Author Interviews, Diabetes, Lancet, McGill / 13.06.2015

MedicalResearch.com Interview with: Dr Ahmad Haidar Ph.D. Division of Experimental Medicine Department of Medicine, McGill University Montreal, QC, CanadaDr. Ahmad Haidar Ph.D Division of Experimental Medicine, Department of Medicine McGill University, Montreal, QC, Canada Medical Research: What is the background for this study? What are the main findings? Dr. Haidar: This is the first head-to-head-to-head comparison in outpatient setting of dual-hormone artificial pancreas, single-hormone artificial pancreas, and conventional pump therapy in children and adolescents with type 1 diabetes. The main finding is that the dual-hormone artificial pancreas seems to outperform the other two systems in reducing nocturnal hypoglycemia in camp settings when the patients are very physically active during the day. Medical Research: What should clinicians and patients take away from your report? Dr. Haidar: Glucagon has the potential to reduce nocturnal hypoglycemia if added to the artificial pancreas. However, this needs to be confirmed in larger and longer studies as the single-hormone artificial pancreas might be sufficient in home settings (this study was conducted at a camp, which is an environment different that home). (more…)
Author Interviews, Cost of Health Care, Endocrinology, OBGYNE, Yale / 12.06.2015

Aileen Gariepy, MD, MPH Assistant Professor Section of Family Planning Department of Obstetrics, Gynecology, and Reproductive Sciences Yale School of Medicine New Haven, CT 06510MedicalResearch.com Interview with: Aileen Gariepy, MD, MPH Assistant Professor Section of Family Planning Department of Obstetrics, Gynecology, and Reproductive Sciences Yale School of Medicine New Haven, CT Medical Research: What is the background for this study? What are the main findings? Dr. Gariepy: Women who have just given birth are often highly motivated to prevent a rapid, repeat pregnancy.  For women who desire the contraceptive implant, a highly effective reversible form of contraception that is placed in the arm and can last for 3 years, new research shows that it is more cost-effective to place the implant while women are still in the hospital after giving birth, compared to delaying insertion to the postpartum visit 6-8 weeks later which is currently the most common practice. When the costs associated with the implant insertion and the costs of unintended pregnancy are compared in women who receive immediate contraceptive implant insertion (while still in the hospital after giving birth) to women who are asked to come back in 6-8 weeks for the implant insertion (delayed insertion), immediate insertion is expected to save $1,263 per patient.  Based on these estimates, for every 1,000 women using postpartum implant, immediate placement is expected to avert 191 unintended pregnancies and save $1,263,000 compared with delayed insertion in the first year. Cost savings would continue to increase for the second and third year after insertion. In fact, over half of U.S. pregnancies are unintended.  Maternal and infant care costs for unintended pregnancies amount to $11.1 billion annually for public insurance programs alone. The immediate postpartum period (after delivery but before discharge home) provides an ideal opportunity for initiating contraceptives as patients are motivated and timing is convenient. However, the majority of insurance company policies do not provide coverage for insertion of the contraceptive implant when the new mother is still in the hospital.  This lack of reimbursement is the most significant barrier to providing this highly effective contraceptive method for women who have just delivered a baby.  Surprisingly, the reason most insurance companies do not offer reimbursement for immediate insertion is due to an outdated insurance protocol, “the global obstetric fee” which precludes separate reimbursement of individual procedures (like inserting the implant). The main reason that immediate insertion results in cost savings is because more women will get the implant compared to a strategy of delayed insertion.  Women can get pregnant again within 4 weeks of delivering a baby.  Starting contraception as soon as possible after giving birth is important because most women will resume sexual activity before their postpartum office visit and therefore will be at risk of pregnancy. And approximately 35% of women do not return for a postpartum visit. Even for women who want another pregnancy soon, the implant has benefits.  When women conceive and deliver a baby within 2 years of last giving birth, there is a significantly higher risk of poor maternal and neonatal outcomes, including preterm birth, low birth weight, and even early neonatal and maternal death.  Birth spacing is better for moms and babies. (more…)
Author Interviews, Cost of Health Care, JAMA, NYU, Surgical Research / 12.06.2015

Joseph A. Ladapo, MD, PhD Assistant Professor of Medicine Section on Value and Effectiveness Department of Population Health NYU School of MedicineMedicalResearch.com Interview with: Joseph A. Ladapo, MD, PhD Assistant Professor of Medicine Section on Value and Effectiveness Department of Population Health NYU Langone School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Ladapo: Routine tests before elective surgery are largely considered to be of low value, and they may also increase costs.  In an attempt to discourage their use, two professional societies released guidance on use of routine preoperative testing in 2002. We sought to examine the long-term national effect of these guidelines from the American College of Cardiology/American Heart Association and the American Society of Anesthesiologists on physicians' use of routine preoperative testing. While we found that overall rates of routine testing declined across several categories over the 14-year study period, these changes were not significant after accounting for overall changes in physicians’ ordering practices. Our findings suggest that professional guidance aimed at improving quality and reducing waste has had little effect on physician or hospital practice. (more…)
Author Interviews, OBGYNE, Weight Research / 12.06.2015

MedicalResearch.com Interview with: Theresa A Lawrie World Health Organization Department of Reproductive Health and Research Geneva, Switzerland MedicalResearch: What is the background for this study? Response: Excessive weight gain in pregnancy is associated with various undesirable outcomes in pregnancy. The aim of the review was to assess data from all relevant clinical trials in the field, to determine whether diet and/or exercise interventions during pregnancy were effective in reducing the chance of excessive weight gain in pregnancy. We also wanted to know whether these interventions could reduce the chance of having large babies (macrosomia), as this is associated with difficult labor, c/section, postpartum hemorrhage, birth injuries and other complications. MedicalResearch: What are the main findings? Response: Altogether 49 trials contributed data to the review. Approximately half the trials recruited women of any pre-pregnancy weight, the other half recruited women who were overweight or obese at the start of pregnancy. Most of the trials were conducted in high income countries. Interventions varied, some involved individual counseling, others group sessions, some were counseling interventions only, other programs were actively supervised by fitness trainers. Health outcomes for women receiving the intervention programs in addition to routine antenatal care (the intervention group) were compared with those of women receiving the routine antenatal care only (the control group). We found that diet or exercise or combined interventions led to an average 20% reduction in the number of women gaining excessive weight in pregnancy. This reduction was fairly consistent across the different types of interventions, although the largest effect was observed for combined diet and supervised exercise interventions. Overall findings suggested a small reduction in caesarean section (of about 5%) and in large babies (of about 7%).  However, a bigger reduction in large babies (in the region of a 19% reduction) was noted for exercise-only interventions, which were more likely to be supervised interventions. Other findings: We also found no difference in the risk of preterm birth between groups. Fewer women in the intervention group were assessed as having high blood pressure during pregnancy (although we assessed this as low quality evidence). Low quality evidence also suggested that women in the intervention group were likely to retain less weight at six months postpartum compared with the control group. Interestingly, data from two studies suggested that women receiving diet and exercise interventions were less likely to have babies with breathing difficulties at birth. These findings will hopefully be corroborated by other studies. A limitation of the review, is that we did not include gestational diabetes as an outcome as this is partly covered in a separate Cochrane review. Our exploratory analyses, however, suggested that there may be a reduction in gestational diabetes for certain types of interventions, and we hope to include these data in future review updates. In general, we did not find differences in outcomes for women according to pre-pregnancy weight or BMI. (more…)
Author Interviews, Cancer Research, Colon Cancer / 12.06.2015

MedicalResearch.com Interview with: Prof. Catherine Quantin Teaching Hospital, Department of Biostatistics and Medical Informatics France; Dijon University Hospital, Clinical Investigation Center, Clinical Epidemiology/Clinical Trials Unit, Dijon, France and Dr Michal Abrahamowicz Ph.D Department of Epidemiology, Biostatistics and Occupational Health McGill University, Montreal, Canada Medical Research: What is the background for this study? Response: One difficulty, common to prognostic studies of cancer, concerns the need to separate the effects of prognostic factors on different clinical endpoints, such as disease recurrence vs recurrence-free death. Some published prognostic studies used a Cox regression model that included recurrence as a time-dependent covariate, to assess the impact of recurrence on mortality, and to adjust for recurrence when estimating the effects of other prognostic factors on mortality. However, the Cox model is limited to the assessment of the effects of covariates on a single endpoint, such as death. This limitation is overcome by multi-state models, that make it possible to model alternative pathways of disease progression and to assess the impact of prognostic factors on both recurrence-free death vs death after recurrence, and recurrence followed by death. Another difficulty, is that the cause of death is not available or not accurately coded. Yet, some patients are likely to die of causes not related to the disease of primary interest, especially in cancers with longer survival and in those that affect older subjects. The effects of prognostic factors estimated with Cox model, or classic multi-state models, are not able to discriminate between their effects on the mortality due to cancer of primary interest vs natural mortality. However, age is a very strong predictor of overall mortality, but is not systematically associated with higher cancer-specific mortality. To deal with this difficulty, many prognostic studies use relative survival methods. The general idea is to use the mortality tables for the relevant general population to estimate survival corrected for the expected natural mortality, due to other causes of death. (more…)
Author Interviews, Education, Prostate Cancer, Urology / 12.06.2015

MedicalResearch.com Interview with: Prajakta Adsul, MBBS, MPH, PhD; Ricardo Wray, PhD, and Sameer Siddiqui, MD Center for Cancer Prevention, Research and Outreach Saint Louis University MedicalResearch: What is the background for this study? What are the main findings? Response: Patient decision aids are interventions designed to help patients engage in shared decision making with their providers when multiple choices with more or less equivalent efficacy are available for a particular medical decision. Several patient decision aids exists for numerous medical conditions and previous research has demonstrated them to be effective in improving the patient's knowledge and understanding of treatment options and their relative efficacy and side-effects and resulting in a higher proportion of decision that are consistent with patient's values and personal preferences. In the context of prostate cancer treatment, the practice of shared decision making is vital as highlighted by recent calls from the American Urological Association and the American Cancer Society. To aid with this process, several patient decision aids exist. However, the content presented, the format and presentation styles of decision aids can be variable and can have an influence on the choice made by the patients. The purpose of this study was to assess the characteristics of the patient decision aids designed for men facing prostate cancer treatment. We used the widely accepted International Patient Decision Aids Standards (IPDAS) for the assessment, supplemented with implementation criteria to strategize successful future improvement and promotion of decision aids in routine urological practice. The main findings of the review were that none of the decision aids reviewed met all standards. The aids had variable content, format and presentation of prostate cancer treatment information. Several decision aids were outdated and critical issues such as the risk of overtreatment and active surveillance as a treatment option for prostate cancer were not always covered in decision aids. (more…)
Author Interviews, Cognitive Issues / 12.06.2015

Dr. Li-Huei Tsai Ph.D. Professor and Director - Picower Institute For Learning and Memory Department of Brain and Cognitive Sciences Massachusetts Institute of Technology Cambridge, MA MedicalResearch.com Interview with: Dr. Li-Huei Tsai Ph.D. Professor and Director - Picower Institute For Learning and Memory Department of Brain and Cognitive Sciences Massachusetts Institute of Technology Medical Research: What is the background for this study? What are the main findings? Dr. Tsai: For a while now, we have been interested in observations made by many labs, including our own, that the accumulation of DNA lesions is a hallmark of the aging brain, and that mutations in DNA repair factors manifest in congenital and neurodegenerative disorders. However, the precise contribution of unrepaired DNA lesions to the development of neurological disorders remains poorly understood. A major confounding factor is that the sources that generate DNA lesions in the brain are not well characterized, and it is not known whether damage accumulates non-specifically throughout the genome, or whether there are certain regions that are more prone to accumulate DNA damage. In this regard, our study reports three major findings: (1) Physiological neuronal activity itself results in the formation of DNA breaks; (2) Neuronal activity-induced DNA breaks form at highly specific locations, including within the promoters of a subset of immediate early genes, including Fos, Npas4, and Egr1. These genes are also rapidly expressed in response to neuronal stimulation, and play crucial roles in experience-driven changes to synapses, and learning and memory; (3) Neuronal activity-induced breaks are generated by a topoisomerase, Topo IIβ, and Topo IIβ-generated DNA breaks facilitate the rapid expression of these immediate early genes following neuronal stimulation. (more…)
Author Interviews, Heart Disease, JAMA, Pulmonary Disease, Surgical Research / 12.06.2015

Louise Sun, MD SM FRCPC Assistant Professor Department of Anesthesiology, University of Ottawa Staff | Division of Cardiac Anesthesiology University of Ottawa Heart InstituteMedicalResearch.com Interview with: Louise Sun, MD SM FRCPC Assistant Professor Department of Anesthesiology, University of Ottawa Staff | Division of Cardiac Anesthesiology University of Ottawa Heart Institute Medical Research: What is the background for this study? What are the main findings? Dr. Sun: Preoperative testing provides important information for perioperative planning and decision-making. However, given the rapid increase in health care costs, there has been growing emphasis on the more rational use of resources and thus the need to better understand the utilization patterns of specific tests. Preoperative pulmonary function tests (PFTs) are important in helping perioperative physicians identify patients at risk for postoperative pulmonary complications, but few appropriate use guidelines exist for this test. We conducted a population-based study using linked administrative databases in Ontario, Canada to describe temporal trends in preoperative pulmonary function tests and assess whether the recent 2006 American College of Physicians (ACP) guidelines on risk assessment and prevention of postoperative pulmonary complications for non-cardiothoracic surgery influenced these trends. We examined 511,625 individuals undergoing non-cardiothoracic surgery, amongst whom 3.6% underwent preoperative pulmonary function tests while 3.3% had non-operative PFTs. Preoperative pulmonary function tests rates decreased over the study period and following the 2006 ACP guidelines while non-operative rates remained stable. By 2013, preoperative pulmonary function tests were performed in fewer than 8% of Ontario patients with risk factors for pulmonary complications, while preoperative testing rates among individuals without known respiratory disease had approached rates seen in the non-operative setting. The decreasing preoperative pulmonary function tests rates contrast starkly against concurrent increases in rates of other perioperative interventions such as preoperative anesthesia consultations and stress testing. (more…)
Author Interviews, Columbia, Heart Disease / 12.06.2015

Nicholas Tatonetti, PhD Department of Biomedical Informatics Department of Systems Biology, Department of Medicine Columbia University New York, NYMedicalResearch.com Interview with: Nicholas Tatonetti, PhD Department of Biomedical Informatics Department of Systems Biology, Department of Medicine Columbia University New York, NY Medical Research: What is the background for this study? What are the main findings? Dr. Tatonetti: For decades, researchers have studied the link between disease incidence and the seasons. We’ve known, for example, that those born when the dust mite population is highest (summer) will have an increased chance of developing asthma. Traditionally, diseases have been studied one at a time to identify these seasonal trends. Because of the rapid adoption of electronic health records, it is now possible to study thousands of diseases, simultaneously. That is what we did in this study. We evaluated over 1,600 diseases and discovered 55 that showed this seasonal trend. Many of these had been studied previously, but several are new discoveries — most prominently, we found that the lifetime risk of developing cardiovascular disease is highest for those born in the spring. (more…)
Author Interviews, Hospital Readmissions, JAMA, Stanford, Surgical Research / 12.06.2015

Jordan M. Cloyd, MD Department of Surgery Stanford University Stanford, CaliforniaMedicalResearch.com Interview with: Jordan M. Cloyd, MD Department of Surgery Stanford University Stanford, California Medical Research: What is the background for this study? What are the main findings? Dr. Cloyd: The motivation for the study was that, anecdotally, we had noticed that several of our patients who had been discharged on a weekend required readmission for potentially preventable reasons. We wanted to investigate whether the data supported the idea that weekend discharge was associated with a higher risk of hospital readmission. (more…)
Author Interviews, BMJ, Osteoporosis, Pediatrics / 12.06.2015

Anne Winther Msc Department of Health and Care Sciences, UiT The Arctic University of Norway Division of Rehabilitation Services, University Hospital of North Norway, Tromsø, NorwayMedicalResearch.com Interview with: Anne Winther Msc Department of Health and Care Sciences, UiT The Arctic University of Norway Division of Rehabilitation Services, University Hospital of North Norway, Tromsø, Norway Medical Research: What is the background for this study? What are the main findings? Response: Norway has one of the highest reported incidences of osteoporotic fractures in the world. Research on fracture risk has primarily focused on bone mass in the elderly. However, there is a growing awareness of the importance of bone mass during growth as a compensation for the inevitable bone loss and prevention of fractures in the elderly . A recent study on Norwegian adolescents´ lifestyle and bone health concluded  that peak bone mass seem to be modifiable by lifestyle factors as higher physical activity levels were strongly associated with bone mass. The other way around; low levels of physical activity may have considerable negative effects on bone health, and increasing sedentary behavior in place of sports and play during growth is worrying. In this study we explored the associations between self-reported hours spent in front of television/computers during weekends along with self reported hours spent on leisure time physical activities and bone mass density (BMD) levels at the hip. This population based study, Fit Futures 1 consisting of 388 girls and 359 boys 15-17 years old was conducted in 2010/2011, and repeated two years later including 66% of the original cohort (Fit Futures 2; 312 girls and 231 boys). Boys spent more time in front of computers and television than girls; approximately 5 and 4 hours, compared with 4 and 3 hours daily in weekends and weekdays, respectively. Physical activity levels were adversely related to leisure time computer use at weekends. However, 20 % of the girls and 25 % of the boys balanced 2-4 hours in front of the screen daily with more than 4 hours of sports and hard training per week. Screen time at weekends was negatively associated with bone mass density levels in boys and positively in girls, after adjustments of several confounders known to affect bone, including age, puberty, physical activity levels and weekday screen time. Moreover; these contrasting patterns persisted two years later. (more…)
Author Interviews, Neurological Disorders, PLoS, Psychological Science / 12.06.2015

Dr. rer. nat. Kristin Prehn, Dipl.-Psych. Charité Universitätsmedizin Berlin Department of Neurology & NeuroCure Clinical Research Cente Berlin GermanyMedicalResearch.com Interview with: Dr. rer. nat. Kristin Prehn, Dipl.-Psych. Charité Universitätsmedizin Berlin Department of Neurology & NeuroCure Clinical Research Cente Berlin Germany MedicalResearch: What is the background for this study? What are the main findings? Dr. Prehn: The study is based on the theory by renowned American psychologist Lawrence Kohlberg stating that people progress through different levels of moral reasoning. At lower levels, individuals judge moral issues based on self-interest or laws and rules. Individuals at the post-conventional level also take into account deeper principles and shared ideals. The Kohlbergian theory influenced moral psychology and education for decades. No study to date, however, had investigated in which way moral development is reflected in human brain structure and function. In our study, we compared gray matter brain volume in healthy young subjects who either reached the post-conventional level or did not reach that level so far. We found that subjects at the post-conventional level showed larger volume in a specific brain region of the prefrontal cortex which is essential for moral reasoning as well as the integration of emotion and cognition during human behavior. (more…)
Author Interviews, Breast Cancer, Duke, Genetic Research, JAMA / 11.06.2015

Michaela Dinan, Ph.D. Duke Clinical Research Institute and Duke Cancer Institute Department of Medicine Duke University School of Medicine Durham, North CarolinaMedicalResearch.com Interview with: Michaela Dinan, Ph.D. Duke Clinical Research Institute and Duke Cancer Institute Department of Medicine Duke University School of Medicine Durham, North Carolina Medical Research: What is the background for this study? What are the main findings? Response: I think it will be critical to further explore the implications of Oncotype DX breast cancer assay (ODX testing) in women with breast cancer.  The ODX test helps predict which cancers will be more aggressive as well as guide recommendations as to which patients would most likely benefit from chemotherapy. I think we should look to see what impact this test is really having on the use of chemotherapy and its associated costs and outcomes for real-world breast cancer patients. (more…)
Author Interviews, Brigham & Women's - Harvard, General Medicine, Hospital Readmissions / 11.06.2015

Jeffrey C. Schneider, M.D. Medical Director, Trauma, Burn & Orthopedic Program Assistant Professor, Dept. of Physical Medicine and Rehabilitation Harvard Medical School Spaulding Rehabilitation Hospital Boston, MA 02129MedicalResearch.com Interview with: Jeffrey C. Schneider, M.D. Medical Director, Trauma, Burn & Orthopedic Program Assistant Professor, Dept. of Physical Medicine and Rehabilitation Harvard Medical School Spaulding Rehabilitation Hospital Boston, MA 02129 Medical Research: What is the background for this study? What are the main findings? Response: Hospitalizations account for the largest share of healthcare costs in the U.S., comprising nearly one-third of all healthcare expenditures.  In 2011, readmissions within 30 days of hospital discharge represented more than $41 billion in hospital costs.  Financial penalties for excess 30-day hospital readmissions were instituted by the Centers for Medicare and Medicaid Services in 20124; more than 2,200 hospitals were fined a total of $280 million in reduced Medicare payments in fiscal year 2013. Most readmission risk prediction models have targeted specific medical diagnoses and have utilized comorbidities and demographic data as the central risk factors for hospital readmission. Yet, large U.S. administrative datasets have demonstrated poor discriminative ability (c-statistics: 0.55-0.65) in predicting readmissions. However, few studies have considered functional status as potential readmission risk factors. There is increasing evidence that functional status is a good predictor of other health outcomes.  To date, acute care hospital administrative databases do not routinely include functional status measures.  Therefore, inpatient rehabilitation setting is an ideal population in which to examine the impact of functional status on readmission risk, because: (1) inpatient rehabilitation patients often have complex care transitions after acute care discharge, and represent a significant proportion of total readmissions; 2) inpatient rehabilitation facilities routinely document functional status using a valid instrument—the FIM®; and (3) a majority of U.S. IRFs participate in one of the only national datasets that contain standardized functional data—the Uniform Data System for Medical Rehabilitation. Limitations of prior work include small and single-center study designs, narrowly defined patient populations, and defining readmissions beyond the 30-day period.  Overall, there is a lack of literature on the utility of function as a readmission predictor in a large population of medical patients. Moreover, function is a modifiable risk factor with potential to impact readmission outcomes if function-based interventions are instituted early. Therefore, the objective of this study was to compare functional status with medical comorbidities as predictors of acute care readmissions in the medically complex rehabilitation population. We hypothesized that acute care readmission prediction models based on functional status would outperform models based on comorbidities,and that the addition of comorbidity variables to function-based models would not significantly enhance predictive performance. (more…)
Annals Internal Medicine, Author Interviews, Infections / 11.06.2015

MedicalResearch.com Interview with: Dr. Philip Molloy, MD Imugen Medical Director Medical Research: What is the background for this study? What are the main findings? Response: There is a newly described tick-borne infection in the US, first case published in NEJM Man 2013 (from Imugen researchers).  We then developed and validated both PCR and serologic blood tests.  Physicians  started ordering these tests, and many additional cases were uncovered, 51 of which are described in this paper. Medical Research: What should clinicians and patients take away from your report? Response: Be aware of yet another pathogen transmitted to humans from ticks, and don't assume it's Lyme.  Tests are available to help sort it out.  Imugen has been offering these tests commercially since 2013. (more…)
Author Interviews, Cost of Health Care, Kaiser Permanente, Long Term Care, Medicare / 11.06.2015

Yan S. Kim, MD PhD Delivery Science Fellow Division of Research Kaiser Permanente Northern California Oakland, CA 94612MedicalResearch.com Interview with: Yan S. Kim, MD PhD Delivery Science Fellow Division of Research Kaiser Permanente Northern California Oakland, CA 94612 Medical Research: What is the background for this study? What are the main findings? Dr. Kim: Long-term care hospitals first emerged in the 1980s as an alternative to lengthy acute-care hospital stays for patients with complex medical problems who need prolonged hospital-level care.  In 2002, Medicare changed its payment method for these facilities from cost-based to a lump sum per admission based on the diagnosis.  Under this system, which is still in place, Medicare pays these hospitals a higher rate for patients who stay a minimum number of days based on the patient's condition.  Shorter stays are paid much less and longer stays do not necessary generate higher reimbursements. Using Medicare data, we analyzed a national sample of patients who required prolonged mechanical ventilation – the most common, and among the most costly, conditions for patients in long-term care hospitals – to examine whether this payment policy has created incentives to base discharge decisions on payments.  We found that in the years after the policy’s implementation there was a substantial spike in the percentage of discharges on and immediately after the minimum-stay threshold was met, while very few patients were discharged before the threshold. By contrast, prior to 2002, discharges were evenly distributed around the day that later became the short-stay threshold.  These findings confirm that the current payment policy has created unintended incentives for long-term care hospitals to base the timing of patient discharges on payments and highlight how responsive these hospitals are to payment incentives. (more…)
Author Interviews, Biomarkers, Lung Cancer, Wistar / 11.06.2015

MedicalResearch.com Interview with: Qihong Huang, M.D., Ph.D. Associate professor in the Tumor Microenvironment and Metastasis Program The Wistar InstituteQihong Huang, M.D., Ph.D. Associate professor in the Tumor Microenvironment and Metastasis Program The Wistar Institute Medical Research: What is the background for this study? What are the main findings? Dr. Huang: Lung cancer is the leading cause of cancer deaths in both men and women in the United States and results in more deaths globally than breast, prostate and colon cancers combined. While the five year survival rate for early stage non-small cell lung cancer (NSCLC) is above 50%, it is less than 5% in patients with metastatic disease.  Clearly, early detection can save lives, but accurate screening tests for high-risk individuals are still lacking. Although low dose computed tomography (LDCT) has been successfully used for screening in high-risk populations, multiple negative factors are associated with recurrent LDCT screening, including false-positives and false-negatives, unnecessary invasive procedures, radiation exposure, global availability of the technology and cost. Although several non-invasive tests for lung cancer using body fluids such as blood, urine or sputum are under investigation, none are currently available. When low dose computed tomography is used for screening, patients who are 50 years old or older are frequently diagnosed with pulmonary nodules.  However, only a small fraction of the nodules detected are subsequently diagnosed as lung cancer.  In cases where it is difficult to differentiate malignant from benign nodules, it is recommended that patients with these indeterminate nodules be followed with serial LDCT, which increases radiation exposure and financial cost. A simple, inexpensive blood test that differentiates malignant from benign nodules would fill an important clinical need. In this study, we validated AKAP4 as a highly accurate biomarker in a cohort of 264 blood samples from patients with known non-small cell lung cance and 135 controls samples from two different sites including a subset of controls with high risk lung nodules.   When all 264 lung cancers were compared with all 135 controls, the area under the ROC curve (AUC) was 0.9714. When 136 stage I NSCLC lung cancers were compared with all controls, the AUC is 0.9795, and when all lung cancer patients were compared to 27 controls with histologically confirmed benign lung nodules – a comparison of significant clinical importance – the AUC was 0.9825. AKAP4 expression increases significantly with tumor stage but independently of age, gender, smoking history or cancer subtype. Follow-up studies in a small number of resected NSCLC patients revealed a decrease of AKAP4 expression post-surgical resection that remained low in patients in remission and increased with tumor recurrence. AKAP4 is a highly accurate biomarker for the detection of early stage lung cancer, lung cancer recurrence, and distinguishing malignant from benign lung nodules. (more…)
Author Interviews, Cancer Research, JAMA, OBGYNE / 11.06.2015

MedicalResearch.com Interview with: Prof. Joris Vermeesch Hoofd Moleculaire Cytogenetica Coordinator Genomics Core University of Leuven, University Hospitals Leuven, Belgium Medical Research: What is the background for this study? What are the main findings? Dr. Vermeesch: We developed a novel analysis methodology for Noninvasive prenatal testing (NIPT), which not only interrogates the common trisomies, but looks at variations across all chromosomes.  We obtain a kind of genome wide copy number variation plot.  By applying this analysis method for Noninvasive prenatal testing, we have strict quality parameters.  If faulty, we ask for a second sample. In one pregnant woman, the second sample showed exactly the same aberrations as in the first sample.  We excluded this variation to be  caused by a maternal constitutional chromosomal rearrangement and also excluded this aberration to be from fetal origin.  This prompted us to assume a maternal cancer was the cause.  Three such cases were observed, all three women were referred to the oncology unit and all three were proven to show a cancer. (more…)
Author Interviews, Heart Disease, Karolinski Institute, NEJM, Technology / 11.06.2015

Jacob Hollenberg M.D., Ph.D. Assistant Professor, Cardiologist Head of Research, Centre for Resuscitation Science Karolinska Institutet, Stockholm, SwedenMedicalResearch.com Interview with: Jacob Hollenberg M.D., Ph.D. Assistant Professor, Cardiologist Head of Research, Centre for Resuscitation Science Karolinska Institutet, Stockholm, Sweden Editor’s note: Dr. Hollenberg and colleagues published two articles in the NEJM this week discussing CPR performed by bystanders in out-of-hospital cardiac arrests. MedicalResearch: What is the background for the first study? Dr. Hollenberg: There are 10,000 cases of cardiac arrest annually in Sweden. Cardiopulmonary Resuscitation (CPR) has been taught to almost a third of Sweden’s population of 9.7 million. In recent years the value of bystander CPR has been debated, largely due to a lack of a randomized trial demonstrating that bystander CPR is lifesaving. In this study, which included all cases of emergency medical services (EMS) treated and bystander-witnessed out-of-hospital cardiac arrests recorded in the Swedish Cardiac Arrest Registry from January 1, 1990, through December 31, 2011, our primary aim was to assess whether CPR initiated before the arrival of EMS was associated with an increase in the 30-day survival rate. MedicalResearch: What were the main findings? Dr. Hollenberg: Early CPR prior to arrival of an ambulance more than doubled the chance of survival. (30-day survival rate was 10.5% among patients who underwent CPR before EMS arrival, as compared with 4.0% among those who did not (P<0.001).) This association held up in all subgroups regardless of sex, age, cause of cardiac arrest, place of arrest, EKG findings or time period (year analyzed). MedicalResearch: How did the patients who survived cardiac arrest do from a disability standpoint? Dr. Hollenberg: We had cerebral performance scores from 474 patients who survived for 30 days after cardiac arrest. (higher scores indicate greater disability). At the time of discharge from the hospital, 81% of these patients had a score of category of 1. Less than 2% had category scores of 4 or 5. MedicalResearch: What should patients and providers take away from this report? Dr. Hollenberg:
  • For patients with an out-of-hospital cardiac arrest, CPR performed by bystanders before the arrival of emergency medical personnel, saves lives. This has been validated by both the size of this study and the consistency of the results over three decades.
  • CPR education needs to continue and to increase. In Sweden about one-third of the population has been taught CPR.       Legislation has recently been passed that mandates CPR be taught to all teenagers in school which should allow an entire generation to become familiar with this lifesaving technique.
  • The willingness of the public to become involved also needs to increase. We need new ways of educating lay people to recognize cardiac arrest and to motivate them to perform it. The knowledge that bystander CPR saves lives may enhance that motivation.
(more…)
Author Interviews, BMJ, Gastrointestinal Disease, Immunotherapy / 11.06.2015

MedicalResearch.com Interview with: Nynne Nyboe Andersen, MD, PhD student Department of Epidemiology Research Statens Serum Institut Copenhagen, Denmark Medical Research: What is the background for this study? What are the main findings? Dr. Andersen: The use of TNF-α inhibitors, including infliximab, adalimumab and certolizumab pegol to treat people with inflammatory bowel disease is increasing worldwide and has upgraded the medical treatment modalities. However, concerns about their safety, including an increased risk of serious infections have persisted because they suppress the immune system. Previous meta-analyses based on randomized controlled trials did not suggest an increased risk of serious infections in people with inflammatory bowel disease treated with TNF-α inhibitors compared to placebo. However, the trials included in the meta-analyses were designed to investigate efficacy, and not to analyze risk of rare adverse events such as serious infections and often represent selected populations. Therefore, observational studies are essential to evaluate safety in a real world setting; however, results from these studies have been conflicting. Thus, as the risk of infections associated with TNF-α inhibitor treatment in people with inflammatory bowel disease is unclear we aimed at investigating this potential risk in a population-based setting based on the entire Danish inflammatory bowel disease population. In a propensity score matched cohort we found a significant 63% increased risk of serious infections within 90 days after treatment initiation. When we prolonged follow-up to 356 days the risk was attenuated and no longer significant.  For site-specific serious infections, we found increased point estimates for sepsis, urological/gynecological infections, and skin and soft tissue infections; but these results should be interpreted cautiously because of limited power. (more…)
Author Interviews, JAMA / 11.06.2015

MedicalResearch.com Interview with: Andrew Grey, MD Department of Medicine University of Auckland Auckland, New Zealand Medical Research: What is the background for this study? What are the main findings? Dr. Grey: Observational research is commonly conducted and often published in prominent medical journals, leading to reporting of the results by news media. Because of methodological limitations, in particular the absence of random allocation of participants to the interventions being studied, observational studies cannot be used to draw conclusions about causality. We wondered whether these important study limitations were apparent in news reporting of observational studies. Our analysis demonstrated low levels of reporting of limitations of observational research in the Abstract section of published papers and accompanying journal press releases, and in news stories generated in response to publication of the research. The reporting of the limitation that causal inferences could not be drawn was very low. Failing to identify and report limitations of observational research might promote the initiation and/or continuation of medical practices based on low level evidence. (more…)
Author Interviews, Heart Disease, JACC, Yale / 10.06.2015

James V. Freeman MD, MPH, MS Yale University School of Medicine New Haven, CTMedicalResearch.com Interview with: James V. Freeman MD, MPH, MS Yale University School of Medicine New Haven, CT Medical Research: What is the background for this study? What are the main findings? Dr. Freeman: Atrial fibrillation (AF) substantially increases the risk of major adverse clinical outcomes such as stroke and death, but it can also cause frequent symptoms, affect patient’s functional status, and impair their quality of life. While prior studies have reported the range of AF-related symptoms in patient populations, these studies were generally from highly selected patients and referral based practices, and may not reflect results in community practice or results with contemporary AF management. Using the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF), a large, contemporary, prospective, community-based outpatient cohort, we evaluated the type and frequency of symptoms in patients with Atrial fibrillation. In addition, we measured the degree to which physician assessed symptom severity (using the European Heart Rhythm Association [EHRA] classification system) was correlated with patient reported quality of life (assessed by the Atrial Fibrillation Effect on QualiTy-of-life [AFEQT] questionnaire). Finally, we association between symptoms or quality of life with clinical outcomes, including death, hospitalization, stroke and major bleeding. In our community-based study, the majority of AF patients (61.8%) were symptomatic (EHRA >2) and 16.5% had severe or disabling symptoms (EHRA 3-4). EHRA symptom class was well correlated with the AFEQT quality of life score (Spearman correlation coefficient -0.39). Over 1.8 years of follow-up, Atrial fibrillation symptoms were associated with a higher risk of hospitalization (adjusted HR for EHRA ≥2 vs EHRA 1 1.23, 95% CI 1.15-1.31) and a borderline higher risk of major bleeding. Lower quality of life was associated with a higher risk of hospitalization (adjusted HR for lowest quartile of AFEQT vs highest 1.49, 95% CI 1.2-1.84), but not other major adverse events including death. (more…)
Author Interviews, Autism, Education / 10.06.2015

Annette Estes, Ph.D. Research Associate Professor of Speech and Hearing Sciences Adjunct Research Associate Professor of Psychology Director, University of Washington Autism Center Susan & Richard Fade Endowed Chair Center on Human Development and Disability University of WashingtonMedicalResearch.com Interview with: Annette Estes, Ph.D. Research Associate Professor of Speech and Hearing Sciences Adjunct Research Associate Professor of Psychology Director, University of Washington Autism Center Susan & Richard Fade Endowed Chair Center on Human Development and Disability University of Washington Medical Research: What is the background for this study? What are the main findings? Dr. Estes: Although a number of studies have shown the positive effects of early intervention on children’s abilities during the preschool period, there have been few studies to date that have followed children longitudinally to find out if these gains are sustained.  We found that two years after completing the intervention, children maintained their gains in cognitive and adaptive behavior skills and also showed a reduction in autism symptoms.  The results suggest that early intervention results in long term benefits for children across a wide range of skills.  Children who received the ESDM intervention as toddlers later showed fewer autism symptoms at school age. Medical Research: What should clinicians and patients take away from your report? Dr. Estes: Early intensive behavioral intervention has been found to be efficacious in improving developmental outcomes for young children with autism spectrum disorder. Children were able to maintain the developmental gains that they made in early, intensive, in-home intervention over a 2-year follow-up period. These children did not exhibit developmental regression or lose skills, even after substantial reductions in services. Intellectual, language, and adaptive functioning gains made as a result of early intervention may generalize to new domains of functioning, such as reduced Autism Spectrum Disorder symptom severity, 2 years later. (more…)
Author Interviews, Psychological Science, Weight Research / 10.06.2015

MedicalResearch.com Interview with: Katie Becofsky Ph.D. Weight Control and Diabetes Research Center The Miriam Hospital Providence, RI Medical Research: What is the background for this study? What are the main findings? Dr. Becofsky: Previous research has provided clear evidence of a relationship between social relations (e.g., frequency of social participation, perceived social support) and mortality risk.  We investigated two specific aspects of social relations- source of social support and size of weekly social network- in more detail.  The purpose of our study was to examine the associations between different sources of social support (relative, friend, and partner support), as well as size (and source) of weekly social network, on mortality risk in a large cohort of patients from the Aerobics Center Longitudinal Study. We found that perceived support from one’s spouse/partner and relatives, as well as weekly social interaction with a network of 6-7 friends, was associated with lower long-term mortality risk.  When the sources were reversed, the effects did not stand- perceived social support from friends did not affect mortality risk, nor did the quantity of weekly familial contacts. (more…)
Author Interviews, Blood Pressure - Hypertension, JAMA, Surgical Research, UCSF / 10.06.2015

MedicalResearch.com Interview with: Susan Ming Lee, MD, FRCPC, MAS (Clinical Research) Clinical Instructor, Dept. of Anesthesia and Perioperative Care University of California, San Francisco Medical Research: What are the main findings? Dr. Lee: Angiotensin receptor blockers (often referred to as ARBs) are common medications used to treat high blood pressure, heart disease, and kidney disease.  Doctors sometimes stop these medications briefly around the time of surgery, since they are known to cause low blood pressure under general anesthesia.  Doctors may hesitate to restart ARBs after surgery because they are worried about low blood pressure or kidney function.  Prior to our research, there was little information to guide the optimal timing of restarting ARBs after surgery. Medical Research: What are the main findings? Dr. Lee: Our study of over 30,000 veterans shows that nearly one third of veterans admitted to hospital for non-cardiac surgery are not restarted on their usual ARBs within two days of their operation.  This delay in resuming ARBs is associated with increased death rates in the first month after surgery.  In fact, even accounting for factors that might contribute to why doctors would withhold ARB (such as low blood pressure, kidney dysfunction, or other comorbidities), 30-day postoperative mortality was increased approximately 50% in those without resumption of ARBs, and this effect was even greater in younger patients under age 60.  Our findings of reduced rates of infections, pneumonia, heart failure, and kidney failure in those that resumed ARBs soon after surgery suggest that early resumption may also reduce complications after surgery. (more…)
Author Interviews, CDC, Gastrointestinal Disease, JAMA, Pediatrics, Vaccine Studies / 10.06.2015

Eyal Leshem, MD Division of Viral Diseases, US Centers for Disease Control and Prevention, Atlanta, GeorgiaMedicalResearch.com Interview with: Eyal Leshem, MD Division of Viral Diseases, US Centers for Disease Control and Prevention, Atlanta, Georgia Medical Research: What is the background for this study? What are the main findings? Response: Routine vaccination of US children to protect against rotavirus began in 2006. The purpose of this study was to examine the effect of implementation of rotavirus vaccine on gastroenteritis and rotavirus hospitalizations of children younger than 5 years old. The main finding from this study is that hospitalizations for diarrhea in U.S. children younger than 5 years old decreased dramatically during 2008 to 2012 following implementation of routine rotavirus vaccination in 2006. Additionally, seasonal peaks of hospitalizations for rotavirus illness were considerably reduced after the vaccine was implemented compared to years prior to rotavirus vaccination. By 2012, rates of rotavirus hospitalization declined by approximately 90% across all settings and age groups. Factors such as increasing vaccine coverage as well as herd immunity resulting in less transmission of rotavirus may be responsible for this large decrease. (more…)
Annals Internal Medicine, Author Interviews, Insomnia, Psychological Science / 10.06.2015

MedicalResearch.com Interview with: Dr David Cunnington Sleep Physician & Director Melbourne Sleep Disorders Centre East Melbourne Australia Medical Research: What is the background for this study? What are the main findings? Response: Insomnia is a very common problem with 15-20% of adults having chronic insomnia, that is, trouble getting to sleep or staying asleep most days for  3 months or more. The most commonly used treatment is sleeping pills or hypnotics, however, they don’t address the underlying disorder, and come with potential side effects. Also, sleeping tablets just mask the symptoms, and as soon as tablets are stopped, symptoms recur. People with chronic insomnia think and behave differently around sleep, which perpetuates their symptoms. The key to improving symptoms in the long run is addressing thoughts and behaviours around sleep, which is what cognitive behaviour therapy does. Our study showed that cognitive behaviour therapy reduced the time taken to get to sleep by 20 minutes and reduced the amount of time spent awake after falling asleep by nearly 30 minutes. These effects were maintained out to 12 months after treatment. These reductions in time taken to get to sleep and time spent awake are similar to those reported in clinical trials of hypnotics.  (more…)
Author Interviews, CDC, Vaccine Studies / 10.06.2015

MedicalResearch.com Interview with: Dr. Pedro Moro, MD, MPH Immunization Safety Office Division of Healthcare Quality Promotion Centers for Disease Control and Prevention Atlanta, GA 3033 Medical Research: What is the background for this study? What are the main findings? Response: The Vaccine Adverse Event Reporting System (VAERS) is a US national vaccine safety surveillance system, co-administered by the Centers for Disease Control and Prevention (CDC) and the US Food and Drug Administration (FDA). VAERS accepts reports of adverse events (possible side effects) following vaccination. Anyone can submit a report to VAERS. The study team searched VAERS for US reports of death after any vaccination from 7/1/1997 to 12/31/2013. During that time period, VAERS received 2,149 death reports, with most (68.4%) occurring in children. Among children, the most common causes of death were: o   sudden infant death syndrome (44%) o   asphyxia, or lack of oxygen to the brain (6%) o   septicemia, or blood poisoning from a bacterial infection (5%) o   pneumonia (5%) Among adults, the most common causes of death were: o   diseases of the circulatory system (47%) o   diseases of the respiratory system (15%) o   infections and parasitic diseases (12%) o   tumors (4%) The main causes of death seen in VAERS reports were consistent with the most common causes of death in the US population. When studied separately, none of these causes of death have found to be related to vaccines. This finding is reassuring, and consistent with previous research on vaccine safety. (more…)
Author Interviews, Dermatology / 10.06.2015

MedicalResearch.com Interview with: Chante Karimkhani MD Columbia University College of Physicians and Surgeons, New York, New York, Erika Hagstrom MD Loyola University of Chicago Stritch School of Medicine, Maywood, Illinois Robert Dellavalle MD, PhD, MPH Department of Dermatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado; Dermatology Service, US Department of Veterans Affairs, Eastern Colorado Health Care System, Denver, Colorado; Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado MedicalResearch: What is the background for this study? What are the main findings? Response: Allocation of funding dollars to research is a critical and daunting task. While many factors may impact research-funding decisions, establishing a transparent priority-setting exercise is paramount. This is particularly important for the National Institutes of Health, which invests over $30 billion for medical research each year. Diseases that have the greatest impact on our population warrant increased research dollars to reduce disease burden. The Global Burden of Disease Study (GBD) is an epidemiological effort to quantify the global burden of disease in a universal metric called disability-adjusted life years (DALYs). Focusing on our particular interest of dermatology, we investigated the 2012-2013 NIH funding for 15 skin diseases and matched this to corresponding DALY metrics. Our results demonstrated that melanoma, non-melanoma skin cancer, and leprosy were over-funded by the NIH according to DALY metrics. In contrast, dermatitis, acne vulgaris, pruritus, urticaria, decubitus ulcer, fungal skin diseases, alopecia areata, cellulitis, and scabies appeared under-funded. Three skin diseases, bacterial skin diseases, viral skin diseases, and psoriasis, were well-matched in terms of NIH funding and disease burden. Disease burden is one of a myriad of factors that may impact funding priorities. (more…)