Medical research slideshare_june_24_2015

MedicalResearch.comExclusive Interviews with Medical Research and

Health Care Researchers from Major and Specialty Medical Research Journals and Meetings

Editor: Marie Benz, MD [email protected]

June 24 2015

For Informational Purposes Only: Not for Specific Medical Advice.

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States With Stroke Legislation Have More Certified Stroke CentersMedicalResearch.com Interview with:Dr. Ken Uchino, MDCleveland Clinic Main CampusCleveland, OH 44195

• Medical Research: What is the background for this study? What are the main findings?

Dr. Uchino: Stroke center designation started in 2003 and more hospitals have been certified as primary stroke centers over time. We asked the question how many are certified now? What are the characteristics of the hospitals that are certified?

• In 2013, nearly a third (23%) of acute short-term adult general hospitals with emergency departments were certified as stroke centers. 74% of the stroke centers were certified by the Joint Commission, a non-profit organization that certifies health care facilities and programs. 20% were certified by state health departments. States varied in percentages of hospitals that were certified, ranging from 4% in Wyoming to 100% in Delaware.

• Not unexpectedly larger hospitals and hospitals in urban locations were more likely to be certified as stroke centers.

• But a hospital being located in a state with so-called “stroke legislation” more than tripled the chance of being a certified stroke centers, even accounting for other factors. These states passed legislation to promote stroke centers and mandated stroke patients to be preferentially transported to qualified hospitals.

Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.

http://medicalresearch.com/stroke/states-with-stroke-legislation-have-more-certified-stroke-centers/15098/







http://medicalresearch.com/stroke/comprehensive-stroke-centers-save-lives-in-patients-with-hemorrhagic-stroke/14030/





http://medicalresearch.com/menopause/should-the-ovaries-be-removed-at-time-of-hysterectomy-for-benign-disease/1236/


• Medical Research: What should clinicians and patients take away from your report?• Dr. Uchino: More hospitals are being designated as stroke centers. Certification can be

accomplished in smaller hospitals with appropriate support such as telemedicine and care protocols. Know whether your local hospital is stroke-certified.

• Changes in policy at state level (stroke legislation) impacts availability of good stroke care. Remind your legislator the importance of stroke and stroke care.









http://medicalresearch.com/author-interviews/telemedicine-may-improve-access-to-chronic-kidney-disease/15072/







• Medical Research: What recommendations do you have for future research as a result of this study?

• Dr. Uchino: Designation of stroke centers and quality improvement programs appear to have improved stroke care and patient outcomes. Further research needs to show what we can do next to improve systematic care, whether higher level of comprehensive stroke center designation improves outcomes, and whether these changes have had impact at population level.

• Citation:• Uchino K, et al “Stroke legislation impacts distribution of certified stroke centers in the United

States”Stroke 2015; DOI: 10.1161/STROKEAHA.114.008007.









http://medicalresearch.com/stroke/fast-treatment-for-acute-ischemic-stroke-improves-recovery/10254/






Neutrophil-to-Lymphocyte Ratio May Identify Melanoma Patients Likely To Benefit From IpilimumabMedicalResearch.com Interview with:Chiara Martinoli, PhDMedical Oncology of MelanomaEuropean Institute of OncologyMilan, Italy

• MedicalResearch: What is the background for this study? What are the main findings?• Dr. Martinoli: The recent advent of new immunomodulatory drugs and targeted therapies is

changing the therapeutic algorithm for metastatic melanoma patients. Immunomodulation with the anti-CTLA-4 antibody ipilimumab improves survival but is not devoid of potential risks. There is an urgent need for biomarkers to identify patients best suited to receive this therapy, in order to maximize treatment benefit and spare toxicities.

• In this study, by analyzing pre-therapy hematological parameters of a large group of metastatic melanoma patients treated with ipilimumab, we showed that neutrophil-to-lymphocyte ratio is strongly and independently associated to patient outcome. Patients with a low baseline neutrophil-to-lymphocyte ratio had a double-reduced risk of disease progression and a two-to-four-fold reduced risk of death, regardless of age, sex and LDH.


http://medicalresearch.com/author-interviews/neutrophil-to-lymphocyte-ratio-may-identify-melanoma-patients-likely-to-benefit-from-ipilimumab/14986/











http://medicalresearch.com/author-interviews/melanoma-nivolumab-vaccine-ipi-refractory-melanoma/2336/







• MedicalResearch: What should clinicians and patients take away from your report?• Dr. Martinoli: We suggest that the pre-therapy neutrophil-to-lymphocyte ratio might help the

identification of patients that are more likely to benefit from ipilimumab.• The identification of patients who are more likely or unlikely to benefit from a therapy in

advance of its initiation would allow to optimize disease-management strategies, by giving patients the treatment they are best suited to receive, sparing them from un-necessary drug-related toxicities, and improving their quality of life.

• Moreover, the neutrophil-to-lymphocyte ratio would represent a convenient objective marker, as it is derived from routine diagnostic procedures, it is does not require additional expenditure, it is easily and promptly computable.



















• MedicalResearch: What recommendations do you have for future research as a result of this study?

• Dr. Martinoli: We would strongly encourage prospective studies with adequately powered sample size and clinical trials to validate these findings for patients receiving ipilimumab or other immunotherapies.

• CITATION:• Br J Cancer. 2015 Jun 9;112(12):1904-10. doi: 10.1038/bjc.2015.180. Epub 2015 May 26.• Baseline neutrophil-to-lymphocyte ratio is associated with outcome of ipilimumab-treated m

etastatic melanoma patients.• Ferrucci PF1, Gandini S2, Battaglia A1, Alfieri S1, Di Giacomo AM3, Giannarelli D4, Cappellini GC5

, De Galitiis F5, Marchetti P6, Amato G3, Lazzeri A3, Pala L1, Cocorocchio E1, Martinoli C1.













http://medicalresearch.com/author-interviews/melanoma-nivolumab-vaccine-ipi-refractory-melanoma/2336/

http://www.ncbi.nlm.nih.gov/pubmed/26010413





































What Is Best Way To Structure Interdisciplinary Hospital Team Work?MedicalResearch.com Interview with:Samuel Pannick, MA, MBBS, MRCP

Imperial Patient Safety Translational Research Center, National Institute for Health Research and Imperial College London, London, England

West Middlesex University Hospital National Health Service Trust, Middlesex, England• Medical Research: What is the background for this study? What are the main findings?

Response: Improving the quality of general medical ward care is a recognized healthcare priority internationally. Ward teams have been encouraged to structure their work more formally, with regular interdisciplinary team meetings and closer daily collaboration with their colleagues. Some early studies suggested that these changes might benefit patients, and help ward teams work more efficiently. However, team interventions on medical wards have been reported with numerous different outcome measures, and prior to this study, it was unclear what their objective benefits were.

• We showed that there is little agreement on the objective outcomes that best reflect the quality of interdisciplinary team care on general medical wards. Changes to interdisciplinary care aren’t reflected in the outcome measures that researchers choose most often, like early readmission rates or length of stay. Complications of care – although harder to record – might have more promise as a measure of the quality of inpatient team care in these specific medical areas.


http://medicalresearch.com/general-medicine/what-is-best-way-to-structure-interdisciplinary-hospital-team-work/15059/

















West Middlesex University Hospital National Health Service Trust, Middlesex, England• Medical Research: What should clinicians and patients take away from your report?• Response: Interdisciplinary work in general medicine remains one of the most important –

and enjoyable – components of patient care. However, it’s vital that we don’t try to assess team performance against inappropriate quality metrics. More nuanced measures require more resources for data collection, but will ultimately give a truer picture of the quality of the care.



















West Middlesex University Hospital National Health Service Trust, Middlesex, England• Medical Research: What recommendations do you have for future research as a result of

this study?• Response: Future research should establish a core set of outcomes that better reflect the

quality of general medical ward care. With these measures in place, new studies can then focus on how interdisciplinary team care interventions are implemented – an important factor in their success. Ultimately, we need to understand the preconditions for good interdisciplinary care, and the way it interacts with other elements of good practice.

• Citation:• Pannick S, Davis R, Ashrafian H, et al. Effects of Interdisciplinary Team Care Interventions on G

eneral Medical Wards: A Systematic Review. JAMA Intern Med. Published online June 15, 2015. doi:10.1001/jamainternmed.2015.2421.












http://archinte.jamanetwork.com/article.aspx?articleid=2301377








Genetic and Environmental Factors Linked To Delay of Aging-Related DiseasesMedicalResearch.com Interview with: Arlene Ash Ph.D., Professor David Hoaglin Ph.D., Professor andAimee R. Kroll-Desrosiers, MS

Department of Quantitative Health SciencesUniversity of Massachusetts Medical SchoolWorcester, MA


Response: The Long Life Family Study (LLFS) is an international collaborative investigation of the genetics and familial components of exceptional survival, longevity, and healthy aging. It has enrolled members of long-lived sibships, their offspring, and spouses of either group. Medicare claims data is a unique, nationally representative source of data on all treated diseases for most Americans over the age of 65.

• Our main question was: Does membership in a long-lived family protect against disease?• For each American LLFS participant who was at least age 65 in 2008 and alive in 2009, we

selected four persons from the general Medicare population who matched the participant on age, sex, and ZIP code of residence. We then used 2008–2010 Beneficiary Annual Summary Files from the Centers for Medicare & Medicaid Services (CMS) to compare the prevalence of 17 conditions among 781 LLFS participants in Medicare with those of 3,227 non-LLFS matches.* Analyses accounted for nesting within LLFS families and adjusted for age, sex, race, and year.


http://medicalresearch.com/author-interviews/genetic-and-environmental-factors-linked-to-delay-of-aging-related-diseases/15053/























• Among LLFS participants identified as members of a long-lived sibship, 7 of the 17 conditions were significantly less common than for similarly aged controls (Alzheimer’s, hip fracture, diabetes, depression, prostate cancer, heart failure and chronic kidney disease); in contrast, 4 (arthritis, cataract, osteoporosis and glaucoma) were significantly more common. Spouses, offspring and offspring spouses of these long-lived siblings share in significantly lower risk for Alzheimer’s, diabetes and heart failure.

• Several additional analyses found suggestive (although not statistically significant) evidence of lower disease prevalence in both genetically and maritally-related LLFS cohort


















http://medicalresearch.com/mental-health-research/alzheimers-dementia/pet-scan-can-detect-amyloid-in-alzheimers-and-other-dementias/14283/








• Medical Research: What should clinicians and patients take away from your report?• Response: Both genetic and environmental factors appear to be involved in familial clustering

of delayed onset of age-related disease.


























• Response: Because most of the offspring generation is still under age 75, it will be fascinating to see whether the early evidence for a health advantage in both genetic and marital relatives of long-lived siblings strengthens as the cohort ages.

• It will also be useful to understand why diagnoses of arthritis, cataract, osteoporosis and glaucoma are more common among the LLFS siblings than in the general population. If this cannot be explained by differences in health-seeking behaviors, it is truly puzzling.

• * A small number of LLFS members and matches had been eliminated for data incompleteness, modestly perturbing the 4:1 study design.

• Citation:• Arlene S. Ash, Aimee R. Kroll-Desrosiers, David C. Hoaglin, Kaare Christensen, Hua Fang, and T

homas T. Perls• Are Members of Long-Lived Families Healthier Than Their Equally Long-Lived Peers? Evidence

From the Long Life Family Study J Gerontol A Biol Sci Med Sci first published online March 5, 2015 doi:10.1093/gerona/glv015


















http://medicalresearch.com/menopause/recommended_osteoporosis_screening_may_not_effectively_screen_younger_patients/8439/

http://biomedgerontology.oxfordjournals.org/citmgr?gca=gerona;glv015v1










Chocolate Linked To Lowered Heart Disease and Stroke RiskMedicalResearch.com Interview with:Professor Phyo Kyaw Myint MBBS MD FRCP(Edin) FRCP(Lond)Clinical Chair in Medicine of Old AgeEpidemiology Group, Division of Applied Health Sciences

University of AberdeenScotland


Response: The research was carried out by academics from the Universities of Aberdeen, Manchester, Cambridge and East Anglia, as well as the Lancashire Teaching Hospital, the Medical Research Council Epidemiology Unit, Cambridge and the Academic Medical Centre, Amsterdam. It has been published online in the journal Heart. The team base their findings on almost 21,000 adults taking part in the EPIC-Norfolk study, which is tracking the impact of diet on the long term health of 25,000 men and women in Norfolk, England, using food frequency and lifestyle questionnaires. The researchers also carried out a systematic review of the available international published evidence on the links between chocolate and cardiovascular disease, involving almost 158,000 people—including the EPIC study participants.

• The EPIC-Norfolk participants (9214 men and 11 737 women) were monitored for an average of almost 12 years, during which time 3013 (14%) people experienced either an episode of fatal or non-fatal coronary heart disease or stroke. Around one in five (20%) participants said they did not eat any chocolate, but among the others, daily consumption averaged 7 g, with some eating up to 100 g.


http://medicalresearch.com/heart-disease/chocolate-linked-to-lowered-heart-disease-and-stroke-risk/15038/



















http://medicalresearch.com/exercise-fitness/dark-chocolate-may-improve-exercise-capacity-and-metabolic-parameters/12507/








• Higher levels of consumption were associated with younger age and lower weight (BMI), waist: hip ratio, systolic blood pressure, inflammatory proteins, diabetes and more regular physical activity —all of which add up to a favourable cardiovascular disease risk profile. Eating more chocolate was also associated with higher energy intake and a diet containing more fat and carbs and less protein and alcohol.

• The calculations showed that compared with those who ate no chocolate higher intake was linked to an 11% lower risk of cardiovascular disease and a 25% lower risk of associated death. It was also associated with a 9% lower risk of hospital admission or death as a result of coronary heart disease, after taking account of dietary factors. And among the 16,000 people whose inflammatory protein (CRP) level had been measured, those eating the most chocolate seemed to have an 18% lower risk than those who ate the least. The highest chocolate intake was similarly associated with a 23% lower risk of stroke, even after taking account of other potential risk factors.

• Of nine relevant studies included in the systematic review, five studies each assessed coronary heart disease and stroke outcome, and they found a significantly lower risk of both conditions associated with regular chocolate consumption. And it was linked to a 25% lower risk of any episode of cardiovascular disease and a 45% lower risk of associated death.

• The study concluded that cumulative evidence suggests higher chocolate intake is associated with a lower risk of future cardiovascular events.




























• Medical Research: What should clinicians and patients take away from your report?• Response: This is an observational study so no definitive conclusions about cause and effect

can be drawn. And the researchers point out that food frequency questionnaires do involve a certain amount of recall bias and underestimation of items eaten. Reverse causation—whereby those with a higher cardiovascular disease risk profile eat less chocolate and foods containing it than those who are healthier—may also help to explain the results.

• The study notes that as milk chocolate, which is considered to be less ‘healthy’ than dark chocolate, was more frequently eaten by the EPIC-Norfolk participants, the beneficial health effects may also extend to this type of chocolate. This may indicate that not only flavonoids, but also other compounds, possibly related to milk constituents, such as calcium and fatty acids, may provide an explanation for the observed association.

• There doesn’t seem to be any evidence of moderate consumption of chocolate increases the risk of cardiovascular disease, conclude the researchers.

• The EPIC-Norfolk population is middle and older age group and most studies examined the relationship in middle or older age. Therefore the study results may not be applicable to children and younger adults.





















http://medicalresearch.com/pediatrics/high-chocolate-intake-lower-body-fat/2689/









• Response: Future research is still needed to explore the association between chocolate and CVD. Studies are needed to better understand the biological mechanism by which chocolate and flavonoids reduce the risk of CVD. It is also possible that some individuals will not benefit from increased chocolate consumption such as those who are overweight or diabetic. More research is needed to identify individuals who would benefit the most.

• Citation:• Habitual chocolate consumption and risk of cardiovascular disease among healthy men and w

omen• Chun Shing Kwok, S Matthijs Boekholdt, Marleen A H Lentjes, Yoon K Loke, Robert N Luben, Je

ssica K Yeong, Nicholas J Wareham, Phyo K Myint, Kay-Tee Khaw• Heart heartjnl-2014-307050Published Online First: 15 June 2015 doi:10.1136/heartjnl-2014-3

07050





















http://medicalresearch.com/author-interviews/pad-polyphenols-dark-chocolate-may-improve-peripheral-artery-disease/6185/

http://heart.bmj.com/citmgr?gca=heartjnl;heartjnl-2014-307050v1











New Drug Idarucizumab First To Reverse Anticoagulant DabigatranMedicalResearch.com Interview with:Dr. Stephan Glund Ph.D.Boehringer Ingelheim Pharma GmbH & Co. KGTransl. Medicine & Clin. Pharmacology


Dr. Glund: There are currently no specific reversal agents available for any of the non-Vitamin K antagonist oral anticoagulants (NOACs). We are working on the development of idarucizumab, a specific reversal agent to dabigatran, the first approved NOAC. The study now published in The Lancet investigated, for the first time in healthy volunteers, the reversal of the anticoagulant effect of dabigatran by idarucizumab.

• Our study in healthy male volunteers showed that idarucizumab led to immediate, complete and sustained reversal of the anticoagulant effect of dabigatran. Participants first received dabigatran and then idarucizumab. The specific reversal agent was given two hours after the last dose of dabigatran, when dabigatran concentrations were at peak levels. After a five-minute infusion of idarucizumab, anticoagulation was immediately reversed back to baseline levels. The reversal effect was sustained for more than 24 hours for all doses of 2g and above. Idarucizumab was well tolerated by the study participants.

• In addition, our study also showed that administration of idarucizumab reversed dabigatran-induced inhibition of wound-site fibrin formation, which plays a key role in the blood clotting mechanism. This suggests that idarucizumab might also reverse impaired haemostasis due to dabigatran anticoagulation at a wound site.


http://medicalresearch.com/author-interviews/new-drug-idarucizumab-first-to-reverse-anticoagulant-dabigatran/15111/


















http://medicalresearch.com/heart-disease/dabigatran-carries-risk-of-gi-bleeding/10462/







• Medical Research: What should clinicians and patients take away from your report?• Dr. Glund: The data now published in The

Lancet show in an impressive manner how effective idarucizumab was for reversing dabigatran in healthy volunteers. This supports the specific reversal agent as a highly targeted treatment option if reversal of the anticoagulant effect is needed, e.g. for urgent interventions.

• But as the current study was conducted in healthy young volunteers, further efficacy and safety testing is of course required and actually ongoing.




















http://medicalresearch.com/heart-disease/dabigatran-vs-warfarin-non-valvular-atrial-fibrillation/9468/

http://medicalresearch.com/heart-disease/dabigatran-vs-warfarin-non-valvular-atrial-fibrillation/9468/








• Dr. Glund: The clinical study programme for idarucizumab is ongoing. In 2014, Boehringer Ingelheim has initiated RE-VERSE AD™, a global Phase III patient study to investigate idarucizumab in emergency settings. Up to 300 patients taking dabigatran, aged 18 years or over are expected to be enrolled from more than 400 centres in 38 countries worldwide. This is the first study in patients investigating a specific reversal agent under development for a non-Vitamin K antagonist oral anticoagulant.

• Citation:• Safety, tolerability, and efficacy of idarucizumab for the reversal of the anticoagulant effect of

dabigatran in healthy male volunteers: a randomised, placebo-controlled, double-blind phase 1 trial

• Glund, Stephan et al.• The Lancet Published Online: 15 June 2015• DOI: http://dx.doi.org/10.1016/S0140-6736(15)60732-2




















http://dx.doi.org/10.1016/S0140-6736(15)60732-2






Average New Yorker Spends More Than Seven Hours Per Day SittingMedicalResearch.com Interview with:Stella Yi, PhD, MPHNew York University Langone School of Medicine,Department of Population HealthNew York, NY 10016

• MedicalResearch: What is the background for this study? What are the main findings?• Dr. Yi: Sedentary behaviors, such as sitting time, are an emerging risk factor in the field of

physical activity epidemiology. Recent studies have demonstrated the negative health consequences associated with extended sitting time, including metabolic disturbances and decreased life expectancy independent of the effects of regular exercise.

• We also assessed mean values of self-reported sitting time to characterize these behaviors in a diverse, urban sample of adults. The average New York City resident sits more than seven hours a day—greatly exceeding the three hours or more per day that is associated with decreased life expectancy.


http://medicalresearch.com/author-interviews/average-new-yorker-spends-more-than-seven-hours-per-day-sitting/15113/
















• Among the findings:• At the lower economic end, individuals spent 6.3 hours per day sitting, while those with

higher incomes spent 8.2 hours per day sitting• College graduates spent 8.2 hours per day sitting, compared with 5.5 hours per day for those

with less than a high school education• Whites spent on average 7.8 hours per day sitting, African Americans spent 7.4 hours sitting,

Hispanics spent 5.4 hours sitting, and Asian Americans spent 7.9 hours per day sitting• Sitting time was highest in Manhattan, compared to other boroughs.• In the current analysis, we also assessed the validity of a two-question survey method of

sitting time during waking hours using accelerometers to measure sedentary time in a subsample of our study participants. The correlation between sitting time reported in the survey and accelerometer-measured sedentary time was modest (r=0.32, p<0.01) with wide limits of agreement. We interpreted this to mean that while self-reported sitting might be useful at the population-level to provide rankings and subgroups, it may be limited in assessing an individual’s actual behavior.


















• MedicalResearch: What should clinicians and patients take away from your report?• Dr. Yi: Sitting is distinct from a lack of recreational or non-recreational physical activity and

may potentially impact health outcomes via alternative biological mechanisms. Research in this area has given rise to the ‘inactivity physiology paradigm,’ or that “sitting too much is not the same as lack of exercise, and as such, has its own unique metabolic consequences” such as decreased lipoprotein lipase activity in skeletal muscles in the legs (Hamilton et al., 2008). Individuals who exercise regularly but are still sedentary for several hours a day may have a risk of adverse health outcomes that is higher than would be expected given their overall physical activity levels.

• Despite this, there are no formal recommendations on how much sitting time is detrimental to health outcomes. Clinicians and patients should use an individual and tailored approach to decreasing sitting time based on age, mobility and cardiometabolic health. It has been suggested that taking breaks and standing up to walk around in between sitting times may be beneficial.












http://medicalresearch.com/exercise-fitness/sitting-time-linked-to-increased-heart-diease-and-cancer-mortality/10652/








• Dr. Yi: Interventions that introduce breaks in sitting time with short walks are feasible, particularly in areas with high walkability scores. This highlights the potential for intervention through locating worksites in walkable neighborhoods around the U.S., and to consider walkability in the design of new business districts. In addition to promoting walking breaks among workers in walkable neighborhoods, other potential interventions include putting sit-stand desks in offices, holding walking meetings, promoting stair use, and encouraging movement during television time, approaches which have not yet been fully characterized in the literature.

• Further, specific public health activities to reduce sitting time should consider cultural and socioeconomic differences, sex, and age, as well as the time of day the sitting is occurring. For example, whites and Asian Americans have the highest sitting times, but Asian Americans tend to hold occupations at both ends of the socioeconomic spectrum. Asian Americans hold desk jobs where sitting may be addressed by broad workplace wellness programs, but interventions should also be targeted toward jobs in commercial settings like nail salons or taxi driving, which offer little opportunity for reducing sitting time.

• Citation:• Yi SS, Bartley KF, Firestone MJ, Lee KK, Eisenhower DL. Self-Reported Sitting Time in New York City

Adults, The Physical Activity and Transit Survey, 2010–2011. Prev Chronic Dis 2015;12:140488. DOI: http://dx.doi.org/10.5888/pcd12.140488.












http://medicalresearch.com/exercise-fitness/workplace-strategies-reduce-sitting-time/3428/

http://dx.doi.org/10.5888/pcd12.140488






Hospital Autopsy Rate Drops To Near ZeroMedicalResearch.com Interview with:Mr. Angus TurnbullImperial College School of Medicine, London UK


Mr. Turnbull: Autopsy has been used to advance medical knowledge and understanding of pathological processes for millennia but increasing evidence indicates its decline in the UK and elsewhere. This study not only confirms that but suggests autopsy for learning purposes has almost disappeared.

• In the United Kingdom autopsy is divided into medico-legal autopsy (that required by law under the jurisdiction of HM Coroner) and consented autopsy (performed with the consent of the bereaved or their family). Over the past half-century, small single site studies have noted a marked decline in consented autopsy rates, however there has been no study for over 20 years to determine the extent of the decline nationwide.

• This study examined all acute NHS Trusts within England, NHS Boards in Scotland and Wales and Social Care Trusts in Northern Ireland. We found that the average autopsy rate (the percentage of adult inpatient deaths which under go consented autopsy) in the United Kingdom in 2013 was only 0.7%. The study showed that in nearly a quarter (23%) of all NHS Trusts in the United Kingdom, consented autopsy is now extinct.

• These findings may have implications for training, for research and for learning from mortality – a key aspect of patient safety.


http://medicalresearch.com/author-interviews/hospital-autopsy-rate-drops-to-near-zero/14998/













• Medical Research: What should clinicians and patients take away from your report?• Mr. Turnbull: Consented autopsy has the potential to bring multiple benefits to the medical

community by aiding in clinical audit, quality assurance, public health, misdiagnosis (a key contributor to avoidable harm), epidemiology and the teaching of trainee pathologists and medical students. For many of today’s consultants and professors, autopsy may have been a frequent and important educational experience yet now the majority of medical students graduate having never seen an autopsy performed.

• Families may request an autopsy or be approached for consent following the loss of a relative. Unfortunately this practice is dwindling despite research showing that autopsy can help relieve feelings of guilt and aid closure. It may also reveal underlying inheritable medical conditions which would have important implications for the health of their children.

• Clinicians and patients should understand that autopsy, which once was of vital importance, has been reduced to a rarity in modern medicine – for the better or the worse. Unless the medical and lay community act now then consented autopsy shall soon be extinct along with all the benefits it can bring. This may be a societal decision but if clinicians recognise an importance in autopsy, they should act soon to prevent its demise.
















• Mr. Turnbull: Further research should be focused on quantifying the benefits of autopsy and examining the reasons for the decline in numbers. It should look at the impact that low autopsy figures have on patient safety, clinical audit and research, public health, and teaching. Ultimately, while this research and the debate on consent autopsy occurs, unless action is swiftly taken it shall be too late to revive this tried and tested method. It should examine whether alternative methods of understanding the cause of death are valid and whether limited, focused autopsy has a role.

• Citation:• Hospital autopsy: Endangered or extinct?Angus Turnbull, Michael Osborn, Nick Nicholas• J Clin Pathol

jclinpath-2014-202700Published Online First: 15 June 2015 doi:10.1136/jclinpath-2014-202700









https://www.google.com/search?q=Hospital+autopsy:+Endangered+or+extinct?&ie=utf-8&oe=utf-8










Breast Cancer Conserving Surgery Still Faces Socioeconomic ChallengesMedicalResearch.com Interview with:Isabelle Bedrosian, M.D., F.A.C.S.Associate Professor, Department of Surgical Oncology, Division of Surgery,

Medical Director, Nellie B. Connelly Breast CenterThe University of Texas MD Anderson Cancer Center, Houston, TX

• Medical Research: What is the background for this study? What are the main findings?• Dr. Bedrosian: There have been a number of reports on the rates of Breast Conserving

Therapy (BCT) and mastectomy among women with early stage breast cancer. These reports have been discordant, with some suggesting that index mastectomy rates have increased and others suggestion Breast Conserving Therapy rates have actually increased. We hypothesized that these differences in reporting may be due to data source (ie tertiary referral centers vs population based studies) and turned to the NCDB, which captures 70% of cancer cases in the US and as such provides us with the most comprehensive overview on patient treatment patterns.


http://medicalresearch.com/cancer-_-oncology/breast-cancer/breast-cancer-conserving-surgery-still-faces-socioeconomic-challenges/15115/










http://medicalresearch.com/cancer-_-oncology/breast-cancer/breast-cancer-breast-conserving-treatment-without-radiotherapy-ductal-situ-disease/2610/








• Medical Research: What should clinicians and patients take away from your report?• Dr. Bedrosian: The most important message is that the majority of women with early stage

breast cancer are opting for Breast Conserving Therapy, and this proportion has increased over time. This increase over time has come in part due to improvements in age based use, geographic disparity and practice based disparities. These are all very important gains.












http://medicalresearch.com/cancer-_-oncology/taking-a-little-more-tissue-after-breast-cancer-removal-may-save-reduce-need-for-further-surgery/14528/









• Dr. Bedrosian: Our results also indicate that further improvements in rates of Breast Conserving Therapy will likely only be made when we address some of the socio-economic factors that currently appear to be driving the disparities in the surgical treatment of breast cancer. Therefore, there is a need to better define the factors behind these socio-economic disparities. These socio-economic factors are likely surrogates for the broad range of considerations such as child care, transportation challenges, time of work, cultural beliefs, etc. Better clarity on these fronts is needed in order to implement strategies to overcome these socio-economic gaps in use of Breast Conserving Therapy for treatment of early stage breast cancer.

• Citation:• Lautner M, Lin H, Shen Y, et al. Disparities in the Use of Breast-Conserving Therapy Among Pat

ients With Early-Stage Breast Cancer . JAMA Surg. Published online June 17, 2015. doi:10.1001/jamasurg.2015.1102.












http://medicalresearch.com/cancer-_-oncology/breast-cancer/socioeconomic_factors_contribute_to_disparities_in_breast_cancer_surgery/7396/

http://archsurg.jamanetwork.com/article.aspx?articleid=2322835









Vascular ALK1 May Be Biomarker Indicating Breast Cancer MetastasesMedicalResearch.com Interview with:Kristian Pietras, Ph.D.Göran & Birgitta Grosskopf Professor of Molecular MedicineStrategic Director of Cancer Research Lund University Dept

of Laboratory Medicine LundDiv of Translational Cancer Research Lund, Sweden


Dr. Pietras: Breast cancer is the largest malignant disease among women with 1.7 million new cases worldwide each year (25% of all new cancer cases for women). The prognosis for breast cancer patients is relatively good when the disease is detected at early stages (close to 90% of patients are still alive 5 years after diagnosis). Nevertheless, metastatic disease is the cause of 90% of all cancer-related deaths. Thus, learning more about the metastatic process and finding new cures for widespread disease is justifiably at the center of clinical attention.

• The current study is part of our ongoing efforts to map support functions performed by the various cell types comprising the tumor stroma with the premise that decisive treatment benefit can only be achieved by targeting multiple, but distinct, cell types and pathways that collectively sustain the growth of tumors. The development of a rich vascular supply is recognized as a key hallmark of a growing tumor necessary for the development into a clinically relevant disease.


http://medicalresearch.com/cancer-_-oncology/breast-cancer/vascular-alk1-may-be-biomarker-indicating-breast-cancer-metastases/15057/




























• Our focus is the role of the tumor vasculature in preventing or promoting metastatic dissemination from the primary tumor. For a metastasis to form, a cancer cell must,

• 1) detach from its neighboring cells in the mother tumor,2) traverse the vascular wall to escape into the blood stream,3) exit the vasculature to enter the metastatic site, and4) colonize the metastatic site.

• Recent evidence points to that the transmigration into and out of the vasculature is a regulated process of previously unrecognized importance for the metastatic process. Importantly, the fact that the process of escape into/from the vasculature is regulated also implies that it is possible to use drugs to block this process.

• In the present study, we have combined functional studies in advanced models of cancer and computational biology approaches to investigate the specific contribution to the metastatic process of a molecular signaling pathway emanating from the ALK1 protein expressed by endothelial cells in the vasculature. Using information from 2 different patient cohorts including a total of nearly 2000 breast tumors, we found that patients specifically having high levels of ALK1 in the vasculature of their tumor were much more likely to develop metastatic/recurrent disease. Accordingly, therapeutic administration of a drug (dalantercept) blocking the action of ALK1 prevented metastatic dissemination in multiple mouse models of breast cancer to a large degree. In addition, combination therapy of dalantercept and a commonly used chemotherapeutic drug (docetaxel) was exceedingly effective in preventing spread of the primary tumor to the lungs.

• Our results suggest that the molecular features of the tumor vasculature are important to consider as potential determinants of breast cancer dissemination and that metastatic spread can be delayed by targeting the tumor vasculature.























http://medicalresearch.com/cancer-_-oncology/breast-cancer/triple-negative-breast-cancer-tryptophan-degradation-pathway-promotes-metastatic-phenotypes/9881/








• Medical Research: What should clinicians and patients take away from your report?• Dr. Pietras: Our results suggest that the presence of high levels of ALK1 in the breast tumor

vasculature is a prognostic biomarker for metastatic disease. Moreover, our work encourages clinical testing of drugs blocking ALK1 in breast cancer with prevention of metastatic dissemination as the primary outcome.

• Furthermore, our study reiterates the active participation of the tumor vasculature in the process of metastatic dissemination, and highlights that specific molecular features of endothelial cells (in this case, high expression of ALK1) can serve as both prognostic biomarkers and drug targets in breast cancer.























http://medicalresearch.com/cancer-_-oncology/lung-cancer/akap4-is-a-promising-blood-biomarker-for-early-detection-of-lung-cancer/14902/









• Dr. Pietras: We are currently more in detail describing the molecular features of a tumor vasculature conducive to metastatic dissemination, as well as those that are protective of metastatic dissemination. Our hope is that this will reveal an even more precise and global prognostic biomarker of recurrent disease, as well as identify additional and complementary drug targets. In addition, we are currently performing therapeutic studies with dalantercept in models of breast cancer in order to pinpoint the precise therapeutic regimen and disease stage at which the treatment is the most effective.

• Citation:• Endothelial ALK1 Is a Therapeutic Target to Block Metastatic Dissemination of Breast Cancer • Sara I. Cunha, Matteo Bocci, John Lövrot, Nikolas Eleftheriou, Pernilla Roswall, Eugenia Corder

o, Linda Lindström, Michael Bartoschek, B. Kristian Haller, R. Scott Pearsall, Aaron W. Mulivor, Ravindra Kumar, Christer Larsson, Jonas Bergh, and Kristian Pietras

• Cancer Res June 15, 2015 75:2445-2456; doi:10.1158/0008-5472.CAN-14-3706























http://cancerres.aacrjournals.org/search?fulltext=pietras&submit=yes&excludeflag=MTG_ABSTRACT_ARTICLE










Childhood Adversity Doubles Heart Disease Risk in AdulthoodMedicalResearch.com Interview with:Jaana Halonen Ph.DFinnish Institute of Occupational HealthKuopio, Finland

• MedicalResearch: What is the background for this study? What are the main findings?• Dr. Halonen: Research on predictors of cardiovascular disease has increasingly focused on

exposures to risk factors other than the conventional behavioral and biological ones, such as smoking, hypertension, dyslipidaemia, or diabetes. One of the potential predictors beyond the conventional risks is exposure to childhood psychosocial adversities. Previous studies have found that people who had experienced financial difficulties, serious conflicts and long-term disease in the family in childhood have a higher level of cardiovascular risk factors and increased cardiovascular morbidity in adulthood, but the underlying mechanisms linking childhood exposure to adult disease remain unclear. It is possible that childhood adversity sets an individual on a risk pathway leading to adverse future exposures. An important source of adversity experienced in adulthood is residence in a socioeconomically disadvantaged neighborhood. However, no previous study had examined the combined effect of childhood psychosocial adversity and adult neighborhood disadvantage on cardiovascular disease risk.

• We found that exposure to childhood psychosocial adversity and adult neighborhood disadvantage in combination was associated with a doubling of the risk of incident cardiovascular disease in adulthood when compared to the absence of such exposures. This association was not explained by conventional cardiovascular risk factors. Neither childhood psychosocial adversity nor adult neighborhood disadvantage alone were significantly associated with incident CVD, although they were associated with CVD risk factors.


http://medicalresearch.com/heart-disease/childhood-adversity-doubles-heart-disease-risk-in-adulthood/15122/

















• MedicalResearch: What should clinicians and patients take away from your report?• Dr. Halonen: Clinical implications of the present findings should be drawn cautiously. Because

factors included in a conventional cardiovascular risk assessment did not explain the association between childhood psychosocial adversity, adult neighborhood disadvantage, and incident cardiovascular heart disease, tackling smoking, hypertension, dyslipidaemia and other conventional risk factors only might not remove the excess CVD risk among individuals exposed to childhood adversity and adult disadvantage. Thus, the reduction of childhood adversity and adult disadvantage remains an important goal for health policies.



















• MedicalResearch:What recommendations do you have for future research as a result of this study?

• More research is needed to increase understanding about the nature of these associations in the aetiology of cardiovascular diseases. We need to assess whether the association is replicable in other populations and whether it is causal or only indicative of other risk factors. We also need evidence of the potential benefits of interventions targeting childhood adversity and adult disadvantage in the prevention of cardiovascular diseases, and how these factors can realistically be modified in clinical settings in a cost-effective manner.

• Circulation. 2015 Jun 11. pii: CIRCULATIONAHA.115.015392. [Epub ahead of print]• Childhood Psychosocial Adversity and Adult Neighborhood Disadvantage as Predictors of C

ardiovascular Disease: A Cohort Study.• Halonen JI1, Stenholm S2, Pentti J3, Kawachi I4, Subramanian SV4, Kivimäki M5, Vahtera J6.













http://circ.ahajournals.org/content/early/2015/06/11/CIRCULATIONAHA.115.015392.abstract























Adolescent Hyperinsulinemic Androgen Excess: Insulin Sensitization May Slow Biologic AgingMedicalResearch.com Interview with:Francis de Zegher, MD, PhDDepartment of Development and Regeneration, University of Leuven Leuven

, Belgium & Lourdes Ibáñez, MD, PhDHospital Sant Joan de Déu, University of BarcelonaBarcelona, Spain

• Medical Research: What is the background for this study?

Response: Hyperinsulinemic androgen excess is the most frequent hormonal disorder of adolescent girls. It seems to be mainly driven by an excessive and/or inappropriate storage of fat due to a chronically positive energy balance.

• The traditional approach (not approved by FDA or EMA) is to silence the ovaries by giving an oral contraceptive.

• An alternative approach is to change the storage of fat by giving an insulin-sensitizing combination of generics in low dose.


http://medicalresearch.com/diabetes/adolescent-hyperinsulinemic-androgen-excess-insulin-sensitization-may-slow-biologic-aging/14996/





























• Medical Research: What are the main findings?

• Response: It has previously been shown that the insulin-sensitizing approach has more normalizing effects than the oral-contraceptive approach.

• Here, we add that prolonged insulin sensitization is also accompanied by a lengthening of telomeres and thus conceivably by a slower biologic aging of the girls.































• Medical Research: What should clinicians and patients take away from your report? What recommendations do you have for future research as a result of this study?

• Response: More head-to-head comparisons are needed before an insulin-sensitizing intervention can be approved (as an adjunct to lifestyle intervention) to treat adolescent girls with hyperinsulinemic androgen excess.

• Citation:• de Zegher F, Díaz M, Ibáñez L. Association Between Long Telomere Length and Insulin

Sensitization in Adolescent Girls With Hyperinsulinemic Androgen Excess. JAMA Pediatr. Published online June 15, 2015. doi:10.1001/jamapediatrics.2015.0439.





























Erythomycin Allows Gastric Emptying To Prevent Aspiration In ER PatientsMedicalResearch.com Interview with:Christoph Czarnetzki MD, MBADivision of AnesthesiologyGeneva University HospitalsGeneva, Switzerland

Medical Research: What is the background for this study? What are the main findings?

Dr. Czarnetzki: In the US, about 40 million patients undergo a general anesthetic each year, and approximately 12,000 broncho-aspirate. Broncho-aspiration of gastric juice may lead to acute respiratory distress syndrome, carrying a 40% mortality rate. The risk is increased 10-fold in patients undergoing emergency surgery. Trauma patients may have ingested food before their accident, or have swallowed blood from oral or nasal injuries. Also, gastric emptying is delayed due to head injury, stress, pain, and opioid medication. Non-trauma patients may have delayed gastric emptying due to paralytic ileus and critical illness, leading to significant residual stomach content even after long fasting periods. Erythromycin, a macrolide antibiotic, and motilin receptor agonist induces antral contractions, and increases the lower esophageal sphincter tone, which is an important barrier against gastro-esophageal reflux. Although gastric emptying properties of erythromycin are well known, its efficacy in patients undergoing emergency surgery has never been investigated before to our knowledge.


http://medicalresearch.com/author-interviews/erythomycin-allows-gastric-emptying-to-prevent-aspiration-in-er-patients/15066/


















In our study we included 132 patients undergoing general anesthesia for emergency procedures and we could show that erythromycin increased the proportion of clear stomach and decreased acidity of residual gastric liquid. Dependent of the definition of empty stomach (less than 40 ml and absence of solid food or completely empty stomach) the absolute risk reduction ranged from 17% to 24%, equivalent to a number needed to treat of four to six patients to produce one completely cleared stomach. Erythromycin was particularly efficacious in non-trauma patients. Adverse effects were minor.




















• Medical Research: What should clinicians and patients take away from your report?• Dr. Czarnetzki: In emergency patients we have now a medication at hand with wich we can

promote gastric emptying. 3 mg/kg of Erythromycin should be given intravenously at least 15 minutes prior to intubation. In patients which ingested solid food Erythomycin should be given earlier, maybe at arrival in the emergency room, as emptying of solid food takes more time than liquids.





















• Dr. Czarnetzki: Future research could investigate to what extent Erythromycine reduces bronchoaspiration and its consequences. On the other hand thousands of patients have to be included in a multicenter study to have sufficient power to investigate this outcome. In view of the strong results of our study it should be questioned if such a study is still necessary.

• Citation:• Czarnetzki C, Elia N, Frossard J, et al. Erythromycin for Gastric Emptying in Patients Undergoin

g General Anesthesia for Emergency Surgery: A Randomized Clinical Trial. JAMA Surg. Published online June 17, 2015. doi:10.1001/jamasurg.2015.0306.























Resveratrol May Help Convert Bad Fat to GoodMedicalResearch.com Interview with:Dr. Min Du Ph.DDepartment of Animal Sciences Washington Center for Muscle Biology Washington State UniversityPullman, WA

Medical Research: What is the background for this study? What are the main findings?

Response: The beige fat is only recently identified and is highly inducible. we observed that polyphenolic compounds including resveratrol enhances AMPK activity, and hypothesized that resveratrol might enhance the formation of beige fat through activation of AMPK. Therefore, we used resveratrol, a very well characterized polyphenolic compound as a representative of polyphenolic compounds in fruits, to check its effects on the formation of beige fat. We found that resveratrol induced the formation of beige adipocytes both in vitro and in vivo. We further found that the lipid oxidation rate was enhanced due to the formation of beige fat, which is correlated with the anti-obesity effect of resveratrol.


http://medicalresearch.com/weight-research/resveratrol-may-help-convert-bad-fat-to-good/15127/


















• Medical Research: What should clinicians and patients take away from your report?• Response: The anti-obesity effects of polyphenolic rich fruits might be stronger than we

thought. In addition to fruits, certain other foods or drinks with high polyphenol contents such as tea and coffee, or red wine, might also have good anti-obesity effects.





















• Response: Studies using the whole fruit supplementation might be warranted. We are planning to conduct a mice study by directly feeding mice with raspberry powder to examine whether we observe similar or even better preventive effects on obesity.

• Citation:• Resveratrol induces brown-like adipocyte formation in white fat through activation of AMP-

activated protein kinase (AMPK) α1• Wang S1, Liang X2, Yang Q2, Fu X2, Rogers CJ2, Zhu M3, Rodgers BD2, Jiang Q4, Dodson MV2,

Du M2.• Int J Obes (Lond). 2015 Jun;39(6):967-76. doi: 10.1038/ijo.2015.23. Epub 2015 Mar 12.














http://www.ncbi.nlm.nih.gov/pubmed/?term=Wang%20S%5BAuthor%5D&cauthor=true&cauthor_uid=25761413

http://www.ncbi.nlm.nih.gov/pubmed/?term=Liang%20X%5BAuthor%5D&cauthor=true&cauthor_uid=25761413

http://www.ncbi.nlm.nih.gov/pubmed/?term=Yang%20Q%5BAuthor%5D&cauthor=true&cauthor_uid=25761413

http://www.ncbi.nlm.nih.gov/pubmed/?term=Fu%20X%5BAuthor%5D&cauthor=true&cauthor_uid=25761413

http://www.ncbi.nlm.nih.gov/pubmed/?term=Rogers%20CJ%5BAuthor%5D&cauthor=true&cauthor_uid=25761413

http://www.ncbi.nlm.nih.gov/pubmed/?term=Zhu%20M%5BAuthor%5D&cauthor=true&cauthor_uid=25761413

http://www.ncbi.nlm.nih.gov/pubmed/?term=Rodgers%20BD%5BAuthor%5D&cauthor=true&cauthor_uid=25761413

http://www.ncbi.nlm.nih.gov/pubmed/?term=Jiang%20Q%5BAuthor%5D&cauthor=true&cauthor_uid=25761413

http://www.ncbi.nlm.nih.gov/pubmed/?term=Dodson%20MV%5BAuthor%5D&cauthor=true&cauthor_uid=25761413

http://www.ncbi.nlm.nih.gov/pubmed/?term=Du%20M%5BAuthor%5D&cauthor=true&cauthor_uid=25761413







Wireless Devices Can Still Cause Interference With Some Medical DevicesMedicalResearch.com Interview with:Mehdi ArdavanConcordia University/Université Concordia

• Medical Research: What is the background for this study?• Response: That thousands patients die each year in US hospitals due to medical errors that

could be prevented if medical staff were provided with instant access to patient records. Wireless technology (such as portable tablets) is one way of providing this instant access. But using such devices can cause electromagnetic interference (EMI) with electronic medical devices and can lead to dangerous consequences for patients. Hospitals may have a policy of minimum separation distance (MSD) which means that the staff members carrying wireless devices cannot approach sensitive medical devices closer than the specified MSD. The problem was that the recommend values of the minimum separation distance were not based on a quantitative and thorough analysis of the problem. We wanted to see what is the correct value of MSD, and how it’s determined.


http://medicalresearch.com/author-interviews/wireless-devices-can-still-cause-interference-with-some-medical-devices/15152/















• Medical Research: What are the main findings?• Response: We developed new and fast methods for estimating the electromagnetic field

distribution. We also mathematically modeled the roaming nature of the staff members carrying the wireless transmitters. Then we modeled the minimum separation distance policy and added an option to account for a possibility of non-compliance with the policy.

• First, we assumed a full compliance with MSD policy and found that the risk of interference decreased constantly as the minimum separation distance was increased. Quantitative recommendations are made for the value of the MSD. But once we considered a small non-compliance probability, an interesting and unexpected phenomenon was observed: the EMI risk does not decrease beyond a certain value and remains almost constant for all MSDs bigger than a value we call the optimal MSD. If we increase the minimum separation distance beyond its optimal value, the risk of EMI does not decrease but more restrictions and thus more inconvenience is put on the staff members. So larger values of MSD are not necessarily safer and are not recommended. We also find that the risk and the optimal minimum separation distance are both sensitive to the rate of compliance with the MSD policy.

















• Medical Research: What should clinicians and patients take away from your report?• Response: Clinicians and patients must recognize that the electromagnetic interference is an

important issue, and compliance with the MSD policy is the key factor in controlling the risk of EMI. An MSD of about arm’s length seems to be sufficient for most general scenarios. We recommend that the staff members are educated in this regard and both staff members and patients are constantly reminded that a near full compliance rate is expected.


















• Response: We modeled up to two roaming transmitters. Future research should develop new algorithms that make it possible to consider more transmitters easily. It would also be interesting to adapt and reapply our model to an operating room where many staff members are constantly near the patient’s bedside with their portable electronic devices.

• Citation:• EMI Risk Assessment in a Hospital Ward With One and Two Roaming Wireless Transmitters• Ardavan, M. ; Eng. & Comput. Sci. Fac., Concordia Univ., Montreal, QC, Canada ; Trueman,

C.W. ; Schmitt, K.A.• 10.1109/TEMC.2014.2362717











http://dx.doi.org/10.1109/TEMC.2014.2362717






Concomitant Proton-Pump Inhibitors With Antiplatelet Drugs Requires CautionMedicalResearch.com Interview with:José C. Nicolau, MD, PhD, FACCProfessor -University of São Paulo Medical SchoolDirector – Acute Coronary Disease Unit, Heart Institute

• MedicalResearch: What is the background for this study?

• Dr. Nicolau: Previous studies, mainly performed in patients undergoing percutaneous coronary intervention (PCI), have shown that concomitant use of proton-pump inhibitors (PPIs) diminishes the antiplatelet effect of the drug clopidogrel. This diminished response to clopidogrel has in turn been associated with an increased risk of stent thrombosis and ischemic events. Our paper presented results from a secondary analysis performed in patients enrolled in the TRILOGY ACS randomized clinical trial. Our study is the first to examine the influence of interactions between PPIs and clopidogrel or the newer, more potent antiplatelet drug prasugrel, as well as correlations with platelet reactivity and clinical outcomes in high-risk patients who were receiving medical management without revascularization following acute coronary syndrome (ACS).


http://medicalresearch.com/medication-research/concomitant-proton-pump-inhibitors-with-antiplatelet-drugs-requires-caution/15157/









http://medicalresearch.com/heart-disease/high-maintenance-dose-clopidogrel-after-pci-may-reduce-adverse-events/10260/







• MedicalResearch: What are the main findings?

• Dr. Nicolau: Among patients who were receiving proton-pump inhibitors at baseline (23% of total), the adjusted hazard ratio (HR) for the composite outcome of cardiovascular death/myocardial infarction/stroke was 0.73 (95% CI, 0.54-0.98) when comparing prasugrel with clopidogrel. Among patients who were not taking PPIs, the HR was 1.01(95% CI, 0.85-1.19). The main factor driving these results was myocardial infarction (HR=0.61 [95% CI, 0.42-0.88]; P for interaction=0.012). These findings could not be explained by the results obtained in a subgroup of patients who participated in platelet reactivity testing.

• MedicalResearch: What should clinicians and patients take away from your report?• Dr. Nicolau: We need to be careful with the concomitant utilization of clopidogrel and

proton-pump inhibitors.











http://medicalresearch.com/pediatrics/ppis-not-helpful-for-irritable-babies/10312/

http://medicalresearch.com/infections/c-difficile/acid-suppression-medications-linked-to-increased-pediatric-c-diff-infections/15093/








• Dr. Nicolau: Additional studies are needed to delineate optimal antiplatelet strategies in high-risk Acute Coronary Syndrome patients who are managed medically without revascularization and who also require long-term proton-pump inhibitors therapy.

• Citation:• Concomitant proton-pump inhibitor use, platelet activity, and clinical outcomes in patients wi

th acute coronary syndromes treated with prasugrel vs. clopidogrel and managed without revascularization: Insights from the TRILOGY ACS Trial

• Nicolau, Jose Carlos et al.• American Heart Journal• Received: December 22, 2014; Accepted: May 31, 2015; Published Online: June 10, 2015 Publ

ication stage: In Press Accepted Manuscript











http://content.onlinejacc.org/article.aspx?articleid=1664186












Comorbidities Increase Mortality Risk of Atrial Fibrillation In Blacks and HispanicsMedicalResearch.com Interview with: Dr. Mary Vaughan Sarrazin Ph.D.Associate Professor University of Iowa Roy and Lucille Carver College of Medicine, and Iowa

City VA Medical Center, Center for Comprehensive Access & Delivery Research and Evaluation (CADRE) Iowa City, IADr. Rajesh Kabra MD Division of Cardiology, Department of Internal Medicine

University of Tennessee Health Science Center, Memphis, Tennessee• MedicalResearch: What is the background for this study? What are the main findings?

• Response: Atrial fibrillation is associated with high risk of stroke and death. It is not known if these outcomes are different in whites, blacks and Hispanics.

• In our study of over 500,000 Medicare patients over the age of 65 years with newly diagnosed atrial fibrillation, we noted that compared to whites, blacks and Hispanics had a higher risk of stroke (46% and 11% higher respectively) and mortality(66% and 21% respectively). However after correcting for other co-morbidities and illnesses, the risk of mortality was the same in all the races; the higher risk of stroke was decreased in blacks and eliminated in Hispanics. This suggests that in blacks and Hispanics, atrial fibrillation is a marker for higher mortality and identifies patients at higher risk of death.


http://medicalresearch.com/heart-disease/comorbidities-increase-mortality-risk-of-atrial-fibrillation-in-blacks-and-hispanics/15168/


























http://medicalresearch.com/general-medicine/women-with-atrial-fibrillation-at-greater-risk-of-stroke-than-men/11921/








University of Tennessee Health Science Center, Memphis, Tennessee•

MedicalResearch: What should clinicians and patients take away from your report?• Response: Blacks and Hispanics with atrial fibrillation are at much higher risk of stroke and

death compared to the whites and need to be aggressively treated not only for atrial fibrillation but also for other associated co-morbidities.




























http://medicalresearch.com/heart-disease/most-patients-with-atrial-fibrillation-symptomatic-and-have-impaired-quality-of-life/14880/








University of Tennessee Health Science Center, Memphis, Tennessee• MedicalResearch: What recommendations do you have for future research as a result of

this study?• Response: Future studies need to address the factors that increase the risk of death and

stroke in blacks and Hispanics with atrial fibrillation so that preventative measures can be taken to prevent these devastating outcomes.

• Citation:• Effect of Race on Outcomes (Stroke and Death) in patients > 65 Years of Age with Atrial

Fibrillation• Kabra, Rajesh et al.• American Journal of Cardiology , Volume 116 , Issue 2 , 230 – 235

DOI: http://dx.doi.org/10.1016/j.amjcard.2015.04.012




























http://medicalresearch.com/sleep-disorders/cpap-for-sleep-apnea-may-decrease-atrial-fibrillation-recurrence/13675/

http://dx.doi.org/10.1016/j.amjcard.2015.04.012






Bariatric Surgery Reduces Urinary Incontinence As Well As ObesityMedicalResearch.com Interview with:Leslee L. Subak, MDUniversity of California, San Francisco

Professor, Departments of Obstetrics, Gynecology & Reproductive Sciences, Urology and Epidemiology & BiostatisticsChief of Gynecology, SF Veterans Affairs Medical CenterUCSF Women’s Health Clinical Research Center

• MedicalResearch: What is the background for this study? What are the main findings?• Dr. Subak: Urinary incontinence is very common, affecting an estimated 30 million adults in

the U.S., and may account for as much as $60 billion in annual medical costs. Incontinence can cause significant distress, limitations in daily functioning, and reduced quality of life. Obesity is an important risk factor, with each 5-unit increase in body mass index – a ratio of someone’s weight divided by the square of their height – above normal weight associated with far higher rates of incontinence. The prevalence of incontinence has been reported to be as high as 70 percent among severely obese women, and 24 percent among severely obese men (BMI greater than 40, or more than about 100 pounds greater than ideal body weight).

• Since obesity is a risk factor for incontinence, several studies have examined whether weight loss is a treatment for incontinence among obese people with the condition. Clinical trials have shown the low calorie diets, behavioral weight reduction, and bariatric surgery are associated with improvement in incontinence in obese women and men through one year, but evidence on the durability of this effect is lacking.

• We performed this study to examine changes in urinary incontinence and identify factors associated with improvement among women and men in the first 3 years following bariatric surgery.


http://medicalresearch.com/weight-research/bariatric-surgery-reduces-urinary-incontinence-as-well-as-obesity/15129/



















• This study included 1987women and men in the Longitudinal Assessment of Bariatric Surgery-2 (LABS-2) study performed at 10 hospitals at 6 clinical centers in the U.S. who underwent bariatric surgery between 2005 and 2009. The study participants ranged in age from 18 to 78 years old – the median age was 47. The analysis controlled for factors such as age, race, smoking status and recent pregnancy. Nearly 79 percent of the participants in the study were women with 49% reporting at least weekly incontinence, compared with 2% of men reporting incontinence.

• Following surgery and large weight loss of 29% for women and 26% for men, substantial improvements in incontinence were observed, with a majority of women and men achieving remission at 3 years post-surgery. The more weight lost, the higher the chances of improvement. While the risk of relapse rose with each gain of about 10 pounds, overall there was substantial improvement for both women and men. People who were older, had severe walking limitations or were recently pregnant showed less improvement.














http://medicalresearch.com/weight-research/bariatric-surgery-linked-lower-long-term-mortality/10419/








• MedicalResearch: What should clinicians and patients take away from your report?

• Dr. Subak: Obesity is a strong risk factor for incontinence, with nearly half of women and more than a fifth of the men with severe obesity reporting having at least one episode of incontinence a week.

• Surgical weight loss for severely obese men and women is an effective treatment with sustained improvement in incontinence through 3 years after surgery.

• Improvement in urinary incontinence may be another important long-term benefit among the extensive health improvements associated with bariatric surgery.

• Improvement in urinary incontinence may help motivate severely obese men and women with incontinence to undergo bariatric surgery or other weight loss interventions and improve long-term weight maintenance.














http://medicalresearch.com/urology/new_anti_incontinence_surgery_uses_no_synthetic_mesh/5302/









• Dr. Subak: Explore why weight loss is an effective treatment and how to use incontinence (and other quality of life conditions such as erectile dysfunction) to motivate weight loss and weight maintenance.

• Citation:• Subak LL, King WC, Belle SH, et al. Urinary Incontinence Before and After Bariatric Surgery.

JAMA Intern Med. Published online June 22, 2015. doi:10.1001/jamainternmed.2015.2609.






















Oncology Evidence Based On Surrogate Survival May Be PoorMedicalResearch.com Interview with:Vinay Prasad, MD, MPH Medical Oncology Service, National Cancer InstituteNational Institutes of HealthBethesda, Maryland

• MedicalResearch: What is the background for this study? What are the main findings?• Dr. Prasad: In medicine, there are two types of endpoints: clinical endpoints and

surrogate endpoints. Clinical endpoints, such as survival or quality of life, measure how a patient, feels, functions or lives. In contrast, a surrogate endpoint is not a measure of patient benefit. Instead, it is merely hoped to correlate with one. LDL levels are a surrogate for cardiovascular risk, for instance.

• Oncologists use and trust surrogate endpoints, such as response rate, progression free survival and disease free survival. The majority of drug approvals and many guideline recommendations are based on improvements in surrogates. Surrogates are assumed to correlate with overall survival, but we wanted to know if this was true, and under what circumstances.

• We reviewed all well done studies of surrogate-survival association. We found that the majority–especially in the setting of metastatic disease–found a poor correlation between a surrogate and survival. In fact, correlations were strong in only a handful of settings, such as adjuvant colorectal cancer. Moreover, we found that correlations were always based on a subset of potentially informative literature, even when authors surveyed unpublished trials. Missing data in these association studies raises the concern that correlations would be different if all data had been considered.

• Our overall conclusion was that most surrogate-survival correlations in oncology are based on weak evidence and are poor.


http://medicalresearch.com/cancer-_-oncology/oncology-evidence-based-on-surrogate-survival-may-be-poor/15173/
















• • MedicalResearch: What should clinicians and patients take away from your report?• Dr. Prasad: Clinicians should be skeptical of new cancer drugs or combinations that merely

improve surrogates. Clinicians should consult our paper to see if the specific surrogate-survival correlation they are considering is strong or weak.



















• Dr. Prasad: Oncologists who have conducted clinical trials, and have access to those primary data should share those datasets, so that researchers may better study the strength of correlation between surrogates and survival.

• Citation:• Prasad V, Kim C, Burotto M, Vandross A. The Strength of Association Between Surrogate End P

oints and Survival in Oncology: A Systematic Review of Trial-Level Meta-analyses. JAMA Intern Med. Published online June 22, 2015. doi:10.1001/jamainternmed.2015.2829.





















Early Palliative Care Consultations Are Well Received By Patients But Don’t Decrease Health ServicesMedicalResearch.com Interview with:Gabrielle Rocque MDDivision of Hematology & OncologyUniversity of AlabamaBirmingham, Alabama

• MedicalResearch: What is the background for this study? What are the main findings?• Dr. Rocque: This study grew out of a retrospective study we conducted in 2010 in which we

evaluated the characteristics of patients admitted to our solid tumor oncology service, what occurred during their hospitalization, and what their outcomes were after discharge. We identified that the average life expectancy of the population was less than 4 months and therefore, inpatient admission was an opportunity for palliative care support. Therefore, we conducted a sequential, prospective cohort study of patients before and after implementation of triggered palliative care consults for patients with advanced cancer. We found that patients’ prognostic awareness meaningfully and significantly improved after the implementation of consults, but there was little impact on utilization of health services. We did identify that providing consults to the entire population of patients was logistically challenging due to short stays, high-acuity symptoms, and individual provider resistance, but overall the oncology providers found the consults to be beneficial.


http://medicalresearch.com/author-interviews/early-palliative-care-consultations-are-well-received-by-patients-by-dont-decrease-health-services/15175/










http://medicalresearch.com/heart-disease/palliative-caer-in-acute-coronary-syndrome-understudied/12320/







• MedicalResearch: What should clinicians and patients take away from your report?• Dr. Rocque: Palliative Care consultation for hospitalized cancer patients are well-received and

enhance communication including an improved understanding of their cancer and their prognosis. The oncologists also report an improved understanding of their patients’ perspective. We recommend implementing a standardized approach to palliative care consultation.












http://medicalresearch.com/cancer-_-oncology/adult_cancer_end_of_life_care_palliative_chemotherapy/4052/








• Dr. Rocque: While hospitalization is a time of high palliative care needs, life expectancy and hospital lengths of stay are short so the impact of palliative care consultation is limited. Given the substantial benefits of early outpatient palliative care, we suggest that future research focus on strategies for earlier integration of ambulatory palliative care services after inpatient consultation.

• Citation:• J Pain Symptom Manage. 2015 Jun 15. pii: S0885-3924(15)00251-1. doi: 10.1016/j.jpainsymm

an.2015.04.022. [Epub ahead of print]• A Quantitative Study of Triggered Palliative Care Consultation for Hospitalized Patients with A

dvanced Cancer.• Rocque GB1, Campbell TC2, Johnson SK2, King J3, Zander MR4, Quale RM4, Eickhoff JC5

, Cleary JF3.












http://medicalresearch.com/author-interviews/community-based-palliative-care-teams-reduce-unnecessary-acute-care-end-life/5826/



























Commuter Patterns Can Help Predict Influenza SpreadMedicalResearch.com Interview with:Brooke Bozick Ph.D. CandidatePopulation Biology, Ecology, & Evolution ProgramEmory University

• MedicalResearch: What is the background for this study? • Response: Previous research at the global scale has shown that air travel is important for the

spread of disease. For example, much work has focused on the recent Ebola epidemic in Africa, identifying where this disease emerged and then using air travel networks to predict the path of spread from there.

• At a more local scale, other modes of transportation may be more important to structuring pathogen populations. We were interested in investigating seasonal influenza in the United States. Previous research has shown that once the winter influenza epidemic starts, it spreads very rapidly across the continental states, suggesting that the US may act as one large, well-mixed population. Previous work using genetic data to look for spatial structure at this scale didn’t identify any patterns. However, these studies used geographic proximity to define the distance between states; we wanted to see whether similar patterns existed at this spatial scale if we instead used movement data as a proxy for the distance between locations. Commuter movements have previously been shown to correlate with influenza timing and spread based on influenza-like-illness and mortality data.


http://medicalresearch.com/infections/flu-influenza/commuter-patterns-can-help-predict-influenza-spread/15180/
















• MedicalResearch: What are the main findings?• Response: We found that spatial structure is detectable within the US. We used data on the

genetic distance between sequences collected from different states and compared that to different measures of ‘distance’ between states—geographic proximity, the daily number of people flying between states and the daily number of commuters traveling between states using ground transportation—to see whether any correlations were present. Further, we did this for two different subtypes of seasonal influenza: A/H3N2 and A/H1N1. These subtypes have different epidemiological properties, so there was reason to believe that the observed patterns might differ depending on subtype.

• We found that some correlations were present for all the distance metrics studied, but that they were observed a greater proportion of the time when looking at commuter movements, and when looking at the A/H1N1 subtype. Since A/H1N1 is generally milder and spreads more slowly throughout the US compared to A/H3N2, we interpret this to mean that spatial structure is likely more easily detected in this subtype. If A/H3N2 spreads rapidly from coast to coast, any signature of spatial structure is likely obscured before we have a chance to observe it












http://medicalresearch.com/infections/flu-influenza/flu_mutations_led_to_more_disease_among_middle_aged_adults/8445/







• MedicalResearch: What should clinicians and patients take away from your report?• Response: The detection of network structure implies that patterns of epidemic spread are,

to some extent, predictable. The absence of predictability is problematic for the design of targeted surveillance and control strategies, since it suggests that the annual seasonal spread of influenza within countries is highly variable and depends heavily on chance events. In that case, broad scale surveillance and mitigation strategies must be utilized, and these generally perform worse than more directed approaches. We showed here that there are underlying spatial patterns in the genetic data, and that these are dependent on how the ‘distance’ between locations is being measured. This information can then be used to target surveillance and control to certain geographic locations or host groups.



















• Response: Our study demonstrates the importance of incorporating host movement data when trying to predict how diseases will spread. Humans can move long distances very rapidly so the idea that geographic proximity is key to determining disease spread doesn’t always hold.

• Our findings based on genetic data are in agreement with previous research using influenza-like illness case data; both show that patterns do exist, with strongly connected states having similarly timed epidemic peaks and similar genetic variants circulating. The patterns we found are likely influenced by states with many commuters, and the identification of these states, as well as network pathways that contribute substantially to influenza spread, is an important next step for epidemiological research.

• Citation:• The Role of Human Transportation Networks in Mediating the Genetic Structure of Seasonal I

nfluenza in the United States• Brooke A. Bozick Leslie A. Real • PLOS Published: June 18, 2015 DOI: 10.1371/journal.ppat.1004898












http://medicalresearch.com/infections/flu-influenza/severe-flu-associated-younger-age-lack-vaccination/3662/

http://www.plospathogens.org/article/related/info:doi/10.1371/journal.ppat.1004898









Newer Glaucoma Treatments May Be Best For Less Advanced DiseaseMedicalResearch.com Interview with:Pradeep Ramulu MD MHS PhDAssociate Professor of OphthalmologyWilmer Eye InstituteJohns Hopkins University

• MedicalResearch: What is the background for this study? What are the main findings?• Dr. Ramulu: Looking at what procedures are used allows us to understand what doctors are

doing, and how the landscape of our field is changing. We noted that overall numbers for glaucoma procedures were down – a surprise given that our population is aging, there are more Medicare beneficiaries, and there have not been recent advances in medical therapy for glaucoma.


http://medicalresearch.com/ophthalmology/newer-glaucoma-treatments-may-be-best-for-less-advanced-disease/15182/

















• MedicalResearch: What should clinicians and patients take away from your report?• Dr. Ramulu: There is a strong trend towards newer glaucoma procedures, particularly

endocyclophotocoagulation, external mini-shunts, and canaloplasty. At the same time, traditional procedures such as trabeculectomy and tube shunts are still quite common, and the growth of these newer procedures should not imply that they treat glaucoma better than conventional therapies. It is also important for patients to realize that these newer therapies are often best suited as an initial therapy for less advanced disease.













http://medicalresearch.com/ophthalmology/decreased-medicare-payment-did-not-mean-increased-volume-for-most-glaucoma-procedures/13647/








• Dr. Ramulu: Our hope is that there is increasing research to help understand the efficacy of these newer treatments in the treatment of glaucoma, particularly in the form of head-to-head trials with more conventional therapy.

• Citation:• Use of Various Glaucoma Surgeries and Procedures in Medicare Beneficiaries from 1994 to

2012• Arora, Karun S. et al.• Ophthalmology

DOI: http://dx.doi.org/10.1016/j.ophtha.2015.04.015













http://dx.doi.org/10.1016/j.ophtha.2015.04.015






New Skin MedicalResearch.com Interview with:Dr. Alexander Golberg Ph.D.Center for Engineering in MedicineDepartment of Surgery, Massachusetts General HospitalHarvard Medical School, and Shriners Burns HospitalBoston, MA, 02114

• MedicalResearch: What is the background for this study? What are the main findings?• Dr. Golberg: Well, the population grows and becomes older. Degenerative skin diseases affect

one third of individuals over the age of sixty. Current therapies use various physical and chemical methods to rejuvenate skin; but since the therapies affect many tissue components including cells and extracellular matrix, they may also induce significant side effects, such as scarring.

• We report on a new, non-invasive, non-thermal technique to rejuvenate skin with pulsed electric fields. The fields destroy cells while simultaneously completely preserving the extracellular matrix architecture and releasing multiple growth factors locally that induce new cells and tissue growth. We have identified the specific pulsed electric field parameters in rats that lead to prominent proliferation of the epidermis, formation of microvasculature, and secretion of new collagen at treated areas without scarring. Our results suggest that pulsed electric fields can improve skin function and thus can potentially serve as a novel non-invasive skin therapy for multiple degenerative skin diseases.


http://medicalresearch.com/author-interviews/new-skin-rejuvenation-technique-uses-pulsed-electric-fields/15184/

















MedicalResearch: What should clinicians and patients take away from your report?Dr. Golberg: We have developed a new method for improving skin metabolism with non-thermal pulsed electric fields. These studies have been done with animals and we are in the process of translating this technology to humans. What is also important is that intervention methods on the cellular and not tissue levels become available for a variety of diseases.




















• Dr. Golberg: The most important direction for the future is to show the improvement of skin in animals with specific disease models.

• The second direction is to show safety and efficiency in humans.• Citation:• Skin Rejuvenation with Non-Invasive Pulsed Electric Fields• Scientific Reports 5, Article number: 10187• doi:10.1038/srep10187• Alexander Golberg,Saiqa Khan,Vasily Belov,Kyle P. Quinn,Hassan Albadawi,G. Felix Broelsch,Mi

chael T. Watkins,Irene Georgakoudi,Mikhail Papisov,Martin C. Mihm Jr.,William G. Austen Jr. & Martin L. Yarmush













http://www.nature.com/srep/2015/150512/srep10187/full/srep10187.html%23affil-auth











Mechanism Linking Excess Fructose Intake To Heart Disease DelineatedMedicalResearch.com Interview with:Prof. Wilhelm KrekInstitute of Molecular Health SciencesZürich, Switzerland

• MedicalResearch: What is the background for this study? What are the main findings?

• Prof. Krek: Fructose and glucose are major components of dietary sugars consumed in the western world. A current prevailing view holds that glucose is used directly by various tissues as an energy source while fructose is first and foremost metabolized to fat by the liver arguing that these dietary sugars are metabolized differently despite having identical caloric values. Accordingly, overconsumption of fructose causes fatty liver disease and through dissemination of fat to peripheral organs such that adipose tissue contributes to obesity.

• The key enzyme in fructose metabolism is ketohexokinase (KHK). KHK-A and KHK-C are two isoforms of KHK that are produced through mutually exclusive alternative splicing of the KHK pre-mRNA. KHK-C displays a much higher affinity for fructose than KHK-A. Unlike other tissues that normally express KHK-A, the liver produces predominantly KHK-C providing a possible explanation of the above-noted pathologies upon overconsumption of fructose. Whether fructose metabolism is subject to signal-induced changes in alternative splicing of KHK isoform expression as a mechanism to mediate context-dependent changes in cell metabolism is not known. In this work, we identify the splicing factor SF3B1 as a key mediator of ketohexokinase alternative splicing and thus activator of fructose metabolism and further show that the SF3B1-KHK system is a direct target of regulation by hypoxia and promoter of heart disease. From the analysis of a series of genetic mouse models of pathologic cardiac hypertrophy and human samples of heart disease, we conclude that activation of the newly identified HIF1α-SF3B1-KHK-C axis and the ensuing promotion of fructose metabolism is essential for pathologic stress-induced anabolic growth and the development of heart disease.


http://medicalresearch.com/heart-disease/mechanism-linking-excess-fructose-intake-to-heart-disease-delineated/15195/














• MedicalResearch: What should clinicians and patients take away from your report?• Prof. Krek: Over the last 3-4 decades fructose spread throughout the food market as it has

been considered less harmful than glucose. Unlike glucose, fructose appears not to increase blood glucose levels and insulin secretion thus avoiding frequently recurring insulin spikes after glucose intake. Fructose can be found in many foods as additive, especially in sweet beverages and soft drinks. This practice drove up per capita consumption of high fructose corn syrup in the USA between 1970 and 1997, from 230 grams per year to over 28 kilograms.Potentially, this surplus of fructose can help trigger the mechanism described in the context of one of more of the stress factors is present, such as cardiac valve disease or high blood pressure.

















• • Prof. Krek: This work delinates a molecular mechanism by which a specific pathologically-

activated signaling pathway enacts a central component of the alternative pre-mRNA splicing machinery to promote fructose-dependent anabolic metabolism and pathologic growth of the heart. The fact that hypoxia is a central feature of many pathologies and SF3B1 has been found recurrently mutated in various human cancers point to a potential broad role of the HIF-SF3B1-KHK axis and deregulated fructose metabolism in driving diseases in various tissue contexts. Future investigations should aim at understanding the role of this signaling circuit in diverse tissue and disease contexts and providing provide rationales for the development of specific therapeutic agents that interfere with the pathologic activation of this fructose-regulatory system in human disease.

• Citation:• HIF-driven SF3B1 induces KHK-C to enforce fructolysis and heart disease• Peter Mirtschink, Jaya Krishnan, Fiona Grimm, Alexandre Sarre,Manuel Hörl, Melis Kayikci, Ni

klaus Fankhauser, Yann Christinat, Cédric Cortijo, Owen Feehan, Ana Vukolic, Samuel Sossalla, Sebastian N. Stehr, Jernej Ule, Nicola Zamboni, Thierry Pedrazzini & Wilhelm Krek

• Nature (2015) doi:10.1038/nature14508










http://medicalresearch.com/weight-research/fructose-linked-to-weight-gain-and-reduced-physical-activity/14693/

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature14508.html










Few Well Done Studies Support Medical Use of CannabisMedicalResearch.com Interview with: Penny F. Whiting, PhDSchool of Social and Community Medicine, University of Bristol

The National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care West at University Hospitals, Bristol NHS Foundation Trust, Bristol UK

Kleijnen Systematic Reviews Ltd, Escrick, York, United Kingdom• MedicalResearch: What is the background for this study? What are the main findings?• Dr. Whiting: Cannabis is one of the most popular recreational drugs – only tobacco, alcohol

and caffeine are more popular. It can result in an alteration to mood and a feeling of “high”. An estimated 141 million people use cannabis worldwide – this is equivalent to 2.5% of the world’s population. Cannabis has a long history of use for the relief of a wide variety of medical symptoms. There is evidence of its use for medical purposes going back to early Egyptian times. The pen-ts’ao ching the world’s oldest herbal book includes reference to cannabis as medicine for rheumatic pain, constipation, disorders of the female reproductive system, and malaria amongst others, this herbal book also contains the first reference to cannabis as a psychoactive drug. However, its use is controversial as it has been included as a controlled drug in the United Nations Single Convention on Narcotic Drugs since 1961, and the use of cannabis is illegal in most countries.


http://medicalresearch.com/author-interviews/few-well-done-studies-support-medical-use-of-cannabis/15199/




















Kleijnen Systematic Reviews Ltd, Escrick, York, United Kingdom Medical cannabis (or medical marijuana) refers to the use of cannabis or cannabinoids (any compound, natural or synthetic, that can mimic the actions of plant-derived cannabinoids) as medical therapy to treat disease or alleviate symptoms. Some countries have legalised medicinal-grade cannabis to chronically ill patients but in others its use remains illegal even for medicinal purposes. Canada and the Netherlands have government run programmes where specialised companies supply quality controlled herbal cannabis. These programmes have been running since 2001 and 2003 respectively. In the US around half of the states have introduced laws to permit the medical use of cannabis; other countries have similar laws.






















Kleijnen Systematic Reviews Ltd, Escrick, York, United Kingdom Kleijnen Systematic Reviews Ltd (see below) were commissioned by the Swiss Federal Office of Public Health to conduct a systematic review for the effects and adverse events of medical cannabis to inform policy decision making. Systematic reviews are studies of studies that offer a systematic approach to reviewing and summarising evidence. They follow a defined structure to identify, evaluate and summarise all available evidence addressing a particular research question. We were asked to focus on the following ten indications which were of particular interest to our commissioners: nausea and vomiting due to chemotherapy, patients with HIV/AIDS, chronic pain, spasticity in patients with multiple sclerosis or paraplegia, depression, anxiety disorder, sleep disorder, psychosis, glaucoma, and Tourette’s syndrome. We only included randomised trials, the most robust design for evaluating the effects of an intervention. We included almost 80 trials (nearly 6500 participants). We had most evidence for chronic pain (28 trials), nausea and vomiting due to chemotherapy (28 trials) and spasticity due to MS or paraplegia (14 trials) with less than five studies included for each of the other indications and none for depression. With the exception of the nausea and vomiting due to chemotherapy population, studies general compared cannabinoids to placebo with only single studies for each indication comparing cannabinoid with an active comparator. In the nausea and vomiting population the majority of studies compared cannabinoids to an active comparator, most commonly prochlorperazine.






















Kleijnen Systematic Reviews Ltd, Escrick, York, United Kingdom Most trials reported greater improvement in symptoms with cannabinoids compared to control groups, however, these did not always reach statistical significance. Cannabinoids were also associated with a greater risk of short term adverse events, including serious adverse events. Common adverse events included dizziness, dry mouth, nausea, fatigue, sleepiness, and euphoria. Overall we found that there was moderate quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity and low-quality evidence to suggest that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep quality, and Tourette syndrome. When determining the quality of the evidence we considered the risk of bias in trials, the consistency of the evidence across the trials, the directness of the evidence (was the trials research question directly applicable to our review question), and the precision of the evidence.















http://medicalresearch.com/addiction/cannabis-withdrawal-nabiximols-agonist-replacement-therapy/3452/








Kleijnen Systematic Reviews Ltd, Escrick, York, United Kingdom• MedicalResearch: What should clinicians and patients take away from your report?• Dr. Whiting: We have used the same robust evidence based methods to evaluate the effects

of medical cannabis (cannabinoids) as we would apply to any other intervention. It is important that all interventions are judged according to the same standards and that the potential benefits and adverse effects of cannabinoids are considered in light of the evidence and are not clouded by the issues around the legal status of cannabis. As systematic reviewers, we have provided a summary of the available evidence which clinicians and policy makers can now use this to make recommendations for practice.






















Kleijnen Systematic Reviews Ltd, Escrick, York, United Kingdom• MedicalResearch: What recommendations do you have for future research as a result of

this study?• Dr. Whiting: Further large, well conducted, randomised controlled trials are needed to

confirm the effects of cannabinoids, particularly on weight gain in patients with HIV/AIDS, depression, sleep disorders, anxiety disorder, psychosis, glaucoma, and Tourette syndrome are required. We only found two studies that evaluated cannabis and so further trials evaluating cannabis itself are also required.

• Two main challenges faced by our review were the poor reporting and lack of standardised outcome measures. Future trials therefore need to adhere to CONSORT reporting standards and report outcome data in a form that can be incorporated into meta-analyses. Poor reporting made it difficult to assess the risk of bias in the included trials and to extract appropriate numerical data for inclusion in meta-analyses (statistical combination of data from primary studies to give an estimate of the effect across all studies). Lack of standardised outcomes meant that included trials reported a wide variety of outcomes measured in different ways making it very difficult to combine data in a meaningful way. Future studies need to assess relevant outcomes (including disease-specific endpoints, quality of life, and adverse events) using standardised outcome measures at similar time points to ensure inclusion in meta-analyses.






















Kleijnen Systematic Reviews Ltd, Escrick, York, United Kingdom• Kleijnen Systematic Reviews Ltd (KSR Ltd)• Staff at KSR Ltd have many years of experience in preparing systematic reviews and health

technology assessments of therapeutic, screening and diagnostic interventions. Such reviews have been used to support policy making, local decision making about commissioning health services, fourth hurdle processes (such as for NICE in the UK, or for IQWiG in Germany), and guideline development. We have extensive experience in all these areas and our names appear as authors on numerous journal publications, technology assessment reports for NICE, systematic reviews for IQWiG, health technology assessment reports, and guidelines.

• KSR Ltd has also been appointed as a “Centre of Excellence” for Technology Assessment Reviews (TARs) by the National Institute for Health Research (NIHR). In this capacity we are involved in providing TARs for national UK NHS decision-making bodies and policy customers, such as the National Institute for Health and Care Excellence (NICE). Such TARs are most commonly produced to inform NICE Appraisal Committee guidance on the use of new and existing medicines, treatments and procedures within the NHS in England and Wales.






















Kleijnen Systematic Reviews Ltd, Escrick, York, United Kingdom• Citation:• Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for Medical Use: A Systematic Review

and Meta-analysis. JAMA.2015;313(24):2456-2473. doi:10.1001/jama.2015.6358.















http://jama.jamanetwork.com/article.aspx?articleid=2338251

http://jama.jamanetwork.com/article.aspx?articleid=2338251






Many Petroleum Product Releases Due To Private Accidents and Damage To Utilities or LinesMedicalResearch.com Interview with:Ayana R. Anderson, MPHDivision of Toxicology and Human Health Sciences

Agency for Toxic Substances and Disease Registry

• MedicalResearch: What is the background for this study? What are the main findings?• Response: Large mass casualty gas explosions and oil spills are widely reported in the media

and receive considerable regulatory attention. However, smaller less catastrophic events are less likely to receive publicity. The Agency for Toxic Substances and Disease Registry (ATSDR) analyzed 2010–2012 data from the National Toxic Substance Incidents Program (NTSIP) to describe the causes and public health impacts of petroleum product release incidents and to better focus and prioritize prevention efforts.

• There were a total of 1,369 petroleum product releases reported from 7 states resulting in 512 injured persons and 36 deaths.

• Approximately one fourth of the incidents were associated with utilities.• Approximately one fifth were associated with private vehicles or residences.• Approximately 10 percent of petroleum product releases resulted from inadvertent

damage to utility lines.


http://medicalresearch.com/author-interviews/many-petroleum-product-releases-due-to-private-accidents-and-damage-to-utilities-or-lines/15203/















• MedicalResearch: What should clinicians and patients take away from your report?• Response: We want clinicians and patients to know that if not managed properly, releases of

petroleum products can adversely affect humans, wildlife, and the environment. Adverse health effects can include skin irritation, eye irritation, dizziness, headache, nausea and, and, in extreme cases, death.


















• Response: Because of the danger posed by petroleum incidents and their continuing occurrence, strategies to prevent releases are needed. Education is also needed to inform the public about the safe use of petroleum products and how to recognize a gas leak and know what steps to take to prevent explosions and fires. Based on the NTSIP data, a comprehensive approach to construction worker training regarding ruptured line prevention might reduce petroleum release incidents and their health consequences.

• Citation:• Health Effects of Cut Gas Lines and Other Petroleum Product Release Incidents — Seven State

s, 2010–2012• MMWRWeekly• June 12, 2015 / 64(22);601-605










http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6422a1.htm









Gut Microbiome May Influence Our Behavior and Long Term MemoryMedicalResearch.com Interview with:Kathy Magnusson D.V.M., Ph.D ProfessorOregon State College of Veterinary Medicine

Principal Investigator with the Linus Pauling Institute

• Medical Research: What is the background for this study?

Dr. Magnusson: There is increasing evidence that the gut microbiome can communicate with our brain. Others had also shown that high-energy diets could alter the composition of the gut microbiome (i.e., shift the percentages of different bacteria within the population) and could alter cognitive function. We decided to use that dietary model to determine whether there was a relationship between the bacterial changes and the behavioral changes.

• Medical Research: What are the main findings?

Dr. Magnusson: We found decreases in Bacteroidales and increases in Clostridiales orders of bacteria, similar to that seen in obese humans and animals on high energy diets. We also found problems with early learning for long-term memory, with delayed short-term memory and with cognitive flexibility, the ability to adapt to new rules and changing conditions. The alterations in Bacteroidales and Clostridiales showed a relationship to this decline in cognitive flexibility.


http://medicalresearch.com/author-interviews/gut-microbiome-may-influence-our-behavior-and-long-term-memory/15237/
















Gut Microbiome May Influence Our Behavior and Long Term MemoryMedicalResearch.com Interview with:Kathy Magnusson D.V.M., Ph.D ProfessorOregon State College of Veterinary Medicine

Principal Investigator with the Linus Pauling Institute

• Medical Research: What should clinicians and patients take away from your report?

• Dr. Magnusson: When you consume high-energy diets, it’s not just about the food directly affecting your brain and body. These diets also alter the bacterial populations within your gut, which may contribute to the negative effects on your brain and other body systems.


• Dr. Magnusson: We need to understand better how these specific bacteria communicate with the brain, how that communication affects the body and whether it benefits the microbes, and whether we can manipulate the microbiome to obtain better, long-term behavioral outcomes.

• Citation:• K.R. Magnusson, L. Hauck, B.M. Jeffrey, V. Elias, A. Humphrey, R. Nath, A. Perrone, L.E.

Bermudez. Relationships between diet-related changes in the gut microbiome and cognitive flexibility. Neuroscience, 2015; 300: 128 DOI: 10.1016/j.neuroscience.2015.05.016













http://dx.doi.org/10.1016/j.neuroscience.2015.05.016






Obesity Largely Driving Health Care and Societal BurdenMedicalResearch.com Interview with:Dr. Yang Lin on behalf of all authorsDepartment of Surgery, Division of Public Health SciencesSiteman

Cancer Center, Washington University School of MedicineSt Louis, Missouri

• Medical Research: What is the background for this study? What are the main findings?• Dr. Lin: Overweight, obesity and associated chronic conditions are largely driving the health

care and societal burden, yet potentially preventable. Using the most recent nationally representative data between 2007 and 2012, we estimated the prevalence of overweight and obesity in the US by gender, age, racial and ethnicity groups to inform clinical practice and the priority for cost-effective prevention strategies.

• Medical Research: What should clinicians and patients take away from your report?• Dr. Lin: Clinicians and patients ought to be aware of the negative health impact of overweight

and obesity. Clinicians are encouraged to discuss the strategies to prevent or treat obesity through behavior change techniques.


http://medicalresearch.com/weight-research/obesity-largely-driving-health-care-and-societal-burden/15164/










http://medicalresearch.com/weight-research/which-bariatric-procedure-is-best-for-patients-with-morbid-obesity/11358/

http://medicalresearch.com/pediatrics/many-overweight-and-obese-children-will-become-obese-adults/14102/






Obesity Largely Driving Health Care and Societal BurdenMedicalResearch.com Interview with:Dr. Yang Lin on behalf of all authorsDepartment of Surgery, Division of Public Health SciencesSiteman

Cancer Center, Washington University School of MedicineSt Louis, Missouri


• Dr. Lin: Combating obesity as a nation requires a political will to support multi-level approaches through individual, health professional, community, environment and policy engagement to address this epidemic as a whole. Population-based strategies may help to alter the obesity trend through physical environment intervention, enhancing primary care efforts and shifting society norms of behavior.

• Citation:• Graham A. Colditz, MD DrPH | Niess-Gain Professor of Surgery, Professor of Medicine | Chief,

Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine | Associate Director Prevention and Control, Alvin J. Siteman Cancer Center | 660 South Euclid Avenue, Campus Box 8100 | Saint Louis, MO 63110












http://medicalresearch.com/diabetes/obesity-leads-to-reversible-changes-in-diabetes-predisposition-genes/14351/






High Blood Pressure In Young Adulthood Increases Risk Of Later Heart FailureMedicalResearch.com Interview with:Satoru Kishi, MDDivision of CardiologyJohns Hopkins UniversityBaltimore, Maryland

• MedicalResearch: What is the background for this study? What are the main findings?• Dr. Kishi: Blood pressure (BP) at the higher end of the population distribution may represent

a chronic exposure that produces chronic injury to the cardiovascular system. Cumulative BP exposure from young adulthood to middle age may adversely influence myocardial function and predispose individuals to heart failure (HF) and other cardiovascular disease (CVD) later in life. The 2005 guidelines for the diagnosis and treatment of HF from the American College of Cardiology and American Heart Association highlight the importance of early recognition of subclinical cardiac disease and the importance of non-invasive tests in the clinical evaluation of heart failure.

• Our main objective was to investigate how cumulative exposure to high blood pressure from young to middle adulthood influence LV function. In the Coronary Artery Risk Development in Young Adults (CARDIA) study, multiple repeated measures of BP and other cardiovascular risk factors was recorded over a 25 year time span, starting during early adulthood (ages 18-30).


http://medicalresearch.com/heart-disease/high-blood-pressure-in-young-adulthood-increases-risk-of-later-heart-failure/15225/










http://medicalresearch.com/heart-disease/emergency-room-coding-of-heart-failure-diagnosis-validated/13910/







• MedicalResearch: What should clinicians and patients take away from your report?• Dr. Kishi: High cumulative exposure to blood pressure may predict clinical heart failure. Our

study findings indicate that high blood pressure in early adulthood or developed during the first 25 years of early adulthood (over 25 years from age 18 to 30 years) is related to early measures of systolic and diastolic dysfunction in middle aged individuals, emphasizing the importance of prevention of high BP development early in life. These findings suggest that uncontrolled BP may increase the lifetime risk of incident heart failure in the general population.

• Hypertension has been long implicated as a risk factor in a range of cardiovascular diseases. But our study suggest that pressure just below that threshold — or high normal pressure — begins to fuel heart damage in people as young as 20 and can lead to changes in myocardial function in as little as 25 years. The latest clinical guidelines issued by the JNC 8 define hypertension as blood pressure above 140/90. However, the results of the new study suggest that a single cutoff measurement does not apply to all ages and what constitutes “normal” should probably change with age.












http://medicalresearch.com/heart-disease/processed_red_meat_linked_to_higher_risk_of_heart_failure/6466/








• Dr. Kishi: We relied on a subclinical end-point (LV systolic and diastolic dysfunction measured by echocardiography); our findings will need validation using clinical end-points. Further studies are needed to determine whether specific lifestyle interventions implemented to reduce blood pressure in early adulthood prevent HF from developing later in life.

• Citation:• Satoru Kishi, MD; Gisela Teixido-Tura, MD, PhD; Hongyan Ning, MD; Bharath Ambale

Venkatesh, PhD; Colin Wu, PhD; Andre Almeida, MD; Eui-Young Choi, MD; Ola Gjesdal, MD; David R. Jacobs, Jr., PhD; Pamela J. Schreiner, PhD; Samuel S. Gidding, MD; Kiang Liu, PhD; João A.C. Lima, MD. Cumulative Blood Pressure in Early Adulthood and Cardiac Dysfunction in Middle Age: The CARDIA Study. Journal of the American College of Cardiology, June 2015DOI: 10.1016/j.jacc.2015.04.042












http://medicalresearch.com/author-interviews/your-smartphone-may-help-you-control-your-blood-pressure/14982/

http://dx.doi.org/10.1016/j.jacc.2015.04.042






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Medical research slideshare_june_24_2015