Author Interviews, FDA, Flu - Influenza, Geriatrics, Lancet, Vaccine Studies / 03.04.2015

Dr Richard Forshee PhD Food and Drug Administration, Silver Spring, MD MedicalResearch.com Interview with: Dr Richard Forshee PhD Associate Director for Research in the Office of Biostatistics and Epidemiology Center for Biologics Evaluation and Research U.S. Food and Drug Administration Silver Spring, MD On behalf of the study authors Medical Research: What is the background for this study? What are the main findings? Dr. Forshee: Influenza continues to be a major public health concern causing illness, hospitalization, and death. The elderly are at highest risk for seasonal influenza complications, including hospitalization and death. As people grow older their ability to raise a strong protective immune response can weaken.  The availability of a vaccine that uses a higher dose to induce a stronger immune response could reduce the serious impact of influenza in this age group.  The purpose of this study was to determine whether a high-dose inactivated influenza vaccine was more effective for prevention of probable influenza infections and influenza-related hospital admissions, compared to standard-dose inactivated influenza recipients. In December 2009, the U.S. Food and Drug Administration (FDA) licensed Fluzone High Dose, an injectable inactivated trivalent seasonal influenza vaccine for people ages 65 years and older. This high-dose vaccine contains four times more hemagglutinin—the active ingredient in influenza vaccines that cause the human body to produce antibodies against the influenza viruses—than the standard-dose vaccine. The FDA approved the high-dose vaccine using the accelerated approval regulatory pathway, which allows the agency to approve products for serious or life-threatening diseases based on reasonable evidence of a product’s effectiveness.  This pathway reduces the time it takes for needed medical products to become available to the public.  Studies conducted prior to licensure showed an enhanced immune response to the high-dose vaccine compared with the standard-dose vaccine in individuals 65 years of age and older indicating that the high-dose vaccine was reasonably likely to be more effective in preventing influenza disease. As part of the accelerated approval process, the manufacturer, Sanofi Pasteur, was required to conduct a randomized clinical study post-licensure to confirm that the high-dose vaccine decreased seasonal influenza disease after vaccination relative to standard dose vaccine. This confirmatory study demonstrated that the high–dose vaccine prevented 24% more cases of laboratory-confirmed influenza illness compared to standard-dose vaccines in people 65 years of age and older. However, the study was not large enough to determine efficacy of the vaccine against severe disease. A team of scientists from FDA, the Centers for Disease Control and Prevention, Centers for Medicare and Medicaid Services, and Acumen LLC ( an independent research organization) studied the relative effectiveness of the high-dose influenza vaccine in the U.S. population ages 65 years and older.  The observational study, which covered the 2012-2013 influenza season, found a significant reduction both in influenza-associated illness and in influenza-related hospitalizations among individuals who received the high-dose vaccine, compared to those receiving the standard dose. Additional background about this study: “Comparative effectiveness of high-dose versus standard-dose influenza vaccines in US residents aged 65 years and older from 2012 to 2013 using Medicare data: a retrospective cohort analysis” is available at: http://dx.doi.org/10.1016/S1473-3099(14)71087-4 A commentary on the study titled “Novel observational study designs with new influenza vaccines” is available at: http://dx.doi.org/10.1016/S1473-3099(15)70020-4
Antibiotic Resistance, Author Interviews, Infections, NEJM / 02.04.2015

Henri van Werkhoven PhD student | Julius Center for Health Sciences and Primary Care University Medical Center Utrecht, Utrecht, The NetherlandsMedicalResearch.com Interview with: Henri van Werkhoven PhD student and Douwe-PostmaDouwe Postma PhD student Julius Center for Health Sciences and Primary Care University Medical Center Utrecht, Utrecht, The Netherlands Medical Research: What is the background for this study? What are the main findings? Response: Community-acquired pneumonia is an important cause of hospitalization and death worldwide. Recommendations for antibiotic treatment in patients hospitalized to a non-ICU ward vary widely between guidelines, because the optimal antibiotic strategy is unknown. Interpretation of the available evidence from clinical studies is complicated by the heterogeneity in designs and findings. In our study, we hypothesized that the most conservative strategy, beta-lactam monotherapy, would be non-inferior to strategies with a broader range of antibiotic coverage. The latter strategies are potentially related to increased antibiotic resistance. For this purpose, we randomized hospitals to follow three different strategies of preferred antibiotic treatment in consecutive periods of four months. Physicians were allowed to deviate from the preferred antibiotic treatment for medical reasons. We found that a strategy with beta-lactam monotherapy (e.g. amoxicillin) as the preferred treatment was non-inferior to the strategies with beta-lactam/macrolide combination therapy or fluoroquinolone monotherapy for 30 and 90-day all-cause mortality. Also there was no difference in length of hospitalization and rate of complications.
Author Interviews, HIV, JAMA, Pediatrics, University of Pennsylvania / 02.04.2015

Elizabeth Lowenthal, MD MSCE Assistant Professor of Pediatrics Children's Hospital of PhiladelphiaMedicalResearch.com Interview with: Elizabeth Lowenthal, MD MSCE Assistant Professor of Pediatrics Children's Hospital of Philadelphia Medical Research: What is the background for this study? What are the main findings? Dr. Lowenthal: Between 2005 and 2012, HIV related deaths declined by 30% worldwide. However, during the same time period, HIV related deaths increased 50% among adolescents. Over 90% of HIV-infected children and adolescents live in sub-Saharan Africa and HIV is the leading cause of death among adolescents in Africa. Treatment is available that can allow babies born with HIV to live to be healthy adults. However, strict adherence to these medicines is necessary and often becomes a great challenge during adolescence. In our study of 300 adolescents (ages 10-19) in Botswana, my team found that adolescents who come to clinic without a parent or guardian have a 4.5X greater odds of failing their HIV treatment.
Author Interviews, C. difficile, Gastrointestinal Disease, Microbiome / 01.04.2015

Michael J Sadowsky Ph.D Director, BioTechnology Institute University of MinnesotaMedicalResearch.com Interview with: Michael J Sadowsky Ph.D Director, BioTechnology Institute University of Minnesota MedicalResearch: What is the background for this study? What are the main findings? Dr. Sadowsky: Fecal microbiota transplantation (FMT) has become increasingly common in the treatment of patients with refractory Clostridium difficile infection (CDI). It also holds promise for the treatment of medical conditions ranging from inflammatory bowel and Crohn’s disease to diabetes and metabolic syndrome. In contrast to standard antibiotic therapies, which further disrupt intestinal microflora and may contribute to the recurrence of CDI, FMT restores intestinal microbiome and healthy gut function. Despite therapeutic successes, little is known about the stability of transplanted microbiota over time. This report contributes to our understanding of the short-and long-term composition of gut microbiota following Fecal microbiota transplantation. In this study, fecal samples collected before and after treatment were compared with data from the Human Microbiome Project (HMP). Treatment using FMT resulted in the rapid normalization of microbial composition in the patient, with the post-treatment profiles closely resembling the normal distribution of fecal microbiota from the donor. While the composition of fecal microbiota in the donor and recipient varied over time, both remained in the large band characterized as normal in hundreds of healthy individuals collected as part of the HMP. Furthermore, while the composition of the microflora in Fecal microbiota transplantation recipients and donors diverges over time, the recipient profiles stay within the same dynamic range as the original implanted donor material.
Author Interviews, Duke, HPV, Stem Cells / 01.04.2015

Marc Ryser PhD Visiting Assistant Professor Department of Mathematics Duke University Durham, North CarolinaMedicalResearch.com Interview with: Marc Ryser PhD Visiting Assistant Professor Department of Mathematics Duke University Durham, North Carolina Medical Research: What is the background for this study Dr. Ryser: Infection with the human papillomavirus (HPV) is responsible for approximately 5% of all cancers worldwide. In addition to cervical cancers, HPV is associated with various other female and male cancers, including cancers of the anus and oropharynx. Despite expansive screening and vaccination programs, HPV-related cancers remain a serious public health concern in the US and abroad. To further improve public health interventions against HPV, a thorough understanding of the underlying biology is critical. The lifetime risk of getting infected with HPV is as high as 80%, yet most individuals remain asymptomatic and clear the virus after 1-2 years.  However, if an infection with a high-risk type of HPV persists, the virus can interfere with the replication mechanism of the host cells, and initiate tumor growth. Even though our understanding is incomplete to date, clearance of HPV infections is primarily attributed to an effective immune response. Interestingly, recent studies about the stem cell dynamics in epithelial tissues - the types of tissues that are affected by HPV -  have shown that the fate of these stem cells is random: most of the time, a stem cell divides into a new stem cell and a differentiating daughter cell; however, every now and then, a stem cell divides either into two stem cells, or into two differentiating daughter cells. These dynamics have not been acknowledged by the HPV community, and our goal was to develop mathematical models to examine whether the random division patterns of stem cells could play a role in the clearance of HPV infections.
Author Interviews, Infections, Microbiome, Urology / 01.04.2015

Alan J. Wolfe PhD, Professor Department of Microbiology and Immunology Stritch School of Medicine, Loyola University Chicago Maywood, ILMedicalResearch.com Interview with: Alan J. Wolfe PhD, Professor Department of Microbiology and Immunology Stritch School of Medicine, Loyola University Chicago Maywood, IL

Medical Research: What is the background for this study? Dr. Wolfe: Several years ago, Dr. Brubaker and I began a conversation. As a urogynecologist, she was concerned about the general lack of improvement in diagnosis and treatment in her urogynecological practice and thus in clinical outcome. As a microbiologist, I was extremely skeptical of the dogma that urine in the bladder was sterile in the absence of a clinical infection. This skepticism was based upon my former work in bacterial motility and biofilm formation and on the knowledge that most bacteria are not cultured by the standard clinical microbiology urine culture method. With the goal of ultimately improving urogynecological practice, and with the help of our colleagues in the Loyola Urinary Education and Research Collaborative (LUEREC), we decided to test the sterile bladder hypothesis by seeking evidence of bacteria in urine taken directly from the bladder to avoid vulva-vaginal contamination. To detect bacterial DNA, we used high-throughput DNA sequencing technology. To detect live bacteria, we developed an Expanded Quantitative Urine Culture (EQUC) protocol. We applied these complementary approaches to women with and without urgency urinary incontinence (UUI) whose standard clinical urine culture was negative. Medical Research: What are the main findings? Dr. Wolfe: First and foremost, the bladder is not sterile. We can detect bacteria and/or bacterial DNA in most women whether they have urgency urinary incontinence (UUI) or not. Thus, the female bladder contains a resident bacterial community, which we call the female urinary microbiome (FUM). We found that bacterial members of the FUM are distinct from the bacteria that typically cause urinary tract infections (UTI). Thus, the bacteria that make up the FUM are not the bacteria that cause typical UTIs. Indeed, detection of the female urinary microbiome was associated with reduced risk of UTIs that often occur after instrumentation or surgery. We therefore hypothesize that the FUM or some members of the FUM could protect against UTI. We also saw that the FUM in women with UUI differs from the FUM in women without UUI and that certain bacterial species were considerably more common in women with urgency urinary incontinence than in women without urgency urinary incontinence . We hypothesize that some of these bacteria could be causative or contributory to UUI or they could be a consequence of urgency urinary incontinence.
Author Interviews, FDA, Infections, Johns Hopkins / 01.04.2015

MedicalResearch.com Interview with: Benjamin Davis BA CLF-Lerner Fellow at the Johns Hopkins Center for a Livable Future. Medical Research: What is the background for this study? What are the main findings? Response: The Food and Drug Administration banned the inter-state sale of raw (i.e. unpasteurized) milk in 1987. Currently 30 states still allow raw milk sales on local farms or in stores. We were requested by the Maryland General Assembly's Health and Government Operations Committee to conduct a review of the health benefits and risks of raw versus pasteurized milk in response to proposed legislation that would legalize raw milk in the state. After reviewing over 80 scientific articles we concluded that raw milk carries a substantially higher risk of foodborne illness when compared to pasteurized milk. However drinking raw milk may reduce allergies among children in rural settings.
Author Interviews, HIV, Race/Ethnic Diversity / 31.03.2015

MedicalResearch.com Interview with: Catherine R. Lesko, MPH Department of Epidemiology UNC School of Global Public Health Chapel Hill, NC Medical Research: What is the background for this study? What are the main findings? Response: There is a lot of evidence out there that HIV-infected minorities, and in particular, African Americans, experience higher morbidity and mortality than do their white, HIV-infected counterparts. This study looked at whether there were still differences in mortality among treated, HIV-infected adults, which was a crude attempt to control for differences in access to HIV-testing, HIV-care, and antiretroviral therapy - all things previously shown to contribute to racial disparities among people infected with HIV. Even among people who had initiated HIV therapy, we still found that black patients had a 10-year risk of mortality that was 8 percentage points greater than white patients. Hispanic patients did marginally better than white patients, but not as much better as their non-HIV-infected counterparts.
Infections, Lancet, Pediatrics / 30.03.2015

[caption id="attachment_13089" align="alignleft" width="125"]Tuberculosis creates cavities visible in x-rays like this one in the patient's right upper lobe. Wikipedia Tuberculosis creates cavities visible in x-rays like this one in the patient's right upper lobe Wikipedia[/caption] MedicalResearch.com Interview with: Dr Anne K Detjen, MD Child Lung Health Consultant International Union Against Tuberculosis and Lung Disease Medical Research: What is the background for this study? What are the main findings? Dr. Detjen: The bacteriological diagnosis of tuberculosis (TB) in children is challenging due to the difficulty in obtaining specimens such as sputum and the lack of an accurate and accessible diagnostic test. In most cases, diagnosis is made on clinical grounds based on a contact history and a combination of signs and symptoms. We included 15 studies in a systematic review and meta-analysis of Xpert for the diagnosis of pulmonary TB in children. The accuracy of Xpert for diagnosing TB in children is suboptimal, and the majority of children will still have to be diagnosed clinically. However, in settings where it replaces smear microscopy Xpert will increase the likelihood of bacteriological confirmation of TB as well as MDR TB among children. Xpert does not increase the number of confirmed TB cases among culture-negative children. We also found that smear status highly impacted Xpert results, i.e. a higher yield among smear positive compared to smear negative children. Smear positivity increases with bacillary load and might be a proxy for disease severity. Unfortunately, we were not able to assess the performance among children with different stages of disease severity since this was not classified in any of the studies included.
Allergies, Author Interviews, Infections, Microbiome / 27.03.2015

Vijay R. Ramakrishnan, MD Assistant Professor University of Colorado Department of Otolaryngology Aurora, CO 80045MedicalResearch.com Interview with: Vijay R. Ramakrishnan, MD Assistant Professor University of Colorado Department of Otolaryngology Aurora, CO 80045 Medical Research: What is the background for this study? What are the main findings? Dr. Ramakrishnan: Chronic rhinosinusitis (CRS) is an extremely common problem, associated with major quality of life alterations and financial burden. Bacteria are thought to play a role in the initiation or sustenance of the disease, at least in a subset of CRS patients. Chronic rhinosinusitis is probably a group of heterogeneous diseases with different pathways that result in the same endpoint. Here, we study the bacterial microbiome of a large group of CRS and healthy sinuses, and discover that a few clinical subtypes display unique bacterial microbiome profiles and that the microbiome may predict outcomes from severe Chronic rhinosinusitis patients electing to undergo surgery.
Author Interviews, CMAJ, Infections, Vaccine Studies / 27.03.2015

MedicalResearch.com Interview with: Dr Fiona McQuaid Clinical Research Fellow University of Oxford, United Kingdom Medical Research: What is the background for this study? Response: Meningococcal B disease is a common cause of sepsis and meningitis with significant mortality and morbidity. A multicomponent vaccine against serogroup B meningococcus has been licensed for use in the Europe, Australia, Canada and recently the USA (though only in the 10-25 years age group) but questions remain about how long the bactericidal antibodies induced by infant vaccination persist and the likely breath of strain coverage. This was a follow on study looking at a group of children aged 5 years who had been vaccinated as infants and a different group who were vaccinated for the first time at 5 years of age. Medical Research: What are the main findings? Response: The percentage of children with protective antibody levels who had been immunized as infants fell in the 20 months since their last immunization but this varied by the strain of meingococcus B tested and by the different infant/toddler vaccination schedules. The children who were vaccinated for the first time at 5 years of age showed a good antibody response, but most reported pain and redness around the site of vaccination and 4-10% had a fever.
Author Interviews, MRSA, NEJM / 20.03.2015

Loren G. Miller, M.D., M.P.H. Los Angeles Biomedical Research Institute (LA BioMed) Infectious Disease SpecialistMedicalResearch.com Interview with: Loren G. Miller, M.D., M.P.H. Los Angeles Biomedical Research Institute (LA BioMed) Infectious Disease Specialist   Medical Research: What is the background for this study? Dr. Miller: Skin and skin structure infections are extremely common reasons for persons to seek medical care in the U.S., accounting for approximately 14.2 million outpatient visits in 2005, the latest year for which statistics are available, and 850,000 hospital admissions. Until this study was completed, the most effective approach to outpatient antibiotic treatment of uncomplicated skin infections in the era of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) was unclear. Prior to this research, there were no data on which antibiotics were best for treatment of these common skin infections. Medical Research: What are the main findings? Dr. Miller: Two antibiotics frequently prescribed to treat serious skin infections - clindamycin and trimethoprim sulfamethoxazole (TMP-SMX) - had similar rates of success in curing uncomplicated infections in outpatients. They also had similar rates of side effects. To conduct the study, we recruited outpatients from emergency departments, clinics and other healthcare facilities associated with Los Angeles County's Harbor-UCLA Medical Center, University of Chicago Medical Center, San Francisco General Hospital and Vanderbilt University Medical Center from May 2009 to August 2011. We studied 524 adults and children with uncomplicated skin infections who had cellulitis, abscesses of 5 centimeters or more or both. In the multicenter, double blind, randomized clinical trial, 264 received clindamycin and 260 received TMP-SMX. We followed the outpatients for a month after their treatment. We found similar outcomes for both groups - 80.3% of the outpatients who received clindamycin and 77.7% of the outpatients in the group that received TMP-SMX were cured within seven to 10 days after the end of their treatment. These are not considered significant differences, so our evaluation is that these two commonly prescribed antibiotics for serious skin infections are similarly effective in treating uncomplicated skin infections in children and adults who have few or no major co-existing conditions.
Author Interviews, Infections, JAMA, University of Michigan / 17.03.2015

Lona Mody, MBBS, MSc Associate Division Chief, Clinical and Translational Research Associate Director, Clinical Programs, VA GRECC Associate Professor, Internal Medicine Research Associate Professor, Institute of Gerontology University of Michigan Geriatrics Ann Arbor, MIMedicalResearch.com Interview with: Lona Mody, MBBS, MSc Associate Division Chief, Clinical and Translational Research Associate Director, Clinical Programs, VA GRECC Associate Professor, Internal Medicine Research Associate Professor, Institute of Gerontology University of Michigan Geriatrics Ann Arbor, MI Medical Research: What is the background for this study? What are the main findings? Response: Over 1.5 million residents live in 15,600 Nursing Homes in the US. The acuity of illness in this population has increased substantially in the last decade, as has the risk of acquiring new infections. Multi-drug resistant organisms, also known as MDROs, are endemic in this setting with prevalence estimates upwards of 35% and surpassing those in the hospitals. Nursing homes historically have had few infection prevention resources, which contributes to these high rates. Patients with indwelling devices such as urinary catheters and feeding tubes present an attractive habitat for these ‘superbugs’ and thus carry the added burden of device-related infections. The authors examined the effect of a targeted infection program, or TIP, to reduce the prevalence of Multi-drug resistant organisms and new catheter or feeding tube infections among patients with indwelling devices. The TIP intervention was three-fold:
  1. Surveillance for infections and Multi-drug resistant organism colonization with regular feedback to facilities;
  2. Extensive and interactive staff education using adult learning theory about key infection prevention practices and hand hygiene; and
  3. Use of gowns and gown when providing assistance to patients for high-risk activities such as bathing and grooming.
Staff education emphasized precautionary measures against the spread of infection and included mock game shows, songs and dances. Hands were cultured for bacteria before and after hand washing. Outcomes were measured by results of the cultures taken for each patient and monitoring infection rates. A team of researchers from the University of Michigan and the Veterans Affairs Ann Arbor Health System has demonstrated that simple measures might be all it takes to push back at the spread of Multi-drug resistant organisms or ‘superbugs’ in nursing homes as well as reduce infections. In their study of patients with indwelling devices, MDROs were reduced by 23 percent among 418 residents in six southeast Michigan nursing homes who participated over the course of the three-year study. The numbers of catheter-associated urinary tract infections and MRSA acquisitions also decreased, 46 percent and 22 percent respectively. The trial examined the relationship between acquisition of antimicrobial resistance among nursing home and assisted living facility residents with the use of devices by adapting new methodological approaches and study designs to study infection prevention interventions including the use of cluster-randomized study design for infection prevention interventions, adopting adult learning practices to engage frontline healthcare personnel and using multi-anatomic site sampling to demonstrate effectiveness of the program.
Annals Internal Medicine, Author Interviews, CDC, Infections / 17.03.2015

MedicalResearch.com Interview with: Dr.Yecai Liu Division of Global Migration and Quarantine Centers for Disease Control and Prevention, Atlanta, Georgia Medical Research: What is the background for this study? What are the main findings? Response: Since the early 1900s, immigrants and refugees applying for a visa to come to the United States undergo a medical examination that includes tuberculosis (TB) screening. In 2007, CDC began implementing the new screening guidelines, which require people suspected of having TB to receive a much more sensitive sputum culture test to confirm TB to ensure that those individuals who do have TB receive treatment before they arrive in the United States. These requirements have now been completely rolled out to all countries with U.S.-bound immigrants and refugees. From 2007 through 2012, half of the 3.2 million arrivals of immigrants and refugees to the United States were screened for TB by the new screening guidelines. Out of more than 4,000 TB cases diagnosed by the new screening guidelines during this period, nearly 2,200 were smear-negative and culture positive. These cases would likely have been missed under the previous screening requirements. The results of this study showed that the updated overseas screening guidelines led to a roughly one-third decrease in the annual number of TB cases among foreign-born persons within their first year in the United States.
Author Interviews, Dermatology, Infections, JAMA / 15.03.2015

MedicalResearch.com Interview with: Dr. Ana Ramírez-Boscá, MD Department of Dermatology and Clinical Research UnitDr. Ana Ramírez-Boscá, MD Department of Dermatology and Clinical Research Unit and Vicente Navarro-López, MD Clinical Research Unit and Infectious Diseases Unit Centro Dermatológico Estético, Alicante, SpainVicente Navarro-López, MD Clinical Research Unit and Infectious Diseases Unit Centro Dermatológico Estético, Alicante, Spain   MedicalResearch: What is the background for this study? What are the main findings? Response: Infections have been related with the pathogenesis of guttate psoriasis, however antibiotic treatment does not improve prognosis nor does it affect the evolution of the disease. The association between psoriasis and other infectious diseases has been reported as well, although in these cases there is scarce information on the causative microbial likely involved and the role of these bacteria in the pathogenesis of this skin disease. MedicalResearch: What are the main findings?  Response: Bacterial DNA may be detected in bloodstream of a significant proportion of patients with active plaque psoriasis. Increased levels of pro-inflammatory cytokines in patients with presence of bacterial DNA but not in patients without presence of bacterial genomic fragments suggest a role of bacterial DNA translocation in inducing an inflammatory response. [caption id="attachment_12680" align="alignleft" width="300"]"Guttate psoriasis" by Bobjgalindo - Own work. Licensed under GFDL via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:Guttate_psoriasis.jpg#/media/File:Guttate_psoriasis.jpg Guttate Psoriasis
from Wikipedia[/caption]
Author Interviews, Critical Care - Intensive Care - ICUs, Hospital Readmissions, Infections, JAMA, University of Michigan / 11.03.2015

Hallie Prescott, MD, MSc Clinical Lecturer, Internal Medicine Division of Pulmonary & Critical Care Medicine University of Michigan Health System Ann Arbor, MI 48109-2800MedicalResearch.com Interview with: Hallie Prescott, MD, MSc Clinical Lecturer, Internal Medicine Division of Pulmonary & Critical Care Medicine University of Michigan Health System Ann Arbor, MI 48109-2800   Medical Research: What is the background for this study? What are the main findings? Dr. Prescott: The post-hospital period has been widely recognized as a vulnerable time for patients. In particular, patients who survive sepsis are frequently readmitted to the hospital in the following three months. In this study, we examined data from 2,600 survivors of sepsis, a severe infection that leads to organ failure. About 42% of the sepsis patients were readmitted in the next 90 days, similar to the rate seen for patients hospitalized for other acute conditions. However, the reasons for hospital readmission after sepsis are different. A greater number of patients are re-hospitalized for “ambulatory-care sensitive conditions”, which are conditions that could potentially be prevented or treated early in the outpatient setting to avoid a hospital stay.
Author Interviews, Infections / 09.03.2015

Dr. Grant Hansman CHS Research Group at CellNetworks Heidelberg University and DKFZ Deutsches Krebsforschungszentrum Heidelberg GermanyMedicalResearch.com Interview with: Dr. Grant Hansman CHS Research Group at CellNetworks Heidelberg University and DKFZ Deutsches Krebsforschungszentrum Heidelberg Germany Medical Research: What is the background for this study? What are the main findings? Dr. Hansman: Human noroviruses are the major cause of outbreaks of acute gastroenteritis. There are several promising vaccine candidates. Vaccines may offer some protection, but the fact that the virus changes every other year produces a challenge. Therefore, my research group investigates the possibility to produce universal antivirals targeting conserved regions on the virus capsid. We found that a Nanobody was able to bind with a high affinity, and broad reactivity to diverse norovirus types. The Nanobody binding on the virus capsid caused the virus particles to disassemble. The disassembly of the particles may render the virus non-infectious and block viral infections.
Author Interviews, Herpes Viruses, Pediatrics, Pediatrics, Vaccine Studies / 07.03.2015

MedicalResearch.com Interview with: Su-Ying Wen, MD Chief of Department of Dermatology, Taipei City Hospital, Renai Branch, Taipei City, Taiwan Department of Dermatology, Taipei City Hospital, Renai Branch, Taipei City, Taiwan Medical Research: What is the background for this study? What are the main findings? Dr. Su-Ying Wen: Though herpes zoster is seen as a disease of the elderly, it can affect individuals in any age group including children. There are limited population-based data regarding pediatric herpes zoster. We reported a higher incidence rate of pediatric herpes zoster than in previous studies. The higher incidence observed in this population-based study might be because it was measured in a cohort of children who were all infected with varicella rather than as other reports including individuals free of varicella infection in the denominator. Children younger than 2 years at the diagnosis of varicella had a significantly higher risk and shorter duration of developing herpes zoster.
Author Interviews, CDC, HIV, Race/Ethnic Diversity, Sexual Health / 05.03.2015

MedicalResearch.com Interview with: Cyprian Wejnert Center For Disease Control MedicalResearch: What is the background for this study? What are the main findings? Cyprian Wejnert: Men who have sex with men (MSM) remain the risk group most severely affected by HIV in the United States, accounting for approximately two-thirds of new infections each year.  Understanding racial and age disparities among MSM is critical to tailor effective prevention efforts. Our study examined data from CDC’s National HIV Behavioral Surveillance system (NHBS) from 20 U.S. cities. We assessed changes in HIV prevalence, awareness of infection, and risk behavior among MSM, by age and race, from 2008 to 2011, finding that: o   Among black Men who have sex with men, 30 percent were HIV-infected overall, and 1 in 5 black MSM aged 18-24 were infected with HIV. Compared to 14 percent and 4 percent among white MSM. o   In all age groups younger than 40 years, black Men who have sex with men were significantly more likely to be HIV-positive compared to all other racial/ethnic groups. o   Disparities in HIV prevalence between black and white MSM were greatest among the youngest MSM, and increased between 2008 and 2011. o   Black MSM were less likely to be aware of their infection than their white counterparts (54 vs. 86 percent). o   Black Men who have sex with men did not report higher levels of condomless sex overall or condomless sex with partners of discordant or unknown HIV status.
Author Interviews, CDC, Gender Differences, HIV, Race/Ethnic Diversity / 05.03.2015

MedicalResearch.com Interview with: Dr. Ndidi Nwangwu-Ike Center Disease Control MedicalResearch: What is the background for this study? What are the main findings? Response: CDC data has shown encouraging signs of a decrease in new HIV infections among black women in recent years.  However, African American women continue to be far more affected by HIV than women of any other race or ethnicity, with a rate of new infection 20 times that of white women and nearly five times that of Hispanic women.  Ensuring people with HIV are diagnosed and remain in care is key to controlling HIV in the nation. When used consistently, antiretroviral medication can keep HIV controlled at very low levels in the body (known as viral suppression), allowing people with HIV to live longer, healthier lives and reducing the likelihood they will transmit HIV to others. Our study finds that viral suppression among women diagnosed with HIV is low, with young women and black women the least likely to achieve viral suppression. Specifically, we found that: o   Of women newly diagnosed with HIV in 2012, 83 percent were linked to care within three months of diagnosis. o   Retention in care varied by age and race/ethnicity; overall, just over half of women (52 percent) diagnosed and living with HIV in 2011 received ongoing HIV care. o   Overall, only 44 percent of women diagnosed and living with HIV in 2011 had a suppressed viral load.
Author Interviews, HPV, Lancet, Vaccine Studies / 05.03.2015

MedicalResearch.com Interview with: Marc Brisson Canada Research Chair in Mathematical Modeling and Health Economics of Infectious Disease Associate Professor, Université LavalMedicalResearch.com Interview with: Marc Brisson Canada Research Chair in Mathematical Modeling and Health Economics of Infectious Disease Associate Professor, Université Laval Medical Research: What is the background for this study? What are the main findings? Response: Since 2007, 52 countries have implemented human papillomavirus vaccination (HPV) programmes. Two HPV vaccines are currently available worldwide: the bivalent vaccine, which targets HPV types 16 and 18, causing 70-80% of cervical cancer, and the quadrivalent vaccine, which also targets HPV types 6 and 11, associated with 85-95% of anogenital wart cases. Large international randomised controlled clinical trials have shown both vaccines to be safe, well tolerated and highly efficacious against vaccine-type persistent infections and precancerous cervical lesions.  Furthermore, both vaccines have shown some level of cross-protection against 3 HPV types (HPV 31, 33 and 45) not included in the vaccine and associated with a supplementary 10-15% of cervical cancers worldwide. Now that 7 years have elapsed since the implementation of the first HPV vaccination program, we verified whether the promising results from clinical trials are materialising at the population level. We conducted a meta-analysis to examine the population-level impact in countries that have introduced HPV vaccination programs. In countries with high female vaccination coverage (<50%), our main findings indicate:
  • sharp declines in HPV-related outcomes among females targeted for vaccination (e.g., HPV-16/18 infection and anogenital warts declined by more than 60% in females younger than 20 years), and
  • evidence of cross-protection with significant reductions in HPV-31/33/45 infection among females younger than 20 years
  • evidence of herd effects (indirect benefit of vaccination among unvaccinated individuals) with significant reductions in anogenital warts among males and older females.
In countries with low coverage (<50%), we report:
  • significant reductions in HPV-16/18 infection and anogenital warts among young females, with no indication of herd effects or cross-protection.
Author Interviews, HIV, Nature, Scripps / 04.03.2015

Dr. Michael Farzan PhD Vice Chairman Department of Immunology and Microbial Science Florida Campus The Scripps Research InstituteMedicalResearch.com Interview with: Dr. Michael Farzan PhD Vice Chairman Department of Immunology and Microbial Science Florida Campus The Scripps Research Institute Medical Research: What is the background for this study? Dr. Farzan: The key points are that HIV-1 needs two receptors – CD4 and CCR5 – to infect cells.  CD4’s primary job is to initially bind the viral entry protein, which upon CD4 binding, uncloaks its CCR5 binding site.   A number of years ago we observed that CCR5 had an unusual modification that was really important to HIV-1.  We later showed that antibodies – protein your body makes to protect from pathogens – mimics CCR5 by incorporating this modification.  We develop a peptide from one of these antibodies that mimics CCR5. Medical Research: What are the main findings? Dr. Farzan: By combined a soluble form of CD4 with this CCR5-mimicking peptide, we created a protein that neutralizes all HIV-1 isolates tested, including the hardest-to-stop viruses, as well as distantly related viruses found in monkeys.  It does so better than the best HIV-1 antibodies.  We expressed this protein using a commonly used gene-therapy vector, and showed that after a one-time inoculation we could protect from doses much higher than most humans are likely to see, and we did so 34 weeks after the inoculation.
Author Interviews, HPV, Vaccine Studies / 28.02.2015

MedicalResearch.com Interview Invitation Frank Struyf MD PhD Director, Lead Clinical Development HPV vaccines at GlaxoSmithKline Biologicals GlaxoSmithKline Vaccines, Rixensart, Belgium MedicalResearch: What is the background for this study? What are the main findings? Dr. Struyf: Cervical cancer is the fourth most common cancer among women, with estimates from 2012 indicating that there are 528,000 new cases and 266,000 deaths each year worldwide, the majority of cases occurring in developing countries (reference: Globocan 2012 at http://globocan.iarc.fr/old/FactSheets/cancers/cervix-new.asp). Persistent infection with oncogenic human papillomavirus (HPV) is a necessary condition for the development of invasive cervical cancer. HPV type 16 (HPV-16) and HPV-18 are found in approximately 70% of cases. We conducted the Papilloma Trial Against Cancer in Young Adults (PATRICIA), a multinational clinical trial in 14 countries in Europe, the Asia-Pacific region, North America, and Latin America and enrolled over 18,000 women. The trial showed that the HPV-16/18 AS04-adjuvanted vaccine not only prevented persistent infections and high-grade cervical lesions associated with HPV types 16 and/or 18 included in the vaccine, but also protected against some common related oncogenic HPV types not included in the vaccine. However, during the analysis of this trial, we also noticed that for some rare nonvaccine oncogenic HPV types, the vaccine efficacy against infections did not seem to match the efficacy against lesions associated with the same HPV type. To investigate this, we re-analyzed the samples from the trial using a different PCR method and found that the HPV PCR methodology used per protocol may have underestimated the efficacy for non-vaccine HPV types in cases of multiple infections. While these results do not replace the results generated according to the study protocol and included in the product label, they are reassuring, as they confirm the cross-protective efficacy of the HPV-16/18 vaccine against some HPV types related to those included in the vaccine.
Author Interviews, Hepatitis - Liver Disease, HIV, JAMA, NIH / 28.02.2015

Shyamasundaran Kottilil MBBS, PhD University of MarylandMedicalResearch.com Interview with: Shyamasundaran Kottilil MBBS, PhD Division of Infectious Diseases, Institute of Human Virology, University of Maryland, Baltimore Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Medical Research: What is the background for this study? What are the main findings? Dr. Kottilil:  Due to shared routes of transmission, almost half of all HIV-infected patients also have HCV infection. Traditionally, interferon based therapies have resulted in lower cure rates of HCV in HIV-infected subjects. Treatment for HCV is rapidly changing from an injection (interferon) based therapy to oral well tolerated pill based therapy for a shorter duration.Our intention was to test whether a treatment regimen without the use of interferon and ribavirin can be effective in HIV/HCV infected patients. Our study demonstrated that HIV/HCV connected patients without cirrhosis can be effectively treated with ledipasvir and sofosbuvir in 12 weeks. Overall 98% of patients were cured.
Author Interviews, HPV, Vaccine Studies / 28.02.2015

Elmar A. Joura, M.D Gynecologist University of ViennaMedicalResearch.com Interview with: Elmar A. Joura, M.D Gynecologist University of Vienna MedicalResearch: What are the main findings of this study? Dr. Joura: This study demonstrates that the new ninevalent HPV vaccine induces a good immunogenicity against HPV 6/11/16/18 and gives a 97% protection against disease caused by HPV 31/33/45/52/58. This has a potential of a 90% reduction of cervical cancer and other HPV related cancers and a similar protection against genital warts. The full benefit is seen in persons without current HPV infection, this reinforces early vaccination against HPV. The safety profile was favourable.
Author Interviews, Infections, Lancet / 27.02.2015

Dr. Masae Kawamura MD Director and TB Controller City and County of San Francisco Department of Health Principal investigator for the Regional TB Training and Medical Consultation CenterMedicalResearch.com Interview with: Dr. Masae Kawamura MD Senior Director, QuantiFERON Medical and Scientific Affairs QIAGEN MedicalResearch: What is the background for this study? What are the main findings? Dr. Kawamura:  The report in The Lancet presents the baseline phase of China’s first large-scale, multi-center prospective study of the epidemiology of latent tuberculosis infection. The comparison study of more than 21,000 patients allowed detailed analysis of demographics and risk factors, along with robust comparisons within subgroups. The study’s follow-up phase is now underway, and patients with Latent Tuberculosis Infection (LTBI) will be evaluated for rates of disease and associated risks. Generally, up to 10% of people with Latent Tuberculosis Infection will develop active, contagious Tuberculosis (TB) disease at some point. The overall TB infection rate was 18.8% measured by QuantiFERON-TB Gold compared to 28% by the traditional tuberculin skin test (TST), a difference of over 125 million people (based on 2014 population estimates from China). Unlike the tuberculin skin test, positive rates of QuantiFERON-TB Gold were not related to prior Bacille Calmette-Guérin (BCG) vaccination, but correlated with background active TB and suspect rates, as well as known risks for TB. BCG vaccination is recommended to newborns by the World Health Organization (WHO) as a matter of TB control policy in many countries, including China.        
Author Interviews, CDC, NEJM, Pediatrics, Respiratory / 27.02.2015

Seema Jain, MD Medical Epidemiologist Epidemiology and Prevention Branch, Influenza Division Centers for Disease Control and Prevention Atlanta, GA 30329MedicalResearch.com Interview with: Seema Jain, MD Medical Epidemiologist Epidemiology and Prevention Branch, Influenza Division Centers for Disease Control and Prevention Atlanta, GA 30329 MedicalResearch: What is the background for this study? What are the main findings? Dr. Jain: Pneumonia is the leading cause of hospitalization among children in the United States with medical costs estimated at almost $1 billion in 2009.  The Centers for Disease Control and Prevention’s Etiology of Pneumonia in the Community (EPIC) study was a multi-center, active population-based surveillance study that aimed to estimate the incidence and etiology of community-acquired pneumonia requiring hospitalization in U.S. children.  Children in the study were enrolled from January 2010 to June 2012 in three U.S. children’s hospitals in Memphis, Nashville, and Salt Lake City. Study staff tested children using a range of laboratory tests for viral and bacterial respiratory pathogen detection. During the study period, the EPIC study team enrolled 2,638 children, of which 2,358 (89 percent) had radiographically-confirmed pneumonia. The median age of children in the study was 2 years old. Intensive care was required for 497 (21 percent) of the children, and three children died.  Among 2,222 children with radiographic pneumonia and specimens available for both bacterial and viral testing, a pathogen was detected in 1802 (81%).  One or more viruses were detected in 1,472 (66%) of these children.  Bacteria were detected in 175 (8%), and bacterial and viral co-detection occurred in 155 (7%).  The study estimated that annual pneumonia incidence was 15.7/10,000 children during the study period.  The highest incidence was among children younger than 2 years old (62.2/10,000).  Respiratory syncytial virus (RSV) was the most common pathogen detected (28%), and it was associated with the highest incidence among children younger than 2 years old with pneumonia.  Human rhinovirus was detected in 22 percent of cases, but it was also identified in 17 percent of asymptomatic controls who were enrolled, by convenience sample, at the same site during the same time period; thus, making it challenging to interpret the meaning of human rhinovirus detection in children hospitalized with pneumonia.  Other detected pathogens were human metapneumovirus (13%), adenovirus (11%), Mycoplasma pneumoniae (8%), parainfluenza viruses (7%), influenza (7%), coronaviruses (5%), Streptococcus pneumoniae (4%), Staphylococcus aureus (1%), and Streptococcus pyogenes (<1%).  The low prevalence of bacterial detections likely reflects both the effectiveness of bacterial conjugate vaccines and suboptimal sensitivity of bacterial diagnostic tests.
Author Interviews, C. difficile, CDC, Hand Washing, Outcomes & Safety / 26.02.2015

Fernanda C. Lessa, M.D., M.P.H. Centers for Disease Control and Prevention Atlanta, GAMedicalResearch.com Interview with: Fernanda C. Lessa, M.D., M.P.H. Centers for Disease Control and Prevention Atlanta, GA MedicalResearch: What is the background for this study? What are the main findings? Dr. Lessa: The epidemiology of Clostridium difficile has gone through dramatic changes over the last decade. C. difficile has become the most common cause of healthcare-associated infections in US hospitals and it has been also increasingly reported outside of healthcare settings. As the epidemiology of this pathogen changes, it is important to understand the magnitude and scope of this infection in the United States to help guide priorities for prevention. Main findings: 1)      C. difficile was responsible for almost half million infections and associated with 29,000 deaths in 2011 in the United States 2)      Among the patients who developed C. difficile, 83,000 had recurrent infections 3)      C. difficile incidence was higher among females, whites, and persons 65 years of age or older 4)       Approximately 345,400 infections occurred outside of the hospital indicating that C. difficile prevention should go beyond hospital settings.