AHA Journals, Author Interviews, Stroke / 13.07.2015

MedicalResearch.com Interview with: Dr. Ángel Chamorro Director, Comprehensive Stroke Center Hospital Clinic Barcelona, Spain Medical Research: What is the background for this study? What are the main findings? Dr. Chamorro: There is a great need of new therapies in patients with acute stroke and our study is based on the clinical observation that patients with acute stroke recover better if at the time of the stroke the levels of uric acid are increased in their blood. That first observation led to a long way of research and administrative challenges but we finally came out with a solution of uric acid (a potent antioxidant) manufactured according to the strict rules which apply to drugs aimed for human use. Thus, we performed a pilot study that showed that uric acid could be safely administered to these patients. We then performed a larger clinical trial in 421 patients which provided very encouraging results overall. Now we are reporting in the Stroke journal appearing on July 9, that women obtained a much greater benefit than men because they had lower levels of uric acid than men because estrogens (female hormones) are efficient excretors of uric acid. In consequence, women were in greater need of uric acid replenishment following the stroke than men. (more…)
Author Interviews, Cancer Research, Cognitive Issues, Radiation Therapy / 13.07.2015

MB. Pinkham, Clinical Oncology Christie NHS Foundation Trust Manchester UKMedicalResearch.com Interview with: MB. Pinkham, Clinical Oncology Christie NHS Foundation Trust Manchester UK Medical Research: What is the background for this study? Response: Brain metastases are a serious complication of advanced malignancy and for most patients the objective is to maximise quality of survival. As treatment decisions become increasingly tailored to the individual, patient-focussed measures of efficacy such as neurocognitive function (NCF) are an important consideration. This is illustrated by the NCCTG N0574 randomised study reported last month at the American Society of Clinical Oncology (ASCO) 2015 Annual Meeting. 208 patients with 1-3 brain metastases each <3cm were randomised to stereotactic radiosurgery (SRS) or SRS with whole brain radiotherapy (WBRT). The addition of WBRT improved intracranial disease control but did not translate into a survival benefit and was associated with a decline in neurocognitive function at 3 months. The objective of our study was to describe the types of changes in neurocognitive function that can occur, summarise how they are assessed and review approaches used to mitigate their effects. We wanted to provide busy physicians with a clear and comprehensive overview of the topic that could be used to inform clinical decisions. Medical Research: What are the main findings? Response: Using sensitive tests, most patients with brain metastases have deficits in neurocognitive function at diagnosis. Evaluating and understanding changes after treatment is complex because neurocognitive function is a dynamic process that is influenced by a long list of inter-related factors. For patients treated using whole brain radiotherapy alone, worsening neurocognitive function is observed in about two-thirds within 2-6 months. Deficits in verbal memory and fine motor control are most common. It is unclear what proportion relates to treatment toxicity as opposed to disease progression or pre-terminal decline because both are unfortunately also common events during this interval. By contrast, in other patients, NCF improves after WBRT due to treatment response. For patients with 1-4 brain metastases treated using SRS, the addition of WBRT improves intracranial disease control at the expense of deficits in verbal memory at 4 months but the impact of recurrence and salvage therapy on neurocognitive function later than this is uncertain. Scant data suggests that some deficits in neurocognitive function after WBRT may improve with time in long term survivors. For patients with ≥5 brain metastases, SRS and/or systemic therapies may be considered in select patients instead of upfront whole brain radiotherapy but high quality evidence is lacking. Advanced radiotherapy technologies, such as hippocampal-sparing WBRT and post-operative cavity SRS, can limit the dose delivered to unaffected areas of the brain in the hope of reducing toxicity. Randomised studies assessing their efficacy and cost-effectiveness in various clinical situations are underway prior to routine use. Small but statistically significant improvements in certain neurocognitive domains can also be achieved using medications such as memantine and donepezil. Preclinical data suggests that some commonly available drugs (such as ramipril, lithium and indomethacin) may have neuroprotective properties following WBRT; further evaluation is warranted. (more…)
Author Interviews, CHEST, Clots - Coagulation / 13.07.2015

MedicalResearch.com Interview with: David Jimenez PhD, FCCP Respiratory Department and Medicine Department Ramon y Cajal Hospital IRYCIS, and Alcala de Henares University Madrid Spain Medical Research: What is the background for this study? What are the main findings? Dr. Jimenez: Normotensive patients that have an estimated high-risk for pulmonary embolism (PE)-related complications (i.e., intermediate-risk PE) might benefit from surveillance in an intensive care setting or from the administration of specific advanced therapy. The Bova score was developed for identifying these patients. This study confirms the validity and reproducibility of the Bova score. (more…)
Author Interviews, Genetic Research / 13.07.2015

MedicalResearch.com Interview with: Chun Chieh Fan Ph.D student USCD Cognitive Science and Professor Anders M. Dale Ph.D Department of Cognitive Science, Multimodal Imaging Laboratory, Department of Radiology University of California, San Diego School of Medicine La Jolla, CA 92037 Medical Research: What is the background for this study? What are the main findings? Response: The shape of human skull is closely associated with the ancestral background. Forensics uses it for determining ethnicity. Anthropologists use it to infer neuroanatomical change in human evolution. Yet it is unclear the inner content of skull, human brain, contains how much information about individual’s ancestry. Our study found that different continental ancestries are associated with unique cortical folding patterns. Even for contemporary populations in modern day USA, a melting pot of ethnicities, cortical folding patterns are highly predictive of the percentage of each continental ancestry, as determined based on the person’s genotype. These shape differences between ancestral heritages are not necessarily related to brain function. It is highly possible that the shape differences are resulting from a random process accumulated along human history, without significant functional consequences. (more…)
Author Interviews, Orthopedics, Surgical Research / 13.07.2015

Brett D. Owens, MD Professor of Orthopaedic Surgery Brown University Alpert Medical School Providence, RIMedicalResearch.com Interview with: Brett D. Owens, MD Professor of Orthopaedic Surgery Brown University Alpert Medical School Providence, RI Medical Research: What is the background for this study? What are the main findings? Response: Last year at this meeting we presented the results of a prospective multicenter study of collegiate contact athletes who experienced in-season shoulder instability events. While most were able to return to sport within a week, only roughly one quarter were able to successfully return without recurrent instability. We continued to follow this cohort and 39 athletes with additional eligibility the subsequent season. We found that 90% of the 29 who underwent arthroscopic stabilization successfully returned the next season compared with 40% of the 10 underwent nonoperative treatment (more…)
Author Interviews, Infections / 11.07.2015

Prof. Urs Greber, PhD Professor of Molecular Cell Biology Institute of Molecular Life Sciences University of Zurich Zurich, SwitzerlandMedicalResearch.com Interview with: Prof. Urs Greber, PhD Professor of Molecular Cell Biology Institute of Molecular Life Sciences University of Zurich Zurich, Switzerland Medical Research: What is the background for this study? What are the main findings? Prof. Greber: This study has addressed two fundamental questions in virology - how do non-enveloped viruses which are lipid-free penetrate through cell membranes, and how is this process tuned by host lipids? We found that certain neutral lipids, ceramide lipids, were upregulated during the entry process of human adenovirus into cells. The ceramide lipids enhanced the uptake of viruses into cells by endocytosis, and they boosted the disruption of endosomal vesicles which carried the virus,, and thereby enhanced infection. The ceramide lipids were found to be produced by the enzyme acid sphingomyelinase (ASMase), which was secreted from lysosomes to the plasma membrane upon virus attachment to cells. ASMase is a clinical target, and can be inhibited by the antidepressant amitriptyline, a small chemical compound, which is widely used to treat mental disorders. (more…)
Author Interviews, Cognitive Issues, Diabetes, JCEM / 11.07.2015

MedicalResearch.com Interview with: Wei-Che Chiu, MD, PhD National Taiwan University College of Public Health, Cathay General Hospital and Fu Jen Catholic University Taipei, Taiwan Medical Research: What is the background for this study? Response: Diabetes mellitus is a common risk factor for dementia and accounts for 6–8% of all cases of dementia in older populations. Cognitive impairment is associated with the presence of diabetic complications and diabetic severity, but the effects of diabetic severity on dementia are unclear. Our study was to investigate the association between the severity and progress of diabetes and the risk of dementia. Medical Research: What are the main findings? Response: The diabetic severity and progression reflected the risk of dementia, and the early progress in diabetic severity could predict the risk of dementia in new-onset diabetic patients. (more…)
Author Interviews, Beth Israel Deaconess, Cognitive Issues, Diabetes, Neurology / 11.07.2015

Vera Novak, MD PhD Associate Professor of Neurology Dept. of Neurology, Stroke Division Director Syncope and Falls in the Elderly Laboratory Beth Israel Deaconess Medical Center Boston, MAMedicalResearch.com Interview with: Vera Novak, MD PhD Associate Professor of Neurology Dept. of Neurology, Stroke Division Director Syncope and Falls in the Elderly Laboratory Beth Israel Deaconess Medical Center Boston, MA MedicalResearch: What is the background for this study? Dr. Novak: Diabetes mellitus (DM) is a major contributor to morbidity and mortality. Type 2 diabetes mellitus affects more than 44 million people in the U.S., and its numbers are growing rapidly, affecting up to 27% of older adults. Diabetes mellitus accelerates brain aging by about 5 years1, manifests as a widespread generalized atrophy2, and promotes earlier onset of vascular dementia and Alzheimer’s disease (AD).3,4 Diabetes mellitus -related atrophy manifests as worse cognitive function, memory, and gait, especially during a dual task, 5,6 and even a tight glycemic control did not improve cognitive function in participants of the large clinical trials 7. MedicalResearch: What are the main findings? Dr. Novak: Sixty-five participants (aged 66± 9.2 years) 35 with T2DM and 30 non-diabetic controls participated in this study. After 2 years of follow-up, participants with T2 Diabetes mellitus had diminished vascular reactivity in the brain (an ability to increase blood flow in responses to a task or metabolic demands) and performed worse on multiple cognitive tasks (in particular verbal learning and memory). In T2DM group, lower cerebral vasoreactivity correlated with worse performance on daily living activities. Specifically, the lower vasodilatation (ability to increase blood flow) was associated with worse mental functions. In addition, those with higher markers of inflammation had greater decline in vascular function in the brain. (more…)
Author Interviews, JCEM, Sexual Health, Testosterone / 11.07.2015

Darius A. Paduch, MD, PhDAssociate Professor of Urology and Reproductive Medicine Director Sexual Health and Medicine Research Director of Male Infertility Fellowship Co-Director Male Infertility Genetics Laboratory Weill Cornell Medical College Dept of Urology New York, NY 10065MedicalResearch.com Interview with: Darius A. Paduch, MD, PhD Associate  Professor of Urology and Reproductive Medicine Director Sexual Health and Medicine Research Director of Male Infertility Fellowship Co-Director Male Infertility Genetics Laboratory Weill Cornell Medical College Dept of Urology New York, NY 10065 Medical Research: What is the background for this study? What are the main findings? Dr. Paduch: Ejaculatory dysfunction, inability to ejaculate or delayed ejaculation affects 10-8% of men. Inability to ejaculate either intravaginally or at all is independent of erectile function. Men with normal erection may take very long time to ejaculate (>30 min) or not able to ejaculate at all. The men in our study had either normal erections or minimal erectile dysfunction. Men of all ages have spontaneous erections but don't ejaculate just from erection, it is progression of arousal and activation of spinal cord motor generator for ejaculation which is necessary for ejaculation. One of important factors in our ability to ejaculate is testosterone (T), testosterone allows for normal function of CNS centers for ejaculation, it is a modulator and is necessary; preadolescent boys don't ejaculate because their spinal cord centers for ejaculations are not mature – process dependent on testosterone. However testosterone is just one of many neurotransmitters and hormones needed of normal ejaculation. Actually our study showed that in men who achieved normal levels of testostosterone the ejaculatory function have improved. As this was first double blinded and randomized clinical trial we had to report our results based on radomization to testosterone treatment or placebo. Unfortunately only 70-80% of men treated with topical testosterone preparation will achieve normal testosterone level , we simply didn’t reach statistical significance based on randomization and  considering relatively low number of patients in each group. But in men who achieved normal testosterone levels the difference was statistically significant. Testosterone should not be used to treat any conditions, including ejaculatory dysfunction, in absence of low testosterone  level. EjD is very common but it bares significant embarrassment stigma, it is difficult for the couple to bear fact that male partner can’t ejaculate, it also creates issues within couple and question about attraction and fidelity. We have previously showed that treatment with tadalafil improves ejaculatory and orgasmic dysfunction and these data has been published. This study was focused on effect of testosterone, but its main significance was it’s design: we developed new tools to assess ejaculatory function and learned a lot about when patients or their partners start to be bothered by EjD. If time to ejaclate takes > 30 min We are now looking into novel and available pharmacotherapy modulating dopaminergic and canabioid signaling and reward mechanisms. I am also very excited about our potential work in direct spinal cord motor generator nano stimulator, this could be very useful for men with spinal cord injuries and diabetic patients. We paved the road for others and I am sure new treatments are just a matter of time. (more…)
Author Interviews, Heart Disease, Psychological Science, Sexual Health, University Texas / 11.07.2015

Amelia Stanton, Graduate Student Department of Psychology The University of Texas at Austin Austin, TXMedicalResearch.com Interview with: Amelia Stanton, Graduate Student Department of Psychology The University of Texas at Austin Austin, TX Medical Research: What is the background for this study? What are the main findings? Response: Heart rate variability (HRV) has emerged as a valuable non-invasive test to assess autonomic nervous system (ANS) activity. Several studies have linked low resting Heart rate variability to mental health conditions including depression, anxiety, and alcohol dependence, indicating these disorders may be related to an imbalance in autonomic activity. As Heart rate variability is an index of the balance of sympathetic nervous system (SNS) and parasympathetic nervous system activity (PNS), it has proven a useful tool for examining the relative role of SNS activity in female sexual arousal. Moderate SNS dominance (relative to PNS activity) has been shown to predict women’s genital arousal in the laboratory, while high levels of SNS activation have been shown to inhibit genital arousal. Based on this background evidence and on a growing clinical literature indicating that low HRV (generally indicative of high SNS) is associated with negative health outcomes, we predicted a positive linear relationship between Heart rate variability and sexual arousal function. That is, we predicted that women with autonomic balance indicating moderate or low resting SNS activity (relative to PNS activity) would be less likely than women with autonomic balance indicating high resting SNS to report clinically relevant sexual arousal dysfunction. We also predicted that this relationship would hold for overall sexual function. To test this hypothesis, sexual arousal function, overall sexual function, and resting HRV were assessed in 72 women, aged 18-39. The main finding of the study is that women with below average Heart rate variability were significantly more likely to report sexual arousal dysfunction (p < .001) and overall sexual dysfunction (p < .001) than both women with average HRV and women with above average HRV. Based on these results, we concluded that low HRV may be a risk factor for female sexual arousal dysfunction and overall sexual dysfunction. (more…)
Author Interviews, Colon Cancer, Duke, Weight Research / 10.07.2015

S. Yousuf Zafar, MD, MHS Associate Professor of Medicine Duke Cancer Institute Duke Clinical Research InstituteMedicalResearch.com Interview with: S. Yousuf Zafar, MD, MHS Associate Professor of Medicine Duke Cancer Institute Duke Clinical Research Institute Medical Research: What is the background for this study? What are the main findings? Dr. Zafar: Multiple studies have suggested that obesity and colorectal cancer are related. For instance, obesity has been linked with an increased incidence of colon cancer. Obesity has also been associated with a greater risk of colon cancer recurrence. To date, no study has looked at the role of obesity in outcomes for patients with metastatic colorectal cancer. In our study of over 6000 patients receiving treatment for metastatic olcolorectal cancer, we found that patients with the lowest body mass index (BMI) were at greatest risk for worse survival. This does not mean that obesity is good. More likely, it means that those who are very underweight are least able to tolerate the best treatment, or being very underweight is a biologic marker of poor prognosis. (more…)
Author Interviews, Blood Pressure - Hypertension, NYU, Pediatrics, Toxin Research / 10.07.2015

MedicalResearch.com Interview with: Teresa M. Attina, MD, PhD, MPH and Leonardo Trasande, MD, MPP Department of Pediatrics NYU Langone Medical Center Medical Research: What is the background for this study? Response: Phthalates are environmental chemicals widely used in consumer and personal care products, and often found in plastic to increase flexibility. Di-2-ethylhexylphthalate (DEHP) is of particular interest because industrial processes to produce food frequently use plastic products containing DEHP. Because recognition of potential health risks related to DEHP exposure has increased, DEHP is being replaced by di-isononyl phthalate (DINP) and di-isodecyl phthalate (DIDP), two phthalates with similar chemical properties. Specifically, DINP is used in plastic products for food packaging, and DIDP is used in furnishings, cookware, medications, and several other consumer products. These alternatives have not been substantially studied for toxicity in laboratory studies because these studies are not required for regulatory approval: unlike the EU, in the US the current regulatory framework assumes that chemicals are safe until proven toxic. Medical Research: What are the main findings? Response: We examined DINP and DIDP levels in urine samples from children and adolescents (6 to 19 years old) who participated in the National Health and Nutrition Examination Survey between 2009 and 2012, to assess if these levels were associated with blood pressure measurements. Diet, physical activity, gender, race/ethnicity, income, and other factors that can contribute to increased blood pressure were also included in the analysis. A significant association was found between high blood pressure and DINP/DIDP levels in study participants. This is not a cause-and-effect relationship but it suggests that phthalates may contribute to increased blood pressure. (more…)
Author Interviews, Gastrointestinal Disease, Microbiome, PLoS / 10.07.2015

MedicalResearch.com Interview with: Mashkoor A.  Choudhry, PhD Professor of Surgery, Microbiology & Immunology Burn & Shock Trauma Research Institute Stritch School of Medicine Loyola University Chicago Health Sciences Division Maywood, IL 60153 Medical Research: What is the background for this study? What are the main findings? Dr. Choudhry: Intestine is the major reservoir of bacteria in the body. We observed that gut bacterial composition is altered after burn injury. We found that burn causes a significant increase in Enterobacteriaceae, a group of bacteria that has the potential to be harmful for the host. Dysbiosis of the healthy intestinal microbiome is associated with a number of inflammatory conditions. (more…)
Author Interviews, Infections / 10.07.2015

MedicalResearch.com Interview with: Dr. J. Todd Kuenstner MD Clinical Laboratories Charleston Area Medical Center, Charleston, Virginia West Virginia School of Medicine, Charleston, West Virginia Medical Research: What is the background for this study? What are the main findings? Dr. Kuenstner: Prior to the advent of recent antiviral therapies with sustained virologic response rates (SVR) of 94%, ultraviolet blood irradiation (UVBI) was proposed as a method to improve the outcome of treatment with interferon and ribavirin which had an virologic response rates of 50%. This therapy was invented by Dr. Emmett Knott in 1928 and used to treat viral and bacterial infectious disease in the 1930s through the 1950s and an estimated 60,000 treatments were conducted in the United States by 1948. The AVIcure hemo-irradiator is a modification of the Knott Hemo-irradiator and meets contemporary safety standards. This study describes the FDA phase II controlled clinical trial that was conducted before the advent of sofosbuvir and ledipasvir with the AVIcure hemo-irradiator using ultraviolet blood irradiation (UVBI) for the treatment of 10 patients infected with the hepatitis C virus (HCV). This study is significant because of the potential of this device for treating other infectious diseases with few treatment options. This therapy was safe and beneficial in the 10 patients that were studied. At the nadir of the viral load, the mean reduction of hepatitis C viral load was 45% (p=0.0048) or 0.35 log viral load (p=0.015). Three of the patients in the group achieved a greater than 0.5 log viral load reduction at some point in the trial. The phase I controlled clinical trial of UVBI in patients with HCV infection on 10 patients (submitted for publication) showed that 7 of 10 patients had a greater than 0.5 log reduction in viral load and a mean viral load reduction of 56% and a mean log viral load reduction of 0.60 (p=0.039). In the phase II clinical trial, 8 of 10 patients also showed a concurrent reduction in their serum transaminase levels, mean reduction in AST of 15% (p=0.0069) and mean reduction in ALT of 19% (p=0.0031). The above phase II trial results were achieved in spite of two therapeutic “holidays” of 7 weeks duration during the trial and during these therapeutic “holidays” the patients did not receive any treatments. (more…)
Author Interviews, Cost of Health Care, OBGYNE, Yale / 10.07.2015

Xiao Xu, Ph.D. Assistant Professor Department of Obstetrics, Gynecology & Reproductive Sciences Yale School of MedicineMedicalResearch.com Interview with: Xiao Xu, Ph.D. Assistant Professor Department of Obstetrics, Gynecology & Reproductive Sciences Yale School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Xiao Xu: While research has shown hospital variation in costs of care for other conditions, we know little about whether and how hospitals differ in costs of childbirth related care. With nearly 4 million births each year, childbirth is the most common reason for hospital admission in the U.S. Understanding the pattern and causes of variation in resource utilization during childbirth among hospitals can help inform strategies to reduce costs. Our study used data from 463 hospitals across the country and analyzed hospital costs of maternity care for low-risk births. We found that hospital varied widely in average facility costs per maternity stay. (more…)
Author Interviews, Mayo Clinic, Opiods, Tobacco Research / 10.07.2015

W. Michael Hooten, M.D Professor of Anesthesiology Mayo ClinicMedicalResearch.com Interview with: W. Michael Hooten, M.D Professor of Anesthesiology Mayo Clinic Medical Research: What is the background for this study? Dr. Hooten: The purpose of the study was to investigate a gap in knowledge related to the progression of short-term opioid use to longer-term use. Medical Research: What are the main findings? Dr. Hooten: The main findings are that a history of substance abuse or tobacco use is associated with the progression from short-term to a longer-term pattern of opioid prescribing. (more…)
Author Interviews, Cancer, Cancer Research, Chemotherapy / 10.07.2015

MedicalResearch.com Interview with: Junichi Nishimura MD, PhD Assistant professor Osaka University in Japan Medical Research: What is the background for this study? What are the main findings? Dr. Nishimura: Oxaliplatin is classified as moderately emetogenic chemotherapy and 2-drug combination antiemetic therapy is recommended for Oxaliplatin based chemotherapy including FOLFOX and XELOX in all guidelines for antiemesis. Nausea and vomiting are still frequent adverse events which decrease the patient’s QOL. However, there was no study investigating whether 3-drug combination antiemetic therapy (5HT3 receptor antagonist+dexamethasone+aprepitant) reduce chemotherapy-induced nausea and vomiting. In this study, we conducted a multicentre, randomized phase III study to evaluate the usefulness of the combined use of aprepitant in colorectal cancer patients treated with Oxaliplatin based chemotherapy. In this phase III study, 3-drug combination therapy significantly increased the inhibition rate of vomiting which was the primary endpoint of this study. Moreover, the inhibition rate of nausea, complete response (no vomiting and no rescue medication use), and complete protection (no vomiting , no rescue medication use and no moderate or worsened nausea) was significantly higher in aprepitant group in overall and delayed phase. We, next, compared the inhibition of vomiting and nausea between males and females in delayed phase. When patients were grouped by sex regardless of the assigned treatment group, females were more affected by nausea and vomiting than males. Finally, in female, aprepitant did significantly prevent nausea and vomiting as well as increased chance of complete protection. (more…)
Author Interviews, Cancer Research, Colon Cancer / 10.07.2015

Howard S. Hochster, MD Associate Director, Yale Cancer Center Professor of Medicine, Yale School of Medicine New Haven, CT 06520MedicalResearch.com Interview with: Howard S. Hochster, MD Associate Director, Yale Cancer Center Professor of Medicine, Yale School of Medicine New Haven, CT 06520 Medical Research: What is the background for this study? What are the main findings? Dr. Hochster: TAS-102 is a novel anti-metabolite, recently combined with a metabolic inhibitor to make it orally bioavailable and active in the treatment of cancer.  In pre-clinical studies, it is non-cross reactive with 5FU.  What this means practically is that we have another chemotherapy agent that can be used for patients with colon cancer.  This drug will be an addition to the approved chemotherapy agents 5FU, oxaliplatin and irinotecan.  It may be combinable with these and with targeted agents to provide new active regimens. The main findings of the study were published in NEJM, May 15, 2015.  The study enrolled 800 patients randomized (2:1 ratio) to drug vs placebo.  Patients with advanced colon cancer who had been treated with all the previously approved drugs were eligible.  The drug was active in reducing time to tumor growth (Progression Free Survival) by 50% and improved overall survival for treated patients by about 25%. The data I presented at ESMO included a further analysis on specific genomic subsets of patients within the 800 patient study.  All patients were tested locally for RAS mutations and about 50% had such mutations (as expected).  There was no differences in benefit or toxicity for those with RAS wild-type tumors or RAS mutated tumors.  We also looked at those with BRAF mutations, but only 15% of patients were tested and this mutation occurs in about 8% of colon cancer, so we had very few patients with BRAF mutation.  Given this limitation, it appeared that this did not make a difference for benefit or toxicity either. (more…)
Author Interviews, Depression, Mental Health Research, Pediatrics / 10.07.2015

MedicalResearch.com Interview with: Katie Burkhouse, Graduate Student and Dr. Brandon Gibb Ph.D Professor of Psychology Director of the Mood Disorders Institute and Center for Affective Science Binghamton University Medical Research: What is the background for this study? What are the main findings? Dr. Gibb:  One of the strongest risk factors for depression is a family history of the disorder.  However, even among this at-risk group, the majority of children of depressed parents do not develop depression themselves.  For those who do become depressed, the depression can severely and negatively affect their social and academic functioning, become chronic or recurrent over the lifespan, and increase risk for suicide.  What is needed therefore, is a good indicator of which children may be at greatest risk for depression so that interventions can be targeted to these individuals.  We believe that pupil dilation may represent one such marker.  Changes in pupil dilation are associated with activity in the brain’s emotional circuits and have been linked in previous research to the presence of depression.  What my graduate student Katie Burkhouse found is that, even among children who are not currently experiencing symptoms of depression, the degree to which their pupil dilates when they look at pictures of sad faces predicts their risk for developing clinically significant episodes of depression over the next two years.  The findings were specific to pupil responses to sad faces and were not observed when children looked at happy or angry faces suggesting that there is something specific to how the children were processing sad images. (more…)
Author Interviews, Cancer Research, End of Life Care, JAMA / 10.07.2015

MedicalResearch.com Interview with: Jennifer Mack, MD, MPH Pediatric oncologist Dana-Farber/Boston Children’s Cancer and Blood Disorders Center Medical Research: What is the background for this study? What are the main findings? Dr. Mack: This study evaluated the intensity of end-of-life care received by adolescents and young adults (AYAs) with cancer. Little was previously known about the kind of end-of-life care these young patients receive. We evaluated the care of 663 Kaiser Permanente Southern California patients who died between the ages of 15 and 39 between the years 2001 and 2010. We found that more than two-thirds of adolescents and young adults received at least one form of intensive end-of-life care before death. This includes chemotherapy in the last two weeks of life (11%), more than one emergency room visit in the last month of life (22%), intensive care unit care in the last month of life (22%), and hospitalization in the last month of life (62%). Medical Research: What should clinicians and patients take away from your report? Dr. Mack: A majority of dying young people with cancer receive intensive measures at the end of life. Older patients who know they are dying usually do not want to receive intensive measures, which are associated with a poorer quality of life near death. High rates of intensive measures raise the concern that young people may experience unnecessary suffering at the end of life. However, it is also important to recognize that adolescents and young adult patients may have different priorities than older patients, and may be more willing to accept intensive measures in order to live as long as possible. Clinicians, patients, and family members should talk about what is most important to patients at the end of life so that their values can be upheld, whether patients prioritize doing everything possible to live as long as possible or focus on quality of life. Medical Research: What recommendations do you have for future research as a result of this study? Dr. Mack: Future research should further examine end-of-life decision-making for adolescents and young adults, including the reasons for receipt of intensive measures. Citation: JAMA Oncology irene.sege@childrens.harvard.edu MedicalResearch.com Interview with: Jennifer Mack, MD, MPH Pediatric oncologist Dana-Farber/Boston Children’s Cancer and Blood Disorders Center Medical Research: What is the background for this study? What are the main findings? Dr. Mack: This study evaluated the intensity of end-of-life care received by adolescents and young adults (AYAs) with cancer. Little was previously known about the kind of end-of-life care these young patients receive. We evaluated the care of 663 Kaiser Permanente Southern California patients who died between the ages of 15 and 39 between the years 2001 and 2010. We found that more than two-thirds of adolescents and young adults received at least one form of intensive end-of-life care before death. This includes chemotherapy in the last two weeks of life (11%), more than one emergency room visit in the last month of life (22%), intensive care unit care in the last month of life (22%), and hospitalization in the last month of life (62%). (more…)
Author Interviews, Education, Outcomes & Safety, Surgical Research / 10.07.2015

Judy A. Tjoe, MD, FACS Breast Oncology Surgeon Aurora Health Care Milwaukee, WIMedicalResearch.com Interview with: Judy A. Tjoe, MD, FACS Breast Oncology Surgeon Aurora Health Care Milwaukee, WI Medical Research: What is the background for this study? What are the main findings? Dr. Tjoe: Numerous national health organizations have confirmed minimally invasive breast biopsy (MIBB), which uses a percutaneous core needle as opposed to open surgical techniques, as the biopsy procedure of choice when a patient’s diagnostic test reveals a breast lesion suggestive of malignancy. Unfortunately, despite the overwhelming evidence supporting use of MIBB, open breast biopsy rates in the United States remain as high as 24-39%. Our study was designed to determine if measuring individual practice patterns and providing subsequent feedback to surgeons across a large, multihospital healthcare system would improve their adherence to the quality metric of using minimally invasive breast biopsy to diagnose indeterminate breast lesions. We found that the proportion of studied surgeons (n=46) appropriately adhering to the MIBB quality metric in every instance (i.e. those who achieved 100% adherence) significantly improved from 80.4% to 95.7% (p=0.0196) after receiving feedback on not only their own practice patterns, but those of their blinded peers. As might be expected, the handful of breast-dedicated surgeons (n=4) who cared for nearly half of the analyzed patient population achieved perfect adherence throughout the study, but interestingly, the gains made in total adherence were driven by the general surgeons (n=42), showing that the study’s direct educational efforts were effective in changing practice patterns for the better. These efforts included sending letters describing adherence to the quality metric to individual surgeons and organizational leadership. (more…)
Author Interviews, Cancer Research, End of Life Care, JAMA, Johns Hopkins / 10.07.2015

Amol Narang MD Radiation Oncology Resident Johns Hopkins MedicineMedicalResearch.com Interview with: Amol Narang MD Radiation Oncology Resident Johns Hopkins Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Narang: The care provided to cancer patients at end-of-life can be intense, including frequent ER visit, hospitalizations, and ICU stays in the last month of life, administration of chemotherapy in last two weeks of life, and late referrals to hospice. Providing high-intensity treatments at end-of-life has been associated with reduced patient quality-of-life and increased caregiver bereavement. Advance care planning represents an opportunity for patients to indicate their preferences for end-of-life care to try to ensure that the care that they receive at end-of-life is consistent with their values, and has been endorsed by oncologic professional societies, such as ASCO and the NCCN. As such, we wanted to assess if oncologists’ long-standing recognition of the merits of advance care planning has translated into increased participation in advance care planning by cancer patients, and to determine which forms of advance care planning are associated with intensity of care given at end-of-life. From 2000-12, we found that the only type of advance care planning that increased was the assignment of a power of attorney (52% in 2000 to 74% in 2012). However, having a power of attorney was not associated with receiving less aggressive end-of-life care. On the other hand, having a living wills and engaging in a discussion with a provider or loved one about preferences for end-of-life care were both associated with reduced treatment intensity. However, the frequency with which cancer patients created a living or discussed their preferences for end-of-life care did not increase over the study period; importantly, 40% of patients dying of cancer never communicated their preferences for care at end-of-life with anyone. (more…)
Author Interviews, Clots - Coagulation, JAMA, Surgical Research / 10.07.2015

Robert J. Lewandowski, MD FSIRAssociate Professor of Radiology Director of Interventional Oncology Department of Radiology Northwestern University Feinberg School of MedicineMedicalResearch.com Interview with: Robert J. Lewandowski, MD FSIR Associate Professor of Radiology Director of Interventional Oncology Department of Radiology Northwestern University Feinberg School of Medicine Medical Research: What is the background for this study? What are the main findings? Response: Retrievable inferior vena cava filters (rIVCF) were designed to provide temporary prevention from pulmonary embolism and then be removed when no longer needed. With permanent United States Food and Drug Administration (FDA) indication, these devices now account for the majority of IVC filters placed. Most rIVCFs placed are never removed because of poor clinical follow up, failed retrieval procedures, or patients not being offered the opportunity for filter removal secondary to prolonged dwell time; the latter has previously been correlated with retrieval failure. Retrievable IVCFs appear to be subject to greater device related complications (e.g., filter penetration of the IVC, filter migration, filter fracture) relative to permanent devices; furthermore, the rates of these complications appear to increase with filter dwell time. This prompted the FDA to issue a 2010 safety alert urging removal of rIVCFs once they are deemed no longer necessary. In the present study, we sought to determine whether rIVCF dwell time affects technical success of the retrieval procedure. Over a six-year period, 648 retrieval procedures were performed at our institution, with filter dwell times ranging from 0-108 months. We found that filter dwell time did not negatively impact IVC filter retrieval success nor did it increase our adverse events from the retrieval procedure. With advanced, adjunctive IVC filter retrieval techniques, rIVCFs can be safely and reliably removed despite long dwell times. (more…)
Author Interviews, Blood Pressure - Hypertension, BMJ, Kidney Disease / 10.07.2015

Gijs Van Pottelbergh, MD, PhD Department of Health and Technology Leuven University College Leuven, BelgiumMedicalResearch.com Interview with: Gijs Van Pottelbergh, MD, PhD Department of Health and Technology Leuven University College Leuven, Belgium Medical Research: What is the background for this study? What are the main findings? Response: Earlier research identified arterial hypertension as a cause of chronic kidney disease but in older persons the relation between blood pressure and kidney function is little investigated.This study analyses the relation between dynamic blood pressure measurements and kidney function over time. A decline in blood pressure over time turned out to be a strong risk factor for kidney function decline in all age strata. (more…)
Author Interviews, Dengue / 10.07.2015

MedicalResearch.com Interview with: Dr. Eng Eong Ooi BMBS PhD FRCPath Associate Professor & Deputy Director Program in Emerging Infectious Diseases Duke-NUS Graduate Medical School Singapore Medical Research: What is the background for this study? What are the main findings? Response: Dengue prevention continues to rely exclusively on vector control guided by disease and virologic surveillance. The latter has focused on detecting changes in the prevalence of the four antigenically distinct viral serotypes as, in general terms, herd immunity depends on long-lived serotype-specific antibodies.  However, epidemiological observations have indicated that a small number of changes within the viral genome have also been associated with several major outbreaks, without any change in viral serotype.  Identifying the genetic changes that alter viral fitness epidemiologically would thus be important to differentiate strains that have a greater potential of causing epidemics and targeted for control. Using the 1994 outbreak in Puerto Rico as a case in point, we identified nucleotide substitutions in the 3’ untranslated region (3’UTR) of the viral genome as critical determinants of dengue virus’ epidemiological fitness.  Mechanistically, mutations in the 3’UTR altered secondary viral RNA structures and changed the relative proportion of genomic to subgenomic RNA of the virus in infected cells.  The epidemiologically fitter viruses produced larger amounts of subgenomic to genomic RNA.  This subgenomic RNA then binds a host protein, TRIM25, which is a E3 ubiquitin ligase that polyubiquitylates RIG-I to amplify and sustain signalling for type-I interferon expression.  By binding to TRIM25, the subgenomic RNA of dengue virus inhibits the activation and thus enzymatic function of TRIM25.  We suggest that with reduced interferon expression, the virus was thus able to spread more effectively from cell to cell within the infected individuals to reach viremia levels for further subsequent mosquito-borne transmission. (more…)
Author Interviews, BMJ, CDC, OBGYNE / 10.07.2015

Jennita Reefhuis, PhD Epidemiologist with CDC National Center on Birth Defects and Developmental DisabilitiesMedicalResearch.com Interview with: Jennita Reefhuis, PhD Epidemiologist with CDC National Center on Birth Defects and Developmental Disabilities Medical Research: What is the background for this study? Dr. Reefhuis: There are previous reports on the link between birth defects and SSRIs. However, the results across some of these studies conflicted. It is not clear whether one SSRI might be safer than other SSRIs. Medical Research: What are the main findings? Dr. Reefhuis: Reassuringly, we found that the five earlier reported links between specific birth defects and sertraline were not found again. We did find that some birth defects occur two to three times more frequently among babies born to mothers who took paroxetine and fluoxetine in early pregnancy. (more…)
Author Interviews, Dermatology, NEJM / 10.07.2015

Prof. Dr. Kristian Reich, Dermatologikum Hamburg, Hamburg 07.04.2009 | Prof. Dr. Kristian Reich, Dermatologikum Hamburg, Hamburg, Germany, 07.04.2009 | [© (c) Martin Zitzlaff, Emilienstr.78, 20259 Hamburg, Germany, Tel. +491711940261, http://www.zitzlaff.com, martin@zitzlaff.com, Postbank Hamburg BLZ 20010020 Kto.-Nr. 10204204, MwSt. 7%, Veroeffentlichung nur gegen Honorar (MFM) und Belegexemplar, mit Namensnennung] MedicalResearch.com Interview with: Prof. Dr. med. Kristian Reich DERMATOLOGIKUM HAMBURG Hamburg Medical Research: What is the background for this study? What are the main findings? Prof. Reich: The Phase 2b X-PLORE study compared a new generation biologic therapy, guselkumab - an inhibitor of IL–23, with the anti–tumor necrosis factor (TNF)–alpha agent adalimumab (Humira®) and placebo in the treatment of moderate-to-severe plaque-type psoriasis. It showed that up to 86 percent of patients treated with guselkumab achieved a Physician’s Global Assessment (PGA) score of cleared psoriasis or minimal psoriasis at week 16, the study’s primary endpoint.  Interestingly, levels of efficacy were higher for several guselkumab doses through week 16 when compared to adalimumab. Improvements with guselkumab continued through week 40 with every eight- or twelve-week maintenance treatment.   (more…)