Annals Internal Medicine, Author Interviews, Infections / 11.06.2015

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

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

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

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

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

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

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

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

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

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

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

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

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

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

MedicalResearch.com Interview with: Chante Karimkhani MD Columbia University College of Physicians and Surgeons, New York, New York, Erika Hagstrom MD Loyola University of Chicago Stritch School of Medicine, Maywood, Illinois Robert Dellavalle MD, PhD, MPH Department of Dermatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado; Dermatology Service, US Department of Veterans Affairs, Eastern Colorado Health Care System, Denver, Colorado; Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado MedicalResearch: What is the background for this study? What are the main findings? Response: Allocation of funding dollars to research is a critical and daunting task. While many factors may impact research-funding decisions, establishing a transparent priority-setting exercise is paramount. This is particularly important for the National Institutes of Health, which invests over $30 billion for medical research each year. Diseases that have the greatest impact on our population warrant increased research dollars to reduce disease burden. The Global Burden of Disease Study (GBD) is an epidemiological effort to quantify the global burden of disease in a universal metric called disability-adjusted life years (DALYs). Focusing on our particular interest of dermatology, we investigated the 2012-2013 NIH funding for 15 skin diseases and matched this to corresponding DALY metrics. Our results demonstrated that melanoma, non-melanoma skin cancer, and leprosy were over-funded by the NIH according to DALY metrics. In contrast, dermatitis, acne vulgaris, pruritus, urticaria, decubitus ulcer, fungal skin diseases, alopecia areata, cellulitis, and scabies appeared under-funded. Three skin diseases, bacterial skin diseases, viral skin diseases, and psoriasis, were well-matched in terms of NIH funding and disease burden. Disease burden is one of a myriad of factors that may impact funding priorities. (more…)
Author Interviews, BMJ, Urology / 09.06.2015

MedicalResearch.com Interview with: Bilal Chughtai, MD & Art Sedrakyan, MD, PhD Department of Urology Weill Cornell Medical College Medical Research: What is the background for this study? What are the main findings? Response: Since 2008, the U.S. Food and Drug Administration has released number of public health notifications cautioning the use of mesh in pelvic organ prolapse (POP) surgery. Despite these notifications and subsequent public scrutiny, studies have reported a large increase of mesh use in female patients with pelvic organ prolapse during the last decade. In light of the reported rise in mesh utilization, we sought to determine the use of mesh in prolapse surgery and compare short-term outcomes of prolapse surgery with or without mesh. After identifying 7,338 and 20,653 patients who underwent prolapse repair procedures with and without mesh in a 4-year period, we found that mesh use increased 44.7%. Most patients were under 65 (62.3%), and there were more patients older than 65 years in the mesh group (44.3% versus 35.4%). Overall, complications were not common. However, patients who received mesh were more likely to experience urinary retention within 90-days and had a higher chance of having re-intervention at 1 year. Mesh use was also associated with higher risk of urinary retention in older patients (≥ 65 year olds) and re-intervention within 1 year in younger patients (<65 year olds). (more…)
Author Interviews, Hospital Acquired, Infections / 08.06.2015

Stephanie Bonne, MD, FACS Assistant Professor Trauma, Acute, and Critical Care Surgery Washington University in St. LouisMedicalResearch.com Interview with: Stephanie Bonne, MD, FACS Assistant Professor Trauma, Acute, and Critical Care Surgery Washington University in St. Louis Medical Research: What is the background for this study? What are the main findings? Response: We had previously implemented education programs in our ICU in an attempt to decrease our Central Line-Associated Bloodstream Infection (CLABSI) rate.  We were, however, unable to come to zero.  We were looking for innovative ways to lower our CLABSI rate, and the use of Clorhexidine/Silver Sulfadiazine catheters was unable to move our CLABSI rate.  We decided to try Minocycline/Rifampin catheters, and monitor our Central Line-Associated Bloodstream Infection rate. Medical Research: What should clinicians and patients take away from your report? Response: The use of Minocycline/Rifampin impregnated catheters can lower Central Line-Associated Bloodstream Infection rate, particularly in ICUs who have been unable to reach a Central Line-Associated Bloodstream Infection rate of zero with other measures. (more…)
Author Interviews, Depression, Diabetes, Heart Disease, Pharmacology, Women's Heart Health / 08.06.2015

Dr. Karin Rådholm MD Ph.D. Division of Community Medicine, Primary Care, Department of Medicine and Health Sciences, Faculty of Health Sciences, Linköping University, Department of Local Care West, County Council of Östergötland, Linköping, SwedenMedicalResearch.com Interview with Dr. Karin Rådholm MD Ph.D. student Division of Community Medicine, Primary Care, Department of Medicine and Health Sciences, Faculty of Health Sciences, Linköping University Department of Local Care West, County Council of Östergötland, Linköping, Sweden MedicalResearch: What is the background for this study? Dr. Rådholm: Psychosocial risk factors and depressive disorders often co-occur with general medical comorbidities, such as myocardial infarction. Depression is more common in patients with diabetes than in patients without diabetes. About 10-30% of patients with diabetes have a comorbid depressive disorder, which is double the estimated prevalence of depression in individuals without diabetes. There is an association between comorbid depressive symptoms and diabetes complications. This is believed to be mainly due to poor adherence to treatment recommendations and diabetes self-management activities, but could also possibly be due to biological and behavioural causes that could predispose for both metabolic and affective disorders. The general risk of myocardial infarction is strongly dependent on age and sex, where men have an earlier disease onset compared to women. In the general population women are at much lower risk for ischemic heart disease mortality than men are. However, women with diabetes are at especially high risk for coronary heart disease, relatively more so than men with type 2 diabetes, meaning that the impact of diabetes on the risk of coronary death is significantly greater for women than men. The age- and gender-specific risk for myocardial infarction due to diabetes with coexistent depression has not previously been described. Data on all dispensed drug prescriptions in Sweden are available in the Swedish Prescribed Drug Register and all myocardial infarctions are registered in the Myocardial Infarction Statistics. These registers are population-based and have a total national coverage and high validity, which has been previously shown. Prescribed and dispensed antidiabetics and antidepressants were used as markers of disease. Our objective was to prospectively explore the gender- and age-specific risk of first myocardial infarction in people treated with antidiabetic and/or antidepressant drugs compared to participants with no pharmaceutical treatment for diabetes or depression in a nationwide register study. (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…)
ASCO, Author Interviews, Biomarkers, Cancer Research / 06.06.2015

MedicalResearch.com Interview with: Dr. Kirsten Timms, PhD Program Director VP Biomarker Discovery at Myriad Genetics Inc Medical Research: What is the background for this study? What are the main findings? Dr. Timms: The Homologous Recombination Deficiency (HRD) score is a tumor biomarker which quantitates genomic rearrangements associated with defects in DNA damage repair. It has been shown in multiple studies that HRD score can identify tumors sensitive to DNA damaging agents such as platinum salts or PARP inhibitors. Many tumors are spatially heterogeneous: different parts of a tumor show variation at both the genomic level, and in their appearance. This tumor heterogeneity has the potential to negatively impact the accuracy of biomarker tests. This study assessed the consistency of the HRD score in multiple biopsies obtained from the same cancer to understand the impact of tumor heterogeneity on the HRD score. The main finding of this study is that the HRD score is highly conserved between different biopsies of the same tumor. (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, BMJ, Heart Disease / 06.06.2015

MedicalResearch.com Interview with: Prachi Bhatnagar, MPH, DPhil Researcher University of Oxford British Heart Foundation Centre on Population Approaches for Non-Communicable Disease Prevention Nuffield Department of Population Health Oxford Medical Research: What is the background for this study? What are the main findings? Response: We know that cardiovascular disease presents a large burden to the UK. We aimed to bring together all the main data on cardiovascular disease mortality, morbidity, treatment and economic costs. We found that there are regional inequalities in cardiovascular disease mortality and prevalence in the UK. (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, Outcomes & Safety, Surgical Research / 06.06.2015

Dr. Janet Martin PharmD, PhD Director, Medical Evidence, Decision Integrity & Clinical Impact (MEDICI) Assistant Professor, Department of Anesthesia & Perioperative Medicine and Department of Epidemiology & Biostatistics Schulich School of Medicine & Dentistry, Western University London, ON Canada MedicalResearch.com Interview with: Dr. Janet Martin PharmD, PhD Director, Medical Evidence, Decision Integrity & Clinical Impact (MEDICI) Assistant Professor, Department of Anesthesia & Perioperative Medicine and Department of Epidemiology & Biostatistics Schulich School of Medicine & Dentistry, Western University London, ON Canada Medical Research: What is the background for this study? What are the main findings? Response: There remains some scepticism regarding the effectiveness of the safe surgery checklist (SSCL) to tangibly improve patient safety in the real world setting, especially with respect to relative benefits in high-income versus lower-income settings. In general, push-back has been related to surgical teams doubting the power of a simple checklist to make significant impact for surgical settings. Despite their deceptive simplicity, checklists can be powerful tools to deal with the sheer volume of information that must be addressed in sequence in order to support safe surgery. The objective of our study was to determine, through meta-analysis, whether clinically-relevant outcomes after implementation of the WHO Safe Surgery Checklist (SSCL) in the clinical trial setting and in the real world setting are improved, and whether greater benefit occurs in low-middle income countries (LMICs) than in high income countries (HICs). A total of 13 studies (262,970 patients) met the inclusion criteria, including 12 cohort studies and 1 randomized trial. For SSCL versus control, the odds of death was significantly reduced by 21% (OR 0.79, 95%CI 0.67-0.93; p=0.003). The odds of surgical site infection was reduced by 28% (OR 0.72, 95%CI 0.62-0.84; p=0.001). Similarly, overall postoperative complications were significantly reduced by 30% (OR 0.70, 95%CI 0.59-0.82; p=0.009). While HIC and LMICs both experienced reductions in death, surgical site infections, and overall complications, the magnitude of reduction was generally greater for LMICs than in HICs. Sub-analysis by study design demonstrated generalizability between the clinical trial setting and the real world setting. (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…)