year period – 1990 through 2010 – and focused on children younger than 18 years of age treated in U.S. hospital emergency departments for cotton tip applicator-related ear injuries. About 263,000 children were injured during the study period, which comes out to approximately 1000 injuries seen in emergency departments every month or 34 per day. The majority of injuries occurred when cotton tip applicators were used to clean a child’s ear canal (73%), and most of those injuries occurred when a child was using a cotton tip applicator on their own (77%), or their parent was using the device (16%) to clean the ear canal. About two out of every three patients were younger than 8 years of age, and patients aged 0-3 years accounted for 40% of all injuries. Surprisingly, the highest rate of injury was in children 0-3 years old. The most common injuries were foreign body sensation (30%), perforated ear drum (25%) and soft tissue injury (23%). (more…)
Author Interviews, Nutrition, Social Issues / 10.05.2017

MedicalResearch.com Interview with: Jay L. Zagorsky Center for Human Resource Research The Ohio State University and Patricia K. Smith PhD Department of Social Sciences University of Michigan-Dearborn MedicalResearch.com: What is the background for this study? Response: The prevalence of adult obesity in the U.S. has risen substantially, from about 13% in the early 1960s to nearly 38% now.  Obesity is associated with a variety of illnesses and imposes significant costs on individuals and society. Socioeconomic (SES) gradients in health and the prevalence of disease, including obesity, have been documented: health improves and disease prevalence falls as we move up each step of the SES ladder.  Differences in nutrition could help explain these health gradients and Americans commonly think the poor eat fast food more often than those in the middle and upper classes. Policy based on this notion has been proposed.  For example, in 2008 Los Angeles placed a moratorium on new fast-food restaurants in poor neighborhoods. (more…)
Allergies, Asthma, Author Interviews, Dermatology, PLoS, Vitamin D / 10.05.2017

MedicalResearch.com Interview with: Brent Richards, MD, MSc Associate Professor of Medicine William Dawson Scholar / FRQS Clinical Research Scholar Departments of Medicine, Human Genetics, Epidemiology and Biostatistics McGill University Senior Lecturer, King's College London (Honorary) MedicalResearch.com: What is the background for this study? What are the main findings? Response: Some previous epidemiological studies have suggested that low vitamin D levels are associated with increased rates of asthma, atopic dermatitis—an itchy inflammation of the skin—and elevated levels of IgE, an immune molecule linked to atopic disease (allergies). In our study, we looked at genetic and health data on more than 100,000 individuals from previous large studies to determine whether genetic alterations that are associated with vitamin D levels predispose people to the aforementioned conditions. We found no statistically significant difference between rates of asthma (including childhood-onset asthma), atopic dermatitis, or IgE levels in people with and without any of the four genetic changes associated with lower levels of 25-hydroxyvitamin D, the form of vitamin D routinely measured in the blood. (more…)
Author Interviews, C. difficile, Infections, Microbiome / 09.05.2017

MedicalResearch.com Interview with: Sheila Connelly, PhD Vice President, Research Synthetic Biologics, Inc. MedicalResearch.com: What is the background for this study? Response: Synthetic Biologics, Inc. is focused on the protection and preservation of the gut microbiome which is the diverse collection of microorganisms that live in the intestinal tract. We are learning that the gut microbiome plays a key role in health. Negative changes to the microbiome, called dysbiosis, are linked to disease states including allergies, autism, and obesity, among a rapidly growing list of other conditions. A consequence of using antibiotics is that, in addition to fighting the bacterial infection being treated, they also kill the gut microbiota. The space left in the gut by the dead bacteria allows other surviving bacteria, many times opportunistic pathogens or microbes that are resistant to multiple antibiotics, to overgrow and fill the open niches. Exposure to antibiotics, particularly broad-spectrum antimicrobials, such as penicillins and cephalosporins, is a major risk factor for acquiring a potentially deadly Clostridium difficile infection. Another consequence of antibiotic use is the emergence of antibiotic-resistant organisms. Widespread use of antibiotics provides selective pressure for the evolution of lethal, multi-drug resistant pathogens, termed “nightmare bacteria”. The gut microbiome acts as a reservoir of antibiotic resistance that can be triggered, by antibiotic exposure, to acquire and propagate resistance genes. A way to protect the microbiome and reduce antibiotic resistance is to limit exposure of the gut microbiota to antibiotics. To this end, we developed an antibiotic inactivation strategy using a beta-lactamase enzyme to degrade beta-lactam antibiotics in the GI tract before they can harm the gut microbiome. Beta-lactamases are naturally-occurring bacterial enzymes that confer resistance to beta-lactams, the most widely used broad spectrum antibiotics, and their presence is normally considered an obstacle to efficacious infection control. We took advantage of the highly efficient antibiotic degradation activity of a beta-lactamase and developed SYN-004 (ribaxamase). Ribaxamase is a beta-lactamase engineered to inactivate penicillins and most cephalosporins, formulated for oral delivery, and intended for use with IV beta-lactam antibiotics to degrade the antibiotics in the GI tract to protect the microbiome. Ribaxamase was demonstrated to significantly reduce the occurrence of C. difficile disease in a recently completed Phase 2b clinical study. The study met its primary endpoint by demonstrating that ribaxamase, when delivered orally with IV ceftriaxone, significantly reduced C. difficile disease in patients treated for a respiratory tract infection. Ribaxamase also resulted in a significant reduction in new colonization by vancomycin-resistant enterococcus (VRE). For the current study, pig models of antibiotic-mediated gut dysbiosis were established using three classes of beta-lactam antibiotics, a cephalosporin, ceftriaxone, a penicillin, amoxicillin, and a carbapenem, ertapenem. The ceftriaxone model was used to evaluate the protective effect of ribaxamase on the microbiome and the amoxicillin and ertapenem models are intended for evaluation of pipeline products. (more…)
Accidents & Violence, Author Interviews, Pediatrics / 09.05.2017

MedicalResearch.com Interview with: Monika Goyal, M.D., M.S.C.E. Assistant Professor of Pediatrics & Emergency Medicine Director of Research, Division of Emergency Medicine and Attending Physician Children’s National Health System The George Washington University MedicalResearch.com: What is the background for this study? What are the main findings? Response: As pediatric emergency clinicians, unfortunately, many of us have cared for a number of children who have been victims of gun violence. We wanted to investigate whether gun laws may make a difference in the rates of firearm-related morbidity and mortality in children. We specifically were interested in emergency department visits because they relate directly to the care we provide to pediatric patients. Our main findings from our five-year study were that children are affected by gun violence nationally and, specifically, we saw regional differences in emergency department visits made by children who were victims of firearm violence. Overall, firearm-related visits by patients 21 and younger to emergency departments remained consistent over time at a rate of 65 per every 100,000 visits until 2013, when they decreased slightly to 51 per 100,000 visits. We also found that regions with more strict gun laws had lower rates of emergency department visits by children for gun violence compared with those regions with less stringent laws. We used the Brady Score, which looks at various state gun laws and assigns a score, to measure strictness. Then, based on state-level scores, we created regional composite scores. (more…)
AACR, Author Interviews, Cancer Research, Genetic Research / 08.05.2017

MedicalResearch.com Interview with: Dr. Youzhi Li Vice President at Boston Biomedical  MedicalResearch.com: What are the main findings? Response: RNAi (RNA interference) technology has the potential to target any genes causing disease, including conventionally “undruggable” targets in cancer. One particularly interesting RNAi target in oncology is the CTNNBI oncogene, which encodes the β-Catenin protein whose nuclear form acts as a transcription factor promoting tumorigenesis. Aberrant β-Catenin signaling has been demonstrated in 90 percent of colorectal carcinomas, 40 percent of hepatocellular carcinoma, and 90 percent of non-ductal pancreatic carcinomas. Recent research also suggests active β-Catenin contributes to tumor immune evasion and to the recurrence of melanoma in patients post the check-point blockage immunotherapy. However, the direct blockade of β-Catenin activity has proved difficult with conventional approaches. While the application of traditional RNAi technology has the potential to block this pathway, in clinical cancer therapy, this approach has proven challenging due to the difficulty in systemic delivery of RNAi to tumor sites located in various organs. We have recently developed BBI-801, a lipid-based nanoparticle that encapsulates therapeutic aiRNAs targeting CTNNB1 and PD-L1 to simultaneously target immune evasion via both these pathways. Here, we investigate the in vivo delivery and anti-tumor activity of BBI-801. (more…)
Author Interviews, NYU, Schizophrenia / 08.05.2017

MedicalResearch.com Interview with: Donald C. Goff, MD Marvin Stern Professor Vice Chair for Research Department of Psychiatry NYU Langone Medical Center MedicalResearch.com: What is the background for this study? Response: Since their introduction in the 1950’s antipsychotic drugs have been an integral part of the treatment of schizophrenia. However, over the past decade concerns have been raised about whether these drugs might negatively affect the long-term course of the illness—either by causing supersensitivity of dopamine receptors, which might make patients more prone to psychosis and relapse, or by direct toxic effects on the brain. To address these concerns, we convened a panel of international experts to review the evidence supporting these concerns, including findings from clinical studies, brain imaging studies, post-mortem examination of the brains of people treated with these drugs, and studies in which these drugs were administered to animals. (more…)
Author Interviews, JAMA, Ophthalmology / 08.05.2017

MedicalResearch.com Interview with: John H Kempen, MD, PhD Protocol Chair, MUST Trial Follow-up Study; Vice Chair, MUST Research Group Director of Epidemiology for Ophthalmology, Massachusetts Eye and Ear Harvard Medical School Editor-in-Chief, Ophthalmic Epidemiology President, Sight for Souls MedicalResearch.com: What is the background for this study? Response: Uveitis is about the fifth leading cause of blindness in the united states.  Among types of uveitis, intermediate, posterior and panuveitis are the leading causes of blindness.  Before 2005, systemic therapy with corticosteroids—supplemented when indicated with immunosuppressive drugs (most of the time)—was the primary treatment recommended for these conditions.  With approval of the fluocinolone acetonide implant in 2005 for intermediate, posterior and panuveitis, it became unclear which of the alternative treatment approaches should be the treatment of choice. The multicenter uveitis steroid treatment (must) trial was initiated in 2005 to directly compare the alternative treatments.  Systemic therapy was administered using high dose prednisone followed by tapering of corticosteroids to maintenance doses of 10 mg/day or less (generally 7.5 mg/day or less) or to zero; this was supplemented by immunosuppressive corticosteroid-sparing drugs in 88% of participants.  Implant therapy was done by initial quieting of the anterior chamber of the eye with topical, injected or systemic corticosteroids followed by surgical implant placement within 28 days (first eye) and 56 days (second eye if it was indicated).  After this, systemic corticosteroids and immunosuppressive drugs were tapered off. (more…)
Author Interviews, CMAJ, Fertility, Karolinski Institute, OBGYNE / 08.05.2017

MedicalResearch.com Interview with: Neda Razaz, PhD, MPH Postdoctoral Fellow Reproductive Epidemiology Unit Karolinska Institutet MedicalResearch.com: What is the background for this study? What are the main findings? Response: Multiple births of twins and triplets – and the associated health risks – have increased in many high-income countries, with a respective two-fold and three-fold increase in recent decades. In Canada, triplet births or higher have increased from 52.2 per 100 000 live births to 83.5 between 1991 and 2009, mainly because of an increase in fertility treatments for older women of child-bearing age. In this study we found that among twin and triplet pregnancies that were reduced to singleton or twin pregnancies, there was a substantial reduction in complications such as preterm birth and very preterm birth. Although rates of death and serious illness were not lower among all multifetal pregnancies that were reduced, pregnancies that resulted from fertility treatments did show a significant reduction in rates of death or serious illness following fetal reduction. (more…)
Author Interviews, Biomarkers, Brain Injury, Pediatrics / 07.05.2017

MedicalResearch.com Interview with: Steven Daniel Hicks, MD, PhD Assistant Professor, Division of Academic General Pediatrics College of Medicine Penn State Health MedicalResearch.com: What is the background for this study? What are the main findings? Response: There are about 3 million concussions in the US each year and the majority occur in children. Parents of children with concussions commonly cite length of recovery as a major concern, but pediatricians have no objective or accurate tests for addressing this concern. Our research group previously identified small regulatory molecules called microRNAs that were altered in both the spinal fluid and saliva in children with traumatic brain injuries. In this study we investigated whether those microRNAs could predict duration of concussion symptoms. In 52 children with concussion we found a set of microRNAs that predict whether concussion symptoms would last beyond one month with over 80% accuracy. This was significantly more accurate than survey based tools such as the sports concussion assessment tool or a modified concussion clinical risk score. Interestingly, the microRNAs with predictive accuracy targeted pathways involved in brain repair and showed correlations with specific concussion symptoms. (more…)
Author Interviews, Baylor College of Medicine Houston, Merck, Rheumatology / 07.05.2017

MedicalResearch.com Interview with: Grace H. Lo MD MSc Department of Medicine, Baylor College of Medicine Medical Care Line and Research Care Line, Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety Michael E. DeBakey Medical Center, Houston, TX MedicalResearch.com: What is the background for this study? What are the main findings? Response: Osteoarthritis is the most common form of arthritis. Many people who have signs of osteoarthritis on x-rays do not necessarily complain of pain. Presently, there are no known strategies for preventing the development of pain in this group of people. This study suggests that if these people have noisy knees (otherwise known as “crepitus”), they are at higher risk for developing pain within the next year compared to the people who do not have noisy knees. Future studies that target people who have x-ray signs of osteoarthritis, who do not complain of pain, but do report noisy knees, hold the promise of identifying interventions that can prevent knee pain. (more…)
Author Interviews, Diabetes, Diabetologia, Nutrition, Pediatrics / 07.05.2017

MedicalResearch.com Interview with: Sari Niinistö, PhD Senior Researcher, Public Health Solutions, Nutrition Unit National Institute for Health and Welfare Helsinki, Finland MedicalResearch.com: What is the background for this study? Response: Previous prospective studies have observed protective association between fish-derived fat and type 1 diabetes related autoimmunity in older children. Also some other fatty acids have been associated with the risk for type 1 diabetes associated autoimmunity. We wanted to study very young children, because type 1 diabetes associated autoimmunity often begins early, already in infancy. Therefore, we investigated whether serum fatty acid levels during infancy or the main dietary sources of fatty acids (breast milk and infant formula) were related to the development of autoimmunity responses among children at increased genetic risk of developing type 1 diabetes. (more…)