Author Interviews, Breast Cancer, Chemotherapy, Lancet / 31.03.2015

Prof Xi-Chun Hu, Department of Oncology Shanghai Medical College Fudan University, Shanghai 200032, ChinaMedicalResearch.com Interview with: Prof Xi-Chun Hu, Department of Oncology Shanghai Medical College Fudan University, Shanghai 200032, China MedicalResearch: What is the background for this study? What are the main findings? Prof. Hu: Triple-negative breast cancer (TNBC) is associated with higher rates of recurrence, shorter disease free survival, and poorer overall survival. Molecular targeting agents tried against Triple-negative breast cancer have nearly all failed. TNBC, concordant with BRCA-associated and basal-like breast cancer, has abnormal DNA repair and genome-wide instability, supporting the use of DNA-damaging agents such as platinum. However, platinum monotherapy is not very potent, combination with other agents, such as gemcitabine has a synergistic effect. The GP regimen could be an alternative or even preferential first-line doublet chemotherapy strategy for patients with mTNBC.
Infections, Lancet, Pediatrics / 30.03.2015

[caption id="attachment_13089" align="alignleft" width="125"]Tuberculosis creates cavities visible in x-rays like this one in the patient's right upper lobe. Wikipedia Tuberculosis creates cavities visible in x-rays like this one in the patient's right upper lobe Wikipedia[/caption] MedicalResearch.com Interview with: Dr Anne K Detjen, MD Child Lung Health Consultant International Union Against Tuberculosis and Lung Disease Medical Research: What is the background for this study? What are the main findings? Dr. Detjen: The bacteriological diagnosis of tuberculosis (TB) in children is challenging due to the difficulty in obtaining specimens such as sputum and the lack of an accurate and accessible diagnostic test. In most cases, diagnosis is made on clinical grounds based on a contact history and a combination of signs and symptoms. We included 15 studies in a systematic review and meta-analysis of Xpert for the diagnosis of pulmonary TB in children. The accuracy of Xpert for diagnosing TB in children is suboptimal, and the majority of children will still have to be diagnosed clinically. However, in settings where it replaces smear microscopy Xpert will increase the likelihood of bacteriological confirmation of TB as well as MDR TB among children. Xpert does not increase the number of confirmed TB cases among culture-negative children. We also found that smear status highly impacted Xpert results, i.e. a higher yield among smear positive compared to smear negative children. Smear positivity increases with bacillary load and might be a proxy for disease severity. Unfortunately, we were not able to assess the performance among children with different stages of disease severity since this was not classified in any of the studies included.
Author Interviews, CMAJ, Infections, Vaccine Studies / 27.03.2015

MedicalResearch.com Interview with: Dr Fiona McQuaid Clinical Research Fellow University of Oxford, United Kingdom Medical Research: What is the background for this study? Response: Meningococcal B disease is a common cause of sepsis and meningitis with significant mortality and morbidity. A multicomponent vaccine against serogroup B meningococcus has been licensed for use in the Europe, Australia, Canada and recently the USA (though only in the 10-25 years age group) but questions remain about how long the bactericidal antibodies induced by infant vaccination persist and the likely breath of strain coverage. This was a follow on study looking at a group of children aged 5 years who had been vaccinated as infants and a different group who were vaccinated for the first time at 5 years of age. Medical Research: What are the main findings? Response: The percentage of children with protective antibody levels who had been immunized as infants fell in the 20 months since their last immunization but this varied by the strain of meingococcus B tested and by the different infant/toddler vaccination schedules. The children who were vaccinated for the first time at 5 years of age showed a good antibody response, but most reported pain and redness around the site of vaccination and 4-10% had a fever.
Author Interviews, BMJ, Johns Hopkins, Mental Health Research / 26.03.2015

Melinda C Power, ScD Post-Doctoral Research Fellow Epidemiology Department, Johns Hopkins Bloomberg School of Public Health Neurology Department, Johns Hopkins School of MedicineMedicalResearch.com Interview with: Melinda C Power, ScD Post-Doctoral Research Fellow Epidemiology Department, Johns Hopkins Bloomberg School of Public Health Neurology Department, Johns Hopkins School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Power: Air pollution may be related to mental health, particularly anxiety, through effects on oxidative stress and systemic inflammation or through promotion or aggravation of chronic diseases.  However, there has been very little research on the relation between air pollution exposures and anxiety in people.   Our study found that those with higher exposures to fine particulate matter, a type of air pollution, were more likely to experience elevated anxiety symptom levels.  Our study also suggests that recent exposures to find particulate matter air pollution are potentially more relevant to anxiety symptom levels than long-term past exposures.
Author Interviews, JAMA, OBGYNE, Toxin Research / 26.03.2015

Dr. Bradley S. Peterson, M.D Director of the Institute for the Developing Mind The Saban Research Institute of Children’s Hospital Los Angeles Children’s Hospital Los AngelesMedicalResearch.com Interview with: Dr. Bradley S. Peterson, M.D Director of the Institute for the Developing Mind The Saban Research Institute of Children’s Hospital Los Angeles Children’s Hospital Los Angeles Medical Research: What is the background for this study? Dr. Peterson: Neurotoxic PAH (polycyclic aromatic hydrocarbons) are ubiquitous in the environment, in the home and in the workplace. Emissions from motor vehicles, oil and coal burning for home heating or power generation, wildfires and agricultural burning, hazardous waste sites, tobacco smoke and charred foods are all sources of exposure. PAH readily crosses the placenta and affects an unborn child’s brain; earlier animal studies showed that prenatal exposure impaired the development of behavior, learning and memory. Our group previously reported that exposure to airborne PAH during gestation was associated with multiple neurodevelopmental disturbances, including development delay by age 3, reduced verbal IQ at age 5, and symptoms of anxiety and depression at age 7. Medical Research: What are the main findings? Dr. Peterson: Together with Virginia Rauh, ScD and Frederica Perera, DrPH, PhD of Columbia University’s Mailman School of Public Health, we conducted a brain imaging study to test the effects on brain structure of PAH exposure during the final trimester of pregnancy.  We used magnetic resonance imaging (MRI) to measure the brains of 40 children from a cohort of more than 600 mother-baby pairs from minority communities in New York City. These 40 children were carefully selected to have no other exposures that would affect brain development. Our findings showed that prenatal PAH exposure led to reductions in nearly the entire white matter surface of the brain’s left hemisphere – losses that were associated with slower processing of information during intelligence testing and more severe behavioral problems, including ADHD and aggression.  Postnatal PAH exposure – measured at age 5 – was found to contribute to additional disturbances in development of white matter in the dorsal prefrontal region of the brain, a portion of the brain that supports concentration, reasoning, judgment, and problem-solving ability.
Author Interviews, BMJ, Stroke, Toxin Research / 26.03.2015

MedicalResearch.com Interview with: Dr Anoop Shah Cardiology Research fellow Centre of Cardiovascular sciences University Of Edinburgh Edinburgh Medical Research: What is the background for this study? What are the main findings? Response: Stroke accounts for five million deaths each year and is a major cause of disability. The incidence of stroke is increasing, particularly in low and middle income countries, where two thirds of all strokes occur. The global burden of stroke related disability is therefore high and continues to rise. This has been primarily attributed to an aging population in high income countries and the accumulation of risk factors for stroke, such as smoking, hypertension, and obesity, in low and middle income countries. The impact of environmental factors on morbidity and mortality from stroke, however, might be important and is less certain. From 103 studies and across 6.2 million fatal and non-fatal strokes, our findings suggest a strong association between short term exposure to both gaseous (except ozone) and particulate air pollution, and admissions to hospital for stroke or mortality from stroke. These associations were strongest in low and middle income countries, suggesting the need for policy changes to reduce personal exposure to air pollutants especially in highly polluted regions.
AHA Journals, Author Interviews, Primary Care / 25.03.2015

Barry L. Carter, PharmD Professor of Pharmacy Professor of Family Medicine U Iowa Carver College of MedicineMedicalResearch.com Interview with: Barry L. Carter, PharmD Professor of Pharmacy Professor of Family Medicine U Iowa Carver College of Medicine Medical Research: What is the background for this study? What are the main findings? Response: Numerous studies and meta-analyses have found physician-pharmacist collaborative models can improve blood pressure (BP) control.  In these models, pharmacists are located within primary care offices to assist with patient management. The physician delegates responsibility to pharmacists to perform a medication history, identify problems and barriers to achieving disease control, perform counseling on lifestyle modification and adjust medications following hypertension guidelines.  However, it was not known if this model would be implemented in a large number of diverse primary care offices, if the effect could be sustained after discontinuation and if the intervention was as effective in under-represented minorities as in Whites. In this study, 32 clinics from throughout the U.S. were randomized to a 9 month intervention that was discontinued, a 24-month pharmacist intervention our usual care.  All subjects received structured research measured blood pressure at baseline, 6, 9, 12, 18 and 24 months.  We enrolled 625 subjects and 53% were from minority groups, 53% had < 12 years of education, 50% had diabetes or chronic kidney disease and 25% had Medicaid or self-pay for their care payments.  All of these variables typically make it much more difficult to achieve BP control.  BP control was 43% in the intervention groups and 34% in the control group at 9-months (adjusted OR 1.57 [95% CI 0.99-2.50], p = 0.059). However, when using the higher BP goals in the 2014 guidelines, blood pressure control was achieved in 61% of intervention subjects and 45% of control subjects at 9 months [(adjusted OR, 2.03 [95% CI 1.29-3.22], p=0.003). Of importance was the finding that the degree of systolic BP reduction (6 mm Hg) with the intervention compared to usual care was not only statistically significant but also the same in minority subjects (2/3 Black and 1/3 Hispanic) compared to all subjects. Interestingly, BP control seemed to be maintained in the subjects from minority groups at 18 and 24 months in both the group with the short (9-month) or sustained (24 month) intervention. In contrast, blood pressure control deteriorated slightly in non-minority subjects in all three groups.
Aging, Author Interviews, Exercise - Fitness, Frailty, JAMA, Vitamin D / 23.03.2015

MedicalResearch.com Interview with: Kirsti Uusi-Rasi, PhD, Adjunct Professor Senior Researcher UKK Institute for Health Promotion Research Tampere Finland Medical Research: What is the background for this study? What are the main findings? Dr. Kirsti Uusi-Rasi: Falls are the leading cause of unintentional injuries and fractures in older adults, head injuries and fractures being the most severe consequences. Therefore, falls prevention is important when trying to prevent injuries. There is strong high-quality evidence from previous studies that exercise that includes strength and balance training can reduce the risk of falling in older adults. However, there are also studies that have reported no benefit in reducing the actual incidence of falls. Effects of vitamin D have also been studied widely, and vitamin D is known to be vital for bone metabolism and health. However, results regarding effects on falls and fractures are inconsistent. Furthermore, persons with low vitamin D levels (serum 25OHD) have been associated with lower physical performance and greater decline in physical functioning, but clinical trials exploring the role of vitamin D in reducing falls and fractures and in improving physical functioning are inconclusive. Because there is hardly any evidence about exercise and vitamin D together, we investigated the separate and combined effects of multimodal exercise training and vitamin D supplementation in reducing falls and injurious falls among older women at risk for falling. We assigned 409 participants randomly to one of four groups with: 1)vitamin D 800 IU/day and exercise 2) placebo and exercise 3) vitamin D 800 IU/day without exercise 4) placebo without exercise. Exercise consisted of strength, balance, mobility and agility group training. At the end of two years, exercise seemed to be more effective in reducing injurious falls in this age group, with or without vitamin D. Exercise also improved physical functioning (strength, balance and mobility). In general, the training program was well tolerated with no severe adverse effects or injuries. Vitamin D helped maintain femoral neck BMD and increased trabecular bone density at the tibia. Our study also suggests that the current vitamin D recommendation (800 IU/d for older people) is adequate.
Author Interviews, Brigham & Women's - Harvard, Dermatology, JAMA / 22.03.2015

Dr. Arash Mostaghimi, MD, MPA Director of Dermatology Inpatient Service Brigham and Women’s Hospital Boston, MAMedicalResearch.com Interview with: Dr. Arash Mostaghimi, MD, MPA Director of Dermatology Inpatient Service Brigham and Women’s Hospital Boston, MA     Medical Research: What is the background for this study? What are the main findings? Dr. Mostaghimi: Spironolactone, a generic drug that’s been used in the clinic since 1959, is commonly prescribed for treating hormonal acne – acne that tends to affect the jaw line most commonly around the time of the month when a woman gets her period. The US Food and Drug Administration recommends frequent potassium monitoring in patients with heart failure who are taking spironolactone as a diuretic and antihypertensive treatment, but it’s been unclear if these guidelines should apply to healthy patients taking spironolactone for the treatment of acne, and, if so, how frequently such patients should have their potassium levels tested. My colleagues and I have found that for young, healthy women taking spironolactone to treat hormonal acne, potassium monitoring is an unnecessary health care expense. For the approximately 1,000 patients we studied, blood tests to monitor potassium levels did not change the course of treatment, but the tests cumulatively totaled up to $80,000. We suggest that routine potassium monitoring should no longer be recommended for this patient population in order to improve the patient care experience, decrease unnecessary office visits and reduce health care spending.
Author Interviews, Heart Disease, NEJM, NYU/NYMC, UCSD / 20.03.2015

Sripal Bangalore, MD, MHA, FACC, FAHA, FSCAI, Director of Research, Cardiac Catheterization Laboratory, Director, Cardiovascular Outcomes Group, The Leon H. Charney Division of Cardiology, Associate Professor of Medicine, New York University School of Medicine, New York, NY 10016.MedicalResearch.com Interview with: Sripal Bangalore, MD, MHA, FACC, FAHA, FSCAI Director of Research, Cardiac Catheterization Laboratory, Director, Cardiovascular Outcomes Group, Associate Professor of Medicine, New York University School of Medicine, New York, NY 10016 Medical Research: What is the background for this study? What are the main findings? Dr. Bangalore: Prior studies have shown a mortality benefit of bypass surgery over stenting. But these studies compared bypass surgery with older generation stents which are no longer used. We used data from the New York state registry of patients who underwent stenting or bypass surgery for 2 or more blockages of coronary arteries. With data from over 18,000 patients we found that there was no difference between stenting and bypass surgery for long term mortality. In addition we found that both procedures have trade offs. Bypass surgery has upfront risk of death and stroke whereas PCI has long term risk of needing a repeat procedure. In addition, in patients who underwent incomplete revascularization, there was increase in myocardial infarction with PCI.
Author Interviews, Kidney Disease, Lancet / 20.03.2015

Prof Vlado Perkovic MBBS PhD FASN FRACP George Institute for Global Health University of Sydney Sydney AustraliaMedicalResearch.com Interview with: Prof Vlado Perkovic MBBS PhD FASN FRACP George Institute for Global Health University of Sydney Sydney Australia   Medical Research: What is the background for this study? What are the main findings? Prof. Perkovic: There has been much discussion about the large number of people with kidney disease around the world- more than 10% of the population in most countries- but the current number of people with kidney failure had not been clearly defined. We therefore systematically collected information on the number of people with kidney failure around the world and found that 2.6 million people were receiving treatment for kidney failure in 2010, almost 80% of whom were undergoing dialysis while the others had received a kidney transplant. We then noticed very large differences in the number of people receiving treatment in different regions and countries, so used mathematical modeling to calculate the number of people who should be receiving treatment for kidney failure. The results of this analysis suggested there should be between 5 and 10 million people receiving treatment for kidney failure, suggesting that between half and three-quarters of people with kidney failure around the world died without access to dialysis, as a result of the high cost of dialysis treatment that is not affordable for many people around the world. These people are doomed to die of kidney failure, a condition for which we have had an effective treatment for over 50 years.
Author Interviews, MRSA, NEJM / 20.03.2015

Loren G. Miller, M.D., M.P.H. Los Angeles Biomedical Research Institute (LA BioMed) Infectious Disease SpecialistMedicalResearch.com Interview with: Loren G. Miller, M.D., M.P.H. Los Angeles Biomedical Research Institute (LA BioMed) Infectious Disease Specialist   Medical Research: What is the background for this study? Dr. Miller: Skin and skin structure infections are extremely common reasons for persons to seek medical care in the U.S., accounting for approximately 14.2 million outpatient visits in 2005, the latest year for which statistics are available, and 850,000 hospital admissions. Until this study was completed, the most effective approach to outpatient antibiotic treatment of uncomplicated skin infections in the era of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) was unclear. Prior to this research, there were no data on which antibiotics were best for treatment of these common skin infections. Medical Research: What are the main findings? Dr. Miller: Two antibiotics frequently prescribed to treat serious skin infections - clindamycin and trimethoprim sulfamethoxazole (TMP-SMX) - had similar rates of success in curing uncomplicated infections in outpatients. They also had similar rates of side effects. To conduct the study, we recruited outpatients from emergency departments, clinics and other healthcare facilities associated with Los Angeles County's Harbor-UCLA Medical Center, University of Chicago Medical Center, San Francisco General Hospital and Vanderbilt University Medical Center from May 2009 to August 2011. We studied 524 adults and children with uncomplicated skin infections who had cellulitis, abscesses of 5 centimeters or more or both. In the multicenter, double blind, randomized clinical trial, 264 received clindamycin and 260 received TMP-SMX. We followed the outpatients for a month after their treatment. We found similar outcomes for both groups - 80.3% of the outpatients who received clindamycin and 77.7% of the outpatients in the group that received TMP-SMX were cured within seven to 10 days after the end of their treatment. These are not considered significant differences, so our evaluation is that these two commonly prescribed antibiotics for serious skin infections are similarly effective in treating uncomplicated skin infections in children and adults who have few or no major co-existing conditions.
AHA Journals, Author Interviews, Heart Disease, Pediatrics, University of Michigan / 19.03.2015

  Donald M Lloyd-Jones, MD/ScM Senior Associate Dean for Clinical and Translational Research Chair, Department of Preventive Medicine Director, Northwestern University Clinical and Translational Sciences Institute (NUCATS) Eileen M. Foell Professor Professor in Preventive Medicine-Epidemiology and Medicine-CardiMedicalResearch.com Interview with: Donald M Lloyd-Jones, MD/ScM Senior Associate Dean for Clinical and Translational Research, Chair, Department of Preventive Medicine Director, Northwestern University Clinical and Translational Sciences Institute (NUCATS) Eileen M. Foell Professor Professor in Preventive Medicine-Epidemiology and Medicine-Cardiology Northwestern University Feinberg School of Medicine MedicalResearch: What is the background for this study? What are the main findings? Dr. Lloyd-Jones: Previous studies have examined the associations of cardiovascular health, as defined by the American Heart Association, with outcomes in younger and middle-aged adults. Prior studies have also examined the status (i.e., prevalence) of cardiovascular health in adults across the age spectrum, and in adolescents ages 12-19 years. However, no study to date has examined the status of cardiovascular health in children under 12 years of age, so we sought to define it in detail using nationally-representative data. Overall, although we have inadequate surveillance systems to monitor cardiovascular health optimally in our youngest children, this study shows that there are concerning signals that they are losing the intrinsic cardiovascular health they are born with, even well before age 12 years. The implications for loss of cardiovascular health before adulthood have been well established, with earlier onset of cardiovascular diseases, cancer and other diseases, earlier mortality, lower quality of life and many other adverse consequences.
Author Interviews, Lancet, Mental Health Research / 19.03.2015

Dr. Angela WoodsMedicalResearch.com Interview with: Dr Angela Woods Associate Editor, BMJ Medical Humanities Journal Senior Lecturer in Medical Humanities Deputy Director, Centre for Medical Humanities Durham University   Medical Research: What is the background for this study? What are the main findings? Dr. Woods: We’ve known for a long time that hearing voices, or auditory hallucinations, is reported by people with a wide range of psychiatric diagnoses as well as by those who have no diagnosis. 5–15 per cent of adults will hear voices at some point during their lives – in circumstances that may be related to spiritual experiences, bereavement, trauma, sensory deprivation or impairment, as well as mental and emotional distress. However, what we know about voices clinically and empirically comes from a small handful of studies, typically conducted in mental health settings with patients with a diagnosis of schizophrenia using quantitative scales and measures. Our study asked people to describe, in their own words, what it is like to hear voices. We designed an open-ended online questionnaire which was completed by 153 people with a range of diagnoses, including 26 who had never had a psychiatric diagnosis. Our study found that a large majority of participants described hearing multiple voices (81%) with characterful qualities (70%). While fear, anxiety, depression and stress were often associated with voices, 31% of participants reported positive and 32% neutral emotions. To our surprise less than half the participants reported hearing literally auditory voices; 45% reported either thought-like or mixed experiences. Perhaps the most startling finding concerned the physicality of voices. Bodily sensations while hearing voices were reported by 66% of participants – these included feelings of tingling, numbness, burning, pressure, and a sense of being distanced or disconnected from the body.
Author Interviews, Heart Disease, JACC / 18.03.2015

Prof. Ran Kornowski, M.D, FACC, FESC. Chairman - Division of Cardiology, Rabin Medical Center Petah-Tikva, IsraelMedicalResearch.com Interview with: Prof. Ran Kornowski, M.D, FACC, FESC Chairman - Division of Cardiology, Rabin Medical Center Petah-Tikva, Israel MedicalResearch: What is the background for this study? Prof. Kornowski: Over the years, the PCI procedure went-through many progresses. Among those are some angioplasty techniques, generalize use of stents and drug eluting stents, and adjuvant novel antithrombotic therapy. Unmistakably, these were associated with an overall improved PCI outcome. As many of the data on PCIs’ adverse outcomes predictors come from predates studies, we sought to update this matter.
Author Interviews, Cognitive Issues, JAMA, University of Michigan / 18.03.2015

Donovan Maust, MD, MS Assistant Professor of Psychiatry University of Michigan Research Scientist, Center for Clinical Management Research VA Ann Arbor Healthcare SystemMedicalResearch.com Interview with: Donovan Maust, MD, MS Assistant Professor of Psychiatry University of Michigan Research Scientist, Center for Clinical Management Research VA Ann Arbor Healthcare System Medical Research: What is the background for this study? What are the main findings? Dr. Maust: From a recent government report, we known that about 1/3 of older adults with dementia in nursing homes and about 14% of those in the community have been prescribed an antipsychotic. While providers focus on what benefit the treatment they offer, it is important to also be aware of the potential harms, particularly when it is death. Prior estimates came from relatively short studies and showed a 1% increase. This paper finds that, over 180 days, the increased mortality comparing antipsychotic users to matched non-users is about 2 to 5 times higher.
Author Interviews, Brigham & Women's - Harvard, JAMA, Race/Ethnic Diversity, Surgical Research / 18.03.2015

Dr. Adil Haider, MD, MPH Kessler Director of the Center for Surgery and Public Health (CSPH) at Brigham and Women’s HospitalMedicalResearch.com Interview with: Dr. Adil Haider, MD, MPH Kessler Director of the Center for Surgery and Public Health (CSPH) at Brigham and Women’s Hospital Medical Research: What is the background for this study? Response: Disparities in the quality of care received by minority and low-income patients have been reported for years across multiple medical conditions, types of care, and institutions.  To determine whether clinicians’ unconscious race and/or social class biases correlated with a lower quality of care for minority patients and those of lower socioeconomic status, my colleagues and I conducted a web-based survey among 215 physicians at an academic, level one trauma center. Participants were asked to review eight clinical vignettes, and then respond to three questions about management of care after each. Following their response, a test known as an Implicit Association Test (IAT Test) was used to assess any unconscious preferences. Medical Research: What are the main findings? Response: We found that race and class biases, as measured by response time to a standardized Implicit Association Test, had no relationship to the way that patients were clinically treated. Whether the lack of association found between implicit bias and decision making in this study represents a true lack of association or the failure of clinical vignettes to capture the nuances of how implicit biases translate into management decisions remains unclear. Existing biases might influence the quality of care received by minority patients and those of lower socioeconomic status in real-life clinical encounters.
Author Interviews, Nature / 18.03.2015

MedicalResearch.com Interview with: Dr. Pak Kin Wong Ph.D. Aerospace& Mechanical Engineering Department Biomedical Engineering and Bio5 Institute The University of Arizona Medical Research: What is the background for this study? What are the main findings? Response: Collective cell migration is central to various (patho)physiological processes, such as tissue development, regeneration, and cancer metastasis. At the onset of the process, a subset of cells acquires distinct leader cell phenotypes in the initially homogeneous population and leads the migration. However, how leader cells are initiated among the initial homogeneous population and how leader cell density is regulated during collective migration remain unknown. In this study, we demonstrate the formation of leader cells is regulated dynamically by Dll4 signaling through Notch1 and cellular stress near the leading edge. Our finding provides a molecular basis for the stochastic emergence of leader cells, a process originally considered random.
Author Interviews, Breast Cancer, JAMA / 18.03.2015

Joann G. Elmore M.D., M.P.H. Professor of Medicine, Adjunct Professor of Epidemiology, University of Washington School of Medicine Harborview Medical Center Seattle, WA 98104-2499MedicalResearch.com Interview with: Joann G. Elmore M.D., M.P.H. Professor of Medicine, Adjunct Professor of Epidemiology, University of Washington School of Medicine Harborview Medical Center Seattle, WA 98104-2499 MedicalResearch: What is the background for this study? What are the main findings? Dr. Elmore: It is estimated that 1.6 million women in the United States each year undergo a breast biopsy. By interpreting these biopsies under the microscope, pathologists provide diagnoses on a spectrum from benign, to atypia, to ductal carcinoma in situ (DCIS), to invasive cancer. Using these diagnostic classifications, clinical doctors work with their patients to decide if they are at increased risk of developing breast cancer in the future, which can lead to additional surveillance, or how to treat them when the diagnosis is invasive breast cancer. As misclassification of breast lesions by pathologists may contribute to overtreatment and undertreatment of breast disease, we decided to study the accuracy of breast pathology diagnoses in the U.S. In the Breast Pathology (B-Path) Study, we used a set of 240 breast biopsy cases to evaluate the interpretive accuracy of 115 U.S. pathologists who were actively interpreting breast biopsies in their clinical practices. Their diagnoses were compared with reference diagnoses established by a consensus panel of experienced breast pathologists. When the panel members each independently diagnosed the slides pre-consensus, they agreed unanimously on 75 percent of their diagnoses; ninety percent of the panel members’ initial independent diagnoses agreed with the final consensus-derived reference diagnoses. When comparing participating pathologists’ diagnoses to the reference diagnoses, we found overall agreement for 75 percent of interpretations. The concordance rate for invasive breast cancer was reassuringly high at 96 percent, and fairly high for benign findings without atypia at 87 percent. However, concordance was lower for atypia at 48 percent and for DCIS at 84 percent. This means that nearly one out of five pathologists disagreed on the diagnosis of DCIS. We found disagreement with the reference diagnosis to be statistically more frequent when pathologists had lower weekly case volumes or worked in smaller labs. Disagreement was also statistically significantly more likely when the patient had dense breast tissue on mammogram; however, the absolute difference was small. Our accuracy findings were not altered when we used different methods of defining the reference diagnosis.
Author Interviews, Infections, JAMA, University of Michigan / 17.03.2015

Lona Mody, MBBS, MSc Associate Division Chief, Clinical and Translational Research Associate Director, Clinical Programs, VA GRECC Associate Professor, Internal Medicine Research Associate Professor, Institute of Gerontology University of Michigan Geriatrics Ann Arbor, MIMedicalResearch.com Interview with: Lona Mody, MBBS, MSc Associate Division Chief, Clinical and Translational Research Associate Director, Clinical Programs, VA GRECC Associate Professor, Internal Medicine Research Associate Professor, Institute of Gerontology University of Michigan Geriatrics Ann Arbor, MI Medical Research: What is the background for this study? What are the main findings? Response: Over 1.5 million residents live in 15,600 Nursing Homes in the US. The acuity of illness in this population has increased substantially in the last decade, as has the risk of acquiring new infections. Multi-drug resistant organisms, also known as MDROs, are endemic in this setting with prevalence estimates upwards of 35% and surpassing those in the hospitals. Nursing homes historically have had few infection prevention resources, which contributes to these high rates. Patients with indwelling devices such as urinary catheters and feeding tubes present an attractive habitat for these ‘superbugs’ and thus carry the added burden of device-related infections. The authors examined the effect of a targeted infection program, or TIP, to reduce the prevalence of Multi-drug resistant organisms and new catheter or feeding tube infections among patients with indwelling devices. The TIP intervention was three-fold:
  1. Surveillance for infections and Multi-drug resistant organism colonization with regular feedback to facilities;
  2. Extensive and interactive staff education using adult learning theory about key infection prevention practices and hand hygiene; and
  3. Use of gowns and gown when providing assistance to patients for high-risk activities such as bathing and grooming.
Staff education emphasized precautionary measures against the spread of infection and included mock game shows, songs and dances. Hands were cultured for bacteria before and after hand washing. Outcomes were measured by results of the cultures taken for each patient and monitoring infection rates. A team of researchers from the University of Michigan and the Veterans Affairs Ann Arbor Health System has demonstrated that simple measures might be all it takes to push back at the spread of Multi-drug resistant organisms or ‘superbugs’ in nursing homes as well as reduce infections. In their study of patients with indwelling devices, MDROs were reduced by 23 percent among 418 residents in six southeast Michigan nursing homes who participated over the course of the three-year study. The numbers of catheter-associated urinary tract infections and MRSA acquisitions also decreased, 46 percent and 22 percent respectively. The trial examined the relationship between acquisition of antimicrobial resistance among nursing home and assisted living facility residents with the use of devices by adapting new methodological approaches and study designs to study infection prevention interventions including the use of cluster-randomized study design for infection prevention interventions, adopting adult learning practices to engage frontline healthcare personnel and using multi-anatomic site sampling to demonstrate effectiveness of the program.
Annals Internal Medicine, Author Interviews, CDC, Infections / 17.03.2015

MedicalResearch.com Interview with: Dr.Yecai Liu Division of Global Migration and Quarantine Centers for Disease Control and Prevention, Atlanta, Georgia Medical Research: What is the background for this study? What are the main findings? Response: Since the early 1900s, immigrants and refugees applying for a visa to come to the United States undergo a medical examination that includes tuberculosis (TB) screening. In 2007, CDC began implementing the new screening guidelines, which require people suspected of having TB to receive a much more sensitive sputum culture test to confirm TB to ensure that those individuals who do have TB receive treatment before they arrive in the United States. These requirements have now been completely rolled out to all countries with U.S.-bound immigrants and refugees. From 2007 through 2012, half of the 3.2 million arrivals of immigrants and refugees to the United States were screened for TB by the new screening guidelines. Out of more than 4,000 TB cases diagnosed by the new screening guidelines during this period, nearly 2,200 were smear-negative and culture positive. These cases would likely have been missed under the previous screening requirements. The results of this study showed that the updated overseas screening guidelines led to a roughly one-third decrease in the annual number of TB cases among foreign-born persons within their first year in the United States.
AHRQ, Author Interviews, Cost of Health Care, JAMA, Medical Imaging, Pain Research / 17.03.2015

Jeffrey (Jerry) G. Jarvik MD MPH Professor, Radiology, Neurological Surgery and Health Services Adjunct Professor, Pharmacy and Orthopedics & Sports Medicine Director, Comparative Effectiveness, Cost and Outcomes Research Center University of Washington Seattle, WA 98104-2499MedicalResearch.com Interview with: Jeffrey (Jerry) G. Jarvik MD MPH Professor, Radiology, Neurological Surgery and Health Services Adjunct Professor, Pharmacy and Orthopedics & Sports Medicine Director, Comparative Effectiveness, Cost and Outcomes Research Center University of Washington Seattle, WA Medical Research: What is the background for this study? Dr. Jarvik:  When I arrived at the Univ of WA over 20 years ago, my mentor, Rick Deyo, had just finished leading a project that was responsible for developing one of the first set of guidelines for the diagnosis and treatment of acute low back pain. These guidelines, published in a booklet by AHRQ (then called AHCPR), recommended that patients with acute low back pain not undergo imaging for 4-6 weeks unless a red flag was present. One of the exceptions was that patients older than 50 could get imaged immediately, the rationale being that older adults had a higher prevalence of potentially serious conditions such as cancer, infections, etc, that would justify the early imaging. As a practicing neuroradiologist, it was clear that a potential problem with this strategy is that the prevalence of age-related changes, which may or may not be related to back pain, also increases with age. So earlier imaging of older adults would almost certainly reveal findings, and these could easily start a series of unfortunate events leading to potentially poor outcomes and more healthcare resource use. Thus this policy of early imaging of older adults didn’t entirely make sense. About 5 years ago, these guidelines hit home when I developed acute low back pain and since I was over 50 (barely) my doctor recommended that I get an imaging study. Being a knowledgeable patient and having a reasonable doctor, we mutually agreed not to get the study. I improved but that wasn’t the end of it. When we had the chance to apply for one of the CHOICE ARRA awards funded by AHRQ, we made answering this question of early imaging in older adults one of our primary goals.
Author Interviews, Brigham & Women's - Harvard, Heart Disease, JACC, Outcomes & Safety / 17.03.2015

MedicalResearch.com Interview with: Stephen W. Waldo, MD Research Fellow in Medicine Massachusetts General Hospital MedicalResearch: What is the background for this study? What are the main findings? Dr. Waldo: Public reporting is intended to improve outcomes for our patients.  Proponents of public reporting applaud the increased transparency that it offers, allowing both patients and physicians to objectively evaluate health care outcomes for a given institution or individual provider.  Previous research has demonstrated, however, that public reporting of procedural outcomes may create disincentives to provide percutaneous coronary intervention for critically ill patients.  The present study sought to evaluate the association between public reporting of outcomes with procedural management and clinical outcomes among patients with acute myocardial infarction.  As the data demonstrate, public reporting of outcomes is associated with a lower rate of percutaneous revascularization and increased overall in-hospital mortality among patients with an acute myocardial infarction, particularly among those that do not receive percutaneous intervention.  This may reflect risk aversion among physicians in states that participate in public reporting, an unintended consequence of this policy.
Annals Internal Medicine, Author Interviews, Hepatitis - Liver Disease, MD Anderson / 17.03.2015

Jagpreet Chhatwal Ph.D. Assistant Professor, Department of Health Services Research Division of Cancer Prevention and Population Sciences The University of Texas MD Anderson Center Houston, TXMedicalResearch.com Interview with: Jagpreet Chhatwal Ph.D. Assistant Professor, Department of Health Services Research Division of Cancer Prevention and Population Sciences The University of Texas MD Anderson Center Houston, TX Medical Research: What is the background for this study? What are the main findings? Dr. Chhatwal: More than two million people in the U.S. are infected with Hepatitis C (HCV), a virus found in the liver. In 2012, the Centers for Disease Control and Prevention and the U.S. Preventive Services Task Force both recommended a one-time hepatitis C screening for baby boomers – people born between the years 1946 and 1964. Last year, the Food and Drug Administration approved the medications sofosbuvir and ledipasvir for Hepatitis C treatment. The newly approved oral regimen comes at a staggering price to payers – as much as $1,125 per day. As a result, several payers have questioned if the price is justified. The study results show that using new therapies is cost-effective in the majority of patients. However, the budget required to treat all eligible patients would be $136 billion over the next five years. Compared with the old drugs, new therapies would cost an additional $65 billion, whereas the cost offsets would be only $16 billion.
Author Interviews, Chocolate, Exercise - Fitness, Heart Disease, JACC, UCLA, UCSD / 17.03.2015

Pam R. Taub, MD, FACC Assistant Professor of Medicine UC San Diego Health System Division of Cardiology Encinitas, CA 92024MedicalResearch.com Interview with: Pam R. Taub, MD, FACC Assistant  Professor of Medicine UC San Diego Health System Division of Cardiology Encinitas, CA 92024 Medical Research: What is the background for this study? Dr. Taub: Epidemiological studies indicate that the consumption of modest amounts of dark chocolate (DC), which contains the natural cacao flavanol (-)-epicatechin (Epi,) is associated with reductions in the incidence of cardiovascular diseases (CVD). The health benefits of dark chocolate have been attributed to Epi. Clinical studies using cocoa and/or DC in normal volunteers or subjects with CVD have reported improvements in peripheral and coronary vascular endothelial function, blood pressure, lipids, insulin resistance, and inflammatory markers. The mechanism underlying these improvements is thought to be due to increased nitric oxide levels and improved endothelial function. We have also shown that capacity of Epi to favorable impact mitochondria under normal and disease states. We previously conducted pilot study in five patients with heart failure and type II diabetes, and showed that in skeletal muscle (SkM) biopsies there is a severe reduction in mitochondrial volume and cristae, as well as, in structural/functional proteins. After treatment with Epi rich dark chocolate , there was a significant recovery of SkM mitochondrial cristae, structural/functional proteins (e.g. mitofilin), as well as in regulators of mitochondrial biogenesis. However, no studies have examined the capacity of Epi rich dark chocolate to enhance exercise capacity in normal subjects and assess its impact on mitochondrial and oxidative control systems. Medical Research: What are the main findings? Dr. Taub: Seventeen subjects were randomized to placebo (n=8) or DC groups (n=9) and consumed 2 squares of chocolate (20 g, provided by Hershey) for 3 months. We showed in the chocolate group subjects had improved levels of HDL cholesterol and enhanced exercise capacity that is linked to the stimulation of SkM metabolic control endpoints which enhance mitochondrial function.
Author Interviews, Cleveland Clinic, Heart Disease, Lancet, Surgical Research / 15.03.2015

Prof Samir R Kapadia MD Director, Sones Cardiac Catheterization Laboratories Cleveland Clinic Cleveland, OH For patients with severe symptomatic aortic stenosis (AS) who are not candidates for surgical valve replacement, transcatheter aortic valve replacement (TAVR) offers superior benefit to standard therapy, as measured by all-cause mortality, cardiovascular mortality, repeat hospital admission and functional status. PARTNER 1B 5 year data were published simultaneously with PARTNER 1A 5 year data in 2 separate manuscripts in the Lancet (March 15 2105). In this landmark trial, TAVR produced a 22 percent survival benefit and a 28 percent reduced risk of cardiovascular mortality, compared with standard treatment. According to Cleveland Clinic interventional cardiologist Samir Kapadia, MD, lead author of PARTNER 1B, these findings have changed the treatment paradigm for severe Aortic Stenosis patients who can’t undergo surgical Aortic Valve Replacement. “This trial is the first—and will probably be the only—randomized AS trial that includes a standard treatment group, since these results will make it unethical to treat severe AS patients with medical therapy alone without aortic valve replacement. ” he says. Superior survival benefit with TAVR PARTNER 1B is the only rigorous randomized trial of extreme-risk aortic stenosis patients that has prospectively reported the outcomes of TAVR versus standard treatment in patients for whom the estimated probability of death or serious irreversible morbidity after surgical aortic valve replacement was 50 percent or greater. The trial enrolled 358 patients between May 11, 2007 and March 16, 2009; 179 patients were assigned to TAVR with the first-generation Sapien valve and 179 to standard therapy which includes medical therapy and balloon aortic valvuloplasty. TAVR was performed under general anesthesia with common femoral artery access. Guidance was provided by transesophagel echocardiography and fluoroscopy. The mean age of participants was 83. The primary endpoint was all-cause survival. Secondary endpoints included cardiovascular mortality, stroke, vascular complications, major bleeding and functional status.
Author Interviews, Heart Disease, NEJM, Surgical Research / 15.03.2015

Barnaby C. Reeves, D.Phil. Professor of Health Services Research, Clinical Trials & Evaluation Unit School of Clinical Sciences, University of Bristol Bristol Royal Infirmary BristolMedicalResearch.com Interview with: Barnaby C. Reeves, D.Phil. Professor of Health Services Research, Clinical Trials & Evaluation Unit School of Clinical Sciences, University of Bristol Bristol Royal Infirmary Bristol Medical Research: What is the background for this study? Response: Variable decisions are made about when to transfuse patients after cardiac surgery. The circumstances of particular patients influence decisions about whether to give a transfusion. Transfusion is a life-saving intervention when a patient is experiencing life-threatening bleeding but most patients have only one or two units of red cells transfused. These transfusions are given at varying levels of anaemia. Some doctors prefer to give a transfusion after cardiac surgery when a patient is only mildly anaemic, believing that the transfusion will promote recovery, while other doctors prefer to wait to transfuse until a patient is substantially anaemic, believing that a transfusion may do more good than harm and is wasteful if it is not needed. Therefore, we carried out a randomized controlled trial comparing restrictive (transfuse when haemoglobin <7.5 g/dL) and liberal transfusion thresholds (transfuse when haemoglobin <9.0 g/dL).* Medical Research: What are the main findings? Response: We obtained written informed consent before surgery but only randomized participants after surgery, in intensive care, if their Hb dropped below 9 g/dL. (Hence, we recruited over 3,500 patients but randomized only 2007.) This design avoids ‘diluting’ any difference between groups by including participants who would not usually be ‘considered’ for transfusion. The primary outcome was the occurrence of one or more serious complications: heart attack, stroke, acute kidney injury, bowel infarction, infection; this included/involved 35.1% of the patients in the restrictive-threshold group and 33.0% of the patients in the liberal-threshold group. This slight difference – more in the restrictive group – was not statistically significant. We then compared the percentages of patients who died; these were 4.2% in the restrictive group and 2.6% in the liberal group. The difference in this secondary outcome was of borderline statistical significance. Frequencies of other secondary outcomes (infections, ischaemic events, days in critical care and hospital, pulmonary complications) were not different in the two groups. We also carried out some pre-specified sensitivity analyses for the primary outcome and all-cause mortality. The two most important ones aimed to avoid dilution of the difference between groups as a result of patients having transfusions or outcome events before randomization. Excluding patients who were transfused before randomization shifted the treatment effect to favour the liberal threshold more strongly, for both the primary outcome and mortality. Excluding patients who experienced an outcome event in the first 24 hours after randomization did not change the treatment effect for either outcome.
Author Interviews, Dermatology, Infections, JAMA / 15.03.2015

MedicalResearch.com Interview with: Dr. Ana Ramírez-Boscá, MD Department of Dermatology and Clinical Research UnitDr. Ana Ramírez-Boscá, MD Department of Dermatology and Clinical Research Unit and Vicente Navarro-López, MD Clinical Research Unit and Infectious Diseases Unit Centro Dermatológico Estético, Alicante, SpainVicente Navarro-López, MD Clinical Research Unit and Infectious Diseases Unit Centro Dermatológico Estético, Alicante, Spain   MedicalResearch: What is the background for this study? What are the main findings? Response: Infections have been related with the pathogenesis of guttate psoriasis, however antibiotic treatment does not improve prognosis nor does it affect the evolution of the disease. The association between psoriasis and other infectious diseases has been reported as well, although in these cases there is scarce information on the causative microbial likely involved and the role of these bacteria in the pathogenesis of this skin disease. MedicalResearch: What are the main findings?  Response: Bacterial DNA may be detected in bloodstream of a significant proportion of patients with active plaque psoriasis. Increased levels of pro-inflammatory cytokines in patients with presence of bacterial DNA but not in patients without presence of bacterial genomic fragments suggest a role of bacterial DNA translocation in inducing an inflammatory response. [caption id="attachment_12680" align="alignleft" width="300"]"Guttate psoriasis" by Bobjgalindo - Own work. Licensed under GFDL via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:Guttate_psoriasis.jpg#/media/File:Guttate_psoriasis.jpg Guttate Psoriasis
from Wikipedia[/caption]