Author Interviews, Emergency Care, Infections, JAMA, Pediatrics, Pulmonary Disease, Respiratory / 29.02.2016

MedicalResearch.com Interview with: Suzanne Schuh, MD, FRCP(C), ABPEM The Hospital for Sick Children affiliated with the University of Toronto Medical Research: What is the background for this study? Dr. Schuh: Routine measurement of oxygen saturation in bronchiolitis is sometimes used as a proxy for illness severity, despite poor correlation between these parameters. This focus on oximetry may in part relate to lack of evidence on the natural history of desaturations in bronchiolitis which are often transient, and frequently not accompanied by increased respiratory distress. Desaturations occurring in infants with mild bronchiolitis in an ED often result in hospitalizations or prolonged hospital stay. They occur in healthy infants and may also occur in infants with mild bronchiolitis at home. The main objective of this study of infants with acute bronchiolitis was to determine if there is a difference in the proportion of unscheduled medical visits within 72 hours of ED discharge in infants who desaturate during home oximetry monitoring versus those without desaturations. Our study shows that the majority of infants with mild bronchiolitis experience desaturations after discharge home. (more…)
Author Interviews, HIV / 26.02.2016

MedicalResearch.com Interview with: Wim Parys MD Global Head R&D Global Public Health Janssen Medical Research: What is the background for this study? What are the main findings? Dr. Parys: In collaboration with ViiV Healthcare, we are working to develop the first long acting all-injectable combination regimen of Janssen’s rilpivirine and ViiV’s cabotegravir. Yesterday, we have announced promising Phase 2b data of this combination regimen which when given together every 4 or 8 weeks was able to maintain viral suppression with similar efficacy to a daily oral regimen of three HIV medicines. The results show that the combination met its primary endpoint at week 32. The study will now continue in its randomized controlled design for another 64 weeks enabling us to assess longer term outcomes. In parallel to this we will work to initiate the next stages of clinical development. (more…)
Author Interviews, Dengue, Zika / 25.02.2016

MedicalResearch.com Interview with: Prof Paul Dyson Institute of Life Science Swansea University Medical School Singleton Park Swansea UK Medical Research: What is the background for this study? What are the main findings? Prof. Dyson: The spread of insect-vectored viruses such as Dengue and, more recently, Zika, underline the urgent necessity to develop new technologies to control insect disease vectors that, due to human activity, are spreading globally. The concept of using RNAi in insects is not new and is widely used as a research tool in the model organism Drosophila melanogaster. However, adapting RNAi for use in non-model insects has been slow, almost entirely due to the problem of delivering interfering RNA to the insect. Manual injection is a less than optimal means of delivery for larger insects, while including interfering RNA in a food source can be effective in smaller insects in the laboratory. But neither delivery system is suited for field applications of RNAi as a biocide. Faced with this challenge, we (myself and Dr Miranda Whitten) conceived the concept of symbiont-mediated RNAi and have advanced it with support from the UK BBSRC and the Gates Foundation, establishing it as a viable mechanism of delivery of RNAi in (a) a tropical disease vector, Rhodnius prolixus, a vector of Chagas disease, exemplified by targeting insect fertility, and (b) a globally invasive vector of plant disease, Western Flower Thrips, targeting larval growth. Interfering RNA is actively produced by symbiotic insect bacteria that multiply within the host. Critical to the technology is to ensure the stability of RNA synthesis by these bacteria. The interfering RNA is then released by the bacteria, absorbed and systemically circulated within the host, thereby causing knock-down of gene expression in specific tissues. We have exploited this technology to severely impair fertility of Rhodnius prolixus, and to cause mortality of developing larvae of Western Flower Thrips. As a biocide, the technology offers exquisite specificity due to the co-evolution and co-dependencies of the symbiont and its insect host, combined with the sequence-specificity of the RNAi. Moreover, development of resistance is highly improbable. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Infections, JAMA / 24.02.2016

MedicalResearch.com Interview with: Dr. Manu Shankar-Hari MB BS MD FRCA EDIC FFICM MSc[Epi] Consultant, Intensive Care Medicine; Guy’s and St Thomas’ NHS Foundation Trust Clinical Research Associate, Intensive Care National Audit and Research Centre Honorary Senior Lecturer in Intensive Care Medicine Division of Asthma Allergy and Lung Biology King’s College London, UK Medical Research: What is the background for this study? What are the main findings? Dr. Shankar-Hari: Septic shock is a complex illness. The previous Consensus Definitions (1991 and 2001) place emphasis on the circulatory abnormalities as the core concept and neither definitions provide data driven clinical criteria. In addition, last ten years of basic science research has established the concept that septic shock is associated with plethora of cellular and metabolic abnormalities (often referred to as cellular stress), alongside circulatory dysfunction. In this background, the paper published in JAMA provides an updated illness concept (definitions) and data driven clinical criteria for diagnosing septic shock at the bedside.

The updated illness concept: 'Septic shock is defined as a subset of sepsis in which underlying circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than sepsis alone.’

The clinical criteria: 'Adult patients with septic shock can be identified using the clinical criteria of hypotension requiring vasopressor therapy to maintain mean arterial blood pressure 65 mm Hg or greater and having a serum lactate level greater than 2 mmol/L after adequate fluid resuscitation.' (more…)
Author Interviews, Hospital Acquired, Infections, Nature / 24.02.2016

MedicalResearch.com Interview with: Ashootosh Tripathi, PhD Postdoctoral Research Fellow Life Sciences Institute I Sherman lab University of Michigan Ann Arbor, MI, USA MedicalResearch: What is the background for this study? What are the main findings? Dr. Tripathi: Acinetobacter baumannii is a nosocomial opportunistic and resistant pathogen that can spread epidemically among patients causing ventilator-associated pneumonia and bacteremia. The mortality rates associated with it can be as high as 60%, representing a paradigm of pathogenesis, transmission and resistance. In addition, numerous reports have shown the startling emergence of multidrug-resistant A. baumannii in hospitals as well as the identification of pan-drug-resistant strains at some locations. Among the various reasons for the antibiotic resistance of this pathogenic microbe, perhaps the most significant is mediated by its tendency to form biofilms (a highly structured extracellular polymeric matrix), which provide the microbe with the alarming ability to colonize medical devices. Interestingly, despite the well-understood role of bacterial biofilm behind aggravating antimicrobial resistance, there are currently no drugs specifically targeting biofilms in clinical trials to date. The study sought to solve this problem through the development of a biofilm inhibitor as a precision medicine, directed towards vulnerable patients, to avoid potential life-threatening infections. A crystal-violet based high throughput in vitro screen was developed to identify inhibitors of A. baumannii biofilms against our natural products extract (NPE) library. The vast NPE library of ~42,000 extracts has been under constant development in Prof David H. Sherman laboratory at University of Michigan, Ann Arbor, for over the past decade, from a relatively underexplored marine microbiome collected from different part of world viz., Costa Rica, Panama, Papua New Guinea, etc., and is available for any research group with a robust high-throughput screening (HTS) assay (http://www.lsi.umich.edu/centers/center-for-chemical-genomics). The HTS assay that was queried against a library of 9,831 NPEs aimed to identify extracts inhibiting biofilm formation as a primary screening. Further secondary screening and activity threshold optimization revealed the extract from Streptomyces gandocaensis (collected from Costa Rica) to be of particular interest due to its ability to inhibit biofilm formation and had a limited effect on A. baumannii growth. Activity based chromatographic separation and analysis of extracts derived from S. gandocaensis resulted in the discovery of three peptidic metabolites (cahuitamycins A–C), with cahuitamycin C being the most effective biofilm inhibitor (IC50 =14.5 µM) with negligible A. baumannii growth inhibition (an important trait for ideal biofilm inhibitor). Following up on the exciting discovery, we also completely characterized the biosynthetic machinery involved in making the active molecules by S. gandocaensis, using sophisticated bioinformatics and molecular biology techniques. The knock out analysis revealed that the biosynthesis of cahuitamycin C proceeds via a convergent biosynthetic pathway, with one of the steps apparently being catalyzed by an unlinked gene encoding a 6-methylsalicylate synthase. Efforts to assess starter unit diversification through selective mutasynthesis led to production of unnatural analogues cahuitamycins D and E with increased potency (IC50=8.4 and 10.5 µM) against A. baumannii biofilm. (more…)
Author Interviews, Global Health, HIV, NEJM, OBGYNE / 22.02.2016

MedicalResearch.com Interview with: Jared Baeten, MD PhD Vice Chair, Department of Global Health Professor, Departments of Global Health, Medicine, and Epidemiology Co-Director, International Clinical Research Center University of Washington MedicalResearch.com: What is the background for this studies? Dr. Baeten: Women account for nearly 60 percent of adults with HIV in sub-Saharan Africa, where unprotected heterosexual sex is the primary driver of the epidemic. While several studies have shown that antiretroviral medications (ARVs) are highly effective in preventing HIV, other studies – such as VOICE and FACTS 001 – suggest that for young, at-risk women in Africa, ARVs delivered as a vaginal gel or as a tablet may not be acceptable. Products must be used to be effective, and that was not the case for most of the participants in previous studies. Medical Research: What was the aim of ASPIRE and The Ring Study? Dr. Baeten: As Phase III clinical trials, ASPIRE and The Ring Study were designed to determine whether a vaginal ring containing an antiretroviral (ARV) drug called dapivirine is safe and effective in protecting women against HIV when used for a month at a time. These trials also sought to determine whether women find the vaginal ring practical and easy to use. As sister studies, ASPIRE and The Ring Study were designed as the centerpiece of a broader licensure program to provide the strength of evidence to support potential licensure of the dapivirine vaginal ring for preventing HIV in women. Because at least two Phase III efficacy trials are usually needed for a product to be considered for regulatory approval, ASPIRE and The Ring Study were conducted in parallel to accelerate the timeline to the ring’s potential approval. (more…)
Author Interviews, CDC, HIV / 21.02.2016

MedicalResearch.com Interview with: Martin Hoenigl, MD Postdoctoral Fellow AntiViral Research Center, Department of Medicine University of California, San Diego Medical Research: What is the background for this study? Response: The detection of acute HIV infection (AHI) is critical to HIV prevention and treatment strategies. Many field-based testing programs rely on point-of-care HIV antibody testing, which will reliably identify persons with established infection, but fail to detect persons with AHI. In many of these programs additional tests for AHI are only performed / recommended in persons presenting with signs and symptoms consistent with an acute retroviral syndrome (ARS). These signs and symptoms are unspecific and include fatigue, headache, pharyngitis, skin rash, GI symptoms, night sweats and others. However, the proportion of persons with acute HIV infection presenting symptomatic for their diagnostic test remains unknown. The objective of our study was therefore to determine the proportion of persons with acute HIV infection presenting with signs and symptoms consistent with ARS for HIV screening. Medical Research: What are the main findings? Response: We analyzed signs and symptoms in 90 patients diagnosed with acute HIV infection in a community-based program in San Diego that offered universal HIV-1 nucleic acid amplification testing, independent of signs and symptoms. Forty-seven (52%) patients reported ongoing signs or symptoms consistent with ARS on the day of NAT screening. Another 25 (28%) reported signs or symptoms that had occurred during the 14 days before testing, but had resolved by the testing date. Another 12 (13%) reported signs and symptoms that started after the diagnostic test. Only 6/90 (7%) reported no signs and symptoms consistent with ARS. As a secondary finding, viral loads were significantly higher (p=0.001) in the 72 individuals reporting signs and symptoms consistent with ARS before or at the time of NAT screening compared to the 18 participants who did not report signs and symptoms at their diagnostic test. Most frequently reported ARS signs and symptoms included fever, myalgia, fatigue and headache. (more…)
Author Interviews, CDC, Ebola, NEJM / 19.02.2016

MedicalResearch.com Interview with: Tim Uyeki MD, MPH, MPP Influenza Division National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention and Associate Clinical Professor of Pediatrics Department of Pediatrics San Francisco General Hospital Medical Research: What is the background for this study? Dr. Uyeki: During 2014-2015, 27 patients with Ebola virus disease (EVD) were hospitalized in the United States and Europe. Frequent international teleconferences were convened among U.S. and European clinicians caring for EVD patients, often on a weekly basis, to share detailed information and suggestions on clinical management of these patients. We collected clinical, epidemiologic, laboratory, and virologic data on all of these patients and performed descriptive data analyses. We summarized our findings in this article. Medical Research: What are the main findings? Dr. Uyeki: Of the 27 patients with Ebola virus disease cared for in 15 hospitals in nine countries, the median age was 36 years; 19 (70%) were male; 9 of 26 (35%) had underlying medical conditions; and 22 (81%) were healthcare personnel, including 17 of 22 (77%) who had worked in an Ebola treatment unit in West Africa. Of the 27 patients, 20 (74%) were medically evacuated from West Africa, 4 (15%) were imported cases, and 3 (11%) were healthcare personnel who acquired Ebola virus infection while caring for EVD patients in the U.S. or Europe. At illness onset, the signs and symptoms of EVD were non-specific; the most common symptom reported was fatigue. At admission to a hospital in the U.S. or Europe, most patients had fever, weakness, and gastrointestinal symptoms. The median time from illness onset to hospitalization was four days. During hospitalization, all patients had diarrhea, often profuse watery diarrhea; and most experienced electrolyte abnormalities such as hyponatremia, hypokalemia, hypocalcemia, and hypomagnesemia, as well as hypoalbuminemia. One third of patients experienced renal abnormalities such as oliguria or anuria, nearly 60% were clinically diagnosed with systemic inflammatory response syndrome, and one third were clinically diagnosed with encephalopathy or encephalitis. Although minor bleeding abnormalities were reported in some patients, only two patients had any gross hemorrhage. Leukopenia was observed during the first week of illness, with increases in white blood cell count during the second week. Thrombocytopenia was common, and aminotransferase levels peaked in the second week of illness. Creatine kinase and lactate levels were elevated in most of the patients who were tested. Ebola virus levels in blood peaked on the seventh day of illness, and critical illness occurred at the end of the first week and during the second week after illness onset. All patients received intravenous fluids; most were treated empirically with antibiotics; and 85% received an investigational therapy, including 70% who received at least two experimental therapies. Eleven (41%) patients were critically ill, including seven who required invasive mechanical ventilation and five who received continuous renal replacement therapy. Five (18.5%) patients died (81.5% survival). (more…)
Alzheimer's - Dementia, Author Interviews, Dental Research, Infections, Stroke / 18.02.2016

MedicalResearch.com Interview with: Dr. Robert Friedland MD Mason C. and Mary D. Rudd Endowed Chair In Neurology Professor, Dept. of Neurology University of Louisville Health Care Outpatient Center Louisville, KY 40292 Medical Research: What is the background for this study? What are the main findings? Dr. Robert Friedland: Oral infectious diseases are associated with stroke. Previous research by this group has shown that oral bacteria, cnm-positive Streptococcus mutans, was associated with cerebral microbleeds and intracerebral hemorrhage. We developed this study to investigate the roles of this bacteria in patients entering the hospital for all types of stroke. Among the patients who experienced intracerebral hemorrhage (ICH), 26 percent were found to have a specific bacterium in their saliva, cnm-positive S. mutans. Among patients with other types of stroke, only 6 percent tested positive for the bacterium. We also evaluated MRIs of study subjects for the presence of cerebral microbleeds (CMB), small brain hemorrhages which may cause dementia and also often underlie ICH. We found that the number of CMBs was significantly higher in subjects with cnm-positive S. mutans than in those without. (more…)
Addiction, Author Interviews, HIV / 16.02.2016

MedicalResearch.com Interview with: Pedro Mateu-Gelabert, Ph. D. Principal Investigator National Development Research Institutes, Inc. New York, NY 10010 Medical Research: What is the background for this study? What are the main findings? Dr. Mateu-Gelabert: Heroin production in Colombia increased dramatically in recent decades, and some studies point to an increase in local heroin consumption since the mid-1990s. Despite this rapid increase, little is known about the effects of these activities on heroin injection within Colombia. One of the biggest concerns surrounding heroin injection is the potential spread of HIV through drug user networks. Medical Research: What should clinicians and patients take away from your report? Dr. Mateu-Gelabert: The key take home message in the paper is that a widespread early implementation of harm reduction services (e.g. opioid substitution therapy, HIV testing, syringe exchange programs) can prevent HIV among young PWID (People Who Inject Drugs) before it rapidly spreads within drug injection networks. Reducing HIV among young drug injectors could prevent the spread of HIV from PWID to the general population. (more…)
Author Interviews, Infections, PLoS / 14.02.2016

MedicalResearch.com Interview with: Tamar Kleinberger, Ph.D. Dept. of Molecular Microbiology Faculty of Medicine Technion – Israel Institute of Technology Haifa ISRAEL Medical Research: What is the background for this study? What are the main findings? Dr. Kleinberger: The cellular DNA damage response (DDR) is a conglomerate of pathways designed to detect DNA damage and signal its presence to cell cycle checkpoints and to the repair machinery, allowing the cell to pause and mend the damage, or if the damage is too severe, to trigger cell death or senescence. Replication intermediates and linear double-stranded genomes of DNA viruses are recognized by the cell as DNA damage and activate the DDR. If allowed to operate, the DDR will stimulate ligation of viral genomes and will inhibit virus replication. To prevent this outcome, many DNA viruses evolved ways to limit the DDR. For example, adenoviruses, a family of viruses that cause respiratory illnesses or gastrointestinal disease or eye infections, have been reported to inhibit the DDR by degrading DNA damage sensor proteins or by removing them from virus replication centers. Our present work reveals that adenovirus evolved an additional mechanism to inhibit the DDR, using its E4orf4 protein. The viral E4orf4 protein, together with its cellular partner, the PP2A phosphatase, inhibits damage signaling by reducing phosphorylation of proteins belonging to different DDR branches. As a result E4orf4 causes accumulation of DNA damage in the cells. Inhibition of the DDR regulators ATM and ATR as well as expression of E4orf4 enhance infection efficiency. We found that, at least in the cells we studied, ATM inhibition was important to the early stage of the virus life cycle, whereas ATR inhibition impacted mostly late protein expression and progeny virus production. Furthermore, we previously reported that E4orf4 induces cancer-specific cell death when expressed alone, and in the present report we found that E4orf4 sensitized cells to killing by sub-lethal concentrations of DNA damaging drugs, likely because it inhibited DNA damage repair. These findings provide one explanation for the cancer-specificity of E4orf4-induced cell death because many cancers have DDR deficiencies leading to increased reliance on the remaining intact DDR pathways and to enhanced susceptibility to DDR inhibitors such as E4orf4. Thus DDR inhibition by E4orf4 contributes both to the efficiency of adenovirus replication and to the ability of E4orf4 to kill cancer cells. (more…)
Author Interviews, Hospital Acquired, Outcomes & Safety / 12.02.2016

MedicalResearch.com Interview with: Christine Greene, Ph.D. and Chuanwu Xi, Ph.D. School of Public Health, Department of Environmental Health Sciences University of Michigan Medical Research: What is the background for this study? Response: Healthcare-associated infections (HAIs) are a serious problem globally. Acinetobacter baumannii, a gram-negative opportunistic pathogen, was mostly unheard of 10-15 years ago, but is now a clinically significant pathogen in hospitals. A. baumannii causes a variety of infections ranging from urinary tract infections to bacteremia and patients who are at high risk of A. baumannii infection are those who are critically ill, who have indwelling catheters or patients with long hospital says. Once infected, the risk of mortality is high – up to 26% for in-hospital patients and as much as 43% for those in the ICU. The mortality rate is high largely due to the rapid ability for this pathogen to develop antibiotic resistance. Despite patient isolation, we still see hospital outbreaks because A. baumannii survives very well in the environment and it is resistant to most biocides, detergents, dehydration, and UV radiation. A. baumannii is also a known biofilm former. Biofilms serve to protect the microorganism. In the open environment, biofilms protect from desiccation and other harsh environmental insults such as biocides, thereby promoting persistence in the open environment. In the human body, biofilms protect against the immune system, provide an additional layer of protection from antibiotics and contribute to reoccurring infections in the patient. This research characterizes the fitness (desiccation tolerance) trade-offs imposed on A. baumannii isolated from clinical and environmental settings. This investigation compares isolates of A. baumannii from both environments on the basis of multidrug resistance, biofilms and desiccation tolerance. We looked to see if either MDR or biofilm formation increased fitness (ability to tolerate desiccation) or impose a fitness cost depending on environmental conditions. Medical Research: What are the main findings? Response: We provide evidence of variation in desiccation tolerance between clinical and environmental isolates of similar phenotypes and show a trend of increased desiccation tolerance for high biofilm forming clinical isolates with additional tolerance when the ability to form biofilms is coupled with the multidrug resistance. By contrast, biofilm formation had a significant impact on desiccation tolerance for environmental isolates.

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Author Interviews, CDC, HIV, Sexual Health / 12.02.2016

MedicalResearch.com Interview with: Laura Kann, PhD Chief of the School-Based Surveillance Branch (SBSB) Division of Adolescent and School Health (DASH). CDC Medical Research: What is the background for this study? Dr. Kann: Young persons aged 13–24 years accounted for an estimated 22% of all new diagnoses of human immunodeficiency virus (HIV) infection in the United States in 2014. Most new HIV diagnoses among youths occur among males who have sex with males (MSM). Among all MSM, young black MSM accounted for the largest number of new HIV diagnoses in 2014 (4,398 among blacks, 1,834 among Hispanics, and 1,366 among whites). Although other studies have examined HIV-related risk behaviors among MSM, less is known about MSM aged <18 years. Medical Research: What are the main findings? Dr. Kann: Among male students who had sexual contact with males, black students had a significantly lower prevalence than white students of drinking five or more drinks of alcohol in a row; ever using inhalants, heroin, ecstasy, or prescription drugs without a doctor’s prescription; and drinking alcohol or using drugs before last sexual intercourse. Black students also had a significantly lower prevalence than Hispanic students of drinking five or more drinks of alcohol in a row and ever using cocaine, inhalants, methamphetamines, ecstasy, or steroids without a doctor’s prescription. However, among male students who had sexual contact with males, black students had a significantly higher prevalence than white students of ever having had sexual intercourse and using a condom during last sexual intercourse; black students also had a higher prevalence than Hispanic students of ever having sexual intercourse. (more…)
Author Interviews, Nursing, Zika / 10.02.2016

MedicalResearch.com Interview with: Nancy Dirubbo, DNP, FNP, FAANP, Certificate in Travel Health, American Association of Nurse Practitioners (AANP) Fellow Cindy Cooke, DNP, FNP-C, FAANP, American Association of Nurse Practitioners (AANP) President of the Board Medical Research: Can you provide some background on what is the Zika virus? Response: Zika virus was first found in monkeys in the Zika Forest of Uganda in 1947 during a research project on mosquito borne viral diseases. From Africa, it spread to India, Indonesia and South East Asia over the next 20-30 years. Not much attention was paid to this illness, as it is often asymptomatic (perhaps as much as 80% of all cases). It causes few symptoms in adults (mild rash, conjunctivitis and headache) and so is often underdiagnosed or misdiagnosed as other self-limiting, viral diseases. Then fast forward to 2015, when a sudden increase in infants born in Brazil with microcephaly occurred and a connection was made with a sharp increase in Zika viral infections, even though the direct mechanism for causing this birth defect is not known. In 2014, there were less than 150 cases of microcephaly in Brazil, and by October 2015, there were 4,700 cases reported. Medical Research: What is the concern regarding pregnant women and their babies? Response: The concern for pregnant women is that there appears to be a link between Zika virus and microcephaly, still birth and miscarriages. Children who do survive have severe intellectual disabilities. The virus is most often transmitted by mosquitos, but may also be sexually transmitted. According to the CDC, “Sexual transmission of Zika virus is possible, and is of particular concern during pregnancy. Current information about possible sexual transmission of Zika is based on reports of three cases.” The CDC also recommends, “Men who reside in or have traveled to an area of active Zika virus transmission who have a pregnant partner should abstain from sexual activity or consistently and correctly use condoms during sex (i.e., vaginal intercourse, anal intercourse or fellatio) for the duration of the pregnancy.” It has yet to be determined if Zika virus can be transmitted in other ways, including blood transfusions. (more…)
Author Interviews, Flu - Influenza, Heart Disease / 10.02.2016

MedicalResearch.com Interview with: Tze-Fan Chao MD PhD Division of Cardiology, Department of Medicine Taipei Veterans General Hospital Institute of Clinical Medicine, and Cardiovascular Research Center National Yang-Ming University, Taipei, Taiwan Su-Jung Chen MD Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Institute of Public Health and School of Medicine, National Yang-Ming University Taipei, Taiwan MedicalResearch: What is the background for this study? What are the main findings? Response: Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice, accounting for frequent hospitalizations, hemodynamic abnormalities, and thromboembolic events. Although the detailed mechanism of the occurrence of Atrial fibrillation remains unclear, systemic inflammation and sympathetic nervous system have been demonstrated to play an important role in the pathogenesis of AF. Flu (influenza infection) is a common disease which could happen to everyone in the daily life. It could cause significant morbidity and mortality, and is a serious human health concern worldwide. Previous studies have shown that influenza infection not only results in the productions of pro-inflammatory cytokines, but also activates the sympathetic nervous system, which are all related to the occurrence of Atrial fibrillation. Therefore, we hypothesized that influenza infection could be a risk factor of new-onset AF. We also tested the hypothesis that influenza vaccination, a useful way to reduce the risk of influenza infection, could decrease the risk of AF. In this large scale nationwide case-control study, a total of 11,374 patients with newly diagnosed Atrial fibrillation were identified from the Taiwan National Health Insurance Research Database. On the same date of enrollment, 4 control patients (without AF) with matched age and sex were selected to be the control group for each study patient. The relationship between AF and influenza infection/vaccination 1 year before the enrollment was analyzed. The results showed that influenza infection was associated with an 18% increased risk of AF, and the risk could be easily reduced through influenza vaccination. (more…)
Author Interviews, HIV, Social Issues, Yale / 10.02.2016

MedicalResearch.com Interview with: Kristina Marie Talbert-Slagle, PhD Lecturer in Epidemiology (Microbial Diseases) and in Public Health (Health Policy); Senior Scientific Officer, Yale Global Health Leadership Institute Yale School of Public Health Medical Research: What is the background for this study? What are the main findings? Dr. Talbert-Slagle: The interest for this study originally came as a result of work done by Elizabeth Bradley, PhD, co-author of The American Health Care Paradox. In the book, Dr. Bradley compared spending rates of social services to health care services between the U.S. and other countries and found that while the U.S. invested more money in health care services than any other country we had worse health outcomes. By contrast, countries that spent more on social services per dollar spent on health care had better outcomes. We applied that same idea to AIDS. There are still more than 50,000 cases of HIV/AIDS diagnosed in the U.S. each year. Although many medical advances have been made in treatment and prevention of this infection, we were curious as to why rates of HIV/AIDS have remained stagnate. We wanted to explore how spending relates to differences in case rates among the states and found a significant difference among states regarding social service and public health spending related to HIV/AIDS. We looked at all 50 states’ spending habits over the past 10 years and discovered that states that invested more money in social services such as education, housing, and nutrition per person in poverty had significantly lower rates of HIV/AIDS deaths. (more…)
Author Interviews, CDC, HIV, Race/Ethnic Diversity / 10.02.2016

MedicalResearch.com Interview with: Sharoda Dasgupta, PhD, MPH US Public Health Service and Epidemic Intelligence Service Officer CDC Medical Research: What is the background for this study? Dr. Dasgupta: Roughly 1.2 million people in the United States are living with HIV, and about 40,000 diagnoses occur each year, according to the most recent CDC data. According to national estimates published by CDC, African Americans remain disproportionately affected by the virus. African Americans represent 12 percent of the U.S. population but accounted for almost 50 percent of HIV diagnoses in 2014. Some signs have emerged that HIV is loosening its grip on the African American community, but persistent disparities are prolonging HIV transmission. Antiretroviral therapy (ART) improves clinical outcomes for people living with HIV and reduces their risk of transmitting the virus to others. Racial and ethnic disparities in HIV care, however, limit access to ART, which perpetuates disparities in survival and HIV transmission. Although previous studies have mostly analyzed HIV care by race and ethnicity during a single year, the purpose of this study was to better understand how people living with HIV remain in care over a longer period in time – and whether their retention in care differed by race and ethnicity. Medical Research: What are the main findings? Dr. Dasgupta: This analysis focused on 12 U.S. jurisdictions that reported comprehensive HIV lab results to CDC from January 2010 – December 2013. They represent approximately 25 percent of HIV diagnoses in 2010. The findings demonstrate yet another persistent disparity that prolongs the epidemic among African Americans. Only 38 percent of African Americans received consistent HIV care from 2011 – 2013, compared with 49% of whites and 50% of Latinos. Additionally, African American males were less likely to receive consistent medical care than African American females (35 percent and 44 percent, respectively). Among African Americans, receiving consistent HIV care was highest among those whose HIV infections were attributable to heterosexual contact. Those who received consistent HIV medical care for three years were considered consistently retained in care. (more…)
Author Interviews, Neurological Disorders, Zika / 06.02.2016

MedicalResearch.com Interview with: Dr. Kenneth C. Gorson, MD President Elect GBS|CIDP Foundation International Global Medical Advisory Board Guillain-Barre syndrome (GBS) Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) Medical Research: What is Guillain-Barré Syndrome? What are the main symptoms? Dr. Gorson: Guillain-Barré Syndrome (GBS) is an immune mediated disorder affecting the peripheral motor and sensory nerves and nerve roots, and is the most common cause of rapidly progressive generalized paralysis in western countries. It is characterized by acute or subacute, progressive, symmetrical limb weakness with distal numbness or tingling in the arms and legs, and reduced or absent deep tendon reflexes in previously healthy patients. Patients notice the sudden onset of difficulty walking, climbing stairs, carrying objects and impaired fine motor skills. Balance is impaired due to sensory loss or weakness and a minority of patients develop facial weakness, trouble speaking and swallowing, and double vision. Severely affected patients may require ventilator support due to respiratory muscle weakness. Symptoms worsen over days to weeks, and most patients reach a maximum deficit (nadir) by 4 weeks, followed by a plateau phase for weeks to months, and then a recovery phase over additional weeks to months. Approximately 80 percent of patients recover to walk with minimal or no residual symptoms or functional disability. Maximal improvement usually occurs by one year, but more severely affected patients may continue to observe subtle improvements for several years after symptom onset. In approximately two thirds of affected patients there is some preceding triggering event, classically a viral syndrome manifest as a transient upper respiratory or gastrointestinal illness with fever that resolves uneventfully prior to the onset of the neuropathy. Current evidence indicates the pathophysiology of GBS is related to molecular mimicry, where the patient's antibody response to the preceding infection interacts with a variety of antigens on peripheral nerve myelin or axons producing a generalized but multifocal inflammatory demyelinating process and associated axonal loss in some instances. The diagnosis is established with nerve conduction studies and electromyography, which shows features indicative of a demyelinating neuropathy affecting multiple motor nerves in the arms and legs. The cerebrospinal fluid protein level is elevated without a cellular response (cyto-albuminological dissociation) in up to 80 percent of patients when performed in the first week of the illness. Treatment is directed toward the immune response, and several large randomized controlled trials have demonstrated that intravenous immunoglobulin and plasma exchange hasten recovery, and both treatments have similar efficacy. (more…)
Author Interviews, Dermatology, Exercise - Fitness, Herpes Viruses, Infections / 06.02.2016

MedicalResearch.com Interview with: Kurt Ashack Fourth year medical student at Michigan State University, Michigan Kyle Burton University of Central Florida College of Medicine, Orlando, Florida Medical Research: What is the background for this study? What are the main findings? Response: Skin infections associated with high school athletics have been reported in literature since the late 20th century and while many skin infections are relatively minor, others can cause serious morbidity. Prior reports on skin infections among high school athletes have focused on specific sports or have evaluated relatively small numbers of athletes. No prior report has evaluated skin infections in a large national sample of United States (US) high school athletes across multiple sports. During the study period, 474 skin infections were reported among 20,858,781 athlete exposures (AE); a rate of 2.27 infections per 100,000 AE. The largest number of skin infections occurred in wrestlers (73.6%), followed by boys’ football (17.9%) and boys’ basketball (1.9%). Baseball and swimming had much fewer cases. The most common infections were bacterial (60.6%), tinea (28.4%) and herpetic (5.2%) infections. Body parts most often affected were the head/face (25.3%), forearm (12.7%) and upper arm (8%). The average time for return to play was 3-6 days (45.5%). It was also interesting to note how many more infections there were in boys than girls. Girls’ volleyball had the most of girls’ sports, but all girl reports did not near the boy's number. (more…)
Author Interviews, CDC, Flu - Influenza, OBGYNE, Vaccine Studies / 04.02.2016

MedicalResearch.com Interview with: Ikwo Oboho, MD, ScMLCDR United States Public Health Service Medical Epidemiologist, Centers for Disease Control and PreventionPriority Populations Treatment Team| HIV Care & Treatment Branch | Division of Global HIV/TB Atlanta, GA 30333 MedicalResearch.com: What is the background for this study? Dr. Oboho: ·Pregnant women with flu are at high risk of serious illness and complications, including death. The study is based on data gathered from a nationwide flu surveillance network that includes 14 states. The analysis focused on pregnant women hospitalized with laboratory-confirmed flu over four recent flu seasons, from 2010 to 2014. MedicalResearch.com: What are the main findings? Dr. Oboho: · During the study period, 865 pregnant women were hospitalized with flu. Sixty-three of these patients, or about 7 percent, had severe illness.
  • After adjusting for underlying medical conditions, vaccination status, and pregnancy trimester, we found that early treatment with the antiviral drug oseltamivir was associated with a shorter hospital stay.
  • Among pregnant women with severe flu illness who were treated early with oseltamivir — within two days of the start of symptoms — the median length of stay was about five days shorter compared to hospitalized pregnant women with severe flu illness who were treated later
  • Pregnant women who were hospitalized with severe cases of flu illness were half as likely to have been vaccinated as women with non-severe illness.
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Author Interviews, Technology, Zika / 03.02.2016

MedicalResearch.com Interview with: Christopher Bibbs Anastasia Mosquito Control District Florida Medical Research: What is the background for this report? Mr. Bibbs: In vector management, the uphill battle is always against the mosquito. And of those, the anthropophilic Yellow Fever mosquito, Aedes aegypti, has become established world-wide as a vector of several emergent diseases. Historically, these mosquitoes carried Yellow Fever and to this day still carry Dengue. Chikungunya, a newly established virus in the Caribbean, has joined the western hemisphere since 2014. And most recently, Zika virus made its way to Brazil and others in South America during 2015. This mosquito thrives in the United States as well, and should a traveler visit a country suffering from these disease and return home sick they risk passing it along to the representative mosquito in your home country. In order to manage these risks, vector management programs employ an integrated approach using multiple techniques and surveillance tools. But oft-neglected are what is available over-the-counter to consumers wanting relief. One such tool is called "spatial repellents." By vaporizing a minute amount of chemical into the air, it creates a flight barrier to the mosquito. The mosquito, upon encountering this vapor, will become disoriented and leave the area, thusly reducing bite contact. But as yet these tools are exclusively considered as repellent. But is that all they do? (more…)
Author Interviews, Compliance, HIV, Lancet / 03.02.2016

MedicalResearch.com Interview with: Dr Marcel Yotebieng, PhD Department of Epidemiology Ohio State University, 304 Cunz Hall Columbus, OH Medical Research: What is the background for this study? What are the main findings? Response: With the current World Health Organization recommended treatment for the prevention of mother-to-child HIV transmission (PMTCT), the risk of transmission of HIV from an infected mother to her baby can be cut from 35-45% to less than 5% in breastfeeding population and <1% in non-breastfeeding population. But in sub-Saharan Africa where over 90% of HIV-infected pregnant women worldwide live, transportation costs and opportunity costs to attend regular clinic visits (to collect drugs) have been identified as important barriers to PMTCT. The provision of economic incentives has the potential to help women overcome these economic barriers. In addition, by creating immediate rewards that “nudge” individuals towards positive health behaviors, financial incentives can also address psychological barriers to health-seeking behavior of HIV-infected pregnant and breastfeeding women. This is the first study to use small cash incentives to encourage women to attend clinic visit and received available PMTCT care. We found that, among newly diagnosed HIV-infected women, small, incremental cash incentives resulted in increased retention along the prevention of mother-to-child HIV transmission cascade and uptake of available services. (more…)
Author Interviews, Hospital Acquired / 02.02.2016

MedicalResearch.com Interview with: Leonard Mermel, DO, ScM, AM (Hon), FSHEA, FIDSA, FACP Professor of Medicine, Warren Alpert Medical School of Brown University Medical Director, Dept. of Epidemiology & Infection Control, Rhode Island Hospital Adjunct Clinical Professor, University of Rhode Island College of Pharmacy Medical Research: What is the background for this study? What are the main findings? Dr. Mermel: There is increasing concern in the US and abroad regarding multi-drug resistant organisms (MDROs), particularly bacteria resistant to carbapenem antibiotics. Concern has been raised about MDRO colonization in high-risk populations, such as nursing home patients and transmission between nursing home and acute care hospitals. Little data exists concerning the incidence of GI tract colonization of such pathogens in nursing home patients at the time of acute care hospitalization. We used rectal swabs on 500 hospital admissions from nursing homes to assess carriage of bacteria resistant to carbapenem antibiotics. We found carbapenem-resistant or carbapenemase-producing gram-negative bacteria in 23 of the 500 (4.6%) hospital admissions from nursing homes, which included 7 carbapenemase-producing CRE bacteria (1.4%). The latter bacteria produce an enzyme that breaks down the carbapenem antibiotic and the resistance genes are located on mobile genetic elements. We also found that use of gastrostomy tubes was associated with fecal carriage of gram-negative bacteria with detectable carbapenem resistance. (more…)
Author Interviews, Brigham & Women's - Harvard, UCSF, Zika / 31.01.2016

MedicalResearch.com Interview with: Mary E. Wilson, MD Visiting Professor of Epidemiology and Biostatistics School of Medicine, University of California San Francisco Adjunct Professor of Global Health and Population Harvard T.H. Chan School of Public Health Boston, Massachusetts Medical Research: What is the background for this study? Response: Zika virus infections are spreading explosively in the Americas. This flavivirus infection, spread by Aedes mosquitoes, is new to the Americas, so the majority clinicians have little knowledge of the infection and its potential complications. The country most affected so far is Brazil, where more than a million infections have been reported in less than a year. Infection has also spread to at least 20 other countries in the Americas (the Caribbean, Mexico, Central and South America). Prior to 2007 Zika virus was known to cause infections only in Africa and Asia. Since then, it has spread and caused epidemics in Micronesia, French Polynesia, Easter Island, and since 2015 in Brazil. Most of the movement of the virus from one region to another is via travelers who are infected and then are bitten by mosquitoes in a new region. In Brazil an increase in cases of infants born with microcephaly (small head) has been noted coincident with the Zika epidemic, and the virus has been recovered from amniotic fluid and from fetal tissue, suggesting that Zika infection during pregnancy may cause microcephaly in the developing fetus. An increase in cases of Guillain-Barre syndrome has also been observed during this and previous outbreaks. Studies are underway to determine if Zika virus is the cause of microcephaly and Guillain-Barre syndrome. In Brazil an increase in cases of infants born with microcephaly (small head) has been noted coincident with the Zika epidemic, and the virus has been recovered from amniotic fluid and from fetal tissue, suggesting that Zika infection during pregnancy may cause microcephaly in the developing fetus. An increase in cases of Guillain-Barre syndrome has also been observed during this and previous outbreaks. Studies are underway to determine if Zika virus is the cause of microcephaly and Guillain-Barre syndrome. Most countries in the Americas, including the United States, are infested with types of mosquitoes that are competent to transmit the virus, but weather conditions also have to be warm enough to permit the virus to disseminate in the mosquito so that it can be transmitted to another person. The symptoms of Zika virus infection are typically mild and self-limited – fever, aches, rash, and conjunctivitis. In fact, the majority of those infected have no symptoms. Because the virus can enter the bloodstream even in asymptomatic infected persons, there is concern that the virus could be spread by blood transfusion, if a person donates blood during the short period (probably a few days at most) when virus is in the blood. Other reasons for the paper are to highlight what is known about some of the insect repellents and to point out important gaps in our knowledge of their use and urgent research needs. (more…)
Author Interviews, Herpes Viruses, Ophthalmology, Vaccine Studies / 30.01.2016

MedicalResearch.com Interview with: Frederick W. Fraunfelder, MD MBA Chairman and Roy E. Mason and Elizabeth Patee Mason Distinguished ProfessorDepartment of Ophthalmology Missouri University School of Medicine Director of the Missouri University Health Care’s Mason Eye Institute Medical Research: What is the background for this study? What are the main findings? Dr. Fraunfelder: The background starts with a paper by Hwang et al (Cornea. 2013 Apr;32(4):508-9.Reactivation of herpes zoster keratitis in an adult after varicella zoster vaccination. Hwang CW Jr1, Steigleman WA, Saucedo-Sanchez E, Tuli SS.) After reading this paper, I started keeping track of keratitis cases that were reported to my registry (www.eyedrugregistry.com) and also to the FDA and WHO spontaneous reporting databases. We found case reports in adults and children of keratitis occurring soon after vaccination, and we presented this at the American Academy of Ophthalmology’s annual meeting that we just held in Las Vegas in November 2015. The main findings are that in rare instances, relatively speaking, herpes infection can occur in the cornea of the eye within days to weeks after vaccination. This may especially be true in adults who have had shingles in the past which caused a keratitis in the past. This keratitis may reoccur after the vaccination, and primary care providers should inquire about this past medical/ocular history and advise of the risk of recurrent keratitis after the vaccination for shingles. (more…)
Author Interviews, Cancer Research, Infections / 27.01.2016

MedicalResearch.com Interview with: Yvonne Kapila, DDS, PhD Professor, Division of Periodontics Department of Periodontics and Oral Medicine University of Michigan School of Dentistry Ann Arbor, MI Medical Research: What is the background for this study? What are the main findings? Dr. Kapila: Our research showed that the preservative nisin induces cancer cell death. When tested on normal control cells to see if they were affected, the control cells were not affected. Thus, the most recent project began in order to find out more details as to why this occurred. We used a cancer mouse model (head and neck cancer) to show that nisin can retard tumor growth and extent the life of these mice. Another thing that we published about the preservative is nisin’s role on biofilms. Biofilms are communities of bacteria that can cause diseases. Nisin has been tested in bacterial biofilms that contain bacteria that cause gum disease and dental decay and nisin has been found to be effective in this setting as well. In laboratory settings, nisin is also cytotoxic to superbugs, including the most resistant bugs found in hospitals, and therefore nisin holds promise for several therapeutic applications. (more…)
Author Interviews, HIV, PLoS / 26.01.2016

MedicalResearch.com Interview with: Julian Falutz, MD Director, HIV Metabolic Clinic MUHC, Coordinator of Chronic Viral Illness Service, HIV and Aging Clinic McGill University Health Center Medical Research: What is the background for this study? What are the main findings? Dr. Falutz: The long-term use of antiretroviral therapy (ART) in HIV-infected patients is associated with body composition changes, including visceral adipose tissue (VAT) accumulation. HIV-infected patients with excess VAT may be at increased risk of type 2 diabetes, cardiovascular diseases, and mortality. Tesamorelin is a synthetic analog of human growth hormone-releasing factor, also known as growth hormone-releasing hormone (GHRH), which is indicated for the treatment of excess abdominal fat in HIV-infected patients with lipodystrophy. The objectives of our paper were to 1) evaluate the utility of patient characteristics and validated disease-risk scores, including indicator variables for the metabolic syndrome and the Framingham Risk Score (FRS), as predictors of visceral adipose tissue reduction during tesamorelin therapy, and 2) to explore the characteristics of patients who reached a threshold of VAT <140 cm2, a level associated with lower risk of adverse health outcomes, after 6 months of treatment with tesamorelin. The basis of the report was a pooled analysis of the two pivotal, randomized Phase 3 trials of tesamorelin in 806 HIV-infected patients with excess abdominal fat. Our results indicate that presence of metabolic syndrome, high triglycerides, and white race are associated with a greater likelihood of responding to 6 months of tesamorelin treatment. The most robust response appears to be in subjects with VAT above 140 cm2, as well as those in the overweight range for body mass index (BMI) measures. (more…)
Author Interviews, Hand Washing, Hospital Acquired, Nursing / 26.01.2016

MedicalResearch.com Interview with: Donna Powers, DNP, RN Kransoff Quality Management Institute North Shore Long Island Jewish Health System New York, NY Medical Research: What is the background for this study? What are the main findings? Dr. Powers: Despite widely published, accessible guidelines on infection control and negative health consequences of noncompliance with the guidelines, significant issues remain around the use of Standard Precautions to protect nurses from bloodborne infectious diseases. Only 17.4% of ambulatory nurses reported compliance with all nine standards. The nurses represented medicine, cardiology, dialysis, oncology, pre - surgical testing, radiation and urology practices. Compliance rates varied considerably and were highest for wearing gloves (92%) when exposure of hands to bodily fluids was anticipated, however only 63% reported washing hands after glove removal. 68% provided nursing care considering all patients as potentially contagious. Overall, the ambulatory care nurses chose to implement some behaviors and not others, and this behavior puts them at risk for acquiring a bloodborne infection.” The study also found knowledge of HCV was variable. Although HCV is not efficiently transmitted by sexual activity, more than one in four nurses (26 %) believed that sexual transmission is a common way that HCV is spread. 14 percent believed incorrectly that most people with HCV will die prematurely because of the infection, 12 percent did not know that HCV antibodies can be present without an infection, and 11 percent did not know there are multiple HCV genotypes. A statistically significant relationship was found between compliance and perception of susceptibility to HCV illness (P = .05) and between compliance and perception of barriers to use of Standard precautions (P=.005). (more…)
Author Interviews, Duke, Genetic Research, Infections / 24.01.2016

MedicalResearch.com Interview with: Ephraim L. Tsalik, MD MHS PhD Assistant Professor of Medicine Division of Infectious Diseases Center for Applied Genomics & Precision Medicine Duke University Medical Center Emergency Department Service Line Durham VA Medical Center Medical Research: What is the background for this study? What are the main findings? Dr. Tsalik: This study was motivated by the convergence of two research interests. The first was spearheaded by Dr. Sack, leading our collaboration at Johns Hopkins. Dr. Sack and his colleagues have a long history and expertise in studying enteric infections such as E. coli. The second is our group here at Duke’s Center for Applied Genomics & Precision Medicine as well as the Durham VA Medical Center. Specifically, we have an interest in studying the host response to infectious disease. One of the ways we’ve done that historically is through challenge studies where healthy volunteers are exposed to a pathogen in a controlled setting. Despite everyone getting the same exposure, not everyone gets sick. That observation gives us a unique opportunity to study the host biology of symptomatic individuals, asymptomatic individuals, and what distinguishes the two from each other. That is precisely what we did here. Volunteers ingested Enterotoxigenic E. coli (ETEC), which is a common cause of traveler’s diarrhea. Some subjects became ill with diarrhea while others remained well. In this study, we focused on gene expression patterns, which is a snapshot of how genes in the body are being used in response to this infection. Some genes are more active, some are less. The pattern of those changes that occur in response to infection is what we call a “signature”. This approach allowed us to generate some key findings. First of all, we were able to define the genes involved in the body’s response to this type of E. coli infection. Second, we discovered genes that were differentially expressed at baseline that could distinguish people who would go on to become ill from those that would remain healthy. Although this study was not designed to identify the mechanism for that resilience to infection, it does focus our attention on where to look. We suspect the genes we identified are likely to play a role in infectious disease resilience and susceptibility based on their known immune function roles. We also have data, which wasn’t published in this study, that implicates some of these genes in the resilience to other infections such as influenza. The last major finding was something called Drug Repositioning Analysis. This is a tool that allowed us to identify drugs and drug classes that could be used to mitigate infections caused by ETEC. That analysis highlighted some compounds already known to be effective such as Zinc. But it also identified several other drug classes that have not previously been investigated and could be important tools to combat such infections especially as antibiotic resistance looms. (more…)