Author Interviews, Global Health, Infections, Pediatrics / 19.06.2017

MedicalResearch.com Interview with: [caption id="attachment_35478" align="alignleft" width="200"]Alexsandra Jakubowski Aleksandra Jakubowski MPH[/caption] Aleksandra Jakubowski, MPH PhD candidate Department of Health Policy and Management Gillings School of Global Public Health University of North Carolina at Chapel Hill MedicalResearch.com: What is the background for this study? Response: The US President’s Malaria Initiative (PMI) provides approximately $600 million annually to fund implementation of key evidence-based malaria prevention and treatment interventions, including insecticide treated nets (ITNs), artemisinin-based combination therapy (ACT), and indoor residual spraying (IRS) to populations in 19 recipient countries in sub-Saharan Africa (SSA). Despite this considerable investment, no study to date has evaluated the impact of PMI on population health outcomes. Previous evaluations have noted improved health outcomes in PMI countries, but comparison groups are needed to establish whether these changes were beyond the declining trends in mortality observed in the rest of the region. Our study sought to generate objective evidence for policy makers about the role this US-funded malaria aid program may have played in curbing child mortality in SSA. We used a quasi-experimental design known as difference-in-differences to compare trends in health outcomes in PMI-recipient vs. PMI non-recipient countries. We analyzed publicly-available data from 32 countries in SSA spanning a period that included about ten years before and after the introduction of the program.
Author Interviews, CDC, Infections, Outcomes & Safety / 13.06.2017

MedicalResearch.com Interview with: Elizabeth A. Soda, MD Epidemic Intelligence Service Divison of Bacterial Diseases National Center of Immunization and Respiratory Diseases CDC MedicalResearch.com: What is the background for this study? What are the main findings? Response: Legionella is a waterborne bacterium responsible for Legionnaires’ disease, an often severe pneumonia. Legionnaires’ disease primarily affects certain groups of individuals such as those ≥50 year of age, current or former smokers, and those with chronic diseases or weakened immune systems. Health care facilities often have large and complex water systems and care for vulnerable populations that are susceptible to developing Legionnaires’ disease. Thus preventing hospitalized patients from developing Legionnaires’ disease is the ultimate goal. This analysis aimed to describe health care-associated Legionnaires’ disease in 2015 from the 21 U.S. jurisdictions that completely reported their health care-associated Legionnaires’ disease cases to the CDC’s Supplemental Legionnaires’ Disease Surveillance System (SLDSS). Over 2,800 cases of Legionnaires’ disease cases were reported to SLDSS by the 21 jurisdictions, and 553 (20%) were considered health care associated. The analysis showed 16 of the 21 (76%) jurisdictions had at least one case of Legionnaires’ disease definitely related to a stay in a hospital or long-term care facility. In total there were 85 (3%) definite health care-associated Legionnaires’ disease cases (as defined by continuous exposure to a hospital or long-term facility for the entire 10 days before symptom onset) that resulted from 72 different health care facilities. Additionally, 20 of 21 jurisdictions (95%) reported 468 (17%) possible health care-associated Legionnaires’ disease cases (as defined by any exposure to a health care facility for a portion of the 10 days before symptom onset) that resulted from approximately 415 different health care facilities. While approximately 9% of Legionnaires’ disease cases overall are fatal, this report showed a case fatality of 25% for definite health care-associated cases.
Author Interviews, Infections, Merck / 08.06.2017

MedicalResearch.com Interview with: [caption id="attachment_35142" align="alignleft" width="196"]Sanjay Merchant, PhD Executive Director Center for Observational and Real-world Evidence (CORE) Merck Dr. Merchant[/caption] Sanjay Merchant, PhD Executive Director Center for Observational and Real-world Evidence (CORE) Merck MedicalResearch.com: What is the background for this study? What are the main findings? Response: In February, the World Health Organization (WHO) published its first ever list of antibiotic-resistant “priority pathogens” that pose the greatest threat to human health. The list highlights in particular the threat of gram-negative bacteria that are resistant to multiple antibiotics, referred to as multidrug-resistant (MDR) bacteria, which have built-in abilities to find new ways to resist treatment. MDR Pseudomonas aeruginosa (MDR PsA) is listed as one of the pathogens in the Critical category in terms of need for new therapies. It poses an urgent threat. We set out to better understand the clinical and economic burden associated with hospital-onset MDR PsA so that appropriate treatment strategies can be employed to mitigate resistance. Our findings were presented at ASM Microbe 2017. Mortality rates for hospital-onset MDR PsA patients (20.1%) were almost twice as high compared to patients who did not have MDR PsA (11.5%). The MDR PsA patient group had a significantly higher odds ratio for mortality even after controlling for various factors that may impact mortality. Hospital-onset MDR PsA patients spent six additional days in the hospital when compared to patients who did not have MDR PsA infectionsThese findings highlight the public health threat of MDR PsA among hospitalized patients and the need for timely and effective therapy.
Author Interviews, Hand Washing, Infections / 05.06.2017

MedicalResearch.com Interview with: [caption id="attachment_35050" align="alignleft" width="152"]Donald Schaffner, PhD Extension Specialist in Food Science and Distinguished Professor Rutgers-New Brunswick Dr. Schaffner[/caption] Donald Schaffner, PhD Extension Specialist in Food Science and Distinguished Professor Rutgers-New Brunswick MedicalResearch.com: What is the background for this study? Response: We been interested in handwashing and cross-contamination research for more than 15 years. About 10 years after I started as a faculty member I was approached about doing research in this area. The first paper republished has turned into my most highly cited paper. I think it was mostly a matter of being in the right place at the right time, with the right idea. This latest bit of research came out of my ongoing participation in the Conference for Food Protection. This is an unusual meeting, and unlike any other scientific conference. It’s a group of industry scientists, government regulators, and academics would get together every two years to help the FDA Center for Food Safety and Applied Nutrition update a document called the Model Food Code. The code has no regulatory standing, but it is used by state health agencies as the basis for state food codes that regulate restaurants, supermarkets, and other food service establishments. There are several provisions in the code that we wanted to try to impact with our research. The code currently states that hands must be washed in warm water. The plumbing section of the code also states that hand wash sinks must be capable of dispensing water at 100°F. We wanted to explore whether there was any scientific basis statements. In some recent survey-based research, graduate student that is also the first author on this manuscript surveyed the Internet for the kind of advice was offered on handwashing posters that provide advice on how to wash your hands. He found that the recommendations varied widely including recommendations on how long to wash your hands.
Author Interviews, Infections, JAMA, UCLA / 31.05.2017

MedicalResearch.com Interview with: Gregory John Moran, MD, FACEP Emergency Medicine Dept. & Infectious Diseases Service UCLA Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: The bacterial etiology of cellulitis is difficult to determine because there is usually no material for culture, but streptococci are believed to be the most common etiology. Since the emergence of MRSA as a common cause of skin infections in the community, many clinicians add a second antibiotic with MRSA activity to an oral cephalosporin, such as a combination of cephalexin plus trimethoprim-sulfamethoxazole. It is unknown if there is an additional benefit to adding MRSA activity for treatment of cellulitis. This randomized, blinded trial compared cephalexin plus placebo to cephalexin plus trimethoprim-sulfamethoxazole for outpatient treatment of cellulitis without an abscess or wound. Bottom line: We did not find a benefit from addition of trimethoprim-sulfamethoxazole.
Author Interviews, Cost of Health Care, HIV, Opiods, PLoS / 31.05.2017

MedicalResearch.com Interview with: [caption id="attachment_34943" align="alignleft" width="150"]Cora Bernard, MS, PhD candidate Pre-doctoral Student in Management Science and Enginnering Affiliate, Center for Health Policy and the Center for Primary Care and Outcomes Research Stanford Health Policy Cora Bernard[/caption] Cora Bernard, MS, PhD candidate Pre-doctoral Student in Management Science and Enginnering Affiliate, Center for Health Policy and the Center for Primary Care and Outcomes Research Stanford Health Policy MedicalResearch.com: What is the background for this study? Response: The US opioid epidemic is leading to an increase in the US drug-injecting population, which also increases the risks of HIV transmission. It is critical to public health that the US invests in a coherent and cost-effective suite of HIV prevention programs. In our model-based analysis, we considered programs that have the potential both to prevent HIV and to improve long-term health outcomes for people who inject drugs. Specifically, we evaluated opioid agonist therapy, which reduces the frequency of injection; needle and syringe exchange programs, which reduce the frequency of injecting equipment sharing; enhanced HIV screening and antiretroviral therapy programs, which virally suppress individuals and decrease downstream transmission; and oral HIV pre-exposure prophylaxis (PrEP), which is taken by an uninfected individual and lowers the risk of infection.
Author Interviews, CDC, Flu - Influenza, OBGYNE, Vaccine Studies / 31.05.2017

MedicalResearch.com Interview with: [caption id="attachment_34939" align="alignleft" width="112"]Dr. Elyse Olshen Kharbanda, MD MPH HealthPartners Institute Minneapolis, MN Dr. Kharbanda[/caption] Dr. Elyse Olshen Kharbanda, MD MPH HealthPartners Institute Minneapolis, MN MedicalResearch.com: What is the background for this study? What are the main findings? Response: Pregnant women who get the flu are at an increased risk for severe illness. To protect pregnant women, the Advisory Committee on Immunization Practices recommends women receive inactivated influenza vaccine (IIV) during any trimester of their pregnancy. This study used data from the Vaccine Safety Datalink to evaluate if there was an increased risk for selected major structural birth defects for infants whose mothers received IIV in the first trimester of pregnancy versus infants who were unexposed to IIV. Among over 425,000 live births, including 52,856 whose mothers received IIV during first trimester, we evaluated risks for major structural birth defects.  In this large observational study, we did not observe increased risks for major structural birth defects in offspring following first trimester maternal inactivated influenza vaccine exposure.
Author Interviews, CDC, Compliance, Infections / 26.05.2017

MedicalResearch.com Interview with: Dr. Jorge Salinas MD Epidemic intelligence service officer Division of Tuberculosis Elimination Centers for Disease Control and Prevention  MedicalResearch.com: What is the background for this study? Response: Because multidrug-resistant TB (MDR TB) treatment regimens are less effective, more complex, and are more likely to have side effects that are difficult to tolerate than regimens for drug-susceptible TB, patients with MDR TB are at a higher risk of dying. Directly observed therapy (a therapy by which patients meet with a healthcare worker at a regularly scheduled time and place so the healthcare worker can observe the patient taking their TB medication) is recommended to treat all forms of TB disease, including MDR TB.
Author Interviews, HIV, Pharmacology / 24.05.2017

MedicalResearch.com Interview with: [caption id="attachment_34848" align="alignleft" width="119"]Martin Markowitz MD Clinical Director and Staff Investigator Aaron Diamond AIDS Research Center Aaron Diamond Professor at The Rockefeller University Dr. Markowitz[/caption] Martin Markowitz MD Clinical Director and Staff Investigator Aaron Diamond AIDS Research Center Aaron Diamond Professor at The Rockefeller University MedicalResearch.com: What is the background for this study? What are the main findings? Response: Cabotegravir ((CAB) is an inhibitor of HIV-1 integrase and is amenable to formulation in both oral and long acting injectable forms. In preclinical studies injectable CAB protected against low dose intrarectal challenge using an HIV-like virus in the rhesus macaque model. These results support the clinical development of CAB as prevention. This study was a first attempt to establish a dosing regimen and evaluate safety and acceptability of intramuscular injections of CAB. The study was a placebo controlled blinded study of approximately 120 subjects with a 5:1 randomization active/placebo. Subjects received 800mg CAB given as 2 2mL injections or placebo every 12 weeks for 3 injections after a 4 week safety lead in of oral therapy. Safety acceptability and PK were assessed. The main findings were that injections were associated with injection site reactions in the vast majority of participants that were mild to moderate and of short duration. Only 4 subjects who entered the injection phase discontinued due to injection intolerance. There were no additional safety signals and the participants considered the injections acceptable when asked to complete questionnaires. PK analysis found that despite modeling that suggested that the 800mg q 12 week dose would be adequate, this was not the case. More rapid uptake and release from the depot resulted in lower than anticipated drug levels at trough. Alternate dosing regimens are under study. Another finding is that there were participants (14%) who had detectable drug in plasma detected at 52 weeks after last injection suggesting the presence of a tail in some individuals.
Author Interviews, Dental Research, Heart Disease, Infections, Mayo Clinic / 24.05.2017

MedicalResearch.com Interview with: [caption id="attachment_34829" align="alignleft" width="150"]Daniel C. DeSimone, M.D.</strong> Infectious Diseases Fellowship, Year 2 Mayo Clinic Dr. DeSimone[/caption] Daniel C. DeSimone, M.D. Infectious Diseases Fellowship, Year 2 Mayo Clinic MedicalResearch.com: What is the background for this study? Response: For over 50 years, the American Heart Association (AHA) has recommended antibiotics to be given to patients with certain cardiac conditions prior to invasive dental procedures (dental cleanings, extractions, root canals) with the hope to prevent infective endocarditis--a potentially deadly infection of the heart valves. Prevention of this infection was preferred to treatment of an established infection due to its high morbidity and mortality rates. However, in 2007, experts found that there was very little, if any, evidence that showed antibiotics prophylaxis prevented infective endocarditis prior to invasive dental procedures. Given this, the AHA revised its guidelines, significant reducing the number of patients where antibiotic prophylaxis would be given--as routine daily activities such as chewing food, tooth brushing, and flossing were much more likely to cause infective endocarditis than a single dental procedure. For over 50 years, patients with cardiac conditions that placed them at "moderate risk" and/or "high risk" were to receive antibiotics prior to dental procedures. In 2007, the "moderate risk" group were to no longer receive antibiotic prophylaxis. This is a significantly large proportion of patients--approximately 90% of all patients who would have received antibiotic prophylaxis. Given the drastic changes made in 2007, there was concern among the medical and dental communities about whether we were leaving patients "unprotected" and at risk for infective endocarditis. Thankfully, several population based studies from our group and others across the United States have not shown an increase in the rate of infective endocarditis. However, the question remained, "Are providers following the 2007 AHA guidelines?" and "Are patients still receiving antibiotics prior to dental procedures when its no longer indicated by the guidelines?". This was the main focus of our paper. We were able to go into the local dental offices and at the same time, have full access to their medical records. Every dental visit between 2005 and 2015 at their dental office was reviewed; the type of dental visit, whether they received antibiotic prophylaxis or not. In addition, we could confirm their cardiac conditions that would place them at "moderate risk" or "high risk" compared to the general population.
Author Interviews, Infections, UCLA / 22.05.2017

MedicalResearch.com Interview with: [caption id="attachment_34782" align="alignleft" width="200"]Dr. James A. McKinnell, MD LA BioMed Assistant Professor of Medicine David Geffen School of Medicine at UCLA Dr. McKinnell[/caption] Dr. James A. McKinnell, MD LA BioMed Assistant Professor of Medicine David Geffen School of Medicine at UCLA MedicalResearch.com: What is the background for this study? Response: Pneumonia is the leading cause of death from infectious disease in the United States. We conducted this study because current community-acquired pneumonia guidelines from the American Thoracic Society and the Infectious Disease Society America, published in 2007, provide some direction about prescribing antibiotics for community-acquired pneumonia. But large-scale, real-world data are needed to better understand and optimize antibiotic choices and to better define clinical risk factors that may be associated with treatment failure. Antibiotic failure for community-acquired pneumonia is associated with substantial morbidity and mortality and results in significant medical expenditures. We examined databases containing records for 251,947 adult patients who were treated between 2011 and 2015 with a single class of antibiotics (beta-lactam, macrolide, tetracycline, or fluoroquinolone) following a visit to their physician for treatment for community-acquired pneumonia. We defined treatment failure as either the need to refill antibiotic prescriptions, antibiotic switch, ER visit or hospitalization within 30 days of receipt of the initial antibiotic prescription.
Author Interviews, Blood Pressure - Hypertension, Cleveland Clinic, Critical Care - Intensive Care - ICUs, Infections, NEJM / 22.05.2017

MedicalResearch.com Interview with: [caption id="attachment_34772" align="alignleft" width="159"]Ashish Khanna, MD, FCCP Assistant Professor of Anesthesiology, Cleveland Clinic Lerner College of Medicine Staff Intensivist Center for Critical Care and Department of Outcomes Research Cleveland Clinic, Cleveland Dr. Khanna[/caption] Ashish Khanna, MD, FCCP Assistant Professor of Anesthesiology, Cleveland Clinic Lerner College of Medicine Staff Intensivist Center for Critical Care and Department of Outcomes Research Cleveland Clinic, Cleveland MedicalResearch.com: How did you become interested in this topic? Response: Anesthesia forms the basis of my training but I also completed a fellowship in critical care and, at the present time, I do more work in critical care than anesthesia. About 75% of my time is spent in the Cleveland Clinic critical care units, including the Medical and surgical ICUs (Intensive Care Units).
Author Interviews, Critical Care - Intensive Care - ICUs, Emergency Care, Infections, NEJM, University of Pittsburgh / 21.05.2017

MedicalResearch.com Interview with: [caption id="attachment_34724" align="alignleft" width="133"]Christopher W. Seymour, M.D., M.Sc. Assistant professor of Critical Care Medicine and Emergency Medicine, and member of Clinical Research Investigation and Systems Modeling of Acute Illness University of Pittsburgh Dr. Seymour[/caption] Christopher W. Seymour, M.D., M.Sc. Assistant professor of Critical Care Medicine and Emergency Medicine, and member of Clinical Research Investigation and Systems Modeling of Acute Illness University of Pittsburgh MedicalResearch.com: What is the background for this study? What are the main findings? Response: Following the tragic and widely publicized death of Rory Staunton, 12, from undiagnosed sepsis in 2012, New York became the first state to require that hospitals follow a protocol to quickly identify and treat the condition. The mandate led to widespread controversy in the medical community as to whether such steps would have saved Rory or anyone else’s life. Rory’s Regulations require hospitals to follow protocols for early identification and treatment of sepsis, and submit data on compliance and outcomes. The hospitals can tailor how they implement the protocols, but must include a blood culture to test for infection, measurement of blood lactate (a sign of tissue stress) and administration of antibiotics within three hours of diagnosis—collectively known as the “three-hour bundle.” We analyzed data from nearly 50,000 patients from 149 New York hospitals to scientifically determine if  Rory’s Regulations worked. We found that they did - 83 percent of the hospitals completed the bundle within the required three hours, overall averaging 1.3 hours for completion. For every hour that it took clinicians to complete the bundle, the odds of the patient dying increased by 4 percent.
Author Interviews, Critical Care - Intensive Care - ICUs, Electronic Records, Infections / 21.05.2017

MedicalResearch.com Interview with: [caption id="attachment_34734" align="alignleft" width="150"]Faheem Guirgis MD  Assistant Professor of Emergency Medicine Department of Emergency Medicine Division of Research UF Health Jacksonville Dr. Guirgis[/caption] Faheem Guirgis MD Assistant Professor of Emergency Medicine Department of Emergency Medicine Division of Research UF Health Jacksonville MedicalResearch.com: What is the background for this study? What are the main findings? Response: Sepsis is quite prevalent among hospitals and the incidence is increasing. It is a life-threatening disease that can lead to poor outcomes if patients are not recognized and treated promptly. We recognized that our institution needed a strategic approach to the problem of sepsis, therefore the Sepsis Committee was created with the goal of creating a comprehensive sepsis program. We developed a system for sepsis recognition and rapid care delivery that would work in any area of the hospital. We found that we reduced overall mortality from sepsis, the number of patients requiring mechanical ventilation, intensive care unit length and overall hospital length of stay, and the charges to the patient by approximately $7000 per patient.
Author Interviews, Infections, Vaccine Studies / 15.05.2017

MedicalResearch.com Interview with: AbivaxJean-Marc Steens, M.D. Chief Medical Officer of Abivax MedicalResearch.com: What is the background for this study? What are the main findings? Response: Antiretroviral therapy (ART) has had an enormous impact on the HIV pandemic since its introduction almost 20 years ago. Most patients treated with ART achieve undetectable or near undetectable plasma levels of the virus. This means that although HIV is controlled, it is not completely eliminated. The virus remains in the body, usually contained in dormant cells (known as the HIV reservoir) that are widely distributed, including to the central nervous system, the gut mucosa, the lymph nodes and other sites. If ART is stopped, the virus rebounds. The goal of any curative therapy would be to eliminate the virus or ensure there is sustained remission in the absence of ART, which until now have been unsuccessful. Abivax’s Phase 2 clinical study with ABX464 demonstrated, for the first time, a reduction in HIV reservoirs in chronically infected HIV patients as measured by total HIV DNA detected in peripheral blood mononuclear cells (PBMCs). In the ABX464-004 trial, 30 HIV patients received either ABX464 or matching placebo in addition to their current antiretroviral treatment over 28 days. The viral load at the start of the study was well controlled with boosted darunavir. After the 28-day treatment period, all treatments were interrupted until viral load rebound. Baseline and day 28 blood samples were taken to assess the potential effect of ABX464 on the HIV reservoir in PBMCs. Safety was the primary endpoint in the trial. ABX464 was well tolerated, with no severe adverse events in the treatment group. Amongst evaluable patients (4 placebo and 14 ABX464-treated patients), a reduction in viral DNA copies/mPBMCs was observed in 7/14 treated patients (mean change of -40%, ranging from -27% to -67%) and no responders were observed in the placebo group. Responders were defined as patients who had a decrease greater than 25% in total HIV DNA in PBMCs and a reduction of at least 50 copies. Total HIV DNA in PBMC has been validated as a widely accepted biomarker for measuring the HIV reservoir. Specifically, in untreated patients, total HIV DNA load influences the course of the infection and is therefore clinically relevant. In addition, a correlation exists between the pool of HIV-1 DNA and the replication-competent reservoir.
Author Interviews, Infections, Respiratory, Vaccine Studies / 12.05.2017

MedicalResearch.com Interview with: [caption id="attachment_34526" align="alignleft" width="128"]Nima Farzan Chief Executive Officer & President of PaxVax Nima Farzan[/caption] Nima Farzan Chief Executive Officer & President of PaxVax MedicalResearch.com: What is the background for this study? What are the main findings? Response: PaxVax is developing a new and improved version of the vaccine, known as the Modernized Production Adenovirus Vaccine (MPAV) Prototype A. The Company was chosen as the Small Business Innovation Research and Regulatory Sponsor for the development of the Modernized Production Adenovirus Vaccine (MPAV) Prototype A due to the company’s prior experience working with multiple strains of Adenovirus. An Investigational New Drug (IND) application for MPACV was submitted to the U.S. Food and Drug Administration (FDA) on January 30, 2017. The Phase I clinical trial has been initiated and will be conducted at the Larner College of Medicine at the University of Vermont and Cincinnati Children’s Hospital. PaxVax expects to see results of the Phase I clinical trial in early 2018. Complications of adenovirus 4/7 can include headache, pneumonia, sore throat and eye infections. In severe cases, adenovirus can lead to acute respiratory distress syndrome and other serious complications related to organ system damage (including GI tract and bladder) that can result in death, if left untreated.
Author Interviews, C. difficile, Infections, Microbiome / 09.05.2017

MedicalResearch.com Interview with: [caption id="attachment_34420" align="alignleft" width="200"]Synthetic Biologics, Inc. Synthetic Biologics, Inc.[/caption] Sheila Connelly, PhD Vice President, Research Synthetic Biologics, Inc. MedicalResearch.com: What is the background for this study? Response: Synthetic Biologics, Inc. is focused on the protection and preservation of the gut microbiome which is the diverse collection of microorganisms that live in the intestinal tract. We are learning that the gut microbiome plays a key role in health. Negative changes to the microbiome, called dysbiosis, are linked to disease states including allergies, autism, and obesity, among a rapidly growing list of other conditions. A consequence of using antibiotics is that, in addition to fighting the bacterial infection being treated, they also kill the gut microbiota. The space left in the gut by the dead bacteria allows other surviving bacteria, many times opportunistic pathogens or microbes that are resistant to multiple antibiotics, to overgrow and fill the open niches. Exposure to antibiotics, particularly broad-spectrum antimicrobials, such as penicillins and cephalosporins, is a major risk factor for acquiring a potentially deadly Clostridium difficile infection. [caption id="attachment_34487" align="alignleft" width="200"]Dr-Sheila-Connelly.jpg Dr. Sheila Connelly[/caption] Another consequence of antibiotic use is the emergence of antibiotic-resistant organisms. Widespread use of antibiotics provides selective pressure for the evolution of lethal, multi-drug resistant pathogens, termed “nightmare bacteria”. The gut microbiome acts as a reservoir of antibiotic resistance that can be triggered, by antibiotic exposure, to acquire and propagate resistance genes. A way to protect the microbiome and reduce antibiotic resistance is to limit exposure of the gut microbiota to antibiotics. To this end, we developed an antibiotic inactivation strategy using a beta-lactamase enzyme to degrade beta-lactam antibiotics in the GI tract before they can harm the gut microbiome. Beta-lactamases are naturally-occurring bacterial enzymes that confer resistance to beta-lactams, the most widely used broad spectrum antibiotics, and their presence is normally considered an obstacle to efficacious infection control. We took advantage of the highly efficient antibiotic degradation activity of a beta-lactamase and developed SYN-004 (ribaxamase). Ribaxamase is a beta-lactamase engineered to inactivate penicillins and most cephalosporins, formulated for oral delivery, and intended for use with IV beta-lactam antibiotics to degrade the antibiotics in the GI tract to protect the microbiome. Ribaxamase was demonstrated to significantly reduce the occurrence of C. difficile disease in a recently completed Phase 2b clinical study. The study met its primary endpoint by demonstrating that ribaxamase, when delivered orally with IV ceftriaxone, significantly reduced C. difficile disease in patients treated for a respiratory tract infection. Ribaxamase also resulted in a significant reduction in new colonization by vancomycin-resistant enterococcus (VRE). For the current study, pig models of antibiotic-mediated gut dysbiosis were established using three classes of beta-lactam antibiotics, a cephalosporin, ceftriaxone, a penicillin, amoxicillin, and a carbapenem, ertapenem. The ceftriaxone model was used to evaluate the protective effect of ribaxamase on the microbiome and the amoxicillin and ertapenem models are intended for evaluation of pipeline products.
Author Interviews, Dengue, Vaccine Studies / 04.05.2017

MedicalResearch.com Interview with: [caption id="attachment_34388" align="alignleft" width="180"]Dr Vianney Tricou DPhil Takeda Vaccines Singapore Dr. Vianney Tricou[/caption] Dr Vianney Tricou DPhil Takeda Vaccines Singapore MedicalResearch.com: What is the background for this study? What are the main findings? Response: Dengue fever is a painful, debilitating mosquito-borne disease caused by any one of four closely related dengue virus serotypes, and persons living in dengue endemic regions may be affected by dengue more than once in their lifetime. Some individuals with dengue fever are hospitalized and may need intensive therapy to prevent shock and death, and severe dengue is a leading cause of hospitalization and death among children and adults in some Asian and Latin American countries. About half of the world’s population lives under the threat of dengue and the disease has a significant medical and economic impact in the tropical and subtropical regions of the world where dengue is endemic. Takeda is committed to improving global public health and to developing a life-saving dengue vaccine candidate for people around the world. Takeda’s tetravalent dengue vaccine candidate (TAK-003) is based on a live-attenuated dengue serotype 2 virus (DENV-2), which provides the genetic ‘backbone’ for all four attenuated dengue virus serotypes present in the vaccine. Takeda’s Phase 1 and Phase 2 clinical study program includes 8 studies to date that assess the safety and/or immunogenicity of this candidate, before moving into Phase 3. Takeda’s ongoing Phase 2 DEN-204 study is designed to assess the safety and immunogenicity of one- and two-dose schedules of TAK-003 in 1,794 healthy children and adolescents ages two through 17 years living in dengue-endemic countries in Latin America and Asia. As published in The Lancet Infectious Diseases in March 2017, an interim analysis of DEN-204 data indicated that TAK-003 elicited antibody responses to all four dengue serotypes in the population studied, regardless of whether they had previous dengue exposure. A second TDV dose improved antibody responses against DENV-3 and DENV-4 in children who were seronegative before vaccination. In this study, the safety profile was consistent with that observed in earlier Phase 1 and 2 studies.
Author Interviews, Respiratory / 04.05.2017

MedicalResearch.com Interview with: [caption id="attachment_25990" align="alignleft" width="180"]Dr-Harri-Hemilae.jpg Dr. Harri Hemilae[/caption] Harri Hemilä, MD, PhD Department of Public Health University of Helsinki MedicalResearch.com: What is the background for this study? What are the main findings? Response: Some zinc lozenges intended for treating the common cold have contained zinc acetate and some others have contained zinc gluconate. There have been proposals that zinc acetate might be more optimal salt for lozenges than zinc gluconate. Therefore I compared the randomized trials that have used zinc acetate with zinc gluconate to see if there is difference between the lozenges. Although the average effect in 3 studies with zinc acetate lozenges was greater (40%) than the average effect in 4 studies with zinc gluconate lozenges (28%), that difference was explained by random variation. I also analyzed the dose dependency of the effect and found that 2 studies that used 192 and 207 mg per day elemental zinc did not find greater benefit than 5 studies that used 80 to 92 mg per day zinc. The overall average effect of zinc lozenges was 33% reduction in common cold duration and that effect seems to be reached with doses less than 100 mg per day.
Author Interviews, CMAJ, Infections, OBGYNE / 03.05.2017

MedicalResearch.com Interview with: [caption id="attachment_20443" align="alignleft" width="187"]Anick Bérard PhD FISPE Research chair FRQ-S on Medications and Pregnancy and Director, Réseau Québécois de recherche sur le médicament (RQRM) and Professor, Research Chair on Medications, Pregnancy and Lactation Faculty of Pharmacy University of Montreal and Director, Research Unit on Medications and Pregnancy Research Center CHU Ste-Justine Dr. Anick Bérard[/caption] Anick Bérard PhD FISPE Research chair FRQS on Medications and Pregnancy Director, Réseau Québécois de recherche sur le médicament (RQRM) Professor, Research Chair on Medications, Pregnancy and Lactation Faculty of Pharmacy, University of Montreal Director, Research Unit on Medications and Pregnancy Research Center, CHU Ste-Justine MedicalResearch.com: The Danish study you cite reported a connection between antibiotics and miscarriage – why was further research of this topic necessary? Response: Given that a single study will assess an association, repetition of findings are essential in order to assess causality. For example, we were able to conclude that smoking was causing lung cancer after 10 years of observational research on the topic showing concordant associations. In addition, antibiotic prescription patterns vary from country to country, hence the importance of studying the research question in various patient populations. Finally, our cohort has validated exposure status, gestational age (first day of pregnancy) and miscarriage cases - our study was also able to look at types of antibiotics.
Author Interviews, HIV, JAMA, Pediatrics, Sexual Health / 25.04.2017

MedicalResearch.com Interview with: [caption id="attachment_34177" align="alignleft" width="200"]Robin Lin Miller, Ph.D. Professor, Ecological-Community Psychology Co-Director, MA in Program Evaluation Chair, Graduate Program in Ecological-Community Psychology Michigan State University East Lansing, MI 48824 Dr. Miller[/caption] Robin Lin Miller, Ph.D. Professor, Ecological-Community Psychology Co-Director, MA in Program Evaluation Chair, Graduate Program in Ecological-Community Psychology Michigan State University East Lansing, MI 48824 MedicalResearch.com: What is the background for this study? Response: We wanted to identify promising strategies for providing access to HIV-testing for gay and bisexual male youth. We were especially interested in testing strategies to reach gay and bisexual male youth of color, as they bear a disproportionate burden of the HIV epidemic and are the least likely to be aware of their HIV status. We also wanted to explore approaches to successfully link these youth with HIV-negative test results to diverse HIV prevention services, including pre-exposure prophylaxis, when warranted. Although some argue that the ideal place to test adolescents and young adults is via emergency rooms and in routine medical care visits, we found that we were able test many more youth with previously undiagnosed HIV-infection through intensive, targeted community outreach efforts. We also tested a much higher proportion of young men of color through targeted outreach.
Addiction, Author Interviews, Infections, JAMA, Ophthalmology / 22.04.2017

MedicalResearch.com Interview with: Aubrey Tirpack, PGY3 New England Eye Center Tufts Medical Center  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Intravenous drug abuse is a known risk factor for the development of endogenous fungal endophthalmitis (EFE), a severe intraocular infection cause by the seeding of mycotic organisms to the eye. Our institution noted a marked increase in cases of EFE beginning in May 2014, which correlates to increasing rates of opioid abuse throughout the New England region. Ten patients were found to have intravenous drug abuse related EFE over the two year time period studied. The most common presenting symptoms were floaters, decreased vision, and pain. All patients were treated with systemic antifungals and nine patients underwent intravitreal antifungal injection. All patients were ambulatory at presentation and the majority were without systemic signs of infection.
Author Interviews, CDC, Infections / 22.04.2017

MedicalResearch.com Interview with: [caption id="attachment_34073" align="alignleft" width="200"]Ms. Ellyn Marder MPH</strong> Surveillance Epidemiologist, CDC Centers for Disease Control and Prevention Atlanta, Georgia Ellyn Marder[/caption] Ms. Ellyn Marder MPH Surveillance Epidemiologist, CDC Centers for Disease Control and Prevention Atlanta, Georgia MedicalResearch.com: What is the background for this study? What are the main findings? Response: CDC’s Foodborne Diseases Active Surveillance Network (FoodNet) report provides the most up-to-date information about foodborne illnesses in the United States. Each year, FoodNet publishes a report that includes preliminary data compared with data from the previous three years. FoodNet has been monitoring illness trends since 1996 and collects data on about 15 percent of the U.S. population. Campylobacter and Salmonella caused the most reported bacterial foodborne illnesses in 2016, according to preliminary data. FoodNet sites alone reported 24,029 foodborne infections, 5,512 hospitalizations, and 98 deaths in 2016. The numbers of reported illnesses by germ are: Campylobacter (8,547), Salmonella (8,172), Shigella (2,913), Shiga toxin-producing E. coli (1,845), Cryptosporidium (1,816), Yersinia (302), Vibrio (252), Listeria (127) and Cyclospora (55). This is the first time the report also includes in the total number of infections those foodborne bacterial infections diagnosed only by rapid diagnostic tests in FoodNet sites. Previously, the report counted foodborne bacterial infections confirmed only by traditional culture-based methods in the total numbers.
Author Interviews, Heart Disease, HIV, JAMA, Vanderbilt / 18.04.2017

MedicalResearch.com Interview with: Matthew S Freiberg, MD, MSc Associate Professor of Medicine, Division of Cardiovascular Medicine Vanderbilt Translational and Clinical Cardiovascular Research Center MedicalResearch.com: What is the background for this study? Response:  HIV infected people are living longer and are at risk for cardiovascular diseases. While acute myocardial infarction has been studied and the increased risk of Acute Myocardial Infarction (AMI) among HIV+ people compared to uninfected people is well documented, there are less data describing the risk of HIV and different types of heart failure, including reduced and preserved ejection fraction heart failure. Understanding more about the link between HIV and different types of HF is important because reduced and preserved ejection fraction heart failure differ with respect to underlying mechanism, treatment, and prognosis. Moreover, as cardiovascular care has improved, HIV infected people who experience an AMI are likely to survive but may live with a damaged heart. Understanding more about the link between HIV and heart failure may help providers and their patients prevent or reduce the impact of HF on the HIV community.
Author Interviews, Nature, Zika / 14.04.2017

MedicalResearch.com Interview with: [caption id="attachment_33892" align="alignleft" width="160"]Dr. Jikui Song PhD Assistant professor of biochemistry University of California, Riverside. Dr. Jikui Song[/caption] Dr. Jikui Song PhD Assistant professor of biochemistry University of California, Riverside. MedicalResearch.com: What is the background for this study? What are the main findings? Response: Recent outbreak of Zika virus (ZIKV) has become a wordwide health concern. However, no vaccines or antiviral drugs against ZIKV are currently available. To explore potential druggable sites for ZIKV, we set out to determine the crystal structure of full-length ZIKV NS5, the molecular machinery responsible for the genomic replication of ZIKV. The major findings of our study include the identification of a conserved domain conformation within flavivirus NS5 family, which may be important for functional regulation of flavivirus NS5. Furthermore, our structural analysis revealed a potential drug-binding site of ZIKV NS5, providing basis for future development of novel antivirals against ZIKV.
Author Interviews, Infections, Microbiome, OBGYNE, Pediatrics / 05.04.2017

MedicalResearch.com Interview with: Hans Bisgaard, MD, DMSc Professor of Pediatrics The Faculty of Health Sciences University of Copenhagen Copenhagen University Hospital, Gentofte Copenhagen, Denmark MedicalResearch.com: What is the background for this study? Response: The consumption of antibiotics is increasing worldwide. Antibiotics alter the maternal bacterial colonization and by vertical transmission this can affect the offspring. An unfavorable microbiome may increase the disease propensity of the offspring. Otitis media is one of the most common infections in early childhood. We hypothesized that antibiotic consumption in pregnancy can increase the children’s risk of otitis media.
Author Interviews, Global Health, Infections / 02.04.2017

MedicalResearch.com Interview with: [caption id="attachment_33617" align="alignleft" width="150"]Dr Mihály Sulyok MD Eberhard Karls University Institute of Tropical Medicine, Tübingen, Germany Dr Mihály Sulyok[/caption] Dr Mihály Sulyok MD Eberhard Karls University Institute of Tropical Medicine, Tübingen, Germany MedicalResearch.com: What is the background for this study? What are the main findings? Response: New antimalarials are desperately needed, not just for treatment, but also for prophylaxis. DSM265, a novel antimalarial compound that selectively inhibits the plasmodial dihydroorotate dehydrogenase has a promising pharmacokinetic profile characterized by a long elimination half-life. We performed a study at the Institute of Tropical Medicine, Eberhard Karls University (Tübingen, Germany) to investigate safety, tolerability and efficacy of DSM265 using controlled human malaria infection. In the first cohort, 400mg of DSM265 was administered orally to five healthy, malaria naive individuals one day before direct venous inoculation of an established infective dose of P. falciparum sporozoites (PfSPZ Challenge). Placebo was administered to two volunteers. The study was randomized and double blinded. In this cohort all placebo participants developed malaria, whereas all DSM265 participants were protected. In a second cohort, 400mg DSM265 was administered 7 days before the sporozoite inoculation for six participants, two participants recieved placebo. In this cohort, the two placebo and three of six DSM265 volunteers developed thick blood smear positive malaria. The remaining three DSM265 volunteers developed transient submicroscopic parasitemia without symptoms or thick blood smear positivity. The only possible DSM265-related adverse event was a slight transient elevation in serum bilirubin in one volunteer. The study was funded by the Global Health Innovative Technology Fund, Wellcome Trust, Bill & Melinda Gates Foundation through Medicines for Malaria Venture, and the German Center for Infection Research.
Author Interviews, Zika / 31.03.2017

MedicalResearch.com Interview with: [caption id="attachment_33551" align="alignleft" width="90"]Daihai He PhD Department of Applied Mathematics The Hong Kong Polytechnic University Hung Hom, Kowloon Hong Kong (SAR), China Dr. Daihai He[/caption] Daihai He PhD Department of Applied Mathematics The Hong Kong Polytechnic University Hung Hom, Kowloon Hong Kong (SAR), China MedicalResearch.com: What is the background for this study? What are the main findings? Response: Zika virus disease has large outbreaks in many Pacific and American countries in 2016, and the outbreaks are still on-going. Our work is conducted against this background. We compared data from three localities: French Polynesia in 2013-2014, Colombia and Brazil in 2016. We found that in French Polynesia the infection attack rate (i.e. the proportion of the population who got infected) is about 3/4, which matched previous serological studies. We then make estimation for the other two place. We found that the infection attack rate in Colombia in 2016 was most likely less than 50%. For Bahia province of Brazil, we did not arrive at a very accurate estimation, as the confidence interval is wide, and our best estimate is 30%. The relatively low infection attack rate in Colombia and Brazil implies that future outbreaks of Zika virus diseases are still possible. Thus control and surveillance efforts should be continued.
Author Interviews, HPV, NEJM, OBGYNE, Vaccine Studies / 30.03.2017

MedicalResearch.com Interview with: Anders Hviid Senior Investigator, M.Sc.,Dr.Med.Sci. Department of Epidemiology Research Division of National Health Surveillance & Research MedicalResearch.com: What is the background for this study? Response: HPV vaccination targeting girls and young women has been introduced in many countries throughout the world. HPV vaccines are not recommended for use in pregnancy, but given the target group, inadvertent exposure will occur in early unrecognized pregnancies. However, data on the safety of HPV vaccination in pregnancy is lacking.