MedicalResearch.com Interview with: Dennis Tsilimingras, M.D., M.P.H. Assistant Professor, Co-Director of Michigan AHEC (Area Health Education Center), Director of Patient Safety, Department of Family Medicine and Public Health Sciences Wayne State University School of Medicine Detroit, Michigan Medical Research: What is the background for this study? Dr. Tsilimingras: There has been little research to examine post-discharge adverse events (AEs)...
MedicalResearch.com Interview with:
Jacqueline Hirth, PhD, MPH
Assistant Professor and
Dr. Abbey B. Berenson MD, MMS, PhD
Center for Interdisciplinary Research in Women's Health
Obstetrics and Gynecology
The University of Texas Medical Branch at Galveston Texas
MedicalResearch.com Interview with:
Lisa M. Nyberg, MD, MPH
Transplant Hepatologist
Director, Hepatology Research
Kaiser Permanente, Garfield Specialty Center
San Diego, CA 92111
Medical Research: What is the background for this study? What are the main findings?
Dr. Nyberg: The overall cancer rates were higher in patients with Hepatitis C (HCV) vs those without HCV. Of note, though, the HCV cohort had higher rates of alcohol abuse, tobacco use, cirrhosis and diabetes mellitus (DM). However, even after stratification for the variables alcohol abuse, tobacco use, body mass index (BMI) and DM; the increased cancer rates remained significant for total cancer sites, liver cancer and NHL.
Note that this study does not establish a cause and effect relationship between Hepatitis C and cancer. A strength of this study is that it is an evaluation of a large patient population (n=35,712 with HCV and 5,297,191 without HCV). Limitations of the study are those inherent in epidemiological studies using large databases. For example, confounders may not be accurately recorded in automated databases (smoking and alcohol abuse may be under-recorded).
MedicalResearch.com Interview with:
Esther Lopez-Garcia, PhD
Dept. Preventive Medicine and Public Health
School of Medicine
Universidad Autónoma de Madrid
Madrid,Spain
Medical Research: What is the background for this study? What are the main findings?
Dr. Lopez-Garcia: Health-related quality of life (HRQL) is a global indicator of perceived health status, which includes physical and mental domains. Assessing the association between individual foods and HRQL is important because both the food industry and the population as a whole are interested in knowing whether general well-being could be improved by consuming specific foods. Several biological mechanisms might support an association between consumption of yogurt and better Health-related quality of life. However, to our knowledge, the effect of yogurt on HRQL has not yet been studied in epidemiological investigations in the general population. Thus, the objective of this article was to examine the prospective association between habitual yogurt consumption and the physical and mental components of HRQL among the general adult population.
In this study, we found no association between yogurt consumption and the physical and mental components of HRQL after 3.5 years of follow-up of a population-based cohort. The results also held for whole-milk and reduced-fat yogurt.
MedicalResearch.com Interview with:
Nasim Mavaddat M.B.B.S. MPhil PhD PhD
Centre for Cancer Genetic Epidemiology
Department of Public Health and Primary Care
University of Cambridge, Cambridge, UK
MedicalResearch: What is the background for this study?
What are the main findings?
Dr. Mavaddat: Recent large-scale genome wide association analyses have led to the discovery of genetic variation- called single nucleotide polymorphisms (SNPs) associated with breast cancer risk. Individually these variants confer risks that are too small to be useful for risk prediction. But when combined as a single score, called a polygenic risk score (PRS), this score may be used to stratify women according to their risk of developing breast cancer. This stratification could guide strategies for screening and prevention.
Our study was a large international collaboration involving 41 research groups from many different countries and included 33,673 breast cancer patients and 33,381 controls. We found that the genetic variants act more or less independently, and that the more risk variants a woman has the higher her risk of breast cancer. When women were ranked according to their PRS, women with scores in the top 1% had a threefold increased risk of breast cancer. This translates into an absolute risk of breast cancer of 29% by age 80. By contrast, women with the lowest 1% scores had a risk of 3.5%.
The PRS was effective in stratifying women with and without a family history of breast cancer, so that highest risk was for women with a family history and a high PRS. Finally, we showed that the PRS was better at predicting the risk of ER-positive breast cancer (potentially relevant to the application of risk stratification to chemoprevention for example, with tamoxifen, raloxifene or aromatase inhibitors).
There has been much debate as to whether genomic profiles are useful for individual risk prediction, especially in the context of the preventative strategies available at the present time. The estimates provided in this study will help inform these debates.
MedicalResearch.com Interview with:
Henry J. Michtalik MD, MPH, MHS
Department of Medicine, Johns Hopkins University
Armstrong Institute for Patient Safety and Quality
Baltimore, Maryland
Medical Research: What is the background for this study? What are the main findings?
Dr. Michtalik: Current healthcare reform emphasizes providing high-value, evidence-based care. Compliance with practice guidelines and best-practices remains a challenge in the ever-changing healthcare environment. Multiple methods are typically used to enhance compliance with these guidelines, including physician education, computerized order entry systems with clinical decision support, provider feedback, and payment incentives. These strategies are used for many conditions, including heart failure and venous thromboembolism (VTE), blood clots.
The purpose of this study was to examine the impact of an individualized physician dashboard and pay-for-performance program on improving VTE prophylaxis rates amongst hospitalists. We performed a retrospective analysis of over 3000 inpatient admissions to a hospitalist service. We examined the impact of a web-based hospitalist dashboard which provided VTE prophylaxis feedback, both alone and in combination with a pay-for performance program which provided a small financial payment for achieving compliance rates greater than 80%.
We found that compliance significantly increased from 86% during baseline to 90% during the dashboard alone phase. Addition of the pay-for-performance program further increased compliance to 94%. The fastest improvement occurred during the dashboard only phase. Annual physician payments ranged from $53 to $1244, with 17 of the 19 payments under $1000.
MedicalResearch.com Interview with:
Stefan Zeuzem, MD
Professor of Medicine
Chief Department of Medicine
Goethe University Hospital
Frankfurt
Medical Research: What is the background for this study? What are the main findings?
Dr. Zeuzem: Interferon- and ribavirin-free regimens are needed to treat HCV infection. The objective of the study was to evaluate the safety and efficacy of grazoprevir (NS3/4A-protease-inhibitor) and elbasvir (NS5A-inhibitor) in previously untreated patients with chronic hepatitis C (without and with liver cirrhosis). Among 421 participants, 194 (46%) were women, 157 (37%) were non-white, 382 (91%) had genotype-1 infection, and 92 (22%) had cirrhosis. Of 316 patients receiving immediate treatment, 299/316 achieved SVR12 (undetectable HCV 12 weeks after treatment), including 144/157 with genotype-1a, 129/131 with genotype-1b, 18/18 with genotype-4, 8/10 with genotype-6, 68/70 with cirrhosis, and 231/246 without cirrhosis. Virologic failure occurred in 13 patients including 1 breakthrough and 12 relapses, and was associated with baseline NS5A-polymorphisms and emergent NS3- and/or NS5A-variants. Serious adverse events occurred in 9 (2.8%) and 3 (2.9%) patients in the active and placebo arms, respectively; none were considered drug-related.
MedicalResearch.com Interview with:
Mary J Hamel, M.D.
Chief, Strategic and Applied Sciences Unit,
And Deputy Branch Chief for Science, CDC Malaria Branch
US Centers for Disease Control and Prevention
1600 Clifton Rd, NE, MS A06
Atlanta GA 30333
Dr. Hamel was principal investigator at the Siaya site in western Kenya.
Medical Research: What is the background for this study? What are the main findings?
Dr. Hamel: Major progress has been made in malaria control during the past decade with the scale up of proven interventions including insecticide treated nets (ITNs), indoor residual spraying, effective diagnosis and treatment for malaria, and intermittent preventive treatment of malaria in pregnancy. Nonetheless, malaria remains a major cause of morbidity and mortality, and a leading cause of pediatric death worldwide. An estimated 198 million cases of malaria and 580,000 deaths occurred in 2013 – most of these in African children.
Now we face additional challenges in malaria control – the emergence of insecticide and drug resistance threatens some of our most effective interventions. New tools are needed to reach the goal of malaria elimination and eventual eradication. Vaccines are some of our most cost-effective interventions, and an effective malaria vaccine would be an important addition to our current malaria control tools.
This week, the RTS,S Clinical Trials Partnership published the final vaccine efficacy and safety results from the RTS,S/AS01 malaria vaccine phase 3 trial in the Lancet (Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial, http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)60721-8/abstract). This large randomized controlled double-blind phase 3 clinical trial was conducted in 11 sites in 7 African countries across a range of malaria transmission levels. In all, 15,460 children and young infants were enrolled in two age-categories, those first vaccinated at 5-17 months of age (referred to as children), and those first vaccinated at 6-12 weeks of age (referred to as young infants) who received the RTS,S/AS01 vaccine along with their routine childhood immunizations. Participants were randomized into 3 groups – the first group received three doses of the RTS,S/AS01 vaccine followed 18 months later by a booster dose; the second group received three doses of the RTS,S/AS01 vaccine without a booster; and the third group received a comparator vaccine. All participants received an ITN. Children were followed for an average of 48 months and infants for an average of 38 months.
We found that vaccine efficacy was modest. Vaccine efficacy against clinical malaria in children was 36% with a booster and 28% without, and vaccine efficacy against severe malaria was 32% with a booster and non-significant without. Efficacy results in young infants were lower than those in children– vaccine efficacy against clinical malaria was 36% with a booster and 28% without, and vaccine efficacy against severe malaria was non-significant.
However, impact, defined as the number of cases averted per 1000 participants vaccinated, was substantial in both age-categories, and highest where malaria burden was greatest. In children who received the booster, during 4 years follow-up, 1700 cases of clinical malaria were averted per 1000 children vaccinated. In young infants, during 3 years follow-up, nearly 1000 cases were averted per 1000 young infants vaccinated.
The safety findings were comparable overall in the different study arms, but two safety findings are notable. Meningitis occurred more frequently among children (but not young infants) who received RTS,S/AS01 than among those who received the comparator vaccines. There was no relationship between when the vaccine was administered and when meningitis occurred, most cases occurred in only two study sites, and the finding may be due to chance. If RTS,S/AS01 is licensed, post-licensing studies will be done to establish the significance of this finding. Both children and young infants experienced more episodes of fever and associated febrile convulsions during the 7 days following vaccination; convulsions occurred in 2.2 - 2.5/1000 vaccine doses.
MedicalResearch.com Interview with
Jay Giri, MD MPH
Director, Peripheral Intervention
Assistant Professor of Clinical Medicine
University of Pennsylvania
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Giri: Carotid artery stents are placed by vascular surgeons or interventional cardiologists to decrease the risk of long-term stroke in patients with severe atherosclerotic disease of the carotid artery. When these procedures are performed, there is a risk of releasing small amounts of debris into the brain’s circulation, causing a stroke around the time of the procedure (peri-procedural stroke). In order to mitigate this issue, embolic protection devices (EPD) have been developed to decrease the chances of small debris reaching the brain.
Two types of EPD exist. The first is a small filter meant to catch the debris released by placement of the carotid stent (distal filter EPD).
The second is a more complex device type that leads to transient halting of blood flow to the brain in the carotid artery being stented (proximal EPD). Debris-containing blood is removed from the body prior to allowing normal blood flow to proceed back to the brain after stent placement.
Our prior research has shown that nearly all (>95%) of domestic carotid stenting procedures are performed with utilization of one of these devices. We sought to compare important clinical outcomes of stroke and death between these 2 device types within a large national sample of patients undergoing carotid stenting.
Some small prior studies have investigated whether the total amount of debris reaching the brain is less with proximal embolic protection devices. These studies have shown mixed results. However, no prior study has investigated important clinical outcomes of stroke and death in relation to these devices.
We found that overall uptake of proximal embolic protection devices utilization in America has not been robust. Less than 7% of all domestic CAS procedures are performed with this technology. Our analysis showed that in-hospital and 30-day stroke/death rates with proximal EPD and distal filter EPD were similar (1.6% vs. 2.0%, p = 0.56 and 2.7% vs. 4.0%, p = 0.22, respectively).
MedicalResearch.com Interview with:
Ojan Assadian, M.D., DTMH
Professor for Skin Integrity and Infection Prevention
Institute for Skin Integrity and Infection Prevention
School of Human & Health Sciences
University of Huddersfield
Queensgate, Huddersfield UK
MedicalResearch: What is the background for this study? What are the main findings?
Prof. Assadian: Although medical gloves serve as an important mechanical barrier to prevent healthcare workers’ hands from getting contaminated with potentially pathogenic microorganisms, their inappropriate and incorrect use may support microbial transmission, eventually resulting in indirect horizontal cross-contamination of other patients.
We conducted a clinical study designed to determine the efficacy of a newly developed synthetic antibacterial nitrile medical glove coated with an antiseptic, polyhexamethylen-biguanid hydrochloride (PHMB), on its external surface, and compared this antibacterial glove to an identical non-antibacterial glove in reducing surface contamination after common patient care measures in an intensive care unit.
We found significantly lower numbers of bacteria on surfaces after performing typical clinical activities such as intravenous fluid handling, oral toilet, or physiotherapy, if touched with antibacterial gloves.
Neel S. Madhukar[/caption]
MedicalResearch.com Interview with:
Neel S. Madhukar
Graduate student in the lab of
Olivier Elemento, PhD, Associate Professor
Head, Laboratory of Cancer Systems Biology
Department of Physiology and Biophysics
Institute for Computational Biomedicine
Weill Cornell Medical College
Medical Research: What is the background for this study? What are the main findings?
Response: It takes on average 2.6 billion dollars and 10-15 years to develop a single new drug. Despite massive investment in drug discovery by pharmaceutical companies, the number of drugs obtaining FDA approval each year has remained constant over the past decade. One of biggest bottlenecks in the process of developing a new drug is to understand precisely how a drug works, that is, what it binds to in cells, how it binds, and what it does when it is bound. This process is collectively called target identification and characterization of mechanisms of action. At present, target identification is a slow and failure-prone process, driven by laborious experimentation. Every time we seek to develop a new drug, such laborious experimentation needs to be redone from scratch. We are not learning from data acquired from our past successes and failures.
MedicalResearch.com Interview with:
Dr. Robert J. Mentz MD
Assistant Professor of Medicine
Director, Duke University Cooperative Cardiovascular Society
Advanced Heart Failure and Cardiac Transplantation
Duke University Medical Center
Duke Clinical Research Institute
Medical Research: What is the background for this study? What are the main findings?
Dr. Mentz: Previous studies have shown that depression is associated with worse outcomes in heart failure patients; however, most of these prior studies were conducted in primarily white patient populations. The impact of depressive symptoms on outcomes specifically in blacks with heart failure has not been well studied. We used data from the HF-ACTION trial of exercise training in heart failure patients, which collected data on depressive symptoms via the Beck Depression Inventory (BDI-II), to assess the association between depressive symptoms and outcomes in black patients as compared with white patients. We found that in blacks with heart failure, baseline symptoms of depression and worsening of symptoms over time were both associated with increased all-cause mortality/hospitalization.
MedicalResearch.com Interview with:
Pedram Gerami, M.D.
Associate Professor of Dermatology
Director, Melanoma Research
Northwestern Skin Cancer Institute
Northwestern University
MedicalResearch: What is the basis and background for performing this study?
Dr. Gerami: Most of the existing literature shows that Sentinel Lymph Node Biopsy (SLNB) will identify 25 to 35 percent of patients who will ultimately die of metastatic melanoma. Hence while SLNB is reported to be the strongest predictor of outcome for melanoma, the vast majority of patients who ultimately die of metastatic melanoma have a negative Sentinel Lymph Node Biopsy result. Hence in this study we aimed to determine whether a GEP assay developed by Castle bioscience could be used independently or in conjunction with SLNB to better detect those patients who are at high risk for developing metastatic disease and dying from melanoma.
MedicalResearch: What are the findings of the study?
Dr. Gerami: Our study, which examined the use of a Gene Expression Profile (GEP) assay developed by Castle Biosciences and Sentinel Lymph Node Biopsy alone and in combination in a multi-center cohort of 217 patients, demonstrated that the use of the GEP identified more than 80 percent of patients who develop melanoma
Combining the two methods showed that patients predicted to be high risk based on the GEP test alone had similar rates of disease progression whether they were SLNB positive or negative. Patients who were SLNB negative and predicted to be low risk using the GEP test had lower rates of disease progression than the SLNB negative group as a whole.
MedicalResearch.com Interview with: Dr. Raj Kapoor National Hospital for Neurology and Neurosurgery University College London Hospitals NHS Foundation Trust Medical Research: What is the background for this study? Dr. Kapoor: Current treatments for Multiple Sclerosis do not prevent disability which accumulates from relapses, or which progresses between relapses. Experimental work suggests that the neurodegeneration which...
MedicalResearch.com Interview with:
Daniel C. Beachler, PhD Postdoctoral fellow
Infections and Immunoepidemiology Branch of the
National Cancer Institute (NCI)
Medical Research: What is the background for this study? What are the main findings?
Dr. Beachler: HPV is a common sexually transmitted infection. Individuals can acquire HPV infections in the epithelium of their cervical, anal and oral sites, and occasionally these infections lead to cancer. There are three prophylactic HPV vaccines on the market that can protect against HPV at these sites among those not been previously exposed to HPV.
This study examined the effect of HPV vaccination of 18-25 year old women at all three anatomic sites. The combined multi-site HPV vaccine efficacy has not been reported previously. It was unknown whether the vaccine may protect non-infected sites against HPV infection or re-infection in women exposed to HPV prior to vaccination.
We observed that the HPV vaccine provides the strongest protection at all three sites among women unexposed to HPV before vaccination. Additionally, we observed some protection at the non-infected sites in women who were previously infected with HPV.
MedicalResearch.com Interview with:
Guijing Wang, PhD
Senior health economist
Division for Heart Disease and Stroke Prevention
Centers for Disease Control and Prevention
Medical Research: What is the background for this study? What are the main findings?
Dr. Wang: Our study is one of the first to analyze the impact of hospital costs related to atrial fibrillation (or AFib) in a younger stroke population. To determine these findings, we examined more than 40,000 hospital admissions information involving adults between the ages of 18 and 64 with a primary diagnosis of ischemic stroke between 2010 and 2012.
Although AFib is more common among those ages 65 and older, with strokes among younger adults on the rise in the U.S., we wanted to take a comprehensive look at AFib’s impact on hospital costs for these patients. AFib is associated with a 4- to 5-fold increased risk of ischemic stroke, which is the most common type of stroke.
Overall, our research found that AFib substantially increased hospital costs for patients with ischemic stroke – and that was consistent across different age groups and genders of those aged 18-64. Of the 33,500 first-time stroke admissions, more than seven percent had AFib, and these admissions cost nearly $5,000 more than those without the condition. In addition, we found that both the costs of hospitalization, as well as the costs associated with AFib, were higher among younger adults (18-54) than those aged 55 to 64.
MedicalResearch.com Interview with:
Elissa Hope Wilker, Sc.D.
Beth Israel Deaconess Medical Center
Cardiovascular Epidemiology Research
Harvard Medical School
Medical Research: What is the background for this study? What are the main findings?
Dr. Wilke: Long-term exposure to ambient air pollution is associated with cerebrovascular disease and cognitive impairment, but the impact on structural changes in the brain is not well understood. We studied older adults living in the greater Boston area and throughout New England and New York and we looked at the air pollution levels and how far they lived from major roads. We then linked this information to findings from MRI studies of structural brain images. Although air pollution levels in this area are fairly low compared to levels observed in other parts of the world, we found that people who lived in areas with higher levels of air pollution had smaller brain volumes, and higher risk of silent strokes. The magnitude of association that we observed for a 2 µg/m3 increase in fine particulate matter (PM2.5) (a range commonly observed across urban areas) was approximately equivalent to one year of brain aging. The association with silent strokes is of concern, because these are associated with increased risk of overt strokes, walking problems, and depression.
MedicalResearch.com Interview with:
Timothy Yap, MD, PhD, NIHR BRC
The Institute of Cancer Research and
The Royal Marsden NHS Foundation Trust
London, United Kingdom.
Medical Research: What is the background for this study? What are the main findings?
Dr. Yap: This is a novel phase I trial assessing for the first time if the PARP inhibitor olaparib can be combined with the AKT inhibitor AZD5363. The study was undertaken at the Royal Marsden and The Institute of Cancer Research in London, England. This targeted combination was based on strong preclinical rationale demonstrating synergy between both drugs in BRCA positive tumors and also antitumor activity in non-BRCA positive tumors. Although olaparib was recently approved by the FDA for treating advanced ovarian cancer associated with defective BRCA genes, antitumor efficacy in different non-BRCA tumors is yet to be established.
The key finding for this study was that it was indeed possible to combine both drugs safely, with multiple patients with different cancers responding, including patients with and without BRCA1/2 mutations. We also assessed a new intrapatient dose escalation phase I trial design in this study, and demonstrated that the novel design could be successfully implemented, with completion of the dose escalation phase in 2 schedules of the combination with just 20 patients in 7.5 months.
MedicalResearch.com Interview with:
Dr. Larry Chinitz MD
Professor of Medicine and Director, Cardiac Electrophysiology
NYU Langone Medical Center
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Chinitz: The treatment algorithms proposed currently for maintenance of sinus rhythm in patients with atrial fibrillation focus on use of anti-arrhythmic drugs and catheter ablation. Data available to evaluate the effect of modification of known adverse clinical factors on atrial fibrillation recurrence is scant.
Obstructive sleep apnea in a known factor associated with both new onset atrial fibrillation as well as its recurrence after catheter ablation. Through a meta-analysis of available data we found that use of continuous positive airway pressure in patients with sleep apnea was associated with a 42% relative risk reduction in recurrence of atrial fibrillation. This effect was similar across patient groups irrespective of whether they were medically managed or with catheter ablation.
MedicalResearch.com Interview with:
Melissa Wilson, MD, PhD
Assisstant Professor
Perlmutter Cancer Center
NYU Langone Medical Center
New York, NY
Medical Research: What is the background for this study? What are the main findings?
Dr. Wilson: Metastatic cutaneous melanoma is an extremely aggressive form of skin cancer. Traditionally, it has been characterized by clinicopathologic characteristics. More recently, melanoma tumors have also been stratified by common somatic mutations for which targeted therapies have been developed or are under investigation, including BRAF, NRAS and KIT. In addition to somatic mutations, aberrant intracellular signaling pathways and cell cycle disruption contribute to melanoma pathogenesis. Indeed, recent next generation sequencing studies have identified a number of new genes involved in melanomagenesis. A comprehensive evaluation and understanding of concurrent and mutually exclusive mutations in tumors has been lacking. Therefore, we developed a comprehensive custom targeted capture of 108 genes previously implicated in melanoma pathogenesis. We used the targeted panel to perform massively parallel sequencing on 94 well-established human melanoma cell lines, 67 patient-derived xenografts (PDX), and 5 cell lines made from PDX, all untreated.
Samples were clustered based on deleterious mutations. Eighty-three percent of samples had deleterious mutations in the MAPK signaling pathway (including BRAF, RAS) and NF1. Ten percent of samples had PI3K pathway mutations which were predominantly associated with BRAF mutations. TP53 was found to be mutated in 24% of the samples and were also associated with mutations in the MAPK pathway. Mutations in chromatin remodeling genes were mutually exclusive with each other, but were associated with BRAF and NRAS mutations. Of particular interest, five of the 10 NF1mutated samples harbored likely deleterious mutations in MAP3K5 or MAP3K9, suggesting the potential involvement of JNK signal transduction pathway in a cohort of samples.
MedicalResearch.com Interview with: Olivier Elemento, PhD Associate Professor Head, Laboratory of Cancer Systems Biology Department of Physiology and Biophysics Institute for Computational Biomedicine Weill Cornell Medical College New York, NY, 10021 Medical Research: What is the background for this study? What are the main findings? Dr. Elemento: In many cancer patients, initial treatment with chemotherapy or targeted therapy...
MedicalResearch.com Interview with:
Dr Mayris P Webber Dr.PH. MPH
Bureau of Health Services Fire Department of the City of New York Brooklyn, NY
Professor of Clinical Epidemiology & Population Health
Montefiore Medical Center NY
Medical Research: What is the background for this study? What are the main findings?
Dr. Webber: