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Author Interviews, JAMA, McGill, Parkinson's / 15.06.2015

Ron Postuma, MD, MSc Associate Professor Department of Neurology Montreal General Hospital Montreal, QuebecMedicalResearch.com Interview with: Ron Postuma, MD, MSc Associate Professor Department of Neurology Montreal General Hospital Montreal, Quebec Medical Research: What is the background for this study? What are the main findings? Dr. Postuma: The background is that we often think about Parkinson’s Disease as a single disease.  However, every clinician knows that there is a great deal of variability from patient to patient.  If we can understand the main aspects that separate patients into groups, we can target therapy better. The analysis used a semi-automated means to divide Parkinson’s patients into groups, using extensive information about motor and non-motor aspects of disease.  We found that the non-motor symptoms, especially cognition, sleep disorders, and blood pressure changes were the most powerful predictors of which group a patient would be in.  Based on these non-motor (and some motor aspects), the most accurate way to divide patients was into three groups - diffuse (many non-motor symptoms), pure motor, and intermediate (halfway between the other).  We then followed patients over time.  The diffuse group had, by far, the worse prognosis.  This was not only for the non-motor aspects, but the motor as well. (more…)
Author Interviews, Biomarkers, Leukemia, NYU, Pediatrics / 15.06.2015

Susan Schwab, PhD Assistant professor at NYU Langone Skirball Institute of Biomolecular Medicine MedicalResearch.com Interview with: Susan Schwab, PhD Assistant professor at NYU Langone Skirball Institute of Biomolecular Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Schwab:  T cell acute lymphoblastic leukemia (T-ALL) remains a devastating pediatric disease.  Roughly 20% of children do not respond to current therapies.  Furthermore, metastasis to the central nervous system is common in T-ALL, and intrathecal chemotherapy, even when successful at eradicating the cancer, causes serious long-term cognitive side-effects. Here we report that the chemokine receptor CXCR4 is essential for T cell acute lymphoblastic leukemia progression in both mouse and human xenograft models of disease.  Consistent with sustained disease remission in the absence of CXCR4, loss of CXCR4 signaling results in decreased levels of c-Myc, which is required for leukemia initiating cell activity.   T-ALL cells reside near cells generating the CXCR4 ligand CXCL12 in the bone marrow, and our data suggest that vascular endothelial cells may be an important part of the T-ALL niche. (more…)
Author Interviews, Cost of Health Care, Education, Johns Hopkins, Primary Care / 15.06.2015

MedicalResearch.com Interview with: Eric T. Roberts and Darrell Gaskin Johns Hopkins University Bloomberg School of Public Health Baltimore, MD Medical Research: What is the background for this study? What are the main findings? Response: This study looked at the implications of the Affordable Care Act’s expansion of Medicaid on the need for additional physicians working in primary care. Since 2014, 11 million low-income adults have signed up for Medicaid, and this figure will likely increase as more states participate in the expansion. Many new Medicaid enrollees lacked comprehensive health insurance before, and will be in need of primary and preventive care when their Medicaid coverage begins. In light of these questions, in this study, we projected the number of primary care providers that are needed to provide care for newly-enrolled adults. We forecast that, if all states expand Medicaid, newly-enrolled adults will make 6.1 million additional provider visits per year. This translates into a need for 2,100 additional full time-equivalent primary care providers. We conclude that this need for additional providers is manageable, particularly if Congress fully funds key primary care workforce training programs, such as the National Health Service Corps. (more…)
Author Interviews, Biomarkers, Kidney Disease, University of Pittsburgh / 14.06.2015

MedicalResearch.com Interview with: Raghavan Murugan MD, MS, FRCP, FCCP Associate Professor of Critical Care Medicine and Clinical and Translational Science Core Faculty, Center for Critical Care Nephrology, CRISMA Center, Raghavan Murugan MD, MS, FRCP, FCCP Associate Professor of Critical Care Medicine and Clinical and Translational Science Core Faculty, Center for Critical Care Nephrology, CRISMA Center, John Kellum, MD Professor and Vice Chair for Research Director, Bioengineering and Organ Support Program, CRISMA Center Director, Center for Assistance in Research using eRecord (CARe)John Kellum, MD Professor and Vice Chair for Research Director, Bioengineering and Organ Support Program, CRISMA Center Director, Center for Assistance in Research using eRecord (CARe) Department of Critical Care Medicine University of Pittsburgh Pittsburgh, PA Medical Research: What is the background for this study? What are the main findings? Response: In our prior studies, we found that nearly one-half of critically ill patients in the intensive care unit who receive dialysis die by 2 months after acute illness and more than one-third of surviving patients are dialysis dependent. We sought to examine whether simple patient characteristics and inflammatory biomarkers predicted death and non-recovery of kidney function after severe acute kidney injury. We found that a combination of four simple and readily available patient characteristics including older age, lower mean arterial pressure, need for mechanical ventilation, and higher serum bilirubin levels predicted death and dialysis dependence. Higher plasma concentration of interleukin (IL)-8 in combination with the clinical characteristics also increased risk prediction. To our knowledge, this study is the first large study to examine risk prediction for outcomes after severe acute kidney injury using a panel of biomarkers in a large cohort of critically ill patients receiving dialysis. (more…)
Author Interviews, Nutrition, PLoS, Race/Ethnic Diversity, Vanderbilt / 14.06.2015

MedicalResearch.com Interview with: Wei Zheng, MD, PhD, Professor of Medicine Anne Potter Wilson Chair in Medicine Director, Vanderbilt Epidemiology Center and Danxia Yu, PhD Research Fellow Vanderbilt Epidemiology Center Vanderbilt University School of Medicine Nashville, TN, 37203 Medical Research: What is the background for this study? What are the main findings? Response: The Dietary Guidelines for Americans (DGA) provide the most authoritative advice in the US about healthy eating. Higher adherence to the DGA, reflected by a higher Healthy Eating Index (HEI) score, has been found to be associated with lower risk of developing or dying from chronic diseases (e.g. diabetes, cardiovascular disease, and certain cancers) in several US studies. However, these studies recruited mostly non-Hispanic white individuals and middle to high income Americans. It has been reported that racial/ethnical background and socioeconomic status may influence food choices and diet quality. However, no previous study has adequately evaluated the association between adherence to the DGA and risk of death due to diseases in racial/ethnical minorities and low-income Americans. Therefore, it is uncertain whether the health benefits of adherence to the current DGA can be generalized to these underserved populations. We analyzed diet and mortality data from the Southern Community Cohort Study (SCCS), a large, prospective cohort study including approximately 85,000 American adults, 40-79 years old, enrolled from 12 southeastern states between 2002 and 2009. Two-thirds of the SCCS participants were African-American and more than half reported an annual household income <$15,000. During a mean follow-up of 6.2 years, we identified 6,906 deaths in the SCCS, including 2,244 from cardiovascular disease, 1,794 from cancer, and 2,550 from other diseases. Using multivariate analysis methods, we found that participants in the top 20% of the HEI score (highest adherence to the DGA) had only about 80% of the risk of death due to any diseases compared with those in the bottom 20% of the HEI score. This protective association was found regardless of sex, race and income levels. (more…)
Author Interviews, Beth Israel Deaconess, Blood Pressure - Hypertension, Technology / 14.06.2015

MedicalResearch.com Interview with: Neetika Garg, MD Fellow in Nephrology Beth Israel Deaconess Medical Center Division of Nephrology, Department of Medicine Boston, MA 02215 MedicalResearch: What is the background for this study? What are the main findings? Dr. Garg: One in every three Americans suffers from hypertension. Since high blood pressure (BP) frequently does not cause any symptoms, self-blood pressure monitoring at home and patient education are critical components of patient management. With more than 58% of the US adults owning a smartphone, mobile-based health technologies (most commonly in the form of applications or “apps”) can serve as useful adjuncts in diagnosis and management of hypertension. At the same time, several smartphone-based applications are advertised as having blood pressure measurement functionality, which have not been validated against a gold standard. In this cross-sectional study, we analyzed the top 107 hypertension related apps available on the most popular smartphone platforms (Google Android and Apple iPhone) to analyze the functional characteristics and consumer interaction metrics of various hypertension related apps. Nearly three-quarters of the apps record and track blood pressure, heart rate, salt intake, caloric intake and weight/body mass index. These app features can facilitate patient participation in hypertension management, medication adherence and patient-physician communication. However, it was concerning to find that 6.5% of the apps analyzed could transform the smartphone into a cuffless BP measuring device. None of these had any documentations of validation against a gold standard. Furthermore, number of downloads and favorable user ratings were significantly higher for these apps compared to apps without blood pressure measurement function. This highlights the need for greater oversight and regulation in medical device development. (more…)
Author Interviews, Diabetes, Immunotherapy, Kidney Disease, University of Michigan / 13.06.2015

MedicalResearch.com Interview with: Frank C. Brosius, MD Professor, Internal Medicine and Physiology Chief, Division of Nephrology University of Michigan Ann Arbor, MI Dr. Matthias Kretzler MD Professor, Internal Medicine Research Professor, Computational Medicine and Biology University of Michigan Ann Arbor, MI Katherine R. Tuttle MD Clinical Professor of Medicine, Division of Nephrology Medical & Scientific Director, Providence Medical Research Center/Sacred Heart Center Professor of Basic Medical Sciences, WWAMI Program Washington State University Medical Research: What is the background for this study? Response: Our University of Michigan team had found that JAK-STAT gene expression was increased in kidneys in patients with diabetic kidney disease and that these changes correlated with progression of kidney disease.  We subsequently substantiated these changes in other studies and have found that by increasing expression of just one of these genes, JAK2, in a single kidney cell type (podocytes) in mice that we can make their diabetic kidney disease much worse. At around the same time, investigators at Eli Lilly and Co. had FDA approval to test a JAK1-2 inhibitor, baricitinib, in patients with rheumatoid arthritis.  The Lilly scientists saw our human results and thought about using baricitinib in patients with diabetic kidney disease.  After initial discussions with Dr. Kretzler and myself they concluded that there was good reason to move ahead with this study and just 14 months after the initial meeting the phase 2 clinical trial of baricitinib in the treatment of patients with diabetic kidney disease was initiated. (more…)
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, 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, 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…)
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, 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, 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, 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, Biomarkers, Chemotherapy, JAMA, Johns Hopkins, Prostate Cancer / 08.06.2015

Emmanuel S. Antonarakis, M.B.B.CH Department of Urology and Oncology Johns Hopkins University School of Medicine Baltimore, MarylandMedicalResearch.com Interview with: Emmanuel S. Antonarakis, M.B.B.CH Department of Urology and Oncology Johns Hopkins University School of Medicine Baltimore, Maryland Medical Research: What is the background for this study? What are the main findings? Dr. Antonarakis: In a previous publication, we reported that detection of the androgen receptor splice variant 7 (AR-V7; an abnormal version of the androgen receptor) in circulating tumor cells from patients with advanced prostate cancer was associated with resistance to hormonal therapies such as abiraterone and enzalutamide. Here, we aimed to explore the role of AR-V7 in the context of chemotherapy treatment. We showed that detection of AR-V7 was not associated with resistance to the chemotherapy drugs docetaxel or cabazitaxel, and that AR-V7-positive patients could still derive benefit from these chemotherapies. (more…)
Author Interviews, Diabetes, JAMA, Ophthalmology, University of Michigan / 06.06.2015

Julia E. Richards, Ph.D. Harold F. Falls Professor of Ophthalmology and Visual Sciences Professor of Epidemiology Director, Glaucoma Research Center The University of MichiganMedicalResearch.com Interview with: Julia E. Richards, Ph.D. Harold F. Falls Professor of Ophthalmology and Visual Sciences Professor of Epidemiology Director, Glaucoma Research Center The University of Michigan Medical Research: What is the background for this study? Response: We have a special interest in how the developmental processes of aging increase the risk of late onset diseases. We wondered whether drugs that target known aging pathways might be able to reduce risk of late onset disease. In the aging field, an emerging area of interest has been the category of drugs called caloric restriction mimetic (CRM) drugs, which have been found to extend life span and to reduce risk or delay onset of some late-onset diseases. These caloric restriction mimetic drugs target a set of pathways that have come to be seen as playing roles in longevity. One of these caloric restriction mimetic drugs, metformin, happens to also be one of the most common drugs used in the treatment of type 2 diabetes. Glaucoma is a leading cause of blindness worldwide and classical open-angle glaucoma shows onset in late middle age or late age, so we hypothesized that a caloric restriction mimetic drug might be able to reduce the risk of open-angle glaucoma. We used data from a large health services database to compare the rate at which open-angle glaucoma developed in individuals with diabetes mellitus who used metformin versus those who did not use metformin. We predicted that metformin would be associated with reduced risk of open-angle glaucoma. Medical Research: What are the main findings? Response: We found that use of metformin was associated with reduced risk of open-angle glaucoma. A 2 gram per day dose of the CRM drug metformin for two years was associated with a 20.8% reduction in risk of developing open-angle glaucoma. When we looked at the highest quartile of drug prescribed (>1,100 grams over a two year period) we found a 25% reduction in risk relative to those taking no metformin. This risk reduction is seen even when we account for glycemic control in the form of glycated hemoglobin, and use of other diabetes drugs was not associated with reduced risk of open-angle glaucoma. A possible explanation for our findings might be that the mechanism of risk reduction is taking place by CRM drug mechanisms that target aging pathways rather than through glycemic control of diabetes. In the long run, the approaches to late onset diseases in general will become much more powerful if we can use parallel approaches that simultaneously target both the aging processes going on and the disease-specific pathways going on. In the literature we see caloric restriction mimetic drugs metformin, rapamycin and resveratrol all being explored for their ability to target points in aging pathways in ways that can impact the risk of a variety of late-onset diseases, so it will be important for those interested in the risk factors affecting late onset diseases to pay attention to how caloric restriction mimetic drugs might be altering risk for those late onset diseases. (more…)
AHA Journals, Author Interviews, Compliance, Duke, Heart Disease / 06.06.2015

Robin Mathews, MD Duke Clinical Research Institute Duke University Medical Center Durham, NCMedicalResearch.com Interview with: Robin Mathews, MD Duke Clinical Research Institute Duke University Medical Center Durham, NC Medical Research: What is the background for this study? What are the main findings? Dr. Mathews: Though treatment for patients with an acute myocardial infarction with evidence based therapies has increased significantly over the years, adherence to these therapies after discharge remain sub optimal. We used a validated instrument, the Morisky scale, to assess patient medication adherence.  We found that in a contemporary population of 7,425 patients across 216 hospitals, about 30% of patients were not adherent to prescribed cardiovascular medications as early as 6 weeks after discharge. Patients with low adherence were more likely to report financial hardship as well as have signs of depression. In addition, we found that patients who had follow up arranged prior to discharge and those that received explanations from the provider on the specific medications, were more often adherent to therapies. There was a non significant increase in risk of death or readmission at 2 months (HR [95% CI]: 1.35 [0.98-1.87]) among low adherence patients. (more…)
Author Interviews, Colon Cancer, Genetic Research, JAMA, Johns Hopkins / 05.06.2015

MedicalResearch.com Interview with: Timothy Michael Pawlik, M.D., M.P.H., Ph.D. Chief, Division of Surgical Oncology Professor of Surgery John HopkinsMedicalResearch.com Interview with: Timothy Michael Pawlik, M.D., M.P.H., Ph.D. Chief, Division of Surgical Oncology Professor of Surgery John Hopkins Medical Research: What is the background for this study? Dr. Pawlik: The prognosis of patients operated on for colorectal liver metastasis (CRLM) is currently defined by various “traditional” clinicopathologic factors. However the insight that they provide is incomplete. KRAS is the most common oncogene of the RAS family and is reported in up to 30 to 40% of patients with colorectal liver metastasis. As a result, KRAS mutational status  recently attracted a lot of attention as a potential prognostic factor in colorectal liver metastasis. However, overall mutant KRAS status (compared to wild type) correlated with worse survival only in some studies. We hypothesized that the specific KRAS activating mutations (codon 12 and codon 13) confer different biologic behaviors to the tumor and in turn, account for different (if any) prognostic values. The different proportions of each KRAS specific mutation could determine whether the overall mutational status would be associated with worse survival. In our view, the different proportions of specific mutations in various cohorts could account for the variability of the outcomes in different studies. Medical Research: What are the main findings? Dr. Pawlik: Our results showed that only codon 12 KRAS mutations conferred a worse prognosis whereas codon 13 ones did not. Furthermore, we examined the different point mutations that constitute codon 12 mutations and we found that among G12A, G12D, G12V, G12C and G12S KRAS point mutations, only G12V and G12S were independent prognostic factors of worse survival. That confirmed our hypothesis that only some of the point mutations do have a significant prognostic role and that the relative incidence of those mutations could determine if overall KRAS mutational status would be associated with worse survival in a certain cohort. (more…)
Author Interviews, HIV, Sexual Health, UCSD / 05.06.2015

MedicalResearch.com Interview with: Dr. Martin Hoenigl Center for AIDS Research University of California, San Diego Medical Research: What is the background for this study? What are the main findings? Dr. Hoenigl: Although men who have sex with men (MSM) represent a dominant risk group for human immunodeficiency Virus, the risk of HIV infection within this population is not uniform. Characterizing and identifying the MSM at greatest risk for incident HIV infection might permit more focused delivery of both prevention resources and selection of appropriate interventions, such as intensive counseling, regular HIV screening with methods that detect acute infection (ie, nucleic acid amplification test), and antiretroviral preexposure prophylaxis (PrEP). By using data collected at a single HIV testing encounter from 8326 unique MSM were analyzed, including 200 with AEH (2.4%), we were able to create the San Diego Early Test (SDET) risk score. The SDET score consist of four risk behavior variables which were significantly associated with an AEH diagnosis (ie, incident infection) in multivariable: condomless receptive anal intercourse (CRAI) with an HIV-positive MSM (3 points), the combination of CRAI plus 5 or more male partners (3 points), 10 or more male partners (2 points), and diagnosis of bacterial sexually transmitted infection (2 points), all as reported for the prior 12 months. The SDET risk score is deployed as a freely available tool at http://sdet.ucsd.edu. (more…)
Author Interviews, Fertility, Genetic Research, NEJM, University of Pittsburgh / 04.06.2015

Alexander N Yatsenko, MD, PhD Assistant Professor, Department of OBGYN and Reproductive Science, Magee-Womens Research Institute, University of Pittsburgh, PA Pittsburgh, PA 15213MedicalResearch.com Interview with: Alexander N Yatsenko, MD, PhD Assistant Professor, Department of OBGYN and Reproductive Science, Magee-Womens Research Institute, University of Pittsburgh, PA Pittsburgh, PA 15213 Medical Research: What is the background for this study? What are the main findings? Dr. Yatsenko: The known causes of male infertility not due to physical obstruction are usually because of sex-chromosome defects, such as deletions of the Y chromosome or duplication of the entire X chromosome in Klinefelter syndrome. Eight times out of 10, conventional genetic testing doesn’t reveal a chromosomal problem and infertility is considered idiopathic. We wanted to try to find other genetic reasons for the problem. We found a deletion in part of the DNA coding of the testis-expressed gene 11 (TEX11) on the X-chromosome, which men inherit from their mothers. The alteration caused meiotic arrest, meaning the precursor cells could not properly undergo meiosis. We also found similar TEX11 gene mutations and meiotic arrest in two out of 49 men diagnosed with idiopathic azoospermia in Pittsburgh or at a Poland infertility clinic, and in five out of 240 infertile men assessed at a collaborating Andrology clinic in Muenster, Germany. These genetic findings were confirmed on protein level using patients’ testis biopsies. (more…)
Annals Internal Medicine, Author Interviews, Beth Israel Deaconess, Hospital Readmissions / 04.06.2015

MedicalResearch.com Interview with: Kelly L. Graham, MD, MPH Instructor in Medicine Harvard Medical School Division of General Medicine and Primary Care Beth Israel Deaconess Medical Center Medical Research: What is the background for this study? What are the main findings? Dr. Graham: 30-day readmissions have become a standard quality metric used to represent inpatient quality of care and unnecessary healthcare utilization.  Effective 10/1/2009, hospitals with excess 30-day readmissions have been faced with financial penalties.  Experts have questioned the validity of this metric, and have raised concerns about the potential unintended consequence of creating health disparities, as critical access hospitals caring for the most socioeconomically burdened patients have faced the highest penalties. We were interested to see if factors associated with readmissions in the early part of the 30 day window (0-7 days post-discharge) differed from those associated with the later window (8-30 days post-discharge), ultimately attempting to better understand the "pathophysiology" of a readmission. Our findings suggest that early readmissions are associated with many factors, including those related to the index admission (acute illness burden and suboptimal discharge timing), and factors that are not related to the index hospitalization, such as chronic illness burden and social determinants of health.  In contrast, late readmissions were only associated with chronic illness burden and social determinants of health. (more…)
Author Interviews, Hepatitis - Liver Disease, NIH / 03.06.2015

Shyamasundaran Kottilil MBBS, PhD University of MarylandMedicalResearch.com Interview with: Shyamasundaran Kottilil MBBS, PhD Division of Infectious Diseases, Institute of Human Virology University of Maryland, Baltimore Laboratory of Immunoregulation National Institute of Allergy and Infectious Diseases National Institutes of Health, Bethesda, Maryland Medical Research: What is the background for this study? What are the main findings? Dr. Kottilil: During treatment with interferon-based therapies, hepatitis C viral load levels were clinically useful as on-therapy markers of treatment outcome. However, the standard-of-care for HCV treatment has recently evolved from interferon-based regimens to short-duration, all-oral, direct-acting antiviral (DAA) therapies. Therefore, it is important that we re-evaluate the utility of HCV viral loads during DAA regimens in guiding clinical decision-making. We found that Hepatitis C viral loads on treatment and at end of treatment were not predictive of treatment success versus relapse with DAA therapy. Contrary to our experience with interferon-containing regimens, low levels of quantifiable HCV RNA at end of treatment did not preclude treatment success. (more…)
Author Interviews, Cancer Research, JAMA, NYU, Surgical Research / 03.06.2015

Wiliam C. Huang, MD FACSAssociate Professor of Urology Division of Urologic Oncology NYU Langone Medical Center/Perlmutter Cancer InstituteMedicalResearch.com Interview with: Wiliam C. Huang, MD FACS Associate Professor of Urology Division of Urologic Oncology NYU Langone Medical Center/Perlmutter Cancer Center Medical Research: What is the background for this study? What are the main findings? Dr. Huang: The presentation of kidney cancers has dramatically evolved over the past two decades with most kidney cancers being incidentally diagnosed at an early stage. We have begun to recognize that at this small size (< 4 cm), the tumors are frequently indolent in nature and some are completely benign. Consequently, the management options for these small cancers have expanded and evolved.  Whereas the entire removal of the kidney was the treatment of choice in the past, alternative options including removal or ablation of the tumor-bearing portion of the kidney has become increasingly utilized. Similar to other early stage cancers, watchful waiting or observation is also becoming a reasonable treatment option. We used the most recent SEER-Medicare Data (2001 – 2009) to evaluate the management trends and outcomes of small kidney cancers in the new millennium.  We believe that this is an important study as it provides important and practical findings, which are useful to both clinical researches as well as practicing physicians. (more…)