Author Interviews, Compliance, Technology / 05.03.2015

MedicalResearch.com Interview with: Avinash Pandey, the study author, is a high school student who conducted this study under the guidance of his mentor, Niteesh K. Choudhry., M.D., Ph.D., executive director of the Center for Healthcare Delivery Sciences, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass. Medical Research: What is the background for this study? What are the main findings? Response: Numerous studies have demonstrated that there is poor adherence to medications in cardiac patients (coronary artery disease patients, CAD). Despite the fact that non-adherence to these medications can have serious consequences on long-term health like disease progression, increased risk of cardiac events and premature mortality, many patients consistently miss their medications and many stop their medications only months after they are prescribed. This non-compliance leads to high costs for the health care system and more potentially preventable cardiac events. Studies suggest, that for the vast majority of patients, non-adherence to medications is not intentional. A significant portion simply forget to take their medications. Although many systems are available today to reduce medication non-adherence, like pill boxes and blisterpacks, these have demonstrated limited effect on medication adherence. Other systems may be expensive to purchase and cumbersome to use or of limited availability. With the proliferation of cellphones, text message reminders could represent a simple, cost-effective method to improve adherence to medications. This research began as a high school science fair project 4 years ago and has evolved into a large ongoing assessment of the impact of mobile technologies on adherence to evidence based therapies and lifestyle interventions in a broad cross-section of cardiovascular patients and those at risk for cardiovascular disease. The current report examines the impact of an automated computer program which sends free, personalized text messages to remind patients to adhere to their medications. 30 CAD patients were recruited from a single centre cardiac practice, in this 2 month cross-over study. Patients were randomized to either receive text message reminders in the first month or the second month. Adherence of each patient was compared between months. Text message reminders were shown to significantly impact medication adherence. Patients missed on average 60% less doses when receiving text message reminders. These numbers were even greater when looking at pre-specified groups identified in previous studies to be at high risk of medication non-adherence, including depression patients, dementia patients, elderly patients, and patients with less than 12 years of education. All patients improved with text message reminders but those with the lowest adherence improved the most. Although this study did not examine clinical outcomes, the text message reminder system appears to be a simple and widely applicable method to improve adherence to medications. The system is free to operate and represents no cost for patients receiving messages. Thus it could be implemented at an individual level or by physicians and clinics to improve patient adherence to medications. (more…)
Author Interviews, Outcomes & Safety, Surgical Research / 05.03.2015

E. Patchen Dellinger, M.D. Professor of Surgery University of Washington, Box 356410 Seattle, Washington MedicalResearch.com Interview with: E. Patchen Dellinger, M.D. Professor of Surgery University of Washington Seattle, Washington Medical Research: What is the background for this study? What are the main findings? Dr. Dellinger: We know from previous large studies that use of checklists is associated with improvements in patient morbidity and mortality. However, recent large studies have also shown that mandating teams to use the checklist without providing the support required for adequate implementation does not result in better outcomes. This report reviews findings from studies examining checklist compliance and use. We found that when compliance with the checklist is poor it is not as effective as when the checklist is carried out as it is intended. Checklist use appears to be a marker for institutional culture of safety, and organizations with a more robust safety culture may be more likely to use the checklist in an effective manner with resulting improvements in patient safety. (more…)
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. (more…)
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. (more…)
Author Interviews, BMJ / 05.03.2015

Minna Johansson, PhD student Department of Public Health and Community Medicine, Institute of Medicine The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Research Unit and Section for General Practice, Vänersborg, Sweden MedicalResearch.com Interview with: Minna Johansson, PhD student Department of Public Health and Community Medicine, Institute of Medicine The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Research Unit and Section for General Practice, Vänersborg, Sweden Medical Research: What is the background for this study? What are the main findings? Response: The decision to introduce screening for abdominal aortic aneurysms (AAA) was based on four randomised controlled trials from the 1980s and 1990s that showed a 50% relative risk reduction in aneurysm-related mortality. Over the last 15 years Sweden, the UK and the USA have introduced AAA screening programmes. However, abdominal aortic aneurysms screening does not only have intended benefits but also unintended harms. The most important harm is overdiganosis; i.e. the overdetection of aneurysms that would not have caused symptoms in that man´s remaining life, nor been the cause of his death. In this study, we estimate that 176 of every 10,000 men invited to screening are overdiagnosed as a consequence of screening. These men are unnecessarily turned into patients and may experience appreciable anxiety throughout their remaining lives. Moreover, 37 of these men unnecessarily have preventive surgery and 1.6 of them die as a consequence. Furthermore, a recent drop in abdominal aortic aneurysms prevalence by over 70% reduces the potential benefits of AAA screening. Unfortunately, the harms are not likely to be reduced by the same rate, thus leading to a worsened benefit:harm ratio. This means that the benefit:harm ratio is likely to be worse in current screening programmes than in the trials on which they were based. Additionally, it has been proposed to lower the cut-off for the abdominal aortic aneurysms-diagnosis from 30 to 25 mm. Our estimates show that such a change of definition would increase the rate of overdiganosis substantially and further worsen the benefit:harm ratio of abdominal aortic aneurysms screening. (more…)
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. (more…)
Allergies, Author Interviews, Microbiome, Pediatrics / 04.03.2015

Anita Kozyrskyj Ph.D Professor, Department of Pediatrics University of AlbertaMedicalResearch.com Interview with: Anita Kozyrskyj Ph.D Professor, Department of Pediatrics University of Alberta Medical Research: What is the background for this study? What are the main findings? Prof. Kozyrskyj: Our study determined what "good" gut bacteria were present in 166 full-term infants enrolled in the Canadian Healthy Infant Longitudinal Development (CHILD) Study. Funded by CIHR and AllerGen NCE, this landmark study involves more than 3,500 families and their newborn infants across Canada. Gut bacteria were identified by DNA sequences extracted from infant poop. Infants with a fewer number of different bacteria in their gut at 3 months of age were more likely to become sensitized to foods such as milk, egg or peanut, by the time they were 1 years old. Infants who developed food sensitization also had altered levels of two specific types of bacteria, Enterobacteriaceae and Bacteroidaceae, compared to infants who didn’t. (more…)
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. (more…)
Author Interviews, Heart Disease / 04.03.2015

MedicalResearch.com Interview with: Joo-Yong Hahn, MD, PhD Associate Professor Heart Vascular Stroke Institute, Samsung Medical Center Sungkyunkwan University School of Medicine Medical Research: What is the background for this study? What are the main findings? Response: In the Effects of Postconditioning on Myocardial Reperfusion in Patients with ST-segment Elevation Myocardial Infarction (POST) trial, ischemic postconditioning failed to improve myocardial reperfusion (Hahn JY et al. Circulation 2013;128:1889-96) . However, long-term effects of ischemic postconditioning on clinical outcomes are not known in patients with ST-segment elevation myocardial infarction (STEMI). Therefore, the aim of this study was to investigate the long-term effects of ischemic postconditioning on clinical outcomes. In this prospective, randomized trial, ischemic postconditioning with primary percutaneous coronary intervention  (PCI) did not improve clinical outcomes compared with conventional primary PCI in patients with STEMI. There was no significant difference in a composite of death, myocardial infarction, severe heart failure, or stent thrombosis between the 2 groups. Beneficial effects of ischemic postconditioning were not found in any of various subgroups. (more…)
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. (more…)
Author Interviews, Mental Health Research, Pediatrics, University of Pennsylvania / 04.03.2015

Courtney Benjamin Wolk, Ph.D. Postdoctoral Researcher Center for Mental Health Policy and Services Research Perelman School of Medicine Department of Psychiatry University of Pennsylvania Philadelphia, PA 19104MedicalResearch.com Interview with: Courtney Benjamin Wolk, Ph.D. Postdoctoral Researcher Center for Mental Health Policy and Services Research Perelman School of Medicine Department of Psychiatry University of Pennsylvania Philadelphia, PA 19104 Medical Research: What is the background for this study? What are the main findings? Response: Previous research investigating the relationship between anxiety and suicidality has been mixed. An ongoing question in the field has been whether anxiety disorders independently increase risk for suicidal ideation and behavior or if the high co-occurrence of anxiety and mood symptoms or other shared demographic factors are driving relationships that have been observed between anxiety and suicidality. We examined the relationship between response to treatment for an anxiety disorder in childhood and suicidal ideation, plans, and attempts 7 to 19 years after treatment with cognitive-behavioral therapy, more commonly referred to as CBT. Our results indicated that participants who responded favorably to cognitive-behavioral therapy during childhood had lower rates of lifetime, past month, and past two-week suicidal ideation endorsement than treatment non-responders. This was the case across both self-report and interview-report of suicidal ideation. Treatment response was not significantly associated with suicide plans or attempts, though plans and attempts were infrequently endorsed in our sample, limiting the ability to detect findings. (more…)
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. (more…)
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. (more…)
Author Interviews, Neurological Disorders / 04.03.2015

MedicalResearch.com Interview with: Dr. Richard H. Myers Ph.D. Department of Neurology and Genome Science Institute Boston University School of Medicine, Boston, MAMedicalResearch.com Interview with: Dr. Richard H. Myers Ph.D. Department of Neurology and Genome Science Institute Boston University School of Medicine, Boston, MA MedicalResearch: What is the background for this study? What are the main findings? Dr. Myers:  Andy Hoss, who is a graduate student in my group is the primary investigator for this project. We are investigating changes that occur in the brain of individuals who had Huntington's disease. We were focused on studying regulatory mechanisms that control the levels of messenger RNAs (mRNAs) in the brain, since that is an area that has been implicated in this disease. MicroRNAs (miRNAs) are known to target mRNAs for degradation or to be sequestered for storage and later use. A few limited studies of microRNAs had been done, but we sought to measure the levels of all of the  miRNAs  present in the brains of persons with Huntington's disease and in controls using next-generation sequencing. (more…)
Author Interviews, Cost of Health Care, Health Care Systems / 04.03.2015

MedicalResearch.com Interview with: Sophie Coronini-Cronberg Honorary research Fellow Department of Primary Care and Public Health, Imperial College London Consultant in public health Centre Medical Directorate with Bupa, United Kingdom. Medical Research: What is the background for this study? What are the main findings? Dr. Coronini-Cronberg: From April 2011, England’s National Health Service (NHS) was challenged to find £20 billion of efficiency savings over four years, in part by reducing the use of ineffective, overused or inappropriate procedures. However, there was no clear instruction as to which procedures are of 'limited clinical value' and also under which circumstances they should be reduced. We looked at hospital admissions statistics for six procedures that appear on local and/or unofficial lists to see which had been affected and whether cuts were applied consistently across commissioners in the first year of the savings programme. We found a significant drop in three procedures considered potentially ‘low value’ compared to the underlying time trend: removal of cataracts, hysterectomy for heavy menstrual bleeding, and myringotomy to relieve eardrum pressure. There was no significant change in three other ‘low-value’ procedures: spinal surgery for lower back pain, inguinal hernia repair, and primary hip replacement, or in two ‘benchmark’ procedures (coronary revascularisation, gall bladder removal). Myringotomy, a procedure to relieve pressure in the ear which is considered relatively ineffective, declined by 11.4 per cent overall. Two procedures considered only effective in certain circumstances also fell overall. Hysterectomy for heavy menstrual bleeding declined by 10.7 per cent overall, and cataract removal declined by 4.8 per cent.ý ýWe also found the reductions were inconsistently applied by commissioning groups (so-called Primary Care Trusts). (more…)
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. (more…)
Genetic Research, MD Anderson, Melanoma, Personalized Medicine / 04.03.2015

Linda Chin, MD Department Chair, Department of Genomic Medicine, Division of Cancer Medicine The University of Texas MD Anderson Cancer Center Houston, TXMedicalResearch.com Interview with: Linda Chin, MD Department Chair, Department of Genomic Medicine, Division of Cancer Medicine The University of Texas MD Anderson Cancer Center Houston, TX Medical Research: What is the background for this study? What are the main findings? Dr. Chin: BRAF inhibitors have worked very well against melanoma in the clinic, but when the tumors relapse on treatment, it is not always clear what causes it. Without this information, it can be difficult for doctors to identify specific second-line therapies likely to overcome the drug resistance. In this study, we used both mouse and patient melanoma samples to identify patterns of selected protein levels that can categorize modes of drug resistance when other assays such as DNA sequencing are uninformative. We hope that this information can provide missing clues for clinicians. (more…)
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. (more…)
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. (more…)
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. (more…)
Author Interviews, Compliance, Diabetes, Pediatrics / 03.03.2015

Dr. Yang Lu Ph.D Los Angeles Biomedical Research Institute Dr. Lu’s research interests include utilization, cost and treatment regimen adherence of chronic conditions, such as obesity and diabetes; behavioral economic interventions, and cost effectiveness studiesMedicalResearch.com Interview with: Dr. Yang Lu Ph.D Los Angeles Biomedical Research Institute Dr. Lu’s research interests include utilization, cost and treatment regimen adherence of chronic conditions, such as obesity and diabetes; behavioral economic interventions, and cost effectiveness studies MedicalResearch: What is the background for this study? Response: Non-adherence is a serious issue in type 1 diabetes management. It leads to poor glycemic control and peaks in adolescence and young adulthood. Peer support is critical for young patients yet few studies examined whether pairing youth with slightly older and more experienced peers with diabetes improves their diabetes self-management and glycemic control. This study had two aims: (1) assess whether adolescents (as prospective mentees) and young adults (as prospective mentors) with diabetes would be interested in peer mentoring as a way to improve adherence, and (2) identify contents and delivery modes for a peer mentoring topic from the perspective of patients and their parents. Fifty-four adolescents and 46 young adults with type 1 diabetes were surveyed. (more…)
Author Interviews, CDC, OBGYNE, Sexual Health / 03.03.2015

MedicalResearch.com Interview with: Amy Branum M.S.P.H., Ph.D and Jo Jones Ph.D Center for Health Statistics Division of Vital Statistics, Reproductive Statistics Branch Medical Research: What is the background for this study? Response: This data brief was based on multiple years of the National Survey of Family Growth (NSFG).  The NSFG, first conducted in 1973, is administered by NCHS in response to a legal mandate that says that NCHS “shall collect statistics on …family formation, growth, and dissolution.” (PHS Act, Sec 306). Up through the 2002 NSFG, the survey was conducted periodically; with the 2006-2010 data collection, the NSFG is a continuous survey with interviews conducted over multiple years.  We felt it was important to examine long-term trends in  Long-acting Reversible Contraception use due to fluctuations over time in IUD and implant acceptability and availability as contraception methods, especially in light of recent efforts to promote LARC use to prevent unintended pregnancies and for birth spacing. Medical Research: What are the main findings? Response: We found that Long-acting Reversible Contraception use declined between 1982 and 1988, remained stable through 2002 and then increased almost five-fold between 2002 and 2011-2013 (from 1.5% to 7.2).  Long-acting Reversible Contraception use has, and continues to be, generally highest among women aged 25-34 but has increased the most among women 15-24 since 2002.  Hispanic women used Long-acting Reversible Contraception at higher rates in 1982 compared to non-Hispanic white and non-Hispanic black women but patterns of use diverged after 1995 so that by 2011-2013, patterns of use were more similar by race and Hispanic origin.  Women who have at least one previous live birth have used, and continue to use, LARCs at a higher rate compared to women with no previous births. (more…)
Author Interviews, Mental Health Research / 03.03.2015

Julie M. Zito, PhD Professor of Pharmacy and Psychiatry Department of Pharmaceutical Health Services Research University of Maryland School of Pharmacy Baltimore, MD 21201MedicalResearch.com Interview with: Julie M. Zito, PhD Professor of Pharmacy and Psychiatry Department of Pharmaceutical Health Services Research University of Maryland School of Pharmacy Baltimore, MD 21201 MedicalResearch: What is the background for this study? Dr. Zito: Atypical antipsychotic (AAP) use in children and adolescents has grown substantially in the past decade, largely for behavioral (non-psychotic) conditions. Poor and foster care children with Medicaid-insurance are particularly affected. This ‘off-label’ usage has insufficient evidence of benefits regarding improved functioning (i.e. appropriate behavior and performance, socially and academically) while the little evidence that accrues tends to emphasize ‘symptoms’, i.e. less acting out. Recent evidence shows that youth treated with Atypical antipsychotics are at risk of serious cardiometabolic adverse events including diabetes emerging after atypical antipsychotics are ‘on board’. MedicalResearch: What are the main findings? Dr. Zito: The continued expansion in Atypical antipsychotics use for behavioral conditions, particularly in poor and foster care youth prompted several government reports asking states to implement oversight programs. In our survey of state Medicaid agencies, we identified programs implementing a new and promising approach to increase the likelihood that these medications are used appropriately. These ‘peer review’ programs have been launched in 15 of the 31 prior authorization state Medicaid programs. There is a distinct advantage in having a qualified peer review, on a case-by-case basis, of the rationale for use of an atypical antipsychotic in a condition or age group that is ‘off-label’ according to the FDA product information label. (more…)
Protein / 03.03.2015

Anestis Dougkas, MSc, PhD Food for Health Science Centre Lund University Lund, SwedenMedicalResearch.com Interview with: Anestis Dougkas, MSc, PhD Food for Health Science Centre Lund University Lund, Sweden MedicalResearch: What is the background for this study? Dr. Dougkas: There has been an increased interest in the macronutrient profile of diets and meals as a factor that influences appetite. Dietary protein is considered as the most satiating macronutrient, yet there is little evidence on whether the effects observed are attributed to the protein or to the concomitant manipulation of carbohydrates and fat. The aim was to examine the effect of consumption of beverages varying in macronutrient content on appetite ratings, energy intake and appetite-regulating hormones. MedicalResearch: What are the main findings? Dr. Dougkas: Increased protein content suppressed more average appetite than carbohydrate and fat with a more pronounced effect of protein intake on subjective ratings of prospective consumption. Protein was also the most influential macronutrient for postprandial glucagon like peptide-1 (GLP-1, an appetite- suppressing hormone) response. This appetite-suppressing effect of protein was independent of the changes in fat and carbohydrates. (more…)
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. (more…)