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, PLoS, Urinary Tract Infections / 18.12.2015

MedicalResearch.com Interview with: Dr Sandra A. Wilks PhD Senior Research Fellow IfLS Knowledge Mobilisation Fellow in Healthcare Technologies Faculty of Natural and Environmental Science & Faculty of Health Sciences Centre for Biological Sciences, University of Southampton, Southampton, UK  Medical Research: What is the background for this study? What are the main findings? Dr. Wilks: The use of indwelling Foley urinary catheters for extended periods of time results in high risks of urinary tract infections (UTI) and catheter blockages. Blockages are often caused by the presence of Proteus mirabilis, a urease-producing bacterium which results in an increase of the urine pH and the development of crystalline biofilms. Biofilms develop when bacteria attach to a surface, forming a community structure, held together by extracellular polymeric substances (EPS). Once in a biofilm, bacteria exhibit high resistance to the action of antibiotics and are protected by other stress factors. The crystalline biofilms resulting from the presence of Proteus are highly complex environments and cause complete blockage of the catheter within days. Such blockages cause pain and trauma for patients, and result in high demands on healthcare resources. In this study, we have used an advanced microscopy technique (episcopic differential interference contrast, EDIC microscopy developed by Best Scientific) to track the development of these crystalline encrustations on two commonly used catheter materials; silicone and hydrogel latex. We have identified four distinct stages to crystalline biofilm formation;
  • (1) an initial foundation layer (conditioning film) formed by individual 'colonising' P. mirabilis cells, which occurred in less than 1 hour;
  • (2) this was rapidly followed by a sheet-like microcrystalline material (after 24 hours) that covers this conditioning film;
  • (3) after 4 days exposure, large amounts of crystalline material was seen to extend out from the surface with;
  • (4) defined struvite crystals embedded within the structure and P. mirabilis visible throughout. This pattern was the same on both materials.
(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, Flu - Influenza, Pharmacology, Pulmonary Disease / 09.12.2015

MedicalResearch.com Interview with: Dr. Irene Braithwaite Deputy Director Medical Research Institute of New Zealand Wellington NZ Medical Research: What is the background for this study? What are the main findings? Dr. Braithwaite: We know from animal models that the reduction of fever is associated with an increased risk of dying from influenza. We also know that some influenza viruses cannot replicate well in the human febrile range (38 to 40 Celsius). Yet, guidelines on the management of community acquired influenza infection in humans is to rest, maintain hydration and to take antipyretics such as paracetamol on the basis that this may help and is unlikely to cause harm. We undertook this study to see whether using regular paracetamol during influenza infection might be harmful, as it may allow the influenza virus to replicate more readily, and increase and/or prolong symptoms. To the best of our knowledge, this is the first randomised controlled trial comparing the effects of regular paracetamol (1gram four times daily for five days) versus placebo in human adults infected with influenza. We found that there was no difference in influenza viral loads, temperature or influenza symptoms between the regular paracetamol group and placebo group. (more…)
Author Interviews, HIV, Immunotherapy, PLoS / 04.12.2015

MedicalResearch.com Interview with: Andreas Meyerhans, PhD ICREA Research Professor at the University Pompeu Fabra Infection Biology Group Department of Experimental and Health Sciences Universitat Pompeu Fabra Barcelona Spain Medical Research: What is the background for this study? What are the main findings? Dr. Meyerhans: In brief, chronic HIV infections lead to a dampening of HIV-specific killer cells. This phenomenon is named exhaustion and is mediated by inhibitory proteins, such as PD-1, on the cell surface. A consequence of exhaustion is a reduction of the immune control over virus expansion. We have studied the effect of blocking the negative signaling from the inhibitory proteins by means of PD-1/PD-L1 pathway inhibition on effector and regulatory T cells (Treg). We found that one can augment antiviral immune control only when the virus load was well controlled in the HIV-infected individuals i.e. by antiviral drugs. In that case, PD-1/PD-L1 pathway blockage led to an expansion of anti-HIV killer cells over Treg cells. This latter are suppressive white blood cells also subject to the same inhibitory pathway regulation. In contrast, when blood cells from viremic HIV-infected individuals were analyzed, Treg cells expanded efficiently and thus reduced the effector to regulatory T cell ratio that controls HIV. Taken together, our data point to Treg cells as an important component in the outcome of PD-1/PD-L1 pathway inhibitor therapies and suggest a net gain in anti-HIV immune responses only when the HIV loads are well controlled during the administration of these novel compounds. (more…)
Author Interviews, CDC, Gender Differences, HIV / 03.12.2015

MedicalResearch.com Interview with: Dr. Andrew Auld MD, MSc Medical Epidemiologist Division of Global HIV & TB CDC MedicalResearch: What is the background for this study? Dr. Auld: Equitable access to antiretroviral therapy for men and women living with HIV is a principle endorsed by most countries and funding bodies, including the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR). This analysis, including more than 765,000 adult patients starting antiretroviral therapy in 12 countries (10 African countries, Haiti, and Vietnam), is the most up-to-date and comprehensive assessment of differences in HIV treatment access among men and women with HIV in developing countries. MedicalResearch: What are the main findings? Dr. Auld: Investigators showed that in all 10 African countries and Haiti, women with HIV were far more likely to be on treatment than men. In these 11 countries, women were 23%–83% more likely to access antiretroviral therapy than men with HIV. In addition, in six African countries and Haiti, gender imbalance in HIV treatment access appears to be getting worse over time. (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, HIV, NEJM, Sexual Health / 02.12.2015

MedicalResearch.com Interview with: Dr Jean-Michel Molina Department of Infectious Diseases Saint-Louis Hospital and University of Paris Diderot Paris France MedicalResearch: What is the background for this study? What are the main findings? Dr. Molina: Men who have sex with men (MSM) are disproportionately affected by HIV worldwide and represent the today in Europe the largest group in which new HIV infections are diagnosed with no decrease over the last 8 years. The first study assessing preexposure prophylaxis (PrEP) efficacy among MSM was published in 2010 (the Iprex study) which reported for the first time a 44% reduced incidence of HIV in those randomized to receive daily tenofovir/emtricitabine  TDF/FTC (one pill per day) as compared to placebo. Adherence to a daily pill regimen was found to be challenging however since only half of the participants (according to drug detection in blood) were taking their daily regimen. Post-hoc analyses suggested that among those with drugs detectable in plasma, PrEP efficacy could be as high as 92%. However, long term adherence to a daily regimen represents the Achille’s heel of daily PrEP, as shown later in other large PrEP trials among women in Africa (VOICE and Fem-PrEP). Based on data from animal models we wished to assess whether PrEP with TDF/FTC taken on demand, at the time of sexual activity, could improve adherence, thereby efficacy and also improve safety and cost. In this randomized double blind placebo controlled trial, on demand PrEP with TDF/FTC reduced the incidence of HIV by 86% in the intent to treat analysis as compared to placebo, and the only 2 participants who became infected in the TDF/FTC arm after more than a year of follow-up, had discontinued the use of PrEP months before infection. The ANRS Ipergay study reports therefore a very high efficacy of PrEP, similar to that also reported in another PrEP study carried out in the UK among MSM with daily TDF/FTC (PROUD), which results were disclosed at the same time. Both studies have increased awareness about the real potential of PrEP and have had a strong impact on WHO and European guidelines. (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, JAMA, Outcomes & Safety, Urinary Tract Infections, Urology / 19.11.2015

MedicalResearch.com Interview with: Jerome A. Leis, MD MSc FRCPC Staff physician, General Internal Medicine and Infectious Diseases Physician Lead, Antimicrobial Stewardship Team Staff member, Centre for Quality Improvement and Patient Safety Sunnybrook Health Sciences Centre Assistant Professor, Department of Medicine, University of Toronto Medical Research: What is the background for this study? What are the main findings? Dr. Leis: Overuse of urinary catheters leads to significant morbidity among hospitalized patients.  In most hospitals, discontinuation of urinary catheters relies on individual providers remembering to re-assess whether patients have an ongoing reason for a urinary catheter.  We engaged all of the attending physicians to agree on the appropriate reasons for leaving a urinary catheter in place and developed a medical directive for nurses to remove all urinary catheters lacking these indications.  This nurse-led intervention resulted in a significant reduction in urinary catheter use and catheter-associated urinary tract infections, compared with wards that continued to rely on usual practice. (more…)
Author Interviews, STD / 18.11.2015

MedicalResearch.com Interview with: Dr Pam Sonnenberg  Reader in Infectious Disease Epidemiology Research Department of Infection & Population Health University College London London MedicalResearch: What is the background for this study? What are the main findings? Dr. Sonnenberg:  This study strengthens growing evidence that Mycoplasma genitalium (MG) is a sexually transmitted infection (STI). Analyses of over 4500 of urine samples from Britain’s third National Survey of Sexual Attitudes and Lifestyles (Natsal-3) showed that MG was prevalent in up to 1% of the general population aged 16-44, who had reported at least one sexual partner. Prevalence was much higher in those who had reported more than four sexual partners in the past year – 5.2% in men and 3.1% in women. Absence of the infection in over 200 16-17 year olds who had not had vaginal, anal, or oral sex provided further evidence that MG is transmitted sexually. The study also analysed risk factors for  Mycoplasma genitalium, such as ethnicity, number of partners, and areas of deprivation. There were strong associations with risky sexual behaviours, with similar behavioural risk factors to other known STIs. The authors found that men of Black ethnicity and those living in the most deprived areas were more likely to test positive for MG. Over 90% of Mycoplasma genitalium in men and over two-thirds of MG cases in women were in those aged 25–44 years; an age group who would not be included in STI prevention measures currently aimed at young people in Britain. Interestingly, the majority of participants who tested positive for MG did not report any STI symptoms in the last month. Over half of women did not report any symptoms, but among those who did, bleeding after sex was most common. Over 90% of MG positive men did not report any symptoms. (more…)
Author Interviews, JAMA, Pediatrics, Respiratory / 17.11.2015

MedicalResearch.com Interview with: Leonard B. Bacharier, MD Professor of pediatrics Clinical Director, Division of Allergy, Immunology and Pulmonary Medicine St Louis School of Medicine Washington University St Louis, Missouri  Medical Research: What is the background for this study? What are the main findings? Dr. Bacharier: Oral corticosteroids such as prednisone have become the standard of care for children whose colds tend to progress and lead to severe wheezing and difficulty breathing. “But there are some studies that suggest these treatments don’t consistently work for young children. That’s why we want to find ways to prevent upper respiratory infections from progressing to lower respiratory tract illnesses. Once the episode gets going, standard interventions are less effective than would be desired”​​​​​​​​​​​​​​​​, reported Dr. Bacharier. (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, Biomarkers, Lyme, Rheumatology / 10.11.2015

MedicalResearch.com Interview with: Robert B. Lochhead PhD Clinical Fellow in Medicine  Division of Rheumatology, Allergy & Immunology Massachusetts General Hospital Harvard Medical School, Boston, MA Medical Research: What is the background for this study? What are the main findings? Dr. Lochhead: Lyme arthritis (LA), caused by the tick-borne spirochete Borrelia burgdorferi, usually resolves appropriately with antibiotic treatment, called antibiotic-responsive Lyme arthritis. However, in some patients, arthritis persists for months or years after spirochetal killing with oral and IV antibiotic therapy, called antibiotic-refractory Lyme arthritis. Synovial lesions in these patients show marked synovial proliferation, inflammation, and vascularization, accompanied by autoimmune T and B cell responses. MicroRNAs (miRNAs) regulate many biological processes including inflammation, immune responses, and cell proliferation, and are effective biomarkers that may reveal molecular mechanisms of disease. Our objective here was to identify extracellular miRNAs (ex-miRNAs) in synovial fluid (SF) that distinguish regulated (responsive) from dysregulated (refractory) immune responses in Lyme arthritis, thereby providing insights into underlying biological processes and potential diagnostic biomarkers to distinguish between  these disease courses. (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…)
Author Interviews, Columbia, Compliance, HIV, JAMA, Pediatrics / 04.11.2015

MedicalResearch.com Interview with: Dr. Louise Kuhn PhD Professor, Epidemiology Sergievsky Center Columbia University  Medical Research: What is the background for this study? What are the main findings? Dr. Kuhn: Ritonavir-boosted lopinavir-based antiretroviral therapy is recommended as first-line treatment for HIV-infected infants and young children while efavirenz is recommended for adults and older children. There are several advantages of transitioning HIV-infected children to efavirenz-based treatment as they get older.  These advantages include the possibility of once-daily dosing, simplification of co-treatment for tuberculosis, avoidance of some metabolic toxicities, preservation of ritonavir-boosted lopinavir for second-line treatment, and alignment of adult and pediatric treatment regimens. However, there have been concerns about possible reduced viral efficacy of efavirenz-based treatment in children exposed to nevirapine for prevention of mother-to-child transmission.  This is because efavirenz and nevirapine are in the same drug class and the majority of children who become infected despite exposure to nevirapine used for prevention have mutations in their virus that usually predict resistance to this drug class. In this study, we randomized HIV-infected children to two different treatment strategies: In the control strategy they remained on their initial ritonavir-boosted lopinavir regimen; in the alternative strategy they transitioned to an efavirenz-based regimen.  All children had been exposed to nevirapine used (unsuccessfully) to prevent mother to child HIV transmission and were virologically-suppressed (HIV in blood < 50 copies/ml) at the time of enrollment into the study.  We observed excellent virological control in both groups with fewer than 3% of children having levels of HIV in their blood greater than 1000 copies/ml.  Sustained suppression of virus in blood below 50 copies/ml throughout follow-up was achieved in 82% of the children transitioned to efavirenz-based treatment compared to 72% of children remaining on the control treatment. (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, Emory, Flu - Influenza, Vaccine Studies / 02.11.2015

MedicalResearch.com Interview with: Saad Omer MBBS MPH PhD Associate Professor Emory Vaccine Center Associate Professor Global Health and Epidemiology Rollins School of Public Health Emory University MedicalResearch: Can you give us a little background on this study? Dr. Omer: My background is in global health, epidemiology and pediatrics and I have been fortunate to conduct field and clinical vaccine trials in a number of countries and with multiple infectious diseases including influenza, polio, measles and pneumococcal vaccines. We were familiar with the data on investigating the potential effects of statins on other infections i.e. sepsis and community acquire pneumonia including Dr. Vandermeer’s study in 2012 suggesting that “statin use may be associated with reduced mortality in patients hospitalized with influenza”. Statins have lipid-lowering effects but they also exhibit anti-inflammatory and immunomodulatory properties. For lack of a better image, I think of statins as acting like a ‘big hammer made of Jell-O’: they have a broad, small dampening effect on immune response (as opposed to a narrow or deep effect). (more…)
Author Interviews, CDC, Cost of Health Care, HPV, Vaccine Studies / 30.10.2015

MedicalResearch.com Interview with: Shannon Stokley, MPH Epidemiologist in the CDC Immunization Services Division Medical Research: What is the background for this study? What are the main findings? Response: To determine whether the recommended HPV vaccination series is currently being administered to adolescents with health insurance, CDC and the National Committee for Quality Assurance (NCQA) assessed 2013 data from the Healthcare Effectiveness Data and Information Set (HEDIS). The HEDIS HPV Vaccine for Female Adolescents performance measure evaluates the proportion of female adolescent members in commercial and Medicaid health plans who complete the recommended HPV vaccination series by age 13 years. In 2013, in the United States, the median HPV vaccination coverage level for female adolescents among commercial and Medicaid plans was 12% and 19%, respectively (ranges = 0%–34% for commercial plans, 5%–52% for Medicaid plans). The results of this study indicate that there are significant opportunities for improvement as HPV vaccination coverage among female adolescents was low for both commercial and Medicaid plans. (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, C. difficile, Gastrointestinal Disease, Transplantation / 22.10.2015

MedicalResearch.com Interview with: Monika Fischer, MD, MSCR Assistant Professor of Clinical Medicine Division of Gastroenterology and Hepatology Indiana University Indianapolis, IN 46202  Medical Research: What is the background for this study? What are the main findings? Dr. Fischer: Cumulative evidence based upon case series and randomized trials suggest high success rate with 10-20 % failing a single FMT (fecal microbiota transplant). Predictors of failures are not known. In a collaborative study between Indiana and Brown Universities we aimed to identify clinical predictors of FMT failure. Results were the following:
  • N= 345 patients
    • Brown: N=166
    • IU: N=179
  • Average age: 62 years
  • Females: 72%
  • IBD: 18%
  • Immunosuppression: 24%
  • Indication for FMT
    • Recurrent CDI: 74%
    • Refractory CDI: 26%
    • Severe/complicated CDI: 13%
  • Inpatient FMT: 17%
  • Patient directed donor: 40%
Overall failure rate was 23.7%. Broken down by fecal microbiota transplant indication, while only 18% of patients failed and  needed further therapy in the non-severe category, 1 in 2 (50%) severe C. difficile infection (CDI) patients failed a single fecal microbiota transplant and needed further therapy for cure. (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…)
Author Interviews, C. difficile, Gastrointestinal Disease, Mayo Clinic, Microbiome, Transplantation / 22.10.2015

MedicalResearch.com Interview with: Dr. Sahil Khanna MBBS Assistant Professor of Medicine Mayo Clinic Medical Research: What is the background for this study? What are the main findings? Response: C. difficile infection patients are at a high risk of complications such as treatment failure. Gut microbiota signatures associated with CDI have been described but it is unclear if differences in gut microbiota play a role in response to therapy. No studies have identified predictors of treatment failure and we aimed to identified gut microbiota signatures to predict response to treatment for primary C. difficile . While there were no clinical predictors of treatment response, there were increases in certain genera in patients with successful treatment response in the fecal samples at initial diagnosis compared to non-responders. A risk index built from this panel of microbes highly differentiated between patients based on response and ROC curve analysis showed that this risk index was a strong predictor of treatment response, with a high area under the curve of 0.83.. (more…)