Author Interviews, Cost of Health Care, JAMA, Macular Degeneration, Ophthalmology, Telemedicine / 02.04.2017

MedicalResearch.com Interview with: John Wittenborn Senior research scientist NORC's Public Health Analytics University of Chicago MedicalResearch.com: What is the background for this study? What are the main findings? Response:The emergence of anti-VEGF treatment for wet-form AMD (choroidal neovascularization) has had a dramatic impact on preserving vision for many Americans. However, community-based studies show that most patients are not diagnosed with wet-form AMD until they have already lost a significant, and largely unrecoverable amount of their vision.  Early detection of wet-form AMD is key to effective treatment and the preservation of vision. The ForeseeHome telemonitoring technology provides patients with a means to check their own eyes on a daily basis to detect the earliest signs of vision loss from wet-form AMD. This is a novel technology that has the potential to improve visual health outcomes for AMD patients.  A prior clinical trial (the AREDS-2 HOME study) demonstrated that this technology can detect wet-form AMD earlier, and with less vision loss than standard care alone. However, that is exactly where that study ended as it reported no cost information nor follow-up. Since the end of this study, the device has been cleared by the FDA and approved for reimbursement by Medicare for certain higher risk patients, but no study has yet considered the long-term implications of adoption of this technology. In our analysis, we use a computer simulation model to essentially estimate what will come next, after patients realize earlier detection of wet-form AMD by utilizing home monitoring. Basically, we follow simulated patients from the time they begin monitoring for the rest of their lives, recording the likely impacts of home monitoring on patients’ long term outcomes including visual status, costs and quality of life. We find that home telemonitoring among the population indicated for reimbursement by Medicare would cost $35,663 per quality adjusted life year (QALY) gained.  Medicare would expect to incur $1,312 in net budgetary costs over 10 years for each patient who initiates monitoring.  However, Medicare patients may expect to achieve lifetime net savings when accounting for the chance of avoided vision loss and its associated costs later in life.
Author Interviews, Global Health, Infections / 02.04.2017

MedicalResearch.com Interview with: [caption id="attachment_33617" align="alignleft" width="150"]Dr Mihály Sulyok MD Eberhard Karls University Institute of Tropical Medicine, Tübingen, Germany Dr Mihály Sulyok[/caption] Dr Mihály Sulyok MD Eberhard Karls University Institute of Tropical Medicine, Tübingen, Germany MedicalResearch.com: What is the background for this study? What are the main findings? Response: New antimalarials are desperately needed, not just for treatment, but also for prophylaxis. DSM265, a novel antimalarial compound that selectively inhibits the plasmodial dihydroorotate dehydrogenase has a promising pharmacokinetic profile characterized by a long elimination half-life. We performed a study at the Institute of Tropical Medicine, Eberhard Karls University (Tübingen, Germany) to investigate safety, tolerability and efficacy of DSM265 using controlled human malaria infection. In the first cohort, 400mg of DSM265 was administered orally to five healthy, malaria naive individuals one day before direct venous inoculation of an established infective dose of P. falciparum sporozoites (PfSPZ Challenge). Placebo was administered to two volunteers. The study was randomized and double blinded. In this cohort all placebo participants developed malaria, whereas all DSM265 participants were protected. In a second cohort, 400mg DSM265 was administered 7 days before the sporozoite inoculation for six participants, two participants recieved placebo. In this cohort, the two placebo and three of six DSM265 volunteers developed thick blood smear positive malaria. The remaining three DSM265 volunteers developed transient submicroscopic parasitemia without symptoms or thick blood smear positivity. The only possible DSM265-related adverse event was a slight transient elevation in serum bilirubin in one volunteer. The study was funded by the Global Health Innovative Technology Fund, Wellcome Trust, Bill & Melinda Gates Foundation through Medicines for Malaria Venture, and the German Center for Infection Research.
Author Interviews, Environmental Risks, Thyroid, Thyroid Disease / 02.04.2017

MedicalResearch.com Interview with: [caption id="attachment_33607" align="alignleft" width="156"]Julie Sosa, MD MA FACS Professor of Surgery and Medicine Chief, Section of Endocrine Surgery Director, Surgical Center for Outcomes Research (SCORES) Leader, Endocrine Neoplasia Diseases Group Duke Cancer Institute and Duke Clinical Research Institute Durham, NC 2771 Dr. Sosa[/caption] Julie Sosa, MD MA FACS Professor of Surgery and Medicine Chief, Section of Endocrine Surgery Director, Surgical Center for Outcomes Research Leader, Endocrine Neoplasia Diseases Group Duke Cancer Institute and Duke Clinical Research Institute Durham, NC 2771 MedicalResearch.com: What is the background for this study? Response: The incidence of thyroid cancer has dramatically increased world-wide over the last several decades. In the United States, thyroid cancer is the fastest increasing cancer among women and men. This observation has been almost exclusively the result of an epidemic of papillary thyroid cancer, or PTC, which now comprises approximately 90% of new cases. The use of flame retardant chemicals, or Flame Retardant Chemicals, also increased over the last several decades due to the implementation of mandatory and voluntary flammability standards for furniture, electronics, and construction materials. Over time, FRs come out of these products and accumulate in indoor environments where humans are exposed. Animal studies suggest that FRs can disrupt thyroid function, and many contribute to cancer risk. But many human health endpoints have not been investigated. Our work was aimed at investigating whether exposure to Flame Retardant Chemicals could be associated with PTC. To address our research question, we recruited 140 adults, 70 with PTC and 70 who were healthy volunteers without evidence for thyroid cancer or thyroid disease. Then we visited participants’ homes and collected dust samples, a metric that we have previously shown is an indicator of long-term exposure to Flame Retardant Chemicals in the home.
Author Interviews, Breast Cancer, Surgical Research / 02.04.2017

MedicalResearch.com Interview with: Ahmedin Jemal, DVM, PHD Vice President, Surveillance and Health Services Research American Cancer Society, Inc. Atlanta, GA 30303 MedicalResearch.com: What is the background for this study? Response: Previous studies reported that Contralateral Prophylactic Mastectomy (CPM) increased in the United States among women diagnosed with unilateral early-stage breast cancer with surgery without evidence for survival benefit. Previous studies also reported that receipt of this procedure is more common in younger than older patients, in white than in black patients, and in privately insured than uninsured patients. However, the extent of variation in receipt of CPM by state of residence was unknown.
Abuse and Neglect, Author Interviews, BMJ, Exercise - Fitness, Mental Health Research / 02.04.2017

MedicalResearch.com Interview with: [caption id="attachment_33615" align="alignleft" width="134"]Tine Vertommen, Criminologist Faculty of Medicine and Health Sciences Universiteitsplein 1 Antwerp, Belgium Tine Vertommen[/caption] Tine Vertommen, Criminologist Faculty of Medicine and Health Sciences Universiteitsplein 1 Antwerp, Belgium MedicalResearch.com: What is the background for this study? What are the main findings? Response: A recent prevalence study into interpersonal violence against child athletes in the Netherlands and Belgium showed that 6% experienced severe sexual violence, 8% experienced severe physical violence, and 9% of respondents experienced severe psychological violence in sport (Vertommen et al., 2016). While general literature has repeatedly shown that exposure to interpersonal violence during childhood is associated with mental health problems in adulthood, this relationship has not yet been demonstrated in (former) athletes. Thus, the objective of the current study is to assess the long-term consequences of these experiences on adult mental health and quality of life.
Author Interviews, Biomarkers, Heart Disease / 31.03.2017

MedicalResearch.com Interview with: [caption id="attachment_33595" align="alignleft" width="141"]Szilard Voros, MD, FACC, FSCCT, FAHA CEO of Global Genomics Group Dr. Voros[/caption] Szilard Voros, MD, FACC, FSCCT, FAHA CEO of Global Genomics Group  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Atherosclerotic coronary artery disease (ASCAD) is the leading cause of death and morbidity in the United States and worldwide, despite relatively successful medical therapies such as statins, like Zocor or Lipitor. A significant majority of patients with ASCAD present with sudden cardiac arrest, and the clinical evaluation of those patients who present with chest pain to their physicians is very inefficient. Based on current clinical guidelines, patients who present to their physician with complaints of new onset chest pain or its equivalent, such as exertional dyspnea should be assessed for the probability of the presence of significant ASCAD based on simple clinical predictors. Approximately 60% of such patients have an intermediate probability, and they are typically referred for initial non-invasive evaluation, such as a stress test with cardiac imaging, or for some other type of non-invasive test. Strikingly, no more that 5% of such stress tests performed in the United States are actually positive, and even when patients with positive stress test are taken for invasive coronary angiography, no more than 40% have significant ASCAD. A blood test that could serve as first step, as a “gatekeeper”, to non-invasive evaluation, would be highly desirable. Global Genomics Group, or G3, has performed one of the largest, unbiased, mass-spectrometry-based discovery studies in over 1,000 patients who underwent detailed cardiac CT to assess the presence or absence of ASCAD, by measuring over 1,000 metabolites from the blood. Using sophisticated bioinformatics tools, the researchers identified 8 important metabolites that were significantly abnormal in patients with ASCAD, and generated a biomarker signature for the detection of ASCAD based on those analytes, called “knowPLAQUETM”. The biomarker signature was generated in approximately 800 subjects, and was validated in an independent set of approximately 400 subjects, showing an area under the curve (“AUC”) of 0.82 for the diagnosis of Atherosclerotic coronary artery disease. This biomarker signature can be adapted relatively easily on commercial mass spectrometry platforms, and the researchers anticipate that this signature may be available for physicians to use by 2018. In addition to its diagnostic power, this biomarker signature also has uncovered important biological insights for the development of ASCAD, which can be leveraged for therapeutic purposes.
Author Interviews, Breast Cancer, Cancer Research, JAMA, Surgical Research / 31.03.2017

MedicalResearch.com Interview with: Rebecca Nash, MPH Rollins School of Public Health Emory University MedicalResearch.com: What is the background for this study? Response: Contralateral prophylactic mastectomy (CPM) in women with invasive early-stage unilateral breast cancer has significantly increased in the U.S. over the past decade, despite the lack of evidence for a survival benefit. This procedure is particularly common among patients younger than 45 years old. It is also more common in whites compared to blacks, and in privately insured patients compared to uninsured or Medicaid insured patients. However, the extent of regional variation across the United States was unknown.
Author Interviews, Heart Disease, Insomnia / 31.03.2017

MedicalResearch.com Interview with: Qiao He Master’s degree student China Medical University Shenyang, China MedicalResearch.com: What is the background for this study? Response: Sleep is an important factor for biological recovery functions, but in modern society, more and more people have complained having sleep problems like insomnia, one of the main sleep disorders. It is reported that approximately one-third of the German general population has been suffering from insomnia symptoms. In decades, many researchers have found associations between insomnia and bad health outcomes. Insomnia seems to be a big health issue. However, the results from previous studies regarding the association of insomnia and cardiovascular or cerebrovascular events were inconsistent. Therefore, we conducted this study.
Author Interviews, BMC, End of Life Care, Pulmonary Disease / 31.03.2017

MedicalResearch.com Interview with: [caption id="attachment_33567" align="alignleft" width="180"]Dr Sabrina Bajwah MBChB MRCGP MSc MA PhD Consultant Palliative Medicine, King’s College NHS Foundation Trust Honorary Senior Lecturer King's College London Cicely Saunders Institute, Department of Palliative Care, Policy and Rehabilitation London, UK Dr Sabrina Bajwah[/caption] Dr Sabrina Bajwah MBChB MRCGP MSc MA PhD Consultant Palliative Medicine, King’s College NHS Foundation Trust Honorary Senior Lecturer King's College London Cicely Saunders Institute, Department of Palliative Care, Policy and Rehabilitation London, UK  MedicalResearch.com: What is the background for this study? Response: Where people die is often important to them and their families, as well as being important for planning health care services. Most people want to die at home, but instead most die in hospital. While the trends have been studied in cancer, other diseases, such as respiratory, are rarely looked at even though they are common and increasing causes of death. Chronic Obstructive Pulmonary Disease (COPD) and Interstitial Pulmonary Diseases (IPD) are common respiratory conditions. Both conditions result in a high use of hospital services, especially among people in advanced stages. This leads to high healthcare costs.1 In the UK in 2010, it is estimated that IPD costs £16.2 million per year in hospitalisations.2 The NHS spends more than £810 million annually managing COPD, with inpatient stays accounting for around £250 million annually. Understanding which factors affect place of death is vital for planning services and improving care, especially given our ageing population, rising chronic diseases and the high costs of hospital admissions. Strategies in many countries have sought to improve palliative care and reduce hospital deaths for non-cancer patients, but their effects are not evaluated. We aimed to determine the trends and factors associated with dying in hospital in COPD and IPD, and the impact of a national end of life care (EoLC) strategy3 to reduce deaths in hospital. This study analysed a national data set of all deaths for COPD and IPD, covering 380,232 people over 14 years.
Author Interviews, Melanoma / 31.03.2017

MedicalResearch.com Interview with: [caption id="attachment_33563" align="alignleft" width="181"]Dr Paolo A Ascierto MD Melanoma Cancer Immunotherapy and Innovative Therapy Unit Istituto Nazionale Tumori Fondazione Naples Italy Dr. Ascierto[/caption] Dr Paolo A Ascierto MD Melanoma Cancer Immunotherapy and Innovative Therapy Unit Istituto Nazionale Tumori Fondazione Naples Italy MedicalResearch.com: What is the background for this study? What are the main findings? Response: Although IPI was approved for the treatment of melanoma at dosage of 3 mg/kg, a dose-ranging phase 2 trial suggested longer overall survival (OS) but more treatment-related adverse events with ipilimumab 10 mg/kg vs 3 mg/kg. However, the study MDX010-020 (randomized phase III study which compared ipilimumab 3 mg/kg + gp100 vaccination and ipilimumab 3mg/kg + placebo vs gp100 vaccination + placebo) performed as second line treatment of advanced melanoma patients, showed an OS curve similar to that of the study CA184-169 (randomized phase III study which compared dacarbazine + ipilimumab 10 mg/kg to dacarbazine + placebo) as first line treatment of metastatic melanoma. For this reason FDA approved ipilimumab at dosage of 3 mg/kg as first and second line treatment for advanced melanoma, but asked for a randomized phase III study of comparison of ipilimumab at the different dosage in order to explore if there was a difference in the outcome of patients with different dosages.
Author Interviews, Zika / 31.03.2017

MedicalResearch.com Interview with: [caption id="attachment_33551" align="alignleft" width="90"]Daihai He PhD Department of Applied Mathematics The Hong Kong Polytechnic University Hung Hom, Kowloon Hong Kong (SAR), China Dr. Daihai He[/caption] Daihai He PhD Department of Applied Mathematics The Hong Kong Polytechnic University Hung Hom, Kowloon Hong Kong (SAR), China MedicalResearch.com: What is the background for this study? What are the main findings? Response: Zika virus disease has large outbreaks in many Pacific and American countries in 2016, and the outbreaks are still on-going. Our work is conducted against this background. We compared data from three localities: French Polynesia in 2013-2014, Colombia and Brazil in 2016. We found that in French Polynesia the infection attack rate (i.e. the proportion of the population who got infected) is about 3/4, which matched previous serological studies. We then make estimation for the other two place. We found that the infection attack rate in Colombia in 2016 was most likely less than 50%. For Bahia province of Brazil, we did not arrive at a very accurate estimation, as the confidence interval is wide, and our best estimate is 30%. The relatively low infection attack rate in Colombia and Brazil implies that future outbreaks of Zika virus diseases are still possible. Thus control and surveillance efforts should be continued.
Author Interviews, Biomarkers, Heart Disease, JAMA / 30.03.2017

MedicalResearch.com Interview with: Stefan Kiechl, MD and Karin Willeit, MD Department of Neurology Medical University Innsbruck Innsbruck, Austria  MedicalResearch.com: What is the background for this study? Response: Atrial fibrillation (AF) is the most common cardiac arrhythmia and a major contributor to thromboembolic stroke and population morbidity and mortality. Aside from well-established risk factors such as age, heart failure, and hypertension, inflammation has been suggested to play a significant role in the pathogenesis of AF. This is evidenced by histologic studies that found marked inflammatory infiltrates in atrial biopsies of AF patients and by epidemiological studies demonstrating an association of circulatory inflammation markers with incident AF. Of note, an increased endocardial expression of vascular intercellular adhesion molecule 1 (VCAM-1), a mediator of leukocyte trafficking, during rapid atrial pacing was demonstrated which was shown to contribute to an inflammatory and prothrombotic environment within atrial tissue. Because it is still unclear whether inflammation related to AF is primarily a systemic or localized phenomenon, we sought to examine the association of 13 baseline inflammation markers with incident atrial fibrillation in the prospective population-based Bruneck Study and to replicate key findings in a second cohort, the SAPHIR Study.
Author Interviews, HPV, NEJM, OBGYNE, Vaccine Studies / 30.03.2017

MedicalResearch.com Interview with: Anders Hviid Senior Investigator, M.Sc.,Dr.Med.Sci. Department of Epidemiology Research Division of National Health Surveillance & Research MedicalResearch.com: What is the background for this study? Response: HPV vaccination targeting girls and young women has been introduced in many countries throughout the world. HPV vaccines are not recommended for use in pregnancy, but given the target group, inadvertent exposure will occur in early unrecognized pregnancies. However, data on the safety of HPV vaccination in pregnancy is lacking.
Asthma, Author Interviews, Nursing / 30.03.2017

MedicalResearch.com Interview with: [caption id="attachment_33542" align="alignleft" width="180"]Catherine M. Pound MD The Ottawa Children’s Treatment Centre Dr. Catherine Pound[/caption] Catherine M. Pound MD The Ottawa Children’s Treatment Centre MedicalResearch.com: What is the background for this study? Response: Asthma is the most common chronic disease of childhood and contributes to a large portion of Canadian hospital pediatric admissions.  Once patients are admitted to hospitals, they receive salbutamol, a medication used for acute asthma exacerbations, at a pre-determined frequency.  In most hospitals, physicians are the ones to decide of the frequency of administration of the salbutamol, and they decide when to wean patients off it. However, children whose salbutamol treatment administration can be decreased are usually considered stable, and often do not require immediate medical attention, which may results in delays in reassessments as well as administration of unneeded salbutamol treatments, particularly if physicians are busy looking after other sicker patients.  Additionally, physicians’ assessments of children with asthma and their decisions to wean salbutamol frequency are not standardized, and vary among physicians. Therefore, in order to improve efficiency and standardize patient assessments, we developed a clinical pathway allowing nurses to wean salbutamol for children hospitalized with asthma based on a validated asthma scoring system.
Author Interviews, Medical Imaging, MRI, Stroke / 30.03.2017

MedicalResearch.com Interview with: Jalal B. Andre M.D., D.A.B.R.® Drector of neurological MRI and MRI safety officer at Harborview Medical Center University of Washington  MedicalResearch.com: What is the background for this study? Response: Acute ischemic stroke (AIS) patients with good collaterals have better clinical outcomes. AIS is characterized by an ischemic penumbra, a region of salvageable brain tissue, that surrounds a core of irreversible ischemic infarct. The penumbra is tenuously perfused by collateral blood vessels which, if extensive enough, can maintain penumbral perfusion, improving the odds that a larger volume of brain tissue will survive. Standard, first-line methods for evaluating collaterals in the acute setting include CT angiography, MR angiography, and (less commonly) digital subtraction angiography. Arterial spin labeling (ASL) is an emerging MRI technique that assesses cerebral perfusion. Its advantages include relatively short scan time (4-6 minutes), lack of ionizing radiation, and independence from an exogenous contrast agent (contraindicated in patients with impaired renal function or documented sensitivity). Collaterals can be identified within ASL images as foci of curvilinear hyperintensity bordering regions of hypoperfusion. We sought to explore a novel relationship between the presence of ASL collaterals (ASLc) and neurological outcome in acute ischemic stroke patients.
Author Interviews, Boehringer Ingelheim, Dermatology, Eli Lilly, Immunotherapy, J&J-Janssen, Merck / 30.03.2017

MedicalResearch.com Eric Hughes Global Development Franchise Head Immunology & Dermatology Novartis MedicalResearch.com: What is the background for this study? What are the main findings? Response: Psoriasis is a chronic immune-mediated inflammatory disease that negatively impacts patients’ quality of life (QOL); therefore QOL outcomes are increasingly recognized as an important measure of efficacy in psoriasis, complementing traditional measures of severity such as the Psoriasis Area and Severity Index (PASI). Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin-17A (IL-17A), exhibits significant efficacy in the treatment of moderate-to-severe psoriasis, ankylosing spondylitis and psoriatic arthritis, demonstrating a rapid onset of action and a favorable safety profile. Biologic therapies for psoriasis have previously been associated with a fall-off in efficacy over time; accordingly, extended follow-up is required to adequately evaluate novel therapeutic strategies like IL-17A inhibition. Recently, results from the extension of the SCULPTURE secukinumab trial showed that high responses initially achieved with secukinumab at year 1 in the SCULPTURE study were sustained over time up to 3 years with no new or unexpected safety concerns. In this analysis, we examined whether the sustained efficacy observed in SCULPTURE up to 3 years was translated into sustained effect of secukinumab on patient’s QOL measured by the Dermatology Life Quality Index (DLQI) questionnaire. SCULPTURE, a multi-center extension study, was conducted with subjects who completed 52 weeks of treatment. Subjects were randomized into two maintenance dosing regimens; a fixed-interval schedule of secukinumab 300 mg every 4 weeks (Fixed interval dosing regimen (FI) cohort), and secukinumab retreatment-as-needed (Retreatment as needed (RAN) cohort), in which subjects received placebo until start of relapse, at which time secukinumab 300 mg every 4 weeks was re-initiated. The analysis using as-observed data showed that at Year 3, improvements in the total score on DLQI was well sustained in both FI and RAN cohorts. Approximately two-thirds of the subjects in the FI cohort reported no impact of skin disease on QOL (corresponding to a score of 0 or 1 on DLQI). The proportion of patients in the RAN cohort reporting no impact of the disease on their QOL was well sustained through 3 years but remained consistently lower than those observed in the FI cohort. The results for each subscale of the DLQI questionnaire were consistent with those with DLQI total score i.e. showing high and sustained proportions of patients reporting no impact of the disease on different domains of health-related QOL in the two secukinumab cohorts with greater effect in the FI cohort compared to the RAN cohort.
Author Interviews, Critical Care - Intensive Care - ICUs, Dermatology, JAMA / 30.03.2017

MedicalResearch.com Interview with: Prof. Dr. Maja Mockenhaupt Dept. of Dermatology Medical Center - University of Freiburg Deutschland / Germany MedicalResearch.com: What is the background for this study? Response: Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are severe cutaneous adverse reactions that are associated with high morbidity and mortality. Primarily due to their rareness, therapeutic effects are often studied in observational settings. An evidence-based standardized treatment protocol for SJS/TEN is still missing.
Author Interviews, Biomarkers, Breast Cancer, Genetic Research, Yale / 29.03.2017

MedicalResearch.com Interview with: [caption id="attachment_33526" align="alignleft" width="133"]Tara Sanft, MD Assistant Professor of Medicine (Medical Oncology) Medical Director of Adult Survivorship Yale Cancer Center Survivorship Clinic Dr. Tara Sanft[/caption] Tara Sanft, MD Assistant Professor of Medicine (Medical Oncology) Medical Director of Adult Survivorship Yale Cancer Center Survivorship Clinic  MedicalResearch.com: What is the background for this study? Response: Previous studies have demonstrated the benefit of extended endocrine therapy (EET) for hormone receptor-positive (HR+) breast cancer in preventing late relapse, however that benefit is limited to 3-5% of women where late recurrence was prevented or staved off. However, EET has become common practice and as a result we are exposing many patients to risks of side effects and toxicities associated with anti-estrogen therapies when they may not be benefitting, and, conversely may not be treating the patients that might actually benefit. There is a real need to better identify the patients who are both at most risk of late distant recurrence, and most likely to benefit from EET. This prospective study included 141 patients with a mean age of 62. In the study, 83% of patients were postmenopausal, 73% were stage I. Breast Cancer Index (BCI) is a gene expression-based test and is the only currently available validated biomarker that is both prognostic for late distant recurrence and predictive for likelihood of benefit from EET. The purpose of this prospective study was to assess the impact of BCI on: physician EET recommendations; physician confidence; patient satisfaction, anxiety, and decision-conflict; and the cost impact of BCI.
Author Interviews, BMJ, Cost of Health Care, Orthopedics / 29.03.2017

MedicalResearch.com Interview with: [caption id="attachment_33519" align="alignleft" width="130"]Bart S Ferket, MD, PhD Assistant Professor, Population Health Science and Policy Icahn School of Medicine at Mount Sinai Dr. Bart Ferket[/caption] Bart S Ferket, MD, PhD Assistant Professor, Population Health Science and Policy Icahn School of Medicine at Mount Sinai MedicalResearch.com: What is the background for this study? Response: The annual rate of total knee replacement in the US has doubled since 2000, and especially in those aged 45-65 utilization of this procedure has increased. The increase in practice cannot fully be explained by an increase in the prevalence of osteoarthritis and population growth, and has been partly attributed to expansion to people with less severe symptoms. The total number of procedures performed each year now exceeds 640,000. The evidence for the benefit of total knee replacement has been based on studies without a comparison group of no total knee replacement, and so far only one randomized clinical trial has been published. Although the published literature shows large improvements of pain, physical functioning and overall quality of life following the procedure, patients included in these studies generally had severe preoperative symptoms. A number of studies have suggested, however, that up to a third of recipients of total knee replacement show no benefit, and that those with poor physical functioning before surgery may show larger improvements. Therefore, the current US patient population undergoing total knee replacement might show less significant improvement in symptoms on average as compared with a hypothetical scenario in which eligibility is limited to those with more severe symptoms.  
Author Interviews, Cost of Health Care, Fertility, OBGYNE / 29.03.2017

MedicalResearch.com Interview with: [caption id="attachment_33423" align="alignleft" width="133"]Emily S. Jungheim, MD, MSCI Assistant Professor, Obstetrics and Gynecology Division of Reproductive Endocrinology and Infertility Washington University St. Louis, Missouri Dr. Jungheim[/caption] Emily S. Jungheim, MD, MSCI Assistant Professor, Obstetrics and Gynecology Division of Reproductive Endocrinology and Infertility Washington University St. Louis, Missouri MedicalResearch.com: What is the background for this study? What are the main findings? Response: Many women with health insurance lack coverage for fertility treatment so they end up being self-pay for fertility treatments which can be expensive and limit access to care. 15 states have responded with mandates for employers to include fertility coverage in their employee insurance benefits, and 5 of these have comprehensive mandates that include IVF. Illinois is one of these states. Washington University is located on the border between Illinois and Missouri so our fertility center treats a number of women with coverage for fertility treatment and a large number of women who are self-pay for fertility treatment. We suspected that women requiring IVF to conceive were more likely to follow through with treatments if they had coverage so we decided to look at our data. Ultimately we confirmed our suspicions. Women with coverage were more likely to come back for additional cycles of IVF if they didn't conceive. Ultimately this ability to come back for additional treatment cycles led to a higher chance of live birth.
Author Interviews, Clots - Coagulation, Heart Disease, Thromboembolism / 29.03.2017

MedicalResearch.com Interview with: [caption id="attachment_33502" align="alignleft" width="200"]Paul Burton, MD, PhD, FACC Vice President, Medical Affairs Janssen Dr. Paul Burton[/caption] Paul Burton, MD, PhD, FACC Vice President, Medical Affairs Janssen MedicalResearch.com: What is the background for this study? What are the main findings? Response: Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), affects more than 900,000 Americans each year; one-third of these occurrences are fatal. Once a person experiences a VTE, they are at risk of having another occurrence. Guidelines currently recommend anticoagulant therapy with a non-vitamin K antagonist oral anticoagulant (NOAC), like XARELTO® (rivaroxaban), for three months or longer. Once anticoagulant therapy is stopped, up to 10 percent of people will experience a recurrence during the first year and up to 20 percent within three years. In people who decide to stop anticoagulant therapy, guidelines currently suggest using aspirin for long-term prevention of recurrent VTE rather than no aspirin at all. The Phase 3 EINSTEIN CHOICE study was designed to compare the efficacy and safety of XARELTO® to aspirin for continued VTE management in people who experienced an initial VTE. The study met its primary endpoint, finding both XARELTO® doses (10 mg or 20 mg once daily) to be superior to aspirin 100 mg once daily in preventing recurrent VTE, with no significant impact on safety. Specifically, XARELTO® 10 mg reduced the risk of recurrent VTE by 74 percent and XARELTO® 20 mg by 66 percent. Rates of major bleeding were comparable and low across all treatment groups. These results were presented at the American College of Cardiology's 64th Annual Scientific Session (ACC.17) during a Joint ACC/Journal of American Medical Association Late-Breaking Clinical Trials session and published simultaneously in The New England Journal of Medicine.
Allergies, Author Interviews, JAMA, Pediatrics / 29.03.2017

MedicalResearch.com Interview with: [caption id="attachment_33418" align="alignleft" width="200"]Dr. Debra Palmer (BSc, BND, PhD) on behalf of my fellow co-authors on this publication Childhood Allergy and Immunology Research University of Western Australia Dr. Debra Palmer[/caption] Dr. Debra Palmer (BSc, BND, PhD) on behalf of my fellow co-authors on this publication Childhood Allergy and Immunology Research University of Western Australia MedicalResearch.com: What is the background for this study? What are the main findings? Response: We conducted a multicentre trial, Starting Time of Egg Protein (STEP) involving 820 infants, and found a 25% risk reduction in egg allergy with early regular egg intake from 4-6.5 months compared with egg avoidance to 10 months of age, although this did not achieve statistical significance. So we also investigated in exploratory analyses whether the effect of regular egg introduction in solid foods was modified by any maternal, family or infant characteristics. Our results found that infants from families of higher socioeconomic status and those families who consume few eggs per week could benefit by less egg allergy at 12 months of age from regular egg intake once they start eating solid foods.
Author Interviews, C. difficile, Gastrointestinal Disease, JAMA, Mayo Clinic / 29.03.2017

MedicalResearch.com Interview with: [caption id="attachment_33270" align="alignleft" width="166"]Sahil Khanna, Dr. Sahil Khanna[/caption] Sahil Khanna, M.B.B.S. MS Division of Gastroenterology and Hepatology Mayo Clinic, Rochester, Minnesota MedicalResearch.com: What is the background for this study? What are the main findings? Response: Clostridium difficile infection (CDI) is the most common cause of hospital-acquired diarrhea and has recently shown increasing incidence especially in the community. Novel risk factors for CDI development include the use of gastric acid suppression medication, presence of systemic comorbid conditions, C difficile carriage in water and food sources, amongst others. Gastric acid suppression medications such as proton-pump inhibitors (PPIs) and histamine-2 receptor blockers (H2Bs) are commonly prescribed and consumed over the counter for gastroesophageal reflux disease, peptic ulcer disease, or functional dyspepsia, but they are also sometimes prescribed for unnecessary indications, which leads to overuse of these medications. Recurrent CDI after a primary infection is a major problem, with the risk being as high as 50% to 60% after 3 or more Clostridium difficile infections. Data on the association between acid suppression and recurrent CDI are conflicting and therefore we performed a systematic review and meta-analysis to study the association between the use of gastric acid suppression medications and the risk of recurrent CDI.
Author Interviews, Dermatology, Immunotherapy / 29.03.2017

MedicalResearch.com Interview with: [caption id="attachment_33490" align="alignleft" width="130"]Emma Guttman, MD, PhD Professor, Dermatology, Medicine and Clinical Immunology Vice Chair of Research in the Dermatology Department Director of the center for Excellence Eczema in the Occupational/Contact Dermatitis clinic Director of the Laboratory of Inflammatory Skin Diseases Icahn School of Medicine at Mount Sinai Medical Center New York Dr. Guttman[/caption] Emma Guttman, MD, PhD Professor, Dermatology, Medicine and Clinical Immunology Vice Chair of Research in the Dermatology Department Director of the center for Excellence Eczema in the Occupational/Contact Dermatitis clinic Director of the Laboratory of Inflammatory Skin Diseases Icahn School of Medicine at Mount Sinai Medical Center New York MedicalResearch.com: Would you briefly explain what is meant by atopic dermatitis? How many people are affected by this disorder? Response: Atopic dermatitis or eczema as most people know it is an itchy red scaly skin disorder characterized by a very severe itch, that disrupts daily activities, and sleep and severely impairs the quality of life of patients. In the US 30 million people are affected by it, and 1/3 of these we expect to be moderate to severe. MedicalResearch.com: What is the background for Dupilumab therapy? How does it differ from emollients, steroids or topical immunomodulator treatments for eczema ie Protopic? Response: The background is that we currently do not have good treatments for long term use for our moderate to severe patients. The only approved drug by the FDA for atopic dermatitis in the US is oral prednisone, that has many long term side effects and causes disease rebound upon discontinuation. Other treatments with many side effects are broad immune suppressants--Cyclopsorin A, Mycophenolate mofetyl and phototherapy that is not feasible for most patients. Thus there is a large unmet need for safer and better treatments for moderate to severe atopic dermatitis patients. Dupilumab is different since it only targets one immune axis--Th2 axis, providing a safer alternative, with high efficacy, that is equal or even better than cyclosporin A, that is the current gold standard immune suppressant, and harbors many side effects including permanent effects on the kidneys after long term use. Topical treatments, while useful for mild patients, are often not adequate or sufficient to control moderate to severe patients that usually have more than 10% body surface area involved and need a systemic treatment.
Author Interviews, Boehringer Ingelheim, Dermatology, Immunotherapy / 29.03.2017

MedicalResearch.com Interview with: Eric Hughes, Global Head of Development, Immunology & Dermatology Novartis Pharma AG Basel, Switzerland MedicalResearch.com: What is the background for this study? What are the main findings? Response: It is well established that psoriasis negatively affects quality of life and work productivity. However, how the treatments affect psoriasis severity (based on skin clearance, itch, pain and scaling symptoms), health-related quality of life (HRQOL), work productivity, and daily activity directly or indirectly (via other factors) are still largely unknown. Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin-17A (IL-17A), exhibits significant efficacy in the treatment of moderate-to-severe psoriasis, ankylosing spondylitis, and psoriatic arthritis, demonstrating a rapid onset of action and a favorable safety profile. In CLEAR, a Phase 3b head-to-head study versus ustekinumab, secukinumab demonstrated sustained superior efficacy in clearing skin through Week 52, greater improvement in symptoms and HRQOL, greater relief of work and activity limitations, and a comparable safety profile. In this sub-analysis of the CLEAR study, Novartis was interested in examining the relationships among multiple variables that are thought to be important to patients with psoriasis. The direct and indirect (i.e. mediated) effects of treatment (secukinumab or ustekinumab) on psoriasis severity and patients’ HRQOL, work productivity, and daily activity were examined. The evaluation was conducted using structural equation modeling (or path analysis) and compared these relationships for secukinumab versus ustekinumab at 16 and 52 weeks. Structural equation modeling or path analysis is a statistical method that models the direct and indirect relationship between multiple patient-relevant outcomes simultaneously. Goodness-of-fit statistics for all models were excellent confirming the robustness of the results. Results at Week 16 and at Week 52 for different Psoriasis Area and Severity Index (PASI) response categories (e.g. PASI 75, PASI 90, PASI 100) indicated that psoriasis treatment indirectly affected HRQOL and work productivity and daily activity, measured with the Dermatology Life Quality Index (DLQI) and the Work Productivity and Activity Impairment (WPAI) questionnaires, respectively. Actually, greater effect of secukinumab over ustekinumab on DLQI was mediated by greater improvement of secukinumab in PASI response as well as by greater improvement in psoriasis-related symptoms (itch, pain and scaling). Greater effect of secukinumab over ustekinumab on work productivity and daily activity was mediated by greater improvement of secukinumab in psoriasis-related symptoms.
Author Interviews, Gastrointestinal Disease, Microbiome / 28.03.2017

MedicalResearch.com Interview with: [caption id="attachment_33446" align="alignleft" width="200"]Dr Pauline Scanlan Royal Society-Science Foundation Ireland University Research Fellow/APC Faculty, APC Microbiome Institute, Biosciences, University College Cork, Éire Dr. Scanlan[/caption] Dr Pauline Scanlan Royal Society-Science Foundation Ireland University Research Fellow/APC Faculty, APC Microbiome Institute, Biosciences, University College Cork, Éire MedicalResearch.com: What is the background for this study? Response: The human gut is host to an incredible diversity of microbes collectively known as the gut microbiome. Each of us has a unique collection of bacterial strains that form part of the gut microbiome. This uniqueness is of potentially crucial importance with respect to host health as we know that differences in bacterial strain diversity within species could have a range of positive or negative consequences for the human host. For example, some strains of a given bacteria are harmless whilst another strain of the same bacterial species could kill you. A classic example of such a difference in strain functionality is exemplified by the gut bacterium Escherichia coli – one strain called E. coli Nissle 1917 is used as a probiotic and another, E. coli O157:H7, has been responsible for a number of deadly food-borne pathogen outbreaks. Therefore a better understanding of what drives bacterial strain diversity is not just fundamental to our understanding of the ecology and evolution of microbes but is also highly relevant for improvements in human health and disease prevention.
Author Interviews, Brigham & Women's - Harvard, HIV, Pediatrics / 28.03.2017

MedicalResearch.com Interview with: [caption id="attachment_33465" align="alignleft" width="135"]Anne M Neilan, MD,MPH Assistant In Medicine, Massachusetts General Hospital Research Fellow, Harvard Medical School Department: Medicine Service Division: Infectious Disease Department: Pediatric Service Massachusetts General Hospital Boston, MA 02114 Dr. Neilan[/caption] Anne M Neilan, MD,MPH Assistant in Medicine and Pediatrics Massachusetts General Hospital Instructor at Harvard Medical School Department: Medicine Service Division: Infectious Disease Department: Pediatric Service Massachusetts General Hospital Boston, MA 02114 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Adolescents infected with HIV – either at birth or later in life – experience poorer health outcomes compared to adults with HIV in nearly every respect. This study found that U.S. youth infected with HIV around the time of their birth are at higher risk throughout their adolescence and young adulthood for experiencing serious health problems, poor control of the HIV virus (having high levels of HIV virus in their bodies and fewer CD4 immune cells which protect the body from infection), or death. The study also found that among those with good HIV control, serious health problems are rare. By combining data from two large, long-term U.S. studies – the Pediatric HIV/AIDS Cohort Study (PHACS, www.phacsstudy.org) and the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT, www.impaactnetwork.org) Network – we were able to study the health of more than 1,400 perinatally HIV-infected children, adolescents and young adults ages 7 to 30 years between 2007 and 2015. The study found that youth ages 13 to 30 were most likely to have poor HIV control AIDS-related illnesses, and death compared to younger participants. Among 18 – 30 year-olds, the study found that poor control of the HIV virus – meaning higher levels of HIV virus and lower levels of CD4 immune cells which protect the body from infection –35 percent of the time, increasing the risk that these youth would stop responding to certain HIV medications and could transmit HIV to others. These findings are consistent with other U.S. and European reports. Despite being engaged in health care, the number of deaths among youth born with HIV in the U.S. is 6 to12 times higher than for youth without HIV of the same age, sex and race. Along with HIV-related health problems, the most commonly reported health conditions concerned mental health and brain and nervous system development. Many women in the study also had sexually transmitted infections, which was found to be associated with lower CD4 immune cell counts. This may suggest a biological mechanism or may reflect that patients who have difficulty with their medications are also engaging in more frequent risky sexual behaviors.
Author Interviews, Cancer Research, JAMA, OBGYNE, Pediatrics / 27.03.2017

MedicalResearch.com Interview with: [caption id="attachment_33458" align="alignleft" width="200"]Hazel B. Nichols, PhD, UNC, assistant professor Lineberger Comprehensive Cancer Center member UNC Gillings School of Global Public Health. Dr. Nichols[/caption] Hazel B. Nichols, PhD, UNC Assistant professor Lineberger Comprehensive Cancer Center member UNC Gillings School of Global Public Health. MedicalResearch.com: What is the background for this study? Response: Each year more than 45,000 adolescent and young adult women (AYA, ages 15-39 years) are diagnosed with cancer in the United States. While many of these women may wish to have children in the years following diagnosis, there is currently little information available to address their concerns about the impact of cancer diagnosis and treatment on future pregnancy. We identified >2,500 women who had a child after their cancer diagnosis using data from the North Carolina Central Cancer registry and statewide birth certificate files. We investigated whether adverse birth outcomes, such as preterm birth and low birth weight, were more common among AYA cancer survivors compared to women without cancer. We also looked at infant Apgar scores, which measure newborn health, and a calculation called small-for-gestational age, which can indicate restricted growth during pregnancy.