Author Interviews, Critical Care - Intensive Care - ICUs, Infections, JAMA / 24.02.2016

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

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

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

MedicalResearch.com Interview with: Ashootosh Tripathi, PhD Postdoctoral Research Fellow Life Sciences Institute I Sherman lab University of Michigan Ann Arbor, MI, USA MedicalResearch: What is the background for this study? What are the main findings? Dr. Tripathi: Acinetobacter baumannii is a nosocomial opportunistic and resistant pathogen that can spread epidemically among patients causing ventilator-associated pneumonia and bacteremia. The mortality rates associated with it can be as high as 60%, representing a paradigm of pathogenesis, transmission and resistance. In addition, numerous reports have shown the startling emergence of multidrug-resistant A. baumannii in hospitals as well as the identification of pan-drug-resistant strains at some locations. Among the  various reasons for the antibiotic resistance of this pathogenic microbe, perhaps the most significant is mediated by its tendency to form biofilms (a highly structured extracellular polymeric matrix), which provide the microbe with the alarming ability to colonize medical devices. Interestingly, despite the well-understood role of bacterial biofilm behind aggravating antimicrobial resistance, there are currently no drugs specifically targeting biofilms in clinical trials to date. The study sought to solve this problem through the development of a biofilm inhibitor as a precision medicine, directed towards vulnerable patients, to avoid potential life-threatening infections. A crystal-violet based high throughput in vitro screen was developed to identify inhibitors of A. baumannii biofilms against our natural products extract (NPE) library. The vast NPE library of ~42,000 extracts has been under constant development in Prof David H. Sherman laboratory at University of Michigan, Ann Arbor, for over the past decade, from a relatively underexplored marine microbiome collected from different part of world viz., Costa Rica, Panama, Papua New Guinea, etc., and is available for any research group with a robust high-throughput screening (HTS) assay (http://www.lsi.umich.edu/centers/center-for-chemical-genomics). The HTS assay that was queried against a library of 9,831 NPEs aimed to identify extracts inhibiting biofilm formation as a primary screening. Further secondary  screening and   activity  threshold optimization revealed the extract from Streptomyces gandocaensis (collected from Costa Rica) to be of particular interest due to its ability to inhibit biofilm formation and had a limited effect on A. baumannii growth. Activity based chromatographic separation and analysis of extracts derived from S. gandocaensis resulted in the discovery of three peptidic metabolites (cahuitamycins A–C),   with cahuitamycin  C  being   the   most effective biofilm inhibitor (IC50 =14.5 µM)   with  negligible A.  baumannii growth inhibition (an important trait for ideal biofilm inhibitor). Following up on the exciting discovery, we also completely characterized the biosynthetic machinery involved in making the active molecules by S. gandocaensis, using sophisticated bioinformatics and molecular biology techniques. The knock out analysis revealed that the biosynthesis of cahuitamycin C proceeds via a convergent biosynthetic pathway, with one of the steps apparently being catalyzed by an unlinked gene encoding a 6-methylsalicylate synthase. Efforts to assess starter unit diversification through selective mutasynthesis led to production of unnatural analogues cahuitamycins D and E with increased potency (IC50=8.4 and 10.5 µM) against A. baumannii biofilm. (more…)
Alzheimer's - Dementia, Author Interviews, Dental Research, Infections, Stroke / 18.02.2016

MedicalResearch.com Interview with: Dr. Robert Friedland MD Mason C. and Mary D. Rudd Endowed Chair In Neurology Professor, Dept. of Neurology University of Louisville Health Care Outpatient Center Louisville, KY 40292 Medical Research: What is the background for this study? What are the main findings? Dr. Robert Friedland: Oral infectious diseases are associated with stroke. Previous research by this group has shown that oral bacteria, cnm-positive Streptococcus mutans, was associated with cerebral microbleeds and intracerebral hemorrhage. We developed this study to investigate the roles of this bacteria in patients entering the hospital for all types of stroke. Among the patients who experienced intracerebral hemorrhage (ICH), 26 percent were found to have a specific bacterium in their saliva, cnm-positive S. mutans. Among patients with other types of stroke, only 6 percent tested positive for the bacterium. We also evaluated MRIs of study subjects for the presence of cerebral microbleeds (CMB), small brain hemorrhages which may cause dementia and also often underlie ICH. We found that the number of CMBs was significantly higher in subjects with cnm-positive S. mutans than in those without. (more…)
Author Interviews, Infections, PLoS / 14.02.2016

MedicalResearch.com Interview with: Tamar Kleinberger, Ph.D. Dept. of Molecular Microbiology Faculty of Medicine Technion – Israel Institute of Technology Haifa ISRAEL Medical Research: What is the background for this study? What are the main findings? Dr. Kleinberger: The cellular DNA damage response (DDR) is a conglomerate of pathways designed to detect DNA damage and signal its presence to cell cycle checkpoints and to the repair machinery, allowing the cell to pause and mend the damage, or if the damage is too severe, to trigger cell death or senescence. Replication intermediates and linear double-stranded genomes of DNA viruses are recognized by the cell as DNA damage and activate the DDR. If allowed to operate, the DDR will stimulate ligation of viral genomes and will inhibit virus replication. To prevent this outcome, many DNA viruses evolved ways to limit the DDR. For example, adenoviruses, a family of viruses that cause respiratory illnesses or gastrointestinal disease or eye infections, have been reported to inhibit the DDR by degrading DNA damage sensor proteins or by removing them from virus replication centers. Our present work reveals that adenovirus evolved an additional mechanism to inhibit the DDR, using its E4orf4 protein. The viral E4orf4 protein, together with its cellular partner, the PP2A phosphatase, inhibits damage signaling by reducing phosphorylation of proteins belonging to different DDR branches. As a result E4orf4 causes accumulation of DNA damage in the cells. Inhibition of the DDR regulators ATM and ATR as well as expression of E4orf4 enhance infection efficiency. We found that, at least in the cells we studied, ATM inhibition was important to the early stage of the virus life cycle, whereas ATR inhibition impacted mostly late protein expression and progeny virus production. Furthermore, we previously reported that E4orf4 induces cancer-specific cell death when expressed alone, and in the present report we found that E4orf4 sensitized cells to killing by sub-lethal concentrations of DNA damaging drugs, likely because it inhibited DNA damage repair. These findings provide one explanation for the cancer-specificity of E4orf4-induced cell death because many cancers have DDR deficiencies leading to increased reliance on the remaining intact DDR pathways and to enhanced susceptibility to DDR inhibitors such as E4orf4. Thus DDR inhibition by E4orf4 contributes both to the efficiency of adenovirus replication and to the ability of E4orf4 to kill cancer cells. (more…)
Author Interviews, Dermatology, Exercise - Fitness, Herpes Viruses, Infections / 06.02.2016

MedicalResearch.com Interview with: Kurt Ashack Fourth year medical student at Michigan State University, Michigan Kyle Burton University of Central Florida College of Medicine, Orlando, Florida Medical Research: What is the background for this study? What are the main findings? Response: Skin infections associated with high school athletics have been reported in literature since the late 20th century and while many skin infections are relatively minor, others can cause serious morbidity. Prior reports on skin infections among high school athletes have focused on specific sports or have evaluated relatively small numbers of athletes. No prior report has evaluated skin infections in a large national sample of United States (US) high school athletes across multiple sports. During the study period, 474 skin infections were reported among 20,858,781 athlete exposures (AE); a rate of 2.27 infections per 100,000 AE. The largest number of skin infections occurred in wrestlers (73.6%), followed by boys’ football (17.9%) and boys’ basketball (1.9%). Baseball and swimming had much fewer cases. The most common infections were bacterial (60.6%), tinea (28.4%) and herpetic (5.2%) infections. Body parts most often affected were the head/face (25.3%), forearm (12.7%) and upper arm (8%). The average time for return to play was 3-6 days (45.5%). It was also interesting to note how many more infections there were in boys than girls. Girls’ volleyball had the most of girls’ sports, but all girl reports did not near the boy's number. (more…)
Author Interviews, Cancer Research, Infections / 27.01.2016

MedicalResearch.com Interview with: Yvonne Kapila, DDS, PhD Professor, Division of Periodontics Department of Periodontics and Oral Medicine University of Michigan School of Dentistry Ann Arbor, MI   Medical Research: What is the background for this study? What are the main findings? Dr. Kapila: Our research showed that the preservative nisin induces cancer cell death. When tested on normal control cells to see if they were affected, the control cells were not affected. Thus, the most recent project began in order to find out more details as to why this occurred. We used a cancer mouse model (head and neck cancer) to show that nisin can retard tumor growth and extent the life of these mice. Another thing that we published about the preservative is nisin’s role on biofilms. Biofilms are communities of bacteria that can cause diseases. Nisin has been tested in bacterial biofilms that contain bacteria that cause gum disease and dental decay and nisin has been found to be effective in this setting as well. In laboratory settings, nisin is also cytotoxic to superbugs, including the most resistant bugs found in hospitals, and therefore nisin holds promise for several therapeutic applications. (more…)
Author Interviews, Duke, Genetic Research, Infections / 24.01.2016

MedicalResearch.com Interview with: Ephraim L. Tsalik, MD MHS PhD Assistant Professor of Medicine Division of Infectious Diseases Center for Applied Genomics & Precision Medicine Duke University Medical Center Emergency Department Service Line Durham VA Medical Center  Medical Research: What is the background for this study? What are the main findings? Dr. Tsalik: This study was motivated by the convergence of two research interests.  The first was spearheaded by Dr. Sack, leading our collaboration at Johns Hopkins.  Dr. Sack and his colleagues have a long history and expertise in studying enteric infections such as E. coli.  The second is our group here at Duke’s Center for Applied Genomics & Precision Medicine as well as the Durham VA Medical Center.  Specifically, we have an interest in studying the host response to infectious disease.  One of the ways we’ve done that historically is through challenge studies where healthy volunteers are exposed to a pathogen in a controlled setting.  Despite everyone getting the same exposure, not everyone gets sick.  That observation gives us a unique opportunity to study the host biology of symptomatic individuals, asymptomatic individuals, and what distinguishes the two from each other.  That is precisely what we did here. Volunteers ingested Enterotoxigenic E. coli (ETEC), which is a common cause of traveler’s diarrhea.  Some subjects became ill with diarrhea while others remained well.  In this study, we focused on gene expression patterns, which is a snapshot of how genes in the body are being used in response to this infection.  Some genes are more active, some are less.  The pattern of those changes that occur in response to infection is what we call a “signature”. This approach allowed us to generate some key findings.  First of all, we were able to define the genes involved in the body’s response to this type of E. coli infection.  Second, we discovered genes that were differentially expressed at baseline that could distinguish people who would go on to become ill from those that would remain healthy.  Although this study was not designed to identify the mechanism for that resilience to infection, it does focus our attention on where to look.  We suspect the genes we identified are likely to play a role in infectious disease resilience and susceptibility based on their known immune function roles.  We also have data, which wasn’t published in this study, that implicates some of these genes in the resilience to other infections such as influenza. The last major finding was something called Drug Repositioning Analysis.  This is a tool that allowed us to identify drugs and drug classes that could be used to mitigate infections caused by ETEC.  That analysis highlighted some compounds already known to be effective such as Zinc.  But it also identified several other drug classes that have not previously been investigated and could be important tools to combat such infections especially as antibiotic resistance looms. (more…)
Author Interviews, Dermatology, Infections / 22.01.2016

More on Dermatology on MedicalResearch.com MedicalResearch.com Interview with: Gregory R. Delost, DO University Hospitals Regional Hospitals Richmond Heights, OH MedicalResearch.com: What is the background for this study? Dr. Delost: Acne vulgaris is a common dermatological disorder with an incidence of approximately 85% in adolescents and young adults. Treatment options include topical antibiotics, topical retinoids, benzoyl peroxide, oral antibiotics and isotretinoin. Antibiotics are generally prescribed for cases of moderate to severe acne. However, long-term antibiotic use may affect the normal flora bacteria and perhaps promote the development of antibiotic resistant bacteria. There is little prospective research in outpatient settings to determine if these concerns are valid. In our study, we used a prospective, cross-sectional, quasi-experimental design, which compared colonization of Staphylococcus aureus in 263 patients undergoing treatment for clinically diagnosed acne in two northeastern Ohio dermatology practices. (more…)
Author Interviews, Heart Disease, Infections, JACC / 20.01.2016

MedicalResearch.com Interview with: François Delahaye, MD, PhD Department of Cardiology Hôpital Louis Pradel, Hospices Civils de Lyon Université Claude Bernard Lyon, France Medical Research: What is the background for this study? Response: Infective endocarditis (IE) is a severe disease, with an in-hospital mortality rate of about 20%. Five percent to 10% of patients will have additional episodes of IE. Thus, looking for and treating the portal of entry (POE) of IE is particularly important. The POE of the present episode must be identified in order to treat it. The potential POE of a new episode must be searched for in order to eradicate it and thus lower the risk for a new IE episode. Yet published research on this topic is nonexistent. The search for and treatment of the POE are not even mentioned in the guidelines on IE. We thus undertook a study of the performance of a systematic search for the portal of entry of the present episode of IE and of a potential new episode of Infective endocarditis. Patients were systematically seen by a stomatologist, an ear, nose, and throat specialist, and a urologist; women were systematically seen by a gynecologist; patients were seen by a dermatologist when there were cutaneous and/or mucous lesions. Colonoscopy and gastroscopy were performed if the microorganism came from the gastrointestinal tract in patients ≥ 50 years of age and in those with familial histories of colonic polyposis. Treatment of the portal of entry was systematically considered. Medical Research: What are the main findings? Response: The POEs of the present Infective endocarditis episodes were identified in 74% of the 318 included patients. The most frequent portal of entry was cutaneous (40% of identified POEs). It was mainly (62% of cutaneous POEs) associated with health care and with intravenous drug use. The second most frequent POE was oral or dental (29%). A dental infectious focus was more often involved (59% of oral or dental POEs) than a dental procedure (12%). POEs were gastrointestinal in 23% of patients. Colonic polyps were found in one-half of the patients and colorectal adenocarcinomas in 14%. Performance was good regarding the search for an oral or dental or a colonic potential POE, which were found in 53% and 40% of patients, respectively. (more…)
Author Interviews, C. difficile, Hospital Acquired, Infections, Microbiome / 07.01.2016

MedicalResearch.com Interview with: Casey M. Theriot, Ph.D. Assistant Professor Infectious Disease College of Veterinary Medicine Department of Population Health and Pathobiology North Carolina State University Raleigh, NC 27607 Medical Research: What is the background for this study? What are the main findings? Dr. Theriot: This study is an extension of the work we did in 2014 in our Nature Communications paper (Theriot et al. Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection, 2014). We really wanted to know how different antibiotics that varied in their mechanism of action altered the gut microbiota in different ways and also in turn how this altered the bile acids present in the small and large intestine of mice. Primary bile acids are made by the host and are further converted to secondary bile acids by members of the microbiota in the large intestine. We know from previous work that secondary bile acids can inhibit the growth of C. difficile, but no one has looked in depth at the bile acid makeup in the actual gut before in the context of C. difficile. In this study we show that specific antibiotics that significantly alter the large intestinal gut microbiota and deplete all secondary bile acids allow for C. difficile to grow without any inhibition. We also showed that C. difficile spores are always germinating in the small intestine, which means in order to prevent this pathogen from colonizing the gut, we will have to target the growth of the pathogen. Moving forward the focus will be on trying to repopulate the gut with bacteria that are capable of restoring the secondary bile acid pools in order to inhibit C. difficile. (more…)
Author Interviews, Hospital Acquired, Infections, OBGYNE, Outcomes & Safety / 30.12.2015

MedicalResearch.com Interview with: Muhammad A. Halwani, MSc, PhD Faculty of Medicine, Al Baha University Al Baha, Saudi Arabia.  Medical Research: What is the background for this study? What are the main findings? Response: The study idea was based on examining the current rate of post cesarean section infections that were detected in the hospital at the time. It was hypothesized that the detected infections were actually less than the real number identified. Therefore, we challenged the traditional surveillance method that was applied in the hospital with a new enhanced methodology which is telephone follow-ups for patients who under go C-section operations. Our main finding proved that this new applied method was able to detect more cases than the traditional one. Using phone calls as a gold standard, the sensitivity of the standard methodology to capture SSI after cesarean increased to 73.3% with the new methodology identifying an extra five cases. These patients represented 26.3% (5 of 19) of all the patients who developed SSI. In other words, for every 100 C-section procedures there were 2.6% missed cases which the new method was able to detect. The duration of the calls ranged from 1 to 5 minutes and were well received by the patients. (more…)
Author Interviews, Infections, JAMA, Microbiome / 24.12.2015

MedicalResearch.com Interview with: Tara F Carr, MD Assistant Professor, Medicine and Otolaryngology Allergy and Immunology Fellowship Training Program Director Director, Adult Allergy Division of Pulmonary, Allergy, Critical Care and Sleep Medicine University of Arizona Tucson, AZ 85724 Medical Research: What is the background for this study? What are the main findings? Dr. Carr: Some patients with chronic rhinosinusitis continue to suffer from symptoms despite aggressive medical and surgical treatments. For these individuals, therapy is generally chosen based on bacterial culture results, and often includes the use of topical antibacterial rinses with a medication called mupirocin.  We found that if patients are still having problems after this treatment, the bacteria identified from repeated sinus cultures are very different than those usually expected, and in general more difficult to treat. (more…)
Author Interviews, HPV, Infections, Pediatrics, Sexual Health / 23.12.2015

MedicalResearch.com Interview with: Seo Yoon Lee, RN Department of Health Policy and Management Graduate School of Public Health Eun-Cheol Park MD, PhD Institute of Health Services Research Department of Preventive Medicine Yonsei University, Seoul, South Korea  Medical Research: What is the background for this study? What are the main findings? Response: Sexually Transmitted Infections (STIs) are a major public health issue which causes acute illness, infertility, long-term disability or other serious medical and psychological consequences, around the world. Adolescence is a key developmental period with rapid cognitive growth. In recent decades, substantial change in the sexual behaviors and attitudes of adolescents has occurred and this would lead them greater risk of STIs than other. Our study looked at the relationship between adolescents’ first sexual intercourse age and their STI experience, as well as to identify vulnerable time table of their sexual activity by considering the time gap between their secondary sex characteristic occurrence age and first sexual intercourse age. The findings from our study show that earlier initiation of sexual intercourse increases the odds of experiencing STIs. Also as the age gap gets shorter, the odds of experiencing STIs increase. Approximately 7.4% of boys and 7.5% of girls reported had STI. For both boys and girls, the chance of experiencing STIs increased as the age of first sexual intercourse decreased [boys: before elementary school (age 7 or under) OR=10.81, first grade (age 7or 8) OR=4.44, second grade (age 8 or 9) OR=8.90, fourth grade (age 10 or 11) OR=7.20, ninth grade (age 15 or 16) OR=2.31; girls: before elementary school OR=18.09, first grade OR=7.26, second grade OR=7.12, fourth grade OR=8.93, ninth grade OR=2.74]. The association between the absolute age gap (AAG: defined as absolute value of “Age gap” = [Age at first sexual intercourse] - [age of secondary sexual manifest]) and STI experience was examined additionally which the result showed, students who had sexual intercourse after their secondary sexual manifestation, as the AAG increases, the odds of STI experience were decreased (boys OR=0.93, girls OR=0.87). (more…)
Author Interviews, Cost of Health Care, Emory, Infections, Pharmacology / 17.12.2015

MedicalResearch.com Interview Questions Carlos del Rio, MD Chair, HIV Medicine Association Department of Medicine Hubert Professor and Chair of the Department of Global Health at the Rollins School of Public Health Professor of Medicine in the Division of Infectious Diseases Emory University School of Medicine MedicalResearch.com Editor's note:  Dr. Carlos del Rio discusses the statement from the Infectious Diseases Society of America (IDSA), HIV Medicine Association (HIVMA) and the Pediatric Infectious Diseases Society (PIDS) regarding the news that Express Scripts is taking steps to improve access to obtaining pyrimethamine for patients with toxoplasmosis. Medical Research: What is the background for this Express Scripts announcement? Dr. del Rio: The HIV Medicine Association (HIVMA) and the Infectious Diseases Society of America initially heard from our members (ID and HIV clinicians) in August about the 5000% price increase in Daraprim® (from $13.50 to $750 per tablet) following Turing Pharmaceuticals’ acquisition of the rights to distribute Daraprim® from Impax Laboratories, Inc.[1] ID and HIV clinicians told us they had been having difficulties obtaining pyrimethamine since earlier in the summer when Impax implemented a controlled distribution system making the drug available only through Walgreen’s Specialty Pharmacy. Despite HIVMA, IDSA and others urging Turing to reverse the price hike, no action was taken and providers continued to report the scarcity of the drug due to the cost and issues with the distribution system. [2] Due to these ongoing challenges, HIVMA and IDSA thought it was important to provide information to our members and other providers regarding the new lower cost option so they could evaluate this option in consultation with their patients. Initially Turing agreed to reconsider the price increase and to lower it; however, on Nov. 24th Turing announced that they would not lower the list price of Daraprim but instead planned to offer discounts of up to 50% to some hospitals. [3] The announcement reinforced the urgent need for affordable treatment options and failed to address that a majority of the eight to twelve month treatment course occurs on an outpatient basis. (more…)
Author Interviews, Biomarkers, Infections, PLoS, Technology / 10.12.2015

MedicalResearch.com Interview with: Leo McHugh, Ph.D. Director, Bioinformatics Immunexpress Seattle, Washington  Medical Research: What is the background for this study? What are the main findings? Dr. McHugh: Sepsis is the leading cause of child mortality in the world, and in developing countries kills more adults than breast cancer, prostate cancer and HIV combined. Approximately 30% of people admitted to ICU have sepsis, and up to 50% of these patients die. It’s a major cost burden also, costing the US health system $17 billion per year. The best way to reduce costs and improve patient outcomes is to detect sepsis early and with confidence, so that appropriate treatments can be applied. Each hour delay in the detection of sepsis has been reported to correspond to an 8% increase in mortality. So the need for a rapid and accurate diagnostic is recognized. Traditional methods rely on detection of the specific pathogen causing the infection, and these methods often take more than 24 hours, and find a pathogen in only 30% of clinically confirmed cases because they’re trying to detect a minuscule amount of pathogen or pathogenic product in the blood. Our approach was to use the host’s own immune system, which is highly tuned to respond to the presence of pathogens. Around 30% of all genes are dysregulated in sepsis, so there is a huge signal base to draw from. The trick with using multi marker host response is to pick out the specific combination of gene expression patterns that cover the broad range of patients that present with sepsis and who may present either early or late in the episode, thus with different gene activation patterns. This paper describes a simple combination of such genes that can be used to detect sepsis and performs over the full range of patients irrespective of stage of infection or severity of infection. In it’s current format, the test is manual and takes 4-6 hours, and is a great advance on the current tools, however the methods we’ve used are specifically designed to meet requirements to port this assay onto a fully automated Point of Care platform that could deliver a result in under 90 minutes. (more…)
Author Interviews, Infections, Nature / 02.12.2015

MedicalResearch.com Interview with: Professor Søren Riis Paludan DMSc, PhD Department of Biomedicine Aarhus University Denmark Medical Research: What is the background for this study? What are the main findings? Prof. Paluden: We were interested in understanding the first immune reactions that occur when an organism meets an infectious agent (virus or bacteria). The main finding is that we have identified an immune reaction that is activated as the microbe disturbed the mucus layer at mucosal surfaces. This is an immune reaction occuring earlier than what has been thought previously, and may represent a mechanism that enables the organism to fight most microbes that we meet without mounting strong immune responses. This is important, since strong immune reactions - in addition to contributing to elimination of microbes - also have negative effects such as fever, etc. (more…)
Author Interviews, Hospital Acquired, Infections / 27.11.2015

MedicalResearch.com Interview with: Prof. Jean-Yves Maillard Professor of Pharmaceutical Microbiology College of Biomedical and Life Sciences Cardiff School of Pharmacy and Pharmaceutical Sciences Cardiff University Cardiff United Kingdom Medical Research: What is the background for this study? What are the main findings? Prof. Maillard: Environmental surfaces in healthcare and other settings become contaminated with a variety of infectious agents which may survive long enough to infect susceptible hosts, either directly or through secondary vehicles such as hands. Therefore, routine decontamination of environmental surfaces, in particular those that are frequently touched, is crucial to reduce the risk of infections. Such decontamination is often performed by wiping the target surface with disinfectant-soaked or pre-wetted wipes. However, the label claims of wipes marketed for this purpose are often based upon testing that does not reflect their field use, where contact times are frequently no more than a few seconds with wide variations in the pressure applied during wiping. In addition, wipes impregnated with a disinfectant or detergent can potentially transfer microbial contaminants to a wider area, when the same wipe is used on multiple surfaces. A device called the ‘Wiperator’ was invented to address these issues. It can be used to test wipes with predetermined pressures, wiping times and number of wiping strokes, using a standardized rotary action. It can not only assess the decontaminating efficiency of the test wipe, but also its ability to transfer the acquired contamination to clean surfaces. The test procedure developed using the device is now a standard (E2967) of ASTM International, a highly-respected standards-setting organization. The Wiperator was used in a multi-laboratory collaborative to test commercially-available wipes for their ability to decontaminate metal disks that had been experimentally-contaminated with vegetative bacteria representing healthcare-associated pathogens. The used wipes were subsequently tested for their potential to transfer viable bacteria to clean surfaces. The contact time for wiping and transfer was 10 seconds. Only one of the wipes tested reduced the contamination to an undetectable level while not transferring any viable bacteria to a clean surface. All others left behind detectable levels of contamination on the wiped disks and transferred the contamination to clean surfaces. (more…)
Author Interviews, Clots - Coagulation, Infections / 19.11.2015

MedicalResearch.com Interview with: Professor Adam Cunningham PhD Institute of Immunology and Immunotherapy MRC Centre for Immune Regulation University of Birmingham Medical Research: What is the background for this study? Dr. Cunningham: Our original question was “Why do people die from Salmonella infections that spread beyond the gut”. Some reasons are known but these do not account for all. In particular infants in sub-Saharan Africa seem particularly prone to Salmonella infections that in the West do no more than cause a self-limiting gastroenteritis. A puzzling feature of many of infections in such infants is that they do not have many bacteria in the blood, probably <10 / ml of blood, yet this low density is a strong predictor of death. Therefore, we thought that it may be the host response to the infection that complicates its control and contributes. (more…)
Author Interviews, CDC, Infections, OBGYNE, STD / 13.11.2015

MedicalResearch.com Interview with: Dr. Virginia Bowen PhD Epidemic Intelligence Service Division of STD Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention,CDC  Medical Research: What is the background for this study? What are the main findings? Dr. Bowen: Congenital syphilis (CS) occurs when a mother infected with syphilis transmits the infection to her child during the course of pregnancy. Our study looked at recent trends in CS between 2008 and 2014. After four years of decline, Congenital syphilis rates increased by 38% from 2012 to 2014. The findings from this report show we are missing opportunities to screen and treat pregnant women for STDs. Syphilis in pregnant women can cause miscarriages, premature births, stillbirths, or death of newborn babies. We have effective tests and treatment for syphilis – there’s no excuse for allowing it to resurge. Every case of CS is one too many. (more…)
Author Interviews, Infections, Pediatrics, Respiratory / 06.11.2015

MedicalResearch.com Interview with: Dominik Mertz, MD, MSc, FMH (CH) Assistant Professor, McMaster University Department of Medicine, Division of Infectious Diseases Associate Membership Department of Clinical Epidemiology and Biostatistics / Pathology and Molecular Medicine Medical Director Infection Prevention & Control, Hamilton Health Sciences Juravinski Hospital and Cancer Center Hamilton, ON, Canada  Medical Research: What is the background for this study? What are the main findings? Dr. Mertz: There was a perception that there was an increase in ICU admissions and deaths, initially in Kansas City and Chicago, which was found to be related to the enterovirus strain EV-D68, which had previously not resulted in any major outbreaks in North America. We have one of the first laboratories that was able to provide a specific EV-D68 PCR routine testing allowing us identify EV-D68 cases and to compare the outcomes in patients infected with this strain to children infected by other rhino/enteroviruses. We found a substantial overlap in how the patients presented between patients with EV-D68 and non-EV-D68 infection. It seems that children infected with EV-D68 were in deed at higher risk for having respiratory distress and needing hospital admission, with children with allergies being at a higher risk. We did not find an increase in more severe outcomes, though, i.e. no higher risk for ICU admission (23 vs 15%) and 0 deaths in the EV-D68 group. We also did not find any evidence of in-hospital transmission of EV-D68. (more…)
Author Interviews, CDC, Infections / 05.11.2015

MedicalResearch.com Interview with: Sam Crowe, PhD, MPH Epidemic Intelligence Service Officer Enteric Diseases Epidemiology Branch Division of Foodborne, Waterborne, and Environmental Diseases Centers for Disease Control and Prevention Medical Research: What were the leading causes of multistate foodborne outbreaks and the most common contaminated foods during the study period? Dr. Crowe: Salmonella, Shiga toxin-producing Escherichia coli, and Listeria monocytogenes were the leading pathogens causing multistate foodborne outbreaks. In order of frequency, fruits, vegetable row crops, beef, sprouts, and seeded vegetables were the leading contaminated foods. Medical Research: How severe are multistate foodborne outbreaks? Dr. Crowe: From 2010 through 2014, multistate foodborne outbreaks accounted for only 3% of all U.S. foodborne outbreaks detected, but caused over one third of the hospitalizations and more than half of the deaths. Medical Research: Are these outbreaks occurring more frequently? Dr. Crowe: Multistate foodborne outbreaks are being identified more often in the United States because of better surveillance. Greater centralization of food processing and distribution practices also could be increasing the frequency and size of multistate foodborne outbreaks. This is why your business should Look for Ruggedised Industrial Pointing Devices Today, to ensure your business is staying up with the industry standards. (more…)
Antibiotic Resistance, Author Interviews, CDC, Infections / 04.11.2015

Dr. Bob Kirkcaldy MD, MPH Epidemiologist, Division of STD Prevention CDCMedicalResearch.com Interview with: Dr. Bob Kirkcaldy MD, MPH Epidemiologist, Division of STD Prevention CDC Medical Research: What is the background for this study? What are the main findings? Dr. Kirkcaldy: Gonorrhea is a common sexually transmitted disease that, if untreated, can cause severe reproductive health complications. While gonorrhea is very common, it is often symptomless and many may not realize they have it. 333,004 cases were diagnosed in 2013, but more than 820,000 are estimated to occur annually. Because antibiotic resistance has jeopardized treatment for gonorrhea, CDC’s Gonoccocal Isolate Surveillance Project (GISP) monitors antimicrobial susceptibility and tracks patterns of resistance among antibiotics currently used to treat gonorrhea. From 2006-2009, susceptibility to the oral cephalosporin antibiotic cefixime declined in GISP, threatening the effectiveness of this drug. Continued use of cefixime in the face of declining susceptibility could theoretically foster broad resistance to the cephalosporin class (including ceftriaxone, the last treatment option). So in 2012,  CDC changed its treatment recommendations to recommend only dual gonorrhea treatment with injectable ceftriaxone plus oral azithromycin. The most recent data from GISP analyzed urethral gonorrhea samples of men from STD clinics in 34 cities from 2006-2014 and found resistance to cefixime increased in 2014 after two years of dramatic decreases. While CDC’s STD Treatment Guidelines suggest cefixime should only be considered as an alternative treatment for gonorrhea when ceftriaxone is not available, trends of cefixime susceptibility have historically been a precursor to trends in ceftriaxone so it’s important to continue monitoring cefixime to be able to anticipate what might happen with other drugs in the future. GISP data also found that resistance remained stable for ceftriaxone and resistance levels remain highest among men who have sex with men (MSM). We’re concerned about the increase in resistance for cefixime; however, more years of data are needed to know if the 2014 increase is the beginning of a new trend. (more…)
Author Interviews, Diabetes, Infections, Surgical Research / 29.10.2015

Emily Toth Martin, Ph.D. MPH Assistant Professor, Epidemiology University of Michigan School of Public HealthMedicalResearch.com Interview with: Emily Toth Martin, Ph.D. MPH Assistant Professor, Epidemiology University of Michigan School of Public Health  Medical Research: What is the background for this study? What are the main findings? Response: Surgical site infections are responsible for billions in health care costs in the U.S. We are working to identify groups of people who are particularly impacted by surgical site infections. By looking at the results of 94 studies, we were able to take a 60,000 foot view of the connection between diabetes and surgical site infection. We found that diabetes raises the risk of infection across many types of surgeries. (more…)
Author Interviews, Geriatrics, Infections / 28.10.2015

MedicalResearch.com Interview with: Christian Hammer, PhD École Polytechnique Fédérale de Lausanne Swiss Institute of Bioinformatics Lausanne, Switzerland Clinical Neuroscience Max Planck Institute of Experimental Medicine Göttingen, Germany Medical Research: What is the background for this study? What are the main findings? Dr. Hammer: The immune response after viral infection or vaccination varies considerably from person to person, which is important because these differences can account for clinical outcome or vaccine effectiveness. It has been shown before that part of this variability is heritable, indicating the possibility that differences in our genes might be involved. To test this, we performed a genome-wide association study in more than 2,300 individuals, using high-performance computing to analyze whether differences in the abundance of antibodies against 14 common viruses are caused by variable sites in our genome. We looked at about 6 million of these variants and found that a region on chromosome 6 that harbors many genes involved in immune regulation showed highly significant associations with immune response to influenza A virus, Epstein-Barr virus (EBV), JC polyomavirus, and Merkel Cell polyomavirus. The genetic variants result in structural differences in proteins whose job it is to present fragments of pathogens that have been taken up by cells to the immune system. Interestingly, a given variant can lead to an increased immune response to one virus, e.g. influenza A, and at the same time to a decreased immune response to another, e.g. EBV, which is likely due to an altered ability of the protein to bind and present specific viruses, depending on the genetic background. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Electronic Records, Infections, Mayo Clinic / 26.10.2015

MedicalResearch.com Interview with: Dr. Pablo Moreno Franco MD Assistant Professor of Medicine MAYO Clinic Medical Research: What is the background for this study? What are the main findings? Dr. Pablo Franco: Early alerts and prompt management of patient with severe sepsis and septic shock (SS/S) starting in the emergency department (ED) have been shown to improve mortality and other pertinent outcomes. With this in mind, we formed a multidisciplinary sepsis and shock response team (SSRT) in September 2013. Automated electronic sniffer alerted ED providers for possible sepsis and when S/SS was identified, they were encouraged to activate SSRT. SSRT-Compliance-Study-Cohort Two blinded reviewers retrospectively abstracted data on clinical trajectory and outcomes of all patients with sepsis and SS/S admitted at a single academic medical center between September 2013 and September 2014. Given importance of timely recognition and interventions in S/SS, we specifically focused on 2 periods: 0-4 hours and 4-12 hours after hospital admission. Additionally, we compared the compliance to “standard of care” between the SSRT pre-implementation period and the study period. There were 167 patients admitted with sepsis, among which there were 3 SSRT activations and sepsis mortality was 3.6%. There were 176 patients with SS, SSRT was called in 42 (23%) and SS mortality was 8.5%. CCS was involved in 66 patients and mortality was 6.9% if SSRT was activated, versus 21.6% if SSRT was not activated. There were 76 patients with septic shock, SSRT was called in 44 (57%) and septic shock mortality was 25%. Critical Care Service (CCS) was involved in 68 patients and mortality rates with and without SSRT were 30.9% and 15.4%, respectively. The all-or-none compliance with applicable goals of resuscitation improved from the baseline 0% to over 50% at the study period end. Overall observed/expected sepsis mortality index improved from 1.38 pre-SSRT to 0.68 post-SSRT implementation. (more…)
Author Interviews, Biomarkers, Infections / 24.10.2015

MedicalResearch.com Interview with: Dr. Johannes Kettunen Computational Medicine, Institute of Health Sciences, University of Oulu National Institute for Health and Welfare, Helsinki NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio Finland   Medical Research: What is the background for this study? What are the main findings? Dr. Kettunen: The initial discovery of the mortality biomarkers was made 1.5 years ago when we published the first paper describing four biomarkers indicative of 5-year mortality in two cohorts totaling over 17 000 population based samples (http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1001606). We wanted to understand the molecular background of the strongest mortality predictor and this is how the current study was started. Here,  The network was enriched with defense response genes and we had an idea to test if the biomarker was predictive of future severe infections. We were able to show that chronic inflammation creates extra stress to immune system and predisposes to future infections. (more…)
Author Interviews, Infections, NEJM, OBGYNE / 24.10.2015

Alfredo Mayor Aparicio PhD Associate Research Professor Barcelona Institute for Global HealthMedicalResearch.com Interview with: Alfredo Mayor Aparicio PhD Associate Research Professor Barcelona Institute for Global Health Medical Research: What is the background for this study? What are the main findings? Dr. Mayor: The malaria parasite is a well-adapted pathogen which can persist and reappear in areas where infection is no longer circulating or at very low levels. Prevention of such reinfections and resurgences is critical for the current goal of malaria eradication. However, little is known about the determinants and consequences of malaria declines and resurgences. For this reason, understanding the relationship between malaria transmission, immunity and disease burdens is essential to rationalise malaria interventions aimed at reducing host-parasite encounters. We have described changes in prevalence among pregnant women delivering between 2003 and 2012 at antenatal clinics in Southern Mozambique, and showed that a reduction of malaria-specific immunity associated with drops in transmission is accompanied with an increase the severity of malaria infection among those women becoming infected. These results suggest that success of control and elimination activities may lead through a transitional period where infrequent infections will likely slowdown the rate of acquisition of host defenses and will be thus associated with more deleterious effects during pregnancy, thus requiring more precise diagnosis and surveillance methods, as well as improved prevention. (more…)
Author Interviews, Infections, Lancet, Outcomes & Safety, Respiratory / 22.10.2015

MedicalResearch.com Interview with: Yuichiro Shindo, M.D., Ph.D. Assistant Professor Institute for Advanced Research, Nagoya University, Department of Respiratory Medicine, Nagoya University Graduate School of Medicine Showa-ku, Nagoya Japan Medical Research: What is the background for this study? What are the main findings? Dr. Shindo: Appropriate initial antibiotic treatment is essential for the treatment of pneumonia.  However, many patients may develop adverse outcomes, even if they receive appropriate initial antibiotics.  To our knowledge, there have been no studies that clearly demonstrated the risk factors in patients who receive appropriate antibiotic treatment.  If these factors are clarified, we can identify those patients with pneumonia for whom adjunctive therapy other than antibiotic treatment can prove beneficial in terms of improved outcomes.  This study aimed to clarify the risk factors for 30-day mortality in patients who received appropriate initial antibiotic treatment and elucidate potential candidates for adjunctive therapy. In this study, the 30-day mortality in 579 pneumonia patients who received appropriate initial antibiotics was 10.5%.  The independent risk factors included albumin < 3.0 mg/dL, nonambulatory status, pH < 7.35, respiration rate ≥ 30/min, and blood urea nitrogen ≥ 20 mg/dL.  The 30-day mortality for the number of risk factors was 0.8% (0), 1.2% (1), 16.8% (2), 22.5% (3), and 43.8% (4–5). (more…)
Anemia, Author Interviews, Infections, Kidney Disease, UCSF / 21.10.2015

Dr. Julie H. Ishida MD San Francisco Veterans Affairs Medical Center Nephrology Section San Francisco, CAMedicalResearch.com Interview with: Dr. Julie H. Ishida MD San Francisco Veterans Affairs Medical Center Nephrology Section San Francisco, CA Medical Research: What is the background for this study? What are the main findings? Dr. Ishida: Intravenous iron is important in the treatment of anemia of end-stage renal disease, but it is biologically plausible that iron may increase infection risk. While results from epidemiologic studies evaluating the association between intravenous iron and infection in hemodialysis patients have been conflicting, guidelines for the treatment of anemia of chronic kidney disease have recommended caution in prescribing, avoidance and withholding of intravenous iron in the setting of active infection. However, no data specifically support the recommendation to withhold intravenous iron during active infection. Our study observed that among hemodialysis patients hospitalized for bacterial infection who had been receiving intravenous iron as an outpatient, continued receipt of intravenous iron was not associated with higher all-cause mortality, readmission for infection, or longer hospital stay. (more…)
Author Interviews, Case Western, Hand Washing, Infections / 17.10.2015

MedicalResearch.com Interview with: Curtis J. Donskey, MD Professor of Medicine Case Western Reserve University Staff Physician, Infectious Diseases Section, Louis Stokes Cleveland VA Medical Center Medical Research: What is the background for this study? Dr. Donskey: Personal protective equipment (PPE) is intended to protect healthcare personnel by preventing them from acquiring an infection and to protect patients by preventing pathogen transmission. This study focused on gloves and gowns which are designed to reduce contamination of the skin and clothing of personnel. There are several concerns about the effectiveness of gloves and gowns.
  • First, several studies have demonstrated that personnel may acquire pathogens such as Clostridium difficile and methicillin-resistant Staphylococcus aureus (MRSA) on their hands and clothing during patient care activities despite wearing gloves and gowns.
  • Second, some studies involving simulations have suggested that contamination of the skin and clothing occurs frequently during removal of gloves and gowns.
  • Finally, lapses in technique for PPE removal may contribute to acquisition of potentially fatal pathogens such as Ebola virus. These concerns highlight the urgent need for improved strategies to prevent contamination of personnel during PPE removal.
We had 3 goals in the study.
  • First, we wanted to determine if contamination with a fluorescent lotion during glove and gown removal would correlate well with contamination with a benign virus. We did this because the fluorescent lotion method could potentially be very useful for training personnel because you can easily visualize contamination with a black light and provide immediate feedback.
  • Second, we used the fluorescent lotion method to evaluate contamination of the skin and clothing of personnel from 4 hospitals during removal of contaminated gloves or gowns.
  • Finally, we tested whether an intervention would reduce contamination in one of the 4 hospitals. The intervention included practice in removal of contaminated gloves and gowns with immediate visual feedback based on fluorescent lotion contamination of skin and clothing.
Medical Research: What are the main findings? Dr. Donskey: Our first key finding was that contamination with the fluorescent lotion correlated well with contamination with the benign virus. This was an important finding because it suggests that the fluorescent lotion method is a useful surrogate method to assess pathogen contamination during Personal protective equipment removal. Our second key finding was that contamination of the skin and clothing of personnel occurred frequently during removal of contaminated gloves or gowns. For 435 total simulations, contamination occurred 46% of the time, with similar results for each the 4 study hospitals (43%-50%). Incorrect donning or doffing technique was common and was associated with an increase in contamination (70% of the time with incorrect technique versus 30% with correct technique). Our final key finding was that the intervention was very effective in reducing contamination during PPE removal. Immediately after the training session, the frequency of contamination decreased from 60% to 20% and then was 12% at 1 and 3 months after the intervention. (more…)