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. (more…)
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. (more…)
Author Interviews, Heart Disease, Ophthalmology / 28.01.2015

MedicalResearch.com Interview with: Ren-Long Jan Department of Pediatrics, Chi Mei Medical Center, Liouying, Tainan, Taiwan Graduate Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan. Medical Research: What is the background for this study? What are the main findings? Response: The pathologenic factors underlying retinal artery occlusion (RAO) are also associated with acute coronary syndrome (ACS). Previous studies showed the relation but was limited by sample sizes. We used Taiwan Longitudinal Health Insurance Database and found the increased risk of ACS following Retinal artery occlusion. (more…)
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. (more…)
Alcohol, Author Interviews, Gastrointestinal Disease / 28.01.2015

Gro Askgaard MD Department of Hepatology, Copenhagen University Hospital, Rigshospitalet National Institute of Public Health, University of Southern Denmark Copenhagen DenmarkMedicalResearch.com Interview with Gro Askgaard MD Department of Hepatology, Copenhagen University Hospital, Rigshospitalet National Institute of Public Health, University of Southern Denmark Copenhagen Denmark Medical Research: What is the background for this study? Dr. Askgaard: Alcohol is the main risk factor of cirrhosis in Europe, where 1.8% of all deaths are attributable to liver disease. Alcohol amount is known to be a significant factor of development of cirrhosis - the greater alcohol amount, the greater risk. Less is known about drinking pattern - how the way you drink alcohol affects your risk. In this study we evaluated the influence of drinking frequency (drinking days/week), of lifetime alcohol consumption versus recent alcohol consumption, and alcohol type (wine, beer, liquor). (more…)
Author Interviews, Cost of Health Care, Heart Disease / 28.01.2015

Andre Lamy MD MHSc COMPASS (CABG sub-group PI) CORONARY Principal Investigator Professor, Dept Surgery, Division Cardiac Surgery Associate Member, Dept Clinical Epidemiology & Biostatistics McMaster University Hamilton General Hospital Hamilton, ON, CanadaMedicalResearch.com Interview with: Andre Lamy MD MHSc COMPASS (CABG sub-group PI) CORONARY Principal Investigator Professor, Dept Surgery, Division Cardiac Surgery Associate Member, Dept Clinical Epidemiology & Biostatistics McMaster University Hamilton General Hospital Hamilton, ON, Canada Medical Research: What is the background for this study? Dr. Lamy: The Canadian healthcare system operates in an environment that must constantly find new ways to make healthcare delivery more efficient. In the TIMACS clinical led by Dr. Shamir Mehta, it was found that the primary outcome was similar for an early invasive procedure within 24 hours and a delayed approach of after 36 hours in outcomes. However, because of the inherent shorter length of stay associated with early invasive procedures within 24 hours there will be definite cost-savings from an early invasive strategy. Dr. Andre Lamy et al looked at the cost implications of this shorter length of stay in the TIMACS trial and explored the impact of the use of a catheterization lab on days when they are normally not in use (i.e. weekends), which may negate the savings of early intervention. Medical Research: What are the main findings? Dr. Lamy: The main findings of our study were that early invasive strategy was cost-saving for Canadian NTSE-ACS patients due to significant savings from the shorter length of stay. These savings were present even if as many as 50% of TIMACS patients were assumed to be weekend cases. Given many high-risk NSTE-ACS patients receive delayed intervention due to weekend catheterization lab status, these findings support operating catheterization labs on weekends to facilitate the use of early invasive intervention. (more…)
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. (more…)
AHRQ, Author Interviews, Cost of Health Care / 28.01.2015

Raynard E. Washington, PhD, MPH Center for Delivery, Organization, and Markets Agency for Healthcare Research and Quality Rockville, MD 20850MedicalResearch.com Interview with: Raynard E. Washington, PhD, MPH Center for Delivery, Organization, and Markets Agency for Healthcare Research and Quality Rockville, MD 20850 Medical Research: What is the background for this study? What are the main findings? Dr. Washington: Many individuals with low income who require a hospital stay are uninsured or covered by Medicaid, a joint Federal-State health insurance program for eligible individuals and families with low income. The difference in hospital utilization among patients covered by Medicaid and those who are uninsured may reflect differences in the characteristics of these populations and their level of access to health care. This HCUP Statistical Brief describes 2012 hospital stays with a primary expected payer of Medicaid and stays that were uninsured. Of the 36.5 million total hospital inpatient stays in 2012, 20.9 percent had an expected primary payer of Medicaid and 5.6 percent were uninsured; 30.6 percent were covered by private insurance. Patients covered by Medicaid were on average younger and more likely to live in low-income areas than were patients with private insurance. Patients who were uninsured were more likely to be male and to live in low-income communities than were patients with private insurance. The majority of the top 10 diagnoses for Medicaid hospitalizations were ambulatory care sensitive conditions. Cholecystectomy (gall bladder removal) was the most common operating room procedure for Medicaid and uninsured stays. (more…)
Author Interviews, Heart Disease, Mayo Clinic, Testosterone / 27.01.2015

Abraham Morgentaler, MD Director and Founder Men’s Health BostonMedicalResearch.com Interview with: Abraham Morgentaler, MD Director and Founder Men’s Health Boston Medical Research: What is the background for this study? What are the main findings? Response: There has been  tremendous media attention over the last 15 months to two retrospective studies that reported increased cardiovascular risks with testosterone. Those reports anchored a variety of stories critical of testosterone therapy for non-scientific reasons, such as alleged dangers of direct-to-consumer advertising.  In this review we investigated the two recent studies in depth, as well as the broader literature regarding testosterone and cardiovascular issues. One primary finding was that the studies alleging risk were remarkably weak and flawed- one reported low rates of MI and had no control group, and the other had such large data errors (nearly 10% of the all-male population turned out to be female!) that 29 medical societies have called for its retraction. In contrast, there is substantial literature suggesting that testosterone therapy, or naturally occurring higher levels of testosterone, is protective against atherosclerosis, and mortality.  Several small randomized controlled trials in men with known heart disease- angina and congestive heart failure- have even shown benefits for men that received testosterone compared with placebo. (more…)
Author Interviews, Brigham & Women's - Harvard, Heart Disease, Kidney Disease, Rheumatology / 27.01.2015

Dr Gomez-Puerta MD, PhD, MPH Division of Rheumatology, Immunology, and Allergy; Brigham and Women's Hospital, Harvard Medical School, Boston, MA Medical Research Interview Dr Gomez-Puerta MD, PhD, MPH Division of Rheumatology, Immunology, and Allergy; Brigham and Women's Hospital, Harvard Medical School, Boston, MA MedicalResearch: What is the background for this study? What are the main findings? Dr. Gomez-Puerta: Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown etiology which can cause multiorgan system damage and which disproportionately affects women and non- Caucasian minorities. Up to 60% of SLE patients develop renal disease, lupus nephritis (LN), and of these, approximately one fifth progress to end-stage renal disease (ESRD). The risk of cardiovascular (CV) events and mortality is higher in patients with ESRD and in particular in patients suffering SLE. However, information about CV outcomes and mortality is limited in patients with LN associated ESRD. We observed important variation in cardiovascular outcomes and mortality by race and ethnicity among lupus nephritis related ESRD patients. After adjusting for multiple demographic and clinical factors and accounting for the competing risk of kidney transplantation and loss to follow-up, our results illustrate for the first time that Asian (vs. White) and Hispanic (vs. non-Hispanic) lupus nephritis related ESRD patients have lower mortality risks. (more…)
Author Interviews, Autism, Radiology / 27.01.2015

Gabriel S. Dichter, PhD Associate Professor UNC Departments of Psychiatry and Psychology Carolina Institute for Developmental Disabilities MedicalResearch.com Interview with: Gabriel S. Dichter, PhD Associate Professor UNC Departments of Psychiatry and Psychology Carolina Institute for Developmental Disabilities Medical Research: What is the background for this study? What are the main findings? Dr. Dichter: The background for this study is that although most brain imaging research in autism spectrum disorders has focused on understanding the brain basis of social communication impairments, we know that autism symptoms are pervasive and may include difficulties with irritability, anxiety, mood, and even in some instances aggression or self injurious behaviors.  Additionally, these types of associated features are among the first that prompt parents to bring their child to a pediatrician for an evaluation for a neurodevelopmental disorder, and so we know these symptoms can be deeply troubling to parents.  All of these associated symptoms of autism suggest difficulty with regulating emotional responses, and so our team set out to investigate the brain basis of these difficulties.  We taught participants with and without autism simple strategies to change their emotion responses and then scanned them using functional MRI to measure brain activity when they actively tried to change their emotional responses to pictures of faces.  Our central finding was that although they reported they were able to change their emotional responses, brain imaging findings told us something quite different.  The dorsolateral prefrontal cortex, a part of the brain that controls emotional responses, was underactive in the participants with autism.  Consequently, they were less able to modulate parts of the brain’s limbic system that produces strong emotional responses.  In other words, they had difficulty “turning on the brakes” to control emotional responses.  Finally, the differences we observed in their brain activity predicted the severity of their overall autism symptoms, suggestion a direct linkage between emotion regulation impairments and autism severity. (more…)
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. (more…)
Author Interviews, Cognitive Issues, HIV / 27.01.2015

Sophie Cohen MD, PhD Student Department of Pediatric Haematology, Immunology and Infectious Diseases, Emma Children's Hospital, Academic Medical Center, Amsterdam, the Netherlands Cairns Base Hospital Australia MedicalResearch.com Interview with: Sophie Cohen MD, PhD Student Department of Pediatric Haematology, Immunology and Infectious Diseases, Emma Children's Hospital, Academic Medical Center, Amsterdam, the Netherlands Cairns Base Hospital Australia Medical Research: What is the background for this study? What are the main findings? Response: Since combination antiretroviral therapy (cART) has become widely available for HIV-infected children, the incidence of severe neurological complications has decreased drastically from 30-50% to less than 2%. Unfortunately, even in cART-treated HIV-infected children a range of cognitive problems have been found, such as a lower intelligence quotient (IQ) and poorer visual-motor integration. Importantly, while most HIV-infected children in industrialized countries are immigrants with a relatively low socioeconomic status (SES), cognitive studies comparing HIV-infected children to SES-matched controls are very scarce.  Understanding the prevalence and etiology of cognitive deficits in HIV-infected children is essential because they may result in more pronounced problems, and influence future intellectual performance, job opportunities and community participation. Also, early detection of cognitive impairment might trigger the development of early intervention strategies. In this study we aimed to compare the neuropsychological profile of HIV-infected children to that of healthy controls, matched for age, gender, ethnicity and SES. Also, we aimed to determine the prevalence of cognitive impairment in the HIV-infected group and detect associations between HIV/cART parameters and cognitive performance. We found that the HIV-infected group had a poorer cognitive performance compared with the healthy children on all tested domains (including intelligence, information processing speed, attention, memory, executive- and visual-motor functioning). Using a novel statistical method called Multivariate normative comparison (MNC), we detected a prevalence of 17% with cognitive impairment in the HIV-infected group. Lastly, we found that the center for disease control (CDC) clinical category at HIV diagnosis was inversely associated with verbal IQ (CDC C: coefficient -22.98, P=0.010). (more…)
Author Interviews, Primary Care, Radiology / 27.01.2015

Christine Hughes Hadley Hart Group, Chicago, IllinoisMedicalResearch.com Interview with: Christine Hughes Hadley Hart Group, Chicago, Illinois Medical Research: What is the background for this study? Response: Value in healthcare is a popular topic today. Yet no clear value measures have been developed which could be used in policy decisions on reimbursement for diagnostic imaging procedures.  Within the imaging sector it is a given that imaging has value.  However efforts to articulate that value to payers and policy makers and others outside the sector have come up short.   We did conduct qualitative research with radiologists but during this process of mapping a value chain it became clear that those M.D.s who use the data that radiology provides to make decisions on patient care could better speak to imaging’s value.  And primary care because of the gatekeeper status for all types of care seemed appropriate. Medical Research: What are the main findings? Response: Primary care physicians highly value access to advanced imaging: 88% of the PCPs indicated that advanced imaging increases their diagnostic confidence; 90% believe imaging provides data not otherwise available; 88% reported access to imaging  permits better clinical decision making;  88% reported increases confidence in treatment choices , and 86% say it shortens time to definitive diagnosis. Most  Primary care physicians ( 85%) believe that patient care would be negatively impacted without access to advanced imaging. One very interesting finding is in differences in attitudes and valuations in younger vs. older physicians towards advanced imaging modalities.  For the purposes of this part of the analysis we divided the survey respondents into those in practice 1-20 years and those practicing radiology more than 21 years.  Presumably those practicing less 21 years trained with ready access to advanced imaging versus those who presumably having practiced without ready access to the advanced imaging modalities of MRI, CT and PET. Respondents who have practiced without ready access attach higher value to the ability to shorten the time to definitive diagnosis, ability to replace invasive procedures, make better clinical decisions, and believe the quality of patient care would be negatively impacted without access to advanced imaging.  The younger physicians attach more value to the practice efficiency issues such as enabling the Primary care physician to see more patients, or patient centric issues like the ability to communicate on a visual level with the patient. (more…)
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. (more…)
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. (more…)
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. (more…)
Alzheimer's - Dementia, Author Interviews, Cognitive Issues / 26.01.2015

MedicalResearch.com Interview with: Craig S. Atwood Associate Professor, University of Wisconsin Madison, WI Richard L. Bowen, M.D. Private Practice, Charleston, SC Medical Research: What is the background for this study? Response: Currently, there is no treatment for Alzheimer’s disease that halts or slows its progression. Alzheimer’s disease is a neurodegenerative disorder resulting in memory loss and impairments of behavioral, language and visuo-spatial skills. A growing body of biological, preclinical and epidemiological data suggests that the age-related changes in hormones of the hypothalamic-pituitary-gonadal (HPG) axis are a major etiological factor in Alzheimer disease. The changes in these hormones include not only the decline in the sex steroids, (i.e. 17-estradiol and testosterone), but the elevations in gonadotropin-releasing hormone and luteinizing hormone. In particular there are encouraging epidemiological studies involving the use of Lupron Depot which suppresses these hormones. In one such study which included hundreds of thousands of patients it was found that men who had prostate disease and were treated with Lupron Depot had a 34 to 55 percent decreased risk of developing Alzheimer’s disease compared with prostate-cancer patients who didn’t receive the drug. (more…)
Author Interviews, Baylor College of Medicine Houston, Cognitive Issues, Sleep Disorders / 26.01.2015

Michael K. Scullin, Ph.D. Principal Investigator of the Sleep Neuroscience & Cognition (SNaC) Laboratory and an Assistant Professor of Psychology & Neuroscience Director Sleep Neuroscience and Cognition Laboratory Baylor UniversityMedicalResearch.com Interview with: Michael K. Scullin, Ph.D. Principal Investigator of the Sleep Neuroscience & Cognition (SNaC) Laboratory and an Assistant Professor of Psychology & Neuroscience Director Sleep Neuroscience and Cognition Laboratory Baylor University Medical Research: What is the background for this study? What are the main findings? Dr. Scullin: One of the purposes of sleep in healthy adults is to optimize cognitive functioning. When we lose out on a few hours of sleep we tend not to be able to focus or think as well as when we get enough sleep (typically 8 hours). Even more interesting is that particular aspects of sleep physiology—our deepest levels of sleep known as slow wave sleep and rapid eye movement sleep—are essential to our brain’s ability to take the information that we learn during the day and stabilize those memories so that we can use them in the future. Sleep quantity and quality change markedly across the lifespan, though there are individual differences in how much one’s sleep changes. Our work was concerned with the possible long-term repercussions of cutting back on sleep and getting lower quality sleep (less slow wave sleep and rapid eye movement sleep).  We reviewed approximately 200 scientific articles on this topic and we found that the amount of total sleep and the quality of that sleep is important to cognitive and memory functioning in young adults and middle-aged adults and can even predict how well someone’s cognitive functioning will be decades later. Thus, if you’re sleeping well when you are 40 then you are investing in preserving your mental functioning at age 50. (more…)
Antibiotic Resistance, Author Interviews, Infections / 26.01.2015

Anu Kantele, MD PhD Associate Professor, Department of Medicine, University of Helsinki Specialist of Infectious Diseases, Helsinki University Hospital Head of Travel Clinic, Aava Medical Centre "Photo taken by Leena Mattila/YLE/science"MedicalResearch.com Interview with: Anu Kantele, MD PhD Associate Professor, Department of Medicine, University of Helsinki Specialist of Infectious Diseases, Helsinki University Hospital Head of Travel Clinic, Aava Medical Centre Medical Research: What is the background for this study? What are the main findings? Dr. Kantele: Increasing antimicrobial resistance is considered a serious global threat for modern medicine. Resistance is rapidly surging in regions with poor hygiene and uncontrolled use of antibiotics. Resistant bacteria are gradually spreading from there to countries in which the prevalence has thus far been low. Our study was conducted among 430 healthy Finnish travelers visiting warm countries (tropical /subtropical regions). The volunteers provided stool samples before and after travel and filled in questionnaires. The stools were analyzed for multidrugresistant bacteria (not only so called ESBL bacteria but also CPE bacteria which are even more resistant). None of the travelers had CPE strains in their stools before or after their journey. 1% carried ESBL before travel, and 21% acquired a strain while overseas. The risk was greatest in the Indian subcontinent and almost similar in Southeast Asia. In Africa, it proved to be increased but did not reach such a high level. Two factors amplified the risk significantly: travellers’ diarrhea and use of antibiotics. Among the entire study population, ESBL was found in 11% of those staying healthy, 22% of those with diarrhea, and 37% of those who took antibiotics for their diarrhea. In the Indian subcontinent, the respective figures were 23%, 47%, and 80%, and in Southeast Asia 14%, 32%, and 69%. Medical Research: Why do antibiotics predispose to contracting resistant bacteria from the surroundings? Dr. Kantele: The effects of antibiotics cannot be restricted to killing merely the bugs we wish them to kill. When doing their job they also wipe out a huge number of our own intestinal bacteria, thereby opening the door for newcomers’ invasion. If antibiotics are taken in an environment exposing people to a multitude of resistant bacteria, part of these newcomers are likely to be resistant ones. Antibiotics may, in fact, kill the sensitive newcomers and favor the resistant ones. (more…)
Antibiotic Resistance, Author Interviews, Infections / 26.01.2015

Dr. Thiago César Nascimento Assistant Professor, Department of Basic Nursing Laboratory of Bacterial Physiology and Molecular Genetics Institute of Biological Sciences Federal University of Juiz de Fora, BrazilMedicalResearch.com Interview with: Dr. Thiago César Nascimento Assistant Professor, Department of Basic Nursing Laboratory of Bacterial Physiology and Molecular Genetics Institute of Biological Sciences Federal University of Juiz de Fora, Brazil Medical Research: What is the background for this study? What are the main findings? Response: Preliminarily, we observed a high incidence of coagulase-negative  Staphylococcus  strains (CoNS) recovered from the leachate of the health care waste in an untreated sanitary landfill. As Staphylococcus sp. especially oxacillin or methicillin-resistant CoNS remains as important putative pathogenic bacteria regarding human and other animals, in this study we investigated the antimicrobial susceptibility patterns and the occurrence of the  mecA  gene. In conclusion, our results raise issues related to the viability of putative pathogenic bacteria resistant to important antimicrobial drugs carrying important resistance markers in untreated healthcare waste in sanitary landfills.These risks regarding the potential spread of leachate from sanitary landfills due to human and animal activities, or even due to weather phenomena, such as torrential rains and floods, should be considered. Our results address a phenomenon related to the incorrect healthcare waste management in Brazil and in other geographical regions. Taking into account environmental health, more conscientious  policies should be considered by authorities to avoid the disposal of healthcare waste without any further treatment. (more…)
Author Interviews, Genetic Research / 26.01.2015

MedicalResearch.com Interview with: Joao Pedro de Magalhaes, PhD Institute of Integrative Biology Biosciences Building, Room 245 University of Liverpool UK Integrative Genomics of Ageing Group: http://pcwww.liv.ac.uk/~aging/ Medical Research: What is the background for this study? What are the main findings? Response: Our understanding of species differences in longevity (e.g., why can mice not live more than 5 years or dogs more than 30, yet bats can live over 40 years, humans over a century and bowheads over two centuries) is very poor and thus our findings provide novel candidate genes and mechanisms for future studies. The candidate genes we found with evidence of bowhead-specific functions may play a role in the exceptional longevity and disease resistance of these animals. In particular, we discovered changes in bowhead genes related to cell cycle, DNA repair, cancer, and aging that suggest alterations that may be biologically-relevant.  So my own view is that this points toward improved DNA repair and cell cycle regulation mechanisms to prevent DNA damage accumulation during the lifescourse which in turn promotes longevity and resistance to age-related diseases like cancer. (more…)
Author Interviews, Breast Cancer, Karolinski Institute / 26.01.2015

Dr Jingmei Li Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm, SwedenMedicalResearch.com Interview with: Dr Jingmei Li Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm, Sweden Medical Research: What is the background for this study? What are the main findings? Response: Some cancers, such as interval breast cancers, which are detected within two years of a negative mammogram, are associated with more aggressive tumour characteristics and worse prognosis. As women with interval cancers were twice as likely to have a personal of family history of breast cancer, it is likely that there exist inherited variants that predispose a woman to the more aggressive form of the disease. Our study is one of the first to show empirical evidence that screen-detected and interval cancers are different genetically and are two distinct subtypes. (more…)
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. (more…)
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. (more…)
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. (more…)
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. (more…)
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.  (more…)
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. (more…)