Author Interviews, HIV, Lancet, Sexual Health / 10.09.2015

Prof-Sheena-McCormack.jpgMedicalResearch.com Interview with: Professor Sheena McCormack Clinical Epidemiology Medical Research Council Clinical Trials Unit University College London Medical Research: What is the background for this study? What are the main findings? Prof. McCormack: PROUD is the first study of pre-exposure prophylaxis (PrEP) to prevent HIV carried out in the UK. The results show that PrEP could play a major role in reducing the number of new infections among men who have sex with men who are at risk of catching HIV. Pre-exposure prophylaxis (PrEP) is a HIV prevention strategy that involves HIV-negative people taking some of the drugs we use for treatment of HIV to reduce the risk of becoming infected. The PROUD study (www.proud.mrc.ac.uk) looked at whether offering daily PrEP to men who have sex with men was an effective way to prevent HIV infection. The results show that pre-exposure prophylaxis is highly protective, reducing the risk of infection for this group by 86%. The drug used in the trial – the antiretroviral Truvada – was already known to reduce the incidence of HIV infection compared to placebo (a dummy pill).  The PROUD study was designed to see how good Truvada would be found as pre-exposure prophylaxis in a real world situation when participants knew they were taking an active drug.  It aimed to address outstanding questions such as whether taking PrEP would change sexual risk behaviour – for example increasing the number of partners they did not use condoms with and increasing the rate of other sexually transmitted infections (STIs) – and whether or not it would be cost-effective to make it available on the NHS.
Author Interviews, Infections / 09.09.2015

MedicalResearch.com Interview with: Yongjie Wang PhD College of Food Science and Technology Shanghai Ocean University Laboratory of Quality and Safety Risk Assessment for Aquatic Products on Storage & Preservation Ministry of Agriculture Shanghai China Medical Research: What is the background for this study? Dr Wang: Norovirus (NoVs) are recognized as the most important food-borne viruses. They cause acute gastroenteritis in humans and infect people of all ages across the world. In our previous study, we found that approximate 90% of human norovirus sequences were discovered in the coastal regions in China, which likely result from the consumption of NoV-contaminated oysters. Oysters are well recognized as the main vectors of environmentally transmitted noroviruses, and disease outbreaks linked to oyster consumption have been commonly observed. In order to gain a better understanding of how noroviruses are transmitted via oysters in the environment, we examined the genetic variants associated with oyster-related NoV outbreaks. Medical Research: What are the main findings? Dr Wang: A high degree of genetic diversity was observed for oyster-related noroviruses, and almost all the human norovirus genotypes were found in oyster-related norovirus sequences. These sequences were widely but unevenly distributed geographically, and most of them were detected in coastal regions. A higher frequency of GI strains was found in oyster-related than in human-related NoV sequences, while the yearly distributions of oyster-related sequences and human outbreak sequences were similar, indicating that oysters may act as a reservoir of noroviruses in the environment.
Author Interviews, Infections, JAMA, OBGYNE / 08.09.2015

Dr. Martin N. Mwangi Researcher Division of Human Nutrition, Nutrition and Health over the lifecourse International Nutrition Unit Wageningen University The Netherlands MedicalResearch.com Interview with: Dr. Martin N. Mwangi Researcher Division of Human Nutrition, Nutrition and Health over the lifecourse International Nutrition Unit Wageningen University The Netherlands   Medical Research: What is the background for this study? Dr. Mwangi : Anemia in pregnancy is a moderate or severe health problem in more than 80 percent of countries worldwide, but particularly in Africa, where it affects 57 percent of pregnant women. Iron deficiency is the most common cause, but iron supplementation during pregnancy has uncertain health benefits. There is some evidence to suggest that iron supplementation may increase the risk of infectious diseases, including malaria. Our main objective was to measure the effect of antenatal iron supplementation on maternal Plasmodium infection risk, maternal iron status, and neonatal outcomes. We randomly assigned 470 pregnant Kenyan women living in a malaria endemic area to daily supplementation with 60 mg of iron (n = 237 women) or placebo (n = 233) until 1 month postpartum. All women received 5.7 mg iron/day through flour fortification during intervention and usual intermittent preventive treatment against malaria. Medical Research: What are the main findings? Dr. Mwangi : Overall, we found no effect of daily iron supplementation during pregnancy on risk of maternal Plasmodium infection. Iron supplementation resulted in an increased birth weight [5.3 ounces], gestational duration, and neonatal length; enhanced maternal and infant iron stores at 1 month after birth; and a decreased risk of low birth weight (by 58 percent) and prematurity. The effect on birth weight was influenced by initial maternal iron status. Correction of maternal iron deficiency led to an increase in birth weight by [8.4 ounces].
Author Interviews, C. difficile, JAMA, UC Davis / 08.09.2015

Christopher R. Polage, M. D. Associate Professor of Pathology and Infectious Diseases University of California, Davis School of Medicine Medical Director, Microbiology Laboratory and SARC UC Davis Health System MedicalResearch.com Interview with: Christopher R. Polage, M. D. Associate Professor of Pathology and Infectious Diseases University of California, Davis School of Medicine Medical Director, Microbiology Laboratory and SARC UC Davis Health System   Medical Research: What is the background for this study? Dr. Polage: Clostridium difficile is a frequent cause of diarrhea and infection in U.S. hospitals but common diagnostic tests often disagree about which patients are infected or need treatment. We compared clinical symptoms and outcomes in hospitalized patients with different C. difficile test results to determine which type of test (molecular or PCR test versus toxin test) was the better predictor of need for treatment and disease. Medical Research: What are the main findings? Dr. Polage: Twice as many patients were positive by the molecular test versus the conventional toxin test. However, patients with a positive molecular test only had a shorter duration of symptoms than patients with toxins, and outcomes that were similar to patients withoutC. difficile by all test methods. Virtually all traditional complications of C. difficile infection occurred in patients with a positive toxin test; none occurred in patients with a positive molecular test only, despite little or no treatment.
Author Interviews, CDC, HIV, JAMA / 02.09.2015

Dr. John Weiser MD MPH Medical epidemiologist Division of HIV/AIDS Prevention CDC MedicalResearch.com Interview with: Dr. John Weiser MD MPH Medical epidemiologist Division of HIV/AIDS Prevention CDC  Medical Research: What is the background for this study? What are the main findings? Dr. Weiser: Ryan White was an Indiana teenager diagnosed with AIDS in the late 1980s. As a result of fear and stigma, he was barred from school and went on to become a national advocate for HIV education and acceptance. This year marks the 25th anniversary of his death and passage of the Ryan White CARE Act creating The Ryan White HIV/AIDS Program (RWHAP) which provides funding for healthcare facilities to deliver needed medical care and support services for hundreds of thousands of poor, uninsured, and underinsured Americans. While increased access to Medicaid and private insurance under the Affordable Care Act will provide coverage for medical care, it might not provide coverage for support services so it is likely that the RWHAP will continue to play a key role in providing these crucial services. Overall, 34.4 percent of facilities received Ryan White HIV/AIDS Program funding and 72.8 percent of patients received care at RWHAP-funded facilities. Many of the patients at Ryan White HIV/AIDS Program -funded facilities had multiple social determinants of poor health, with patients at RWHAP-funded facilities more likely to be ages 18 to 29; female; black or Hispanic; have less than a high school education; income at or below the poverty level; and lack health care coverage. Despite the greater likelihood of poverty, unstable housing and lack of health care coverage, nearly 75 percent of patients receiving care at RWHAP-funded facilities achieved viral suppression. The percentage of ART (antiretroviral therapy) prescribing was similar for patients at RWHAP-funded compared with non-funded facilities. Patients at RWHAP-funded facilities were less likely to be virally suppressed. However, individuals at or below the poverty level and those ages 30 to 39 who received care at a RWHAP-funded facility compared with those who received care at a non-RWHAP-funded facility were more likely to achieve viral suppression.
Author Interviews, CDC, Infections / 01.09.2015

[caption id="attachment_17159" align="alignleft" width="300"]The White-Throated Wood Rat, is a proven carrier of plague vector fleas. The White-Throated Wood Rat, is a proven carrier of plague vector fleas.[/caption] Medical Research: What is the background for this study? What are the main findings? Response: Plague, a bacterial disease that is endemic to the Western United States, is most famous for the destruction it caused during the Middle Ages when it killed over half the population of Europe.  Today, plague still infects people around the world and there are a handful of cases each year here in the U.S.  However, this year where there are normally 3-7 cases, there have been 12 cases since the beginning of April. Medical Research: What should clinicians and patients take away from your report? Response: One of the main reasons CDC issued our report on this year’s plague cases was because we want to remind clinicians and their patients that plague should be considered as a diagnosis if the symptoms, travel history, and exposure fit.  Most cases occur between late spring and early fall, so there might still be more cases this year.  It’s good to be aware of three things: where cases occur, how the disease is spread, and how to prevent it.
  1. Most cases occur in the Western United States, and so far this year the cases have been from Arizona (two), California (one), Colorado (four), Georgia (one, but exposed in California), New Mexico (two), Oregon (one), and Utah (one).
  2. Plague is spread when fleas become infected by feeding on rodents, such as chipmunks, prairie dogs, ground squirrels, mice, and other mammals that are infected with the plague bacterium Yersinia pestis. Fleas then spread the plague bacteria to humans and other mammals during their next feeding.
  3. Most important, CDC recommends that people who live in or travel to the Western United States wear long pants when possible and use insect repellent on clothing and skin when outside. People also should avoid direct contact with ill or dead animals and never feed squirrels, chipmunks, or otherwild rodents. In addition, pet owners should regularly use flea control products on their pets and consult a veterinarian if their pet is ill. Rodent habitat can be reduced around the home by removing brush, clutter, and potential rodent food sources such as garbage or pet food. If you have any symptoms of plague, please see a clinician and let them know where you’ve traveled and if you’ve had contact with rodents.
Author Interviews, Critical Care - Intensive Care - ICUs, Infections, Outcomes & Safety / 01.09.2015

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   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: Arterial catheters are an under recognized source of hospital-associated bloodstream infection. As a result, arterial catheter infection prevention strategies are less well studied than with central lines.  We did a national survey and our findings reaffirmed the fact that physicians using these catheters underestimate the risk of infection.  Additionally and not surprisingly, infection prevention strategies are variable particularly concerning barrier precautions at insertion. Medical Research: What should clinicians and patients take away from your report? Dr. Mermel: Arterial catheters can cause catheter-related bloodstream infections.  These devices should be aseptically inserted and managed post-insertion and removed as soon as no longer required for patient care.  We are also in need of better studies to clearly delineate the ideal infection prevention strategies with these catheters based on our understanding of the pathogenesis of such infections. 
Author Interviews, Hospital Acquired, Infections, Pediatrics / 31.08.2015

Daryl R. Cheng, MBBS Monash Children's Hospital Victoria, AustraliaMedicalResearch.com Interview with: Daryl R. Cheng, MBBS Monash Children's Hospital Victoria, Australia   Medical Research: What is the background for this study? What are the main findings? Response: Inanimate objects worn and used by health care workers (HCW), such as neckties and stethoscopes,  have been shown to be reservoirs for potential pathogens. Of particular concern in the pediatric setting are identity (ID) badges and lanyards. Many pediatric health care workers use them not only for identification but also as a distraction tool during examination or procedures. Children have an increased tendency to place these items in their mouth as health care workers lean over to examine or care for them, therefore completing the chain of transmission for a potential nosocomial infection. Whilst previous studies have demonstrated that ID badges and lanyards worn by health care workers may harbor pathogenic bacteria , there is paucity of comparative data suggesting that ID badges may be similarly contaminated with viral pathogens. However, given the higher incidence of viral infections in pediatrics up to 50% of preterm infants screened during their hospital stay y had viruses detected in  their nasopharynx, further evaluation of the viral burden and potential for nosocomial transmission of  prevalent viruses are of both clinical and economic significance.
Author Interviews, Infections / 27.08.2015

Kyong Sup Yoon, Ph.D. Assistant Professor Department of Biological Sciences and Environmental Sciences Program Southern Illinois University-Edwardsville Edwardsville, IL 62026MedicalResearch.com Interview with: Kyong Sup Yoon, Ph.D. Assistant Professor Department of Biological Sciences and Environmental Sciences Program Southern Illinois University-Edwardsville Edwardsville, IL 62026  Medical Research: What is the background for this study? What are the main findings? Response: Dr. John Clark (Professor, University of Massachusetts-Amherst) and I have been studying this matter for 15 years. The goal of our current study is to determine resistance (knockdown resistance or kdr conferred by 3 point mutations in voltage gated sodium channel alpha subunit gene) frequencies in US head louse populations collected from 48 contiguous states. We were able to analyze 109 populations from 30 states and found 100% kdr frequencies in 104 populations.  Hopefully, we can achieve our original goal in near future and publish it. head lice, cdc imageMedical Research: What should clinicians and patients take away from your report? Response: We need to implement practical resistance management. Now, for the first time since introduction of pyrethroids, we have different compounds already available or will be (hopefully) available in near future. We suggest to use mixture strategies to minimize development of resistance to any new products.
Author Interviews, Emergency Care, Infections / 25.08.2015

John P. Haran MD Assistant Professor of Emergency Medicine University of Massachusetts Medical School, Worcester, MA MedicalResearch.com Interview with: John P. Haran MD Assistant Professor of Emergency Medicine University of Massachusetts Medical School, Worcester, MA Medical Research: What is the background for this study? What are the main findings? Dr. Haran: The Infectious Disease Society of America (IDSA) publishes evidence based guidelines for the treatment of skin and soft tissue infections, however, how closely clinicians follow these guidelines is unknown. Observation units have been increasingly used over the past decade in emergency medicine for short-term care of patients for many medical conditions including skin infections. These units offer a great alternative to hospitalization especially for older adults. We set out to describe the treatment patterns used in the observation unit of an academic institute and compare them to the IDSA guidelines. We found that physicians had poor adherence to these guidelines. Additionally, we discovered that older adults were at increased risk of being over-treated while women were at increased risk for being under-treated. These age and gender biases are not new to medicine and emergency departments should standardize antibiotic treatments to reduce treatment bias.
Author Interviews, Infections / 22.08.2015

Nichola Kinsinger, Ph.D Postdoctoral Researcher, Chemical & Environmental Engineering University of California, Riverside USDA National Institute for Food and Agricultural Postdoctoral Fellow DoD Office of Naval Research National Defense Science and Engineering Graduate Research Fellow EIT (Chemical Engineering)MedicalResearch.com Interview with: Nichola Kinsinger, Ph.D Postdoctoral Researcher, Chemical & Environmental Engineering University of California, Riverside USDA National Institute for Food and Agricultural Postdoctoral Fellow DoD Office of Naval Research National Defense Science and Engineering Graduate Research Fellow, EIT (Chemical Engineering) Medical Research: What is the background for this study? What are the main findings? Dr. Kinsinger: Outbreaks observed in produce are becoming increasing common possibly due to contaminated irrigation waters or contaminated waters used during processing.  In 2006 California had spinach-borne E. coli outbreak that impacted 26 states and 200 confirmed sickened.  Leafy greens account for 20% of the outbreaks alone and are of increased concern since they are frequently consumed raw. These outbreaks drew our attention over the past few years and we started applying methods originally developed for studying bacterial adhesion on engineered surfaces to the issue of food safety.  Although food safety is a new area of study for our lab, the project is based upon the concept of pathogen adhesion transport which has been the focus of my advisor’s lab for many years previously.  Rather than the previous scenario looking at pathogen interaction with engineered or mineral surfaces, we are looking at a spinach leaf instead. salad-cdc-image We are using a parallel plate flow chamber system developed by Professor Sharon Walker to evaluate the real time attachment and detachment of the pathogens to the spinach epicuticle layer (surface layer of the leaf) in realistic water chemistries and flow conditions.  Subsequently we can evaluate the efficacy of the rinsing process to kill the bacteria that may remain on the leaf.  Initially we were finding that at low concentrations of bleach, bacteria will detach from the leaf surface allowing for potential cross-contamination later in the process.   However above 500ppb we observed 100% of the attached bacterial cells are killed. So how in commercial rinsing operations that use bleach concentration ranging from 50-200ppm result in outbreaks?  Through this study we analyzed the topography of the leaf and modeled the concentration gradient across the surface of a leaf based on commercial rinsing practices.  We found that even at high bleach concentrations within rinse water result in low bleach concentrations at the leaf surface on the order of 5-1000 ppb bleach, which in our study has shown to that the bacteria can survive when attached to the leaf and/or detach causing concern for cross-contamination.   In this case the very disinfection processes intended to clean, remove, and prevent contamination was found to be a potential pathway to amplifying foodborne outbreaks.
Author Interviews, Infections, University of Pennsylvania, Vaccine Studies / 22.08.2015

David B. Weiner, Ph.D. Professor, Department of Pathology and Laboratory Medicine Chair, Gene Therapy and Vaccine Program, CAMB Co-Leader Tumor Virology Program, Abramson Cancer Program University of Pennsylvania, Perelman School of MedicineMedicalResearch.com Interview with: David B. Weiner, Ph.D. Professor, Department of Pathology and Laboratory Medicine Chair, Gene Therapy and Vaccine Program, CAMB Co-Leader Tumor Virology Program, Abramson Cancer Program University of Pennsylvania, Perelman School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Weiner: MERS, like the Severe Acute Respiratory Syndrome (SARS), is characterized by high fever and severe cough from pneumonia. MERS is caused by an emerging human coronavirus, which is distinct from the SARS coronavirus. Since its identification in 2012, MERS has been linked to over 1,300 infections and close to 400 deaths. It has occurred in the Arabian Peninsula, Europe, and in the US and in Asia. It can be spread in a hospital setting. Scientists now report that a novel synthetic DNA vaccine can, for the first time, induce protective immunity against the Middle EastRespiratory Syndrome (MERS) coronavirus in animal species.   Researchers from the Perelman School of Medicine at the University of Pennsylvania. The NIH, the Public Health agency of Canada, and from a leading company in the development of synthetic DNA vaccine technology, Inovio described the results in a paper  published their work in Science Translational Medicine (STM) this week.  The experimental, preventive vaccine, given six weeks before exposure to the MERS virus, fully protects rhesus macaques from disease. The vaccine also generated potentially protective antibodies in blood drawn from camels, the purported source of MERS transmission in the Middle East.
Author Interviews, Cost of Health Care, Infections, JAMA, Pharmacology / 19.08.2015

Jerome A. Leis, MD MSc FRCPC Division of Infectious Diseases, Sunnybrook Health Sciences Centre Physician Lead, Antimicrobial Stewardship Team Faculty Quality Improvement Advisor, Centre for QuIPS Assistant Professor, Department of Medicine, University of Toronto Sunnybrook Health Sciences Centre Toronto, OntarioMedicalResearch.com Interview with: Jerome A. Leis, MD MSc FRCPC Division of Infectious Diseases Sunnybrook Health Sciences Centre Physician Lead, Antimicrobial Stewardship Team Faculty Quality Improvement Advisor, Centre for QuIPS Assistant Professor, Department of Medicine University of Toronto Sunnybrook Health Sciences Centre Toronto, Ontario Medical Research: What is the background for this study? What are the main findings? Dr. Leis: We know that urinary tract infections are frequently diagnosed among general medicine patients who lack symptoms of this infection.  We wondered whether urinalysis ordering practices in the Emergency Department influence diagnosis and treatment for urinary tract infection among these asymptomatic patients.  We found that over half of patients admitted to the general medicine service underwent a urinalysis in the Emergency Department of which over 80% lacked a clinical indication for this test.  Urinalysis results among these asymptomatic patients did influence diagnosis as patients with incidental positive results were more likely to undergo urine cultures and treatment with antibiotics for urinary tract infection.  The study suggests that unnecessary urinalysis ordering contributes to over-diagnosis and treatment of urinary tract infection among patients admitted to general medicine service.
Annals Internal Medicine, Author Interviews, Infections, Respiratory / 16.08.2015

Reed A.C. Siemieniuk, MD Department of Clinical Epidemiology & Biostatistics Ontario CanadaMedicalResearch.com Interview with: Reed A.C. Siemieniuk, MD Department of Clinical Epidemiology & Biostatistics Ontario Canada Medical Research: What is the background for this study? What are the main findings? Dr. Siemieniuk: Local and cytokine-mediated systematic inflammatory responses help clear bacterial pathogens in community-acquired pneumonia (CAP), but often they can also cause harm. Pneumonia is the most common cause of the acute respiratory distress syndrome (ARDS), an often fatal inflammatory complication. Two randomized trials were published earlier this year, each of which suggested the possibility of  benefit from adjunctive corticosteroid therapy. We decided to perform a systematic review and meta-analysis, taking all available data into consideration. Corticosteroids may be effective for reducing the incidence of ARDS by 6%, the need for mechanical ventilation by 5%, and mortality by 3% (all moderate confidence). They also reduce time to clinical stability and time to discharge by approximately 1 day (high confidence).
Author Interviews, HIV, NIH, Pediatrics, Vaccine Studies / 15.08.2015

George K Siberry, MD, MPH, Medical Officer Maternal and Pediatric Infectious Disease (MPID) Branch Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health Bethesda, MDMedicalResearch.com Interview with: George K Siberry, MD, MPH, Medical Officer Maternal and Pediatric Infectious Disease (MPID) Branch Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health Bethesda, MD Medical Research: What is the background for this study? Dr. Siberry:  Vaccines may not work as reliably in children with HIV infection, especially when their HIV is not under effective treatment. Today, most children in the United States who were born with HIV infection are receiving effective HIV treatment and have reached school age or even young adulthood. However, many received their childhood vaccines before they got started on their HIV treatment (because modern HIV treatments weren’t available when they were very young or their HIV infection was diagnosed late). So we wanted to see if these older children still had immunity from the vaccines they received when they were much younger. Medical Research:  What are the main findings? Dr. Siberry: We looked specifically at whether older children with HIV since birth were protected against measles, mumps, and rubella, the three viral infections covered by the measles-mumps-rubella (or MMR) vaccine. We found that 1/3 up to almost 1/2 of these children were not protected against these viruses, even though nearly all of the children had received at least 2 MMR doses, as recommended. And even if their HIV was currently under excellent control.  When we analyzed factors that were linked to being protected, we found that one of the most important factors was whether you got your MMR vaccine doses after you got on good treatment for your HIV infection.  For instance, over 85% of children who had gotten at least 2 MMR vaccine doses after being on effective HIV treatment were protected against measles compared to less than half of those who didn’t get both of their MMR vaccine doses while on effective HIV treatment.
Author Interviews, Case Western, Diabetes, Infections, PLoS / 14.08.2015

Wesley M. Williams, PhD Cell molecular biologist Department of Biological Sciences Case Western Reserve University School of Dental MedicineMedicalResearch.com Interview with: Wesley M. Williams, PhD Cell molecular biologist Department of Biological Sciences Case Western Reserve University School of Dental Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Williams: Individuals with uncontrolled blood sugar levels frequently present with higher than normal rates of infection and protracted wound healing. The beta-defensin family of antimicrobial peptides responds to bacterial, fungal and viral invasion. As part of the innate immune system, these cationic peptides normally expressed by epithelial cells are important early responders that, together with other components of the innate immune response, act to inhibit microbial infection. Our initial observations led us to question whether glucose or a metabolite of glucose could contribute to antimicrobial peptide dysfunction, and thus compromise control of infection. Elevated levels of glucose result in increased production of dicarbonyls, a class of molecule that can selectively react with proteins having an unusually high content of cationic amino acids, such as arginine and lysine. We first investigated the effects of two well-characterized dicarbonyls, methylglyoxal (MGO) and glyoxal (GO) on recombinant beta-defensin 2 (rHBD-2) structure using MALDI TOF and LC/MS/MS mass spectral analysis of the recombinant peptide. We found MGO to be particularly reactive with the rHBD-2 peptide as it readily and irreversibly adducted to two arginine residues and the N-terminal glycine. Next we tested in vitro for the effects of adducted rHBD-2 on antimicrobial and chemotactic functions, both essential to an effective innate and adaptive immune response in vivo. Through radial diffusion testing on gram-negative E. coli and P. aeruginosa, and gram-positive S. aureus, and a chemotaxis assay for CEM-SS cells, we found that both antimicrobial and chemotactic functions of rHBD-2 were significantly compromised by MGO.
Addiction, Author Interviews, HIV, Lancet / 10.08.2015

MedicalResearch.com Interview with: Dr. Keith Ahamad, a clinician scientist at the BC Centre for Excellence in HIV/AIDS and a Family Doctor trained and certified in Addiction Medicine. He is Division Lead for Addiction Medicine in the department of Family and Community Medicine at Providence Health Care, and is also an addiction physician at the St. Paul’s Addiction Medicine Consult Service, the Immunodeficiency Clinic and Vancouver Detox. He is also Lead Study Clinician for CHOICES, a US National Institutes of Drug Abuse (NIDA) funded clinical trial looking at an opioid receptor blocker (Vivitrol) to treat opioid or alcohol addiction in HIV positive patients.Dr. Keith Ahamad, a clinician scientist at the BC Centre for Excellence in HIV/AIDS and a Family Doctor trained and certified in Addiction Medicine. He is Division Lead for Addiction Medicine in the department of Family and Community Medicine at Providence Health Care, and is also an addiction physician at the St. Paul’s Addiction Medicine Consult Service, the Immunodeficiency Clinic and Vancouver Detox. He is also Lead Study Clinician for CHOICES, a US National Institutes of Drug Abuse (NIDA) funded clinical trial looking at an opioid receptor blocker (Vivitrol) to treat opioid or alcohol addiction in HIV positive patients. MedicalResearch: What is the background for this study? Dr. Ahamad: Previous methadone research has mostly been done in restrictive settings, such as the USA, where methadone can only be dispensed through restrictive methadone programs and cannot be prescribed through primary care physician’s offices. Since a systematic review in 2012, randomised controlled trials have compared methadone treatment provided at restrictive specialty clinics with primary care clinics, which have shown the benefits of primary care models of methadone delivery on heroin treatment outcomes, but not on HIV incidence. MedicalResearch: What are the main findings? Dr. Ahamad: After adjusting for factors commonly associated with HIV, methadone remained independently associated in protecting against HIV in this group of injection drug users. Those study participants who were not prescribed methadone at baseline were almost four times more likely to contract HIV during study follow up. MedicalResearch: What should clinicians and patients take away from your report? Dr. Ahamad: Methadone is an effective medication in treating opioid addiction. Through international randomized control trials, we already know that when prescribed though primary care offices, access to this life-saving medication is increased, effective, and increases patient satisfaction. Now, through our study, we have evidence that when delivered in this manner, it also decreases the spread of HIV.
Author Interviews, Hand Washing, Infections, Lancet / 07.08.2015

MedicalResearch.com Interview with: Paul Little MBBS, BA, MD, DLSHTM, MRCP, FRCGP, FMedSci Professor of Primary Care Research University of Southampton

Medical Research: What is the background for this study? What are the main findings? Prof. Little: Hand washing has been recommended to help prevent respiratory infections (coughs, colds flu, sore throats) - this can be important in normal winters but might be especially important in pandemic flu years. However, there has been little evidence from randomised trials to date to show that handwashing works. [caption id="attachment_16369" align="alignleft" width="350"]A simple internet based intervention to support increasing handwashing behaviour reduced the numbers of infections caught and the number of infections given to family members, A simple internet based intervention to support increasing hand washing behavior reduced the numbers of infections caught and the number of infections given to family members,[/caption]
Author Interviews, CDC, HIV, Sexual Health / 06.08.2015

Adaora Adimora, MD, MPH Chair of the HIV Medicine Association Professor of Medicine School of Medicine University of North Carolina, Chapel Hill.MedicalResearch.com Interview with: Adaora Adimora, MD, MPH Chair,Professor of Medicine School of Medicine University of North Carolina, Chapel Hill. MedicalResearch: What is the current scope of the HIV epidemic? Dr. Adimora: The Centers for Diseases Control and Prevention (CDC) estimates that there are 1.2 million people living with HIV in the U.S. Nearly 13% are undiagnosed and unaware of their status. Men who have sex with men represented 54% of all people living with HIV in 2011. While new infection rates are stable, a majority of new infections (63%) are occurring among men who have sex with men. We have seen alarming increases among young black men who have sex with men who account for 55% of new infections among men who have sex with men. New infections among women have decreased slightly but black and Hispanic/Latina women represent 62% and 17% of new infections respectively among women.[i] While there have been decreases in new HIV infections among people who inject drugs in recent years, the serious outbreak largely among injection drug users in Scott County, Indiana identified this past spring[ii] puts us on high alert to improve access to preventive services and substance use treatment, including access to sterile syringes and equipment. My responses will generally focus on the U.S. epidemic but want to acknowledge that globally an estimated 36.9 million people were living with HIV at the end of 2014 with just 51% of them being diagnosed and more than 34 million deaths were attributed to HIV-related causes.[iii]
Author Interviews, Herpes Viruses, HIV, NEJM / 06.08.2015

Dr. Salim Abdool Karim at CAPRISA Doris Duke Medical Research Institute South AfricaMedicalResearch.com Interview with: Dr. Salim Abdool Karim at CAPRISA Doris Duke Medical Research Institute South Africa Medical Research: What is the background for this study? What are the main findings? Response: Globally, Herpes simplex virus type-2 (HSV-2) is among the most common sexually transmitted infections and is the leading cause of genital ulcers. Available global estimates indicate that approximately 417 million sexually active adults between the ages of 15 and 49 years had an existing prevalent HSV-2 infection in 2012. Current interventions to prevent HSV-2 infection, including condoms, circumcision, and antiviral treatment among heterosexual, HSV-2-discordant couples, have demonstrated protection levels ranging from 6% to 48%. This study showed that peri-coital tenofovir gel reduced HSV-2 acquisition in women by 51%, rising to 71% in high gel-users.
Author Interviews, HIV, PLoS, UC Davis / 31.07.2015

Dr. Satya Dandekar PhD Professor and Chair Department of Medical Microbiology and Immunology UC DavisMedicalResearch.com Interview with: Dr. Satya Dandekar PhD Professor and Chair Department of Medical Microbiology and Immunology UC Davis Medical Research: What is the background for this study? What are the main findings? Dr. Dandekar: Current anti-retroviral therapy is effective in suppressing HIV replication and enhancing immune functions in HIV infected individuals. However, it fails to eradicate the latent HIV reservoirs. Therapy interruption leads to a rapid viral rebound in these patients.  Eradication of latent HIV reservoirs is essential to achieve HIV cure. A “shock and kill” strategy for HIV cure has been proposed that involves reactivation of latent viral reservoirs using latency reversal agents (LRA) and eradication by the immune response. This highlights the need to identify potent LRAs to optimally activate latent HIV reservoirs so that immune surveillance and clearance mechanisms can be effectively engaged in the process of viral eradication. We have found that ingenol-3-angelate (PEP005), an anti-cancer drug can effectively reactivate latent HIV. It is a protein kinase C agonist that activates NF-kB and stimulates HIV expression. In combination with another compound, JQ1, a previously known p-TEFb agonist, the efficacy of PEP005 for HIV reactivation is markedly increased. In addition, ingenol-3-angelate decreases the expression of HIV co-receptors on immune cells, which potentially will help preventing further spread of the virus. The use of ingenol-3-angelate in combination with other latency reversal agents provides an excellent opportunity to optimally activate latent HIV reservoirs and target them for eradication.
Author Interviews, C. difficile, Infections / 30.07.2015

Dr. Monika Pogorzelska-Maziarz PhD MPH Thomas Jefferson University, Jefferson School of Nursing Philadelphia, PA 19107MedicalResearch.com Interview with: Dr. Monika Pogorzelska-Maziarz PhD MPH Thomas Jefferson University, Jefferson School of Nursing Philadelphia, PA 19107 Medical Research: What is the background for this study? What are the main findings? Dr. Pogorzelska-Maziarz: Sharps disposal containers are ubiquitous in healthcare facilities and there is a growing trend toward hospitals using reusable sharps containers. Several research studies have raised concerns about the potential for sharps containers to become a source of pathogen transmission within the healthcare setting but this issue that has not been systematically studied. This is an important issue given that contamination of the hospital environment has been shown to be an important component of pathogen transmission. To examine whether the use of reusable versus single use sharps containers was associated with rates of Clostridium difficile, we conducted a cross-sectional study of acute care hospitals. Survey data on the different types of sharps containers used were collected from over 600 hospitals and this data was linked to the Medicare Provider Analysis and Review (MedPAR) dataset, which contains facility characteristics and C. diff infections data. We found that hospitals using single-use containers had significantly lower rates of C. diff versus hospitals using reusable containers after controlling for hospital characteristics such as geographic region, teaching status, ownership type, hospital size and urbanicity. This is an important finding giving the ubiquitous nature of sharps containers in the health care setting, the growing trend toward hospitals using reusable sharps containers and the high burden of C. diff in the hospital setting.
Author Interviews, Infections, NEJM / 22.07.2015

MedicalResearch.com Interview with: Alison E. Heald, M.D Harborview Medical Center Seattle, WA 98104 MedicalResearch: What is the background for this study? What are the main findings? Dr. Heald: Marburg virus causes a very serious, potentially fatal infection in humans for which there is currently no licensed or approved treatments or vaccines.  We demonstrated that AVI-7288, an investigational drug specifically directed against Marburg virus, is effective in preventing death in monkeys exposed to Marburg virus in an experimental model, and that AVI-7288 raises no safety concerns in parameters measured in the healthy human volunteers dosed at or above the estimated efficacious dose. Importantly, taken together, these results have allowed us to predict a dose that could be expected to protect humans exposed to Marburg virus.
Author Interviews, Infections / 11.07.2015

Prof. Urs Greber, PhD Professor of Molecular Cell Biology Institute of Molecular Life Sciences University of Zurich Zurich, SwitzerlandMedicalResearch.com Interview with: Prof. Urs Greber, PhD Professor of Molecular Cell Biology Institute of Molecular Life Sciences University of Zurich Zurich, Switzerland Medical Research: What is the background for this study? What are the main findings? Prof. Greber: This study has addressed two fundamental questions in virology - how do non-enveloped viruses which are lipid-free penetrate through cell membranes, and how is this process tuned by host lipids? We found that certain neutral lipids, ceramide lipids, were upregulated during the entry process of human adenovirus into cells. The ceramide lipids enhanced the uptake of viruses into cells by endocytosis, and they boosted the disruption of endosomal vesicles which carried the virus,, and thereby enhanced infection. The ceramide lipids were found to be produced by the enzyme acid sphingomyelinase (ASMase), which was secreted from lysosomes to the plasma membrane upon virus attachment to cells. ASMase is a clinical target, and can be inhibited by the antidepressant amitriptyline, a small chemical compound, which is widely used to treat mental disorders.
Author Interviews, Infections / 10.07.2015

MedicalResearch.com Interview with: Dr. J. Todd Kuenstner MD Clinical Laboratories Charleston Area Medical Center, Charleston, Virginia West Virginia School of Medicine, Charleston, West Virginia Medical Research: What is the background for this study? What are the main findings? Dr. Kuenstner: Prior to the advent of recent antiviral therapies with sustained virologic response rates (SVR) of 94%, ultraviolet blood irradiation (UVBI) was proposed as a method to improve the outcome of treatment with interferon and ribavirin which had an virologic response rates of 50%. This therapy was invented by Dr. Emmett Knott in 1928 and used to treat viral and bacterial infectious disease in the 1930s through the 1950s and an estimated 60,000 treatments were conducted in the United States by 1948. The AVIcure hemo-irradiator is a modification of the Knott Hemo-irradiator and meets contemporary safety standards. This study describes the FDA phase II controlled clinical trial that was conducted before the advent of sofosbuvir and ledipasvir with the AVIcure hemo-irradiator using ultraviolet blood irradiation (UVBI) for the treatment of 10 patients infected with the hepatitis C virus (HCV). This study is significant because of the potential of this device for treating other infectious diseases with few treatment options. This therapy was safe and beneficial in the 10 patients that were studied. At the nadir of the viral load, the mean reduction of hepatitis C viral load was 45% (p=0.0048) or 0.35 log viral load (p=0.015). Three of the patients in the group achieved a greater than 0.5 log viral load reduction at some point in the trial. The phase I controlled clinical trial of UVBI in patients with HCV infection on 10 patients (submitted for publication) showed that 7 of 10 patients had a greater than 0.5 log reduction in viral load and a mean viral load reduction of 56% and a mean log viral load reduction of 0.60 (p=0.039). In the phase II clinical trial, 8 of 10 patients also showed a concurrent reduction in their serum transaminase levels, mean reduction in AST of 15% (p=0.0069) and mean reduction in ALT of 19% (p=0.0031). The above phase II trial results were achieved in spite of two therapeutic “holidays” of 7 weeks duration during the trial and during these therapeutic “holidays” the patients did not receive any treatments.
Author Interviews, Dengue / 10.07.2015

MedicalResearch.com Interview with: Dr. Eng Eong Ooi BMBS PhD FRCPath Associate Professor & Deputy Director Program in Emerging Infectious Diseases Duke-NUS Graduate Medical School Singapore Medical Research: What is the background for this study? What are the main findings? Response: Dengue prevention continues to rely exclusively on vector control guided by disease and virologic surveillance. The latter has focused on detecting changes in the prevalence of the four antigenically distinct viral serotypes as, in general terms, herd immunity depends on long-lived serotype-specific antibodies.  However, epidemiological observations have indicated that a small number of changes within the viral genome have also been associated with several major outbreaks, without any change in viral serotype.  Identifying the genetic changes that alter viral fitness epidemiologically would thus be important to differentiate strains that have a greater potential of causing epidemics and targeted for control. Using the 1994 outbreak in Puerto Rico as a case in point, we identified nucleotide substitutions in the 3’ untranslated region (3’UTR) of the viral genome as critical determinants of dengue virus’ epidemiological fitness.  Mechanistically, mutations in the 3’UTR altered secondary viral RNA structures and changed the relative proportion of genomic to subgenomic RNA of the virus in infected cells.  The epidemiologically fitter viruses produced larger amounts of subgenomic to genomic RNA.  This subgenomic RNA then binds a host protein, TRIM25, which is a E3 ubiquitin ligase that polyubiquitylates RIG-I to amplify and sustain signalling for type-I interferon expression.  By binding to TRIM25, the subgenomic RNA of dengue virus inhibits the activation and thus enzymatic function of TRIM25.  We suggest that with reduced interferon expression, the virus was thus able to spread more effectively from cell to cell within the infected individuals to reach viremia levels for further subsequent mosquito-borne transmission.
Author Interviews, Biomarkers, Infections / 09.07.2015

Yingfu Li, PhDProfessor, Dept of Biochemistry and Biomedical Sciences and Dept of Chemistry and Chemical Biology McMaster University, Hamilton, CanadaMedicalResearch.com Interview with: Yingfu Li, PhD Professor, Dept of Biochemistry and Biomedical Sciences and Dept of Chemistry and Chemical Biology McMaster University, Hamilton, Canada Medical Research: What is the background for this study? What are the main findings? Dr. Li: Simple, accurate and sensitive diagnostic tests are highly sought-after in modern medicine. Take bacterial infection as an example. Many microbial pathogens pose serious threats to public health and are responsible for many annual outbreaks that result in numerous human illnesses and deaths. Early and accurate detection of specific pathogens has long been recognized as a crucial strategy in the control of infectious diseases because such a measure can provide timely care of patients, prevent potential outbreaks, and minimize the impact of on-going epidemics. To detect the infection early, we need highly sensitive tests. We have developed a molecular device made of DNA that can be turned on by a molecule of choice, such as a biomarker for a disease. When it gets switched on, the system will undergo massive signal amplification allowing for extremely sensitive detection of the target molecule. The test has the best sensitivity ever reported for a detection system of this kind – it is as much as 10,000 times more sensitive than other detection systems. The scientific report can be found at http://onlinelibrary.wiley.com/doi/10.1002/anie.201503182/abstract
Author Interviews, Infections, Surgical Research / 08.07.2015

Paul M. Sethi, MD Orthopaedic & Neurosurgery Specialists Greenwich, CT MedicalResearch.com Interview with: Paul M. Sethi, MD Orthopaedic & Neurosurgery Specialists Greenwich, CT MedicalResearch: What is the background for this study? Dr. Sethi: Propionibacterium acnes is one of the most significant pathogens in shoulder surgery; the cost of a single infection after shoulder arthroplasty may be upwards $50,000. Residual P. acnes may be found on the skin 29% of the time immediately after surgical skin preparation and in 70% of dermal biopsy specimens. Identifying more ideal skin preparation may help reduce the risk of infection. MedicalResearch: What is the purpose of this study? Dr. Sethi: The purpose of this study was to evaluate the ability of topical benzoyl peroxide (BPO) cream, along with chlorhexidine skin preparation, to reduce the chance of identifying residual bacteria after skin preparation. Our hypothesis was that adding topical benzoyl peroxide to our skin preparation would reduce the number of positive P. acnes cultures identified during surgery.
Author Interviews, Ebola, Lancet / 02.07.2015

MedicalResearch.com Interview with: Jana Broadhurst, MD, PhD Stanford University Nira R Pollock MD PhD Boston Children's Hospital, Boston, MA Medical Research: What is the background for this study? What are the main findings? Response: At present, diagnosis of Ebola virus disease (EVD) in west Africa requires transport of venipuncture blood to field laboratories for testing by real-time RT-PCR, resulting in delays that complicate patient care and infection control efforts. Therefore, an urgent need exists for a point-of-care rapid diagnostic test (RDT) for this disease. In this study, we performed a field validation of the Corgenix ReEBOV Antigen Rapid Test kit, the only Ebola RDT authorized for emergency use by the WHO and FDA. This test is a dipstick lateral flow immunoassay designed to detect the Ebola virus VP40 protein in whole blood (collected by either fingerstick or whole blood) or plasma. We performed the rapid diagnostic test at the point-of-care on fingerstick blood samples from 106 individuals with suspected EVD presenting at two Ebola clinical centers in Sierra Leone. Separately, we performed the RDT on 284 venous whole blood samples submitted to the Public Health England field reference laboratory for clinical testing. Two readers independently scored each RDT as positive, negative, or invalid, with any disagreements resolved by a third. RDT results were compared with clinical real-time RT-PCR results obtained with the RealStar Filovirus RT-PCR kit 1.0 (altona Diagnostics GmBH). In point-of-care testing of fingerstick blood, the RDT had 100% sensitivity (95% CI 87.7-100) and 92% specificity (95% CI 83.8-97.1). Similarly, in venipuncture blood tested in the reference laboratory the rapid diagnostic test had 100% sensitivity (95% CI 92.1-100) and 92% specificity (95% CI 88.0-95.3). The two independent readers agreed for 95.2% of point-of-care and 98.6% of reference laboratory RDT results. The maximum cycle threshold (Ct) value was 26.3 in PCR-positive samples tested from both point-of-care (mean Ct 22.6) and reference laboratory (mean Ct 21.5) cohorts. Six of 16 banked plasma samples from RDT-positive and altona-negative patients were positive by an alternative real-time RT-PCR assay (the Trombley assay); 3 of 18 samples from individuals who were negative by both the RDT and altona test were also positive by Trombley.