tbuckley/cabot-search huggingface dataset:
International study of video review of concussion in professional sports
Authors: Gavin A Davis, Michael Makdissi, Paul Bloomfield, Patrick Clifton, Ruben J Echemendia, Éanna Cian Falvey, Gordon Ward Fuller, Gary Green, Peter Rex Harcourt, Thomas Hill, Nathan McGuirk, Willem Meeuwisse, John W Orchard, Martin Raftery, Allen K Sills, Gary S Solomon, Alex Valadka, Paul McCrory
Journal: British Journal of Sports Medicine (2018)

Video review has become an important tool in professional sporting codes to help sideline identification and management of players with a potential concussion.To assess current practices related to video review of concussion in professional sports internationally, and compare protocols and diagnostic criteria used to identify and manage potential concussions.Current concussion management guidelines from professional national and international sporting codes were reviewed. Specific criteria and definitions of video signs associated with concussion were compared between codes. Rules and regulations adopted across the codes for processes around video review were also assessed.Six sports with specific diagnostic criteria and definitions for signs of concussion identified on video review participated in this study (Australian football, American football, world rugby, cricket, rugby league and ice hockey). Video signs common to all sports include lying motionless/loss of responsiveness and motor incoordination. The video signs considered by the majority of sports as most predictive of a diagnosis of concussion include motor incoordination, impact seizure, tonic posturing and lying motionless. Regulatory requirements, sideline availability of video, medical expertise of video reviewers and use of spotters differ across sports and geographical boundaries. By and large, these differences reflect a pragmatic approach from each sport, with limited underlying research and development of the video review process in some instances.The use of video analysis in assisting medical staff with the diagnosis or identification of potential concussion is well established across different sports internationally. The diagnostic criteria used and the expertise of the video review personnel are not clearly established, and research efforts would benefit from a collaborative harmonisation across sporting codes.
CQC inspections have “little measurable impact” on services, analysis finds
Authors: Nigel Hawkes
Journal: BMJ (2018)

The inspection regime introduced by the Care Quality Commission (CQC) in 2013 has had little measurable impact on services such as emergency care, maternity care, and GP prescribing, a government funded report has said.1

Although care providers generally say that the regulator’s regime of intensive inspection has been beneficial, a team from the King’s Fund and Manchester University found that supporting evidence is elusive.

The report concludes that a “resource-intensive and very high-profile system of inspection and rating does not seem to have had more than quite small and mixed effects on available performance indicators.”

Commissioned by the Department of Health and Social Care’s Policy Research Programme, the report also finds little evidence that patients used CQC ratings to choose where to go for care or that “intelligent monitoring,” used by the regulator to target inspections towards particular organisations, showed any correlation with what inspectors found when they got there.

The CQC’s renewed approach in 2013 promised more intensive inspections, prioritised more accurately by risk based analysis using …
Multi-Imaging Method to Assay the Contractile Mechanical Output of Micropatterned Human iPSC-Derived Cardiac Myocytes
Authors: Alexandre J.S. Ribeiro, Olivier Schwab, Mohammad A. Mandegar, Yen-Sin Ang, Bruce R. Conklin, Deepak Srivastava, Beth L. Pruitt
Journal: Circulation Research (2017)

Rationale: During each beat, cardiac myocytes (CMs) generate the mechanical output necessary for heart function through contractile mechanisms that involve shortening of sarcomeres along myofibrils. Human-induced pluripotent stem cells (hiPSCs) can be differentiated into CMs (hiPSC-CMs) that model cardiac contractile mechanical output more robustly when micropatterned into physiological shapes. Quantifying the mechanical output of these cells enables us to assay cardiac activity in a dish. Objective: We sought to develop a computational platform that integrates analytic approaches to quantify the mechanical output of single micropatterned hiPSC-CMs from microscopy videos. Methods and Results: We micropatterned single hiPSC-CMs on deformable polyacrylamide substrates containing fluorescent microbeads. We acquired videos of single beating cells, of microbead displacement during contractions, and of fluorescently labeled myofibrils. These videos were independently analyzed to obtain parameters that capture the mechanical output of the imaged single cells. We also developed novel methods to quantify sarcomere length from videos of moving myofibrils and to analyze loss of synchronicity of beating in cells with contractile defects. We tested this computational platform by detecting variations in mechanical output induced by drugs and in cells expressing low levels of myosin-binding protein C. Conclusions: Our method can measure the cardiac function of single micropatterned hiPSC-CMs and determine contractile parameters that can be used to elucidate mechanisms that underlie variations in CM function. This platform will be amenable to future studies of the effects of mutations and drugs on cardiac function.
Using Best Practice Advisory alert to increase early advanced care planning discussion and palliative care referral in advanced cancer patients.
Authors: Chintan Pandya, Amy An, Paul Duberstein, David W. Dougherty, Marcus Smith Noel
Journal: Journal of Clinical Oncology (2018)

320 Background: Patients with advanced cancer can benefit from early initiation of palliative care (PC) and advanced care planning (ACP). In theory, the Medical Order for Life-Sustaining Treatments (MOLST), which provides a vehicle for end-of-life discussion, could lead to improved uptake of ACP and PC. In order for MOLST forms to influence these care process outcomes, methods are needed to help clinicians introduce the forms to patients in a compassionate manner. The objective of this study is to develop a best practice advisory (BPA) alert in the electronic medical record (EMR) to help oncologists identify appropriate patients for ACP and PC referral and evaluate its impact on improving MOLST form and palliative referral order documentation in EMR for these patients. Methods: BPA alert criteria included Lung and GI cancer patients with stage IV disease or undergoing treatment with palliative intent. The oncologists could act on the alert by either acknowledging it with action statement (I have already discussed ACP, I intend to discuss ACP in this or next visit, Patient unlikely to die in next 12 months, other) or dismiss it. We examined the rates of MOLST form and PC referral orders in the EMR 12-months before and after the BPA was implemented in 03/2018. Results: The BPA fired in 424 patients who met the criteria over a period of 9 weeks. It was acknowledged in 409 and cancelled in 15 patients. Following the alert, 40 (9%) patients had a MOLST form added to the chart compared to only 9 (2%) patients before the alert and 17 (4%) patients had palliative care referral order placed vs. 10 (2%) patients before the alert. Physicians acknowledged discussing ACP in 145 patients, most of whom (25/30) initiated these conversations after the BPA was implemented. Data collection is ongoing to capture BPA effect for longer follow-up. Conclusions: The BPA alert intervention resulted in significant increase in documentation of ACP and palliative referral order suggesting the potential of this tool in improving adherence to national guidelines calling for early initiation of palliative care and advance care planning in patients with advanced cancers.
A comprehensive analysis of 195 DNA methylomes reveals shared and cell-specific features of partially methylated domains
Authors: Abdulrahman Salhab, Karl Nordström, Gilles Gasparoni, Kathrin Kattler, Peter Ebert, Fidel Ramirez, Laura Arrigoni, Fabian Müller, Julia K. Polansky, Cristina Cadenas, Jan G.Hengstler, Thomas Lengauer, Thomas Manke, Jörn Walter
Journal: Genome biology (2018)

Partially methylated domains are extended regions in the genome exhibiting a reduced average DNA methylation level. They cover gene-poor and transcriptionally inactive regions and tend to be heterochromatic. We present a comprehensive comparative analysis of partially methylated domains in human and mouse cells, to identify structural and functional features associated with them. Partially methylated domains are present in up to 75% of the genome in human and mouse cells irrespective of their tissue or cell origin. Each cell type has a distinct set of partially methylated domains, and genes expressed in such domains show a strong cell type effect. The methylation level varies between cell types with a more pronounced effect in differentiating and replicating cells. The lowest level of methylation is observed in highly proliferating and immortal cancer cell lines. A decrease of DNA methylation within partially methylated domains tends to be linked to an increase in heterochromatic histone marks and a decrease of gene expression. Characteristic combinations of heterochromatic signatures in partially methylated domains are linked to domains of early and middle S-phase and late S-G2 phases of DNA replication. Partially methylated domains are prominent signatures of long-range epigenomic organization. Integrative analysis identifies them as important general, lineage- and cell type-specific topological features. Changes in partially methylated domains are hallmarks of cell differentiation, with decreased methylation levels and increased heterochromatic marks being linked to enhanced cell proliferation. In combination with broad histone marks, partially methylated domains demarcate distinct domains of late DNA replication.
Meningococcal Disease Surveillance in Men Who Have Sex with Men — United States, 2015–2016
Authors: Catherine H. Bozio, Amy Blain, Jessica MacNeil, Adam Retchless, Lauren M. Weil, Xin Wang, Laurel T. Jenkins, Lorraine D. Rodriguez-Rivera, Claire Jarashow, Van Ngo, Susan Hariri, Sarah A. Mbaeyi, Sara Oliver
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Meningococcal disease is a rare, but serious, bacterial infection that progresses rapidly and can be life-threatening, even with prompt antibiotic treatment. Men who have sex with men (MSM) have previously been reported to be at increased risk for meningococcal disease compared with other men, and recent outbreaks of serogroup C meningococcal disease among MSM have occurred (1). However, the epidemiology of meningococcal disease among MSM in the United States is not well described, in part, because information about MSM has not historically been collected as part of routine meningococcal disease surveillance. To better characterize and identify risk factors for meningococcal disease in general, supplementary data and isolates have been collected since 2015 through enhanced meningococcal disease surveillance activities. During 2015-2016, 271 cases of meningococcal disease in men aged ≥18 years were reported to the National Notifiable Diseases Surveillance System (NNDSS) in 45 states participating in this enhanced surveillance. Forty-eight (17.7%) cases were in men identified as MSM, including 17 (37.8%) with human immunodeficiency virus (HIV) infection. Among MSM, 39 (84.8%) cases were caused by Neisseria meningitidis serogroup C, whereas this serogroup was responsible for only 16.4% of cases among men who were not known to be MSM (non-MSM). Despite improvements in surveillance, MSM likely remain underascertained among men with meningococcal disease. Improved surveillance data are needed to understand the prevalence of and risk for meningococcal disease among MSM and inform policy and prevention strategies. Vaccination with quadrivalent meningococcal conjugate (MenACWY) vaccine is recommended for the control of meningococcal disease outbreaks caused by serogroups A, C, W, or Y, including during outbreaks among MSM; in addition, all persons aged ≥2 months with HIV infection should receive MenACWY vaccine because of the increased risk for meningococcal disease.
Abstract MP22: The Association of Dietary Intake Biomarkers with Rapid Kidney Function Decline: The CARDIA (Coronary Artery Risk Development in Young Adults) Study
Authors: Kristin Hirahatake, Andrew Odegaard, Myron Gross, Carmen Peralta, Kirsten Bibbins-Domingo, Michael Shlipak, Holly Mattix-Kramer, David Jacobs
Journal: Circulation (2016)

Introduction: Chronic kidney disease (CKD) is a major risk factor for cardiovascular disease. Evidence linking dietary intake to CKD is largely focused on management, rather than prevention of CKD. To provide evidence that addresses this gap we analyzed data from CARDIA using objective biomarkers of dietary intake (serum carotenoids and ascorbic acid marking fruit and vegetable intake, tocopherols marking nuts/seeds and oil intake) and serum cystatin C as a measure of kidney filtration. Hypothesis: Higher levels of serum carotenoids, tocopherols and plasma ascorbic acid are inversely associated with rapid kidney function decline. Methods: We analyzed data of subjects from the CARDIA study (N=2,210) with blood measures of dietary biomarkers at year 15 (2000-2001, black and white men and women aged 33-45y), concurrent clinical risk factor data, and measures of cystatin-C at years 15 and 20. GFRcys (ml/min/1.73m 2 ) was estimated from the CKD-EPI (CKD Epidemiology Collaboration) equation for calibrated cystatin C at years 15 and 20. Only subjects with GFRcys &gt; 60 ml/min/1.73m 2 at year 15 were analyzed. Rapid decline was defined as &gt;15% decline in GFRcys over 5 years (or &gt;3% decline per year). Multivariable logistic regression was used to estimate the Odds Ratio of incident rapid decline over 5 years by quartile of the dietary biomarkers and adjusted for demographic, lifestyle and clinical measures. Results: From year 15 to 20, 15.3% (339 of 2,210) of subjects experienced rapid kidney function decline. There was a strong inverse association after adjustment (P=0.016) between higher levels of the carotenoid index and incidence of rapid decline, but no association with any other measure. There was no evidence that the associations differed by diabetes or hypertension status. Conclusions: These results underscore how a nutrient rich, plant based dietary pattern in early middle-age inversely associates with subsequent rapid kidney function decline and provide insight for dietary recommendations related to CKD prevention.
Abstract P319: Association of Heart Rate Reserve with Incidence of Hypertension in Men
Authors: Vivek K Prasad, Gregory A Hand, Mei Sui, Duck C Lee, Deepika Shrestha, Jason Jaggers, Steven N Blair
Journal: Circulation (2013)

Abstract Objectives— We examined the association between heart rate reserve (HRR) and incident hypertension in men in the Aerobics Center Longitudinal Study. Research design and Methods— A total of 10418 healthy normotensive men, who did not have an abnormal electrocardiogram or a history of heart attack, stroke, cancer, or diabetes, performed a maximal treadmill exercise test and were followed for the incidence of hypertension. HRR was defined as the difference between maximal heart rate during exercise test and resting heart rate. Results— During a mean follow-up of 6 years, there were 2831 cases of incident hypertension. Compared with men in the reference category (the lowest quartile of HRR), the risk of incident hypertension was significantly lower in the highest quartile of HRR with a hazard ratio 0.67 (95% CI: 0.60-0.75) when adjusted for age and baseline examination year. Further adjustment for smoking, heavy drinking, body mass index (BMI), resting systolic and diastolic blood pressure, cholesterol, blood glucose and cardio respiratory fitness, resulted a hazard ratio of 0.84 (95% CI:0.74-0.95). This result was almost similar when we stratified them into younger and older men with hazard ratio of 0.77(95% CI: 0.62-0.98) and 0.78 (95% CI: 0.66-0.90) respectively. We also found a significant lower hypertension risk associated with higher HRR among high risk groups such as overweight, low fitness, or prehypertension with hazard ratio of 0.82(95% CI:0.70-0.97), 0.80(95% CI:0.67-0.96), 0.76(95% CI:0.64-0.88) respectively. Conclusion— Risk of Incident hypertension was significantly lower in men with higher HRR. High HRR was also associated with lower risk of developing hypertension irrespective of age and status of risk factors such as high BMI, low fitness and prehypertension. Therefore, HRR may be considered as a reliable exercise parameter for predicting the risk of incident hypertension.
Long-term quality-adjusted survival following therapeutic bronchoscopy for malignant central airway obstruction
Authors: Philip Ong, Horiana B Grosu, Labib Debiane, Roberto F Casal, George A Eapen, Carlos A Jimenez, Laila Noor, David E Ost
Journal: Thorax (2018)

Background While therapeutic bronchoscopy has been used to treat malignant central (CAO) airway obstruction for &gt;25 years, there are no studies quantifying the impact of therapeutic bronchoscopy on long-term quality-adjusted survival. Methods We conducted a prospective observational study of consecutive patients undergoing therapeutic bronchoscopy for CAO. Patients had follow-up at 1 week and monthly thereafter until death. Outcomes included technical success (ie, relief of anatomic obstruction), dyspnoea, health-related quality of life (HRQOL) and quality-adjusted survival. Results Therapeutic bronchoscopy was performed on 102 patients with malignant CAO. Partial or complete technical success was achieved in 90% of patients. At 7 days postbronchoscopy, dyspnoea improved (mean ∆Borg-day-7=−1.8, 95% CI −2.2 to −1.3, p&lt;0.0001) and HRQOL improved (median prebronchoscopy 0.618 utiles, 25%–75% IQR 0.569 to 0.699, mean ∆utility-day-7+0.047 utiles, 95% CI +0.023 to 0.071, p=0.0002). Improvements in dyspnoea and HRQOL were maintained long-term. Compared with the prebronchoscopy baseline, HRQOL per day of life postbronchoscopy improved (mean ∆utility-long-term+0.036 utiles, 95% CI +0.014 to 0.057, p=0.002). Median quality-adjusted survival was 109 quality-adjusted life-days (QALDs) (95% CI 74 to 201 QALDs). Factors associated with longer quality-adjusted survival included better functional status, treatment-naïve tumour, endobronchial disease, less dyspnoea, shorter time from diagnosis to bronchoscopy, absence of cardiac disease, bronchoscopic dilation and receiving chemotherapy. Conclusions Therapeutic bronchoscopy improves HRQOL as compared with baseline, resulting in approximately a 5.8% improvement in HRQOL per day of life. The risk-benefit profile in these carefully selected patients was very favourable. Trial registration number Results; NCT03326570 .
Identifying potentially preventable emergency department (PPED) visits among patients with cancer in Ontario.
Authors: Jane Yao, Bo Green, Monika K. Krzyzanowska
Journal: Journal of Clinical Oncology (2018)

25 Background: Cancer patients (pts) often visit the emergency department (ED) when symptoms and side effects occur. Growing evidence suggests that some treatment-related toxicities can be managed proactively in outpatient clinics, improving patient experience and optimizing acute care utilization. Understanding PPED visits is crucial to developing and evaluating such improvement efforts. Our objectives were to quantify the extent of PPED visits in Ontario among cancer pts and identify the best measure of PPED for province-wide quality improvement. Methods: By linking Activity Level Reporting to the Discharge Abstract Database and the National Ambulatory Care Reporting System, we identified cancer pts who had ED visits or hospitalizations up to 30 days after receiving chemotherapy and/or radiotherapy from April 1, 2014 to March 31, 2015 in Ontario. Episodes were stratified as ED Only or Indirect Admission (ED visit leading to hospitalization). We mapped the presenting Canadian Emergency Department Information System (CEDIS) complaints against the PPED metric proposed by Panattoni et al (JOP, 2018) that combined the CMS preventable visits typology with the STAR PRO tool (Basch et al, JCO, 2016) which found 49.8% were considered potentially preventable (PP). Results: We identified 43,593 ED visits (67% ED Only&amp; 33% Indirect Admissions) among 64,407 pts. The most common presenting CEDIS complaints were pain (20%), fever (13%) and shortness of breath (SoB, 7%) among chemotherapy pts, and pain (19%), SoB (11%) and general weakness (9%) among radiotherapy pts. By applying the CEDIS-based PPED definition, which includes 17 presenting complaints, 50% of ED Only and 68% of Indirect Admission visits were considered PPED. Conclusions: We were able to adapt the PPED algorithm for the Canadian context, which can aid cross-jurisdiction comparisons. We found a substantial proportion of PPED visits. While common presenting complaints had face validity for being PP and a similar proportion of visits were PP compared to the US-based definition, further validation of this approach against healthcare records and in other jurisdictions would be helpful as these metrics become increasingly used for quality improvement.
Dose escalation results from a first-in-human, phase 1 study of glucocorticoid-induced TNF receptor–related protein agonist AMG 228 in patients with advanced solid tumors
Authors: Ben Tran, Richard D. Carvajal, Aurelien Marabelle, Sandip Pravin Patel, Patricia M. LoRusso, Erik Rasmussen, Gloria Juan, Vijay V. Upreti, Courtney Beers, Gataree Ngarmchamnanrith, Patrick Schöffski
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> This open-label, first-in-human, phase 1 study evaluated the safety, pharmacokinetics, pharmacodynamics, and maximum tolerated dose (MTD) of AMG 228, an agonistic human IgG1 monoclonal antibody targeting glucocorticoid-induced tumor necrosis factor receptor−related protein (GITR), in patients with refractory advanced solid tumors. <h3>Methods</h3> AMG 228 was administered intravenously every 3&nbsp;weeks (Q3W). Dose escalation was in two stages: single-patient cohorts (3, 9, 30, and 90&nbsp;mg), followed by "rolling six" design (<i>n</i> = 2–6; 180, 360, 600, 900, and 1200&nbsp;mg). Primary endpoints included incidence of dose-limiting toxicities (DLTs), AEs, and pharmacokinetics. Additional endpoints were objective response and pharmacodynamic response. <h3>Results</h3> Thirty patients received AMG 228, which was well tolerated up to the maximum planned dose (1200&nbsp;mg). No DLTs occurred; the MTD was not reached. The most common treatment-related AEs were fatigue (13%), infusion-related reaction (7%), pyrexia (7%), decreased appetite (7%), and hypophosphatemia (7%). Two patients had binding anti−AMG 228 antibodies (one at baseline); no neutralizing antibodies were detected. AMG 228 exhibited target-mediated drug disposition, and serum exposure was approximately dose proportional at 180–1200&nbsp;mg and greater than dose proportional at 3–1200&nbsp;mg. Doses &gt; 360&nbsp;mg Q3W achieved serum trough coverage for 95% in vitro GITR occupancy. Despite GITR coverage in peripheral blood and tumor biopsies, there was no evidence of T-cell activation or anti-tumor activity. <h3>Conclusions</h3> In patients with advanced solid tumors, AMG 228 Q3W was tolerable up to the highest tested dose (1200&nbsp;mg), exhibited favorable pharmacokinetics, and provided target coverage indicating a pharmacokinetic profile appropriate for longer intervals. However, there was no evidence of T-cell activation or anti-tumor activity with AMG 228 monotherapy. <h3>Trial registration</h3> ClinicalTrials.gov, NCT02437916.