MedicalResearch.com Interview with:
Courtney Benjamin Wolk, Ph.D.
Postdoctoral Researcher
Center for Mental Health Policy and Services Research
Perelman School of Medicine Department of Psychiatry
University of Pennsylvania Philadelphia, PA 19104
Medical Research: What is the background for this study? What are the main findings?
Response: Previous research investigating the relationship between anxiety and suicidality has been mixed. An ongoing question in the field has been whether anxiety disorders independently increase risk for suicidal ideation and behavior or if the high co-occurrence of anxiety and mood symptoms or other shared demographic factors are driving relationships that have been observed between anxiety and suicidality.
We examined the relationship between response to treatment for an anxiety disorder in childhood and suicidal ideation, plans, and attempts 7 to 19 years after treatment with cognitive-behavioral therapy, more commonly referred to as CBT. Our results indicated that participants who responded favorably to cognitive-behavioral therapy during childhood had lower rates of lifetime, past month, and past two-week suicidal ideation endorsement than treatment non-responders. This was the case across both self-report and interview-report of suicidal ideation. Treatment response was not significantly associated with suicide plans or attempts, though plans and attempts were infrequently endorsed in our sample, limiting the ability to detect findings.
MedicalResearch.com Interview with:
Fernando Pardo-Manuel De Villena, PhD
Professor and Associate Chair for Research
Department of Genetics
School of Medicine
University of North Carolina at Chapel Hill
Medical Research: What is the background for this study? What are the main findings?
Response: We set out to identify mutations that affect diseases through changes in gene expression. Our first major finding is that some mouse populations such as the Collabaorative Cross are exceptionally good models to achieve this goal.
We also wanted to sort out an ongoing controversy about the number, location and type of genes that are differentially expressed when you inherit them from your mom or your dad (so called imprinted genes). We conclude that to some extent both sides were right; there are only a limited number of imprinted genes in the classical sense but there are also hundreds or thousands of genes that are preferentially expressed from the father.
MedicalResearch.com Interview with:
Dr. Richard H. Myers Ph.D.
Department of Neurology and Genome Science Institute
Boston University School of Medicine, Boston, MA
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Myers: Andy Hoss, who is a graduate student in my group is the primary investigator for this project.
We are investigating changes that occur in the brain of individuals who had Huntington's disease. We were focused on studying regulatory mechanisms that control the levels of messenger RNAs (mRNAs) in the brain, since that is an area that has been implicated in this disease.
MicroRNAs (miRNAs) are known to target mRNAs for degradation or to be sequestered for storage and later use.
A few limited studies of microRNAs had been done, but we sought to measure the levels of all of the miRNAs present in the brains of persons with Huntington's disease and in controls using next-generation sequencing.
MedicalResearch.com Interview with: Yaron Arbel, M.D. Department of Cardiology Tel Aviv Medical Center Medical Research: What is the background for this study? What are the main findings? Dr. Arbel: We examined 715,000 Israeli adolescents, both male and female, aged 16-20, who had received medical exams from 1998-2011 before enlisting in the army. They were all...
MedicalResearch.com Interview with:
Dr. Michael Farzan PhD
Vice Chairman
Department of Immunology and Microbial Science
Florida Campus
The Scripps Research Institute
Medical Research: What is the background for this study?
Dr. Farzan: The key points are that HIV-1 needs two receptors – CD4 and CCR5 – to infect cells. CD4’s primary job is to initially bind the viral entry protein, which upon CD4 binding, uncloaks its CCR5 binding site. A number of years ago we observed that CCR5 had an unusual modification that was really important to HIV-1. We later showed that antibodies – protein your body makes to protect from pathogens – mimics CCR5 by incorporating this modification. We develop a peptide from one of these antibodies that mimics CCR5.
Medical Research: What are the main findings?
Dr. Farzan: By combined a soluble form of CD4 with this CCR5-mimicking peptide, we created a protein that neutralizes all HIV-1 isolates tested, including the hardest-to-stop viruses, as well as distantly related viruses found in monkeys. It does so better than the best HIV-1 antibodies. We expressed this protein using a commonly used gene-therapy vector, and showed that after a one-time inoculation we could protect from doses much higher than most humans are likely to see, and we did so 34 weeks after the inoculation.
MedicalResearch.com Interview with:
Linda Chin, MD
Department Chair, Department of Genomic Medicine, Division of Cancer Medicine
The University of Texas MD Anderson Cancer Center
Houston, TX
Medical Research: What is the background for this study? What are the main findings?
Dr. Chin: BRAF inhibitors have worked very well against melanoma in the clinic, but when the tumors relapse on treatment, it is not always clear what causes it. Without this information, it can be difficult for doctors to identify specific second-line therapies likely to overcome the drug resistance. In this study, we used both mouse and patient melanoma samples to identify patterns of selected protein levels that can categorize modes of drug resistance when other assays such as DNA sequencing are uninformative. We hope that this information can provide missing clues for clinicians.
Prof. Dr. med. Paul Erne
AMIS Plus Data Center, Epidemiology, Biostatistics and Prevention Institute
University of Zurich
Department of Cardiology
Clinic St. Anna, Lucerne and University Hospital Zurich
Zurich, Switzerland
MedicalResearch: What is the background for this study? What are the main findings?
Prof. Erne: Very little is known on this important subgroup of patients with Acute Coronary Syndrome (ACS) at admission who for various reasons receive restricted or palliative treatment only. Reasons for withholding comprehensive and/or invasive therapy may be the very limited life expectancy, advanced age or severe comorbidities. These patients are not represented in prospective trials and often not included in outcome statistics and registries.
This study provides evidence that the population which received palliative therapy is older and sicker when compared to patients who underwent conservative or reperfusion treatment. However, this study shows that these decisions are very individually addressed. Acute Coronary Syndrome patients treated palliatively were older, sicker, with more heart failure at admission and very high in-hospital mortality. Changes of treatment decisions over time and the proportion of patients surviving 1 year suggest in part non homogenous and potentially questionable decision criteria. While refraining from more active therapy may be the most humane and appropriate approach in many patients, in others it represents under treatment.
MedicalResearch.com Interview with Irene Shui ScD MPH Staff Scientist Fred Hutchinson Cancer Research Center Seattle, WA 98109 MedicalResearch: What is the background for this study? What are the main findings? Dr. Shui: Given the high prevalence of prostate cancer and the wide international variation in vitamin D status, identifying causal links between the two could have...
MedicalResearch.com Interview with:
Professor Andrew W. Munro FRSC FSB
Professor of Molecular Enzymology
Manchester Institute of Biotechnology
Faculty of Life Sciences University of Manchester
Manchester UK
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Munro: Statins are blockbuster drugs that inhibit the key enzyme in cholesterol synthesis: 3-beta-hydroxymethylglutaryl CoA reductase (HMG-CoA reductase), which catalyzes the rate-limiting step in the biosynthesis of cholesterol. As a consequence, statin drugs reduce levels of low-density lipoprotein (LDL-) cholesterol, are effective against hypercholesterolemia and reduce the risk of atherosclerosis and heart attack. One of the major statin drugs is pravastatin, which is derived from a fungal natural product called compactin. The process of conversion of compactin into pravastatin involves the use of an oxygen-inserting enzyme called a cytochrome P450 (or P450), which catalyzes the hydroxylation of compactin to form pravastatin. In order to produce a more cost-efficient and streamlined route to pravastatin production, our teams from the University of Manchester (UK) and DSM (Delft, The Netherlands) developed a single-step process for pravastatin production. This process involved harnessing the productive efficiency of an industrial strain of the beta-lactam (penicillin-type) antibiotic producing fungus Penicillium chrysogenum. The beta-lactam antibiotic genes were deleted from this organism, and replaced by those encoding for compactin biosynthesis (transferred from a different Penicillium species). This led to high level production of compactin, but also to substantial formation of a partially degraded (deacylated) form. To get around this problem and in order to further improve compactin production, the enzyme responsible for the deacylation (an esterase) was identified and the gene encoding this activity was deleted from the production strain. The final stages of development of the novel, one-step pravastatin production process involved the identification of a suitable P450 enzyme that could catalyze the required hydroxylation of compactin. A bacterial P450 was identified that catalyzed hydroxylation at the correct position on the compactin molecule. However, the stereoselectivity of the reaction was in favour of the incorrect isomer – forming predominantly epi-pravastatin over the desired pravastatin. This was addressed by mutagenesis of the P450 – ultimately leading to a variant (named P450Prava) that hydroxylated compactin with the required stereoselectivity to make pravastatin in large amounts. Determination of the structure of P450Prava in both the substrate-free and compactin-bound forms revealed the conformational changes that underpinned the conversion of the P450 enzyme to a pravastatin synthase. The expression of P450Prava in a compactin-producing strain of P. chrysogenum enabled pravastatin production at over 6 g/L in a fed-batch fermentation process, facilitating an efficient, single-step route to high yield generation of pravastatin.
MedicalResearch.com Interview with:
Dr. Yang Lu Ph.D
Los Angeles Biomedical Research Institute
Dr. Lu’s research interests include utilization, cost and treatment regimen adherence of chronic conditions, such as obesity and diabetes; behavioral economic
interventions, and cost effectiveness studies
MedicalResearch: What is the background for this study?
Response: Non-adherence is a serious issue in type 1 diabetes management. It leads to
poor glycemic control and peaks in adolescence and young adulthood. Peer
support is critical for young patients yet few studies examined whether
pairing youth with slightly older and more experienced peers with diabetes
improves their diabetes self-management and glycemic control.
This study had two aims:
(1) assess whether adolescents (as prospective mentees) and young
adults (as prospective mentors) with diabetes would be interested in peer
mentoring as a way to improve adherence, and
(2) identify contents and delivery modes for a peer mentoring topic from the perspective of patients and their parents. Fifty-four adolescents and 46 young adults with type 1
diabetes were surveyed.
MedicalResearch.com Interview with:
Julie M. Zito, PhD
Professor of Pharmacy and Psychiatry
Department of Pharmaceutical Health Services Research
University of Maryland School of Pharmacy
Baltimore, MD 21201
MedicalResearch: What is the background for this study?
Dr. Zito: Atypical antipsychotic (AAP) use in children and adolescents has grown substantially in the past decade, largely for behavioral (non-psychotic) conditions. Poor and foster care children with Medicaid-insurance are particularly affected. This ‘off-label’ usage has insufficient evidence of benefits regarding improved functioning (i.e. appropriate behavior and performance, socially and academically) while the little evidence that accrues tends to emphasize ‘symptoms’, i.e. less acting out. Recent evidence shows that youth treated with Atypical antipsychotics are at risk of serious cardiometabolic adverse events including diabetes emerging after atypical antipsychotics are ‘on board’.
MedicalResearch: What are the main findings?
Dr. Zito: The continued expansion in Atypical antipsychotics use for behavioral conditions, particularly in poor and foster care youth prompted several government reports asking states to implement oversight programs. In our survey of state Medicaid agencies, we identified programs implementing a new and promising approach to increase the likelihood that these medications are used appropriately. These ‘peer review’ programs have been launched in 15 of the 31 prior authorization state Medicaid programs. There is a distinct advantage in having a qualified peer review, on a case-by-case basis, of the rationale for use of an atypical antipsychotic in a condition or age group that is ‘off-label’ according to the FDA product information label.
MedicalResearch.com Interview with:
Anestis Dougkas, MSc, PhD
Food for Health Science Centre
Lund University Lund, Sweden
MedicalResearch: What is the background for this study?
Dr. Dougkas: There has been an increased interest in the macronutrient profile of diets and meals as a factor that influences appetite. Dietary protein is considered as the most satiating macronutrient, yet there is little evidence on whether the effects observed are attributed to the protein or to the concomitant manipulation of carbohydrates and fat. The aim was to examine the effect of consumption of beverages varying in macronutrient content on appetite ratings, energy intake and appetite-regulating hormones.
MedicalResearch: What are the main findings?
Dr. Dougkas: Increased protein content suppressed more average appetite than carbohydrate and fat with a more pronounced effect of protein intake on subjective ratings of prospective consumption. Protein was also the most influential macronutrient for postprandial glucagon like peptide-1 (GLP-1, an appetite- suppressing hormone) response. This appetite-suppressing effect of protein was independent of the changes in fat and carbohydrates.
MedicalResearch.com Interview with: Dr. David T. Hsu Ph.D Department of Psychiatry, Stony Brook University, Stony Brook, NY Department of Psychiatry The Molecular & Behavioral Neuroscience Institute University of Michigan, Ann Arbor, MI Medical Research: What is the background for this study? What are the main findings? Dr. Hsu: The opioid system is known for its role in...
MedicalResearch.com Interview with:
Mallika L. Mendu, MD, MBA
Division of Renal Medicine
Brigham and Women’s Hospital, Harvard Medical School
Boston, MA
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Mendu: Chronic kidney disease affects a significant number of adults in the United States, approximately 13%, and is associated with significant morbidity, mortality and cost. We conducted a review of 1487 patients referred for initial evaluation of chronic kidney disease to two academic medical centers in Boston over a 3-year period, and examined how often laboratory and imaging tests were ordered and how often these tests affected diagnosis and/or management. The main finding was that a number of tests (renal ultrasound, paraprotein testing, serologic testing) were commonly ordered despite low diagnostic and management yield. Urine quantification and hemoglobin A1c testing had the highest diagnostic and management yield.
MedicalResearch.com Interview with: Dr. Alex Johnstone PhD Rowett Institute of Nutrition and Health Aberdeen Medical Research: What is the background for this study? Response: Previous work has indicated that high-protein (30% of diet as protein) meat-based weight loss diets are highly satiating, and reduce the free food intake over a four-week period (1,2). There is limited...
MedicalResearch.com Interview with: Antti Saari, M.D. Department of Pediatrics University of Eastern Finland and Kuopio University Hospital Kuopio Finland MedicalResearch: What is the background for this study? What are the main findings? Dr. Saari: Growth monitoring is a fundamental part of the preventive child healthcare. It aims at early detection of growth disorders in children. Systematic...
MedicalResearch.com Interview with:
Xiao-ou Shu M.D., MPH, Ph.D
Associate Director of Global Health
Co-Leader, Cancer Epidemiology Research Program
Ingram Professor of Cancer Research
Professor of Medicine (Epidemiology)
Cancer Epidemiologist
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Shu: Nuts are rich in nutrients, such as unsaturated fatty acids, fiber, vitamins, phenolic antioxidants, arginine, and other phytochemicals. These are all known to be beneficial to cardiovascular health, probably through their anti-oxidative, anti-inflammatory, and endothelial function maintenance properties. Previous studies, primarily conducted in white and affluent populations, have shown that nut consumption may be related to cardiovascular health. Much of the nut consumption in those populations would be tree nuts. In our study, we found that peanut consumption was associated with reduced total mortality and CVD mortality in a predominantly low-income black and white population in the US, and among Chinese men and women living in Shanghai. Because peanuts are much less expensive than tree nuts, as well as more widely available to people of all races and all socioeconomic backgrounds, increasing peanut consumption may provide a potentially cost-efficient approach to improving cardiovascular health.
MedicalResearch.com Interview with:
Alexander W. Pastuszak, MD, PhD
Male Reproductive Medicine and Surgery
Scott Department of Urology
Baylor College of Medicine Houston, TX
Medical Research: What is the background for this study?
Dr. Pastuszak: The link between erectile dysfunction (ED) and cardiovascular disease (CVD) has been growing stronger in recent years, and recommendations have recently been made to screen men with ED for CVD risk factors. The arteries in the penis are much smaller than those in the heart, and if vascular disease contributes to ED, which we know it does, then ED should be detected before CVD in affected men. We also know that treating men with CVD risk factors results in improvement in their risk of having acute cardiovascular events (i.e. heart attack, stroke, etc.). Because of these relationships, we wanted to assess the economic impact of screening men with erectile dysfunction for CVD, identifying men with CVD risk factors, and treating these men on the incidence of cardiovascular events and new cases of ED. Specifically, we wanted to look at the costs associated with screening and treatment of CVD and erectile dysfunction, and the cost savings resulting from screening and treating men with CVD risk factors and ED when preventing acute cardiovascular events.
Medical Research: What are the main findings?
Dr. Pastuszak: We modeled the reduction in acute cardiovascular events and the associated cost savings over 20 years. We predicted that approximately 5.8 million men with both CVD and ED would be identified over 20 years if we screened men with ED for CVD risk factors, and the cost of this screening would be $2.7 billion. We assumed that if we treated these at-risk men, there would be an approximately 20% decrease in cardiovascular events, which would prevent 1.1 million cardiovascular events over 20 years, saving $21.3 billion that would otherwise be put to treatment of these acute events. Since ED and CVD arise from the same pathology, we predicted that in treating the CVD risk factors, a similar decrease in ED cases would be seen as well, which would save $9.7 billion that would otherwise be put to ED treatment. In screening these men, a combined $28.5 billion would be saved over 20 years.
MedicalResearch.com Interview with:
Rebecca S. Williams, MHS, PhD
University of North Carolina at Chapel Hill
Chapel Hill, NC
MedicalResearch: What is the background for this study?
Dr. Williams: In recent years, the e-cigarette industry has ballooned into a multi-billion dollar market, with at least 466 brands and 7764 unique flavors of e-cigarettes sold online. With both smokers and people who never smoked turning to e-cigarettes, there are concerns about their safety, lack of regulation and accessibility to teens. The CDC reported that 17% of high school seniors use e-cigarettes, more than twice as many as use traditional cigarettes; furthermore, that hundreds of thousands of youth annually are using e-cigarettes who never smoked cigarettes.
Our previous studies of Internet cigarette sales indicated that Internet Tobacco Vendors did a poor job of preventing sales to minors, which helped inform development of state and federal regulations to regulate such sales. In 2013, North Carolina passed a law requiring age verification for online e-cigarette sales. This study was the first study to examine age verification used by Internet e-cigarette vendors and the first to assess compliance with North Carolina’s e-cigarette age verification law.
MedicalResearch: What are the main findings?
Dr. Williams: It was very easy for minors to buy e-cigarettes online. It took little effort for them to bypass the age verification practices of the vendors because there was very little use of rigorous age verification. With only 5 orders rejected by vendors due to age verification, there was a youth e-cigarette purchase success rate of 94.7%. No vendors used age verification at delivery, and few used rigorous methods of age verification that could potentially block youth access. While 7 vendors claimed to use age verification techniques that could potentially comply with North Carolina’s law, only one actually did.
MedicalResearch.com Interview with:
Eili Y. Klein Ph.D. Assistant Professor
Department of Emergency Medicine
Johns Hopkins University
Baltimore, MD 21209
Medical Research: What is the background for this study? What are the main findings?
Dr. Klein: Antibiotic prescriptions rates vary widely across the country. We saw this at the state level, where rates in the highest prescribing states were as high as 1,200 prescriptions per 1,000 people to the lowest rates which were around 500 prescriptions per 1,000 people (see resistancemap.org). Europe has similar variation in prescribing rates across countries, and research there has documented a number of potential reasons for this such as education, access to health insurance, use of childcare centers, and cultural differences. However, the healthcare system in the US is structured differently than in Europe, so we set out to see if similar factors underlay differences in antibiotic prescribing in the US.
Understanding the drivers of differences in prescribing is important because it can help predict how future changes in demographics and socioeconomic characteristics will affect future antibiotic consumption. It also enables predictions in consumption as a result of interventions that target the healthcare delivery system, and also enables better targeting of information campaigns, such as the CDC's Get Smart Program, on appropriate antibiotic prescribing to specific sub-populations. Finally, it allows providers to better understand how their practice is driven by external factors.
The results of the study found that a primary factor driving differences in prescribing was the density of physicians. In other words, the more physicians there are per capita, the more prescriptions per capita. This result could just be due to more physicians making it easier to access a doctor and thus people go to visit a physician more. However, it could also suggest that physicians are competing to attract or retain patients in some manner and this is driving up prescriptions. To try to understand which of these effects was dominating the change, we examined the role of retail and urgent care clinics.
Stand-alone urgent care clinics and clinics incorporated into the retail arm of a store (e.g., CVS minute clinic) are truly an American-style invention, and bear little similarity to how most Europeans receive healthcare. Over the last decade these establishments have exploded in popularity and greatly expanded their reach. Surprisingly what we found was that in low-income areas, a clinic increased the prescribing rate, but didn't affect the rate that physicians were prescribing antibiotics. Thus, in these areas the story is all about access. Improving access to healthcare increases the likelihood that people will go to the doctor when they are sick and that increases the rate that people get prescribed antibiotics. This contrasted with wealthier areas, where we found that a clinic increased the rate of prescribing by physicians, which is likely due to competition. This competition can take multiple forms, from increasing the probability of getting an antibiotic as a physician is worried you won't come back otherwise, to changes in how physician offices work so that it is easier to walk-in to your doctor or get a same-day appointment. Though we were not able to quantify which of these effects was dominant in this research.
MedicalResearch.com Interview with:
Saskia Haitjema MD PhD candidate
Division Heart and Lung, Laboratory of Experimental Cardiology
University Medical Center Utrecht
Medical Research: What is the background for this study? What are the main findings?
Response: Although cardiovascular diseases are often considered a disease of men, more women than men die each year of cardiovascular diseases. Sex-differences are increasingly being researched and acknowledged. For treatment and prognosis of coronary artery disease, however, many discrepancies exist between studies that investigated sex-differences. For example, it remains unclear whether the observed differences in the outcome after coronary artery bypass grafting (CABG) are due to a different risk burden between men and women or whether female sex is an independent risk factor.
In a group of 2553 patients followed up during a median of 2.5 years after CABG we found an increased risk for worse outcome in women versus men. We found a strong indication for female sex as an independent risk factor, but lacked power to definitively prove th
MedicalResearch.com Interview with:
Ann M. Sheehy, M.D., M.S.
Associate Professor
Division Head, Hospital Medicine
University of Wisconsin Department of Medicine
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Sheehy: Outpatient (observation) and inpatient status determinations are important for hospitalized Medicare beneficiaries. The Recovery Audit program, more commonly known as the RACs (Recovery Audit Contractors), is charged with surveillance and enforcement of such status determinations. Surveillance in the Medicare program is necessary, and Medicare fraud and abuse should not be tolerated. However, there are increasing concerns regarding RAC accuracy, auditor financial incentives, and the volume of audits and overpayment determinations auditors allege. We therefore studied Complex Medicare Part A RAC audits at 3 academic medical centers, the University of Wisconsin, the University of Utah, and Johns Hopkins, to determine the impact and trends of such audits.
There was a nearly 300% increase in RAC overpayment determinations in just 2 years at the study hospitals. Each year, the hospitals won a greater percent of contested cases, winning 68.0% of cases with decisions in 2013. Two-thirds of all favorable decisions for the hospitals occurred in the discussion period. Because discussion is not considered part of the formal appeals process, this is omitted from reports of RAC accuracy. None of the overpayment determinations contested the need for the care delivered, rather contested the billing location, outpatient or inpatient. The hospitals averaged 5 FTE each to manage the audit and appeals process. Claims still in appeals had been in process for a mean of 555 days without decisions.