Author Interviews, HPV, OBGYNE / 29.03.2016 Interview with: Andrew Combs MD Alan Fishman MD Obstetrix Medical Group San Jose, California What is the background for this study? Response: Vaginal ultrasound is a common procedure in gynecology and obstetrics. To perform vaginal ultrasound, an ultrasound probe is placed in the vagina in order to get a close-up view of a woman’s pelvic organs. In non-pregnant women, this is the preferred method for ultrasound of the uterus and ovaries. In early pregnancy, vaginal ultrasound often yields better images of the developing embryo than abdominal ultrasound. In later pregnancy, vaginal ultrasound gives more accurate pictures of the cervix and placenta than abdominal ultrasound. In order to prevent transmission of disease from patient to patient, it is mandatory to clean and disinfect the probe after each vaginal exam. The FDA has a list of “high level” disinfectants that neutralize or kill a variety of bacteria and viruses. Several manufacturers make disinfectant systems that are approved for disinfection of ultrasound probes. It is also mandatory to cover the probe with a barrier during each exam. Various companies manufacture ultrasound probe covers intended to be barriers against infection. What are the main findings? Response: Recent studies found that two widely-used disinfectants (glutaraldehyde and ortho-ophthalaldehyde) do not neutralize human papilloma virus (HPV) even though they are on the FDA list of high level disinfectants. HPV is the most common sexually transmitted infection in the USA, affecting over 8 million women of reproductive age. HPV is responsible for 60% of cervical cancer worldwide. Clearly, it is critical to neutralize this virus on vaginal ultrasound probes. A different high-level disinfectant system, sonicated hydrogen peroxide, was found to be highly effective at neutralizing HPV. Other studies show that commercial ultrasound probe covers have a high rate of leakage, 8-81%. Condoms are safer probe covers, with leakage rates of 0.9 to 2%. (more…)
Author Interviews, Pediatrics, Respiratory, Vaccine Studies / 28.03.2016 Interview with: Tasnee Chonmaitree, M.D. Professor, Pediatrics and Pathology Division of Pediatric Infectious Diseases Department of Pediatrics University of Texas Medical Branch Galveston, TX 77555-0371 What is the background for this study? Dr. Chonmaitree: Respiratory infections are common in infants and young children; they are caused by viruses and/or bacteria. Viral upper respiratory tract infection or the common cold is exceedingly common and leads to bacterial complications such as ear infection, which the leading cause of antibiotic prescription in the US and the most common reason children undergo surgery (ear tube placement). In the past few decades, some bacterial and viral vaccines have become available aiming to reduce respiratory infections in children. What are the main findings? Dr. Chonmaitree: Our study looked to update information on how often infants in the first year of life acquired the common cold, and ear infection in the new vaccine era. The study was performed between 2009 and 2014 and included 367 infants followed closely from near birth up to one year of age. We found that on average, an infant had about 3 colds in the first year of life, and almost half of infants had ear infection by age 1 year. This was less than what happened in the past few decades. The reduction of ear infection may have been the result of many factors from bacterial and viral vaccine use, to increased breastfeeding rate and reduction in household smoking. Risk factors for ear infection included carriage of bacteria in the nose, frequencies of common cold and lack of breastfeeding. (more…)
Author Interviews, Herpes Viruses, Vaccine Studies / 28.03.2016 Interview with: Zeena Y. Nawas, MD Clinical Research Fellow Center for Clinical Studies Houston, TX, 77004 What is the background for this study? What are the main findings? Dr. Nawas: T cell immunity is believed to be particularly critical to the control of genital herpes, an incurable, lifelong sexually transmitted disease that affects roughly 500 million people worldwide. Genital herpes is characterized by recurrent, painful genital lesions and can be transmitted to sexual partners, even when there is no visible sign of the infection. Current genital herpes therapies only partially control the infection in some patients. These individuals continue to experience clinical symptoms and viral shedding, which drives disease transmission. Incomplete control of genital lesions and transmission risk, and the inconvenience of taking a daily medication are hurdles for effective long-term disease management. GEN-003, is a first-in-class immunotherapy developed by Genocea Biosciences and is intended to treat genital herpes by inducing both a T cell and B cell (antibody) immune response. GEN-003 has demonstrated promising results to date by showing statistically significant reductions in the clinical signs of genital herpes and viral shedding, as well as safety and tolerability in its Phase 1/2 and Phase 2 clinical studies. (more…)
Author Interviews, CDC, Infections / 28.03.2016 Interview with: Meghan Weinberg PhD Epidemic Intelligence Service CDC Michigan Department of Health and Human Services What is the background for this study? What are the main findings? Dr. Weinberg: Tuberculosis (TB) is a deadly disease. Once a leading killer in the United States, national, state, and local TB program efforts have dramatically reduced cases. With fewer cases occurring each year in the United States, health care providers might not consider TB when a patient has symptoms of TB disease. Every year, temporary visa holders come to the United States to work in a variety of tourist locations including amusement parks, ski lodges, national parks, and cultural or historical sites. TB testing is not required for persons entering the United States on a temporary visa. This report documents three cases of infectious TB disease among temporary workers in the tourism industry. Increased Tuberculosis awareness is needed among employers, health care providers, and public health officials. (more…)
Author Interviews, Hospital Acquired, Outcomes & Safety / 28.03.2016 Interview with: Peggy Luebbert, MS, MT, CIC, CHSP, CBSPD; Infection Preventionist at Nebraska Orthopaedic Hospital; Owner and Consultant at Healthcare Interventions, Inc.; and Brian Heimbuch, MS, Associate Division Manager/Sr. Bioaerosol Scientist, Applied Research Associates MedicalResearch: What is the background for this study? Mr. Heimbuch: The purpose of the study was to examine the ability of sterilization packaging systems to maintain sterility of surgical instruments and devices from the time of sterilization until use. Ms. Luebbert: Maintaining a sterile environment in the operating room is essential for preventing the estimated 300,000 surgical site infections (SSIs) that occur annually in U.S. hospitals and result in approximately 9,000 deaths.[i]-iii Sterilization packaging systems are designed to maintain the sterility of surgical instruments and devices from the time of sterilization until use in the operating room. The two primary types of sterilization packaging systems include trays covered in sterilization wrap and rigid containers. Sterilization wrap is composed of polypropylene or cloth and is disposed of after use. Rigid containers are reusable and come in a variety of materials (including metals, aluminum and polymers) and sizes. (more…)
Author Interviews, Infections, PLoS / 27.03.2016 Interview with: Dr. Cameron Stewart PhD Team Leader within the Emerging Infectious Diseases Program CSIRO Biosecurity Flagship Commonwealth Scientific and Industrial Research Organisation What is the background for this study? What are the main findings? Dr. Stewart: Hendra and Nipah viruses (referred to jointly as henipaviruses) are deadly cousins of the more common mumps, measles, and respiratory syncytial viruses, all members of the paramyxovirus family. Henipavirus outbreaks are on the rise, but little is known about the viruses, partly because research has to be undertaken under extreme containment conditions.  Our team performs research at the largest high containment facility in the Asia-Pacific region, the CSIRO Australian Animal Health Laboratory in Geelong, Australia. To understand the henipavirus infection cycle and to identify targets for new antiviral therapies, we performed a genome-wide screen to identify the host molecules required by henipaviruses for infection. The host gene with the largest impact, called fibrillarin, codes for a protein present in the nucleolus. Inhibiting fibrillarin impaired henipavirus infection greater than 1,000-fold in human cells.  We examined closely which step of the viral life cycle was blocked by interfering with fibrillarin function, and found it was required for the early synthesis of viral RNA. Results from our study suggest that fibrillarin could be targeted therapeutically to combat henipavirus infections. This research was undertaken by an international team of researchers from CSIRO, the Victorian Centre for Functional Genomics, Duke-NUS, the University of Georgia and the Centers for Disease Control and Prevention. (more…)
Author Interviews, HPV, JAMA, OBGYNE, Sexual Health, UCSD / 24.03.2016 Interview with: Ryan K. Orosco, MD Division of Head and Neck Surgery Department of Surgery University of California, San Diego What is the background for this study? What are the main findings? Dr. Orosco: Our group at UC San Diego is interested in HPV as it relates to diseases of the head and neck.  HPV is a well-publicized cause of cervical cancer, and awareness about its link to throat (oropharynx) cancer is rapidly increasing. Less well-known, is the relationship between HPV and benign (non-cancerous) diseases such as genital warts and papilloma of the throat.  As we strive to understand how to best care for patients with HPV-related disorders, it is important to understand the entire process of disease progression, which begins with HPV infection. Our group wanted to explore the relationship between HPV infection in the two most commonly infected body sites: oral and vaginal. (more…)
Annals Internal Medicine, Author Interviews, Flu - Influenza, Kaiser Permanente, Surgical Research, Vaccine Studies / 16.03.2016 Interview with: Sara Y. Tartof, PhD, MPH Kaiser Permanente Southern California Department of Research & Evaluation What is the background for this study? What are the main findings? Dr. Tartof: The flu is a highly contagious respiratory infection that can cause serious complications, hospitalizations and, in some cases, even death. Some people, such as older adults, young children and people with certain health conditions, are at high risk for serious complications. In addition to recommending annual flu vaccination for people 6 months of age and older, the Centers for Disease Control and Prevention recommends that hospitalized patients who are eligible receive the flu vaccine before discharge. Historically, inpatient rates of vaccination have been low. There has been concern among surgeons that vaccinating patients while they are in the hospital can contribute to increased risk of vaccine-related fever or muscle pain, which might be incorrectly attributed to surgical complications. However, there have been no data to support that concern. The objective of this study was to provide clinical evidence that would either substantiate or refute concerns about the safety of perioperative vaccination. (more…)
Author Interviews, Urinary Tract Infections / 16.03.2016 Interview with: Maureen Maurer, MS  American Institute for Research Makawao, HI What is the background for this study? Response: Complications from UTIs are a serious medical problem for many people with neurological impairment such as spinal cord injuries. Detection is often difficult in these patients, resulting in delayed diagnosis and more serious infections such as pyelonephritis and sepsis.  UTIs are also the most common hospital acquired infection for all patients. Given the prevalence of UTIs, their complications, and increasing drug therapy resistance, improved early detection methods are needed. The olfactory acuity of dogs is over 100,000 times stronger than humans. Dogs’ superior olfactory capabilities have been employed to assist humans by detecting bombs, drugs, and more recently, cancer. Trained dogs may present a novel method for early UTI detection. Our objective was to determine whether canines could be trained to discriminate culture-positive from culture-negative urine samples.  (more…)
Author Interviews, Hand Washing, Hospital Acquired, JAMA, University of Michigan / 15.03.2016 Interview with: Lona Mody, MD, MS Veterans Affairs Healthcare System, Geriatric Research, Education, and Clinical Center Division of Geriatric and Palliative Medicine, University of Michigan Medical School, School of Public Health University of Michigan, Ann Arbor What is the background for this study? Dr. Mody: Hand hygiene is considered to be the most important strategy to prevent infections and spread of drug resistant organisms. Surprisingly, all strategies and efforts have predominantly involved healthcare workers and that too mainly in acute care hospitals.  We are now facing a tsunami of an aging population in our hospitals, post-acute care facilities and long-term care facilities.  Hand hygiene falls off when patients are hospitalized compared to when they are at home.  So, we were very interested, first, in hand colonization in older patients who have recently been transferred from the acute care hospital to a post-acute care (PAC) facility for rehabilitation or other medical care before fully returning home. We were also interested in evaluating whether these organisms persisted. What are the main findings? Dr. Mody: We recruited and followed 357 patients (54.9 percent female with an average age of 76 years). The dominant hands of patients were swabbed at baseline when they were first enrolled in a post-acute care facility, at day 14 and then monthly for up to 180 days or until discharge. The study found:
  • To our surprise, nearly one-quarter (86 of 357) of patients had at least one multi-drug resistant organism on their hands when they were transferred from the hospital to the post-acute care facility
  • During follow-up, 34.2 percent of patients’ hands (122 of 357) were colonized with a resistant organism and 10.1 percent of patients (36 of 357) newly acquired one or more resistant organisms.
  • Overall, 67.2 percent of colonized patients (82 of 122) remained colonized at discharge from PAC.
Author Interviews, Infections, OBGYNE, Pediatrics / 14.03.2016 Interview with: Elaine Tuomanen, MD Chair and Full Member Dept of Infectious Diseases St Jude Children’s Research Hospital 262 Danny Thomas Place Memphis, TN 38105 What is the background for this study? What are the main findings? Dr. Tuomanen: While investigating mechanisms of brain repair during infection in a mouse model system, we found that components from the surfaces of bacteria could traffic from the mother to the fetus. The bacterial components moved across the placenta and into the fetal brain. To our surprise, the fetal brain did not respond with neuronal death like we see in children with meningitis. Rather, fetal neurons proliferated. This response involved the innate immune system (TLR2) inducing the neuronal transcription factor, FoxG1, which is known to drive proliferation. The newly born neurons migrated appropriately to the cortical plate, the area on the surface of the fetal brain that forms the cortex, a major part of the adult brain. Although the neurons moved to the right place in the brain, there were too many and they crowded together in the cortex, changing the architecture of the brain. At birth, affected mice seemed to have no abnormalities. However, when we tested if this change in architecture would affect brain function after birth, mice were shown to progressively develop defects in learning, memory and other cognitive functions. This indicates there is a window during pregnancy where components of bacteria from the mother can change fetal brain architecture and subsequent postnatal behavior (more…)
Author Interviews, CDC, Lyme, Race/Ethnic Diversity / 08.03.2016 Interview with: Christina Nelson, MD, MPH, FAAP Medical Epidemiologist Centers for Disease Control and Prevention Division of Vector-Borne Diseases | Bacterial Diseases Branch Fort Collins, CO What is the background for this study? What are the main findings? Dr. Nelson: Since Lyme disease is a nationally notifiable disease, state and local health departments collect reports of Lyme disease cases in their jurisdictions then share this data with CDC. This surveillance data is very informative and can be used to track disease patterns. Hispanics comprise roughly 45% of the U.S. workforce in outdoor jobs such as grounds maintenance, farming, fishing, and forestry, so they potentially have an increased risk of Lyme disease. Since information on Lyme disease in Hispanics is very limited, we decided to look into this topic further by analyzing surveillance data. (more…)
Author Interviews, CMAJ, Outcomes & Safety, Pulmonary Disease, Respiratory / 08.03.2016 Interview with: Dr. Gary Garber MD Chief of infection prevention and control Public Health Ontario Professor of medicine University of Ottawa What is the background for this study? What are the main findings? Dr. Garber: There are conflicting recommendations regarding the use of respirators vs face masks to protect healthcare workers against acute respiratory infections. Our systematic review and meta-analysis show that although N95 respirators have improved efficiency in reducing filter penetration under laboratory conditions, there is insufficient data to show a protective advantage compared to surgical mask in clinical settings. (more…)
Author Interviews, Dengue, Lancet, OBGYNE / 07.03.2016 Interview with: Mrs Enny S Paixão London School of Hygiene & Tropical Medicine London UK What is the background for this study? What are the main findings? Response: Dengue is a vector borne disease endemic in more than 100 countries (mainly in South America and southeast Asia) and is spreading to new areas, with outbreaks of increasing magnitude and severity. It is estimated that each year, 390 million people are infected with dengue and 96 million develop clinical symptoms. Despite of the importance of this disease, the effects of disease during pregnancy on fetal outcomes remain unclear. Using the published scientific literature, we investigated the risk of stillbirth, miscarriage, preterm birth, and low birth weight for women who had dengue infection during pregnancy. This study showed some evidence that dengue infection alone, in the absence of clinical symptoms, does not affect the outcome of pregnancy, but also that clinical dengue during pregnancy seems to increase the frequency of stillbirth, prematurity, and low birthweight. (more…)
Author Interviews, Global Health, Heart Disease, Infections, JAMA / 04.03.2016 Interview with: Thomas Pilgrim, Prof. Dr. med. Oberarzt, Invasive Kardiologie Universitätsspital Bern Bern Switzerland What is the background for this study? Dr. Pilgrim: Three quarters of all children worldwide grow up in regions endemic for rheumatic heart disease. Clinically manifest rheumatic heart disease represents only the tip of the iceberg: only one in in 5 to 8 children with valvular lesions consistent with rheumatic heart disease have a heart murmur or clinical symptoms; the remaining children have clinically silent disease that goes undetected unless echocardiography is performed. An understanding of incidence, prevalence, and progression of disease is an important prerequisite to guide active surveillance and secondary prevention. We therefore performed a school-based cross-sectional study among more than 5000 children from 26 schools in Nepal. The objective of the study was to assess prevalence of clinically silent and manifest rheumatic heart disease as a function of age, gender and socioeconomic status and to estimate the age-specific incidence from available prevalence data. What are the main findings? Dr. Pilgrim: In our population-based observational cross-sectional study, the prevalence of borderline or definite rheumatic heart disease among schoolchildren in Eastern Nepal amounted to 10.2 (95% CI 7.5-13.0) per 1000 children between the ages of 5 and 15 years, and was more common in girls as compared to boys. The prevalence increased across age categories in a nearly linear fashion from 5.5 (95% CI 3.5-7.5) per 1000 in children 5 years of age to 16.0 (95% CI 14.9-17.0) in children 15 years of age, while the average incidence remained stable at 1.1 per 1000 children per year. The prevalence of clinically silent rheumatic heart disease was 5 times higher compared to manifest disease and the ratio of manifest to subclinical disease increased with increasing age. (more…)
Author Interviews, Hand Washing, Hospital Acquired, Infections / 04.03.2016 Interview with: Dr Laurence Senn, médecin associée Service de médecine préventive hospitalière Mont Paisible Lausanne What is the background for this study? What are the main findings? Dr. Senn: Pseudomonas aeruginosa is a ubiquitous environmental bacterium that can cause infection in patients severely ill, and is thus a major cause of nosocomial infections in intensive care units. During an environmental investigation on potential reservoirs of P. aeruginosa, the liquid hand soap was found highly contaminated with this pathogen. The fact that unopened soap containers were found contaminated with P. aeruginosa proved that the contamination occurred during product manufacturing. Contaminated batches had been used in our hospital over the previous 5 months. In order to evaluate the burden of this contamination on patients, our infection control team conducted an epidemiological investigation combining two molecular methods. First, we analyzed with a classical molecular typing method all P. aeruginosa isolated from patients during the period of exposition to the contaminated soap. Secondly, we targeted the analysis on some isolates sharing the same genotype that the one found in the soap with a modern, recently developed tool which consists in sequencing the whole genome of the bacteria. This method allowed us to have the "fingerprint" of each isolate. Our investigation ruled out any impact of the contaminated soap on patients. (more…)
Author Interviews, Dental Research, Esophageal, Infections / 02.03.2016 Interview with: Dr. Huizhi Wang Assistant Professor Department of Oral Immunology and Infectious Diseases University of Louisville School of Dentistry Louisville, KY What is the background for this study? What are the main findings? Dr. Wang: Esophageal cancer is the eighth most frequent tumor and sixth leading cause of cancer death worldwide, characterized by rapid development and poor prognosis, including high mortality. Whereas the majority of cases occur in Asia, particularly in central China, recent data suggest that the frequency of new cases is rising in Western Europe and the USA. Mounting evidence suggests a causal relationship between specific bacterial infections and the development of certain malignancies. However, the possible role of the keystone periodontal pathogen, Porphyromonas gingivalis, in esophageal squamous cell carcinoma (ESCC) was unknown before our study. We found P. gingivalis infects epithelium of cancerous tissues up to 61%, as compared with 12% of adjacent tissues and non-infected in normal esophageal mucosa. A similar distribution of lysine-specific gingipain, a catalytic endoprotease uniquely secreted by P. gingivalis, and P. gingivalis DNA was observed. Moreover, we found infection of P. gingivalis was positively associated with the multiple clinicopathologic characteristics, including differentiation status, metastasis, and overall survival rate.  (more…)
Author Interviews, Emory, HIV / 01.03.2016 Interview with: Dr. Igho Ofotokun MD MSc Division of Infectious Diseases, Department of Medicine Emory University School of Medicine, Atlanta, Georgia Grady Healthcare System, Atlanta, Georgia What is the background for this study? What are the main findings? Dr. Ofotokun:  This work is focused on preventing further bone loss in HIV-infected patients and thus reducing the risk of future bone fractures. HIV infection is associated with a state of enhanced bone loss. HIV treatment with highly active antiretroviral therapy (HAART) further worsens rather than improve bone loss. Almost all HAART regimens that have been examined have been associated with bone loss. The consequence of this skeletal assualt is markedly elevated fracture prevalence among individuals living with HIV across a wide age range. It turns that the predominance of HAART associated bone loss occur within the first year of initiating therapy. In this study, we administered a single dose of 5 mg IV zoledronic acid, a long-acting bisphosphonate at the same time of HAART initiation to prevent HAART associated bone loss. At this dose, zoledronic acid prevented enhance bone resorption in all participants and completely blunted bone mineral density loss over the 48 weeks study follow up period. (more…)
Author Interviews, Emergency Care, Infections, JAMA, Pediatrics, Pulmonary Disease, Respiratory / 29.02.2016 Interview with: Suzanne Schuh, MD, FRCP(C), ABPEM The Hospital for Sick Children affiliated with the University of Toronto Medical Research: What is the background for this study? Dr. Schuh: Routine measurement of oxygen saturation in bronchiolitis is sometimes used as a proxy for illness severity, despite poor correlation between these parameters. This focus on oximetry may in part relate to lack of evidence on the natural history of desaturations in bronchiolitis which are often transient, and frequently not accompanied by increased respiratory distress. Desaturations occurring in infants with mild bronchiolitis in an ED often result in hospitalizations or prolonged hospital stay. They occur in healthy infants and may also occur in infants with mild bronchiolitis at home. The main objective of this study of infants with acute bronchiolitis was to determine if there is a difference in the proportion of unscheduled medical visits within 72 hours of ED discharge in infants who desaturate during home oximetry monitoring versus those without desaturations. Our study shows that the majority of infants with mild bronchiolitis experience desaturations after discharge home. (more…)
Author Interviews, HIV / 26.02.2016 Interview with: Wim Parys MD Global Head R&D Global Public Health Janssen  Medical Research: What is the background for this study? What are the main findings? Dr. Parys: In collaboration with ViiV Healthcare, we are working to develop the first long acting all-injectable combination regimen of Janssen’s rilpivirine and ViiV’s cabotegravir. Yesterday, we have announced promising Phase 2b data of this combination regimen which when given together every 4 or 8 weeks was able to maintain viral suppression with similar efficacy to a daily oral regimen of three HIV medicines. The results show that the combination met its primary endpoint at week 32. The study will now continue in its randomized controlled design for another 64 weeks enabling us to assess longer term outcomes. In parallel to this we will work to initiate the next stages of clinical development. (more…)
Author Interviews, Dengue, Zika / 25.02.2016 Interview with: Prof Paul Dyson Institute of Life Science Swansea University Medical School Singleton Park Swansea UK Medical Research: What is the background for this study? What are the main findings? Prof. Dyson: The spread of insect-vectored viruses such as Dengue and, more recently, Zika, underline the urgent necessity to develop new technologies to control insect disease vectors that, due to human activity, are spreading globally. The concept of using RNAi in insects is not new and is widely used as a research tool in the model organism Drosophila melanogaster. However, adapting RNAi for use in non-model insects has been slow, almost entirely due to the problem of delivering interfering RNA to the insect. Manual injection is a less than optimal means of delivery for larger insects, while including interfering RNA in a food source can be effective in smaller insects in the laboratory. But neither delivery system is suited for field applications of RNAi as a biocide. Faced with this challenge, we (myself and Dr Miranda Whitten) conceived the concept of symbiont-mediated RNAi and have advanced it with support from the UK BBSRC and the Gates Foundation, establishing it as a viable mechanism of delivery of RNAi in (a) a tropical disease vector, Rhodnius prolixus, a vector of Chagas disease, exemplified by targeting insect fertility, and (b) a globally invasive vector of plant disease, Western Flower Thrips, targeting larval growth. Interfering RNA is actively produced by symbiotic insect bacteria that multiply within the host. Critical to the technology is to ensure the stability of RNA synthesis by these bacteria. The interfering RNA is then released by the bacteria, absorbed and systemically circulated within the host, thereby causing knock-down of gene expression in specific tissues. We have exploited this technology to severely impair fertility of Rhodnius prolixus, and to cause mortality of developing larvae of Western Flower Thrips. As a biocide, the technology offers exquisite specificity due to the co-evolution and co-dependencies of the symbiont and its insect host, combined with the sequence-specificity of the RNAi. Moreover, development of resistance is highly improbable. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Infections, JAMA / 24.02.2016 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 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 ( The HTS assay that was queried against a library of 9,831 NPEs aimed to identify extracts inhibiting biofilm formation as a primary screening. Further secondary  screening and   activity  threshold optimization revealed the extract from Streptomyces gandocaensis (collected from Costa Rica) to be of particular interest due to its ability to inhibit biofilm formation and had a limited effect on A. baumannii growth. Activity based chromatographic separation and analysis of extracts derived from S. gandocaensis resulted in the discovery of three peptidic metabolites (cahuitamycins A–C),   with cahuitamycin  C  being   the   most effective biofilm inhibitor (IC50 =14.5 µM)   with  negligible A.  baumannii growth inhibition (an important trait for ideal biofilm inhibitor). Following up on the exciting discovery, we also completely characterized the biosynthetic machinery involved in making the active molecules by S. gandocaensis, using sophisticated bioinformatics and molecular biology techniques. The knock out analysis revealed that the biosynthesis of cahuitamycin C proceeds via a convergent biosynthetic pathway, with one of the steps apparently being catalyzed by an unlinked gene encoding a 6-methylsalicylate synthase. Efforts to assess starter unit diversification through selective mutasynthesis led to production of unnatural analogues cahuitamycins D and E with increased potency (IC50=8.4 and 10.5 µM) against A. baumannii biofilm. (more…)
Author Interviews, Global Health, HIV, NEJM, OBGYNE / 22.02.2016 Interview with: Jared Baeten, MD PhD Vice Chair, Department of Global Health Professor, Departments of Global Health, Medicine, and Epidemiology Co-Director, International Clinical Research Center University of Washington What is the background for this studies? Dr. Baeten: Women account for nearly 60 percent of adults with HIV in sub-Saharan Africa, where unprotected heterosexual sex is the primary driver of the epidemic. While several studies have shown that antiretroviral medications (ARVs) are highly effective in preventing HIV, other studies – such as VOICE and FACTS 001 – suggest that for young, at-risk women in Africa, ARVs delivered as a vaginal gel or as a tablet may not be acceptable. Products must be used to be effective, and that was not the case for most of the participants in previous studies. Medical Research: What was the aim of ASPIRE and The Ring Study? Dr. Baeten: As Phase III clinical trials, ASPIRE and The Ring Study were designed to determine whether a vaginal ring containing an antiretroviral (ARV) drug called dapivirine is safe and effective in protecting women against HIV when used for a month at a time. These trials also sought to determine whether women find the vaginal ring practical and easy to use. As sister studies, ASPIRE and The Ring Study were designed as the centerpiece of a broader licensure program to provide the strength of evidence to support potential licensure of the dapivirine vaginal ring for preventing HIV in women. Because at least two Phase III efficacy trials are usually needed for a product to be considered for regulatory approval, ASPIRE and The Ring Study were conducted in parallel to accelerate the timeline to the ring’s potential approval. (more…)
Author Interviews, CDC, HIV / 21.02.2016 Interview with: Martin Hoenigl, MD Postdoctoral Fellow AntiViral Research Center, Department of Medicine University of California, San Diego Medical Research: What is the background for this study? Response: The detection of acute HIV infection (AHI) is critical to HIV prevention and treatment strategies. Many field-based testing programs rely on point-of-care HIV antibody testing, which will reliably identify persons with established infection, but fail to detect persons with AHI. In many of these programs additional tests for AHI are only performed / recommended in persons presenting with signs and symptoms consistent with an acute retroviral syndrome (ARS). These signs and symptoms are unspecific and include fatigue, headache, pharyngitis, skin rash, GI symptoms, night sweats and others. However, the proportion of persons with acute HIV infection presenting symptomatic for their diagnostic test remains unknown. The objective of our study was therefore to determine the proportion of persons with acute HIV infection presenting with signs and symptoms consistent with ARS for HIV screening. Medical Research: What are the main findings? Response: We analyzed signs and symptoms in 90 patients diagnosed with acute HIV infection in a community-based program in San Diego that offered universal HIV-1 nucleic acid amplification testing, independent of signs and symptoms. Forty-seven (52%) patients reported ongoing signs or symptoms consistent with ARS on the day of NAT screening. Another 25 (28%) reported signs or symptoms that had occurred during the 14 days before testing, but had resolved by the testing date. Another 12 (13%) reported signs and symptoms that started after the diagnostic test. Only 6/90 (7%) reported no signs and symptoms consistent with ARS. As a secondary finding, viral loads were significantly higher (p=0.001) in the 72 individuals reporting signs and symptoms consistent with ARS before or at the time of NAT screening compared to the 18 participants who did not report signs and symptoms at their diagnostic test. Most frequently reported ARS signs and symptoms included fever, myalgia, fatigue and headache. (more…)
Author Interviews, CDC, Ebola, NEJM / 19.02.2016 Interview with: Tim Uyeki MD, MPH, MPP Influenza Division National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention and Associate Clinical Professor of Pediatrics Department of Pediatrics San Francisco General Hospital Medical Research: What is the background for this study? Dr. Uyeki: During 2014-2015, 27 patients with Ebola virus disease (EVD) were hospitalized in the United States and Europe. Frequent international teleconferences were convened among U.S. and European clinicians caring for EVD patients, often on a weekly basis, to share detailed information and suggestions on clinical management of these patients. We collected clinical, epidemiologic, laboratory, and virologic data on all of these patients and performed descriptive data analyses. We summarized our findings in this article. Medical Research: What are the main findings? Dr. Uyeki: Of the 27 patients with Ebola virus disease cared for in 15 hospitals in nine countries, the median age was 36 years; 19 (70%) were male; 9 of 26 (35%) had underlying medical conditions; and 22 (81%) were healthcare personnel, including 17 of 22 (77%) who had worked in an Ebola treatment unit in West Africa. Of the 27 patients, 20 (74%) were medically evacuated from West Africa, 4 (15%) were imported cases, and 3 (11%) were healthcare personnel who acquired Ebola virus infection while caring for EVD patients in the U.S. or Europe. At illness onset, the signs and symptoms of EVD were non-specific; the most common symptom reported was fatigue. At admission to a hospital in the U.S. or Europe, most patients had fever, weakness, and gastrointestinal symptoms. The median time from illness onset to hospitalization was four days. During hospitalization, all patients had diarrhea, often profuse watery diarrhea; and most experienced electrolyte abnormalities such as hyponatremia, hypokalemia, hypocalcemia, and hypomagnesemia, as well as hypoalbuminemia. One third of patients experienced renal abnormalities such as oliguria or anuria, nearly 60% were clinically diagnosed with systemic inflammatory response syndrome, and one third were clinically diagnosed with encephalopathy or encephalitis. Although minor bleeding abnormalities were reported in some patients, only two patients had any gross hemorrhage. Leukopenia was observed during the first week of illness, with increases in white blood cell count during the second week. Thrombocytopenia was common, and aminotransferase levels peaked in the second week of illness. Creatine kinase and lactate levels were elevated in most of the patients who were tested. Ebola virus levels in blood peaked on the seventh day of illness, and critical illness occurred at the end of the first week and during the second week after illness onset. All patients received intravenous fluids; most were treated empirically with antibiotics; and 85% received an investigational therapy, including 70% who received at least two experimental therapies. Eleven (41%) patients were critically ill, including seven who required invasive mechanical ventilation and five who received continuous renal replacement therapy. Five (18.5%) patients died (81.5% survival). (more…)
Alzheimer's - Dementia, Author Interviews, Dental Research, Infections, Stroke / 18.02.2016 Interview with: Dr. Robert Friedland MD Mason C. and Mary D. Rudd Endowed Chair In Neurology Professor, Dept. of Neurology University of Louisville Health Care Outpatient Center Louisville, KY 40292 Medical Research: What is the background for this study? What are the main findings? Dr. Robert Friedland: Oral infectious diseases are associated with stroke. Previous research by this group has shown that oral bacteria, cnm-positive Streptococcus mutans, was associated with cerebral microbleeds and intracerebral hemorrhage. We developed this study to investigate the roles of this bacteria in patients entering the hospital for all types of stroke. Among the patients who experienced intracerebral hemorrhage (ICH), 26 percent were found to have a specific bacterium in their saliva, cnm-positive S. mutans. Among patients with other types of stroke, only 6 percent tested positive for the bacterium. We also evaluated MRIs of study subjects for the presence of cerebral microbleeds (CMB), small brain hemorrhages which may cause dementia and also often underlie ICH. We found that the number of CMBs was significantly higher in subjects with cnm-positive S. mutans than in those without. (more…)
Addiction, Author Interviews, HIV / 16.02.2016 Interview with: Pedro Mateu-Gelabert, Ph. D. Principal Investigator National Development Research Institutes, Inc. New York, NY 10010  Medical Research: What is the background for this study? What are the main findings? Dr. Mateu-Gelabert: Heroin production in Colombia increased dramatically in recent decades, and some studies point to an increase in local heroin consumption since the mid-1990s. Despite this rapid increase, little is known about the effects of these activities on heroin injection within Colombia. One of the biggest concerns surrounding heroin injection is the potential spread of HIV through drug user networks. Medical Research: What should clinicians and patients take away from your report? Dr. Mateu-Gelabert: The key take home message in the paper is that a widespread early implementation of harm reduction services (e.g. opioid substitution therapy, HIV testing, syringe exchange programs)  can prevent HIV among young PWID (People Who Inject Drugs) before it rapidly spreads within drug injection networks. Reducing HIV among young drug injectors could prevent the spread of HIV from PWID to the general population. (more…)