Author Interviews, JAMA, OBGYNE, Surgical Research / 14.05.2015

Robert A. Meguid, MD MPH FACS Assistant Professor Section of General Thoracic Surgery Division of Cardiothoracic Surgery Department of Surgery University of Colorado Denver | Anschutz Medical Campus Aurora, CO 80045MedicalResearch.com Interview with: Robert A. Meguid, MD MPH FACS Assistant Professor Section of General Thoracic Surgery Division of Cardiothoracic Surgery Department of Surgery University of Colorado Denver | Anschutz Medical Campus Aurora, CO 80045 Medical Research: What is the background for this study? What are the main findings? Dr. Meguid: The surgical literature on adverse outcomes after surgery on pregnant patients is conflicting.  We know that the majority of surgery performed on pregnant patients is not elective (and just over 50% of it in the database studied was emergency surgery).  We expected to find an increased rate of adverse outcomes in those pregnant patients.  However, when we matched the pregnant and non-pregnant women who underwent surgery in the database, with excellent matching on all available preoperative characteristics and on the actual operation performed, we found similar, low rates of 30-day postoperative death and complication.  In this study, pregnant patients had undergone a broad spectrum of different types of operations, including general, vascular, thoracic, head and neck, non-obstetric gynecologic and urologic, orthopedic, reconstructive, and neuro-surgery.  Given the concern that we as surgeons have over operating on pregnant patients, both for the well-being of the patient and her child, our findings are reassuring.  This suggests that we as a medical profession are diligent in minimizing risk to pregnant women who need surgery that cannot be delayed until after the child's birth.  Again, this study faces the limitations of being unable to assess any short term harm done to the fetus and the subsequent long term outcome of the child.
Author Interviews, Cancer Research, Wistar / 14.05.2015

Katherine Aird, Ph.D. Gene Expression and Regulation Program The Wistar Institute, Philadelphia, PAMedicalResearch.com Interview with: Katherine Aird, Ph.D. Gene Expression and Regulation Program The Wistar Institute, Philadelphia, PA MedicalResearch: What is the background for this study? What are the main findings? Dr. Aird: Senescence is considered an important tumor suppressor mechanism. In normal cells, activation of certain oncogenes decreases the levels of dNTPs (the building blocks of DNA), leading to replication stress. We previously found that loss of the rate-limiting enzyme in dNTP synthesis, ribonucleotide reductase M2 (RRM2), is the cause of this replication stress. Restoration of RRM2 expression could rescue the loss of dNTPs and replication stress, which overcame the senescence-associated growth arrest. Indeed, RRM2 is highly expressed in many cancer types, including melanoma and ovarian cancer. Therefore, we found that increased dNTP levels can overcome senescence and potentially lead to transformation of cells and cancer. We next wanted to further our understanding of replication stress in the context of senescence. In the current study, we suppressed nucleotide metabolism by decreasing RRM2 expression as a model for replication stress and then determined what proteins are necessary for the induction of senescence. We found that loss of ATM could overcome replication stress-induced senescence. This was due to increased dNTP levels. dNTPs were increased due to a coordinated inactivation of p53 and activation of c-MYC by loss of ATM. These changes at the molecular level correlate with reprogramming of cellular metabolism by generating dNTPs. Thus, loss of ATM in the context of replication stress can change cellular metabolism to a more cancer-like phenotype.
Author Interviews, Breast Cancer, Chemotherapy, Journal Clinical Oncology, Stanford / 13.05.2015

MedicalResearch.com Interview with: Melinda L. Telli, M.D. Assistant Professor of Medicine Stanford University Division of Medical Oncology Stanford, CAMelinda L. Telli, M.D.
Assistant Professor of Medicine
Stanford University
Division of Medical Oncology
Stanford, CA 94305-5826 Medical Research: What is the background for this study? What are the main findings? Response: A major goal of this study was to explore a DNA damaging chemotherapy regimen in patients with newly diagnosed early-stage triple-negative or BRCA1/2 mutation-associated breast cancer. This was based on the hypothesis that these types of tumors are more responsive to DNA damaging therapeutics. A second major goal was to identify predictors of response to this platinum-based therapy among patients with sporadic triple-negative breast cancer (TNBC). Overall, this study demonstrated that the non-anthracycline and non-taxane neoadjuvant regimen of gemcitabine, carboplatin and iniparib resulted in a 36% pathologic complete response rate (pCR). This compares favorably to pCR rates commonly observed with anthracycline and taxane-based regimens in this group of patients. The response rate was higher among triple-negative breast cancer patients with a germline BRCA1 or BRCA2 mutation (56%). Given the hypothesis of underlying DNA repair defects in sporadic triple-negative breast cancer, we also evaluated a novel measure of genomic instability to detect the accumulation of changes in the genomic landscape of a tumor attributable to defective homologous recombination DNA repair. Homologous recombination deficiency was assessed by loss of heterozygosity (HRD-LOH) in pretreatment core breast biopsies. Very importantly, we found that the HRD-LOH assay was able to identify patients with sporadic TNBC lacking a BRCA1 or BRCA2 mutation, but with an elevated HRD-LOH score, who achieved a favorable pathologic response.
Author Interviews, Nature, NIH / 13.05.2015

Humphrey Yao, Ph.D. Lead Researcher Reproductive and Developmental Biology Laboratory National Institute of Environmental Health Sciences (NIEHS) National Institutes of Health (NIH) Research Triangle Park, North CarolinaMedicalResearch.com Interview with: Humphrey Yao, Ph.D. Lead Researcher Reproductive and Developmental Biology Laboratory National Institute of Environmental Health Sciences (NIEHS) National Institutes of Health (NIH) Research Triangle Park, North Carolina Medical Research: What is the background for this study? What are the main findings? Dr. Yao: We wanted to understand how an organ forms, and what basic cell types were needed to form an organ. So, we used a mouse ovary model system to understand the process. The functional unit of the ovary is called the follicle, and it is made up of three types of cells — the maturing egg, granulosa cells, and theca cells. Scientists knew where the egg and the granulosa cells came from, but no one knew where theca cells came from. Theca cells are important, because they allow females to produce the hormones that sustain follicle growth. Researchers also lacked information about how the egg, granulosa cells, and theca cells talked to each other to promote growth and maintain a healthy ovary. We made two discoveries. First, we answered the long-standing question of theca cell origin by determining that they have two sources, both inside and outside of the ovary. We don’t yet know why theca cells have two sources. Second, we uncovered the molecular signaling system that the egg, granulosa cells, and theca cells use to communicate. We didn’t expect to find this three-way cellular crosstalk, but now that we know how they signal each other, I believe we are closer to understanding how an ovary develops and what happens when something goes wrong. Ovarian disorders, such as premature ovarian failure and polycystic ovarian syndrome, may start when cellular communication is altered or if the various cells fail to develop properly.
Author Interviews, BMJ, Exercise - Fitness, Technology / 13.05.2015

Dr. Shang-Ming Zhou Senior Lecturer in Statistical Modelling and Analytics for Epidemiology and Public Health, Public Health Informatics Group, Health Information Research Unit (HIRU), UKCRC DECIPHer (Development and Evaluation of Complex Interventions for Public Health Improvement) Centre, College of Medicine, Swansea University, Swansea, MedicalResearch.com Interview with: Dr. Shang-Ming Zhou Senior Lecturer in Statistical Modelling and Analytics for Epidemiology and Public Health, Public Health Informatics Group, Health Information Research Unit (HIRU), UKCRC DECIPHer (Development and Evaluation of Complex Interventions for Public Health Improvement) Centre, College of Medicine, Swansea University, Swansea, UK Medical Research: What is the background for this study? What are the main findings? Response: In medical and sport science research, body-worn accelerometers are widely used to provide objective measurements of physical activity. However, accelerometers collect data continuously even during periods of nonwear (i.e. periods when participants may not be wearing their monitor, such as during sleeping). It is important to distinguish time of sedentary behaviours (eg. watching television) from time of nonwear. The clinical consequence of misclassification of accelerometer wear and nonwear would overestimate or underestimate physical activity level, and mislead the interpretation of the relationship between physical activity and health outcomes. Automated estimation of accelerometer wear and nonwear time events is particularly desired by large cohort studies, but algorithms for this purpose are not yet standardized and their accuracy needs to be established. This study presents a robust method of classifying wear and nonwear time events under free living conditions for triaxial accelerometers which combines acceleration and surface skin temperature data. The new findings are: Either acceleration data or skin temperature data alone is inadequate to accurately predict wear and nonwear events in some scenarios under a free living condition; This study provides a simple and efficient algorithm on use of short time periods of consecutive data blocks for accurately predicting triaxial accelerometer wear and nonwear events; Combining both types of acceleration and skin temperature data can significantly improve the accuracy of accelerometer wear and nonwear events classification in monitoring physical activity.
Author Interviews, Biomarkers, Brain Injury / 13.05.2015

MedicalResearch.com Interview with: Pashtun Shahim, MD Departement of Neurosurgery, University Hospital, Linköping, Sweden Clinical Neurochemistry Laboratory Institute of Neuroscience and Physiology Sahlgrenska University Hospital Mölndal Sweden Medical Research: What is the background for this study? What are the main findings? Response: Visinin-like protein-1 (VLP-1 or VILIP-1) is a neuronal calcium-sensor protein, originally studied as a stroke marker and identified as a marker of neuronal injury in brain injury models. Increased plasma and cerebrospinal fluid (CSF) VILIP-1 hase been reported in Alzheimer’s disease, where CSF VILIP-1 correlates with CSF total tau (T-tau) and with brain volume. Recently, using a novel ultrasensitive method to measure tau in plasma, increased levels of plasma T-tau were found in concussed professional ice hockey players, where the levels correlated with the resolution of post-concussive symptoms and the players returning to play. The main findings of this study were that VILIP-1 did not increase significantly in serum after sports-related concussion. However, the serum levels of VILIP-1 increased after a friendly game without concussion, signaling extracerebral expression.
Author Interviews, HPV, Vaccine Studies / 13.05.2015

Maria Blomberg Virus, Lifestyle & Genes Danish Cancer Society Research Centre Copenhagen, DenmarkMedicalResearch.com Interview with: Maria Blomberg Virus, Lifestyle & Genes Danish Cancer Society Research Centre Copenhagen, Denmark Medical Research: What is the background for this study? What are the main findings? Response: Two vaccines against human papillomavirus (HPV) were licensed almost one decade ago. Since then multiple countries have implemented HPV vaccination programs to help reduce genital warts (one of the kinds of warts most harmful to people), but many struggle with low coverage rates. An important barrier to vaccination is the cost of the vaccines and less developed countries also face considerable logistical challenges. Both vaccines were administered as three dose schedules, but in early 2014 the WHO’s Strategic Advisory Group of Experts and the European Medicines Agency reviewed the evidence of reduced dose schedules of HPV vaccination, and subsequently recommended a two dose schedule for young girls. A reduction of the number of doses has obvious advantages; it would lower the costs, ease implementation of vaccination schedules and potentially increase coverage rates. Based on these recommendations, countries around the world have reduced the dosing schedule in their HPV vaccination programs for young girls to two doses. However, the current evidence is based primarily on immunological studies, and because the immune correlate of protection is not known, studies with disease endpoints are very important. Using the biologically relevant endpoint of genital warts, this study aimed to assess the clinical effectiveness of a two dose schedule of quadrivalent HPV vaccine compared with the standard three-dose regimen administered at month 0, 2 and 6. We found that with the standard vaccination schedule, completion of the three dose regimen is important to gain maximal protection. However, the effectiveness of two doses increased significantly with increasing time between the doses, and with an interval of approximately 6 months between dose one and two, no differences could be found between two and three doses.
Addiction, Author Interviews, Columbia, Emergency Care, Pharmacology / 13.05.2015

MedicalResearch.com Interview with: Joanne Brady, PhD candidate Department of Anesthesiology, College of Physicians and Surgeons Department of Epidemiology, Mailman School of Public Health Columbia University, New York, NY Medical Research: What is the background for this study? What are the main findings? Response: Prescription drug overdose is a major public health problem in the United States. Prescription drug overdose mortality has increased dramatically over the past twenty five years. Frequent emergency department utilization may be a marker for risk of prescription drug overdose death. The current study assessed how frequency of emergency department visits in the past year related to risk of subsequent prescription drug overdose death. In a cohort of patients visiting the emergency department, patients with four or more visits to the emergency department in the past year were at substantially higher risk for prescription drug overdose death than patients who visited the emergency department one or fewer times. As the number of visits to the emergency department increased from 0 - 1 to 4 or more for any reason the risk of dying from prescription drug overdose also increased.
Author Interviews, Diabetes, Weight Research / 13.05.2015

MedicalResearch.com Interview with: Martin Reinhardt, MD Postdoctoral Fellow PECRB, NIDDK, NIH Phoenix, AZ 85016 Medical Research: What is the background for this study? What are the main findings? Dr. Reinhardt:  It can be very difficult for some people with obesity to lose weight despite great efforts. There is an immense deal of individual variability in weight loss success. Beyond differences in diet adherence, it is not clear what causes this variability in weight loss. Through a study conducted at our facilities at the National Institutes of Health in Phoenix, Arizona, we have now shown that individual differences in biology – more precisely, differences in the amount of energy bodies use during fasting – make it difficult for certain obese people to lose weight.
Author Interviews, BMJ, Gender Differences, HPV, Vaccine Studies / 13.05.2015

MedicalResearch.com Interview with: Dr. Johannes Berkhof Department of Epidemiology and Biostatistics, VU University Medical Centre Amsterdam Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, Netherlands Medical Research: What is the background for this study? What are the main findings? Response: Vaccination against the sexually transmitted human papillomavirus (HPV) is offered free-of-charge to 12-year-old girls in the Netherlands. There is strong evidence that HPV also causes cancer in men: the virus is associated with cancers of the penis, anus, and oropharynx, and possibly with a small proportion of oral cancers. A number of these cancers will be prevented because vaccination of girls leads to a decrease of  HPV in the general population and thus provides indirect protection to heterosexual men. However, vaccine uptake among girls is only about 60 percent in the Netherlands. Moreover, men who have sex with men are at increased risk of HPV-related cancer and will not be protected by vaccination of girls. On the basis of data from several epidemiological studies and a dynamic model for virus transmission, we calculated that, if the vaccine uptake is low, about 200 girls need to be vaccinated to prevent one case of cervical cancer and 470 boys need to be vaccinated to prevent one case of cancer in men. An increase in vaccine uptake in girls will decrease the HPV infection risk in heterosexual men and if the uptake in girls is 60 percent, around 800 boys need to be vaccinated to prevent one additional case of cancer in men.
Author Interviews, Diabetes, Diabetes Care, Exercise - Fitness, Weight Research / 13.05.2015

MedicalResearch.com Interview with: Edward "Ted" Weiss, Ph.D. Associate Professor Department of Nutrition and Dietetics Saint Louis University Saint Louis MO Medical Research: What is the background for this study? What are the main findings? Dr. Weiss:  Results from one of our previous study yielded a surprising result that diet-induced weight loss improved insulin sensitivity (major diabetes risk factor) by the same amount as exercise induced weight loss. We thought that the exercise-induced weight loss would have yielded benefits from the weight loss itself but also from a weight loss-independent benefit that has been reported in other studies. One explanation for dietary restriction providing the same benefit of exercise was that it also provides benefits besides those that are attributable to weight loss. Our recently completed/published study was designed to evaluate this possibility and the finding do suggest what we hypothesized... i.e. that dietary restriction provides benefits above and beyond that which are attributable to weight loss.
Author Interviews, Global Health, Pediatrics, Primary Care / 12.05.2015

MedicalResearch.com Interview with: Elizabeth Cecil, MSc Department of Primary Care and Public, Health, Imperial College London London, United Kingdom Medical Research: What is the background for this study? What are the main findings? Response: Unplanned hospital admissions in children have been rising for more than a decade placing strain on health care resources in the UK. Unnecessary hospital admission exposes children to hospital acquired infections and an over invasive approach, and is inconvenient for their families as well as adding to pressures on staff dealing with sicker children. Our team from Imperial College London were interested in assessing the impact of primary care policy reforms on short stay admissions, in England. The reforms were nationally implemented in April 2004 and reduced the availability of primary care physicians for children. Our study, found that reforms coincided with an increase in short-stay admission rates for children with primary care-sensitive chronic conditions and with fewer children’s admissions being referred by a primary care physician. Over the study period from April 2000 to March 2012, we found that more than half of the 7.8 million unplanned hospital admissions for children younger than 15 years were short-stay admissions for potentially avoidable infections and chronic conditions. The primary care policy reforms implemented in April 2004 were associated with an 8 percent increase in short-stay admission rates for chronic conditions, equivalent to 8,500 additional admissions, above the 3 percent annual increasing trend. Notably, the policy reforms were not associated with an increase in short-stay admission rates for infectious illness.
Author Interviews, Heart Disease, Infections, JACC / 12.05.2015

J L Mehta, MD, PhD Professor of Medicine and Physiology and Biophysics Stebbins Chair in Cardiology University of Arkansas for Medical Sciences Little Rock, AR 72205MedicalResearch.com Interview with: J L Mehta, MD, PhD Professor of Medicine and Physiology and Biophysics Stebbins Chair in Cardiology University of Arkansas for Medical Sciences Little Rock, AR 72205 Medical Research: What is the background for this study? What are the main findings? Dr. Mehta: In 2007, ACC/AHA published new guidelines regarding infective endocarditis (IE) prevention. This guideline drastically differed from the way we practiced and prescribed antibiotics to our patients when they undergo surgery or any other procedure like dental procedure, endoscopy, etc. to prevent infective endocarditis. As a result of these guideline, antibiotic use is now being restricted to only a small number of patients who have cardiac conditions that puts them at very high risk for adverse outcomes from IE. However, there is paucity of data on IE trends in the community following such a major change in practice. Therefore evaluated the trend in incidence of infective endocarditis and their outcomes before and after the advent of new guideline. Our study has several important findings. First, there has been a steady increase in the incidence of infective endocarditis hospitalizations over the last decade in the US. However, the incidence of IE pre- and post-inception of new antibiotic prophylaxis guidelines is not significantly different. In parallel to these findings, the rate of valve replacement for infective endocarditis did not change after the release of new guidelines in 2007. Secondly, the increase in IE incidence was seen across all types of pathogens- Staphylococcus, Streptococcus, gram negative bacteria and fungi. The major offender involved in IE in the United States is Staphylococcus. Finally, the rate of Streptococcus infective endocarditis related hospitalization increased significantly following the release of new guideline in the US, while Staphylococcus IE hospitalizations although on rise, did not increase significantly following the 2007 ACC/AHA guideline update.
Author Interviews, Weight Research / 12.05.2015

MedicalResearch.com Interview with: Dr Margaret Ashwell OBE, FAfN, RNutr (Public Health) Ashwell Associates Ashwell, Hertfordshire, United Kingdom. Visiting Research Fellow, Oxford Brookes University

MedicalResearch: What are the main findings from this study?

Dr. Ashwell: In this study, the authors explore the differences in CVD risk factors between overweight and non-overweight people (by BMI) according to their shape (waist-to-height ratio -WHtR) Data for their analysis was taken from the Health Survey for England 2009 (HSE). They found significant differences in levels of total cholesterol (TC) and glycat­ed haemoglobin (HbA1c—a measure of blood sugar control used to diagnose diabetes). Out of 2917 people aged 16 years and over, 346 classified as ‘normal’ by BMI, have WHtR exceeding 0.5 (12% of the total,sample, or 34% of normal weight people). These could be called non-overweight ‘apples’, who have a lot of fat around the waist but not a high BMI. The researchers classified the HSE population into four groups (2×2) using standard boundary values of BMI (above or below 25kg/m2) and WHtR (above or below 0.5). The group with ‘low/normal BMI but high WHtR (non-overweight ‘ap­ples’) had significantly higher mean TC than the group with high BMI but low WHtR (overweight ‘pears’—people with a higher than normal BMI but less fat around the waist): 5.73mmol/L vs. 4.98mmol/L. Similarly, HbA1c levels were higher among non-over­weight ‘apples’ than among overweight ‘pears’ (5.62% vs. 5.33%). These differences were similar and also significant in both sexes.

MedicalResearch: Why do you say that piece so string can be used for primary screening?

Dr. Ashwell: Since a good boundary value for waist-to-height ratio is 0.5, you don't even need a tape measure to screen those at risk. It can be done with a piece of string. Measure the height of child with string, fold it in half and see if it fits around his/her waist.   If it doesn't, that child should proceed to the next stage of screening.
Author Interviews, Clots - Coagulation, JAMA, Radiology / 12.05.2015

MedicalResearch.com Interview with: Dott. Michelangelo Sartori U.O. di Angiologia e Malattie della Coagulazione Azienda Ospedaliera di Bologna Policlinico Sant'Orsola Malpighi Bologna Medical Research: What is the background for this study? What are the main findings? Response: The safety of withholding anticoagulation only on the basis of ultrasound imaging has not been evaluated in patients with suspected (Upper Extremity Deep Vein Thromobsis) UEDVT. The purpose of this management study was to evaluate the failure rate of ultrasound testing for UEDVT diagnosis in outpatients. Our data show that, similarly to the lower extremity, a negative complete ultrasound assessment of the upper extremity can safely exclude DVT. We found a 3-month VTE rate of 0.6% after a negative ultrasound and such figure is not different from the 3-month VTE incidence in management studies for lower limb DVT.  Thus anticoagulant therapy can be withheld for clinically suspected UEDVT after negative ultrasound examination without further testing in the ambulatory office setting.
Author Interviews, Pediatrics, Weight Research / 12.05.2015

Matthew PearceMedicalResearch.com Interview with: Matthew Pearce NHS Gloucestershire Clinical Commissioning Group UK Medical Research: What is the background for this study? What are the main findings? Response: Despite evidence to suggest that the prevalence of childhood obesity in the UK has stabilized in recent years, we know that approximately one in five children start their school life either overweight or obese, increasing to one in three children by the last year in primary school. Our research was the first to undertake an in-depth analysis on the UK’s National Child Measurement Programme (NCMP) and retrospectively track the weights of individual children over a 7-year period. Our study included a sample of 1863 children in South Gloucestershire, Bristol in the UK. Our results were found to be similar to cross sectional data with obesity prevalence approximately doubling between the first (4/5yrs old) and last year (10/11yrs old) of primary school. Our findings provide little reassurance that those children who are obese in early childhood ‘grow out of ’ excess adiposity. Including overweight, we found that 84% of obese children at Reception year went on to be either overweight or obese by Year 6. Although previous studies have failed to identify any significant differences in BMI change between boys and girls during mid-childhood, our research found that more boys than girls dropped a weight category (from overweight or obese) by the time they reached Year 6. We found that the odds ratios of being overweight (BMI ?85th percentile) or obese (?95th percentile) based on BMI at Reception were similar to published literature. Our data found children who are within the upper range of the healthy weight category (75th–85th percentile) at Reception had an increased risk of being overweight or obese by the time they reach year 6.
Author Interviews, Heart Disease, Kidney Disease / 12.05.2015

MedicalResearch.com Interview with: Kirolos A. Jacob, MD, MSc PhD Candidate Division Vital Functions, Cardiothoracic Surgery and Intensive Care Medicine University Medical Center Utrecht Medical Research: What is the background for this study? What are the main findings? Dr. Jacob: Heart surgery carries many risks for a patient undergoing such a procedure. One of the most devastating complications following open heart surgery is kidney failure requiring dialysis. Most of these patients who develop kidney failure requiring dialysis after surgery have some form of chronic kidney disease before the operation, which placed them at especially high risk. Approximately one out of every 100 patients undergoing open heart surgery develops severe kidney failure. When such kidney failure occurs, the patient has more than 40% chance of dying. 1% sounds like a small percentage, however given the fact that each year, over half a million people undergo heart surgery in the USA alone, this means that an estimated 5,000 patients develop renal failure and of those about 2,500 die as a result of this complication. This figure is rising yearly as more and more patients are being operated due to the aging population. Also, this elderly population has often significant pre-existing kidney disease, further increasing the incidence of kidney failure after a heart operation. Thus, treatment strategies are needed for this relatively small yet very important and expanding group of patients. Heart surgery initiates an inflammatory reaction across the human body due to the surgical trauma and the heart-lung machine. This systemic immune system reaction is thought to play a vital role in the development of kidney injury after heart surgery. Our study investigated the effects of dexamethasone, a strong anti-inflammatory drug, on severe kidney injury after heart surgery. Severe kidney injury was defined as the use of dialysis during the hospital stay after surgery. We discovered that patients who receive the drug used 56% less frequently kidney dialysis, when compared to those receiving a placebo. Thus patients who did not receive the drug had about 2.5x higher risk for developing kidney failure when compared to those receiving dexamethasone. The beneficial effects of dexamethasone were particularly present in those who already had pre-existing kidney disease before heart surgery. This reinforces the fact that this drug could be of major importance for the increasing elderly population with pre-existing kidney disease undergoing a heart operation.
Author Interviews, Genetic Research, Karolinski Institute, Nature, Neurological Disorders / 11.05.2015

[caption id="attachment_14115" align="alignleft" width="150"]Kristina Bečanovič Ph.D. Photo: Ulf Sirborn[/caption] MedicalResearch.com Interview with: Kristina Bečanovič Ph.D. Department of Clinical Neuroscience Karolinska Institutet, Stockholm, Sweden Medical Research: What is the background for this study? Dr. Bečanović: While the symptoms normally debut in middle-age, there is wide individual variation in how Huntington disease manifests itself, and even though two people carry the exact same genetic mutation that codes for the huntingtin protein, there can be up to a 20-year difference in onset of motor symptoms. This suggests that genetic variants, transcription factors and environmental factors could contribute to the observed differences in disease expressivity. As the identification of regulatory factors of the huntingtin gene would be targets for therapeutic intervention, we set out to study the regulation of the huntingtin gene as it has not been well-known which factors regulate the expression levels. We were interested in identifying both genetic variants and transcription factors that are of importance for gene regulation. We therefore used DNA from Huntington disease patients to study the regulation of the huntingtin gene promoter in cells.
Author Interviews, Gastrointestinal Disease, Transplantation, University of Pennsylvania / 11.05.2015

MedicalResearch.com Interview with: Dr. David Goldberg MD, MSCE Assistant Professor of Medicine LDI Fellow, Leonard Davis Institute, University of Pennsylvania Medical Director for Living Donor Liver Transplantation, Hospital of the University of Pennsylvania Senior Scholar, Center for Clinical Epidemiology and Biostatistics MedicalResearch: What is the background for this study? What are the main findings? Dr. Goldberg: While there are data that demonstrate differences in authorization (consent) rates for deceased donation among racial and ethnic minorities, it is unknown how these differences contribute to geographic differences in the number of deceased organ donors.  It has been postulated that geographic differences in the distribution of racial and ethnic minorities may contribute to differences in the deceased organ supply, yet there have been no empiric data to support this.  Using data on “eligible deaths,” defined as potential brain-dead organ donors <=70 years of age, we demonstrated that even after accounting for differences in the racial/ethnic demographics of the potential donor population, there are dramatic differences in authorization (consent) rates across geographic areas that are not explained by demographics alone. If the source of these differences could be identified, then there could be large increases in the number of organ donors, and lifesaving transplants, in areas with lower authorization rates.
Author Interviews, JAMA / 11.05.2015

William M. Sage MD JD James R. Dougherty Chair for Faculty Excellence School of Law The University of TexasMedicalResearch.com Interview with: William M. Sage MD JD James R. Dougherty Chair for Faculty Excellence School of Law The University of Texas Medical Research: What is the background for this study? What are the main findings? Response: We reviewed settlement agreements in malpractice claims closed by The University of Texas System as part of a larger study on incorporating patient perspectives into safety improvement funded by the Agency for Health Care Research and Quality. Over the five years studied, we found that 88.7% of the 124 settlement agreements that met our study criteria contained non-disclosure provisions, but with little standardization or consistency. Restrictions on disclosure, which selectively burdened patients and their families, seemed broader than needed to protect health care providers from disparagement or to avoid attracting additional litigation. Medical malpractice could happen to anyone at any time during your visit to your hospital. If you or a member of your family have been the victim of medical palpractice you might want to look into getting help from someone like this Tate Law Offices Ft. Worth Personal Injury Law Firm or a law firm that is local to you that might be able to help with your case. Nearly half of the agreements (46.4%) prohibited disclosure of the underlying facts, which may be inconsistent with emerging principles of patient safety and compassionate care, and 26.4% prohibited reporting to regulatory bodies, a restriction that the health system subsequently eliminated in response to our findings. Settlements reached after tort reform took full effect in Texas had stricter non-disclosure provisions than earlier settlements, suggesting greater leverage by defendants notwithstanding the reduced risk of additional litigation.
Author Interviews, Diabetes / 11.05.2015

Meir Stampfer, MD, DrPH Professor of Medicine, Harvard Medical School Professor of Epidemiology and Nutrition, Harvard T.H. Chan School of Public Health Assoc Director, Channing Division of Network Medicine Department of Medicine, Brigham and Women's Hospital Boston, MAMedicalResearch.com Interview with: Meir Stampfer, MD, DrPH Professor of Medicine, Harvard Medical School Professor of Epidemiology and Nutrition Harvard T.H. Chan School of Public Health Assoc Director, Channing Division of Network Medicine Department of Medicine, Brigham and Women's Hospital Boston, MA Medical Research: What is the background for this study? What are the main findings? Response: Moderate alcohol has repeatedly been linked to lower risk of developing diabetes, and among diabetics, those who drink moderately at at substantially lower risk for cardiovascular outcomes. However, there have been no long term trial of alcohol among diabetics. In this two-year randomized trial, we found that wine caused modest improvements in glucose metabolism and in blood lipid levels, with a somewhat greater benefit observed for red wine, for changes in lipids.
Author Interviews, Brigham & Women's - Harvard, Infections, Vaccine Studies / 11.05.2015

Manoj Duraisingh Ph.D. John LaPorte Given Professor of Immunology and Infectious Diseases Harvard T.H. Chan School of Public Health Department of Immunology and Infectious DiseasesBoston, MassachusettsMedicalResearch.com Interview with: Manoj Duraisingh Ph.D. John LaPorte Given Professor of Immunology and Infectious Diseases Harvard T.H. Chan School of Public Health Department of Immunology and Infectious Diseases Boston, Massachusetts MedicalResearch: What is the background for this study? What are the main findings? Dr. Duraisingh: The malaria parasite P. falciparum is one of the most important pathogens of humans, with enormous mortality resulting from blood-stage infections, when parasites replicate exponentially in red blood cells. Although anti-Plasmodial drugs are in clinical use, widespread and increasing parasite drug-resistance has contributed to an ongoing public health crisis, and we urgently need to find novel approaches to prevent and treat disease. Targeting host red blood cell molecules presents an unexploited alternative. However, the highly differentiated and enucleated red blood cell poses a significant technical hurdle for genetic experimentation, due to the lack of a nucleus. Here we have developed a novel, forward genetic screen to identify critical factors of malaria infection of red blood cells in an unbiased fashion. Our screen takes advantage of recent advances in human stem cell biology that enable the ex vivo culture of red blood cells from nucleated hematopoietic precursors which are amenable to in vitro genetics. We have now identified a surface molecule CD55 (alias Decay-Accelerating Factor, DAF) as an essential host factor required for the invasion of red blood cells by P. falciparum. We demonstrate that this protein is required by all P. falciparum strains tested (laboratory and field) for invasion. Furthermore, we demonstrate that CD55 acts at the initial stage of invasion when the P. falciparum parasite attaches to the surface of the red blood cell. Collectively, our findings indicate that CD55 is an ideal target for the development of new host-directed and vaccine therapeutics for malaria.
Author Interviews, Brigham & Women's - Harvard, Electronic Records, JACC, Stroke / 11.05.2015

Dr. Karen E. Joynt, MD MPH Cardiovascular Division Brigham and Women's Hospital and VA Boston Healthcare System Department of Health Policy and Management, Harvard School of Public HealthMedicalResearch.com Interview with: Karen E. Joynt, MD MPH Cardiovascular Division, Brigham and Women's Hospital and VA Boston Healthcare System Department of Health Policy and Management Harvard T.H. Chan School of Public Health MedicalResearch: What is the background for this study?  What are the main findings? Dr. Joynt: While there is a great deal of optimism about the potential of Electronic Health Records (EHRs) to improve health care, there is little national data examining whether hospitals that have implemented EHRs have higher-quality care or better patient outcomes.  We used national data on 626,473 patients with ischemic stroke to compare quality and outcomes between hospitals with versus without EHRs.  We found no difference in quality of care, discharge home (a marker of good functional status), or in-hospital mortality between hospital with versus without EHRs.  We did find that the chances of having a long length of stay were slightly lower in hospitals with EHRs than those without them.
Author Interviews, Breast Cancer, JNCI, Surgical Research / 11.05.2015

Bernadette A.M. Heemskerk-Gerritsen, Ph.D. Department of Medical Oncology Erasmus MC Cancer Institute Roterdam, the NetherlandsMedicalResearch.com Interview with: Bernadette A.M. Heemskerk-Gerritsen, Ph.D. Department of Medical Oncology Erasmus MC Cancer Institute Roterdam, the Netherlands Medical Research: What is the background for this study? What are the main findings? Dr. Heemskerk-Gerritsen: Women with a BRCA1 or BRCA2 mutation have substantially higher risks of developing both primary and contralateral breast cancer (BC) and ovarian cancer than women from the general population. Options to reduce these increased cancer risks include risk-reducing mastectomy (RRM) and/or risk-reducing salpingo-oophorectomy (RRSO). The latter intervention obviously reduces the risk of developing ovarian cancer, but has been reported also to reduce the risk of developing a subsequent breast cancer with approximately 50%. However, studies on the efficacy of risk-reducing surgery in BRCA1/2 mutation carriers are confined to observational studies, thus challenging several methodological issues. Consequently, previous studies on breast cancer risk-reduction after RRSO may have been influenced by bias associated with selection of study subjects, bias associated with start of follow-up, or by confounding, and breast cancer risk-reduction may have been overestimated. In the current study, we revisited the association between risk-reducing salpingo-oophorectomy and breast cancer risk in BRCA1/2 mutation carriers, focusing on the impact of different analytical methods and potential types of bias. First, we replicated the analyses of four previously performed studies, to examine if our Dutch cohort was comparable with the cohorts used in the previous studies. We replicated the approximately 50% breast cancer risk reduction after RRSO in the Dutch cohort. Second, we estimated the effect of RRSO on breast cancer risk in the Dutch cohort using a revised analytical approach for observational studies in BRCA1/2 mutation carriers in order to minimize bias as much as possible. Using this method of analysis, we found no evidence of first BC risk-reduction after RRSO in BRCA1/2 mutation carriers.
Author Interviews, BMJ, Emergency Care, Hospital Readmissions / 11.05.2015

dr-brian-roweMedicalResearch.com Interview with: Dr. Brian Rowe, MD, MSc, CCFP(EM), FCCP Professor, Department of Emergency Medicine University of Alberta, Edmonton, Alberta, Canada MedicalResearch: What is the background for this study? Dr. Rowe: Frequent users are also called “familiar faces” or “heavy users” and they represent an important sub-group of patients in the emergency setting, with often complex needs that contribute to overcrowding and excess health care costs. The evidence suggests that frequent users account for up to one in 12 patients seeking emergency care, and for around one in four of all visits. MedicalResearch: What are the main findings? Dr. Rowe: Frequent users of emergency department care are more than twice as likely to die, be admitted to hospital, or require other outpatient treatment as infrequent users, concludes an analysis of the available evidence, published in Emergency Medicine Journal. These conclusions are based on a thorough search of seven electronic databases of relevant research relating to the frequency and outcomes of emergency department use by adults. Out of a total of more than 4000 potential studies, 31 relevant research reports published between 1990 and 2013 were included in the final analysis. Frequent users were variably defined as visiting emergency care departments from four or more times up to 20 times a year. Among the seven studies looking at deaths, the analysis showed that frequent attenders at emergency care departments were more than twice as likely to die as those who rarely sought emergency care. Most of the studies included hospital admission as an outcome, and these showed that frequent users were around 2.5 times as likely to be admitted as infrequent users. Ten studies looked at use of other hospital outpatient care, and these showed that frequent users were more than 2.5 times as likely to require at least one outpatient clinic after their visit to the emergency care department.
Author Interviews, Infections, PLoS / 11.05.2015

MedicalResearch.com Interview with: Dr. Gordon Langsley Laboratoire de Biologie Cellulaire Comparative des Apicomplexes, Institut Cochin, INSERM U1016, CNRS UMR 8104, Faculté de Medecine Université Paris Descartes, Paris Medical Research: What is the background for this study? What are the main findings? Response: We have been studying the role of cAMP-dependent PKA signaling in Plasmodium falciparum-infected red blood cells for some time; see just a few examples: PMID: 25522250; PMID: 22626931; PMID: 18248092; PMID: 11559352 and we came to the conclusion that intra cellular cAMP levels regulate infected red blood cell deformability and adhesion to for example, brain endothelial cells.
Author Interviews, Sleep Disorders / 10.05.2015

Hans P.A. Van Dongen, Ph.D. Director, Sleep and Performance Research Center Research Professor, College of Medical Sciences Washington State University Spokane, Spokane, WA MedicalResearch.com Interview with: Hans P.A. Van Dongen, Ph.D. Director, Sleep and Performance Research Center Research Professor, College of Medical Sciences Washington State University Spokane, Spokane, WA On behalf of the authors: Paul Whitney PhD, John Hinson PhD, Melinda Jackson PhD, Hans Van Dongen PhD MedicalResearch: What is the background for this study? What are the main findings? Research: Our main interest is in better understanding why people sometimes are able to manage perfectly well with sleep loss, while at other times sleep loss can have profoundly negative effects. We found that sleep deprivation reduces the effectiveness of signals used to tell when you are right or wrong, an effect we labeled feedback blunting. Subjects in the study performed a decision making task that was simple but required feedback, i.e., a signal indicating the response was correct or incorrect, to perform correctly. We found that people who were sleep deprived were no longer able to use the feedback information to make correct responses. And when people had to adapt to unexpected changes in when to respond, sleep deprived people were completely unable to adapt to these changing circumstances. The finding of feedback blunting in this study indicates that people who are sleep deprived not only have trouble sustaining attention to details in the environment (a well established effect of sleep loss), they also have trouble changing the focus of attention to deal with changing circumstances. An interesting paradox in the research literature has been that people have been shown in many circumstances to perform complex tasks at a very high level while sleep deprived. Yet, we know from real-world experience that sleep deprived people can make catastrophic, life-threatening decisions that they would never have made if they were well rested. The current study is the first to shed light on this issue. It showed that sleep deprived people who get feedback, telling them that their actions are not effective, are less capable of changing their behavior. The study is part of a line of research in which we are trying to identify how sleep loss changes specific components of cognition, and how these changes may lead to serious problems in everyday life activities. Being able to study and understand these effects of sleep deprivation under controlled conditions is an important step toward preventing human error under real world conditions.
Author Interviews, Biomarkers, UCSF / 10.05.2015

Alan H.B. Wu, PhD, DABCC Professor Laboratory Medicine Chief, Clinical Chemistry Laboratory University of California San Francisco, CAMedicalResearch.com Interview with: Alan H.B. Wu, PhD, DABCC Professor Laboratory Medicine Chief, Clinical Chemistry Laboratory University of California San Francisco, CA Medical Research: What is the background for this study? What are the main findings? Response: Clinical trials are conducted for validation of novel biomarkers.  There is considerable heterogeniety in the quality design and documentation of findings. This can have a major impact on the conclusions rendered.
Author Interviews, Heart Disease, Mediterranean Diet, Nutrition / 10.05.2015

Miguel Á. Martínez-González, MD, MPH, PhD Department of Preventive Medicine & Public Health School of Medicine, University of Navarra Navarra, SpainMedicalResearch.com Interview with: Miguel Á. Martínez-González, MD, MPH, PhD Department of Preventive Medicine & Public Health School of Medicine, University of Navarra Navarra, Spain Medical Research: What are the main findings? Response: The diet-heart hypothesis has been researched during decades. A common mistake was to assume that a high intake of all types of fat was detrimental for cardiovascular health and could cause heart attacks and strokes. Therefore a low-fat diet was proposed as the best way to prevent heart attacks and strokes. This was wrong. Alternatively, the Mediterranean diet, rich in fat from natural vegetable sources (olive oil, tree nuts), was also considered a healthy dietary pattern. However, most of the evidence to support these benefits of a fat-rich Mediterranean diet came from observational studies and no randomized clinical trial had ever assessed the Mediterranean diet in PRIMARY prevention (i.e. in initially healthy people)
Author Interviews, Genetic Research / 09.05.2015

Rebecca Todd Ph.D. Assistant Professor University of British Columbia Department of Psychology Centre for Interactive Research on Sustainability Vancouver, BCMedicalResearch.com Interview with: Rebecca Todd Ph.D. Assistant Professor University of British Columbia Department of Psychology Centre for Interactive Research on Sustainability Vancouver, BC Medical Research: What is the background for this study? What are the main findings? Dr. Todd: This study brings together two lines of research. First, a couple of years ago my colleagues and I reported that in general people literally see emotional aspects of the world as more vivid - as if they burn more brightly on the eye - than mundane things. We call this effect emotionally enhanced vividness, or EEV. Here we wanted to look at how this phenomenon of emotionally enhanced vividness might differ between individuals. Second, in another previous study we found that people who carry a very common variation in the ADRA2b gene, which influences levels of norepinephrine (a neuromodulator in the brain that is important to the stress response and for emotional influences on memory) were more likely to have their attention captured by emotionally relevant aspects of the world. We also found that how arousing they perceived an event to be at the time it happened predicted how well they remembered it better than for people who did not carry this variation. Here we continued to examine what is unique to this group of people by testing to see if they showed higher levels of the other phenomenon we had found, emotionally enhanced vividness, and what patterns of brain activation would play a role.