Author Interviews, Cleveland Clinic, JAMA, Prostate Cancer / 30.06.2015

Hui Zhu, MD, ScD Section Chief, Urology Section Louis Stokes Cleveland Veterans Affairs Medical Center and Staff, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation Cleveland, Ohio MedicalResearch.com Interview with: Hui Zhu, MD, ScD Section Chief, Urology Section Louis Stokes Cleveland Veterans Affairs Medical Center and Staff, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation Cleveland, Ohio MedicalResearch: Tell me a little bit about the impetus for this study. What gap in knowledge were you trying to fill?  Dr. Zhu: Prostate cancer is a very challenging disease to understand and manage. For the minority of men, prostate cancer is a lethal disease, and in fact, it is the second leading cause of cancer death in American men, behind only lung cancer. However, for the majority of men, prostate cancer poses little risk of death. In fact, about 1 man in 7 will be diagnosed with prostate cancer during his lifetime, but only 1 man in 38 will die from prostate cancer. In an effort to avoid suffering and death from prostate cancer for those men with the lethal form, the early detection of prostate cancer (before the disease has reached a stage when it is no longer curable) through widespread prostate cancer screening was instituted in the late 1980s and early 1990s. As a result, prostate cancer diagnosis increased substantially, and most prostate cancers were detected at an early, treatable stage. Screening successfully reduced the risk of death from prostate cancer by 20%. Unfortunately, our best available screening tests, i.e. prostate-specific antigen (PSA) testing and the digital rectal exam, do not differentiate well between lethal and nonlethal prostate cancer. Consequently, screening is associated with a high risk of overdiagnosis of nonlethal prostate cancer. As a result, about 800 men must be screened and about 30 men must be diagnosed and treated to avoid one death from the prostate cancer, according to recent results from the largest prostate cancer screening trial. Since the natural history of newly diagnosed screen-detected prostate cancer is difficult to predict (i.e. lethal or nonlethal), most prostate cancers have been treated aggressively, leading to overtreatment of many nonlethal cancers. Aside from receiving unnecessary treatment, these men are exposed to the potential side effects and complications of treatment, including erectile dysfunction and urinary incontinence. In response to the harms associated with screening and treatment, the US Preventative Services Task Force issued a statement in 2011 (formalized in 2012) recommending against prostate cancer screening in all men. Unfortunately, while minimizing the risks of overdiagnosis and overtreatment for men with nonlethal prostate cancer, this solution eliminates any of the potential benefits of screening for those men with the lethal form of the disease. As urologists, our solution is different. Rather than throw the baby out with the bathwater, we prefer to preserve PSA screening and its benefits by addressing and hopefully minimizing its associated risks. To achieve this, our goal is to better distinguish between those men who have lethal vs. nonlethal prostate cancer, limiting treatment only to those men who have the lethal form of the disease at an early stage when it is still curable. The dilemma is that our currently available diagnostic tests are unable to accurately differentiate lethal from nonlethal prostate cancer with 100% certainty at the time of initial diagnosis. The solution, or at least part of the solution, is active surveillance. In men who appear to have nonlethal (“low risk”) cancer at the time of diagnosis, it now appears to be safe to observe these cancers, at least initially. This is the concept behind active surveillance. Active surveillance entails carefully monitoring men with low-risk prostate cancer using serial testing and reserving the option of treatment for those men with prostate cancers that exhibit lethal characteristics. In this way, active surveillance preserves the benefits of screening while minimizing the harms of overdiagnosis and overtreatment. Active surveillance was first introduced in the early 2000s, but its efficacy and safety have only been elucidated recently over the last 5 years. Given that active surveillance may be one solution to the screening dilemma, we wanted to evaluate contemporary active surveillance utilization, which is the impetus for our study. Based on the most recent data available to us, we chose the years 2010-2011, which coincide to the time immediately before and during the release of the US Preventative Services Task Force statement against PSA screening. (more…)
AHRQ, Antibiotic Resistance, Author Interviews, Baylor College of Medicine Houston, JAMA, Urinary Tract Infections / 25.06.2015

Barbara W. Trautner, MD, PhD Houston Veterans Affairs Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center Section of Infectious Diseases, Department of Medicine Baylor College of Medicine, Houston, TexasMedicalResearch.com Interview with: Barbara W. Trautner, MD, PhD Houston Veterans Affairs Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center Section of Infectious Diseases Department of Medicine Baylor College of Medicine, Houston, Texas Medical Research: What is the background for this study? What are the main findings? Dr. Trautner: Reducing antimicrobial overuse, or antimicrobial stewardship, is a national imperative. If we fail to optimize and limit use of these precious resources, we may lose effective antimicrobial therapy in the future. CDC estimates that more than $1 billion is spent on unnecessary antibiotics annually, and that drug-resistant pathogens cause 2 million illnesses and 23,000 deaths in the U.S. each year. The use of antibiotics to treat asymptomatic bacteriuria (ASB) is a significant contributor to antibiotic overuse in hospitalized and nursing home patients, especially among patients with urinary catheters. In catheterized patients, ASB is very often misdiagnosed and treated as catheter-associated urinary tract infection (CAUTI). Therefore, we designed the “Kicking CAUTI: The No Knee-Jerk Antibiotics Campaign intervention” to reduce overtreatment of ASB and to reduce the confusion about distinguishing CAUTI from asymptomatic bacteriuria. This study evaluated the effectiveness of the Kicking CAUTI intervention in two VAMCs between July 2010 and June 2013. The primary outcomes were urine cultures ordered per 1,000 bed-days (inappropriate screening for ASB) and cases of ASB receiving antibiotics (overtreatment). The study included 289,754 total bed days, with 170,345 at the intervention site and 119,409 at the comparison site. Through this campaign, researchers were able to dramatically decrease the number of urine cultures ordered. At the intervention site, the total number of urine cultures ordered decreased by 71 percent over the course of the intervention. Antibiotic treatment of asymptomatic bacteriuria decreased by more than 75 percent during the study. No significant changes occurred at the comparison site over the same time period. Failure to treat catheter-associated urinary tract infection when indicated did not increase at either site. (more…)
Author Interviews, Autism, JAMA, OBGYNE / 25.06.2015

MedicalResearch.com Interview with: Ali S. Khashan, Ph.D. Irish Centre for Fetal and Neonatal Translational Research (INFANT) Cork, Ireland Medical Research: What is the background for this study? What are the main findings? Dr. Khashan: The Caesarean section rate is increasing worldwide reaching 30% in some western countries and 50% in China and Brazil. As a result, it is becoming increasingly important to understand the long-term effects this procedure may have on both mother and child. Previously, our group conducted a systematic review and meta-analysis of published literature and found birth by Caesarean to be associated with approximately 20% increased risk of autism spectrum disorder (ASD), compared to birth by vaginal delivery. This means if the risk of ASD in children born by vaginal delivery were 1%, and the association was causal, the risk of autism spectrum disorder in children born by Caesarean section is 1.2% i.e. two additional ASD cases per 1000 births. However, studies were limited, and we were unable to determine what was driving this association. In our new study, now published in JAMA Psychiatry, we investigated this issue further with the largest study on this subject to date, including all children born in Sweden between 1982 and 2010. Our study included data on over 2.9 million people and accounted for variety of factors known to be associated with both Caesarean section and autism spectrum disorder. After controlling for known confounders, such as maternal age and psychiatric history as well as various other perinatal and socio-demographic factors, we confirmed our previous findings that birth by Caesarean was associated with approximately 20% increased risk of autism spectrum disorder, compared to birth by vaginal delivery. However, with this analysis it remained unclear whether the increased risk was due to the Caesarean section itself, or some genetic or environmental factor that we were unable to measure. To determine if it was birth by Caesarean section or another unknown factor which led to an increased risk of ASD, we compared children with autism spectrum disorder to their non-diagnosed brothers and sisters. In other words, we analysed pairs of siblings in which one was diagnosed with ASD and one was not, to determine if birth by Caesarean was associated with increased risk of ASD within families. In this way, we attempted to indirectly account for genetic and family environment factors that are shared by siblings but we were unable to measure in the general population. In this analysis, which included data on over 13,000 sibling pairs, there was no longer any association between birth by Caesarean section and ASD. Overall, these results indicate that though birth by Caesarean section may be associated with an increased risk of ASD, it is likely due to family factors such as genetics or environment, rather than the Caesarean section itself. These findings are more informative than many previous studies as we had the largest sample size on this topic to date and estimated the association between Caesarean section and the risk of autism spectrum disorder while comparing siblings born by different methods of delivery. This allowed us to control for many factors that other studies did not. (more…)
Author Interviews, Cannabis, JAMA, Johns Hopkins / 25.06.2015

Ryan Vandrey, Ph.D. Associate Professor Behavioral Pharmacology Research Unit Johns Hopkins University School of Medicine Baltimore, MD 21224MedicalResearch.com Interview with: Ryan Vandrey, Ph.D. Associate Professor Behavioral Pharmacology Research Unit Johns Hopkins University School of Medicine Baltimore, MD 21224 Medical Research: What is the background for this study? What are the main findings? Dr. Vandrey: The background for the study was that I have had several conversations with individuals that led me to believe that there was insufficient regulation of products of all types being sold in medical cannabis dispensaries.  In order to evaluate that, we needed to do a study.  We decided to test edible products because that is a growing market, and, because it involves some level of manufacturing, there is greater chance for dose variability and inaccuracy.  The main finding was that the majority of products were purchased from retail stores selling cannabis products for medical use were significantly mislabeled with regards to the dose of THC and other cannabinoids. (more…)
Author Interviews, JAMA, Surgical Research, Technology / 25.06.2015

Vanita Ahuja, MD, MPH Department of General Surgery York Hospital, York, PennsylvaniaMedicalResearch.com Interview with: Vanita Ahuja, MD, MPH  Department of General Surgery York Hospital, York, Pennsylvania MedicalResearch: What is the background for this study? What are the main findings? Dr. Ahuja: Robotic-assisted surgery has been slowly accepted within the medical community. Felger et al. (1999), Falk et al. (2000), and Loumet et al. (2000) state that specific to cardiac surgery, the advantages of the robot in coronary artery bypass grafting (CABG) and valvular operations were demonstrated with increased visualization, ease of harvest, and quality of vascular anastomoses as early as 1999. However, Giulianotti, et al. (2003), Morgan et al. (2005), and Barbash et al. (2010) suggest that although safety and efficacy are supported, it is not conclusive yet that robot-assisted surgery is cost-effective, given the high cost of the robot itself, longer operating times, and the short life of the robotic instruments. The purpose of our paper was to compare outcomes of complications, length of stay (LOS), actual cost, and mortality between non-robotic and robotic-assisted cardiac surgery. In general surgery and subspecialties, the use of the robot has increased significantly over the past few years. It has been noted that robotic surgery improves on laparoscopic surgery by providing increased intra-cavity articulation, increased degrees of freedom, and downscaling of motion amplitude that may reduce the strain on the surgeon. The biggest growth in robotic surgery has been seen in the fields of gynecology and urology. Recently, Wright et al. reported an increase in robotic assisted hysterectomy from 0.5 percent of the procedures in 2007 compared to 9.5 percent in 2010 for benign disease. In their study, robotic assisted surgery had similar outcomes to laparoscopic surgery but higher total cost of $2,189 more per case. In urologic surgery, Leddy et al. reported in 2010 that radical prostatectomy remains the biggest utilization of robotic assisted surgery in urology with 1% in 2001 to 40% of all cases in 2006 performed in the United States. Utilizing a nationwide database from 2008-2011, subjects were propensity matched by 14 patient characteristics to reduce selection bias in a retrospective study. The patients were then divided into three groups by operation types: valves, vessels and other type. Univariate analysis revealed that robotic-assisted surgery, compared to non-robotic surgery, had higher cost ($39,030 vs. $36,340), but lower LOS (5 vs. 6 days) and mortality (1% vs. 1.9%, all p<0.001). For those who had one or more complications, robotic-assisted cardiac surgery had fewer complications (27.2%) to non-robotic cardiac surgery (30.3%, p < .001). (more…)
Author Interviews, Cancer Research, JAMA / 25.06.2015

Dr. Ayalew Tefferi, M.D.Department of Medicine, Mayo Clinic Rochester, Minnesota MedicalResearch.com Interview with: Dr. Ayalew Tefferi, M.D. Department of Medicine, Mayo Clinic Rochester, Minnesota MedicalResearch: What is the background for this study? What are the main findings? Dr. Tefferi: William Vainchenker discovered and reported an activating JAK2 mutation (JAK2V617F) in myelofibrosis and related myeloproliferative neoplasms in 2005 (Nature. 2005;434:1144-1148). This seminal observation led to the recognition of activated JAK-STAT as the potential disease-driving pathway in myeloproliferative neoplasms and development of several JAK inhibitors, including fedratinib, ruxolitinib and momelotinib, for treatment of myelofibrosis. In phase 2 studies, these JAK inhibitors showed similar activity in alleviating constitutional symptoms and reducing spleen size. However, none of them were able to induce complete or partial remissions or reversal of bone marrow fibrosis or significant lowering of JAK2 mutant allele burden. A subsequent phase 3 study provided the information required for FDA approval of ruxolitinib and the current phase 3 study was meant to do the same for fedratinib. (more…)
Author Interviews, Erectile Dysfunction, JAMA, Melanoma, NYU, Pharmacology / 24.06.2015

Dr. Stacy Loeb, MD, MScDepartment of Urology, Population Health, and Laura and Isaac Perlmutter Cancer CenterNew York University, New York MedicalResearch.com Interview with: Dr. Stacy Loeb, MD, MSc Department of Urology, Population Health, and Laura and Isaac Perlmutter Cancer Center New York University, New York Medical Research: What is the background for this study? Dr. Loeb: A paper published last year suggested a relationship between use of (Viagra) and melanoma.  That study had only 142 cases of melanoma, and of these men 14 had used sildenafil.  This study got a lot of publicity leading numerous patients to express concern over whether erectile dysfunction drugs could cause melanoma. Our goal was to look more closely at this issue in a larger population from Sweden (including 4065 melanoma cases of whom 435 used any type of erectile dysfunction drug- Viagra, as well as Levitra and Cialis).  Sweden has a national health system so we were able to access prescription records for men across the entire country, which we linked to the national registries for melanoma and basal cell skin cancer.   (more…)
Author Interviews, Duke, Heart Disease, JAMA / 24.06.2015

Sean D. Pokorney, MD, MBA Division of Cardiology, Duke University Medical Center Duke Clinical Research Institute, Durham, North Carolina MedicalResearch.com Interview with: Sean D. Pokorney, MD, MBA Division of Cardiology, Duke University Medical Center Duke Clinical Research Institute, Durham, North Carolina Medical Research: What is the background for this study? Dr. Pokorney: About 350,000 people die of sudden cardiac death in the US each year. Patients who have weakened heart function, particularly those with heart muscle damage as a result of a heart attack, are more likely to experience sudden cardiac death.  Defibrillators have been around since the 1980s, and have prolonged countless lives.  A previous study showed that 87% of patients who had a cardiac arrest were eligible for an implantable-cardioverter defibrillator (ICD) beforehand but did not get an ICD implanted prior to their arrest.  The timing of ICD implantation is critical, as studies have not found a benefit to ICD implantation early after myocardial infarction (MI).  Guidelines recommend primary prevention ICD implantation in patients with an EF ≤ 35% despite being treated with optimal medical therapy for at least 40 days after an MI.  Given the need to wait for at least 40 days after an MI, ICD consideration is susceptible to errors of omission during the transition of post-MI care between inpatient and outpatient care teams.  Also, the benefit of ICDs remains controversial among older patients, as these patients were underrepresented in clinical trials. Medical Research: What are the main findings? Dr. Pokorney: We looked at Medicare patients discharged from US hospitals after a heart attack between 2007 and 2010.  We focused on those patients who had weak heart function, and this left us with a little over 10,300 patients from 441 hospitals for our study.  This was an older patient population with a median age of 78 years.  We looked to see how many of these patients got an ICD within the first year after MI, and how many patients survived to 2 years after their heart attack.  Only 8% of patients received an ICD within 1 year of their heart attack.  ICD implantation was associated with a third lower risk of death within 2 years after a heart attack, and this was consistent with the benefit that were seen in the randomized clinical trials.  Importantly, 44% of the patients in our study were over 80 years old, and we found that the relationship between ICD use and mortality was the same for patients over and under age 80 years.  Increased patient contact with the health care system through early cardiology follow-up or re-hospitalization for heart failure or MI was associated with higher likelihood of ICD implantation.  Rates of ICD implantation remained around 1 in 10 patients within 1 year of MI even among patients with the largest heart attacks and the weakest hearts (lowest ejection fractions), who were least likely to have improvement in their heart function over time.  Similarly, even after excluding patients at highest risk for non-arrhythmic death (prior cancer, prior stroke, and end stage renal disease), ICD implantation rates remained around 1 in 10 patients. (more…)
Author Interviews, Cannabis, JAMA / 23.06.2015

MedicalResearch.com Interview with: Penny F. Whiting, PhD School of Social and Community Medicine, University of Bristol The National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care West at University Hospitals, Bristol NHS Foundation Trust, Bristol UK Kleijnen Systematic Reviews Ltd, Escrick, York, United Kingdom MedicalResearch: What is the background for this study? What are the main findings? Dr. Whiting: Cannabis is one of the most popular recreational drugs - only tobacco, alcohol and caffeine are more popular. It can result in an alteration to mood and a feeling of “high”. An estimated 141 million people use cannabis worldwide – this is equivalent to 2.5% of the world’s population. Cannabis has a long history of use for the relief of a wide variety of medical symptoms. There is evidence of its use for medical purposes going back to early Egyptian times. The pen-ts’ao ching the world’s oldest herbal book includes reference to cannabis as medicine for rheumatic pain, constipation, disorders of the female reproductive system, and malaria amongst others, this herbal book also contains the first reference to cannabis as a psychoactive drug. However, its use is controversial as it has been included as a controlled drug in the United Nations Single Convention on Narcotic Drugs since 1961, and the use of cannabis is illegal in most countries. Medical cannabis (or medical marijuana) refers to the use of cannabis or cannabinoids (any compound, natural or synthetic, that can mimic the actions of plant-derived cannabinoids) as medical therapy to treat disease or alleviate symptoms, this is different from CBD oil that also has been found to help with certain medical conditions, click to see details about CBD oil. Some countries have legalised medicinal-grade cannabis to chronically ill patients but in others its use remains illegal even for medicinal purposes. Canada and the Netherlands have government-run programmes where specialised companies supply quality controlled herbal cannabis. There are different strains of cannabis can help with aliments, those who are interested in finding out more about a list of low odor strains by GreenBudGuru.com might be interested in visiting or doing some research to find out more. These programmes have been running since 2001 and 2003 respectively. In the US around half of the states have introduced laws to permit the medical use of cannabis; other countries have similar laws. Kleijnen Systematic Reviews Ltd (see below) were commissioned by the Swiss Federal Office of Public Health to conduct a systematic review for the effects and adverse events of medical cannabis to inform policy decision making. Systematic reviews are studies of studies that offer a systematic approach to reviewing and summarising evidence. They follow a defined structure to identify, evaluate and summarise all available evidence addressing a particular research question. We were asked to focus on the following ten indications which were of particular interest to our commissioners: nausea and vomiting due to chemotherapy, patients with HIV/AIDS, chronic pain, spasticity in patients with multiple sclerosis or paraplegia, depression, anxiety disorder, sleep disorder, psychosis, glaucoma, and Tourette’s syndrome. We only included randomised trials, the most robust design for evaluating the effects of an intervention. We included almost 80 trials (nearly 6500 participants). We had most evidence for chronic pain (28 trials), nausea and vomiting due to chemotherapy (28 trials) and spasticity due to MS or paraplegia (14 trials) with less than five studies included for each of the other indications and none for depression. With the exception of the nausea and vomiting due to chemotherapy population, studies general compared cannabinoids to placebo with only single studies for each indication comparing cannabinoid with an active comparator. In the nausea and vomiting population the majority of studies compared cannabinoids to an active comparator, most commonly prochlorperazine. Most trials reported greater improvement in symptoms with cannabinoids compared to control groups, however, these did not always reach statistical significance. Cannabinoids were also associated with a greater risk of short term adverse events, including serious adverse events. Common adverse events included dizziness, dry mouth, nausea, fatigue, sleepiness, and euphoria. Overall we found that there was moderate quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity and low-quality evidence to suggest that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep quality, and Tourette syndrome. When determining the quality of the evidence we considered the risk of bias in trials, the consistency of the evidence across the trials, the directness of the evidence (was the trials research question directly applicable to our review question), and the precision of the evidence. (more…)
Author Interviews, Cancer Research, JAMA, NIH / 22.06.2015

MedicalResearch.com Interview with: Vinay Prasad, MD, MPH Medical Oncology Service, National Cancer Institute National Institutes of Health Bethesda, Maryland MedicalResearch: What is the background for this study? What are the main findings? Dr. Prasad: In medicine, there are two types of endpoints:  clinical endpoints and surrogate endpoints. Clinical endpoints, such as survival or quality of life, measure how a patient, feels, functions or lives.  In contrast, a surrogate endpoint is not a measure of patient benefit. Instead, it is merely hoped to correlate with one.  LDL levels are a surrogate for cardiovascular risk, for instance. Oncologists use and trust surrogate endpoints, such as response rate, progression free survival and disease free survival.  The majority of drug approvals and many guideline recommendations are based on improvements in surrogates.  Surrogates are assumed to correlate with overall survival, but we wanted to know if this was true, and under what circumstances. We reviewed all well done studies of surrogate-survival association.  We found that the majority--especially in the setting of metastatic disease--found a poor correlation between a surrogate and survival.  In fact, correlations were strong in only a handful of settings, such as adjuvant colorectal cancer.  Moreover, we found that correlations were always based on a subset of potentially informative literature, even when authors surveyed unpublished trials.  Missing data in these association studies raises the concern that correlations would be different if all data had been considered. Our overall conclusion was that most surrogate-survival correlations in oncology are based on weak evidence and are poor. (more…)
Anesthesiology, Author Interviews, Emergency Care, JAMA / 21.06.2015

MedicalResearch.com Interview with: Christoph Czarnetzki MD, MBA Division of Anesthesiology Geneva University Hospitals Geneva, Switzerland Medical Research: What is the background for this study? What are the main findings? Dr. Czarnetzki: In the US, about 40 million patients undergo a general anesthetic each year, and approximately 12,000 broncho-aspirate. Broncho-aspiration of gastric juice may lead to acute respiratory distress syndrome, carrying a 40% mortality rate. The risk is increased 10-fold in patients undergoing emergency surgery. Trauma patients may have ingested food before their accident, or have swallowed blood from oral or nasal injuries. Also, gastric emptying is delayed due to head injury, stress, pain, and opioid medication. Non-trauma patients may have delayed gastric emptying due to paralytic ileus and critical illness, leading to significant residual stomach content even after long fasting periods. Erythromycin, a macrolide antibiotic, and motilin receptor agonist induces antral contractions, and increases the lower esophageal sphincter tone, which is an important barrier against gastro-esophageal reflux. Although gastric emptying properties of erythromycin are well known, its efficacy in patients undergoing emergency surgery has never been investigated before to our knowledge. In our study we included 132 patients undergoing general anesthesia for emergency procedures and we could show that erythromycin increased the proportion of clear stomach and decreased acidity of residual gastric liquid. Dependent of the definition of empty stomach (less than 40 ml and absence of solid food or completely empty stomach) the absolute risk reduction ranged from 17% to 24%, equivalent to a number needed to treat of four to six patients to produce one completely cleared stomach. Erythromycin was particularly efficacious in non-trauma patients. Adverse effects were minor. (more…)
Author Interviews, Diabetes, Endocrinology, JAMA / 21.06.2015

MedicalResearch.com Interview with: Francis de Zegher, MD, PhD Department of Development and Regeneration, University of Leuven Leuven, Belgium & Lourdes Ibáñez, MD, PhD Hospital Sant Joan de Déu, University of Barcelona Barcelona, Spain Medical Research: What is the background for this study? Response: Hyperinsulinemic androgen excess is the most frequent hormonal disorder of adolescent girls. It seems to be mainly driven by an excessive and/or inappropriate storage of fat due to a chronically positive energy balance. The traditional approach (not approved by FDA or EMA) is to silence the ovaries by giving an oral contraceptive. An alternative approach is to change the storage of fat by giving an insulin-sensitizing combination of generics in low dose. (more…)
Author Interviews, Breast Cancer, JAMA, Race/Ethnic Diversity, Surgical Research, University Texas / 21.06.2015

Isabelle Bedrosian, M.D., F.A.C.S. Associate Professor, Department of Surgical Oncology, Division of Surgery, Medical Director, Nellie B. Connelly Breast Center The University of Texas MD Anderson Cancer Center, Houston, TXMedicalResearch.com Interview with: Isabelle Bedrosian, M.D., F.A.C.S. Associate Professor, Department of Surgical Oncology, Division of Surgery, Medical Director, Nellie B. Connelly Breast Center The University of Texas MD Anderson Cancer Center, Houston, TX Medical Research: What is the background for this study? What are the main findings? Dr. Bedrosian: There have been a number of reports on the rates of Breast Conserving Therapy (BCT) and mastectomy among women with early stage breast cancer. These reports have been discordant, with some suggesting that index mastectomy rates have increased and others suggestion Breast Conserving Therapy rates have actually increased. We hypothesized that these differences in reporting may be due to data source (ie tertiary referral centers vs population based studies) and turned to the NCDB, which captures 70% of cancer cases in the US and as such provides us with the most comprehensive overview on patient treatment patterns. (more…)
Author Interviews, General Medicine, JAMA, Outcomes & Safety / 19.06.2015

Samuel Pannick, MA, MBBS, MRCP Imperial Patient Safety Translational Research Center, National Institute for Health Research and Imperial College London, London, England West Middlesex University Hospital National Health Service Trust, Middlesex, EnglandMedicalResearch.com Interview with: Samuel Pannick, MA, MBBS, MRCP Imperial Patient Safety Translational Research Center, National Institute for Health Research and Imperial College London West Middlesex University Hospital National Health Service Trust Middlesex, England Medical Research: What is the background for this study? What are the main findings? Response: Improving the quality of general medical ward care is a recognized healthcare priority internationally. Ward teams have been encouraged to structure their work more formally, with regular interdisciplinary team meetings and closer daily collaboration with their colleagues. Some early studies suggested that these changes might benefit patients, and help ward teams work more efficiently. However, team interventions on medical wards have been reported with numerous different outcome measures, and prior to this study, it was unclear what their objective benefits were. We showed that there is little agreement on the objective outcomes that best reflect the quality of interdisciplinary team care on general medical wards. Changes to interdisciplinary care aren’t reflected in the outcome measures that researchers choose most often, like early readmission rates or length of stay. Complications of care - although harder to record - might have more promise as a measure of the quality of inpatient team care in these specific medical areas. (more…)
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, 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, 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, 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, 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, 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, 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…)
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, JAMA, Obstructive Sleep Apnea / 06.06.2015

Marie Marklund, DDS senior lecturer Department of Odontology, Faculty of Medicine Umeå University SwedenMedicalResearch.com Interview with: Marie Marklund, DDS senior lecturer Department of Odontology, Faculty of Medicine Umeå University Sweden MedicalResearch: What is the background for this study? What are the main findings? Response: Snoring and obstructive sleep apnea are common in the population and these disorders continuously increase because of the ongoing obesity epidemic in many countries. Today, 34% of men and 17% of women in the US suffer from obstructive sleep apnea of all severities. Symptoms include daytime sleepiness, poor sleep quality, headache, insomnia and restless legs. In the longer term, a more severe sleep apnea is associated with serious consequences, such as hypertension, stroke, cancer, traffic accidents and early death. Continuous positive airway pressure is a highly effective treatment for sleep apnea patients. Adherence problems, for instance from nasal stuffiness and claustrophobia reduces its effectiveness. An oral appliance holds the lower jaw forwards during sleep in order to reduce snoring and sleep apneas. This therapy has primarily been suggested for snorers and patients with mild and moderate sleep apnea. No previous placebo-controlled study has, however, evaluated this specific group of patients. Results from more severe sleep apnea patients have shown a good effect on sleep apneas. The effect of oral appliances on daytime symptoms is unclear. Symptomatic improvement is an important outcome for milder sleep apnea patients. The primary aims of the present study were to study the effects on daytime sleepiness and quality of life of a custom-made, adjustable oral appliance in patients with daytime sleepiness and snoring or mild to moderate sleep apnea, i.e. the primary target group for this type of therapy. Secondary aims included the effects on sleep apnea, snoring and various other symptoms of sleep disordered breathing such as headaches and restless legs. We found that oral appliance therapy was effective in reducing sleep apneas, snoring and symptoms of restless legs. The apnea-hypopnea index was normal (<5) in 49% of patients using the active appliance and in 11% using placebo, with a numbers needed to treat of three. Daytime sleepiness and quality of life did not differ during active treatment and the placebo intervention. The patients experienced reduced headaches with active treatment, but the results did not differ from placebo. It was concluded, that a custom-made, adjustable oral appliance reduces obstructive sleep apneas, snoring and possibly restless legs. The efficacy on daytime sleepiness and quality of life was weak and did not differ from placebo in this group of patients. (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…)