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. (more…)
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. (more…)
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. (more…)
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. (more…)
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 of the HIV Medicine Association 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] (more…)
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. (more…)
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. (more…)
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. (more…)
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. (more…)
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. (more…)
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. (more…)
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. (more…)
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 (more…)
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. (more…)
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. (more…)
Author Interviews, Flu - Influenza, Vaccine Studies, Wistar / 29.06.2015

Scott E. Hensley, Ph.D. Assistant Professor Wistar Institute Philadelphia, PA 1910MedicalResearch.com Interview with: Scott E. Hensley, Ph.D. Assistant Professor Wistar Institute Philadelphia, PA 1910   Medical Research: What is the background for this study? What are the main findings? Response: Previous studies documented that the the 2014-2015 H3N2 flu vaccine strain was antigenically distinct compared to most recent H3N2 flu strains.  Recent H3N2 strains possess several mutation and it was previously unknown which of these mutations contributed to the 2014-2015 vaccine mismatch.  We used a reverse-genetic engineering approach to identify specific viral mutations that contributed to the 2014-2015 vaccine mismatch. (more…)
Author Interviews, Infections, Microbiome, Urinary Tract Infections / 29.06.2015

MedicalResearch.com Interview with: Jeffrey P. Henderson, M.D., Ph.D. Assistant Professor of Medicine and Molecular Microbiology Center for Women's Infectious Diseases Research Division of Infectious Diseases and Robin Shields-Cutler, Ph.D Ph.D. Student, Molecular Microbiology and Microbial Pathogenesis Washington University School of Medicine St. Louis, Missouri Medical Research: What is the background for this study? Response: Increasing antibiotic resistance, together with an appreciation that many patients are particularly susceptible to recurrent Urinary Tract Infections UTIs following antibiotic therapy, motivated interest in the events that occur during early stages of UTI pathogenesis. Abundant evidence suggests that uropathogenic E.coli must obtain iron from human hosts in order to cause a clinical infection. Early in infection, human cells secrete a protein called siderocalin that is known to limit bacterial growth by sequestering iron. This protein is detectable in the urine of Urinary Tract Infections patients. Medical Research: What are the main findings? Response: We obtained urine from a diverse panel of healthy volunteers, inoculated them individually with a uropathogenic E.coli strain, and monitored growth in the presence and absence of a fixed amount of siderocalin. Siderocalin exhibited a remarkably wide range of activity between individuals. We traced this variation back to differences in urinary pH and to phenolic urinary metabolites. We could significantly facilitate siderocalin’s antibacterial activity in urine by alkalinizing it above 6.5 and adding phenolic metabolites. The metabolites that potentiate siderocalin’s antibacterial effect have been linked to dietary sources such as coffee, tea, and berries. Some of these compounds may further derive from the actions of gut microbes on dietary phenols. The functional basis for these compounds’ properties seems to arise from siderocalin’s ability to use them as molecular grips that chelate iron ions in a form that is difficult for bacteria to access. From the pathogen perspective, we found that enterobactin, a molecule secreted by E.coli, acts as a microbial countermeasure to urinary siderocalin. Adding a drug-like inhibitor to urine that blocks enterobactin biosynthesis greatly increased siderocalin’s antibacterial effect. (more…)
AHRQ, Author Interviews, Hospital Acquired, Outcomes & Safety / 27.06.2015

Ann Scheck McAlearney, Sc.D., M.S. Professor, Family Medicine Vice Chair for Research, Department of Family Medicine College of Medicine Ohio State University Columbus, OhioMedicalResearch.com Interview with: Ann Scheck McAlearney, Sc.D., M.S. Professor, Family Medicine Vice Chair for Research, Department of Family Medicine College of Medicine Ohio State University Columbus, Ohio MedicalResearch: What is the background for this study? What are the main findings? Dr. McAlearney: In this study, we sought to explore the potential role high-performance work practices (HPWPs) may play in explaining differences in the success of central line-associated blood stream infection (CLABSI) reduction efforts involving otherwise similar organizations and approaches. We analyzed data from 194 key informant interviews across eight hospitals participating in the federally funded ‘‘On the CUSP: Stop BSI’’ initiative. We found evidence that at sites more successful at reducing central line-associated blood stream infection, HPWPs facilitated the adoption and consistent application of practices known to prevent CLABSIs; these HPWPs were virtually absent at lower performing sites. In this paper we present examples of management practices and illustrative quotes categorized into four HPWP subsystems: (a) staff engagement, (b) staff acquisition/development, c) frontline empowerment, and (d) leadership alignment/development. (more…)
Author Interviews, BMJ, Infections, Vaccine Studies / 26.06.2015

MedicalResearch.com Interview with: Siv Klevar, DVM,PhD. Norwegian Veterinary Institute Department of Diagnostics Section of Immunology Oslo Medical Research: What is the background for this study? Dr. Klevar:  Border control veterinary officers reported a surge in the number of imported dogs after the pet travel regulations were relaxed in 2012. At the same time rescue groups, through social media advertisement, encouraged and facilitated the adoption of dogs from shelters in Eastern Europe. The removal of the requirement regarding individual serological testing for antibodies to rabies before importing pets into UK, Ireland, Sweden, Malta and Norway, made it much easier to import pets into these countries. Previously import required several months of preparation and additional costs whereas under the new regulations it could be done after a single vaccination and a 3 week wait. The Norwegian Food Authority initiated a project to look at exotic pathogens in these re-homed dogs. This study reports the rabies antibody levels detected in some of the rehomed stray dogs entering Norway during 2012. The Norwegian Veterinary Institute and National Veterinary Institute in Sweden carried out the study. Medical Research: What are the main findings? Dr. Klevar: Our results showed that a high proportion of stray dogs, compared to a control group of pet dogs from Sweden, didn’t have sufficient protection against rabies virus after vaccination. Although we do not know exactly why this was the case, the exceedingly low levels of antibodies detected in some of the stray animals would suggest that they were not properly vaccinated, even though all the paperwork showed they were fully compliant with Pet Travel Regulations. The main issue highlighted by this study is that the current regulations are not sufficient to prevent rabies introduction when importing rescue dogs from countries where the virus is present to countries free from the disease. The reason for this is that the current regulations do not require a check to see if the pet has been properly vaccinated (by testing the animal’s blood for antibodies). In addition to this, the 21 day waiting period after vaccination isn’t long enough for rabies to develop if the dog had been infected prior to vaccination. (more…)
AHRQ, Antibiotic Resistance, Author Interviews, Baylor College of Medicine Houston, JAMA, Urinary Tract Infections / 25.06.2015

Barbara W. Trautner, MD, PhD Houston Veterans Affairs Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center Section of Infectious Diseases, Department of Medicine Baylor College of Medicine, Houston, TexasMedicalResearch.com Interview with: Barbara W. Trautner, MD, PhD Houston Veterans Affairs Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center Section of Infectious Diseases Department of Medicine Baylor College of Medicine, Houston, Texas Medical Research: What is the background for this study? What are the main findings? Dr. Trautner: Reducing antimicrobial overuse, or antimicrobial stewardship, is a national imperative. If we fail to optimize and limit use of these precious resources, we may lose effective antimicrobial therapy in the future. CDC estimates that more than $1 billion is spent on unnecessary antibiotics annually, and that drug-resistant pathogens cause 2 million illnesses and 23,000 deaths in the U.S. each year. The use of antibiotics to treat asymptomatic bacteriuria (ASB) is a significant contributor to antibiotic overuse in hospitalized and nursing home patients, especially among patients with urinary catheters. In catheterized patients, ASB is very often misdiagnosed and treated as catheter-associated urinary tract infection (CAUTI). Therefore, we designed the “Kicking CAUTI: The No Knee-Jerk Antibiotics Campaign intervention” to reduce overtreatment of ASB and to reduce the confusion about distinguishing CAUTI from asymptomatic bacteriuria. This study evaluated the effectiveness of the Kicking CAUTI intervention in two VAMCs between July 2010 and June 2013. The primary outcomes were urine cultures ordered per 1,000 bed-days (inappropriate screening for ASB) and cases of ASB receiving antibiotics (overtreatment). The study included 289,754 total bed days, with 170,345 at the intervention site and 119,409 at the comparison site. Through this campaign, researchers were able to dramatically decrease the number of urine cultures ordered. At the intervention site, the total number of urine cultures ordered decreased by 71 percent over the course of the intervention. Antibiotic treatment of asymptomatic bacteriuria decreased by more than 75 percent during the study. No significant changes occurred at the comparison site over the same time period. Failure to treat catheter-associated urinary tract infection when indicated did not increase at either site. (more…)
Author Interviews, Hand Washing, Infections / 25.06.2015

Laila Cure, Ph.D. Assistant Professor Dept. of Industrial and Manufacturing Engineering Wichita State UniversityMedicalResearch.com Interview with: Laila Cure, Ph.D. Assistant Professor Dept. of Industrial and Manufacturing Engineering Wichita State University Medical Research: What is the background for this study? What are the main findings? Response: It is widely known that healthcare work, particularly inpatient care work, is mostly knowledge-based. Healthcare workers are constantly assessing the clinical state of their patients and making decisions that affect their workflow. This type of work is difficult to study and organize as a whole using traditional work design techniques, which are mostly designed for routine, repetitive work. Nevertheless, there are components of inpatient work that can be improved using basic workstation design principles. Hand hygiene is one of them. Hand hygiene is still the single most important intervention to prevent infection in hospitals. Guidelines state that health care workers should clean their hands before touching a patient, before an aseptic procedure, after body fluid exposure, after touching a patient, after touching patient surroundings. Hand sanitizer dispensers are practical resources to support hand hygiene because they can be placed almost anywhere throughout hospital units. This study aimed at determining whether “good” placement of sanitizer dispensers correlates with compliance of staff in using the sanitizer. “Good placement” was defined in terms of usability characteristics extracted from hand hygiene literature recommendations. Of the usability characteristics included in the study, visibility and accessibility had some statistical influence on improving compliance. (more…)
Author Interviews, Emory, Flu - Influenza, PLoS / 23.06.2015

MedicalResearch.com Interview with: Brooke Bozick Ph.D. Candidate Population Biology, Ecology, & Evolution Program Emory University MedicalResearch: What is the background for this study? Response: Previous research at the global scale has shown that air travel is important for the spread of disease. For example, much work has focused on the recent Ebola epidemic in Africa, identifying where this disease emerged and then using air travel networks to predict the path of spread from there. At a more local scale, other modes of transportation may be more important to structuring pathogen populations. We were interested in investigating seasonal influenza in the United States. Previous research has shown that once the winter influenza epidemic starts, it spreads very rapidly across the continental states, suggesting that the US may act as one large, well-mixed population. Previous work using genetic data to look for spatial structure at this scale didn’t identify any patterns. However, these studies used geographic proximity to define the distance between states; we wanted to see whether similar patterns existed at this spatial scale if we instead used movement data as a proxy for the distance between locations. Commuter movements have previously been shown to correlate with influenza timing and spread based on influenza-like-illness and mortality data. MedicalResearch: What are the main findings? Response: We found that spatial structure is detectable within the US. We used data on the genetic distance between sequences collected from different states and compared that to different measures of ‘distance’ between states—geographic proximity, the daily number of people flying between states and the daily number of commuters traveling between states using ground transportation—to see whether any correlations were present. Further, we did this for two different subtypes of seasonal influenza: A/H3N2 and A/H1N1. These subtypes have different epidemiological properties, so there was reason to believe that the observed patterns might differ depending on subtype. We found that some correlations were present for all the distance metrics studied, but that they were observed a greater proportion of the time when looking at commuter movements, and when looking at the A/H1N1 subtype. Since A/H1N1 is generally milder and spreads more slowly throughout the US compared to A/H3N2, we interpret this to mean that spatial structure is likely more easily detected in this subtype. If A/H3N2 spreads rapidly from coast to coast, any signature of spatial structure is likely obscured before we have a chance to observe it. (more…)
Author Interviews, C. difficile, Columbia, Gastrointestinal Disease, Microbiome, Pediatrics / 19.06.2015

Daniel E. Freedberg, MD, MS Assistant Professor of Medicine Division of Digestive and Liver Diseases Columbia University, New YorkMedicalResearch.com Interview with: Daniel E. Freedberg, MD, MS Assistant Professor of Medicine Division of Digestive and Liver Diseases Columbia University, New York Medical Research: What is the background for this study? Dr. Freedberg: Acid suppression medications are increasingly prescribed to relatively healthy children without clear indications, but the side effects of these medications are uncertain. Medical Research: What are the main findings? Dr. Freedberg: Acid suppression with (proton pump inhibitors ) PPIs or (histamine-2 receptor antagonists) H2RAs was associated with increased risk for C. diff infection in both infants and older children. Medical Research: What should clinicians and patients take away from your report? Dr. Freedberg: Increased risk for C. diff should be factored into the decision to use acid suppression medications in children.  Our findings imply that acid suppression medications alter the bacterial composition of the lower gastrointestinal tract. (more…)
Author Interviews, Cancer Research, HPV, OBGYNE, Vaccine Studies / 18.06.2015

MedicalResearch.com Interview with: Ann Goding Sauer Epidemiologist, American Cancer Society, Inc. Atlanta, GA 30303 MedicalResearch: What is the background for this study? Response: Among US women, a positive association between Pap test uptake and HPV vaccination has been shown, though potential variation of the association by race/ethnicity had not been explored previously. The prevalence of some HPV types varies across different racial/ethnic groups so it is important to explore the association between Pap test uptake and HPV vaccination in detail. MedicalResearch: What are the main findings? Response: Pap test uptake was significantly lower among those who had not initiated HPV vaccination (81.0%) compared to women who had initiated vaccination (90.5%) (adjusted prevalence ratio = 0.93, 95% CI: 0.90–0.96). This result was seen across most of the sociodemographic factors examined, though not statistically significant for non-Hispanic blacks, Hispanics, those with lower levels of education, or those with higher levels of income. (more…)
Author Interviews, Heart Disease, Infections, Surgical Research / 13.06.2015

MedicalResearch.com Interview with: Mariusz Kowalewski, MD Department of Cardiac Surgery, Dr Antoni Jurasz Memorial University Hospital Bydgoszcz, Systematic Investigation and Research on Interventions and Outcomes Medicine Research Network, Poland Medical Research: What is the background for this study? What are the main findings? Dr. Kowalewski: Sternal wound infections occurring after heart surgery performed via median sternotomy, and in particular, after coronary artery bypass grafting (CABG), although rare, still pose serious postoperative complications that increase the length of hospital stay and healthcare costs. One of many ways to prevent them from happening, except from optimal glucose control, tight-fixed closure of the sternum at the end of surgery and perioperative iv. antibiotics, is to insert a gentamicin collagen sponge between two sternal edges, just before wiring them together. High local concentrations of gentamicin were shown to eliminate any microbial growth in the area, in the same time, not affecting the kidneys, as would be the case with systemic administration. Gentamicin sponges are widely used in orthopadic, gastro-intestinal and vascular surgery and were shown to reduce postoperative infection rates. Although extensively tested in the field of heart surgery, findings of one recent multicenter study have questioned their true benefit. We aimed to perform a comprehensive meta-analysis of studies assessing the efficacy of implantable gentamicin-collagen sponges in sternal wound infection prevention. After screening multiple databases, a total of 14 studies (N = 22,135 patients, among them 4 randomized controlled trials [N = 4,672 pts]) were included in the analysis. Implantable gentamicin-collagen sponges significantly reduced the risk of sternal wound infection by approximately 40% when compared with control (risk ratio [RR], 0.61; 95% confidence interval [CI], 0.39-0.98; P = .04 for randomized controlled trials and RR, 0.61; 95% CI, 0.42-0.89; P = .01 for observational studies). A similar, significant benefit was demonstrated for deep sternal wound infection (RR, 0.60; 95% CI, 0.42-0.88; P = .008) and superficial sternal wound infection (RR, 0.60; 95% CI, 0.43-0.83; P = .002). The overall analysis revealed a reduced risk of mediastinitis (RR, 0.64; 95% CI, 0.45-0.91; P = .01). The risk of death was unchanged. In addition, we investigated, by means of meta-regression, the correlation between sternal wound infections and extent to which the bilateral internal thoracic artery (BITA) was harvested. We found that the benefit provided by the gentamicin sponge was attenuated when BITA was harvested; these results suggest that another potentially preventive measure must be taken in such patients, as with severely reduced blood supply to the sternum (as is the case with BITA), sponge itself might not be enough to prevent wound infection. (more…)
Annals Internal Medicine, Author Interviews, Infections / 11.06.2015

MedicalResearch.com Interview with: Dr. Philip Molloy, MD Imugen Medical Director Medical Research: What is the background for this study? What are the main findings? Response: There is a newly described tick-borne infection in the US, first case published in NEJM Man 2013 (from Imugen researchers).  We then developed and validated both PCR and serologic blood tests.  Physicians  started ordering these tests, and many additional cases were uncovered, 51 of which are described in this paper. Medical Research: What should clinicians and patients take away from your report? Response: Be aware of yet another pathogen transmitted to humans from ticks, and don't assume it's Lyme.  Tests are available to help sort it out.  Imugen has been offering these tests commercially since 2013. (more…)
Author Interviews, Hospital Acquired, Infections / 08.06.2015

Stephanie Bonne, MD, FACS Assistant Professor Trauma, Acute, and Critical Care Surgery Washington University in St. LouisMedicalResearch.com Interview with: Stephanie Bonne, MD, FACS Assistant Professor Trauma, Acute, and Critical Care Surgery Washington University in St. Louis Medical Research: What is the background for this study? What are the main findings? Response: We had previously implemented education programs in our ICU in an attempt to decrease our Central Line-Associated Bloodstream Infection (CLABSI) rate.  We were, however, unable to come to zero.  We were looking for innovative ways to lower our CLABSI rate, and the use of Clorhexidine/Silver Sulfadiazine catheters was unable to move our CLABSI rate.  We decided to try Minocycline/Rifampin catheters, and monitor our Central Line-Associated Bloodstream Infection rate. Medical Research: What should clinicians and patients take away from your report? Response: The use of Minocycline/Rifampin impregnated catheters can lower Central Line-Associated Bloodstream Infection rate, particularly in ICUs who have been unable to reach a Central Line-Associated Bloodstream Infection rate of zero with other measures. (more…)
Author Interviews, HIV, Sexual Health, UCSD / 05.06.2015

MedicalResearch.com Interview with: Dr. Martin Hoenigl Center for AIDS Research University of California, San Diego Medical Research: What is the background for this study? What are the main findings? Dr. Hoenigl: Although men who have sex with men (MSM) represent a dominant risk group for human immunodeficiency Virus, the risk of HIV infection within this population is not uniform. Characterizing and identifying the MSM at greatest risk for incident HIV infection might permit more focused delivery of both prevention resources and selection of appropriate interventions, such as intensive counseling, regular HIV screening with methods that detect acute infection (ie, nucleic acid amplification test), and antiretroviral preexposure prophylaxis (PrEP). By using data collected at a single HIV testing encounter from 8326 unique MSM were analyzed, including 200 with AEH (2.4%), we were able to create the San Diego Early Test (SDET) risk score. The SDET score consist of four risk behavior variables which were significantly associated with an AEH diagnosis (ie, incident infection) in multivariable: condomless receptive anal intercourse (CRAI) with an HIV-positive MSM (3 points), the combination of CRAI plus 5 or more male partners (3 points), 10 or more male partners (2 points), and diagnosis of bacterial sexually transmitted infection (2 points), all as reported for the prior 12 months. The SDET risk score is deployed as a freely available tool at http://sdet.ucsd.edu. (more…)