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, Breast Cancer, Chemotherapy, Cleveland Clinic, NEJM / 04.03.2015

Halle C.F. Moore, M.D. Cleveland Clinic Foundation Taussig Cancer Institute Cleveland, OH 44195MedicalResearch.com Interview with: Halle C.F. Moore, M.D. Cleveland Clinic Foundation Taussig Cancer Institute Cleveland, OH 44195 Medical Research: What is the background for this study? What are the main findings? Dr. Moore: Ovarian failure is a common long-term side effect of chemotherapy. Previous studies investigating whether suppressing ovarian function during chemotherapy treatment will preserve ovarian function following chemotherapy have had mixed results. Our study found that suppressing the ovaries with the GnRH analog goserelin during chemotherapy treatment for early stage ER-negative breast cancer resulted in a reduced risk of ovarian failure two years after initiation of treatment. Also, more women who received the goserelin with chemotherapy became pregnant than women who received chemotherapy without goserelin. In addition, there was an apparent improvement in survival among the goserelin group, confirming the safety of this approach in this patient population.
Author Interviews, Breast Cancer, Chemotherapy, Lancet / 04.03.2015

MedicalResearch.com Interview with: Dr. Lucia Del Mastro MD Department of Medical Oncology Istituto Nazionale per la Ricerca sul Cancro Genova, Italy Medical Research: What is the background for this study? What are the main findings? Response: Adjuvant chemotherapy regimens with anthracyclines and taxanes improve the outcome of patients with early breast cancer. Among the most widely used anthracycline-based chemotherapy in sequential combinations with the taxane paclitaxel (P) there are epirubicin and cyclophosphamide (EC) and fluorouracil, epirubicin, and cyclophosphamide (FEC). The contribution of fluorouracil to the anthracycline-cyclophosphamide regimen (EC) was unclear until now. Various randomized trials attempted to assess the role of a more intense schedule of chemotherapy (i.e. dose-dense chemotherapy with cycles administered every 2 weeks instead of every 3 weeks) in patients with early breast cancer. However, most of these trials compared dose-dense chemotherapy with regimens that use standard intervals but with different drugs or dose in the treatment groups, thus making difficult to extrapolate the true role of the dose-dense strategy. The results of GIM2 study show that the addition of fluorouracil to  a sequential regimen with epirubicin, cyclophosphamide and paclitaxel increases the toxicity, in terms of neutropenia, fever, nausea, and vomiting, and is not associated with an improved outcome compared with the same treatment without fluorouracil.
Author Interviews, Genetic Research, Nature / 04.03.2015

Fernando Pardo-Manuel De Villena, PhD Professor and Associate Chair for Research Department of Genetics School of Medicine University of North Carolina at Chapel HMedicalResearch.com Interview with: Fernando Pardo-Manuel De Villena, PhD Professor and Associate Chair for Research Department of Genetics School of Medicine University of North Carolina at Chapel Hill Medical Research: What is the background for this study? What are the main findings? Response: We set out to identify mutations that affect diseases through changes in gene expression. Our first major finding is that some mouse populations such as the Collabaorative Cross are exceptionally good models to achieve this goal. We also wanted to sort out an ongoing controversy about the number, location and type of genes that are differentially expressed when you inherit them from your mom or your dad (so called imprinted genes).  We conclude that to some extent both sides were right; there are only a limited number of imprinted genes in the classical sense but there are also hundreds or thousands of genes that are preferentially expressed from the father.
Author Interviews, Cancer Research, MD Anderson, PNAS / 04.03.2015

MedicalResearch.com Interview with: Kristen Turner PhD. (first author) and Wei Zhang, Ph.D. Professor Department of Pathology Director, Cancer Genomics Core Lab University of Texas MD Anderson Cancer Center Houston, Texas 77030 Medical Research: What is the background for this study? What are the main findings? Response: Glioblastoma (GBM) is the most commonly diagnosed type of brain tumor and is among the most aggressive and challenging cancer types to treat. The traditional approaches to combat this pervasive cancer include surgery combined with radiation and chemotherapy (temozolomide); yet, most will succumb to the disease in just over one year. In this study, we investigated the Akt family of proteins that are known to be highly active in the majority of Glioblastoma cases. We compared each Akt family member and its ability to initiate glioma progression. We discovered that activation of the third Akt member (Akt3) led to glioma progression and very aggressive tumors. We then studied these tumors to compare their molecular attributes and found evidence of increased DNA repair. Finally, we discovered that the Akt3-induced DNA repair function led to increased survival of Glioblastoma cells after treatment with the DNA damaging agents, radiation and temozolomide.
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, BMJ, End of Life Care, Heart Disease / 04.03.2015

MedicalResearch.com Interview with: Prof. Dr. med. Paul Erne AMIS Plus Data Center, Epidemiology, Biostatistics and Prevention Institute University of Zurich Department of Cardiology Clinic St. Anna, Lucerne and University Hospital Zurich Zurich, SwitzerlandProf. Dr. med. Paul Erne AMIS Plus Data Center, Epidemiology, Biostatistics and Prevention Institute University of Zurich Department of Cardiology Clinic St. Anna, Lucerne and University Hospital Zurich Zurich, Switzerland MedicalResearch: What is the background for this study? What are the main findings? Prof. Erne: Very little is known on this important subgroup of patients with Acute Coronary Syndrome (ACS) at admission who for various reasons receive restricted or palliative treatment only. Reasons for withholding comprehensive and/or invasive therapy may be the very limited life expectancy, advanced age or severe comorbidities. These patients are not represented in prospective trials and often not included in outcome statistics and registries. This study provides evidence that the population which received palliative therapy is older and sicker when compared to patients who underwent conservative or reperfusion treatment. However, this study shows that these decisions are very individually addressed. Acute Coronary Syndrome patients treated palliatively were older, sicker, with more heart failure at admission and very high in-hospital mortality. Changes of treatment decisions over time and the proportion of patients surviving 1 year suggest in part non homogenous and potentially questionable decision criteria. While refraining from more active therapy may be the most humane and appropriate approach in many patients, in others it represents under treatment.
Author Interviews, PNAS, Statins / 04.03.2015

Professor Andrew W. Munro FRSC FSB Professor of Molecular Enzymology Manchester Institute of Biotechnology Faculty of Life Sciences University of Manchester Manchester UKMedicalResearch.com Interview with: Professor Andrew W. Munro FRSC FSB Professor of Molecular Enzymology Manchester Institute of Biotechnology Faculty of Life Sciences University of Manchester Manchester UK MedicalResearch: What is the background for this study? What are the main findings? Dr. Munro: Statins are blockbuster drugs that inhibit the key enzyme in cholesterol synthesis: 3-beta-hydroxymethylglutaryl CoA reductase (HMG-CoA reductase), which catalyzes the rate-limiting step in the biosynthesis of cholesterol. As a consequence, statin drugs reduce levels of low-density lipoprotein (LDL-) cholesterol, are effective against hypercholesterolemia and reduce the risk of atherosclerosis and heart attack. One of the major statin drugs is pravastatin, which is derived from a fungal natural product called compactin. The process of conversion of compactin into pravastatin involves the use of an oxygen-inserting enzyme called a cytochrome P450 (or P450), which catalyzes the hydroxylation of compactin to form pravastatin. In order to produce a more cost-efficient and streamlined route to pravastatin production, our teams from the University of Manchester (UK) and DSM (Delft, The Netherlands) developed a single-step process for pravastatin production. This process involved harnessing the productive efficiency of an industrial strain of the beta-lactam (penicillin-type) antibiotic producing fungus Penicillium chrysogenum. The beta-lactam antibiotic genes were deleted from this organism, and replaced by those encoding for compactin biosynthesis (transferred from a different Penicillium species). This led to high level production of compactin, but also to substantial formation of a partially degraded (deacylated) form. To get around this problem and in order to further improve compactin production, the enzyme responsible for the deacylation (an esterase) was identified and the gene encoding this activity was deleted from the production strain. The final stages of development of the novel, one-step pravastatin production process involved the identification of a suitable P450 enzyme that could catalyze the required hydroxylation of compactin. A bacterial P450 was identified that catalyzed hydroxylation at the correct position on the compactin molecule. However, the stereoselectivity of the reaction was in favour of the incorrect isomer – forming predominantly epi-pravastatin over the desired pravastatin. This was addressed by mutagenesis of the P450 – ultimately leading to a variant (named P450Prava) that hydroxylated compactin with the required stereoselectivity to make pravastatin in large amounts. Determination of the structure of P450Prava in both the substrate-free and compactin-bound forms revealed the conformational changes that underpinned the conversion of the P450 enzyme to a pravastatin synthase. The expression of P450Prava in a compactin-producing strain of P. chrysogenum enabled pravastatin production at over 6 g/L in a fed-batch fermentation process, facilitating an efficient, single-step route to high yield generation of pravastatin.
Accidents & Violence, Author Interviews, JAMA, Pediatrics / 03.03.2015

MedicalResearch.com Interview with: Dr. Kevin Vagi, Ph.D Division of Violence Prevention, CDC’s Injury Center. MedicalResearch: What is the background for this study? What are the main findings? Dr. Vagi: Although there has been research on teen dating violence (TDV) for several decades, the subject has only received attention as a public health concern in recent years. Over time, prevalence estimates of physical teen dating violence victimization from CDC’s national Youth Risk Behavior Survey (YRBS) (first measured in 1999) have remained around 9% with similar rates among female and male students. Until recently, there have been no ongoing national studies of sexual TDV to our knowledge. This article describes new physical and sexual teen dating violence victimization questions first administered in the 2013 YRBS, shares the prevalence and frequency of TDV and national estimates using these new questions, and assesses associations of teen dating violence experience with health-risk behaviors. By including questions on both physical and sexual TDV, we are able to look at those youth who experienced physical TDV only, sexual TDV only, both physical and sexual TDV, any TDV, and none. These distinctions were important when investigating health outcomes associated with different types or combinations of TDV, as some health-risk behaviors have been shown to be associated with certain types of teen dating violence but not others. In 2013, among high school students who dated, 1 in 5 females and 1 in 10 males experienced physical and/or sexual TDV in the 12 months before the survey. The majority of students who experienced physical and sexual teen dating violence experience it more than once. Students who experienced both physical and sexual TDV are more likely to have other health-risks, such as suicidal ideation and behavior, fighting, carrying a weapon, being electronically bullied, alcohol and drug use, and risky sexual behaviors. This report also offers the first national estimate of sexual TDV. Findings suggest that comprehensive prevention efforts should focus on helping students develop healthy relationship skills to prevent teen dating violence and other risk behaviors.
Author Interviews, Brigham & Women's - Harvard, JAMA, Kidney Disease / 03.03.2015

Mallika L. Mendu, MD, MBA Division of Renal Medicine Brigham and Women’s Hospital, Harvard Medical School Boston, MAMedicalResearch.com Interview with: Mallika L. Mendu, MD, MBA Division of Renal Medicine Brigham and Women’s Hospital, Harvard Medical School Boston, MA MedicalResearch: What is the background for this study? What are the main findings? Dr. Mendu: Chronic kidney disease affects a significant number of adults in the United States, approximately 13%, and is associated with significant morbidity, mortality and cost. We conducted a review of 1487 patients referred for initial evaluation of chronic kidney disease to two academic medical centers in Boston over a 3-year period, and examined how often laboratory and imaging tests were ordered and how often these tests affected diagnosis and/or management. The main finding was that a number of tests (renal ultrasound, paraprotein testing, serologic testing) were commonly ordered despite low diagnostic and management yield. Urine quantification and hemoglobin A1c testing had the highest diagnostic and management yield.
Author Interviews, Blood Pressure - Hypertension, Cognitive Issues, Geriatrics, JAMA / 03.03.2015

MedicalResearch.com Interview with: Dr. Enrico Mossello Research Unit of Medicine of Ageing Department of Experimental and Clinical Medicine University of Florence MedicalResearch: What is the background for this study? What are the main findings? Dr. Mossello: In spite of the high prevalence of high blood pressure (HBP) and cognitive impairment in old age, their relationship is still controversial. While several (but not all) studies have identified high blood pressure as a risk factor for incident cognitive impairment, evidence regarding the prognostic role of blood pressure in cognitively impaired older subjects is scarce and inconsistent. To our knowledge, no longitudinal study has been published up to now regarding Ambulatory Blood Pressure Monitoring (ABPM) in subjects with cognitive impairment. Moreover recent European and American guidelines on HBP leave decisions on antihypertensive therapy of frail elderly patients to the treating physician and do not provide treatment targets for cognitively impaired patients. In the present cohort study of subjects with dementia and Mild Cognitive Impairment (MCI) low values of day-time systolic blood pressure measured with ABPM were associated with greater progression of cognitive decline after a median 9-month follow-up. This association was limited to subjects treated with anti-hypertensive drugs and was independent of age, vascular comorbidity and baseline cognitive level, holding significant both in dementia and in Mild Cognitive Impairment subgroups. A similar trend of association was observed for office systolic blood pressure, although this was weaker and did not reach statistical significance in all analyses.
Author Interviews, Heart Disease, JAMA, Nutrition / 03.03.2015

Xiao-ou Shu M.D., MPH, Ph.D Associate Director of Global Health Co-Leader, Cancer Epidemiology Research Program Ingram Professor of Cancer Research Professor of Medicine (Epidemiology) Cancer EpidemiologistMedicalResearch.com Interview with: Xiao-ou Shu M.D., MPH, Ph.D Associate Director of Global Health Co-Leader, Cancer Epidemiology Research Program Ingram Professor of Cancer Research Professor of Medicine (Epidemiology) Cancer Epidemiologist MedicalResearch: What is the background for this study? What are the main findings? Dr. Shu: Nuts are rich in nutrients, such as unsaturated fatty acids, fiber, vitamins, phenolic antioxidants, arginine, and other phytochemicals. These are all known to be beneficial to cardiovascular health, probably through their anti-oxidative, anti-inflammatory, and endothelial function maintenance properties.   Previous studies, primarily conducted in white and affluent populations, have shown that nut consumption may be related to cardiovascular health. Much of the nut consumption in those populations would be tree nuts. In our study, we found that peanut consumption was associated with reduced total mortality and CVD mortality in a predominantly low-income black and white population in the US, and among Chinese men and women living in Shanghai. Because peanuts are much less expensive than tree nuts, as well as more widely available to people of all races and all socioeconomic backgrounds, increasing peanut consumption may provide a potentially cost-efficient approach to improving cardiovascular health.
Author Interviews, JAMA, Pediatrics, Smoking / 03.03.2015

Rebecca S. Williams, MHS, PhD University of North Carolina at Chapel Hill Chapel Hill, NCMedicalResearch.com Interview with: Rebecca S. Williams, MHS, PhD University of North Carolina at Chapel Hill Chapel Hill, NC MedicalResearch: What is the background for this study?  Dr. Williams: In recent years, the e-cigarette industry has ballooned into a multi-billion dollar market, with at least 466 brands and 7764 unique flavors of e-cigarettes sold online. With both smokers and people who never smoked turning to e-cigarettes, there are concerns about their safety, lack of regulation and accessibility to teens. The CDC reported that 17% of high school seniors use e-cigarettes, more than twice as many as use traditional cigarettes; furthermore, that hundreds of thousands of youth annually are using e-cigarettes who never smoked cigarettes. Our previous studies of Internet cigarette sales indicated that Internet Tobacco Vendors did a poor job of preventing sales to minors, which helped inform development of state and federal regulations to regulate such sales.  In 2013, North Carolina passed a law requiring age verification for online e-cigarette sales. This study was the first study to examine age verification used by Internet e-cigarette vendors and the first to assess compliance with North Carolina’s e-cigarette age verification law. MedicalResearch: What are the main findings? Dr. Williams: It was very easy for minors to buy e-cigarettes online. It took little effort for them to bypass the age verification practices of the vendors because there was very little use of rigorous age verification.  With only 5 orders rejected by vendors due to age verification, there was a youth e-cigarette purchase success rate of 94.7%.  No vendors used age verification at delivery, and few used rigorous methods of age verification that could potentially block youth access. While 7 vendors claimed to use age verification techniques that could potentially comply with North Carolina’s law, only one actually did.
Author Interviews, JAMA, Outcomes & Safety, Surgical Research / 03.03.2015

MedicalResearch.com Interview with: Dr. Stephen Duquette MD Indiana University Department of Surgery, Division of Plastic Surgery R.L Roudebush VA  Indianapolis, IN Medical Research: What is the background for this study? What are the main findings? Dr. Duquette: Carpal tunnel syndrome is the most common compressive peripheral neuropathy, causing pain, numbness and weakness.  Conservative treatment options include splinting, NSAID pain medications, and steroid injections.  Most often the definitive therapy is carpal tunnel release (CTR).  Over 500,000 procedures are performed in the US yearly, making it one of the most commonly performed hand surgery procedures.  In the United States it is most common to perform this operation in the operating room, under sedation and locoregional anesthesia.  Because it is a very common disease that is treated surgically, process improvement can have a major impact in time to OR, patient recovery, patient satisfaction, and overall throughput.  This is especially valuable in the Veterans Administration (VA) system, where recent problems have arisen due to lack of adequate resources to care for all veterans. This study examined the impact of opening an office-based procedure room in a VA to perform awake hand surgery under local anesthesia only.   This was compared to the prior practice of operating room carpal tunnel release though a number of performance metrics, including time to OR and complications.  Although office carpal tunnel releases are performed routinely in Canada, some surgeons still believe that the complications would increase outside the very sterile environment of the operating room. The current study showed that wait times from initial consultation and initial visit to surgical intervention were significantly decreased in the procedure room group compared to the operating room.  The complication rate was the same for both groups, showing that the procedure room and the operating room were both equally safe and efficacious in providing an environment that was ideal for the performance of carpal tunnel releases.
Author Interviews, BMJ, Pediatrics / 02.03.2015

MedicalResearch.com Interview with: Ina S. Santos (on behalf of the co-authors) Iná S. Santos, MD, PhD Professora Titular Depto Medicina Social Programa Pós-graduação Epidemiologia Universidade Federal de Pelotas,  Brasil MedicalResearch: What is the background for this study? What are the main findings? Response: Early regulatory problems (excessive crying, sleeping and feeding problems in infancy) have been considered early markers for similar processes of inadequate or under-controlled behavior in childhood and psychosocial problems in childhood are associated with psychological disorders later in life. The prevalence of excessive crying during the first 3 months of life in representative community-based samples from high-income countries has been reported to range between 14% and 29%. There is no consensus regarding the definition of excessive crying. A frequently used definition is the excessive paroxysmal crying, that is most likely to occur about the same time every day (usually in the late afternoon or evenings) without any identifiable cause in an otherwise healthy baby aged 2 weeks to 4 months and lasting more than three hours per day, occurring in more than three days in any week for three weeks (rule of three) that is typically known as colic. Others give less emphasis to the amount of crying and give relevance to maternal or parental stress due to the child unresponsiveness to soothing or to the maternal perception of the intensity of crying. Negative consequences of excessive crying on maternal and child health have been described: it is associated with early weaning from breast milk, frequent changes of formulae, and maternal mental symptoms, besides being the most common proximal risk factor for shaken baby syndrome. In a study conducted in a middle-sized city located in Southern Brazil, 4231 children enrolled in the 2004 Pelotas Birth Cohort were followed-up from birth to four years of age. At the 3-month post-partum follow-up mothers were asked whether their infants cried more, less or as the same as others of the same age. Infants whose mothers perceived them as crying more than others of the same age were classified as “crying babies”. When the cohort reached four years old, all children were screened to assess their risk of presenting psychological problems. After taking into account a series of maternal and child characteristics (like, maternal age, maternal level of education, type of delivery, gestational age at birth, and child sex, among others) “crying babies” were at increased risk of presenting behavior problems in comparison to “non-crying babies”.
Author Interviews, Cancer Research, MD Anderson, Nature, Personalized Medicine / 28.02.2015

Dr. Anil Sood MD Professor of Gynecologic Oncology and Reproductive Medicine The University of Texas MD Anderson Cancer CenterMedicalResearch.com Interview with: Dr. Anil Sood MD Professor of Gynecologic Oncology and Reproductive Medicine The University of Texas MD Anderson Cancer Center Medical Research: What is the background for this study? What are the main findings? MedicalResearch: What is the background for this approach? What are the main findings? Dr. Sood: The background involves several different issues: management approaches have varied quite a bit across the US; definition of “optimal” surgery and rates of complete surgical removal of tumor (R0) have also varied. It is quite apparent that patients who benefit the most from surgery upfront are those who have removal of tumor resection. To address these issues, we have implanted a much more personalized approach whereby patients with suspected advanced ovarian cancer undergo laparoscopic assessment using a validated scoring system (based on the pattern and extent of disease noted during laparoscopic assessment); patients with a score <8 undergo upfront debulking surgery and those with a score ≥8 receive neoadjuvant chemotherapy followed by surgery after 3-4 cycles. To date, this program has been fully implemented as part of the Moonshot Program at M.D. Anderson. This program has already resulted in several benefits – for example, prior to this algorithm being put into place among all patients with suspected advanced ovarian cancer, around 20% would have removal of tumor resection; after the implementation of the algorithm, of those going to upfront debulking surgery (after laparoscopic assessment), almost 85% of times removal of tumor resection can be achieved. Also, this method of treatment is allowing for new and innovative clinical trial designs.
Author Interviews, CMAJ, Cognitive Issues / 28.02.2015

Optimized-dr-raza-naqviMedicalResearch.com Interview with: Dr. Raza M. Naqvi, MD, FRCPC Assistant Professor of Medicine Division of Geriatric Medicine Western University Victoria Hospital London, ON Medical Research: What is the background for this study? What are the main findings? Dr. Naqvi: The rates of dementia are rising worldwide. Currently we have over 35 million individuals with dementia in the world and this number will triple to over 100 million by 2050 according to the WHO. Many of these cases are in countries where English is not the first language and thus it is important to ensure that the diagnostic and assessment tools we use are valid in the populations being assessed. The Rowland Universal Dementia Assessment Scale (RUDAS) was developed in Australia in 2004 specifically to address the challenges of detecting cognitive impairment in culturally and linguistically diverse populations. This assessment tool is a brief questionnaire that clinicians can use as part of their initial assessment in those with memory loss or cognitive decline. It is freely available online (Search ‘RUDAS’) and takes less than 10 minutes for a clinician to complete with the individual being assessed. Our study was a systematic review and meta-analysis of the RUDAS which aimed to clarify the diagnostic properties of the test and see how it compares to other similar tests that are available. Through our detailed search of the literature we found 11 studies including over 1200 patients that assessed the RUDAS. The studies showed a combined sensitivity of 77.2% and specificity of 85.9%. This means that a positive test increases one’s likelihood of having dementia more than 5-fold and a negative test decreases their likelihood by 4-fold. Across the various studies, the Rowland Universal Dementia Assessment Scale performed similarly to the Mini-Mental State Examination (MMSE), the most commonly used cognitive assessment tool worldwide. The RUDAS appeared to be less influenced by language and education than the MMSE.
AHA Journals, Author Interviews, Heart Disease, Mayo Clinic, Women's Heart Health / 28.02.2015

dr-shannon-dunlayMedicalResearch.com Interview with: Shannon M. Dunlay, M.D. M.S. Advanced Heart Failure and Cardiac Transplantation Assistant Professor of Medicine and Health Care Policy and Research Mayo Clinic Rochester MedicalResearch: What is the background for this study? Dr. Dunlay: Loss of mobility and independence can complicate the care of patients with chronic conditions such as heart failure, and can degrade their quality of life.  However, we have a very poor understanding of the burden of disability in patients with heart failure and how it impacts outcomes.  What are the main findings?  In this study, patients with heart failure were asked whether they had difficulty performing activities of daily living (ADLs)—these include normal activities that most people do in daily life such as eating, bathing, dressing, and walking.  Most patients with heart failure reported having difficulty with at least one ADL at the beginning of the study, and over 1/3 had moderate or severe difficulty with activities of daily living.  Patients who were older, female and had other chronic conditions such as diabetes, dementia and obesity had more difficulty with activities of daily living.  Patients that reported more difficulty with ADLs (worse mobility) were more likely to die and be hospitalized over time.  Some patients had a decline in function over time, and this was also predictive of worse outcomes.
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, Diabetes, Diabetologia, Nutrition / 28.02.2015

Professor Daniela Jakubowicz MD Diabetes Unit. E. Wolfson Medical Center Sackler Faculty of Medicine, Tel Aviv University and Tel Aviv Medical Center IsraelMedicalResearch.com Interview with: Professor Daniela Jakubowicz MD Diabetes Unit. E. Wolfson Medical Center Sackler Faculty of Medicine, Tel Aviv University and Tel Aviv Medical  Center Israel MedicalResearch: What is the background for this study? What are the main findings? Professor Jakubowicz: Obesity epidemic have lead to alarming rise of type 2 diabetes. It is estimated that more than 382 million worldwide have diabetes, predominately type 2 diabetes. In these persons the cardiovascular disease is the leading complication, carrying 10 to 20-fold increase in the risk compared with persons without diabetes. It has been shown that large glucose peaks after meals along the day, are strongly associated with increased a risk for cardiovascular complications. Therefore the mitigation of glucose excursions after meals becomes a major target in the treatment of type 2 diabetes in order to improve glucose balance and prevent complications. Accordingly, dietary modification focused on reduction post meal glucose peaks is needed. Even though still there is no consensus on which of the dietary strategies (i.e. low-fat diet, Mediterranean and low-carbohydrate, higher fiber, low GI glycemic index meals, etc.) is more suitable in improving post-meal glycemic responses along the day. However in none of these interventions has been considered that modifying the meal timing pattern or daily caloric distribution, may lead to improved post-meal glycemic responses in type 2 diabetic patients. The circadian clock genes existing in the pancreatic β-cells, gut, liver and in skeletal muscle, regulate the diurnal (circadian) oscillation of post-meal glucose responses. In fact, post-meal glycemia displays a clear diurnal variation: it is higher and more prolonged in the evening than in the morning. Meal timing schedule, on the other hand, exerts strong controlling influence on circadian clock regulation, thereby influencing the variation and degree of the post meal glycemic elevations. Indeed meal timing non-aligned with the clock gene circadian rhythms, such as breakfast skipping or high-energy intake at dinner, is associated with obesity, higher HbA1C and poor glycaemic control in type 2 diabetes. To clarify the impact of meal timing and composition on overall post-meal glucose responses, we tested the effect of 2 isocaloric diets with different meal timing one with high energy breakfast (704 kcal), mid-sized lunch (600 kcal) and reduced dinner (200 kcal) and other with similar lunch but reduced breakfast (704 kcal) and high energy dinner(704 kcal). The study clearly demonstrated that in type 2 diabetic patients, a diet consisting on high energy breakfast, and reduced dinner, resulted in significantly reduced glucose response after meals and lower overall plasma glucose levels along the entire day, when compared to a diet with the same caloric content but inverse distribution: breakfast (200 kcal) , lunch (600 kcal) and high energy dinner(704 kcal). Moreover, when we compared the glucose response after high energy meal consumed at breakfast (700 kcal) versus in the dinner (700 kcal), it comes out that the glucose response was significantly higher after dinner than after breakfast. It shows that just by changing the time of the high energy meal we may achieve significant reduction in the glucose response.
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, Diabetes, Karolinski Institute, NEJM, OBGYNE, Weight Research / 27.02.2015

Kari Johansson, Phd Department of Medicine Solna, Karolinska Institutet Clinical Epidemiology Karolinska University Hospital Stockholm, SwedenMedicalResearch.com Interview with: Kari Johansson, PhD Department of Medicine Solna, Karolinska Institutet Clinical Epidemiology Karolinska University Hospital Stockholm, Sweden   MedicalResearch: What is the background for this study? What are the main findings? Dr. Johannson: The number of women who are obese in early pregnancy has increased dramatically over the last decades. Consequently, there has been a dramatic rise in the number of women becoming pregnant after bariatric surgery. In Sweden the number of births of women with a history of bariatric surgery has increased from 150 (≈0.15%) to more than 500 (0.5%) per year between 2006 and 2011. The positive effects of bariatric surgery on health outcomes, such as diabetes and cardiovascular disease, are reasonably well-studied, but less is known about the effects on pregnancy and perinatal outcomes. We therefore conducted a population-based study, using data from nationwide Swedish registers. The main findings are that women who had a history of bariatric surgery were much less likely to develop gestational diabetes (2% compared to 7%; P<0.001) and give birth to large-for-gestational age babies (9% vs 22%; P<0.001). On the other hand, the operated women were twice as likely to give birth to babies who were small for gestational age (16% vs 8%), and have pregnancies of shorter duration (273 vs 277.5; P<0.001). 
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, JAMA, Ophthalmology / 27.02.2015

Eric Crouch, MD, FAAO, FAAP, FACS Vice Chair, PEDIGAssociate Professor Department of Ophthalmology Eastern Virginia Medical School Assistant Professor Department of Pediatrics Eastern Virginia Medical School Chief of Ophthalmology Children's Hospital of the King's Daughters Norfolk, VirginiaMedicalResearch.com Interview with: Eric Crouch, MD, FAAO, FAAP, FACS Vice Chair, PEDIGAssociate Professor Department of Ophthalmology Eastern Virginia Medical School Assistant Professor Department of Pediatrics Eastern Virginia Medical School Chief of Ophthalmology, Children's Hospital of the King's Daughters Norfolk, Virginia MedicalResearch: What is the background for this study?  Dr. Crouch: In this letter PEDIG is reporting on the improvement in vision during the run-in phase of a study in children 3 years of age to less than 8 years old.  During the run-in phase, the children were followed at 6 weeks intervals and served as the baseline for entering into a randomized trial for increasing the amount of patching. The patients were randomized to either 2 hours of prescribed patching or 6 hours of prescribed patching once they completed the run-in phase. MedicalResearch: What are the main findings? Dr. Crouch: For amblyopic children, even those who have moderate or severe amblyopia in the 20/100 - 20/400 range, clinicians can start treatment with patching two hours a day.
AHA Journals, Author Interviews, Gender Differences, Heart Disease, University of Pennsylvania, Women's Heart Health / 26.02.2015

Dawn Pedrotty, MD, PhD Cardiovascular Medicine Fellowship University of PennsylvaniaMedicalResearch.com Interview with: Dawn Pedrotty, MD, PhD Cardiovascular Medicine Fellowship University of Pennsylvania MedicalResearch: What is the background for this review? What are the main findings? Dr. Pedrotty: Heart failure (HF) is the most common cause for hospitalization among patients 65 years and older, affecting approximately 6 million Americans; at 40 years of age, American males and females have a one in five lifetime risk of developing heart failure. There are two distinct heart failure phenotypes: a syndrome with normal or near-normal left ventricular ejection fraction (LVEF) referred to as HF with preserved ejection fraction (HFpEF), and the phenotype associated with poor cardiac contractility or heart failure with reduced ejection fraction (HFrEF). Risk factors associated with HFpEF include female gender, especially women with diabetes, higher body mass index, smoking, hypertension, concentric left ventricular hypertrophy (LVH), and atrial fibrillation (AF). There has been a growing interest in the development of criteria for specific subsets of HFpEF, a syndromal disease where multiple cardiac and vascular abnormalities exist. One approach is to implement phenomapping, identifying phenotypically distinct HFpEF categories and developing a classification system to group together pathophysiologically similar individuals who may respond in a more homogeneous, predictable way to intervention. Another option would be to focus on a known physiologic differences which might shed light on pathologic mechanisms e.g. gender and the influences of obesity and atrial fibrillation.
AHA Journals, Author Interviews, General Medicine, Heart Disease, Women's Heart Health / 26.02.2015

MedicalResearch.com Interview with: Gregory YH Lip MD, FRCP (London, Edinburgh, Glasgow), DFM, FACC, FESC Professor of Cardiovascular Medicine, Adjunct Professor of Cardiovascular Sciences, Thrombosis Research Unit, Aalborg University, Denmark; Aston Centre for Cardiovascular Sciences City Hospital Birmingham England UK Medical Research: What is the background for this study? What are the main findings? Prof. Lip: Women with atrial fibrillation are at higher risk of stroke than men with atrial fibrillation. The reasons for this elevated risk remain unclear. The results from our worldwide study suggest that women are treated no differently to men in terms of anticoagulant therapy for stroke prevention. Thromboprophylaxis was, however, suboptimal in substantial proportions of men and women, with underuse in those at moderate-to-high risk of stroke and overuse in those at low risk.