tbuckley/cabot-search huggingface dataset:
Drivers of Payment Variation in 90-Day Coronary Artery Bypass Grafting Episodes
Authors: Vinay Guduguntla, John D. Syrjamaki, Chad Ellimoottil, David C. Miller, Richard L. Prager, Edward C. Norton, Patricia Theurer, Donald S. Likosky, James M. Dupree
Journal: JAMA Surgery (2017)

Coronary artery bypass grafting (CABG) is scheduled to become a mandatory Medicare bundled payment program in January 2018. A contemporary understanding of 90-day CABG episode payments and their drivers is necessary to inform health policy, hospital strategy, and clinical quality improvement activities. Furthermore, insight into current CABG payments and their variation is important for understanding the potential effects of bundled payment models in cardiac care.To examine CABG payment variation and its drivers.This retrospective cohort study used Medicare and private payer claims to identify patients who underwent nonemergent CABG surgery from January 1, 2012, through October 31, 2015. Ninety-day price-standardized, risk-adjusted, total episode payments were calculated for each patient, and hospitals were divided into quartiles based on the mean total episode payments of their patients. Payments were then subdivided into 4 components (index hospitalization, professional, postacute care, and readmission payments) and compared across hospital quartiles. Seventy-six hospitals in Michigan representing a diverse set of geographies and practice environments were included.Ninety-day CABG episode payments.A total of 5910 patients undergoing nonemergent CABG surgery were identified at 33 of the 76 hospitals; of these, 4344 (73.5%) were men and mean (SD) age was 68.0 (9.3) years. At the patient level, risk-adjusted, 90-day total episode payments for CABG varied from $11 723 to $356 850. At the hospital level, the highest payment quartile of hospitals had a mean total episode payment of $54 399 compared with $45 487 for the lowest payment quartile (16.4% difference, P < .001). The highest payment quartile hospitals compared with the lowest payment quartile hospitals had 14.6% higher index hospitalization payments ($34 992 vs $30 531, P < .001), 33.9% higher professional payments ($8060 vs $6021, P < .001), 29.6% higher postacute care payments ($7663 vs $5912, P < .001), and 35.1% higher readmission payments ($3576 vs $2646, P = .06). The drivers of this variation are diagnosis related group distribution, increased inpatient evaluation and management services, higher utilization of inpatient rehabilitation, and patients with multiple readmissions.Wide variation exists in 90-day CABG episode payments for Medicare and private payer patients in Michigan. Hospitals and clinicians entering bundled payment programs for CABG should work to understand local sources of variation, with a focus on patients with multiple readmissions, inpatient evaluation and management services, and postdischarge outpatient rehabilitation care.
Effect of Oral Prednisolone on Symptom Duration and Severity in Nonasthmatic Adults With Acute Lower Respiratory Tract Infection
Authors: Alastair D. Hay, Paul Little, Anthony Harnden, Matthew Thompson, Kay Wang, Denise Kendrick, Elizabeth Orton, Sara T. Brookes, Grace J. Young, Margaret May, Sandra Hollinghurst, Fran E. Carroll, Harriet Downing, David Timmins, Natasher Lafond, Magdy El-Gohary, Michael Moore
Journal: JAMA (2017)

<h3>Importance</h3> Acute lower respiratory tract infection is common and often treated inappropriately in primary care with antibiotics. Corticosteroids are increasingly used but without sufficient evidence. <h3>Objective</h3> To assess the effects of oral corticosteroids for acute lower respiratory tract infection in adults without asthma. <h3>Design, Setting, and Participants</h3> Multicenter, placebo-controlled, randomized trial (July 2013 to final follow-up October 2014) conducted in 54 family practices in England among 401 adults with acute cough and at least 1 lower respiratory tract symptom not requiring immediate antibiotic treatment and with no history of chronic pulmonary disease or use of asthma medication in the past 5 years. <h3>Interventions</h3> Two 20-mg prednisolone tablets (n = 199) or matched placebo (n = 202) once daily for 5 days. <h3>Main Outcomes and Measures</h3> The primary outcomes were duration of moderately bad or worse cough (0 to 28 days; minimal clinically important difference, 3.79 days) and mean severity of symptoms on days 2 to 4 (scored from 0 [not affected] to 6 [as bad as it could be]; minimal clinically important difference, 1.66 units). Secondary outcomes were duration and severity of acute lower respiratory tract infection symptoms, duration of abnormal peak flow, antibiotic use, and adverse events. <h3>Results</h3> Among 401 randomized patients, 2 withdrew immediately after randomization, and 1 duplicate patient was identified. Among the 398 patients with baseline data (mean age, 47 [SD, 16.0] years; 63% women; 17% smokers; 77% phlegm; 70% shortness of breath; 47% wheezing; 46% chest pain; 42% abnormal peak flow), 334 (84%) provided cough duration and 369 (93%) symptom severity data. Median cough duration was 5 days (interquartile range [IQR], 3-8 days) in the prednisolone group and 5 days (IQR, 3-10 days) in the placebo group (adjusted hazard ratio, 1.11; 95% CI, 0.89-1.39;<i>P</i> = .36 at an α = .05). Mean symptom severity was 1.99 points in the prednisolone group and 2.16 points in the placebo group (adjusted difference, −0.20; 95% CI, −0.40 to 0.00;<i>P</i> = .05 at an α = .001). No significant treatment effects were observed for duration or severity of other acute lower respiratory tract infection symptoms, duration of abnormal peak flow, antibiotic use, or nonserious adverse events. There were no serious adverse events. <h3>Conclusions and Relevance</h3> Oral corticosteroids should not be used for acute lower respiratory tract infection symptoms in adults without asthma because they do not reduce symptom duration or severity. <h3>Trial Registration</h3> ISRCTN.com Identifier:ISRCTN57309858
Increased human intestinal barrier permeability plasma biomarkers zonulin and FABP2 correlated with plasma LPS and altered gut microbiome in anxiety or depression
Authors: Bruce R Stevens, Ruby Goel, Kim Seungbum, Elaine M Richards, Richard C Holbert, Carl J Pepine, Mohan K Raizada
Journal: Gut (2017)

We read with interest the recent work by Uhde et al ,1 which demonstrated that physically asymptomatic non-coeliac gluten/wheat sensitivity involves compromised intestinal epithelium barrier dysfunction in conjunction with systemic immune activation events. We also read with interest the recent work by Marchesi et al ,2 which comprehensively reviewed the role of microbiota in physical disorders of the gut and extra-gut organs.

But common to these Gut papers was the lack of accounting for anxiety and depression, comorbidities often experienced in gastroenterology clinics. Patients who are otherwise physically asymptomatic often do not explicitly divulge these mental disorders, or the disorders are unintentionally overlooked, yet they report ‘diminished quality of life’.

In response to this gap, we explored roles of dysbiosis and gut barrier integrity in individuals physically asymptomatic for gastrointestinal distress, yet nonetheless experiencing mental distress. We hypothesised that anxiety and depressive disorders are linked to human gut dysbiosis with microbiota that secrete lipopolysaccharide (LPS) endotoxin into plasma, which in conjunction with compromised gut barrier integrity has systemic manifestations including the brain. We further hypothesised that this correlates with altered intestinal epithelium paracellular integrity molecules discharged …
High-fidelity genome editing using NextGEN CRISPR (Clo51-dCas9) system for the production of allogeneic CAR-T cells.
Authors: Xinxin Wang, Xianghong Li, Burton Barnett, Christopher Martin, David Hermanson, Jenessa Smith, Srinivas Rengarajan, Yening Tan, Min Tong, Rebecca Codde, Eric M. Ostertag, Devon J. Shedlock
Journal: Journal of Clinical Oncology (2017)

3048 Background: Autologous chimeric antigen receptor (CAR) T therapies are highly efficient at targeting hematological malignancies, but the clinical applications have been limited by individualized manufacturing. Furthermore, there has been little success in treating solid tumors due to immunosuppressive microenvironments. Currently, genome editing technologies are being used to address both issues. However, the CRISPR/Cas9 system has significant safety concerns due to high incidence of off-target mutations and TALEN only works sufficiently in activated cells. A hybrid gene editing system, NextGEN (NG) Clo51-dCas9, can be targeted using gRNA, like CRISPR/Cas9, but exhibits little-to-no off-target cutting like TALEN, thereby overcoming limitations in the genome editing of resting T cells. Methods: We successfully developed a platform for production of allogeneic CAR-T cells with reduced receptivity to inhibitory signaling. Here, T cells were modified by piggyBac-mediated BCMA CAR gene delivery, along with NG reagents to knock out critical genes mediating rejection responses. Gene edited CAR-T cells were assessed by mixed lymphocyte reaction (MLR) and tumor killing. In addition, NG was used to knockout multiple checkpoint inhibitory receptors known to mediate key suppressive signals in T cells. Results: NG demonstrated high gene disruption efficiencies for all targets (84% for TCRα, 91% for TCRβ, 64% for β-2 microglobulin, and 40-60% for the surface inhibitory receptors PD-1, CTLA-4, Tim3, Lag-3, and TGFBRII). In contrast to CRISPR/Cas9, no off-target mutations were detected for multiple targets by deep-sequencing. In MLRs, disruption of TCR eliminated the GvHD response, while disruption of MHCI completely abrogated graft-rejection. Lastly, TCR/MHCI double knockout did not affect the ability to kill BCMA+ multiple myeloma cells in vitro. Conclusions: NG overcomes significant limitations of the CRISPR/Cas9 and TALEN systems with highly efficient genome editing in resting T cells. NG has great potential and flexibility for the manufacture of allogeneic CAR-T cells and for enhancing efficacy against solid tumors.
Pericyte-targeting prodrug overcomes tumor resistance to vascular disrupting agents
Authors: Minfeng Chen, Xueping Lei, Changzheng Shi, Maohua Huang, Xiaobo Li, Baojian Wu, Zhengqiu Li, Weili Han, Bin Du, Jianyang Hu, Qiulin Nie, Weiqian Mai, Nan Ma, Nanhui Xu, Xinyi Zhang, Chunlin Fan, Aihua Hong, Minghan Xia, Liangping Luo, Ande Ma, Hongsheng Li, Qiang Yu, Heru Chen, Dongmei Zhang, Wencai Ye
Journal: Journal of Clinical Investigation (2017)

Blood vessels in the tumor periphery have high pericyte coverage and are resistant to vascular disrupting agents (VDAs). VDA treatment resistance leads to a viable peripheral tumor rim that contributes to treatment failure and disease recurrence. Here, we provide evidence to support a hypothesis that shifting the target of VDAs from tumor vessel endothelial cells to pericytes disrupts tumor peripheral vessels and the viable rim, circumventing VDA treatment resistance. Through chemical engineering, we developed Z-GP-DAVLBH (from the tubulin-binding VDA desacetylvinblastine monohydrazide [DAVLBH]) as a prodrug that can be selectively activated by fibroblast activation protein α (FAPα) in tumor pericytes. Z-GP-DAVLBH selectively destroys the cytoskeleton of FAPα-expressing tumor pericytes, disrupting blood vessels both within the core and around the periphery of tumors. As a result, Z-GP-DAVLBH treatment eradicated the otherwise VDA-resistant tumor rim and led to complete regression of tumors in multiple lines of xenografts without producing the drug-related toxicity that is associated with similar doses of DAVLBH. This study demonstrates that targeting tumor pericytes with an FAPα-activated VDA prodrug represents a potential vascular disruption strategy in overcoming tumor resistance to VDA treatments.
Polarizing CD8+ Central Memory T Cells and Th1 Cells By Lenalidomide Contributes to the Antitumor Function of CD19 CAR-T Cells in Killing Diffused Large B Cell Lymphoma in Vitro
Authors: Zhen Jin, Han Liu, Molly Allen, Xiaoyang Li, Rufang Xiang, Dan Li, Yingxiao Wang, Junmin Li, Jiong Hu
Journal: Blood (2016)
Consolidative proton therapy after chemotherapy for patients with Hodgkin lymphoma
Authors: B.S. Hoppe, C.E. Hill-Kayser, Y.D. Tseng, S. Flampouri, H.M. Elmongy, O. Cahlon, N.P. Mendenhall, A. Maity, L.A. McGee, J.P. Plastaras
Journal: Annals of Oncology (2017)

We investigated early outcomes for patients receiving chemotherapy followed by consolidative proton therapy (PT) for the treatment of Hodgkin lymphoma (HL).From June 2008 through August 2015, 138 patients with HL enrolled on either IRB-approved outcomes tracking protocols or registry studies received consolidative PT. Patients were excluded due to relapsed or refractory disease. Involved-site radiotherapy field designs were used for all patients. Pediatric patients received a median dose of 21 Gy(RBE) [range 15-36 Gy(RBE)]; adult patients received a median dose of 30.6 Gy(RBE) [range, 20-45 Gy(RBE)]. Patients receiving PT were young (median age, 20 years; range 6-57). Overall, 42% were pediatric (≤18 years) and 93% were under the age of 40 years. Thirty-eight percent of patients were male and 62% female. Stage distribution included 73% with I/II and 27% with III/IV disease. Patients predominantly had mediastinal involvement (96%) and bulky disease (57%), whereas 37% had B symptoms. The median follow-up was 32 months (range, 5-92 months).The 3-year relapse-free survival rate was 92% for all patients; it was 96% for adults and 87% for pediatric patients (P = 0.18). When evaluated by positron emission tomography/computed tomography scan response at the end of chemotherapy, patients with a partial response had worse 3-year progression-free survival compared with other patients (78% versus 94%; P = 0.0034). No grade 3 radiation-related toxicities have occurred to date.Consolidative PT following standard chemotherapy in HL is primarily used in young patients with mediastinal and bulky disease. Early relapse-free survival rates are similar to those reported with photon radiation treatment, and no early grade 3 toxicities have been observed. Continued follow-up to assess late effects is critical.
Relapse-Free Survival as a Surrogate for Overall Survival in the Evaluation of Stage II–III Melanoma Adjuvant Therapy
Authors: Stefan Suciu, Alexander M M Eggermont, Paul Lorigan, John M Kirkwood, Svetomir N Markovic, Claus Garbe, David Cameron, Srividya Kotapati, Tai-Tsang Chen, Keith Wheatley, Natalie Ives, Gaetan de Schaetzen, Achmad Efendi, Marc Buyse
Journal: JNCI Journal of the National Cancer Institute (2017)

We assessed whether relapse-free survival (RFS; time until recurrence/death) is a valid surrogate for overall survival (OS) among resected stage II–III melanoma patients through a meta-analysis of randomized controlled trials. Individual patient data (IPD) on RFS and OS were collected from 5826 patients enrolled in 11 randomized adjuvant trials comparing interferon (IFN) to observation. In addition, IPD from two studies comparing IFN and vaccination in 989 patients were included. A two-level modeling approach was used for assessing Spearman's patient-level correlation (rho) of RFS and OS and the trial-level coefficient of determination (R²) of the treatment effects on RFS and on OS. The results were validated externally in 13 adjuvant studies without available IPD. We then tested the results on the European Organisation for Research and Treatment of Cancer (EORTC) 18071 double-blind trial comparing ipilimumab 10 mg/kg with placebo, which showed a statistically significant impact of the checkpoint inhibitor on RFS and OS. All statistical tests were two-sided. With a median follow-up of seven years, 12 of 13 trials showed a consistency between the IFN vs No IFN differences regarding RFS (hazard ratio [HR]RFS = 0.88) and OS (HROS = 0.91), but the small trial, Eastern Cooperative Oncology Group 2696, was an outlier (HRRFS = 0.72 vs HROS = 1.11). Therefore, even if rho was high, R² was low and could not reliably be estimated. Based on the 12 trials, rho remained high (0.89), and the hazard ratios for RFS and OS were strongly correlated (R² = 0.91). The surrogate threshold effect for RFS was estimated to be 0.77. For the EORTC 18071 trial, the hazard ratio for RFS was 0.75, predicting an effect of ipilimumab on OS. This was subsequently confirmed (HROS = 0.72, 95.1% confidence interval = 0.58 to 0.88, P = .001). In high-risk stage II–III melanoma, RFS appeared to be a valid surrogate end point for OS for adjuvant randomized studies assessing interferon or a checkpoint inhibitor. In future similar adjuvant studies, a hazard ratio for RFS of 0.77 or less would predict a treatment impact on OS.
Collaborative genome-wide association analysis of 10,596 individuals supports a role for Ankyrin-G (ANK3) and the alpha-1C subunit of the L-type voltage-gated calcium channel (CACNA1C) in bipolar disorder
Authors: Mod Ferreira, Yaji M Meng, Dmj A Ruderfer, Gprg L Fan J Kirov, Jwg E Smoller, JN D Stone, KH I Chambert, VM M L Nimgaonkar, Mec V Thase, Gsf S Sachs, KA J Gordon-Smith, Sbf K G Gabriel, BD C Blumenstiel, GG M Breen, Dwe M Morris, Wjm A Muir, RM K Williamson, Asc D J McLean, MP D VanBeck, RM A Kandaswamy, Dab A Collier, Ahl N J Young, Jna J Ferrier, AC A Farmer, EM D Scolnick, Mjc P Daly, Pab A P Holmans, Hmo D H Gurling, Shs M J Purcell, N P Craddock
Journal: Nature Genetics (2008)
Prolonged, Uninterrupted Sedentary Behavior and Glycemic Biomarkers Among US Hispanic/Latino Adults
Authors: Keith M. Diaz, Jeff Goldsmith, Heather Greenlee, Garrett Strizich, Qibin Qi, Yasmin Mossavar-Rahmani, Denise C. Vidot, Christina Buelna, Carrie E. Brintz, Tali Elfassy, Linda C. Gallo, Martha L. Daviglus, Daniela Sotres-Alvarez, Robert C. Kaplan
Journal: Circulation (2017)

Excessive sedentary time is ubiquitous in developed nations and is associated with deleterious health outcomes. Few studies have examined whether the manner in which sedentary time is accrued (in short or long bouts) carries any clinical relevance. The purpose of this study was to examine the association of prolonged, uninterrupted sedentary behavior with glycemic biomarkers in a cohort of US Hispanic/Latino adults.We studied 12 083 participants from the HCHS/SOL (Hispanic Community Health Study/Study of Latinos), a population-based study of Hispanic/Latino adults 18 to 74 years of age. Homeostatic model assessment of insulin resistance and glycosylated hemoglobin were measured from a fasting blood sample, and 2-hour glucose was measured after an oral glucose tolerance test. Sedentary time was objectively measured with a hip-mounted accelerometer. Prolonged, uninterrupted sedentariness was expressed as mean sedentary bout length.After adjustment for potential confounders and moderate to vigorous physical activity, longer sedentary bout duration was dose-dependently associated with increased homeostatic model assessment of insulin resistance (P for trend<0.001) and 2-hour glucose levels (P for trend=0.015). These associations were not independent of total sedentary time; however, a significant interaction between sedentary bout duration and total sedentary time was observed. Evaluation of the joint association of total sedentary time and sedentary bout duration showed that participants in the upper quartile for both sedentary characteristics (ie, high total sedentary time and high sedentary bout duration) had the highest levels of homeostatic model assessment of insulin resistance (P<0.001 versus low group for both sedentary characteristics) and 2-hour glucose (P=0.002 versus low group for both sedentary characteristics). High total sedentary time or high sedentary bout duration alone were not associated with differences in any glycemic biomarkers.Accruing sedentary time in prolonged, uninterrupted bouts may be deleteriously associated with biomarkers of glucose regulation.
Vitamin D in Boeck's Sarcoidosis
Authors: R. F. Robertson
Journal: BMJ (1948)

manufacturing area would present its own problems of organization, but in a congested area such as Birmingham a considerable proportion of the factory population could be included.The prevention of deafness is an important factor in the nation's health.An ear-treatment service based on the factory is a feasible method, causing the minimum interference with the productive capacity, of arranging treatment for a part of that section of the community of great importance to the economic wealth of the country. SummaryChronic ear diseases, in particular chronic suppurative otitis media, are potent causes of inefficiency, invalidism, or early death.Experience during the 1939-45 war showed that disease of the ear was a serious cause of wastage of man-power.The high incidence of this disease is largely due to inefficient treatment resulting from the absence of an ear-treatment service adapted to the economic needs of the population.Before and during the last war many industrial concerns set up medical departments to safeguard the health of the employees and to treat minor injuries sustained at work.This' report gives an account of otological work carried out in seven factory medical departments over a period of eighteen months, with the object of ascertaining (a) the incidence of suppurative otitis media in factory workers and (b) the results of treatment of ear disease in the factory medical department.To determine the incidence of ear disease in the factory population 1,902 employees, selected at random, were examined.Of these, 3.3% were found to be suffering from suppuration in the middle ear and 17.8% had active or healed middle-ear disease.A total of 1,711 patients complaining of ear, nose, or throat symptoms were examined at c'inics set up in the factory medical department: 389 were found to be suffering from disease of the pinna and external auditory meatus, and 274 from chronic