Dr. Joseph A. Ladapo[/caption]
Joseph A. Ladapo, MD, PhD
David Geffen School of Medicine at UCLA
Department of Medicine, Division of General Internal Medicine and Health Services Research
Los Angeles, California
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Four million stable patients in the US undergo testing for suspected ischemic heart disease (IHD) annually. There is substantial variation in how these patients are managed by physicians, and both clinical and economic factors have been used to explain this variation. However, it is unknown whether patients’ beliefs and preferences influence management decisions, and we aimed to answer this question. Based on interviews of 351 stable patients at Geisinger Health System newly referred for cardiac stress testing/coronary computed tomographic angiography (CTA) for suspected IHD, we found that patients with an accurate understanding of their initial test result were less likely to undergo follow-up tests/procedures if the initial test was negative and more likely to undergo follow-up tests/procedures if the initial test was positive.
Dr. Dong Chang[/caption]
Dr. Dong W. Chang, MD MS
Division of Respiratory and Critical Care Physiology and Medicine
Los Angeles Biomed Research Institute at Harbor-University of California
Los Angeles, Medical Center
Torrance California
MedicalResearch.com: What is the background for this study?
Response: The study was based on our overall impression that ICU care is often delivered to patients who are unlikely to derive long-term benefit (based on their co-morbidities/severity of illness, etc.). However, what surprised us was the magnitude of this problem. Our study found more than half the patients in ICU at a major metropolitan acute-care hospital could have been cared for in less expensive and invasive settings.
Dr. James Moon[/caption]
James Moon, PhD
John Gideon Searle Assistant Professor
University of Michigan
Dept. of Pharmaceutical Sciences and Biomedical Engineering
Biointerfaces Institute
Ann Arbor, MI, 48109
MedicalResearch.com: What is the background for this study?
Response: The field of cancer immunotherapy has recently made a breakthrough with the clinical success of immune checkpoint inhibitors, which work by removing the brakes on immunosuppressed T-cells. However, these approaches generally work by augmenting pre-existing T-cell immunity and benefit only a subset of patients. In addition, because the majority of somatic mutations in cancer cells are unique to each patient, cancer immunotherapy may benefit from a personalized approach.
Prof Richard Quek[/caption]
Dr. Richard Quek MBBS, MRCP, FAMS
Senior Consultant, Medical Oncology
Parkway Cancer Centre
Singapore
MedicalResearch.com: What is the background for this study?
Response: Angiosarcoma is an uncommon form of aggressive soft tissue sarcoma (STS). It comprises of 2 distinct subgroups of patients: one originating from the skin - typically scalp, seen predominantly in elderly patients while the second subgroup affects younger patients and tends to originate from visceral organs including the liver and breasts. Angiosarcoma may also develop as a complication of prior radiation treatment. Prognosis in patient is poor, with survival generally less than 1 year in those with advanced or unresectable disease. Optimal treatment remains unclear; most published series on angiosarcoma tends to be small singlecenter studies.
In our previous Asian STAR study evaluating epidemiology, treatment patterns and outcomes in Asian patients diagnosed with STS [J Clin Oncol 33, 2015 (suppl; abstract 10549)], we found that angiosarcoma represented 7% of the cohort, a proportion higher than what we would have expected from published series coming out of the west and hence our interest in this subject.
Dr. Connie J. Mulligan[/caption]
Connie J. Mulligan, PhD
Professor, Department of Anthropology
University of Florida
Gainesville, FL
MedicalResearch.com: What is the background for this study?
Response: Lance Gravlee (UF Dept of Anthropology, UF Genetics Institute) started this research over 10 years ago. As a cultural anthropologist, Lance uses ethnographic (open-ended questions) interviews and discovered that over half of the participants in our study talked about experiences of discrimination that happened to people close to them.
As a geneticist (UF Dept of Anthropology, UF Genetics Institute), I came into the project because I was interested in seeing how genetics and sociocultural stressors, like discrimination, interact. In our project, we look at blood pressure because hypertension is a disease that shows racial disparities and also because it is a complex disease that is caused by both genetic and environmental factors (like discrimination).
Dr. Michael Murray[/caption]
Michael F. Murray MD
Geisinger Health System
Danville, PA 17822
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The DiscovEHR cohort was formed as a result of a research collaboration between Geisinger Health System and Regeneron Pharmaceuticals. There are over 50,000 patient participants in the cohort who have volunteered to have their de-identified genomic sequence data linked to their de-identified EHR data for research purposes. We report in this paper findings around the identification of 229 individuals (1:256) with pathogenic or likely pathogenic variants in one of the three genes (LDLR, APOB, PCSK9) associated with Familial Hypercholesterolemia (FH). The study found that these individuals are unlikely to carry a diagnosis of FH and are at risk for early coronary artery disease.
Dr. Kai Wang[/caption]
Dr. Kai Wang
Zilkha Neurogenetic Institute, University of Southern California
Institute for Genomic Medicine, Columbia University
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Cancer is a genetic disease caused by a small number of “driver mutations” in the cancer genome that drive disease initiation and progression. To understand such mechanism, there are increasing community efforts in interrogating cancer genomes, transcriptomes and proteomes by high-throughput technologies, generating huge amounts of data. For example, The Cancer Genome Atlas (TCGA) project has already made public 2.5 petabytes of data describing tumor and normal tissues from more than 11,000 patients. We were interested in using such publicly available genomics data to predict cancer driver genes/variants for individual patients, and design an "electronic brain” called iCAGES that learns from such information to provide personalized cancer diagnosis and treatment.
iCAGES is composed of three consecutive layers, to infer driver variants, driver genes and drug treatment, respectively. Unlike most other existing tools that infer driver genes from a cohort of patients with similar cancer, iCAGES attempts to predict drivers for individual patient based on his/her genomic profile.
What we have found is that iCAGES outperforms other tools in identifying driver variants and driver genes for individual patients. More importantly, a retrospective analysis on TCGA data shows that iCAGES predicts whether patients respond to drug treatment and predicts long-term survival. For example, we analyzed two groups of patients and found that using iCAGES recommend drugs can increase patients’ survival probability by 66%. These results suggest that whole-genome information, together with transcriptome and proteome information, may benefit patients in getting optimal and precise treatment.
Dr. Joyce O'Shaughnessy[/caption]
Joyce O'Shaughnessy, MD
Co-Chair, Breast Cancer Research
Texas Oncology-Baylor Charles A. Sammons Cancer Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The MONALEESA-2 trial is a Phase III, randomized, double-blind, international study of LEE011 in combination with letrozole vs. letrozole alone, in postmenopausal women with HR+/HER2- advanced breast cancer who had received no prior systemic therapy for advanced disease.
Because de novo disease has not been previously treated with systemic treatment for early-stage breast cancer, tumors may exhibit a different disease biology, which could result in varied responses compared to patients who experience recurrence of their initial breast cancer. We analyzed a pre-defined subgroup of women with de novo HR+/HER2- advanced breast cancer to better understand the response of LEE011 plus letrozole in this patient population.
In the de novo advanced breast cancer patient sub-group, progression free survival was significantly prolonged; LEE011 plus letrozole reduced the risk of disease progression or death by 55% over letrozole alone (HR=0.448 [95% CI: 0.267–0.750]). The 12-month PFS rate was 82% in the LEE011 plus letrozole arm compared to 66% with letrozole alone.
Most adverse events were mild to moderate in severity, identified early through routine monitoring, and generally managed through dose interruption and reduction. The most common all-grade adverse events (≥30% of patients with de novo advanced breast cancer) in the LEE011 plus letrozole arm were neutropenia (70.2%), nausea (48.2%), fatigue (42.1%), alopecia (39.5%), and leukopenia (31.6%).
Dr. Herbert Loong[/caption]
Herbert H F Loong
MBBS(HK), PDipMDPath(HK), MRCP(UK), FHKCP, FHKAM(Medicine)
Specialist in Medical Oncology
Clinical Assistant Professor, Department of Clinical Oncology
Deputy Medical Director, Phase 1 Clinical Trials Centre
The Chinese University of Hong Kong
Prince of Wales Hospital
Hong Kong SAR
MedicalResearch.com: What is the background for this study?
Response: Advanced melanoma have previously been known to be a disease with a dismal prognosis. Over the last few years, clinical trials data and real-world clinical experience of checkpoint inhibitors have significantly changed the treatment landscape for advanced melanoma patients. This was first demonstrated with the Anti-CTLA4 Ab Ipilimumab, and more recently with the Anti-PD1 Ab pembrolizumab. Whilst we have seen dramatic improvements in disease control with the use of these agents, the high costs of these drugs may be prohibitive to the average patient who has to pay out-of-pocket and potentially may place significant burdens on healthcare systems. There is a need to rationally assess the cost-effectiveness of these new agents, specifically addressing the potential benefits to the individual patient and to society, whilst balancing the costs that such a treatment may entail.
The assessment of cost-effectiveness of a particular treatment is extremely important in Hong Kong, as this has direct implications on drug reimbursement and accessibility of the particular drug in question at public hospitals in Hong Kong. The aim of the study is to assess the cost-effectiveness of pembrolizumab in patients with advanced melanoma used in the first-line setting in Hong Kong, and comparing it to (1) ipilimumab and (2) cytotoxic chemotherapy. Cytotoxic chemotherapy chosen for comparison were drugs commonly used in the first line setting in Hong Kong, which included dacarbazine, temozolomide and carboplatin+paclitaxel combination. It is important to note that whilst ipilimumab is registered for this indication in Hong Kong, there is no reimbursement of this drug by the Hospital Authority in Hong Kong and patients have to pay out-of-pocket. The cost of ipilimumab and the associated side effects has been prohibitive to most advanced melanoma patients in the public setting.
Dr. Sandra Costa Fuchs[/caption]
MedicalResearch.com: What is the background for this study?
Response: High blood pressure is the worldwide leading cause of cardiovascular disease. It has been estimated that more than 50%, maybe as much as 70%, of cardiovascular diseases are due to hypertension. Approximately 30% among the Brazilian adult population has hypertension and can reach 70% of individuals over 60 years of age.
Prehypertension (systolic BP 120–139 or diastolic BP 80–89 mm Hg) conveys three potentially deleterious consequences.
Dr. Ann Kurth[/caption]
MedicalResearch.com: What is the background for this study? What are the main findings?
Genital herpes is a sexually transmitted infection that is caused by one of two subtypes of the herpes simplex virus (HSV-1 and HSV-2). The condition is common in the United States, as the CDC estimates that almost one in six people between the ages of 14 and 49 are afflicted.
Unfortunately, there are no good screening tests for herpes and it cannot be cured. After a systematic review of the evidence, the U.S. Preventive Services Task Force determined that, for adolescents and adults who have no signs or symptoms, including pregnant women, the harms of screening for genital herpes outweigh the benefits. These harms include high rates of false-positive screening tests, potential concerns around unnecessary antiviral medication use, and anxiety and relationship issues related to diagnosis. Additionally, the benefits of screening proved small, in part because early identification and treatment do not alter the course of the condition.
In the end, due to the lack of benefits in the face of serious harms, the Task Force recommended against routine serologic screening for genital herpes simplex virus (HSV) infection.
Dr. Jerry Wolinsky,[/caption]
Jerry S. Wolinsky, MD
Emeritus Professor in Neurology
McGovern Medical School
The University of Texas Health Science Center at Houston
Houston’s Health University
Department of Neurology
Houston, Texas 77030
MedicalResearch.com: What is the background for this study?
Response: Multiple sclerosis (MS) clinically is a very heterogeneous disease. It presents in considerably different ways and has a very poorly predictable clinical course. In an attempt to better communicate between experts in the field, there have been multiple attempts to categorize “typical” courses of the disease. How we think about the disease is in part driven by these somewhat artificial categories that lump our patients into those with relapsing forms of the disease (relapsing remitting with or without accumulating clinical disability, and secondary progressive with accumulating disability eventually occurring even in the absence of apparent clinical episodes of the disease), and primary progressive MS, where patients are slowly or sometimes rather rapidly accumulating disability in the absence of prior clinical relapses.
However, the distinctions between multiple sclerosis patients are not always as clear as the definitions would suggest, and it is certain that patients with primary progressive multiple sclerosis sometimes have clinical relapses after years of never having had relapses, and show MRI evidence of having accumulated many lesions in the brain over the course of their disease. Until now, none of the drugs that have shown benefit for relapsing disease have been able to convincingly show clinical benefit for patients with primary progressive disease, and for that matter have shown variable results when attempted in patients categorized as having secondary progressive courses. While some of our currently approved drugs have shown hints of benefit when tried in major clinical trials in primary progressive MS, the results were not been robust enough to seek regulatory approval.
The Oratorio study design was based on lessons learned from prior trials in primary progressive and relapsing forms of MS, as well as the recognition that B cells might play an important role in the immunopathogenesis of disease based on a considerable amount of preclinical work and observations in patients with multiple sclerosis.
Dr. Nicola Barclay[/caption]
Dr. Nicola Barclay, BA(Hons), MSc, PhD.
Lecturer in Sleep Medicine
Sleep and Circadian Neuroscience Institute (SCNi)
Nuffield Department of Clinical Neurosciences
Sir William Dunn School of Pathology
University of Oxford
MedicalResearch.com: What is the background for this study?
Response: We know that extreme sleep deprivation impairs our cognitive functions, particularly attention. This impairment in attention is likely to be driven by physiological mechanisms that change across the waking day (increasing sleep pressure), but also by factors associated with our biological clock. The timing of physiological processes particularly related to attention differ between morning and evening type people (our so called early morning larks and night owls), and so we hypothesised that morning and evening types would differ in their impairments in attention at different times of day, prior to and following 18 hours of sustained wakefulness.
Prof. Jamal Tazi[/caption]
Prof. Jamal Tazi
Institut de Génétique Moléculaire de Montpellier
University of Montpellier
Montpellier, Cedex, France
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Intense drug discovery efforts in the metabolic field highlight the need for novel strategies for the treatment of obesity. In this study we have used a novel approach to uncover novel drugs to treat obesity. Our approach is based on the finding that in humans the energy expenditure balance can be controlled by a single gene LMNA gene that can produce two different proteins with opposing effect on energy expenditure. We identified a molecule ABX300 that targets the expression of LMNA gene and favors energy expenditure leading to fat loss.
Prof. Cathryn Glazener[/caption]
Prof. Cathryn Glazener PhD
Health Services Research Unit
University of Aberdeen
Aberdeen,UK
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Prolapse is a condition that affects up to half of all women after childbirth. Women notice a bulge or discomfort in their vaginas due to pressure from the bladder, bowel or womb moving downwards. Women who have surgery for their prolapse have a 3 in 10 chance of needing at least one more operation, so the success rate is not great. Gynaecologists hoped that by reinforcing their repairs the success rate would get better.
PROSPECT was a pragmatic, multicentre randomised controlled trial conducted in 35 centres across the UK. Women undergoing their first operation for prolapse were randomised to having a standard repair of the front or back wall of the vagina, or a repair reinforced by synthetic non-absorbable mesh, or a biological graft.
We found that, in contrast to previous research, women were just as likely to be cured after standard surgery rather than reinforced repairs. They were just as likely to have other symptoms such as bladder or sexual problems, and other adverse effects such as infection, bleeding or pain.
However, about 1 in 10 of the women who had mesh did have mesh exposure when a small portion of the mesh becomes visible through the vaginal wall. Although many women did not have symptoms, about half of those women needed a small operation to remove or bury the exposed mesh.
Dr. Roger Zemek[/caption]
Roger Zemek, MD, FRCPC
Associate Professor, Dept of Pediatrics and Emergency Medicine, Clinical Research Chair in Pediatric Concussion, University of Ottawa
Director, Clinical Research Unit,
Children’s Hospital of Eastern Ontario
Ottawa, ON
MedicalResearch.com: What is the background for this study?
Response: While current concussion protocols endorse the conservative view that children should avoid physical activity until completely symptom-free, there is little evidence beyond expert opinion regarding the ideal timing of physical activity re-introduction. In fact, while rest does play a role in concussion recovery, protracted physical rest may actually negatively impact concussion recovery. Further, physiological, psychological, and functional benefits of early physical rehabilitation are observed in other disease processes such as stroke (which is an example of a severe traumatic brain injury). Therefore, our objective was to investigate the relationship between early physical activity (defined within 7 days of the concussion) and the eventual development of persistent post-concussion symptoms at one month.
Dr. Eyal Cohen[/caption]
Eyal Cohen, MD, MSc, FRCP(C)
Staff Physician, Paediatrics
The Hospital for Sick Children
Associate Scientist, Research Institute
Child Health Evaluative Sciences
Associate Professor, University of Toronto
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Major structural or genetic congenital anomalies affect approximately 2 percent to 5 percent of all births in the United States and Europe. Mothers of children born with major congenital anomalies face serious challenges such as high financial pressures, as well as the burden of providing care to a child with complex needs within the home setting, which can impair a mother's health. Little is known about the long-term health consequences for the mother. We assessed whether the birth of an infant with a major congenital anomaly was subsequently associated with an increased risk of death of the infant's mother.
The population-based study (n = 455,250 women) used individual-level linked Danish registry data for mothers who gave birth to an infant with a major congenital anomaly between 1979 and 2010, with follow-up until December 31, 2014. A comparison group was constructed by randomly sampling, for each mother with an affected infant, up to 10 mothers matched on maternal age, parity (the number of children a woman has given birth to), and year of infant's birth. Mothers in both groups were an average age of 29 years at delivery. After a median follow-up of 21 years, there were 1,275 deaths (1.60 per 1,000 person-years) among 41,508 mothers of a child with a major congenital anomaly vs 10,112 deaths (1.27 per 1,000 person-years) among 413,742 mothers in the comparison group. Mothers with affected infants were more likely to die of cardiovascular disease, respiratory disease, and other natural causes.