Hot Topics: New Free Database Crowdsources Cancer Mutation Research

CIViC is a Community Knowledgebase for Expert Crowdsourcing the Clinical Interpretation of Variants in Cancer

Griffith M, Spies NC, Krysiak K, et al. CIViC is a community knowledgebase for expert crowdsourcing the clinical interpretation of variants in cancer. Nat Genet. 2017;49(2):170-174. http://dx.doi.org/10.1038/ng.3774.

CIViC is an expert-crowdsourced knowledgebase for Clinical Interpretation of Variants in Cancer describing the therapeutic, prognostic, diagnostic and predisposing relevance of inherited and somatic variants of all types. CIViC is committed to open-source code, open-access content, public application programming interfaces (APIs) and provenance of supporting evidence to allow for the transparent creation of current and accurate variant interpretations for use in cancer precision medicine.

Posted in Front Page, Hot Topics in Research, Oncology

Journal of Medical Insight (JoMI) trial

The PCOM Library is offering a one month trial to the Journal of Medical Insight.

JoMI is a surgical video journal / virtual operating theater that seeks to impact health care and education through filming and publishing surgical procedures performed by top teaching physicians.

JoMI was filmed at Massachusetts General Hospital, Brigham and Women’s Hospital, and other top institutions and, at present, primarily focuses on orthopedics, orthopedic trauma, and general surgery and patient care.

Access from the web, tablet, laptop and smartphones. You need only to create an account on JoMI.com and list Philadelphia College of Osteopathic Medicine as the “Institution”. This will allow for complete access (including off-campus and on tablets, laptops, and smartphones).

The institutional trial starts 02/01/17 and expires on 3/01/17.

Did you find this resource useful? Please send comments to library@pcom.edu.

Posted in Front Page, Library News, New Resources

Hot Topics: Women in Poverty More at Risk for Heart Attacks Than Men

Sex differences in the relationship between socioeconomic status and cardiovascular disease: A systematic review and meta-analysis

Backholer K, Peters SAE, Bots SH, Peeters A, Huxley RR, Woodward M. Sex differences in the relationship between socioeconomic status and cardiovascular disease: A systematic review and meta-analysis. Journal of Epidemiology and Community Health. 2016. http://dx.doi.org/10.1136/jech-2016-207890.

Background Low socioeconomic status (SES) is a known risk factor for cardiovascular disease (CVD) but whether its effects are comparable in women and men is unknown.

Methods PubMed MEDLINE was systematically searched. Studies that reported sex-specific estimates, and associated variability, of the relative risk (RR) for coronary heart disease (CHD), stroke or CVD according to a marker of SES (education, occupation, income or area of residence), for women and men were included. RRs were combined with those derived from cohort studies using individual participant data. Data were pooled using random effects meta-analyses with inverse variance weighting. Estimates of the ratio of the RRs (RRR), comparing women with men, were computed.

Results Data from 116 cohorts, over 22 million individuals, and over 1 million CVD events, suggest that lower SES is associated with increased risk of CHD, stroke and CVD in women and men. For CHD, there was a significantly greater excess risk associated with lower educational attainment in women compared with men; comparing lowest with highest levels, the age-adjusted RRR was 1.24 (95% CI 1.09 to 1.41) and the multiple-adjusted RRR was 1.34 (1.09 to 1.63). For stroke, the age-adjusted RRR was 0.93 (0.72 to 1.18), and the multiple-adjusted was RRR 0.79 (0.53 to 1.19). Corresponding results for CVD were 1.18 (1.03 to 1.36), 1.23 (1.03 to 1.48), respectively. Similar results were observed for other markers of SES for all three outcomes.

Conclusions Reduction of socioeconomic inequalities in CHD and CVD outcomes might require different approaches for men and women.

Posted in Cardiology, Front Page, Hot Topics in Research

ScienceDirect Technical Issue

Due to a technical issue, some users are experiencing trouble accessing ScienceDirect content off-campus.

If you experience trouble, try re-accessing ScienceDirect through this link or by installing the Remote Access Bookmarklet and clicking the bookmarklet while on ScienceDirect to reload the page through the library’s proxy.

Please contact us if you have any questions.

Posted in Front Page, Library News, Service Disruptions

Hot Topics: Bed Cycling Safe for ICU Patients

TryCYCLE: A Prospective Study of the Safety and Feasibility of Early In-Bed Cycling in Mechanically Ventilated Patients

Kho ME, Molloy AJ, Clarke FJ, et al. TryCYCLE: A prospective study of the safety and feasibility of early in-bed cycling in mechanically ventilated patients. PLOS ONE. 2016;11(12):e0167561.

Introduction

The objective of this study was to assess the safety and feasibility of in-bed cycling started within the first 4 days of mechanical ventilation (MV) to inform a future randomized clinical trial.

Methods

We conducted a 33-patient prospective cohort study in a 21-bed adult academic medical-surgical intensive care unit (ICU) in Hamilton, ON, Canada. We included adult patients (≥ 18 years) receiving MV who walked independently pre-ICU. Our intervention was 30 minutes of in-bed supine cycling 6 days/week in the ICU. Our primary outcome was Safety (termination), measured as events prompting cycling termination; secondary Safety (disconnection or dislodgement) outcomes included catheter/tube dislodgements. Feasibility was measured as consent rate and fidelity to intervention. For our primary outcome, we calculated the binary proportion and 95% confidence interval (CI).

Results

From 10/2013-8/2014, we obtained consent from 34 of 37 patients approached (91.9%), 33 of whom received in-bed cycling. Of those who cycled, 16(48.4%) were female, the mean (SD) age was 65.8(12.2) years, and APACHE II score was 24.3(6.7); 29(87.9%) had medical admitting diagnoses. Cycling termination was infrequent (2.0%, 95% CI: 0.8%-4.9%) and no device dislodgements occurred. Cycling began a median [IQR] of 3 [2, 4] days after ICU admission; patients received 5 [3, 8] cycling sessions with a median duration of 30.7 [21.6, 30.8] minutes per session. During 205 total cycling sessions, patients were receiving invasive MV (150 [73.1%]), vasopressors (6 [2.9%]), sedative or analgesic infusions (77 [37.6%]) and dialysis (4 [2.0%]).

Conclusions

Early cycling within the first 4 days of MV among hemodynamically stable patients is safe and feasible. Research to evaluate the effect of early cycling on patient function is warranted.

Posted in Critical Care, Hot Topics in Research, January, Physical Therapy

Hot Topics: Lifestyle Makes a Difference in Heart Disease

Genetic Risk, Adherence to a Healthy Lifestyle, and Coronary Disease

Khera AV, Emdin CA, Drake I, et al. Genetic risk, adherence to a healthy lifestyle, and coronary disease. N Engl J Med. 2016;375(24):2349-2358. http://dx.doi.org/10.1056/NEJMoa1605086.

BACKGROUND
Both genetic and lifestyle factors contribute to individual-level risk of coronary artery disease. The extent to which increased genetic risk can be offset by a healthy lifestyle is unknown.

METHODS
Using a polygenic score of DNA sequence polymorphisms, we quantified genetic risk for coronary artery disease in three prospective cohorts — 7814 participants in the Atherosclerosis Risk in Communities (ARIC) study, 21,222 in the Women’s Genome Health Study (WGHS), and 22,389 in the Malmö Diet and Cancer Study (MDCS) — and in 4260 participants in the cross-sectional BioImage Study for whom genotype and covariate data were available. We also determined adherence to a healthy lifestyle among the participants using a scoring system consisting of four factors: no current smoking, no obesity, regular physical activity, and a healthy diet.

RESULTS
The relative risk of incident coronary events was 91% higher among participants at high genetic risk (top quintile of polygenic scores) than among those at low genetic risk (bottom quintile of polygenic scores) (hazard ratio, 1.91; 95% confidence interval [CI], 1.75 to 2.09). A favorable lifestyle (defined as at least three of the four healthy lifestyle factors) was associated with a substantially lower risk of coronary events than an unfavorable lifestyle (defined as no or only one healthy lifestyle factor), regardless of the genetic risk category. Among participants at high genetic risk, a favorable lifestyle was associated with a 46% lower relative risk of coronary events than an unfavorable lifestyle (hazard ratio, 0.54; 95% CI, 0.47 to 0.63). This finding corresponded to a reduction in the standardized 10-year incidence of coronary events from 10.7% for an unfavorable lifestyle to 5.1% for a favorable lifestyle in ARIC, from 4.6% to 2.0% in WGHS, and from 8.2% to 5.3% in MDCS. In the BioImage Study, a favorable lifestyle was associated with significantly less coronary-artery calcification within each genetic risk category.

CONCLUSIONS
Across four studies involving 55,685 participants, genetic and lifestyle factors were independently associated with susceptibility to coronary artery disease. Among participants at high genetic risk, a favorable lifestyle was associated with a nearly 50% lower relative risk of coronary artery disease than was an unfavorable lifestyle. (Funded by the National Institutes of Health and others.)

Posted in Cardiology, Hot Topics in Research, Internal Medicine, January

Hot Topics: Experimental Ebola Vaccine Gives 100% Protection

Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!)

Henao-Restrepo A, Camacho A, Longini IM, et al. Efficacy and effectiveness of an rVSV-vectored vaccine in preventing ebola virus disease: Final results from the guinea ring vaccination, open-label, cluster-randomised trial (ebola ça suffit!). The Lancet. http://dx.doi.org/10.1016/S0140-6736(16)32621-6.

Background
rVSV-ZEBOV is a recombinant, replication competent vesicular stomatitis virus-based candidate vaccine expressing a surface glycoprotein of Zaire Ebolavirus. We tested the effect of rVSV-ZEBOV in preventing Ebola virus disease in contacts and contacts of contacts of recently confirmed cases in Guinea, west Africa.

Methods
We did an open-label, cluster-randomised ring vaccination trial (Ebola ça Suffit!) in the communities of Conakry and eight surrounding prefectures in the Basse-Guinée region of Guinea, and in Tomkolili and Bombali in Sierra Leone. We assessed the efficacy of a single intramuscular dose of rVSV-ZEBOV (2×107 plaque-forming units administered in the deltoid muscle) in the prevention of laboratory confirmed Ebola virus disease. After confirmation of a case of Ebola virus disease, we definitively enumerated on a list a ring (cluster) of all their contacts and contacts of contacts including named contacts and contacts of contacts who were absent at the time of the trial team visit. The list was archived, then we randomly assigned clusters (1:1) to either immediate vaccination or delayed vaccination (21 days later) of all eligible individuals (eg, those aged ≥18 years and not pregnant, breastfeeding, or severely ill). An independent statistician generated the assignment sequence using block randomisation with randomly varying blocks, stratified by location (urban vs rural) and size of rings (≤20 individuals vs >20 individuals). Ebola response teams and laboratory workers were unaware of assignments. After a recommendation by an independent data and safety monitoring board, randomisation was stopped and immediate vaccination was also offered to children aged 6–17 years and all identified rings. The prespecified primary outcome was a laboratory confirmed case of Ebola virus disease with onset 10 days or more from randomisation. The primary analysis compared the incidence of Ebola virus disease in eligible and vaccinated individuals assigned to immediate vaccination versus eligible contacts and contacts of contacts assigned to delayed vaccination. This trial is registered with the Pan African Clinical Trials Registry, number PACTR201503001057193.

Findings
In the randomised part of the trial we identified 4539 contacts and contacts of contacts in 51 clusters randomly assigned to immediate vaccination (of whom 3232 were eligible, 2151 consented, and 2119 were immediately vaccinated) and 4557 contacts and contacts of contacts in 47 clusters randomly assigned to delayed vaccination (of whom 3096 were eligible, 2539 consented, and 2041 were vaccinated 21 days after randomisation). No cases of Ebola virus disease occurred 10 days or more after randomisation among randomly assigned contacts and contacts of contacts vaccinated in immediate clusters versus 16 cases (7 clusters affected) among all eligible individuals in delayed clusters. Vaccine efficacy was 100% (95% CI 68·9–100·0, p=0·0045), and the calculated intraclass correlation coefficient was 0·035. Additionally, we defined 19 non-randomised clusters in which we enumerated 2745 contacts and contacts of contacts, 2006 of whom were eligible and 1677 were immediately vaccinated, including 194 children. The evidence from all 117 clusters showed that no cases of Ebola virus disease occurred 10 days or more after randomisation among all immediately vaccinated contacts and contacts of contacts versus 23 cases (11 clusters affected) among all eligible contacts and contacts of contacts in delayed plus all eligible contacts and contacts of contacts never vaccinated in immediate clusters. The estimated vaccine efficacy here was 100% (95% CI 79·3–100·0, p=0·0033). 52% of contacts and contacts of contacts assigned to immediate vaccination and in non-randomised clusters received the vaccine immediately; vaccination protected both vaccinated and unvaccinated people in those clusters. 5837 individuals in total received the vaccine (5643 adults and 194 children), and all vaccinees were followed up for 84 days. 3149 (53·9%) of 5837 individuals reported at least one adverse event in the 14 days after vaccination; these were typically mild (87·5% of all 7211 adverse events). Headache (1832 [25·4%]), fatigue (1361 [18·9%]), and muscle pain (942 [13·1%]) were the most commonly reported adverse events in this period across all age groups. 80 serious adverse events were identified, of which two were judged to be related to vaccination (one febrile reaction and one anaphylaxis) and one possibly related (influenza-like illness); all three recovered without sequelae.

Interpretation
The results add weight to the interim assessment that rVSV-ZEBOV offers substantial protection against Ebola virus disease, with no cases among vaccinated individuals from day 10 after vaccination in both randomised and non-randomised clusters.

Henao-Restrepo A, Camacho A, Longini IM, et al. Efficacy and effectiveness of an rVSV-vectored vaccine in preventing ebola virus disease: Final results from the guinea ring vaccination, open-label, cluster-randomised trial (ebola ça suffit!). The Lancet. http://dx.doi.org/10.1016/S0140-6736(16)32621-6.

Posted in Hot Topics in Research, Infectious Disease, Internal Medicine, January

Hot Topics: Common Gene Sets Link Bipolar Disorder, Major Depression, and Schizophrenia

Consistently altered expression of gene sets in postmortem brains of individuals with major psychiatric disorders

Darby M,M., Yolken R,H., Sabunciyan S. Consistently altered expression of gene sets in postmortem brains of individuals with major psychiatric disorders. Transl Psychiatry. 2016;6:e890. http://dx.doi.org/10.1038/tp.2016.173.

The measurement of gene expression in postmortem brain is an important tool for understanding the pathogenesis of serious psychiatric disorders. We hypothesized that major molecular deficits associated with psychiatric disease would affect the entire brain, and such deficits may be shared across disorders. We performed RNA sequencing and quantified gene expression in the hippocampus of 100 brains in the Stanley Array Collection followed by replication in the orbitofrontal cortex of 57 brains in the Stanley Neuropathology Consortium. We then identified genes and canonical pathway gene sets with significantly altered expression in schizophrenia and bipolar disorder in the hippocampus and in schizophrenia, bipolar disorder and major depression in the orbitofrontal cortex. Although expression of individual genes varied, gene sets were significantly enriched in both of the brain regions, and many of these were consistent across diagnostic groups. Further examination of core gene sets with consistently increased or decreased expression in both of the brain regions and across target disorders revealed that ribosomal genes are overexpressed while genes involved in neuronal processes, GABAergic signaling, endocytosis and antigen processing have predominantly decreased expression in affected individuals compared to controls without a psychiatric disorder. Our results highlight pathways of central importance to psychiatric health and emphasize messenger RNA processing and protein synthesis as potential therapeutic targets for all three of the disorders.

Posted in Hot Topics in Research, January, Mood Disorders, Psychology and Psychiatry, Schizophrenia

PCOM Full Text in Google Scholar

There is a current issue where PCOM Full Text links are not showing up in Google Scholar. Our vendor is working with Google to restore these links.

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Posted in Service Disruptions

Atlas of Osteopathic Techniques 3rd Edition Videos

There is currently an issue with viewing videos from the 3rd edition of Atlas of Osteopathic Techniques.

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Posted in Service Disruptions