Author Interviews, JAMA, Stroke / 07.01.2016

MedicalResearch.com Interview with: Michael F. Waters, MD, PhD Department of Neurology Department of Neuroscience McKnight Brain Institute University of Florida College of Medicine Gainesville, Florida Medical Research: What is the background for this study? What are the main findings? Dr. Waters: This study was based on a subgroup of medically managed patients with severe, symptomatic, intracranial, atherosclerotic disease. Historically we know that these patients have a very high rate of additional strokes, and multiple studies have attempted to determine the best management for these patients. In SAMMPRIS, we were able to prove that aggressive medical management was superior to stenting in these patients. However, certain patients in the medically managed group still had a very high rate of repeat strokes, as much as 30% of those with certain risk factors. This study was an attempt to identify those risk factors to determine which patients were at the greatest risk for another stroke. (more…)
Author Interviews, Heart Disease, JAMA, Stanford, Surgical Research / 04.01.2016

MedicalResearch.com Interview with: Dr. Mary Hawn MD MPH Chair, Department of Surgery Stanford School of Medicine Stanford, California Medical Research: What is the background for this study? What are the main findings? Dr. Hawn: Patients with known coronary artery disease are at higher risk for adverse cardiac events in the peri-operative period.  Revascularization with coronary stents does not appear to mitigate this risk and in fact, may elevate the risk if surgery is in the early post-stent period.  Drug eluting stents pose a particular dilemma as these patients require 12 months of dual anti platelet therapy to prevent stent thrombosis, thus elective surgery is recommended to be delayed during this period.  In contrast, bare metal stents with early epithilialization are not at the same risk for stent thrombosis with anti platelet cessation.   In our retrospective cohort study, however, we observed that stent type was not a major driver of adverse events in the early post-stent period and that underlying cardiac disease and acuity of the surgery explained most of the risk.  We undertook this study to determine the influence of the underlying indication for the stent procedure on surgical outcomes over time following the stent. (more…)
Author Interviews, JAMA, Mental Health Research / 04.01.2016

MedicalResearch.com Interview with: Josephine Mollon MSc Department of Psychosis Studies Institute of Psychiatry, Psychology, and Neuroscience King’s College London London, England  Medical Research: What is the background for this study? What are the main findings? Dr. Mollon: Psychotic symptoms, such as hallucinations and delusions, are core features of psychotic disorders. A significant minority of the general population also reports subclinical psychotic experiences. Evidence suggests that these experiences may lie on a continuum with clinically significant psychotic symptoms. For example, cognitive deficits, which are a hallmark of psychotic disorders, are also seen in people with subclinical psychotic experiences. We used population-based survey data to characterize cognitive functioning in adults with psychotic experiences while adjusting for important sociodemographic characteristics and investigating the effect of age. The 171 (9.7%) adults with psychotic experiences showed significant memory and verbal deficits, but not IQ or processing speed deficits. Only participants 50 years and older with psychotic experiences showed medium to large impairments in general IQ, verbal knowledge, working memory and memory after adjusting for socioeconomic status, cannabis use, and common mental disorders. (more…)
Author Interviews, Beth Israel Deaconess, CT Scanning, JAMA, Neurological Disorders, Stroke / 04.01.2016

MedicalResearch.com Interview with: Sandeep Kumar, MD Assistant Professor of Neurology Harvard Medical School Director, Inpatient Stroke Service Department of Neurology, Stroke Division Beth Israel Deaconess Medical Center Boston, MA 02215 Medical Research: What is the background for this study? What are the main findings? Dr. Kumar: Transient deficits that start suddenly and typically last for a few minutes to a few hours are the hallmark of a transient ischemic attack (TIA) or a minor ischemic stroke. In this single-center observational study, we have reported similar clinical presentation in some patients with intracerebral hemorrhage (ICH) that are difficult to distinguish from cerebral ischemia based only on clinical signs and symptoms. (more…)
Author Interviews, Brigham & Women's - Harvard, JAMA, Prostate Cancer, Surgical Research, Testosterone / 04.01.2016

MedicalResearch.com Interview with: Quoc-Dien Trinh MD Assistant Professor, Harvard Medical School Brigham and Williams Hospital  Medical Research: What is the background for this study? What are the main findings? Dr. Trinh: Among elderly Medicare beneficiaries with metastatic prostate cancer, surgical castration is associated with lower risks of any fractures, peripheral arterial disease, and cardiac-related complications compared to medical castration using GnRH agonists. (more…)
Author Interviews, CT Scanning, JAMA, Lung Cancer / 02.01.2016

  MedicalResearch.com Interview with: Jan Marie Eberth, PhD Assistant Professor, Department of Epidemiology and Biostatistics Deputy Director, SC Rural Health Research Center Core Faculty, Statewide Cancer Prevention and Control Program Arnold School of Public Health University of South Carolina Columbia, SC 29208 Medical Research: What is the background for this study? Dr. Eberth: With the breakthrough findings of the National Lung Screening Trial released in 2011, professional organizations have largely embraced population-based screening guidelines for patients at high risk for lung cancer. The diffusion of screening into broad clinical practice has been slow to be adopted, given concerns about the efficacy of screening in community settings, lack of insurance reimbursement and unclear billing logistics, and difficulty weighing the pros of screening against the known cons (e.g., high rate of false positives). Medical Research: What are the main findings? Dr. Eberth: Provisions of the Patient Protection and Affordable Care Act mandate that US Preventive Services Task Force-recommended screening tests with an A or B rating receive full insurance coverage by private payers. The Centers for Medicare and Medicaid (CMS) soon thereafter approved full coverage for lung cancer screening in high-risk patients (i.e., those aged 55-77 years, asymptomatic for lung cancer, tobacco smoking history of 30+ pack-years, is a current smoker or has quit smoking within the past 15 years). Coding is rapidly evolving; as of November 2015, CMS released HCPCS codes G0296 (pre-screening counseling visit) and G0297 (screening visit). These codes will be accepted retroactively starting January 4, 2016 to the date of the final coverage determination (back to February 5, 2015). No coinsurance or deductibles shall be charged to the patient for either the pre-screening counseling visit, or the screening visit itself. Quality of screening  is an important, but understudied, area of research. Several publications have focused on aspects of quality programs, and how to achieve quality benchmarks, but data is still being collected to assess variation across programs. In the future, data from screening registries, such as the American College of Radiology Lung Cancer Screening Registry (LCSR), can be leveraged to examine these quality metrics and improve risk-prediction models for lung cancer. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Heart Disease, JAMA, Kidney Disease, Surgical Research / 29.12.2015

MedicalResearch.com Interview with: Azra Bihorac, MD, MS and Department of Anesthesiology Charles Hobson, MD, MHA Department of Surgery, Malcolm Randall Veterans Affairs Medical Center, Department of Health Services Research, Management, and Policy University of Florida Gainesville Florida  Medical Research: What is the background for this study? What are the main findings? Response:   Background is that as ICU clinicians we see acute kidney injury (AKI) and chronic kidney disease (CKD) frequently and have to deal with the consequences, and as AKI researchers we have shown that even mild and moderate AKI – even if there is complete resolution of the AKI by the time of hospital discharge – result in significantly increased morbidity and mortality for the surgical patient. Furthermore we are aware of the existing relationship between CKD and cardiovascular mortality, and we wanted to explore any relationship between AKI and cardiovascular mortality in the vascular surgery patients that we care for on a daily basis. The most important finding was the strong association between AKI and cardiovascular mortality in these patients – equal to the well-known association between CKD and cardiovascular mortality. (more…)
Author Interviews, Brigham & Women's - Harvard, End of Life Care, JAMA, Leukemia / 28.12.2015

MedicalResearch.com Interview with: Oreofe O. Odejide, MD Instructor in Medicine, Harvard Medical School Dana-Farber Cancer Institute Medical Research: What is the background for this study? What are the main findings? Dr. Odejide: The care that patients with hematologic cancers receive near the end of life is distinct from patients with solid tumors. For instance, previous research has shown that patients with blood cancers are more likely to receive intensive care at the end of life such as chemotherapy within 14 days of death, intensive care unit admission within 30 days of death, and they are less likely to enroll in hospice. My colleagues and I hypothesized that timing of discussions regarding end-of-life preferences with patients may contribute to these findings, and we wanted to examine hematologic oncologists’ perspectives regarding end-of-life discussions with this patient population. We conducted a survey of a national sample of hematologic oncologists obtained from the publicly available clinical directory of the American Society of Hematology. We received responses from 349 hematologic oncologists, giving us a response rate of 57.3%. In our survey, we asked hematologic oncologists about the typical timing of EOL discussions in general, and also about the timing of the first discussion regarding resuscitation status, hospice care, and preferred site of death for patients. Three main findings emerged:
  • First, the majority of hematologic oncologists (56%) reported that typical EOL discussions occur “too late.”
  • Second, hematologic oncologists practicing primarily in tertiary care settings were more likely to report late discussions compared to those in community settings.
  • Third, a substantial proportion of respondents reported that they typically conduct the initial discussions regarding resuscitation status, hospice care, and preferred site of death at less optimal times.
(more…)
Author Interviews, Infections, JAMA, Microbiome / 24.12.2015

MedicalResearch.com Interview with: Tara F Carr, MD Assistant Professor, Medicine and Otolaryngology Allergy and Immunology Fellowship Training Program Director Director, Adult Allergy Division of Pulmonary, Allergy, Critical Care and Sleep Medicine University of Arizona Tucson, AZ 85724 Medical Research: What is the background for this study? What are the main findings? Dr. Carr: Some patients with chronic rhinosinusitis continue to suffer from symptoms despite aggressive medical and surgical treatments. For these individuals, therapy is generally chosen based on bacterial culture results, and often includes the use of topical antibacterial rinses with a medication called mupirocin.  We found that if patients are still having problems after this treatment, the bacteria identified from repeated sinus cultures are very different than those usually expected, and in general more difficult to treat. (more…)
Author Interviews, Breast Cancer, Cancer Research, Chemotherapy, JAMA / 24.12.2015

MedicalResearch.com Interview with: Filippo Montemurro, M.D. Director, Investigative Clinical Oncology (INCO) Fondazione del Piemonte per l'Oncologia Candiolo Cancer Institute (IRCCS) Torino, Italy Medical Research: What is the background for this study? Dr. Montemurro: The evaluation of treatment-related side effects is a critical step in cancer patient management. It is important in the clinical practice, where the decision to modify doses, omit administrations or establish supportive care measures is based on treatment tolerance and side effects severity and duration. It is also important in the context of clinical trials. In the latter setting, the mere information of the antitumor activity of a new drug or regimen under investigation is worth little if it not accompanied by an accurate reporting of the side effect profile. For this reason, over the years reference protocols to standardize the process of toxicity reporting in clinical trials have been established. The most recent and widespread is the Common Terminology Criteria for Adverse Events (CTCAE), that is issued and constantly updated by the National Cancer Institute. The CTCAE allows the description of the incidence and on the grade of severity on a scale ranging from 0 (no toxicity) to 5 (death due to that toxicity). Normally, the medical or nursing staff data collects information to fill in the CTCAE reports either by interviewing patients or extracting data from the clinical notes taken by physicians. The "indirectness" of this process has consequences that are becoming acknowledged for their potential implications. The incidence and severity of toxicities results often underestimated by doctors when their reports are compared with corresponding reports provided directly by patients without intermediaries (so called Patient reported outcomes-PRO). If this phenomenon is described in the context of clinical trials, it might occur to a greater extent also in the clinical practice, where the process of toxicity reporting is not mandated by a protocol and no reference standard is recommended. Based on these premises, we designed a study to pursue two aims;
  • the first was to assess whether a 10-item questionnaire derived by the CTCAE could be used by breast cancer patients receiving adjuvant chemotherapy after surgery in the daily clinical practice;
  • the second was to compare doctors and patients reports of toxicities at corresponding time-points.
Medical Research: What are the main findings? Dr. Montemurro: We administered the 10-item questionnaire after the first and third cycle of adjuvant chemotherapy to 601 women who had undergone surgery for breast cancer. To develop this questionnaire, CTCAE definitions of severity for each item (nausea, vomiting, constipation, anorexia, dysgeusia, diarrhea, fatigue, pain, paresthesia, and dyspnea) were translated into Italian and rephrased into statements. Patients were asked to choose the statement that best represented the worst experience with that side effect after the reference cycle of chemotherapy. At the same time-points, research nurses extracted information from the medical charts and reported them in paired doctor questionnaires. A total of 99% and 97% of the patient returned filled in questionnaires. Pairwise comparisons showed that doctors systematically underestimated both incidence and severity for all the side effects. Interestingly, comparison of the two patient questionnaires revealed temporal changes that were possibly related to the effect of prophylactic measures taken after the first cycle (i.e. reduction in vomiting, diarrhea and pain) or to cumulative toxicties (i.e. worsening dysgeusia and dyspnea). No such changes except for worsening dyspnea were observed comparing the two doctors questionnaires. Finally, we found a direct relationship between number of patients and magnitude of discrepancy in side effects reporting was observed, suggesting that the workload could be a factor influencing this phenomenon. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, JAMA, Nutrition / 23.12.2015

MedicalResearch.com Interview with: Philipp Schuetz, MD, MPH University Department of Medicine Clinic for Endocrinology/Metabolism/Clinical Nutrition, Kantonsspital Aarau, Aarau, Switzerland Medical Faculty of the University of Basel Basel, Switzerland Medical Research: What is the background for this study? What are the main findings? Dr. Schuetz: Malnutrition is common in hospitalised patients and associated with detrimental metabolic consequences. The current clinical approach is to provide at risk patients nutritional support as a strategy to tackle malnutrition and its associated adverse outcomes. Yet, whether this strategy is effective and improves clinical outcomes in the medical inpatient population is unclear. In addition, recent trials from critical care have shown adverse outcomes when nutritional therapy was used too aggressively. Herein, our metaanalysis is the first to systematically investigate effects of nutritional support in medical inpatients. Our analysis shows that nutritional support is highly effective in increasing energy and protein intake and helps to stabilize weight loss. Also, risk for unplanned readmission after discharge from the hospital was reduced and length of stay was shorter in the patient population with established malnutrition. Yet, for other important clinical outcomes such as mortality and functional outcomes effects of nutritional support remained uncertain. Also, the quality of evidence was found to be moderate to low. (more…)
Author Interviews, Diabetes, JAMA, Ophthalmology, Telemedicine / 23.12.2015

MedicalResearch.com Interview with: Christina Y. Weng, MD, MBA Assistant Professor-Vitreoretinal Diseases & Surgery Baylor College of Medicine-Cullen Eye Institute  Medical Research: What is the background for this study? What are the main findings? Dr. Weng: Telemedicine has been around for a long time, but only recently have technological advances solidified its utility as a reliable, effective, and cost-efficient method of healthcare provision.  The application of telemedicine in the field of ophthalmology has been propelled by the development of high-quality non-mydriatic cameras, HIPAA-compliant servers for the storage and transfer of patient data, and the growing demand for ophthalmological care despite the relatively stagnant supply of eye care specialists.  The global epidemic of diabetes mellitus has contributed significantly to this growing demand, as the majority of patients with diabetes will develop diabetic retinopathy in their lifetime. Today, there are over 29 million Americans with diabetes, and diabetic retinopathy is the leading cause of blindness in working age adults in the United States.  The American Academy of Ophthalmology’s and American Diabetes Association’s formal screening guidelines recommend that all diabetic patients receive an annual dilated funduscopic examination.  Unfortunately, the compliance rate with this recommendation is quite dismal at an estimated 50-65%.  It is even lower amongst minority populations which comprise the demographic majority of those served by the Harris Health System in Harris County, Texas, the third most populous county in the United States. In 2013, the Harris Health System initiated a teleretinal screening program housed by eight of the district’s primary care clinics.  In this system, patients with diabetes are identified by their primary care provider (PCP) during their appointments, immediately directed to receive funduscopic photographs by trained on-site personnel operating non-mydriatic cameras, and provided a follow-up recommendation (e.g., referral for in-clinic examination versus repeat imaging in 1 year) depending on the interpretation of their images.  The images included in our study were interpreted via two different ways—once by the IRISTM (Intelligent Retinal Imaging Systems) proprietary auto-reader and then again by a trained ophthalmic specialist from the IRISTM reading center.  The primary aim of this study was to evaluate the utility of the auto-reader by comparing its results to those of the reading center. Data for 15,015 screened diabetic patients (30,030 eyes) were included.  The sensitivity of the auto-reader in detecting severe non-proliferative diabetic retinopathy or worse, deemed sight threatening diabetic eye disease (STDED), compared to the reading center interpretation of the same images was 66.4% (95% confidence interval [CI] 62.8% - 69.9%) with a false negative rate of 2%.  In a population where 15.8% of diabetics have STDED, the negative predictive value of the auto-reader was 97.8% (CI 96.8% - 98.6%). (more…)
Author Interviews, Cancer Research, Colon Cancer, Cost of Health Care, JAMA, Social Issues, University of Michigan / 23.12.2015

MedicalResearch.com Interview with: Christine Veenstra MD Clinical Lecturer, Internal Medicine Medical Oncology University of Michigan Ann Arbor, MI  48109-5343 MedicalResearch: What is the background for this study? What are the main findings? Dr. Veenstra: Patients with cancer face many costs and incur financial burden as they go through diagnosis and treatment. For working patients, cancer diagnosis and treatment may come with the additional burden of time away from work, lost income, and even long-term job loss. Although 40% of US workers do not have access to paid sick leave, we hypothesized that availability of paid sick leave could reduce the need to take unpaid time away from work during cancer treatment and might therefore be associated with job retention and reduced personal financial burden. In a survey of over 1300 patients with Stage III colorectal cancer, we found that only 55% of those who were employed at the time of their cancer diagnosis retained their jobs. Working patients with paid sick leave were nearly twice as likely to retain their jobs compared with working patients who did not have paid sick leave. This held true even when controlling for income, education and health insurance. Furthermore, working patients without paid sick reported significantly higher personal financial burden than those who had paid sick leave available. (more…)
Author Interviews, Cancer Research, JAMA, Lung Cancer, Surgical Research / 23.12.2015

MedicalResearch.com Interview with: Dr Najib Rahman D Phil MSc MRCP Consultant and Senior Lecturer Lead for Pleural Diseases Oxford Centre for Respiratory Medicine Clinical Director, Oxford Respiratory Trials Unit Tutor in Clinical Medicine University College, Oxford Medical Research: What is the background for this study? Dr. Rahman : Up to TIME1, the evidence base behind optimal pleurodesis for malignant pleural effusion in terms of tube size and analgesia was poor. Optimal pleurodesis in this context is one which is successful (i.e. the patient needs no further pleural interventions for that malignant effusion), but occurs with the minimum discomfort. This is particularly important as the treatment intent in malignant effusion pleurodesis is palliative. This is the first adequately powered randomized trial to address two important issues in pleurodesis for malignant pleural effusion - that of whether NSAIDs reduce pleurodesis efficacy, and if smaller chest tubes (12F) are "as good as" larger chest tubes (24F) for pleurodesis success and in terms of pain. Medical Research: What are the main findings? Dr. Rahman : The main and somewhat surprising findings are that:
  1. NSAIDs given short term but at high dose do not impair pleurodesis - they are no better than morphine for pain control (in fact, they needed modestly more rescue medication), but can be freely used during malignant effusion pleurodesis with no fear of reducing pleurodesis success.
  1. Smaller tubes were marginally less painful than larger tubes - but this difference was not clinically very relevant
  1. Smaller tubes cannot now be said to be "as good as" larger tubes for malignant effusion pleurodesis. Our data shows that they failed in non-inferiority to larger tubes for pleurodesis success at 3 months. 
  1. Smaller tubes resulted in higher fall our rates, a higher incidence of not being able to administer talc and were associated with more complications during insertion .
(more…)
Author Interviews, JAMA, MRI, Stroke / 22.12.2015

MedicalResearch.com Interview with: Sepideh Amin-Hanjani, MD FAANS FACS FAHA Professor & Program Director Co-Director, Neurovascular Surgery Department of Neurosurgery University of Illinois at Chicago Past Chair, AANS/CNS Cerebrovascular Section  Medical Research: What is the background for this study? What are the main findings? Dr. Amin-Hanjani: Posterior circulation strokes account for up to 30% of all ischemic strokes, and atherosclerotic occlusive disease of the vertebrobasilar (VB) is responsible for approximately one third of these cases. Symptomatic atherosclerotic VB occlusive disease is associated with a high risk of recurrent stroke despite medical therapy, in the range of 10-15% within 2 years. There have been advances in treatment options, particularly endovascular angioplasty and stenting, aimed at reverting the blockage; however these procedures themselves carry risks, and are likely to benefit only selected patients who are at highest risk without intervention. Our study, VERiTAS, aimed to determine if measurement of blood flow in the posterior circulation vessels could identify the high risk patients. Flow measurements were performed using the technique of quantitative magnetic resonance angiography (QMRA) relying on standard MR sequences and  the commercial software NOVA. These flow measurements were used to designate patients presenting with symptomatic vertebrobasilar disease as flow compromised or not, and patients were then followed for a median of 23 months in a blinded fashion to determine the risk of subsequent strokes. We found that among 72 such patients, only one quarter (18 patients) demonstrated flow compromise on QMRA, but that this group had a significantly higher risk of subsequent stroke at one year, 22% vs only 4% in the other group. The hazard ratio for subsequent stroke was markedly elevated at 11.5 even after adjusting for age and other stroke risk factors. (more…)
Author Interviews, Cost of Health Care, Education, JAMA / 16.12.2015

MedicalResearch.com Interview with: Lorette A. Stammen, MD Department of Educational Development and Research Faculty of Health, Medicine, and Life Sciences Maastricht University, Maastricht The Netherlands Medical Research: What is the background for this study? What are the main findings? Dr. Stammen: Research indicated that we can improve the quality of care and reduce the health care costs by eliminating health care waste. Health care waste are health care services that are not beneficial to patients. There are many ways to reduce health care waste, like through insurance and government policies modification,  but we were especially interested in how the medical expertise of physicians could improve high-value, cost-conscious care. We conducted a systematic review with the aim of understanding how training programs cause learning among physicians, residents and medical students. We analyzed 79 articles using realist review method and found three important factors that facilitate the learning of physicians (in training).
  • First, educational programs should focus on knowledge transmission. Knowledge that is essential entails knowledge regarding prices and general health economics, scientific evidence, and patient preferences.
  • Besides knowledge, the second factor of training for high-value, cost-conscious care is reflective practice. Reflective practice for example using feedback and asking reflective questions, by peers, colleagues and supervisors to reflect on decisions made in daily practice.
  • The third element of training programs should address an supportive environment in which physicians, residents and medical students learn. A supportive environment is important to cultivate the importance of high-value, cost-conscious care on multiple levels in the health care system. Since physicians are a part of a health care team their training programs should incorporate the training of health care professionals.
  • Furthermore, it is important that role models demonstrate high-value cost-conscious care.
(more…)
Author Interviews, JAMA, Pediatrics, Surgical Research / 16.12.2015

MedicalResearch.com Interview with: Dr. Peter C. Minneci, M.D., MHSc Center for Innovation in Pediatric Practice Assistant Professor, Pediatric Surgery The Ohio State's Wexner Medical Center Medical Research: What is the background for this study? What are the main findings? Dr. Minneci: Non-operative management of uncomplicated appendicitis has been shown to safe and effective studied in several international adult trials. To be a reasonable treatment alternative to urgent appendectomy, non-operative management of appendicitis in children must have a clinically acceptable success rate with minimal harm in patients that fail and subsequently undergo appendectomy. We performed a prospective single-institution patient choice trial allowing the families of children with acute uncomplicated appendicitis to choose between urgent appendectomy or non-operative management with antibiotics alone. We enrolled 102 patients, with 65 choosing surgery and 37 choosing non-operative management with antibiotics alone. Non-operative management had an in-hospital success rate of 94%, a 30-day success rate of 89%, and a 1-year success rate of 76%. Compared to the surgery group, patients managed non-operatively reported higher quality of life scores at 30 days and had significantly fewer disability days and lower costs, with no differences in the rates of complicated appendicitis or treatment-related complications at 1 year of follow-up. With this being said, there are some cases that I have read about where doctors have failed to diagnose patients for Appendicitis even after they have complained about having a number of the symptoms associated with it. Following this, some patients have even contacted companies like Negligence Claimline to get back what they deserve. You go to doctors as they are the ones who can help you get your health back in order, but when something like this happens, it is understandable as to why some people lose faith in this system. (more…)
Author Interviews, Gastrointestinal Disease, JAMA, Stem Cells / 16.12.2015

MedicalResearch.com Interview with: Dr. Chris J. Hawkey, DM, FRCP, FMedSci. University of Nottingham and Nottingham University Hospital England Medical Research: What is the background for this study?  Dr. Hawkey: ASTIC (The Autologous Stem Cell Transplantation International Crohn's Disease) systematically investigated the effect of immunoablation and autologous haemopoietic stem cell transplantation (HSCT) on objective signs of disease, symptoms and need for treatment and is the only controlled trial to have done so. The body’s immune system normally protects us from infections but in Crohn’s disease it turns on itself.  The treatment involves wiping out the body’s immune system (immunoablation) and replacing it with the patient’s own (autologous haemopoietic stem cell transplantation) innocent stem cells, a sort of immunological spring clean. Patients were randomly assigned to undergo transplantation (n=23) or just continue on best conventional treatment (n=22). ASTIC was stimulated by reports which suggested that long-term regression of disease amounting to potential cure could be achieved. But the treatment is hazardous with major potentially lethal risks, so recruitment to the trial was cautious and only the most resistant cases were studied. And we used the most stringent criteria ever developed for the trial’s primary endpoint. Medical Research: What are the main findings?  Dr. Hawkey: In fact the criteria we used for success were so stringent (no symptoms, no signs of disease on total bowel examination and no need for treatment) that few patients achieved them. Nevertheless, there were improvements in the individual measures underlying this composite endpoint. Objective signs of disease disappeared so that the gut looked normal from mouth to anus in about a quarter of actively treated patients vs no controls. Eight vs two patients were adjudicated free of active disease on endoscopy and radiology at final assessment (p=0.054). Patients were able to come off drug treatments: by the end of a year 61% of HSCT patients off immunosuppressive drugs for >3 months vs 23% of controls (p=0.012). Ten vs two patients had lost symptoms of active disease, eight vs two for of them for > 3 months (p=0.052). But treatment was challenging: there were 76 serious adverse events in HSCT patients (particularly infections) vs 38 in controls. One HSCT patient died. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Cancer Research, JAMA / 16.12.2015

MedicalResearch.com Interview with: Roger Stupp, MD Professor & Chairman Department of Oncology & Cancer Center University of Zurich & University Hospital Zurich (USZ) Zürich / Switzerland Medical Research: What is the background for this study? Dr. Stupp: Tumor Treating Fields are an entirely novel modality in cancer treatment. Over 10 years ago researchers demonstrated that alternating electrical fields will block cell growth, interfere with organelle assembly, in particular perturb the spindle apparatus and cell division, all leading to mitotic arrest and ultimately apoptosis. This was shown in vitro, but importantly also in vivo animal models including not only mice and rats, but also hamsters and rabbits with deep seated solid tumours. So the question was whether we can demonstrate such an effect also in the clinic. Glioblastoma are locally invasive and aggressive tumours in the brain. They usually do not metastasise however they grow diffusely within the CNS and despite the best possible surgery, radiation and chemotherapy virtually always recur. We thus applied alternating electrical fields therapy, so called Tumor Treating Fields to the scalp of patients with newly diagnosed glioblastoma. After the end of standard chemoradiotherapy (TMZ/RT), patients were randomized to receive either standard maintenance TMZ-chemotherapy alone or in combination with TTFields. Almost 700 patients were randomized, here we report on a preplanned interim analysis looking at the first 315 patients included once they were followed for at least 18 months. The data on the first 315 patients are mature and allowed the IDMC to conclude that the trial should be stopped and the results made available. Medical Research: What are the main findings? Dr. Stupp: The study demonstrated a consistent prolongation of both progression-free and also of overall survival for patients who have been treated with TTFields in addition to standard therapy. The median progression-free survival and overall survival were prolonged by 3 months, translating to an absolute increase in overall survival at 2 years of 14%, from 29% to 43%. Or a hazard ratio of 0.74 for overall survival and of 0.62 for progression-free survival. (more…)
Author Interviews, JAMA, Mental Health Research, MRI, Neurological Disorders / 12.12.2015

MedicalResearch.com Interview with: Stephane De Brito, PhD Birmingham Fellow School of Psychology Robert Aitken Building, Room 337a University of Birmingham  UK Medical Research: What is the background for this study? What are the main findings? Dr. De Brito: In the last decade, an increasing number of neuroimaging studies have used structural magnetic resonance imaging (sMRI) to examine the brains of youths who show behavioural problems that include antisocial and aggressive behaviour. Those studies have mostly relied on a method called voxel-based morphometry (or VBM), which is a whole-brain and automated technique that allows researchers to objectively assess the local composition of brain tissue, such as grey matter volume. The main problem is that the findings from those sMRI studies have been quite disparate and few have been replicated, partly due to differences in sample sizes and characteristics across studies. Therefore, we set out to carry out a meta-analysis of the available data to provide a clearer account of the literature on this topic. A particular strength of our meta-analysis is that we used the original brain imaging maps (also referred to as statistical parametric maps) from 11 of the 13 studies, which makes our analysis more accurate and reliable. The final sample comprised of 394 youths with behavioural problems and 350 typically developing youths, making it the largest study on this topic to date. Our results showed that, compared to typically developing youths, those with behavioural problems show reduced grey matter volume in the amygdala, the insula, and the prefrontal cortex. These brain areas have been shown to be important for decision-making, empathic responses, processing facial expressions and emotion regulation; key cognitive and affective processes that are shown to be deficient in youths with behavioural problems. (more…)
Author Interviews, Cancer Research, Chemotherapy, Dermatology, JAMA / 11.12.2015

MedicalResearch.com Interview with: Chia-Yu Chu, MD, PhD Associate Professor, Department of Dermatology National Taiwan University Hospital Medical Research: What is the background for this study? What are the main findings? Dr. Chia-Yu Chu: It has been well known that EGFR TKIs could cause skin toxicities (acneiform eruptions, pruritus, xerosis and paronychia). However, incidences of these skin toxicities have varied according to the different clinical trials, some of which even simply use “skin rash” instead of specific cutaneous findings in the reports. Afatinib, in contrast to first generation EGFR TKIs like gefitinib and erlotinib, is a second generation EGFR TKI with irreversible inhibition to not only EGFR, but also HER2 and ErbB4. Whether afatinib cause more skin toxicities remained unknown. Many of our patients received 2 or even 3 different EGFR TKIs with adequate drug exposure and washout period. Therefore, we had an opportunity to compare skin toxicities in “same patients” receiving different EGFR TKIs, and we found that around 30% of patients receiving afatinib developed paronychia whereas only 10% in gefetinib or erlotinib. This was the only significant difference between the 3 drugs. We also found afatinib treated patients needed significantly more dermatologic visits within 180 days of treatments and the reason was due to higher incidence of afatinib-related paronychia. Interestingly, regardless of causative agents, once skin toxicities developed they could be managed effectively in the same manners. (more…)
Author Interviews, Dermatology, Genetic Research, JAMA, Melanoma / 10.12.2015

MedicalResearch.com Interview with: Susana Puig MD PhD Chief Dermatology Service Research Director "Melanoma: Imaging, genetics and immunology" at IDIBAPS Consultant & Assistant Professor Melanoma Unit, Dermatology Department Hospital Clinic, University of Barcelona Barcelona Spain  Medical Research: What is the background for this study? What are the main findings? Dr. Puig: CDKN2A is the main high-penetrance melanoma susceptibility gene. A rare functional variant in MITF, p.E318K (rs149617956), has been identified as a moderate risk allele in melanoma susceptibility and also predisposes to renal cell carcinoma. In this study MITF p.E318K was associated with an increased melanoma risk (OR=3.3, p<0.01), especially in patients with multiple primary melanoma (OR=4.5, p<0.01) and high nevi count (>200 nevi) (OR=8.4, p<0.01). Interestingly, two fast growing melanomas were detected among two MITF p.E318K carriers during dermatologic digital follow-up. Furthermore, we have detected a similar prevalence of MITF p.E318K in CDKN2A wild-type and mutated individuals. (more…)
Author Interviews, Diabetes, JAMA, Pediatrics / 10.12.2015

MedicalResearch.com Interview with: Maria C. Magnus PhD Norwegian Institute of Public Health Department of Chronic Diseases Nydalen Norway Medical Research: What is the background for this study? What are the main findings? Dr. Magnus: Type 1 diabetes mellitus is one of the most common chronic diseases with onset in childhood, but environmental risk factors have not been convincingly established. A few previous studies report that childhood weight increase might influence the development of type 1 diabetes. This study combined information from two Scandinavian birth cohorts, including more than 99,000 children. The results showed that a higher weight increase during the first year of life increased the risk of type 1 diabetes. The same was not seen for height increase during the first year of life. (more…)
Author Interviews, Depression, Education, JAMA / 09.12.2015

MedicalResearch.com Interview with: Douglas A. Mata, M.D., M.P.H. Anatomic and Clinical Pathology Resident Physician, Brigham & Women’s Hospital Clinical Fellow, Harvard Medical School Boston, MA 02115 Marco A. Ramos, M.Phil., M.S.Ed. History of Science and Medicine M.D./Ph.D. Candidate, Yale School of Medicine New Haven, CT 06511 Medical Research: What is the background for your study? Dr. Mata: Training to be a doctor is clearly stressful, but the prevalence of depression among trainees is not well known. They may get especially depressed during their grueling years of residency, when young physicians are learning their craft by working long hours and taking care of critically ill patients. Coming up with a reliable estimate of the prevalence of depression among graduate medical trainees would help us identify causes of resident depression and begin to treat or prevent it. We thus aimed to find answers to two questions:
  • First, what percentage of new doctors might be depressed?
  • Second, how much has that changed over time?
Medical Research: What are the main findings? Dr. Mata: We set out to find every study ever published on this subject. We analyzed 50 years of research on depression in resident physicians. We collected and combined data from 54 studies conducted around the world, and found that a startling 29% of physicians in training have signs of depression. We also detected a small but significant increase in the prevalence of depression over the five decades the study covered. Mr. Ramos: Twenty-nine percent is a concrete number you can hang your hat on, so to speak. But this number alone doesn’t capture the extent of the problem. We conducted additional studies that revealed that up to 43% of residents have depressive symptoms. (more…)
Author Interviews, Education, JAMA / 09.12.2015

MedicalResearch.com Interview with: Henry Sondheimer, MD Senior director of student affairs American Association of Medical Colleges Medical Research: What is the background for this study? What are the main findings? Dr. Sondheimer: The background for this study in JAMA's Med Ed issue of December 8th is that a group of the medical schools' deans asked us (AAMC staff) in 2014 whether there was a differential in placement of African-American, Hispanic, and Native American graduates into Graduate Medical Education at the time of their graduation from medical school. In fact, as shown in this short paper, there is a difference with more current graduates from the under-represented in medicine graduates not beginning their GME immediately post-graduation. However, over time this difference diminishes substantially but does not disappear completely. (more…)
Author Interviews, Education, Electronic Records, JAMA / 08.12.2015

MedicalResearch.com Interview with: David Ouyang MD Department of Internal Medicine Stanford University School of Medicine Stanford, California Medical Research: What is the background for this study? What are the main findings? Dr. Ouyang: In American teaching hospitals, trainee resident physicians are an integral part of the medical team in performing procedures, writing notes, and coordinating care. As more care is being facilitated by electronic medical record (EMR) systems, we are just now finally able to understand how much residents work and how residents spend their time. In our study, we examined the types and timing of electronic actions performed on the EMR system by residents and found that residents spend about a third (36%) of their day in front of the computer and frequently perform many simultaneous tasks across the charts of multiple patients. Additionally, residents often do work long hours, with a median of 69.2 hours per week when on the inpatient medicine service. (more…)
Author Interviews, Cleveland Clinic, Emergency Care, JAMA, Stroke, Telemedicine / 08.12.2015

MedicalResearch.com Interview with: Ken Uchino, MD FAHA FANA Director, Vascular Neurology Fellowship Research Director, Cerebrovascular Center, Cleveland Clinic Associate Professor of Medicine (Neurology) Cleveland Clinic Lerner College of Medicine of CWRU Cleveland, OH 44195 Medical Research: What is the background for this study? What are the main findings? Dr. Uchino: Treatment for acute ischemic stroke is time dependent. Multiple studies have reported strategies to improve time to treatment after arrival in the hospital. Mimicking pre-hospital thrombolysis of acute myocardial infarction pioneered 30 years ago, two groups in Germany have implemented pre-hospital ischemic stroke thrombolysis using mobile stroke unit (“stroke ambulance”) that includes CT scan and laboratory capabilities. These units have been demonstrated to provide stroke treatment earlier than bringing patients to the emergency departments. Our report extends the concept mobile stroke unit further by using telemedicine for remote physician presence. The other mobile stroke units were designed to have at least one physician on board. This allows potential multiple or geographically distant units to be supported by stroke specialists. The study demonstrates that after patient arrival in the ambulance, the time to evaluation (CT scanning and blood testing) and to thrombolytic treatment is as quick or better as patient arrival in emergency department door. We are reporting the overall time efficiency after emergency medical service notification (911 call) in a separate paper. (more…)
Anemia, Author Interviews, Brigham & Women's - Harvard, JAMA, Transfusions / 07.12.2015

MedicalResearch.com Interview with: Dr. Walter H. Dzik MD Associate Pathologist, Massachusetts General Hospital Associate Professor of Pathology Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Dr. Dzik: Millions of Red Blood Cell transfusions are given each year.  To maintain adequate blood inventories worldwide, Red Blood Cell units are stored under refrigerated conditions.  Previous animal and laboratory research has highlighted the fact that red cells undergo biochemical, morphologic, and biophysical changes during prolonged refrigerated blood storage.    Researchers and clnicians have questioned whether the changes that occur during storage would impair the ability of transfused Red Cells to delivery oxygen to tissues. Our study was a randomized controlled trial conducted in patients with extreme anemia and insufficient global tissue oxygenation.    We randomly assigned children with severe anemia and lactic acidosis to receive Red Blood Cells stored 1-10 days versus Red Blood Cells stored 25-35 days.   We measured the recovery from lactic acidosis in response to transfusion in the two groups.   We also measured cerebral tissue oxygenation using a non-invasive tissue oximeter.    We found that the proportion of patients who achieved reversal of lactic acidosis was the same in the two RBC storage-duration groups.   The rate of decline of lactic acidosis was also equal.   There was also no difference in cerebral oxygenation, resolution of acidosis, correction of vital signs, clinical recovery, survival and 30-day followup.    (more…)
Author Interviews, Heart Disease, JAMA, Kidney Disease / 05.12.2015

MedicalResearch.com Interview with: Girish N. Nadkarni, MD, MPH Division of Nephrology, Department of Medicine Icahn School of Medicine at Mount Sinai New York, New York MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Nadkarni: Cardiovascular disease is one of the major causes of morbidity and mortality in patients with kidney disease. Moreover, there is a lack of good quality evidence in kidney disease patients. In addition, previous studies have shown that cardiovascular trials exclude patients with kidney disease. We wanted to analyze all of the clinical trials on acute myocardial infarctions and heart failure in the last decade and see if they continued excluding patients with kidney disease. We discovered that in 371 trials including close to six hundred thousand patients, the majority (57%) excluded patients with kidney disease. A large proportion of the trials excluded patients for non-specific reasons, rather than a prespecified threshold of kidney function and did not report kidney function at baseline. Finally, in trials that did include kidney patients and reported outcomes by kidney function, only 13% showed an interaction or suggestion of harm. (more…)
Abuse and Neglect, Author Interviews, JAMA, OBGYNE / 04.12.2015

MedicalResearch.com Interview with: Alex Haynes, MD, MPH Assistant Professor of Surgery, Harvard Medical School Assistant in Surgery, Massachusetts General Hospital Division of Surgical Oncology Associate Program Director, Safe Surgery, Ariadne Labs Research Associate Harvard School of Public Health and George Molina, MD, MPH Surgical Research Resident Massachusetts General Hospital  Medical Research: What is the background for this study? What are the main findings? Response: We have previously done work looking at the global volume of operations, and in particular the surgical volume at a country level. This work was based on the hypothesis that a certain level of surgical care is necessary for healthy populations. In doing this work, we found that cesarean delivery makes up a large proportion of all operations that happen globally. In the mid-1980’s, based on existing data the World Health Organization made the recommendation that at a country-level, the cesarean delivery rate should not exceed 10 to 15 per 100 live births. We wanted to see if this recommendation was still applicable using current data. In order to answer this question, we used multiple imputation to estimate country-level cesarean delivery rates for all 194 countries in the world in 2012 to investigate the association between country-level cesarean delivery rates and maternal and neonatal mortality. We found that at a population level, as the cesarean delivery rate increased up to about 19 per 100 live births, there was a decrease in country-level maternal and neonatal mortality. However, as country-level cesarean delivery rates rose above this level there were no associated changes in maternal or neonatal mortality. (more…)