Author Interviews, Cancer Research, Cost of Health Care, JAMA / 10.04.2015

Gabriel Brooks, MD Gastrointestinal Cancer Center Dana-Farber Cancer Institute MedicalResearch.com Interview with: Gabriel Brooks, MD Gastrointestinal Cancer Center Dana-Farber Cancer Institute Medical Research: What is the background for this study? What are the main findings? Dr. Brooks: The background for our study is that hospitalizations in patients with cancer are common, costly, and distressing to patients.  Acute hospital care is the single largest expenditure category in cancer care, accounting for substantially greater costs than even chemotherapy. However, patients generally wish to avoid hospitalization, and they certainly want to avoid complications of treatment that can lead to hospitalization. For these reasons, we sought to identify the extent to which hospitalizations are perceived as potentially avoidable by clinicians who are directly involved in patient care. We interviewed three physicians for each of 103 patients with cancer who experienced a hospitalization. For 24 patients (23%) two or more of the three physicians agreed that hospitalization had been potentially avoidable.
Author Interviews, Genetic Research, Nature, Pancreatic, UT Southwestern / 10.04.2015

Dr. Agnieszka Witkiewicz MD Associate Professor of Pathology Harold C. Simmons Comprehensive Cancer Center UT SouthwesternMedicalResearch.com Interview with: Dr. Agnieszka Witkiewicz MD Associate Professor of Pathology Harold C. Simmons Comprehensive Cancer Center UT Southwestern MedicalResearch: What is the background for this study? Dr. Witkiewicz: Pancreatic ductal adenocarcinoma (PDA) has a dismal prognosis, with a five year survival rate of approximately 6%. This poor outcome is related to multiple factors, including the relatively late stage of diagnosis, many patients presenting with unresectable disease, and therapy recalcitrance resulting in disease recurrence in spite of operable disease and systemic therapy. Thus far, insights into how to target the treatment of Pancreatic ductal adenocarcinoma have remained unclear in spite of prior sequencing efforts. MedicalResearch: What are the main findings? Dr. Witkiewicz: The underlying critical finding of the study was that Pancreatic ductal adenocarcinoma is genetically diverse and that, in principle, this diversity could be exploited for the treatment of disease.   Specifically, many cases harbored deregulation in pathways that are the target for drug development.   For example, we identified cases that were driven by BRAF V600E and that were sensitive to the FDA approved drug Vemurafenib.   Similarly, multiple cases harbored defects in DNA repair processes that impart sensitivity to select chemotherapeutic agents and PARP inhibitors.  Common pathway deregulation was observed in reference to beta-catenin, notch, hedgehog, chromatin remodeling, and cell cycle regulatory pathways that are all targets for therapeutic intervention.
Author Interviews, Microbiome, Pediatrics, Weight Research / 10.04.2015

MedicalResearch.com Interview with: Lisa J. Martin PhD Professor Division of Human Genetics Jessica G. Woo PhD Associate Professor Division of Biostatistics and Epidemiology Cincinnati Children’s Hospital Medical Center Cincinnati, OH MedicalResearch: What is the background for this study? Response: Obesity is a major public health concern. In the past 30 years, more and more children are being considered obese. Because treatment is challenging, researchers are looking toward prevention. The health benefits of breastfeeding over infant formula feeding are well recognized, including evidence that breastfeeding may protect against obesity. But, how much protection it provides and the reasons for protection are unclear. Thus, the purpose of this paper was to examine the relationship between breastfeeding and reduced risk of obesity later in life, with special emphasis on potential mechanisms. MedicalResearch: What are the main findings? Response: After reviewing more than 80 studies conducted over a period of 20 years, the authors showed that breastfeeding is associated with a 10 to 20 percent reduction in obesity prevalence in childhood. Mechanisms that connect human milk and infant physiology include maternal obesity, development of a healthy gut environment (microbiome) in the infant, and the development of taste preference and diet quality. Importantly, each of these mechanisms can be influenced by biologic and social factors which may directly and indirectly affect the child’s obesity risk.
Author Interviews, Genetic Research, JAMA, Melanoma / 10.04.2015

Nancy E. Thomas, MD, PhD Department of Dermatology University of North CarolinaMedicalResearch.com Interview with: Nancy E. Thomas, MD, PhD Department of Dermatology University of North Carolina MedicalResearch: What is the background for this study? Dr. Thomas: BRAF and NRAS mutations found in melanomas are important for tumor initiation and maintenance. There are drugs that target BRAF mutations or the pathway that are approved for BRAF-mutant metastatic melanoma and help improve survival. However, it remains unknown whether these mutations in primary melanoma are markers for melanomas with a worse prognosis. MedicalResearch: What are the main findings? Dr. Thomas:
  • In a large international population-based study, we found that of primary melanomas, 30% harbor BRAF mutations, 13% have NRAS mutations and the other 57% do not have these mutations (wildtype).
  • In higher primary tumor stage melanomas, BRAF or NRAS mutations were associated with an approximately 3-fold increased rate of death from melanoma compared to wildtype melanoma adjusted for other prognostic factors.
  • Primary melanomas with NRAS mutations were less likely to have tumor infiltrating lymphocytes (TILs) in the tumor microenvironment.
Author Interviews, Diabetes, Diabetologia, Pediatrics, Social Issues / 10.04.2015

MedicalResearch.com Interview with: Maria Nygren Division of Pediatrics Linköping University, Sweden MedicalResearch: What is the background for this study? What are the main findings? Response: What factors that cause type 1 diabetes is still unknown, but we know that environmental factors are involved besides the genetics. Since the incidence of type 1 diabetes among children have increased worldwide in recent decades, it is important to find out the reasons behind the disease to hopefully be able to prevent new cases. We have in a prospective study of over 10000 children and their parents in Sweden investigated if psychological stress can be a risk-factor, and found that childhood experience of serious life events (such as death/illness in family, divorce, new adult/child in the family) was associated with increased risk for diagnosis of type 1 diabetes up to 14 years of age.
Author Interviews, Infections / 10.04.2015

Catherine M. Stein, PhDAssociate professor of epidemiology and biostatistics Case Western Reserve Dr. Stein is a leader of international research on resistance to Mycobacterium tuberculosis (MTB) infectionMedicalResearch.com Interview with: Catherine M. Stein, PhD Associate professor of epidemiology and biostatistics Case Western Reserve Dr. Stein is a leader of international research on resistance to Mycobacterium tuberculosis (MTB) infection MedicalResearch: What is the background for this study? What do you hope to learn? Dr. Stein: In a 2002 study, we began to clinically characterize people who lived in households where there were infectious tuberculosis cases. We followed them for a two-year period and noticed that approximately 9 percent of household members were resistant to Mycobacterium tuberculosis (MTB) infection, even though they were highly exposed to the organism. This finding surprised us because the prevailing notion had been that everyone living in TB-endemic settings or living with someone who has TB would become infected eventually. After several years of study, we found a substantial number of these people who do not have any evidence for MTB infection, so we wanted to do studies to learn if we could figure out why. MedicalResearch: Is MTB resistance a new phenomenon? Do MTB resisters react to a tuberculin purified protein derivative (PPD) or a gold immunoassay but don’t develop clinical disease? Dr. Stein: We don’t have any reason to believe that MTB-infection resistance is a new phenomenon. It’s just that no one has thought to look for it before. In terms of the PPD or gold immunoassays, MTB-resisters produce a negative response to both tests. The way gold immunoassays are done, three tubes are collected. One is a control. Another is a test for reacting to MTB. Still another is a positive control to make sure immune cells are alive. The MTB-resisters show a response to that positive control but not to MTB. It’s not that these patients don’t have an immune response. It’s just that they have no response to MTB, which means they have no previous exposure to cause their T-cells to make that response. MedicalResearch: Are MTB-resisters immune to the newer multi-drug resistant strains of TB? Dr. Stein: Resistance to MTB infection is independent of the drug resistance pattern of the bacteria. Thus we would expect them to resist multidrug resistant (MDR)-TB as well. There is no strong evidence that MDR-TB is more aggressive or virulent.
Author Interviews, Depression, Endocrinology, Testosterone / 09.04.2015

Mohamed Kabbaj, PHD Professor of Biomedical Sciences & Neurosciences College of Medicine Florida State UniversityMedicalResearch.com Interview with: Mohamed Kabbaj, PHD Professor of Biomedical Sciences & Neurosciences College of Medicine Florida State University Medical Research: What is the background for this study? What are the main findings? Dr. Kabbaj: While anxiety and depressive disorders a major public health concern worldwide, so too are the pervasive sex differences that exist within these pathologies. Fluctuations in the predominant female reproductive hormones, estradiol and progesterone, are thought to be a major contributor to the higher prevalence of anxiety and depression in women compared to men. However, many studies in humans and rodents alike have demonstrated that testosterone, the primary male sex hormone, also influences affective status and may yield protective benefits against the development of mood-related disturbances. Indeed, hypogonadal males with low testosterone levels experience increased rates of anxiety and depressive symptoms. In many of these cases, testosterone replacement alone or in addition to antidepressant medication have been shown to effectively improve mood. How this hormone acts in the brain to exert its beneficial effects, however, is much less clear. Interestingly, it is well-known that many of testosterone’s effects in the brain occur via its conversion to estrogen by the enzyme aromatase. What remained unclear was whether or not this conversion to estrogen was critical for testosterone’s protective anxiolytic and antidepressant effects—so Nicole Carrier and Samantha Saland from Dr. Kabbaj’s lab aimed to figure out just that. To do this, Carrier and Saland targeted an area of the hippocampus in the brain involved in mood regulation where testosterone is known to act to carry out some of its anxiolytic and antidepressant effects in male rats. Here, they inhibited the enzyme responsible for the conversion of testosterone into estrogen and investigated performance in mood-related behaviors. In doing so, they discovered that testosterone’s anxiolytic- and antidepressant-like effects were lost unless this hormone was first converted into estrogen. Importantly, they also found that continuous testosterone and estrogen treatments had very similar effects on the expression of genes within this brain region that are highly implicated in the regulation of mood as well as antidepressant treatments.
Author Interviews, Cost of Health Care, Emergency Care, Primary Care / 09.04.2015

Haichang Xin, PhD Department of Health Care Organization and policy School of Public Health University of Alabama at BirminghamMedicalResearch.com Interview with: Haichang Xin, PhD Department of Health Care Organization and policy School of Public Health University of Alabama at Birmingham MedicalResearch: What is the background for this study? Dr. Xin: Research suggests that nearly half of all emergency department (ED) visits in the United States are for nonurgent conditions, leading to billions of dollars in potentially avoidable spending annually. A well-functioning primary care system has the capacity to provide timely, adequate, and effective care for patients in order to avoid nonurgent emergency department use and care costs. This study examined how deficiencies in ambulatory care were associated with nonurgent emergency department care costs nationwide, and to what extent these costs can be reduced if deficiencies in primary care systems could be improved. MedicalResearch: What are the main findings? Dr. Xin: Patient perceived poor and intermediate levels of primary care quality had higher odds of nonurgent emergency department care costs (OR=2.22, p=0.035, and OR=2.05, p=0.011, respectively) compared to high quality care, with a marginal effect (at means) of 13.0% and 11.5% higher predicted probability of nonurgent ED care costs. These ambulatory care quality deficiency related costs amounted up to $229 million for private plans (95% CI: $100 million, $358 million), $58.5 million for public plans (95% CI: $33.9 million, $83.1 million), and an overall of $379 million (95% CI: $229 million, $529 million) at the national level.
Author Interviews, Circadian Rhythm, Ophthalmology, Sleep Disorders, UCSD / 09.04.2015

MedicalResearch.com Interview with: Carolina P B Gracitelli, M.D. Ophthalmology - PhD Candidate/ Research Fellow University of California San Diego - Hamilton Glaucoma Center Medical Research: What is the background for this study? What are the main findings? Dr. Gracitelli: Of all the diseases that can lead to blindness, glaucoma is one of the most important diseases; it affects more than 70 million people worldwide, of whom approximately 10 % are bilaterally blind. Different studies have reported that the damage caused by glaucomatous disease lead to retinal ganglion cell (RGC) loss and consequently loss of intrinsically photosensitive retinal ganglion cells (ipRGCs), which is a subtype of RGC. This subpopulation of RGC is clearly related with non-image-forming visual function such as photic synchronization of circadian rhythms and the pupillary light reflex. However, the true impact of glaucoma on sleep quality, sleep disturbance or circadian rhythm was until nowadays controversial. The main clinical finding of our study was that glaucoma leads to RGC death, including ipRGC death. These cells are connected to several non-image-forming functions, including circadian photoentrainment and pupillary reflexes. Therefore, the image-forming and non-image-forming visual systems are associated with glaucoma. Circadian function has not been well investigated in clinical daily practice, but it can interfere with the quality of life of these patients. Concerns about sleep disturbances in glaucoma patients should be incorporated into clinical evaluations. Medical Research: What should clinicians and patients take away from your report? Dr. Gracitelli: Our data support the concept that glaucoma is associated with a loss of ipRGCs that mediate the pupillary light response, particularly to the sustained component of the blue flash with a luminance of 250 cd/m2. Additionally, glaucoma patients had significant sleep disturbances that were inversely correlated with a measure of ipRGC function, the pupillary light reflex. These results suggest that the loss of ipRGCs in glaucoma may also lead to sleep disturbances. Both non-visual functions of ipRGCs are correlated, indicating that attention should be paid to the non-image forming visual functions in glaucoma patients. Medical Research: What recommendations do you have for future research as a result of this study? Dr. Gracitelli: Sleep disorders is a complex system, therefore, some conclusions in this study should be carefully evaluated. Further studies with larger cohorts could also help to elucidate the association between the pupillary reflex and the polysomnography parameters. And longitudinal studies can better explain the associations between sleep disorders and glaucoma progression. In addition, we know that there are several types of ipRGCs and they have specific functions (pupillary reflex or circadian rhythms), therefore, evaluations would also need to include a more thorough assessment to understand better the specific role of ipRGCs in sleep disturbances. However, it is true that these ipRGCs functions are impaired in glaucoma, affecting the quality of life of these patients. Citation: Intrinsically Photosensitive Retinal Ganglion Cell Activity Is Associated with Decreased Sleep Quality in Patients with Glaucoma Gracitelli, Carolina P.B. et al. Ophthalmology Published Online: April 06, 2015 DOI: http://dx.doi.org/10.1016/j.ophtha.2015.02.030MedicalResearch.com Interview with: Carolina P B Gracitelli, M.D. Ophthalmology - PhD Candidate/ Research Fellow University of California San Diego - Hamilton Glaucoma Center Medical Research: What is the background for this study? What are the main findings? Dr. Gracitelli: Of all the diseases that can lead to blindness, glaucoma is one of the most important diseases; it affects more than 70 million people worldwide, of whom approximately 10 % are bilaterally blind. Different studies have reported that the damage caused by glaucomatous disease lead to retinal ganglion cell (RGC) loss and consequently loss of intrinsically photosensitive retinal ganglion cells (ipRGCs), which is a subtype of retinal ganglion cell. This subpopulation of RGC is clearly related with non-image-forming visual function such as photic synchronization of circadian rhythms and the pupillary light reflex. However, the true impact of glaucoma on sleep quality, sleep disturbance or circadian rhythm was until nowadays controversial. The main clinical finding of our study was that glaucoma leads to retinal ganglion cell death, including ipRGC death. These cells are connected to several non-image-forming functions, including circadian photoentrainment and pupillary reflexes. Therefore, the image-forming and non-image-forming visual systems are associated with glaucoma. Circadian function has not been well investigated in clinical daily practice, but it can interfere with the quality of life of these patients. Concerns about sleep disturbances in glaucoma patients should be incorporated into clinical evaluations.
Author Interviews, Blood Pressure - Hypertension, Compliance / 08.04.2015

MedicalResearch.com Interview with: Amneet Sandhu, MD Department of Internal Medicine Division of Cardiovascular Medicine University of Colorado Aurora, CO 80045. Medical Research: What is the background for this study? What are the main findings? Dr. Sandhu: Control of hypertension has improved nationally to guideline recommended levels.  To date, the focus of hypertensive care has been around identification and appropriate treatment to blood pressure goals.  Less emphasis has been placed on maintenance of control or tracking patients with high rates of relapse after achieving control. This study sought to assess the rate of recidivism in a cohort of hypertensive patients with controlled blood pressure and identify patient and process of care factors associated with recidivism.  We found approximately 25% of hypertensive patients with baseline controlled blood pressure relapse over a median time period of 7.3 months.  Patients with diabetes, high normal baseline blood pressure and poor medication adherence were more likely to suffer from recidivism.
Author Interviews, Blood Pressure - Hypertension, Social Issues, University of Michigan / 08.04.2015

Kira S. Birditt, Ph.D. Research Associate Professor Life Course Development Program The Institute for Social Research University of Michigan Ann Arbor, MI MedicalResearch.com Interview with: Kira S. Birditt, Ph.D. Research Associate Professor Life Course Development Program The Institute for Social Research University of Michigan Ann Arbor, MI Medical Research: What is the background for this study? What are the main findings? Dr. Birditt: We know that negative marital quality (e.g., conflict, irritation) has important implications for physical health but the mechanisms that account for these links are still unclear. This study explored links between negative marital quality (e.g., criticism, demands), stress (long term chronic stresses) and blood pressure among older married couples in  a large longitudinal nationally representative sample of couples in the U.S..  We found that husbands had higher blood pressure when wives reported greater stress and that this link was even greater when husbands felt more negative about the relationship.  In addition, negative marital quality experienced by only one member of the couple was not associated with blood pressure but when both members of the couple reported higher negative marital quality they had higher blood pressure. 
Author Interviews, Genetic Research, OBGYNE / 08.04.2015

Jeanne M. Meck, PhD FACMG Director, Prenatal Diagnosis & Cytogenomic GeneDx Gaithersburg, MD 20877MedicalResearch.com Interview with: Jeanne M. Meck, PhD FACMG Director, Prenatal Diagnosis & Cytogenomic GeneDx Gaithersburg, MD 20877 Medical Research: What is the background for this study? Dr. Meck: Non-invasive prenatal screening (NIPS) for fetal aneuploidy is a new test which requires only a blood sample from the pregnant mother to provide a risk estimate of whether or not her fetus has a chromosomal aneuploidy such as trisomy 21 (Down syndrome), trisomies 13 or 18, or a sex chromosome abnormality. This testing relies on the fact that circulating maternal blood contains cell free fetal DNA. Published studies have reported very high specificities and sensitivities. However, the more important question is what is the positive predictive value (PPV= #true positive results/#true positive + false positive results) since it answers the question of interest to physicians and patients: “Given an Non-invasive prenatal screening result that shows a high risk for a given fetal aneuploidy, what is the chance that the fetus is affected?” We attempted to answer this question by looking at the results of fetal chromosome analyses on chorionic villus samples (CVS) or amniotic fluid that were referred to our cytogenetics laboratories after Non-invasive prenatal screening in order to see if NIPS correctly predicted the fetal karyotype.
Author Interviews, Cancer Research, Cost of Health Care / 08.04.2015

MedicalResearch.com Interview with: Stacie B. Dusetzina PhD Assistant professor in the Eshelman School of Pharmacy and the Gillings School of Global Public Health University of North Carolina at Chapel Hill Member of the Lineberger Comprehensive Cancer CenterMedicalResearch.com Interview with: Stacie B. Dusetzina PhD Assistant professor in the Eshelman School of Pharmacy and the Gillings School of Global Public Health University of North Carolina at Chapel Hill Member of the Lineberger Comprehensive Cancer Center Medical Research: What is the background for this study? What are the main findings? Dr. Dusetzina: Charges for health services — the amounts providers request before payments are negotiated — have not been widely known for services delivered in physicians’ offices. Charges can be considered the maximum amount that would be paid by a person without insurance who does not or is unable to negotiate for a lower price. In this study we used recently released data from the Medicare Provider Utilization and Payment Public Use File and other sources to measure what physicians charged for chemotherapy drugs delivered intravenously in 2012 and the amounts reimbursed by Medicare and private health plans for the same services. We found that uninsured cancer patients may be asked to pay from 2 to 43 times what Medicare pays for chemotherapy drugs. Medicare and insurers don’t pay the sticker price of health care. They pay a discounted rate. However, uninsured patients don’t have the bargaining power, or they may not try to negotiate for a better price. On average, Medicare paid approximately 40 percent of the charged amounts for chemotherapy drugs. Private insurers paid nearly 57 percent of the charged amounts on average. We also looked at what cancer patients were asked to pay for an office visit. Uninsured patients may be asked to pay from $129 to $391, depending on the complexity of the visit. Medicare paid between $65 and $188 and private insurance paid between $78 and $246 for the same visits.
Author Interviews, Cancer Research / 08.04.2015

MedicalResearch.com Interview with: Dr. Riccardo Capocaccia Evaluative Epidemiology Unit Department of Preventive and Predictive Medicine Fondazione Istituto Nazionale Tumori Milan, Italy Medical Research: What is the background for this study? What are the main findings? Dr. Capocaccia: Life expectancy of cancer patients is usually provided at diagnosis, as a measure of cancer burden. However, no systematic data are available on life expectancy at different times after diagnosis, as a measure of the residual impact of the disease in survivors. At diagnosis, young patients face a higher loss in life expectancy, with respect to cancer-free people of the same age, than older ones. Thereafter, life expectancy gradually approaches, but hardly reaches,  that of all patients of the general population.
Author Interviews, Dermatology, HPV / 08.04.2015

MedicalResearch.com Interview with: Luis Squiquera, MD Tamir Biotechnology MedicalResearch: What is the background for this study? What are the main findings? Dr. Squiquera: Ranpirnase is a small peptide that has a characteristic enzymatic activity against double stranded RNA (dsRNA). As a drug it has been extensively tested intravenously in high concentration for oncology in over 1000 patients with different types of malignancy, especially mesothelioma, with minimal side effects and mainly a transient increase of serum creatinine level observed. In the last year we started a comprehensive antiviral program and obtained encouraging results in several RNA and DNA virus families. Several research groups have already studied the anti HIV activity. HPV was one of many viruses that showed a high selectivity index in our antiviral screening (the relationship between efficacy and cytotoxicity). We were encouraged by the low concentrations (nanomolar range) needed to stop virus reproduction in cell cultures. We performed in vitro analysis of two of the main HPV types that cause human disease (HPV 11 and 16). HPV 11 was highly sensitive to ranpirnase; and since this is one of the main virus type responsible for inducing genital warts, we decided to focus our efforts in bringing the drug to a new route of administration. We set out to obtain and did obtain a formulation that was extremely stable, even at high temperatures. Before using it in patients, we performed testing for irritation using standardized Draize animal models. Even though we ran these tests in high concentrations (1 mg/ml) the final product was not irritant and was deemed safe to use in a clinical setting. With these safety data on hand – plus extensive experience in IV dosing and non-irritation in animal models – we decided to make the formulation available as a compassionate use for patients with genital warts. As we reported in our presentation in San Francisco, all cases that completed an 8-week treatment showed clearance of the lesions. Some of the cases were cleared in as soon as two weeks and the average time for clearance was 33 days. One of the patients had to be discontinued due to an eczematous skin reaction. We will be studying the characteristic of this effect in our trials.
Author Interviews, Cognitive Issues, Memory / 07.04.2015

[caption id="attachment_13389" align="alignleft" width="300"]Associate Professor Lim Lee Wei (Sunway University, Malaysia) and Assistant Professor Ajai Vyas (Nanyang Technological University, Singapore) discover a new treatment using deep brain stimulation of the Prefrontal Cortex for dementia. Associate Professor Lim Lee Wei (Sunway University, Malaysia) and Assistant Professor Ajai Vyas (Nanyang Technological University, Singapore) discover a new treatment using deep brain stimulation of the Prefrontal Cortex for dementia.[/caption] MedicalResearch.com Interview with: Dr. Lim Lee Wei School of Biological Sciences, Nanyang Technological University, Singapore; Department of Biological Sciences, Sunway University, Malaysia Medical Research: What is the background for this study? What are the main findings? Response: To date, pharmacological treatments for dementia have limited effects (most of the drugs failed in the second or third clinical trials) and there are no known treatments that cure or delay the progression of this memory impairment. Therefore, a novel non-pharmacological approach such as deep brain stimulation (DBS) is currently considered as an alternative treatment to reduce the symptomatic and progression of this memory deterioration. Deep brain stimulation for dementia-related disease is currently evaluated as a potential therapy. In line with this development, evidence from recent studies suggests that deep brain stimulation might enhance memory functions when particular brain areas are stimulated. Of particular interest in our study, electrical stimulation of the Prefrontal Cortex induced striking antidepressant activity in both patients and animals studies (see our recent study, Lim et al., 2015 Translational Psychiatry; http://www.nature.com/tp/journal/v5/n3/full/tp201524a.html). However, no studies have shown the putative role of Prefrontal Cortex deep brain stimulation in learning and memory performance. In our finding, we have shown that deep brain stimulation of this region (Prefrontal Cortex) improved the short-term and long-term memory by a very important mechanism, which led to the formation of new brain cells in another region of the brain called the hippocampus, which is also involved in memory. Therefore, our findings suggest that deep brain stimulation of the Prefrontal Cortex has the potential to be developed into a therapy to treat dementia and other conditions that lead to memory loss in humans.
Author Interviews, Kidney Disease, UCLA / 07.04.2015

MedicalResearch.com Interview with: Bryan B. Shapiro Harold Simmons Center for Kidney Disease Research and Epidemiology and Division of Nephrology and Hypertension Los Angeles Biomedical Research Institute Harbor–UCLA Medical Center Torrance, California Medical Research: What is the background for this study? What are the main findings? Response: The inverse relationship between body mass index (BMI) and mortality rates is well-documented in maintenance hemodialysis (MHD) patients. Virtually everyone has assumed that this relationship reflects the effect of body weight, and especially fat mass, on mortality in these patients. However, height is also a component of the BMI equation (BMI = body weight (kg)/height (m²)) and may be independently associated  with mortality in MHD patients. The results of this study, which examined 117, 644 MHD patients and was controlled for many demographic and laboratory variables, indicate that height, adjusted for body weight, is directly associated with mortality in a manner that is opposite to the weight-mortality relationship. Moreover, we found that the contribution of height to the inverse BMI-mortality relationship in dialysis is essentially as great as the contribution of weight.
Author Interviews, JAMA, Surgical Research, UCSF / 07.04.2015

Emily Finlayson, MD, MS Department of Surgery, Division of General Surgery Department of Medicine, Division of Geriatrics Philip R Lee Institute for Health Policy University of California, San Francisco Director, UCSF Center for Surgery in Older AdultsMedicalResearch.com Interview with: Emily Finlayson, MD, MS Department of Surgery, Division of General Surgery Department of Medicine, Division of Geriatrics Philip R Lee Institute for Health Policy University of California, San Francisco Director, UCSF Center for Surgery in Older Adults Medical Research: What is the background for this study? What are the main findings? Dr. Finlayson: In general, the goal of lower extremity revascularization is to preserve the leg so that patients can maintain the ability to ambulate and maintain functional independence.  We evaluated the results of this operation in older nursing home residents in the United States.  We found that over the 3 year study period, over 10,000 nursing home residents underwent this procedure.  Most of them were functionally dependent before surgery, 3/4 were unable to walk, and over half had dementia. After 1 year, half of the residents had died.  Among residents who could not walk before surgery, 89% were dead or non ambulatory 1 year after surgery.
Author Interviews, Occupational Health, Orthopedics / 06.04.2015

Thomas Karakolis Department of Kinesiology University of Waterloo Waterloo, Ontario, CanadaMedicalResearch.com Interview with: Thomas Karakolis Department of Kinesiology University of Waterloo Waterloo, Ontario, Canada Medical Research: What is the background for this study? What are the main findings? Response: Major League Baseball (MLB) pitchers have an injury rate approaching 1 in 4, depending on the study you look at. As an occupational injury rate, this number is extremely high. In fact, I think you would be hard pressed to find another industry where the injury rate is that high. One way that coaches and managers in MLB are trying to lower the injury rate is to restrict the total 'workload' on pitchers per season. Particularly in young pitchers, many MLB organizations restrict the number of innings a pitcher can pitch based upon the number of innings they pitched the previous year. Essentially, they are using innings pitched as a surrogate for workload. If this is an effective strategy, you would expect a correlation between the increase in number of innings pitched between successive seasons and future injury. Our study found that no such correlation exists. Innings pitched does not appear to be a sensitive enough measure to asses the true workload a pitcher experiences throughout the season.
Annals Internal Medicine, Author Interviews, Johns Hopkins, Weight Research / 06.04.2015

Kimberly Gudzune, MD, MPH Assistant Professor; The Johns Hopkins University School of Medicine Core Faculty; Welch Center for Prevention, Epidemiology, and Clinical Research The Johns Hopkins Digestive Weight Loss CenterMedicalResearch.com Interview with: Kimberly Gudzune, MD, MPH Assistant Professor; The Johns Hopkins University School of Medicine Core Faculty; Welch Center for Prevention, Epidemiology, and Clinical Research The Johns Hopkins Digestive Weight Loss Center Medical Research: What is the background for this study? What are the main findings? Dr.Gudzune: Changes in healthcare policy may encourage healthcare providers to screen their patients for obesity, so it is critical to then have a weight management plan if obesity is identified. Recent guidelines recommend that clinicians consider referring patients to high intensity weight loss programs. Commercial weight loss programs may be one of the options available, so providers need to know which programs help people lose weight and keep it off. We found that only 11 out of 32 programs that we looked at had rigorous studies reporting on weight loss, which means that we do not know whether most programs work. Several well-known commercial programs have been scientifically tested and two programs, Weight Watchers and Jenny Craig, achieved significant weight loss that was sustained 12 months later.
Author Interviews, Breast Cancer, Genetic Research, Journal Clinical Oncology, University of Michigan / 06.04.2015

Dr. Reshma Jagsi MD, DPhil Associate Professor and Deputy Chair for Faculty and Financial Operations in the Department of Radiation Oncology at the University of Michigan Health System Research Investigator at the Center for Bioethics and Social Sciences in Medicine University of MichiganMedicalResearch.com Interview with: Dr. Reshma Jagsi MD, DPhil Associate Professor and Deputy Chair for Faculty and Financial Operations in the Department of Radiation Oncology at the University of Michigan Health System Research Investigator at the Center for Bioethics and Social Sciences in Medicine University of Michigan Medical Research: What is the background for this study? What are the main findings? Dr. Jagsi: We surveyed women diagnosed with breast cancer and found that many women were concerned about the genetic risk of developing other cancers themselves or of a loved one developing cancer.  Overall, 35 percent of the women we studied expressed a strong desire for genetic testing, but 43 percent of those did not have a relevant discussion with a health care professional. In addition, minority patients with a strong desire for testing were less likely to discuss it with a professional, even though studies show that minority patients are not at lower risk for these mutations.
Annals Internal Medicine, Author Interviews, Surgical Research, University of Pittsburgh / 06.04.2015

Anthony Delitto, PT, Ph.D, FAPTA Professor and Chair Department of Physical Therapy Associate Dean for Research, SHRS School of Health and Rehabilitation Sciences Pittsburgh,MedicalResearch.com Interview with: Anthony Delitto, PT, Ph.D, FAPTA Professor and Chair Department of Physical Therapy Associate Dean for Research, SHRS School of Health and Rehabilitation Sciences University of Pittsburgh Medical Research: What is the background for this study? What are the main findings? Dr. Delitto: I work with a team, many of whom were authors on the paper, and we see a lot of patients with lumbar spinal stenosis. Some of them did very well with Physical Therapy and avoided surgery. Some people didn’t do well and we ended up having surgery. We really wanted to do a study that compared, in a randomized format, doing surgery vs. a non-surgical approach to lumbar spinal stenosis. The idea we had was to really put the two approaches head to head – a randomized trial of surgery vs. physical therapy for people with lumbar spinal stenosis. We decided only to recruit patients after they had consented to surgery in order to avoid the pitfalls of previous studies where people crossed over after being assigned to a group, for example, being assigned to surgery and then deciding against having surgery. Medical Research: What should clinicians and patients take away from your report? Dr. Delitto: Probably the biggest point to put across to physicians, patients and practitioners, one of the things we realized was: patients don’t exhaust all of their non-surgical options before they consent to surgery. And physical therapy is one of the non-surgical options. The obvious finding is, when you compare the two groups, they seem to do the same. The results were equivalent at two years. Now, embedded in that, there are patients who did well in surgery, and patients who failed in surgery. There are patients who did well in Physical Therapy, and there are patients who failed with PT. But when we looked across the board at all of those groups, their success and failure rates were about the same. So it tells us that for the most part there were equivalent outcomes at two years.
Author Interviews, Brigham & Women's - Harvard, Cannabis, JAMA, Lipids, Pediatrics / 06.04.2015

Holly Gooding, MD, MS Harvard T.H. Chan School of Public Health Instructor in Pediatrics at Harvard Medical School Division of Adolescent/Young Adult Medicine, Boston Children’s Hospital Division of General Internal Medicine, Brigham and Women’s Hospital Boston, MAMedicalResearch.com Interview with: Holly Gooding, MD, MS Harvard T.H. Chan School of Public Health Instructor in Pediatrics at Harvard Medical School Division of Adolescent/Young Adult Medicine, Boston Children’s Hospital Division of General Internal Medicine Brigham and Women’s Hospital Boston, MA Medical Research: What is the background for this study? What are the main findings? Dr. Gooding: As an adolescent medicine physician, I primarily care for patients between the ages of 12 and 30, although I first trained in internal medicine.  One of the things I noticed when I started working with this age group is that pediatric and adult guidelines differ for many conditions.  Cholesterol treatment is one condition that comes up frequently, because the NHLBI and the AAP recommend screening youth ages 17 to 21 for cholesterol problems. The study team and I set out to discover the proportion of American youth ages 17 to 21 who would meet criteria for pharmacologic treatment of abnormal cholesterol levels if clinicians applied the pediatric versus the adult guidelines.  We found that 2.6% of young people ages 17 to 21 would qualify for pharmacologic treatment of abnormal LDL cholesterol levels under the pediatric guidelines, but less than 1% would qualify under the adult guidelines.  This translates to almost 500,000 youth qualifying for treatment under the pediatric guidelines, but only about 78,000 under the adult guidelines.  Those who met pediatric criteria had lower LDL levels but higher proportions of high blood pressure, smoking, and obesity.
Author Interviews, Biomarkers, Lancet, Lymphoma, NIH / 06.04.2015

MedicalResearch.com Interview with: Dr. Mark Roschewski, MD and Dr Wyndham H Wilson MD-PhD Lymphoma Therapeutics Section Lymphoid Malignancies Branch, Center for Cancer Research National Cancer Institute, National Institutes of Health Bethesda, MD 20892 Medical Research: What is the background for this study? What are the main findings? Response: Monitoring patients with diffuse large B-cell lymphoma (DLBCL) has relied on computed tomography (CT) scans which are imprecise, expensive and include radiation. We investigated the ability of a blood-based assay to monitor patients with DLBCL during and after their initial therapy. The assay we studied amplifies and quantifies small amounts of circulating tumor DNA from the patient’s blood. We showed that this assay effectively predicts which patients will relapse and identifies recurrence 3.5 months before CT scans.
Author Interviews, End of Life Care / 06.04.2015

Prof. Chetna Malhotra M.B.B.S., M.D. M.P.H. Lien Centre for Palliative Care Duke-NUS Graduate Medical School Singapore, SingaporeMedicalResearch.com Interview with: Prof. Chetna Malhotra M.B.B.S., M.D. M.P.H. Lien Centre for Palliative Care Duke-NUS Graduate Medical School Singapore, Singapore Medical Research: What is the background for this study? What are the main findings? Dr. Malhotra: Patients with advanced cancer often have to make difficult decisions, such as how much to spend on moderately life- extending treatments. This and other end-of-life decisions are also influenced by their informal caregivers. In this study, we aim to understand the relative value that advanced cancer patients and their caregivers place on various aspects of end-of-life care. We conducted a cross-sectional survey of 211 patients with stage IV cancer and their primary informal caregivers.  Participants were asked to choose their most-preferred end-of-life scenarios out of a series of options that varied along key dimensions, including years of life remaining, degree of pain experienced, place of death, level of burden on caregivers, quality of healthcare experience, cost, and source of payment (cash, Medisave, or family members’ cash or  Medisave). Using the results, we quantified patients and caregivers willingness to pay to improve their end of life experience. We found that the patients’ willingness to pay to extend their life by one year was valued at S$18,570, which is lower than their willingness to pay to avoid severe pain (S$22,199), or to die at home (S$31,256). Caregivers had a three-fold greater willingness to pay than patients to extend life by one year and for most of the other features considered. These results suggest that health insurers and physicians may be putting too much emphasis on life extending treatments for these patients. Further, there is a need to elicit patient preferences during treatment decision making as opposed to just relying on caregiver input.
Breast Cancer, Health Care Systems / 06.04.2015

MedicalResearch.com Interview with: Dr. Karla Unger-Saldaña Unit of Epidemiology Instituto Nacional de Cancerología Mexico City, Mexico. Medical Research: What is the background for this study? Dr. Unger-Saldaña: Even though Breast Cancer is most common in the developed world, most cancer deaths actually occur in developing regions. This is mainly because patients are diagnosed in advanced stages, with poor chances of survival. Most studies have shown that long times between symptom discovery and treatment start (total delay) are associated with advanced clinical stage. Like total delay, patient delay -a prolonged time between symptom discovery and the first medical consultation- has also shown to be associated with advanced clinical stage. But the impact of health system delay -the time between the first clinical consultation and the start of cancer treatment- is less clear. Studies have shown contradictory findings. For example, studies in developed countries have found the reverse association: advanced stages associated with short times between first medical consultation and treatment start. This has been attributed to the ability of doctors to quickly identify patients with advanced cancer and somehow accelerate their care. Medical Research: What are the main findings? Dr. Unger-Saldaña: In this study, done among 886 patients, we found that the majority started cancer treatment in advanced stages, with only 15% being diagnosed in stages 0 and I. Also, we found long delays for breast cancer diagnosis and treatment in most cases. The median time between symptom discovery and cancer treatment start was 7 months. The longest subinterval was that between the first medical consultation and diagnosis confirmation, which had a median of 4 months. The most relevant result was that not only was patient delay associated with advanced stage, but also health system delay. For every additional month of health system delay, the probability of starting treatment in advanced stage was increased by 1%.
Author Interviews, Exercise - Fitness, JAMA, NIH / 06.04.2015

MedicalResearch.com Interview with: Hannah Arem, MHS, PhD Division of Cancer Epidemiology and Genetics National Cancer Institute, Bethesda, MarylandMedicalResearch.com Interview with: Hannah Arem, MHS, PhD Division of Cancer Epidemiology and Genetics National Cancer Institute, Bethesda, Maryland Medical Research: What is the background for this study? Dr. Arem: The 2008 Physical Activity Guidelines for Americans recommend a minimum of 150 minutes of moderate-intensity or 75 minutes of vigorous-intensity activity per week for “substantial” health benefit, and suggest “additional” benefit with more than double the exercise minimum. However, the guidelines note that there is a lack of evidence for an upper limit of health benefit. We set out to define the dose-response relationship between leisure-time physical activity and mortality and to determine the upper limit of benefit associated with higher levels of aerobic exercise. Medical Research: What are the main findings? Dr. Arem: We found that study participants who met the recommended minimum level of leisure-time physical activity derived most of the mortality benefit, with a 31% lower risk of death compared to inactive individuals. Study participants who engaged in three to five times the recommended minimum level of leisure-time physical activity had a marginally increased mortality benefit, with a 39% lower risk of death compared to inactive individuals. Three to five times the recommended minimum is equivalent to a weekly minimum of walking 7 hours or running 2 hours 15 minutes.
Author Interviews, Exercise - Fitness, JAMA / 06.04.2015

Klaus Gebel GradDipExRehab, MExSc, MAppSc, PhD Senior Research Fellow Centre for Chronic Disease Prevention College of Public Health, Medical & Veterinary Sciences James Cook University Cairns AUSTRALIAMedicalResearch.com Interview with: Klaus Gebel GradDipExRehab, MExSc, MAppSc, PhD Senior Research Fellow Centre for Chronic Disease Prevention College of Public Health, Medical & Veterinary Sciences James Cook University Cairns Australia Medical Research: What is the background for this study? Response: The physical activity guidelines in most countries recommend for adults to accumulate at least 150 minutes of moderate physical activity (e.g. brisk walking) or 75 minutes of vigorous activity (e.g. jogging or cycling) or an equivalent combination of moderate and vigorous activities where 2 minutes of moderate-intensity activity counts the same as 1 minute of vigorous-intensity activity. However, there have only been a few studies that examined the health benefits of different proportions of moderate and vigorous activity in the composition of total activity. The objective of this study was to examine whether the proportion of total moderate-to-vigorous activity that is achieved through vigorous activity is associated with all-cause mortality, independently of the total amount of moderate-to-vigorous activity. Data were used from the 45 and Up study from the state of New South Wales in Australia, the largest cohort study ever conducted in the Southern hemisphere. Medical Research: What are the main findings? Response: During 1,444,927 person-years of follow-up, 7,435 deaths were registered. Compared with those who reported no moderate-to-vigorous activity (crude death rate=8.34%), the adjusted hazard ratios for all-cause mortality were 0.66 (95% CI 0.61-0.71; crude death rate=4.81%), 0.53 (0.48-0.57; 3.17%), and 0.46 (0.43-0.49; 2.64%) for reporting 10-149, 150-299, and for ≥300 minutes of activity per week respectively. Among those participants who reported any moderate-to-vigorous physical activity, the proportion of vigorous activity showed a dose-response relationship with all-cause mortality: compared with those reporting no vigorous activity (crude death rate=3.84%) the fully-adjusted hazard ratio was 0.91 (95% CI=0.84-0.98; crude death rate=2.35%) in those who reported some vigorous activity (but <30% of total activity); and 0.87 (0.81-0.93; 2.08%) among those who reported ≥30% of activity as vigorous. These associations were consistent in men and women, across categories of body mass index and volume of moderate-to-vigorous physical activity, and in those with and without existing cardiovascular disease or diabetes mellitus.