Author Interviews, HIV, J&J-Janssen, Merck, Pharmacology / 26.07.2017

MedicalResearch.com Interview with: Dr. Kathleen Squires MD Professor and Director of Infectious Diseases Thomas Jefferson University Philadelphia, PA  MedicalResearch.com: What is the background for this study? What are the main findings?
  • The pivotal Phase 3 DRIVE-AHEAD study evaluated the safety and efficacy of a once-daily, single tablet, fixed-dose combination containing doravirine, an investigational non-nucleoside reverse transcriptase inhibitor (NNRTI) for the treatment of HIV-1 infection, compared to a fixed-dose combination containing efavirenz.
    • After 48 weeks of treatment, 84 percent of the 364 treatment-naïve patients taking once-daily DOR/3TC/TDF achieved levels of HIV-1 RNA <50 copies/mL compared to 81 percent of the 364 patients taking once-daily EFV/FTC/TDF, with an estimated treatment difference of 3.5 percent.
    • Increases in mean CD4+ T-cell counts from baseline for the DOR/3TC/TDF and EFV/FTC/TDF groups were 198 and 188 cells/mm3, respectively, with an estimated treatment difference of 10.1.
    • In addition, comparable efficacy was observed across both treatment groups among individuals with high viral load (HIV-1 RNA >100,000 copies/mL) at baseline, which consisted of 69 patients in the DOR/3TC/TDF group and 73 patients in the EFV/FTC/TDF group (Observed Failure approach).
      • Of those patients with a high viral load (HIV-1 RNA >100,000 copies/mL) at baseline, 81 percent in the DOR/3TC/TDF group and 81 percent in the EFV/FTC/TDF group achieved the study’s primary endpoint of <50 copies/mL of HIV-1 RNA, with a treatment difference of 1.0 percent.
    • The study also met its primary safety endpoint, showing that treatment with DOR/3TC/TDF resulted in fewer patients reporting events of several pre-specified neuropsychiatric adverse events compared to EFV/FTC/TDF by Week 48, including dizziness (8.8 percent versus 37.1 percent); sleep disorders and disturbances (12.1 percent versus 25.5 percent); and inability to think clearly or concentrate (4.4 percent versus 8.2 percent).
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Author Interviews, HIV, Merck, Pharmacology / 25.07.2017

MedicalResearch.com Interview with: Dr. Pedro Cahn Chief of the infectious disease unit at Juan A. Fernandez Hospital Buenos Aires, Argentina, and ONCEMRK lead study investigator MedicalResearch.com: What is the background for this study? What are the main findings? The ONCEMRK Phase 3 study was conducted to evaluate the efficacy and safety of once-daily ISENTRESS (raltegravir) HD 1200 mg (given as two 600 mg oral tablets) compared to twice daily raltegravir 400 mg, each in combination therapy with emtricitabine plus tenofovir disoproxil fumarate in previously untreated adults with HIV-1 infection with levels of HIV-1 RNA ≥ 1,000 copies/mL.
  • Week 96 data showed:
    • 5 percent of the 531 patients taking once-daily raltegravir 1200 mg (2 x 600 mg) achieved viral suppression of less than 40 copies/mL of HIV-1 RNA, compared to 80.1 percent of the 266 patients taking twice-daily raltegravir 400 mg, both in combination therapy with emtricitabine plus tenofovir disoproxil fumarate, with a treatment difference of 1.4 percent.
    • Increases in CD4+T-cell counts from baseline were comparable for the two treatment regimens, with an average increase of 261.6 cells/mm3 for once-daily raltegravir (1200 mg) and 262.2 cells/mm3 for twice-daily raltegravir (400 mg).
    • Efficacy was consistent across a variety of patient populations, including those with high viral load at baseline (HIV-1 RNA >100,000 copies/mL).
    • Treatment-emergent viral mutations leading to any drug resistance were detected in less than 1 percent of patients in both treatment arms, with 4/531 (0.8 percent) in the once-daily raltegravir (1200 mg) treatment arm, and 2/266 (0.8 percent) in the twice-daily raltegravir (400 mg) treatment arm through 96 weeks.
    • The rate of discontinuation of therapy due to adverse events through 96 weeks was low (1.3 percent in patients receiving once-daily raltegravir (1200 mg) and 2.3 percent in patients receiving twice-daily raltegravir (400 mg).
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Author Interviews, Infections, JAMA, Pediatrics, Respiratory, Vitamin D / 18.07.2017

MedicalResearch.com Interview with: Jonathon Maguire MD MSc FRCPC Scientist, Li Ka Shing Knowledge Institute Staff Pediatrician, Department of Pediatrics, St. Michael’s Hospital MedicalResearch.com: What is the background for this study? What are the main findings? Response: Vitamin D has been hypothesized as being protective of seasonal viral upper respiratory tract infections.  In this randomized clinical trial, high dose wintertime vitamin D supplementation (2000 IU/day) was compared with standard-dose vitamin D supplementation (400 IU/day) among 703 children.  The number of laboratory confirmed viral upper respiratory tract infections was not statistically different between groups. (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Dermatology, HIV, JAMA, Kaiser Permanente, Merck / 13.07.2017

MedicalResearch.com Interview with: Maryam M. Asgari, MD, MPH Department of Dermatology Massachusetts General Hospital, Department of Population Medicine Harvard Medical School, Boston, Massachusetts Division of Research, Kaiser Permanente Northern California, Oakland MedicalResearch.com: What is the background for this study? What are the main findings? Response: Nonmelanoma skin cancer – defined as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) – is a common malignant condition, affecting more than 2 million Americans every year. BCCs are more common than SCCs among individuals with healthy immune systems, while SCCs are more predominate than BCCs among people who are immunocompromised. We examined how laboratory markers used to evaluate HIV disease progression may be associated with subsequent nonmelanoma skin cancer risk in white patients previously diagnosed with at least one such cancer from 1996 to 2008.  We measured CD4 count, viral load and subsequent nonmelanoma skin cancer. The study included 455 participants with HIV and 1,952 without HIV. All were members of the Kaiser Permanente Northern California health care plan. (more…)
Author Interviews, Infections, Lancet, STD, Vaccine Studies / 11.07.2017

MedicalResearch.com Interview with: Helen Petousis-Harris. BSc, PhD Senior Lecturer, Dept General Practice and Primary Health Care Academic Head, Immunisation Research and Vaccinology Immunisation Advisory Centre School of Population Health, Faculty of Medical and Health Sciences University of Auckland MedicalResearch.com: What is the background for this study? What are the main findings? Response: Early thinking came from two quarters. One, the observation that the NZ OMV vaccine appeared broadly protective – beyond the clone it was based on and two, the observation of graphs depicting annual number of cases from both Cuba and NZ. There is nothing to suggest other types of meningococcal vaccine have had any effect on gonorrhoea so we are interested in the OMV vaccines. This led to the hypothesis that as these two Neisseria species are related the meningococcal OMV in the form of a vaccine may offer some kind of cross protection. To explore this possibility we conducted a case-control study that compared the vaccination status of cases (gonorrhoea) and controls (Clamydia). We found that the cases with gonorrhoea were less likely to be vaccinated than the controls and after we controlled for confounders – ethnicity, SE deprivation, age we found a vaccine effectiveness of 31%. (more…)
Author Interviews, Emory, Flu - Influenza, Lancet, Technology, Vaccine Studies / 28.06.2017

MedicalResearch.com Interview with: Dr Nadine G Rouphael MD Associate Professor of Medicine, Emory University Director of the VTEU and HIPC networks at the Hope Clinic of the Emory Vaccine Center Decatur GA 30030, USA MedicalResearch.com: What is the background for this new technology and study? What are the main findings? Response: Different groups including a group of researchers at Georgia Tech have been working on the microneedle technology for more than 20 years. The dissolvable microneedle patches are already used in several cosmetic products and drugs. However, vaccination with microneedle patches has been studied mostly in animals. Our phase 1 trial published this week in The Lancet showed that vaccination with the microneedle patches was safe, with no related serious adverse events reported. Local skin reactions to the patches were mostly mild itching and faint redness that lasted two to three days. No new chronic medical illnesses or influenza-like illnesses were reported with either the patch or the injection groups. Antibody responses generated by the vaccine, as measured through analysis of blood samples, were similar in the groups vaccinated using patches and those receiving intramuscular injection, and these immune responses were still present after six months. When asked after immunization, more than 70 percent of patch recipients reported they would prefer patch vaccination over injection or intranasal vaccination for future vaccinations. (more…)
Author Interviews, CDC, Lyme / 23.06.2017

MedicalResearch.com Interview with: Dr. Christina Nelson, MD MPH Medical epidemiologist, Division of Vector-Borne Diseases CDC  MedicalResearch.com: What is the background for this study? Response: Patients who are given a diagnosis of “chronic Lyme disease” have been offered a variety of treatments that have not been shown to be effective.  Many patients are treated with prolonged courses of antibiotics (for months or years), which have not been shown to provide substantial long-term benefit to patients.  Anecdotal reports about adverse outcomes associated with these treatments for chronic Lyme disease are common, but there have not been systematic efforts to collect data about the frequency of these events. MedicalResearch.com: Why is the diagnosis of 'Chronic Lyme Disease' so common? Response: The term “chronic Lyme disease” (CLD) has been used to describe people with different illnesses. While the term is sometimes used to describe illness in patients with Lyme disease, in many occasions it has been used to describe symptoms in people who have no evidence of a current or past infection with Lyme disease.  Because of the confusion in how the term CLD is employed, experts in this field do not support its use. (more…)
Author Interviews, Dermatology, Infections / 22.06.2017

MedicalResearch.com Interview with: Dr. Sue Cammarata, MD Chief Medical Officer Melinta Therapeutics MedicalResearch.com:   Would you explain what is meant by MRSA? Response: MRSA is methicillin-resistant Staphylococcus aureus, a type of staph bacteria that is  resistant to many antibiotics. MRSA is noted by the CDC as one of the top 18 drug-resistant bacteria threats to the United States.  (from CDC https://www.cdc.gov/drugresistance/biggest_threats.html  )  MedicalResearch.com:   Why is infection with MRSA so serious? Response:  MRSA can cause skin infections, lung infection and other issues. If left untreated, MRSA infections can become severe and cause sepsis - a life-threatening reaction to severe infection in the body - and even death.  MRSA can also cause major issues, such as bloodstream infections, pneumonia and surgical site infections in a healthcare setting, such as a hospital or nursing home. “Resistance to first-line drugs to treat infections caused by Staphlylococcus aureus—a common cause of severe infections in health facilities and the community—is widespread. People with MRSA (methicillin-resistant Staphylococcus aureus) are estimated to be 64% more likely to die than people with a non-resistant form of the infection.”  (quote from WHO website http://www.who.int/mediacentre/factsheets/fs194/en/  )   (more…)
Author Interviews, Infections / 22.06.2017

MedicalResearch.com Interview with: Deborah Linder, DVM, MS, DACVN Research assistant professor Cummings School of Veterinary Medicine Tufts University and Associate director of the Tufts Institute for Human-Animal Interaction MedicalResearch.com: What is the background for this study? Response: In our experience with our own therapy animal program, Tufts Paws for People, we have seen facilities and organizations put animals and people at risk by not following rigorous health and safety policies, and this certainly was confirmed by the results of our study. Lax health and safety policies typically aren’t intentional but occur as a result of enthusiasm for therapy animal programs without being aware of potential risks and what questions to ask. Also, it’s not just obvious problems that can occur, such as bites or allergies. It also can be an animal spreading infections due to diet or inadequate grooming, or unwanted stress on the animal. (more…)
Author Interviews, Dermatology, HPV, PLoS / 22.06.2017

MedicalResearch.com Interview with: Prof. Dr. med. Sigrun Smola Institute of Virology, Saarland University Homburg/Saar, Germany MedicalResearch.com: What is the background for this study? Response: Non-melanoma skin cancer (NMSC), the most common cancer in humans, is caused by UV-irradiation. The potential co-factor role of cutaneous genus beta-human papillomaviruses (beta-HPV) in skin carcinogenesis, particularly in immunosuppressed patients, has become a major field of interest. However, the underlying mechanisms were unclear. The skin has natural mechanisms providing protection against UV-induced damage. One important factor suppressing UV-induced skin carcinogenesis is the transcription factor C/EBPα belonging to the CCAAT/enhancer binding protein family. C/EBPα can induce cellular differentiation and is regarded as a tumor suppressor in various tissues. When C/EBPα expression is blocked in these tissues, tumorigenesis is enhanced. Another important factor is the microRNA-203. It has been shown to control “stemness” in normal skin by suppressing a factor called p63. In many tumors miR-203 expression is shut off releasing this “brake”. In our study we demonstrate that cutaneous beta-HPV interferes with both protective factors providing an explanation how cutaneous beta-HPV enhances the susceptibility to UV-induced carcinogenesis. Moreover, we provide evidence that these viruses regulate miR-203 via C/EBPα. We have investigated this mechanism in Epidermodysplasia verruciformis (EV) patients that serve as a human model disease for studying the biology of genus beta-HPVs. They are highly susceptible to persistent genus beta-HPV infection, such as HPV8, and have an increased risk to develop non-melanoma skin cancer at sun-exposed sites. (more…)
Author Interviews, Flu - Influenza, NEJM, Vaccine Studies / 22.06.2017

MedicalResearch.com Interview with: Lisa M. Dunkle, M.D. Chief Medical Officer Protein Sciences Corporation 1000 Research Parkway Meriden, CT MedicalResearch.com: What is the background for this study? What are the main findings? Response: The first and only recombinant protein influenza vaccine (RIV, Flublok) was approved in 2013 as a trivalent formulation for use in adults 18 years of age and older. This approval was based on demonstration of clinical efficacy (full approval) in adults 18-49 years of age and accelerated approval was granted for adults 50 years of age and older. Two clinical trials were conducted in 2014-2015 with RIV4 (Flublok Quadrivalent), of which the trial reported in the current NEJM is one. These studies supported full approval of Flublok in adults 50 years of age and older and approval of Flublok Quadrivalent in all adults 18 years of age and older. The second trial of immunogenicity of Flublok Quadrivalent in adults 18-49 years of age will be the subject of another publication in the near future. The main findings of the current trial are well summarized in the Conclusion of the Abstract: “RIV4 provided better protection than standard-dose IIV4 against confirmed influenza-like illness in older adults.” Additionally, the recombinant vaccine (RIV4, Flublok Quadrivalent) demonstrated significantly less injection site pain and tenderness following vaccination. Based on the characteristics of the study participants, one can conclude that RIV4 is safe and effective in most individuals with underlying chronic diseases (more…)
Author Interviews, Global Health, Infections, Pediatrics / 19.06.2017

MedicalResearch.com Interview with: 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. (more…)
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. (more…)
Author Interviews, Infections, Merck / 08.06.2017

MedicalResearch.com Interview with: 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 infections. These findings highlight the public health threat of MDR PsA among hospitalized patients and the need for timely and effective therapy. (more…)
Author Interviews, Hand Washing, Infections / 05.06.2017

MedicalResearch.com Interview with: 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. (more…)
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. (more…)
Author Interviews, Cost of Health Care, HIV, Opiods, PLoS / 31.05.2017

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, CDC, Flu - Influenza, OBGYNE, Vaccine Studies / 31.05.2017

MedicalResearch.com Interview with: 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. (more…)
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. (more…)
Author Interviews, HIV, Pharmacology / 24.05.2017

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Dental Research, Heart Disease, Infections, Mayo Clinic / 24.05.2017

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Infections, UCLA / 22.05.2017

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Blood Pressure - Hypertension, Cleveland Clinic, Critical Care - Intensive Care - ICUs, Infections, NEJM / 22.05.2017

MedicalResearch.com Interview with: 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). (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Emergency Care, Infections, NEJM, University of Pittsburgh / 21.05.2017

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Electronic Records, Infections / 21.05.2017

MedicalResearch.com Interview with: 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. (more…)
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. (more…)
Author Interviews, Infections, Respiratory, Vaccine Studies / 12.05.2017

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, C. difficile, Infections, Microbiome / 09.05.2017

MedicalResearch.com Interview with: 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. 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. (more…)
Author Interviews, Dengue, Vaccine Studies / 04.05.2017

MedicalResearch.com Interview with: 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. (more…)