Author Interviews, Brigham & Women's - Harvard, Cost of Health Care, HIV, NEJM / 30.01.2015

Douglas B. Jacobs B.S., MD/MPH Candidate Harvard T.H. Chan School of Public HealthMedicalResearch.com Interview with: Douglas B. Jacobs B.S., MD/MPH Candidate Harvard T.H. Chan School of Public Health Medical Research: What is the background for this study? Response: In May 2014, a formal complaint submitted to the Department of Health and Human Services contended that four Florida insurers were structuring their formularies in a way that discouraged enrollment from HIV positive beneficiaries. These insurers placed all HIV drugs, including generics, on the highest cost-sharing tiers. This formal complaint served as the impetus for this research. We wanted to discover if this was a phenomenon that was isolated to Florida, or if it was national in scope, and what the implications would be for HIV positive beneficiaries. As such, we analyzed what we called “adverse tiering”—in which all drugs for certain conditions are placed in the highest cost sharing tiers—in 12 states in the federal marketplace. We compared cost-sharing for a commonly prescribed class of HIV medication, called Nucleoside Reverse Transcriptase Inhibitors, or NRTIs.
Asthma, Author Interviews, Compliance, Lancet, Technology / 30.01.2015

Amy Chan BPharm(Hons) RegPharmNZ MPS ANZCP Pharmacist / PhD candidate Department of Paediatrics Auckland Hospital Faculty of Medical & Health Sciences University of Auckland Auckland, New ZealandMedicalResearch.com Interview with: Amy Chan   BPharm(Hons) RegPharmNZ  MPS  ANZCP Pharmacist / PhD candidate Department of Paediatrics Auckland Hospital Faculty of Medical & Health Sciences University of Auckland  Auckland, New Zealand Medical Research: What is the background for this study? What are the main findings? Response: Asthma is one of the most common childhood conditions, affecting 1 in 4 children in New Zealand.  Although there are many effective medications available for asthma, of which the most important are inhaled corticosteroids, asthma control remains suboptimal due to poor adherence.  In children, adherence to regular preventive asthma therapy is about 50%, and can be as low as 30%.  Our randomised controlled trial looked at use of an electronic monitoring device with an in-built audiovisual reminder to see if it improved adherence and asthma control.  We recruited 220 children aged between 6-15yrs, who presented to the emergency department with asthma and randomised them to receive the device either with the audiovisual function enabled or disabled.  It found that those who received the audiovisual reminder (the intervention arm) took a median of 84% of their inhaled corticosteroids compared to just 30% in those who did not receive the reminder (control arm).  This equates to a 180% improvement in adherence.  We found significant improvements also in asthma control (including reduced asthma symptoms and increased participation in daily activities) and a reduction in reliever use from 17.4% to 9.5% in those who received the reminder.
Author Interviews, Breast Cancer, Journal Clinical Oncology, Mayo Clinic / 30.01.2015

MedicalResearch.com Interview with: Dr. Amy C. Degnim MD Professor of Surgery Mayo Clinic, Rochester.Dr.  Amy C. Degnim MD Professor of Surgery Mayo Clinic, Rochester. Medical Research: What is the background for this study? What are the main findings? Dr. Hartmann: Approximately 1 million women in the US every year have a breast biopsy that shows benign findings. We have found that the specific features of the breast tissue seen under the microscope can help to predict the risk of breast cancer in the future.  We developed a mathematical formula to calculate breast cancer risk based on the features seen in the biopsy tissue (named the BBD-BC model).  We found that using these microscopic features provides more accurate predictions of risk than the previous standard- the Breast Cancer Risk Assessment Tool (BCRAT).
Author Interviews, Blood Pressure - Hypertension, Cost of Health Care, NEJM / 29.01.2015

Andrew Moran, MD, MPH Herbert Irving Assistant Professor of Medicine Columbia University Division of General Medicine Presbyterian Hospital 9th floor East room 105 New York, NY 10032MedicalResearch.com Interview with: Andrew Moran, MD, MPH Herbert Irving Assistant Professor of Medicine Columbia University Division of General Medicine Presbyterian Hospital  New York, NY 10032 Medical Research: What is the background for this study? What are the main findings? Response: In 2014, a panel appointed by the Eighth Joint National Committee on the Detection, Evaluation and Treatment of High Blood Pressure (JNC 8) recommended new guidelines for high blood pressure (hypertension ) treatment in U.S. adults.  The guidelines made sweeping changes to the prior guidelines and stirred up controversy among hypertension and public health experts.  Essentially, the panel recommended more conservative treatment targets that narrowed the population eligible for treatment with blood pressure-lowering medications.  Nonetheless, about 28 million U.S. adults have uncontrolled hypertension even under the new more conservative guidelines.  We asked the question:  are the new guidelines cost-effective? That is, does treating this common condition with the available medicines add more health and reduce medical costs?  It is surprising that this question has rarely been answered before.
Author Interviews, Nature, Ovarian Cancer / 29.01.2015

Dr. Terry Magnuson PhD Vice Dean for Research Department of Genetics, School of Medicine University of North Carolina at Chapel Hill Chapel Hill, North Carolina 27599MedicalResearch.com Interview with: Dr. Terry Magnuson PhD Vice Dean for Research Department of Genetics, School of Medicine University of North Carolina at Chapel Hill Chapel Hill, North Carolina 27599 Medical Research: What is the background for this study? What are the main findings? Response: Ovarian clear-cell carcinoma is a lethal form of ovarian cancer with limited therapeutic options. Recent patient-derived tumor sequencing studies support a strong genetic basis for the disease, but the roles of gene mutations in cancer causation are still unclear. We observed rapid induction of ovarian clear-cell carcinoma in mice that were genetically engineered to carry mutations in ARID1A and PIK3CA−the two most frequently mutated genes. Comparisons between human and mouse tumors uncovered a downstream role for the Interleukin-6 (IL-6) cytokine-signaling pathway in tumor progression. Thus, ARID1A and PIK3CA mutations cause ovarian clear-cell carcinoma and promote tumor cell growth by acting upon the IL-6 signaling pathway.
Author Interviews, Dermatology, PLoS, Stem Cells / 29.01.2015

Alexey Terskikh, Ph.D. Associate Professor Department of Developmental and Stem Cell Biology Sanford-Burnham Medical Research Institute La Jolla, CAMedicalResearch.com Interview with: Alexey Terskikh, Ph.D. Associate Professor Department of Developmental and Stem Cell Biology Sanford-Burnham Medical Research Institute La Jolla, CA Medical Research: What is the background for this study? What are the main findings? Dr. Terskikh: Hair loss is a wide spread human condition with an unmet need for hair replacement. In the United States alone, over 40 million men and 21 million women are affected by hair loss. I have been interested in the differentiation of human pluripotent stem cells into various cell including neural crest cells. In-vivo neural crest cells give rise to a multitude of cell types, including dermal papilla cells, which populate the bulb of hair follicles and regulate hair growth. We have established new method to differentiate human pluripotent stem cells into dermal papilla-like (DP-like) cells, with a goal of inducing hair growth. To find out whether DP-like cells induce hair growth we transplanted these cells under the skin of mice (which have a small amounts of white hair) along with the skin cells from dark-haired mice. We observed the growth of new black hairs suggesting the induction of hair growth by transplanted human DP-like cells.
Author Interviews, General Medicine, Journal Clinical Oncology, Leukemia, Pediatrics / 29.01.2015

MedicalResearch.com Interview with: Jun J. Yang  Ph.D. Assistant Member Dept. of Pharm. Sci. St. Jude Children's Research Hospital Memphis, TN 38105 Medical Research: What is the background for this study? What are the main findings? Dr. Yang: Mercaptopurine is highly effective in acute lymphoblastic leukemia (ALL) and essential for the cure of this aggressive cancer. However, it also has a narrow therapeutic index with common toxicities. Identifying genetic risk factors for mercaptopurine toxicity will help us better understand how this drug works and also potentially enable clinicians to individualize therapy based on patients’ genetic make-up (precision medicine). In addition to confirming the role of TPMT, we have identified another important genetic risk factor (a genetic variation in a gene called NUDT15) for mercaptopurine intolerance. Patients carrying the variant version of NUDT15 are exquisitely sensitive and required up to 90% reduction of the normal dose of this drug. TPMT variants are more common in individuals of African and European ancestry, whereas NUDT15 variants are important in East Asians and Hispanics.
Author Interviews, JAMA, Prostate Cancer, Radiology / 29.01.2015

MedicalResearch.com Interview with: Mohummad Minhaj Siddiqui, MD AssiMohummad Minhaj Siddiqui, MD Assistant Professor of Surgery - Urology Director of Urologic Robotic Surgery University of Maryland School of Medicine andstant Professor of Surgery - Urology Director of Urologic Robotic Surgery University of Maryland School of Medicine and Peter A. Pinto, M.D Head, Prostate Cancer Section Director, Fellowship Program Urologic Oncology Branch National Cancer Institute National Institutes of Health Bethesda, Maryland 20892-1210 Peter A. Pinto, M.D Head, Prostate Cancer Section  Director, Fellowship Program Urologic Oncology Branch National Cancer Institute  National Institutes of Health  Bethesda, Maryland Medical Research: What is the background for this study? What are the main findings? Response: For men suspected of having prostate cancer due to an elevated PSA or abnormal digital rectal exam, the next step in their diagnostic workup has traditionally been a standard 12-core biopsy to evenly sample the entire gland.  Unlike most other cancers, prostate cancer is one of the few solid tumors left which is diagnosed by randomly sampling the gland with the hope of biopsying the tumor, if it is present.  This paradigm has been largely due to the fact that imaging to date has been limited in its ability to identify prostate cancer.  Recent advancements in multiparametric MRI of the prostate however has significantly improved clinician's ability to identify regions in the prostate suspicious for cancer.  This has led to the emergence of MR/Ultrasound fusion technology which allows for targeted biopsy of the prostate into regions suspicious for cancer. Although conceptually, it makes sense that a targeted biopsy has the potential to perform better than the standard random sampling of the prostate in the diagnosis of prostate cancer, studies were needed to understand if this is true, and if so, if the improvement was substantial enough to justify the extra expense and effort needed to obtain a MRI guided biopsy.  This study performed at the National Cancer Institute's Clinical Center sought to address this clinical question of interest.  From 2007-2014, a total of 1003 men suspected to have prostate cancer underwent an MRI of the prostate.  If an area of suspicion was seen in the prostate, these men underwent both the targeted biopsy of the suspicious region in the prostate as well as the standard 12-core needle biopsy during the same session.  The results from the targeted biopsy were compared to the results of the standard biopsy. The key findings in this study was that targeted biopsy improved the rate at which high-risk clinically significant cancer was diagnosed by 30%.  Of interest, the study also found that low-risk, clinically insignificant disease (the type of prostate cancer that is unlikely to cause any harm to the patient over the course of his natural life) was decreased in diagnosis by 17%.  Decrease of diagnosis of such disease has the potential benefit that it could lead to less over-treatment of cancer that never needed to be treated.  In a subset of 170 men that ultimately underwent surgery to remove the prostate to treat their cancer, we were further able to examine how well the prostate biopsy reflected the actual cancer burden in the whole gland.   It is well known that standard biopsy can actually underestimate the total cancer grade in the whole prostate in upwards of 30-40% of cases.  We found that the targeted biopsy was significantly better at predicting whether the patient had intermediate to high-risk cancer compared to standard biopsy.  Through further analysis using a statistical method called decision curve analysis, we further found that for men who wish to undergo surgery for intermediate to high-risk cancer, but wish to go on active surveillance for low-risk cancer, targeted biopsy led to better decision making compared to standard biopsy, or even the two techniques combined.
Author Interviews, NEJM, Opiods, Pharmacology / 29.01.2015

Richard C. Dart, M.D., Ph.D Denver Health & Hospital Authority Professor, University of Colorado School of MedicineMedicalResearch.com Interview with: Richard C. Dart, M.D., Ph.D Denver Health & Hospital Authority Professor, University of Colorado School of Medicine   Medical Research: What is the background for this study? What are the main findings? Dr. Dart: For the past two decades, prescription opioid medication abuse has increased significantly in the US. An estimated 25 million people initiated nonmedical use of pain relievers between 2002 and 2011.  In 2010 the number of death attributed to prescription opioid medications reached 16,651. The  RADARS® System (Researched Abuse, Diversion and Addiction Related Surveillance) has been monitoring prescription drug abuse and diversion for over 13 years. We use a “mosaic” approach, measuring abuse and diversion from multiple perspectives, to describe this hidden phenomenon as comprehensively as possible. For the current publication we used 5 separate RADARS® System programs to collect data and the study period was from January 2002 through December 2013. We noticed a substantial increase  of prescription drug abuse from 2002 through 2010, followed by a flattening or decrease in 2010 and, lastly, a decline in 2011 through 2013. We also noticed a similar pattern in opioid-related deaths. Nonmedical use did not change significantly among college students.
Author Interviews, Geriatrics, Hearing Loss, JAMA / 28.01.2015

Margaret T. Dillon, AuD University of North Carolina School of MedicineMedicalResearch.com Interview with: Margaret T. Dillon, AuD University of North Carolina School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Dillon: The goal of this study was to evaluate whether age at revision cochlear implantation influences post-revision speech perception performance. A cochlear implant is an implantable auditory prosthesis that aims to provide sound to patients with certain degrees of hearing loss, by converting and transmitting the acoustic sound into electric stimulation. Research has shown cochlear implant recipients experience improved speech perception in quiet and noise as compared to preoperative performance with conventional amplification (ie, hearing aids). There is variability in postoperative performance. Understanding the cause or causes of this variability is the primary goal of a number of research studies. One suspected indicator for this variability is advanced age at the time of surgery. Though the incidence of revision cochlear implantation is low, it may be warranted when the internal device is no longer functional or not functioning optimally. We reviewed the pre-revision and post-revision speech perception performance of younger (< 65 years of age) and older (> 65 years of age) adult cochlear implant recipients. There was no difference between the post-revision speech perception performance between the two groups.
Author Interviews, Breast Cancer, Brigham & Women's - Harvard, Cancer / 28.01.2015

Rachel A. Freedman MD, MPH Assistant Professor of Medicine, Harvard Medical School Department of Medical Oncology Dana-Farber Cancer Institute, Boston, MassachusettsMedicalResearch.com Interview with: Rachel A. Freedman MD, MPH Assistant Professor of Medicine, Harvard Medical School Department of Medical Oncology Dana-Farber Cancer Institute, Boston, Massachusetts Medical Research: What is the background for this study? What are the main findings? Dr. Freedman: Studies have previously looked at how general cancer knowledge may impact health conditions and rates of screening but none (to my knowledge) have focused on one’s knowledge about his/her own breast cancer. We surveyed 500 women who were diagnosed with early-stage breast cancer within the Northern California Cancer Registry and asked questions about their breast cancer subtype (I.e. Hormone receptor status and HER2 status), tumor grade, and stage. We then matched women’s answers to those collected by the registry to examine the correctness of the answers given. We found low overall rates of having knowledge about one’s disease and this was even more apparent for black and Hispanic patients. When education and health literacy were accounted for, disparities in knowledge remains for black women but were narrowed for Hispanic women in some cases.
Author Interviews, Brigham & Women's - Harvard, Infections, PNAS / 28.01.2015

Rakesh K. Jain, Ph.D. A.W.Cook Professor of Tumor Biology Director, E.L. Steele Laboratory Department of Radiation Oncology Harvard Medical School and Massachusetts General Hospital Boston, MA 02114MedicalResearch.com Interview with: Rakesh K. Jain, Ph.D. A.W.Cook Professor of Tumor Biology Director, E.L. Steele Laboratory Department of Radiation Oncology Harvard Medical School and Massachusetts General Hospital Boston, MA    02114 Medical Research: What are the primary findings of this study and why are they important? Dr. Jain: Pulmonary granulomas are the hallmark of the Tuberculosis (TB) infection, yet it is not fully understood how these structures contribute to disease progression and treatment resistance. In this study, we applied our insight in tumor biology – gained over three decades – to explore and exploit the similarities between vasculature (blood vessel network) in solid cancerous tumors and TB pulmonary granulomas. We demonstrate for the first time that TB granulomas have abnormal vasculature. This abnormality provides a mechanism for the observation that TB granulomas are often hypoxic (have low oxygen conditions) and have differential distribution of anti-TB drugs. We showed that bevacizumab, a widely prescribed anti-VEGF antibody for cancer and eye diseases, is able to create more structurally and functionally normal granuloma vasculature and improve small molecule delivery. This study suggests that vasculature normalization in combination with anti-TB drugs has the potential to enhance treatment in patients with TB. Tuberculosis (TB) is a global scourge that is responsible for nearly 2 million deaths annually. Due to the inability of currently available treatment regimens to eradicate this devastating disease, it is clear that new treatment strategies are urgently needed. Unlike many researchers in the TB field, we do not seek to discover new therapeutics that target bacterial resistance; instead, we strive to overcome physiological resistance to treatment resulting from abnormalities in the granuloma vasculature that impair drug delivery and create hypoxia that impairs efficacy of drugs and immune system. By using an FDA-approved drug, our study has the potential to be rapidly translated into the clinic. Medical Research: Has any association previously been made between the vascular structure of TB granulomas and the challenges of treating TB – both the fact that treatment takes so long and the development of multidrug resistance? Dr. Jain: Our study is the first to implicate a specific facet of the granuloma – the abnormal vasculature – as a potential contributor to disease progression and treatment resistance. Granuloma hypoxia is known to negatively affect the local immune system while conferring resistance to some of the TB drugs. Our collaborators have shown that different anti-TB drugs have differential abilities to penetrate the granuloma structure, especially to the interior granuloma regions where the TB bacteria are found in greatest numbers. Our study is the first to provide evidence that by modulating the granuloma vasculature, hypoxia can be alleviated and drug delivery can be improved.
Author Interviews, Infections, PNAS, University Texas / 28.01.2015

Christopher S. Sullivan, Ph.D. Associate Professor Dept. Molecular Biosciences The University of Texas at Austin anMedicalResearch.com Interview with: Christopher S. Sullivan, Ph.D. Associate Professor Dept. Molecular Biosciences The University of Texas at Austin and Jennifer Cox, lead author Graduate student in Dr. Sullivan’s laboratory. Jennifer Cox, lead author Graduate student in Dr. Sullivan’s laboratory. Jennifer Cox's Replies: MedicalResearch: What is the background for this study? What are the main findings? Jennifer Cox: In the last decade, researchers have identified that many viruses encode small regulatory molecules known as microRNAs. Some viral microRNAs are able to manipulate host processes including stress responses, proliferation, and cell death. However, there are many viral microRNAs with unknown functions. Many of the viruses that encode microRNAs are associated with severe pathologies including various cancers so understanding the role of viral microRNAs can shed light on virus biology. For this study, we focused on identifying viral microRNAs that can regulate innate immune signaling for several reasons. First, all viruses have proteins to combat interferon signaling. Second, we have identified microRNAs from two diverse viruses (retro and annello) that can inhibit interferon signaling so we hypothesized that additional viral microRNAs will perform this same function. We screened ~70 viral microRNAs for the ability to regulate innate immune signaling and identified three herpesviruses, Epstein-Barr Virus, Kaposi’s Sarcoma Associated Virus, and Human Cytomegalovirus, that inhibit the interferon response. Epstein-Barr Virus, causes an estimated 200,000 cancers every year, including lymphomas, nasopharyngeal cancers and some stomach cancers. Interestingly, most of these cancers harbor latent EBV – a state of limited gene expression that produces no virus. microRNAs are one of the few viral gene product expressed during latency. Our further work identified that Epstein-Barr Virus, KSHV, and Human Cytomegalovirus have converged to inhibit interferon signaling in the same manner – through decreasing expression of a central hub of innate immune signaling, CREB binding protein (CBP). We show that this regulation conveys partial resistance to the negative effects of interferon treatment on an EBV+ lymphoma cell line. Additionally, removing the microRNA from a similar cell line increases the sensitivity to interferon. Interferon can be used in combination with other chemotherapies to treat lymphomas but varies in success. Our results may partially explain the variability seen in patients with EBV-associated cancers.
Author Interviews, Heart Disease, JACC, Lipids / 28.01.2015

MedicalResearch.com Interview with: Dong Zhao MD.PhD Deputy Director & Professor andDong Zhao MD.PhD Deputy Director & Professor and Dr. Que Qi, MD.PhD Assistant Professor Beijing Institute of Heart,Lung & Blood Vessel Diseases Capital Medical University Beijing Anzhen HospitalDr. Que Qi, MD.PhD Assistant Professor Beijing Institute of Heart,Lung & Blood Vessel Diseases Capital Medical University Beijing Anzhen Hospital Medical Research: What is the background for this study? What are the main findings? Dr. Dong Zhao: Lower serum HDL-C level used to be considered as a key risk factor of atherosclerotic cardiovascular diseases. This knowledge was based on very consistent findings from researcher of basic science and observational studies of epidemiology. HDL-C has been also introduced as "good cholesterol" to the public. However, this well accepted knowledge was challenged when two large RCTs demonstrated that increased serum HDL-C by CETP inhibitor (ILLUMINATE and dal-OUTCOMES) failed to show benefits on reducing the risk of atherosclerotic cardiovascular disease. Therefore, many researchers questioned whether serum HDL-C can fully represent the capacity of cholesterol reverse transport of HDL particle, an underpinning of the anti-atherogenic function of HDL. And HDL particle number was considered to be better than HDL-C as a proper parameter to assess the function of HDL. In fact, RCTs that increased serum HDL-C substantially by CETP inhibitor had little effect on HDL particle number, thus resulting in increased cholesterol-overloaded HDL particle. Previous experimental studies observed that cholesterol-overloaded HDL particle exerted a negative impact on cholesterol reverse transport. However, it remains unclear whether cholesterol-overloaded HDL is involved in the development of atherosclerosis in humans. In our study, we measured HDL particle number using nuclear magnetic resonance spectroscopy, and calculated the ratio of HDL-C to HDL particles number to estimate the cholesterol content per HDL particle (HDL-C/P ratio). We found that cholesterol-overloaded HDL particles, indicated by high HDL-C/P ratio, are independently associated with the progression of carotid atherosclerosis in asymptomatic individuals from a community-based cohort study of the Chinese Multi-provincial Cohort Study-Beijing Project.
Author Interviews, Endocrinology, JCEM, OBGYNE / 28.01.2015

Roger Hart MD FRANZCOG MRCOG CREI Winthrop Professor of Reproductive MedicineSchool of Women's and Infants Health Director of Fertility Specialists of Western Australia The University of Western Australia Perth Western Australia 6008MedicalResearch.com Interview with: Roger Hart MD  FRANZCOG MRCOG CREI Winthrop Professor of Reproductive MedicineSchool of Women's and Infants Health Director of Fertility Specialists of Western Australia The University of Western Australia Perth Western Australia 6008 Medical Research: What is the background for this study? What are the main findings? Dr. Hart: PCOS is a very common condition affecting approximately 1 in 12 women and has an estimated annual impact upon the health system in the USA of up to $4.36 billion per year. PCOS is a condition that often manifests itself early in girls life with menstrual problems in adolescence and may lead to reduced fertility in later life due to problems with ovulation. Previous studies have suggested that women with this condition may have other problems in later life, however they have generally been small studies over a short duration. We studied women from 15 years of age, who were admitted to a hospital in Western Australia where a diagnosis of PCOS was recorded on admission. We compared them to women who did not have a PCOS diagnosis recorded on admission using our state-wide hospital database system data linkage. The medical records of 2,566 women with a PCOS diagnosis were followed from 1980 onwards until an average of almost 36 years, and these women were matched to 25,660 women without PCOS. Women with PCOS on average had twice as many hospital admissions and unfortunately were twice as likely to die during the study period. As expected women with PCOS women had a higher rate of menstrual problems and infertility, and require IVF treatment, have a miscarriage or an ectopic pregnancy, and ultimately require surgical intervention for heavy periods and a hysterectomy. In pregnancy women with PCOS were more likely to deliver preterm or have a stillbirth. In addition women with PCOS were four times more likely to develop late onset diabetes, even after taking into consideration obesity. These women wore more likely to have problems with blood pressure and ischemic heart disease, despite being relatively young. They were more likely to develop a deep vein thrombosis and have a diagnosis of asthma. With regard to mental health women with PCOS were twice as likely to have a diagnosis of stress and anxiety and depression. They were more likely to be a victim of self-harm and be involved with a land transport accidents. With regard to cancer; cervical cancer was diagnosed less frequently in women with PCOS, but they had an increased risk of cancer of the womb. The incidence of breast and skin cancers was no different between the groups.
Author Interviews, Circadian Rhythm, CMAJ / 27.01.2015

Scott R. Garrison MD PhD Associate Professor, Department of Family Medicine Director, Pragmatic Trials Collaborative Faculty of Medicine University of Alberta EdmontonMedicalResearch.com Interview with: Scott R. Garrison MD PhD Associate Professor, Department of Family Medicine Director, Pragmatic Trials Collaborative Faculty of Medicine University of Alberta Edmonton MedicalResearch: What is the background for this study? What are the main findings? Dr. Garrison: Nocturnal leg cramps (also called rest cramps) are painful muscle tightenings, most often in the legs or feet, that are brought on by rest and often wake the sufferer from sleep. They are very common in older adults and can also occur during pregnancy. Having read anecdotal mention that the rest cramps of pregnancy appeared to be worse in summer we sought cohort level evidence to determine whether the more common presentation of age-related rest cramps was also seasonal. To do this we primarily looked at new quinine starts in the province of British Columbia over a period of several years. British Columbia has a publicly funded health care system and maintains electronic records on all health services, including prescription drugs, provided to its roughly 4.2 million residents. Quinine is approved for the treatment of acute malaria in Canada but is instead almost exclusively used off-label to prevent rest cramps. As such, new quinine starts are an excellent marker for new or escalating cramp burden. We also looked at Internet searches, geographically limited to the USA, for the term “leg cramps” (reflecting public interest) obtained from the Google Trends Search Volume Index Tool. Seasonality for both of these indicators of cramp burden was assessed by determining how well a least squares minimizing sinusoidal model predicted variability. We found that quinine starts and "leg cramp" related Internet queries were both strikingly sinusoidal with a 365-day periodicity (mid-summer high, mid-winter low) and a peak-to-peak variability that is approximately 2/3 of the mean. Seasonality accounted for 88% of the observed monthly variability (p < 0.0001) in quinine starts, and 70% of the observed variability (p < 0.0001) in “leg cramp” related internet searches.
Author Interviews, Cognitive Issues, JAMA / 26.01.2015

Shelly L. Gray, PharmD, MS Professor of Pharmacy School of Pharmacy, University of Washington, SeattleMedicalResearch.com Interview with: Shelly L. Gray, PharmD, MS Professor of Pharmacy School of Pharmacy, University of Washington, Seattle Medical Research: What is the background for this study? What are the main findings? Dr. Gray: Many medications have anticholinergic effects such as those used to treat overactive bladder, seasonal allergies, and depression.  The general view is that anticholinergic-induced cognitive impairment is reversible, however, emerging evidence suggests that these medications may be associated with increased dementia risk.  We conducted a prospective population-based cohort study in 3434 older adults to examine whether cumulative anticholinergic medication use is associated with increased risk of incident dementia.  Using automated pharmacy data, we found that higher 10-year cumulative dose was associated with increased risk for dementia and Alzheimer disease over an average of 7.3 years of follow-up.  In particular, people with the highest use (e.g. taking the equivalent of oxybutynin 5 mg/day or chlorpheniramine 4 mg/day for longer than 3 years) were at greatest risk.
Author Interviews, JAMA, Ophthalmology / 26.01.2015

MedicalResearch.com Interview with: Simone L. Li, PhD Retina Foundation of the Southwest Dallas, Texas Medical Research: What is the background for this study? What are the main findings? Dr. Li: In a previous study, we found that binocular iPad game play significantly improved visual acuity in the amblyopic eye. The purpose of the current study was to determine the longevity of these effects and we found that the visual acuity improvements obtained with binocular iPad game play had been retained for at least 12 months after the treatment ended.
Author Interviews, FASEB, Genetic Research, Stanford / 26.01.2015

Dr. John Ramunas PhD Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Clinical Sciences Research Center, Stanford University School of Medicine, Stanford, CaliforniaMedicalResearch.com Interview with: Dr. John Ramunas PhD Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Clinical Sciences Research Center, Stanford University School of Medicine, Stanford, California Medical Research: What is the background for this study? Dr. Ramunas: Telomeres comprise repetitive DNA sequences at the ends of chromosomes.  Telomeres protect the ends of chromosomes, but become shorter with each cell division and due to oxidative damage.  Critically short telomeres are implicated in diseases of aging and devastating genetic disorders of insufficient telomere maintenance . Medical Research: What are the main findings? Dr. Ramunas: Our main finding is that telomeres in human cells can be lengthened by a new method with therapeutic potential.  We delivered modified mRNA encoding TERT, the protein component of telomerase, the enzyme that increases the length of telomeres by adding DNA repeats.  The protein TERT is usually the rate limiting component of the enzyme. In this study, we used four groups of cells.  The first group received modified mRNA encoding TERT, and the other three groups were controls that received either mRNA encoding an inactive form of TERT, the solution in which TERT is delivered, or no treatment.  The telomeres of the first group (telomere extending treatment group) were extended rapidly over a period of a few days, whereas the telomeres of the three control groups were not extended.  The first group was also able to undergo more cell divisions, whereas the controls were not.  Importantly for the potential safety of our approach, the telomeres of the first group resumed shortening after they were extended.  This is important because it shows that due to the short, transient treatment, the cells were not immortalized, ie. not tumorigenic. Further, all of the cell populations treated to date eventually stopped dividing, further indicating that they were not immortalized.  We have tested the approach on cell types including fibroblasts and myoblasts and are now testing it on stem cells. A surprising and exciting finding was that we could treat the cells several times with enhanced effects on the capacity of cells to divide.  For instance, after a first treatment, we saw an increase of 50,000-fold in cell numbers before cells stopped dividing, compared to untreated cells.  If we waited a few weeks and repeated this treatment, we saw a similar gain in cell division and number.  Since the increase in numbers is compounded with each treatment, a small sample of cells, for example from a small biopsy, can be amplified to very large numbers.
Author Interviews, Cost of Health Care, NEJM, University of Pennsylvania / 26.01.2015

Daniel Polsky PhD Executive Director, Leonard Davis Institute of Health Economics Professor of Medicine and Health Care Management Perelman School of Medicine and the Wharton School University of PennsylvaniaMedicalResearch.com Interview with: Daniel Polsky PhD Executive Director, Leonard Davis Institute of Health Economics Professor of Medicine and Health Care Management Perelman School of Medicine and the Wharton School University of Pennsylvania Medical Research: What is the background for this study? What are the main findings? Dr. Polsky: The Medicaid Fee bump, a provision of the Affordable Care Act (ACA), raised Medicaid payments to Medicare levels in 2013 and 2014 for selected services and providers expired on January 1, 2015 before policymakers had much empirical evidence about its effects.   The federally funded increase in reimbursements was aimed at expanding access to primary care for the growing number of Medicaid enrollees. The reimbursement increase expired at the end of 2014 in most states.  We found that this policy worked to increase the number of providers offering primary care appointments to Medicaid patients.  The Medicaid pay bump was associated with a 7.7 percentage points increase in new patient appointment availability without longer wait times.   This increase in availability was largest in the states where primary care physicians received the largest increase in their Medicaid reimbursements.
Author Interviews, Blood Pressure - Hypertension, BMJ, Heart Disease / 25.01.2015

MedicalResearch.com Interview with: Dr. Maria Guzman-Castillo Department of Public Health and Policy University of Liverpool, Liverpool, UK Medical Research: What is the background for this study? What are the main findings? Dr. Guzman-Castillo: The UK has experienced a remarkable 60% reduction in coronary heart disease (CHD) mortality since the 1970s. However CHD remains the leading cause of premature death. The aim of our study was to analyse the recent falls in coronary heart disease mortality and quantify the relative contributions from preventive medications and from population-wide changes in blood pressure and cholesterol levels, particularly exploring the potential effects on socioeconomic inequalities, an aspect not well explored in the past. Our study found that, approximately 22,500 fewer deaths were attributable to reductions in blood pressure and cholesterol in the English population between 2000-2007. The substantial decline in blood pressure was responsible for approximately 13,000 fewer deaths. Approximately 1,800 fewer deaths came from medications and some 11,200 fewer deaths from population-wide changes. Reduction in population blood pressure fewer deaths in the most deprived quintile compared with the most affluent. Reduction in cholesterol resulted in substantially smaller gains, approximately 7,400 fewer deaths; approximately 5,300 fewer deaths were attributable to statin use and approximately 2,100 DPPs to population-wide changes. Interestingly, statins prevented more deaths in the most affluent quintile compared with the most deprived. Conversely, population-wide changes in cholesterol prevented threefold more deaths in the most deprived quintile compared with the most affluent.
Author Interviews, OBGYNE, PLoS / 25.01.2015

Charles Morrison PhD FHI 360 Clinical Sciences Durham, North CarolinaMedicalResearch.com Interview with: Charles Morrison PhD FHI 360 Clinical Sciences Durham, North Carolina MedicalResearch: What is the background for this study? What are the main findings? Dr. Morrison: The possible connection between hormonal contraception and HIV acquisition has been an open question for 25 years. Some studies have suggested that there is an increased risk associated with hormonal contraception, particularly with the 3-month injectable contraceptive called depot-medroxyprogesterone acetate (DMPA). Other studies have found that no such risk exists. The World Health Organization (WHO) has held several technical consultations on this subject. WHO’s current guidelines state that “because of the inconclusive nature of the body of evidence on the possible increased risk of HIV acquisition, women using progestogen-only injectable contraception should be strongly advised to also always use condoms, male or female, and other HIV preventive measures.” Two meta-analyses focusing on hormonal contraception and HIV acquisition have recently been published. One of them, FHI 360’s collaborative study, is an individual participant data meta-analysis. It found that users of injectable DMPA were 50 percent more likely to become infected with HIV than women not using hormonal contraceptives. For women using a different injectable progestin, norethisterone enanthate (NET-EN), or combined oral contraceptives (COC), the study investigators did not find a significantly increased risk of acquiring HIV compared to those who were not using hormonal contraceptives. Furthermore, DMPA users were 43 percent and 32 percent more likely to become infected with HIV compared to oral contraceptives users and NET-EN users, respectively. It is important to point out a key secondary finding. The associations between hormonal contraception and risk of becoming infected with HIV were attenuated in studies that had a lower risk of methodological bias compared to those with higher risk of bias. This suggests that some of the risk found to be associated with hormonal contraception in fact may be attributed to inherent flaws in the nonrandomized studies themselves.
Author Interviews, Genetic Research, Melanoma, Nature / 25.01.2015

MedicalResearch.com Interview with: Prof Lukas Sommer. Ph.D. Cell and Developmental Biology University of Zurich Institute of Anatomy Zurich Switzerland MedicalResearch: What is the background for this study? What are the main findings? Prof. Lukas Sommer:   Melanoma, the most aggressive of all skin cancers, is often fatal for patients due to the pronounced formation of metastases. Up to date, a melanoma’s rampant growth was mainly attributed to genetic causes, such as mutations in certain genes. However, we now reveal that so-called epigenetic factors also play a crucial role in the formation of metastases in malignant skin cancer. Epigenetic factors do not influence the gene sequence directly, but rather cause certain genes and chromosomal segments to be packed in different densities – and thus make them accessible for reading. In our study we identified “EZH2” as an epigenetic control protein found very frequently in malignant melanoma cells compared to normal cells. In these cells, “EZH2” controls genes that govern both tumor growth and genes that are important for the formation of metastases. We exploited this central position of EZH2 to combat the cancer by using a pharmacological inhibitor to suppress the activity of EZH2. As a result, we were able to prevent the growth and malignant spread of the cancer in an animal model and in human melanoma cells.
Author Interviews, Heart Disease, JACC, Outcomes & Safety / 25.01.2015

Herbert Aronow, MDMedicalResearch.com Interview with: Herbert D. Aronow, MD, MPH, FACC, FSCAI, FSVM Governor, American College of Cardiology (ACC) – Michigan Chapter Chair, ACC Peripheral Vascular Disease Section Trustee, Society for Vascular Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Aronow: Psychomotor and cognitive performance may be impaired by sleep deprivation.  Interventional cardiologists perform emergent, middle-of-the-night procedures, and may be sleep-deprived as a consequence.  Whether performance of middle-of-the-night percutaneous coronary intervention (PCI) procedures impacts outcomes associated with PCI procedures performed the following day is not known. 
Author Interviews, BMJ, Gastrointestinal Disease, Pediatrics / 25.01.2015

Dr Laila J Tata PhD Associate Professor in Epidemiology Faculty of Medicine & Health Sciences University of NottinghamMedicalResearch.com Interview with: Dr Laila J Tata PhD Associate Professor in Epidemiology Faculty of Medicine & Health Sciences University of Nottingham Medical Research: What is the background for this study? What are the main findings? Response: Over the last decades there has been increased clinical awareness of coeliac disease (CD) partially because of improvements in the accuracy and availability of diagnostic tests, however, we do not have current estimates of actual celiac disease diagnoses in children and it is important to know whether diagnostic patterns vary socioeconomic group. Funded by CORE/Coeliac UK and conducted at the University of Nottingham, this study analysed 2,063,421 children aged less than 18 years who were registered with general practices (primary care doctors) across the United Kingdom contributing to their routine electronic health records to The Health Improvement Network (THIN) database  between 1993 and 2012. The study found 1,247 children were diagnosed with coeliac disease, corresponding to about 1 new case in every 10,000 children each year. Girls consistently had more diagnoses than boys and whilst the incidence of new celiac disease cases among children up to age 2 years remained stable over time, diagnoses in older children almost tripled over the past 20 years. Moreover, the study found a socioeconomic gradient in celiac disease diagnoses, such that children living in less socioeconomically deprived areas were about twice as likely to be diagnosed as those from more deprived areas. This pattern held for boys and girls and for all ages.
Author Interviews, Diabetes, Nature, University of Michigan / 23.01.2015

MedicalResearch.com Interview with: Martin G. Myers, Jr., M.D., M.P.H. Director, Michigan Diabetes Research & Training Center Associate Professor of Internal Medicine - MEND Division Professor of Molecular & Integrative Physiology Marilyn H. Vincent Professor of Diabetes Research and Department of Pharmacology, University of Cambridge, Cambridge, UK.MedicalResearch.com Interview with: Martin G. Myers, Jr., M.D., M.P.H. Director, Michigan Diabetes Research & Training Center Associate Professor of Internal Medicine - MEND Division Professor of Molecular & Integrative Physiology Marilyn H. Vincent Professor of Diabetes Research and Department of Pharmacology, University of Cambridge, Cambridge Medical Research: What is the background for this study? What are the main findings? Dr. Myers: Diabetic people who take insulin to treat their diabetes are at risk of low blood sugar, which can cause serious consequences (including death).  This risk increases as blood sugar control improves, and so this risk limits the ability to control blood sugar.  The body has a system (the counter-regulatory response) that acts to prevent blood sugar from going too low, but this is often impaired in diabetic patients. We identified a brain circuit that senses and responds to falling blood sugar, and which acts to increase blood sugar.  Furthermore, we showed that the hormone leptin modulates the sensitivity of this circuit, and identified the neurotransmitter (CCK) that acts in this circuit to increase blood sugar.  Thus, we have identified several potential drug targets that could be used to prevent or treat low blood sugar in insulin-treated diabetics.  If we are able to pharmacologically modulate the activity of this brain circuit, it could improve the treatment of these patients.
Asthma, Author Interviews, CHEST, Omega-3 Fatty Acids / 23.01.2015

John Brannan PhD Firestone Institute for Respiratory Health at St Joseph’s Healthcare & McMaster University, Hamilton, Ontario, CanadaMedicalResearch.com Interview with: John Brannan PhD Firestone Institute for Respiratory Health at St Joseph’s Healthcare & McMaster University, Hamilton, Ontario, Canada Medical Research: What is the background for this study? Response: The use of omega-3 acid supplements as treatments for allergic diseases including asthma is controversial. Studies by investigators from Indiana University in the USA have repeatedly demonstrated a beneficial effect of high dose omega-3 fatty acid supplements over 3 weeks in attenuating exercise-induced bronchoconstriction (EIB) similar or possibly better in potency to what may be expected with a regular inhaled corticosteroids. The study by Brannan et al. attempted to validate these findings by using inhaled mannitol, a bronchial provocation test that was derived from the understanding of exercise-induced bronchoconstriction and which has demonstrated experimentally to be a useful model for exercise-induced bronchoconstriction. All pharmacotherapies that modify exercise-induced bronchoconstriction can modify the airway sensitivity to inhaled mannitol in persons with asthma, thus it was of interest to see if an 'alternative' treatment that demonstrated efficacy in exercise-induced bronchoconstriction could too modify the airway response to mannitol. Medical Research: What are the main findings? Response: The main findings were, to our surprise, there was no benefit of high dose omega-3 fatty acid supplements on bronchial hyperresponsiveness to mannitol over 3 weeks. This was associated with no changes in airway inflammation (sputum eosinophils), lung function or asthma symptom control. We also found no benefit on resting urinary mast cell metabolites, in contrast to the findings in studies showing a benefit of omega-3 fatty acids on EIB. Our findings suggest that omega-3 supplements in tissues may not be able to penetrate tissue and/or modify the substrate flow of eicosanoids in tissue such as the airways of the asthmatic. We did observed the expected reductions in blood triglycerides which suggests that these doses of omega-3s can modify metabolism in the blood or to some extent tissues that are highly perfused.
Author Interviews, BMJ, Exercise - Fitness / 23.01.2015

Sarah Hanson Norwich Medical School University of East AngliaMedicalResearch.com Interview with: Sarah Hanson Norwich Medical School University of East Anglia Medical Research: What is the background for this study? What are the main findings? Response: Physical inactivity is a global problem. Walking is an easy way to increase physical activity. One way to increase physical activity may be through the use of outdoor walking groups. Walking groups are increasingly popular but until now we have not known if there are wider health benefits from walking groups, apart from increasing physical activity. Medical Research: What was the study method? Response: A systematic review and meta-analysis of outdoor walking group interventions found 42 studies which met the eligibility criteria. These studies involved 1,843 participants in 14 countries doing approximately 74,000 hours of walking.
Author Interviews, Diabetes, PLoS / 23.01.2015

Dr. Holger Rehmann Department of Molecular Cancer Research UMC Utrecht The NetherlandsMedicalResearch.com Interview with: Dr. Holger Rehmann Department of Molecular Cancer Research UMC Utrecht The Netherlands Medical Research: What is the background for this study? What are the main findings? Dr. Rehmann: We have developed a chemical modified version of the second messenger cAMP, Sp-8-BnT-cAMPS that allows selective activation of Epac2, a protein that augments glucose induced insulin secretion. The second messenger cAMP activates a couple of receptor proteins, which controls such divergent physiological effects as gene transcription, pacemaker activity, olfaction, and cell adhesion. Almost any cell responses in one or the other way to cAMP and thus selective action on only one cAMP receptor would be a requirement for a drug to induce specific effects. The study confirms that it is possible to pharmacologically discriminate between structurally highly related cAMP receptors. And indeed, Sp-8-BnT-cAMPS augments glucose induced insulin secretion in primary human islets. Epac2 is thus a putative target for the development of an antidiabetic drug.