tbuckley/cabot-search huggingface dataset:
Factors affecting adherence with treatment advice in a clinical trial of patients with severe asthma
Authors: John Busby, John G. Matthews, Rekha Chaudhuri, Ian D. Pavord, Timothy C. Hardman, Joseph R. Arron, Peter Bradding, Christopher E. Brightling, David F. Choy, Douglas C. Cowan, Ratko Djukanovic, Catherine E. Hanratty, Tim W. Harrison, Cecile T. Holweg, Peter H. Howarth, Stephen J. Fowler, James L. Lordan, Adel H. Mansur, Andrew Menzies-Gow, Robert M. Niven, Douglas S. Robinson, Samantha M. Walker, Ashley Woodcock, Liam G. Heaney
Journal: European Respiratory Journal (2021)

Background Understanding why patients with severe asthma do not follow healthcare provider (HCP) advice to adjust treatment is critical to achieving personalised disease management. Methods We reviewed patient choice to follow HCP advice to adjust asthma treatment in a UK-based randomised, controlled, single-blind (study participant), multicentre, parallel group 48-week clinical study comparing biomarker-directed treatment adjustment with standard care in severe asthma. Results Of 1572 treatment advisories (291 participants), instructions were followed in 1377 cases (87.6%). Patients were more likely to follow advice to remain on treatment (96.7%) than to either reduce (70.3%) or increase (67.1%) their treatment, with 64% of patients following all treatment advice. Multivariate analysis associated belonging to an ethnic minority group (OR 3.10, 95% CI 1.68–5.73) and prior study medication changes (two or more changes: OR 2.77, 95% CI 1.51–5.10) with failure to follow treatment advice. In contrast, emergency room attendance in the prior year (OR 0.54, 95% CI 0.32–0.92) was associated with following treatment advice. The largest effect was seen with transition onto or off oral corticosteroids (OR 29.28, 95% CI 16.07–53.36) when compared with those requested to maintain treatment. Centre was also an important determinant regarding the likelihood of patients to follow treatment advice. Conclusions Belonging to an ethnic minority group and multiple prior treatment adjustments were associated with not following HCP treatment advice. Patients also responded differently to HCP advice across UK specialist centres. These findings have implications for the generalisability of models of care in severe asthma and require further focused studies.
KS01.3.A Tumoral MHC class II expression in gliomas drives T cell exhaustion
Authors: Y Chih, K Sahm, A Sadik, T Bunse, N Trautwein, S Pusch, S Stevanovic, C Opitz, A Deimling, W Wick, F Sahm, L Bunse, M Platten
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Neoepitopes are presented on major histocompatibility class II (MHCII) molecules. In glioma, for instance, the recurrent driver mutation IDH1R132H was shown to bear an MHCII-restricted epitope in preclinical and clinical vaccine studies. The general relevance of MHCII expression in glioma for antitumor immunity, however, remains unknown. Here we evaluate stromal and tumoral MHCII expression, functionality, and its association with survival in gliomas. MATERIAL AND METHODS Immunostaining of human glioma tissues was used to identify tumoral, endothelial, and microglial MHCII expression and to enumerate T cell infiltrates. To gain insights into tumoral MHCII expression, bulk transcriptomic data from TCGA and single-cell transcriptomic data from publicly available datasets were analyzed. MHC ligandome analyses of an MHCII+ glioma cell line and human glioma tissues were used to determine the functionality of MHCII in vitro and ex vivo. Functional in vitro co-culture assays with an HLA-DR-matched tetanus toxoid (TT) epitope-overexpressing glioma cell line and in vitro-expanded TT-reactive T cells from healthy donors were used to examine direct target recognition by T helper cells. CRISPR-Cas9-mediated knockout of MHCII in preclinical hypermutant glioblastoma cell line GL261 was employed to further validate the consequences of tumoral MHCII expression and to probe potential clinical intervention with existing therapies. RESULTS MHCII is expressed in the majority of gliomas and associated with increased infiltration of T cells. In 10% of the analyzed glioma tissues and a subset of single cells, tumoral MHCII expression is detected. Clinical and transcriptomic data reveal that tumoral MHCII is associated with poor prognosis, cytokine responses, immune inhibition and T cell differentiation. Ligandome analyses evidence presentation of peptides by MHCII molecules on glioma cells. In in vitro assays, TT-reactive T helper cells specifically produce IFNg when co-cultured with MHCII+ glioma cells upon the presence of co-stimulation. In agreement with the clinical data, preclinical murine models demonstrate that tumoral MHCII expression leads to reduced survival. Co-culture assay shows that tumoral MHCII results in upregulation of PD-1 on T helper cells antigen-specifically. Concordantly, immune checkpoint blockade (ICB) therapy slows the disease progression of mice carrying MHCII+ tumors. CONCLUSION MHCII is expressed in gliomas by a subset of tumor cells. Although tumoral MHCII is functional, it is associated with poor survival in both clinical data and preclinical models. T cell exhaustion induced by tumoral MHCII expression can, in part, be overcome by ICB in vivo. Further experiments are required to decipher tumor cell intrinsic and microenvironmental consequences of tumoral MHCII expression.
Secondary prevention of coronary heart disease in a sample of primary care practices in eastern England: evidence of unmet need
Authors: Sarah H Wild, Christine A Macleod
Journal: Circulation (2001)

P44 Objective: To investigate prevalence of risk factors and use of secondary prevention strategies for recurrent coronary heart disease (CHD) in primary care. Design: Cross-sectional study of a 50% sample of medical records. Subjects: Patients aged 35-75 years with a record of coronary heart disease from 13 primary care practices in eastern England. Main outcome measures: Recorded prevalence of smoking, body mass index and use of aspirin, beta-blockers and statins. Results: Records were reviewed for 1205 patients with CHD of whom 76% were over 60 years of age and 34% were women. Crude age-specific prevalence of CHD was 4.1%. CHD was categorised as angina (52% of subjects), past myocardial infarction (33% of subjects) and history of coronary revascularisation (15% of subjects). Prevalence of smoking and obesity (body mass index &gt;30kg/m 2 ) was based on available data for 1080 and 973 subjects and was 23% and 31% respectively. Seventy percent of all subjects were recorded as receiving aspirin, 40% were being prescribed beta-blockers and 37% were being prescribed statins. These proportions varied by age, sex and category of CHD. Conclusion: Despite evidence of effectiveness most strategies for reducing risk of recurrent coronary heart disease are still not widely used in primary care. Possible explanations include absence of systematic care for CHD patients, limited availability of behavioral interventions and concerns over the cost of treatment. National guidelines for secondary prevention of CHD in primary care are being developed.
Association of Occupational Exposure to Inhaled Agents in Operating Rooms With Incidence of Chronic Obstructive Pulmonary Disease Among US Female Nurses
Authors: Wubin Xie, Orianne Dumas, Raphaëlle Varraso, Krislyn M. Boggs, Carlos A. Camargo, Andrew C. Stokes
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Employment in operating rooms (ORs) may involve exposure to several inhaled agents, including surgical smoke and disinfectants, which are associated with adverse respiratory health effects. However, the association of long-term employment in ORs and chronic obstructive pulmonary disease (COPD) remains unknown. <h3>Objective</h3> To examine the association of working in an OR with incidence of COPD among female nurses in the US. <h3>Design, Setting, and Participants</h3> This cohort study used data from the Nurses’ Health Study for US female registered nurses who provided information on questionnaires regarding OR employment history in 1984 and job type in 1982 and who had no history of COPD in 1984 (baseline). Data analyses were conducted from April 1, 2020, to January 31, 2021. <h3>Exposures</h3> Duration of nursing in the OR and job type. <h3>Main Outcomes and Measures</h3> The associations of any employment as an OR nurse, duration of employment, and duration and job type with incidence of self-reported, physician-diagnosed COPD. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards regression models stratified by age and calendar year. Models were adjusted for covariates, with model 1 adjusting for age, model 2 also adjusting for cigarette smoking status and pack-year of smoking, and model 3 also adjusting for race and ethnicity, US Census region, and body mass index. <h3>Results</h3> Among 75 011 female nurses included in the analyses, the mean (SD) age at baseline was 50.5 (7.2) years; 29% had a history of employment in an OR, and 3% had 15 or more years of OR experience. In model 3, employment in an OR for 15 or more years was associated with a 46% increased risk of developing COPD compared with no history of OR employment (HR, 1.46; 95% CI, 1.10-1.93). Compared with nurses who never worked in an OR and had an administrative or nursing education function or a nonnursing job in 1982, the risk of developing COPD was greater among nurses who provided outpatient care (HR, 1.24; 95% CI, 1.04-1.47) and nurses employed in inpatient units (HR, 1.31; 95% CI, 1.07-1.59) who had no history of OR employment and was 69% greater among nurses with OR experience of 15 years or more (HR, 1.69; 95% CI, 1.25-2.28). <h3>Conclusions and Relevance</h3> In this cohort study, OR employment of 15 years or more was associated with an increased risk of developing COPD among female nurses. Additional studies with more recent and direct environmental monitoring data of multiple occupational exposures are needed to assess the relative role of exposure to surgical smoke and disinfectants in the observed association.
Limited access to antigen drives generation of early B cell memory while restraining the plasmablast response
Authors: Vassilis Glaros, René Rauschmeier, Artem V. Artemov, Annika Reinhardt, Sebastian Ols, Aikaterini Emmanouilidi, Charlotte Gustafsson, Yuanyuan You, Claudio Mirabello, Åsa K. Björklund, Laurent Perez, Neil P. King, Robert Månsson, Davide Angeletti, Karin Loré, Igor Adameyko, Meinrad Busslinger, Taras Kreslavsky
Journal: Immunity (2021)

Cell fate decisions during early B cell activation determine the outcome of responses to pathogens and vaccines. We examined the early B cell response to T-dependent antigen in mice by single-cell RNA sequencing. Early after immunization, a homogeneous population of activated precursors (APs) gave rise to a transient wave of plasmablasts (PBs), followed a day later by the emergence of germinal center B cells (GCBCs). Most APs rapidly exited the cell cycle, giving rise to non-GC-derived early memory B cells (eMBCs) that retained an AP-like transcriptional profile. Rapid decline of antigen availability controlled these events; provision of excess antigen precluded cell cycle exit and induced a new wave of PBs. Fate mapping revealed a prominent contribution of eMBCs to the MBC pool. Quiescent cells with an MBC phenotype dominated the early response to immunization in primates. A reservoir of APs/eMBCs may enable rapid readjustment of the immune response when failure to contain a threat is manifested by increased antigen availability.
Impact of the covid-19 pandemic on healthrelated quality of life and anxiety in pediatric hematology/oncology patients: A single egyptian center experience
Authors: E. Hassan, D. N. Rizk, N. Aly, Y. E. Chazli
Journal: HemaSphere (2021)

Background: Since the World Health Organization declared coronavirus disease 2019 (COVID-19) pandemic, the strain on healthcare services affected patients suffering from various comorbidities and added to the psychological burden. Aims: To assess anxiety level and it's impact on the health-related quality of life (HRQoL) of pediatric Hematology/Oncology patients during the COVID-19 pandemic. Methods: A cross-sectional study on convenience sample of 292 children with chronic hematological/oncological disorders attending Alexandria University Children's Hospital with their parents/guardians available were included. Patients' recruitment was done from May to June 2020 during the peak of the pandemic in Egypt. A Three groups were included: Patients with bleeding/coagulation disorders, transfusion-dependent patients, and patients receiving chemotherapy. HRQoL was assessed using a validated Arabic version of Parent proxy-report of Pediatric Quality of Life Inventory TM (PedsQLTM 4.0 Generic Core Scales). Anxiety was assessed using the Arabic version of the Spence Children's Anxiety Scale (SCAS). The preschool (PAS) and parent versions of the scale (SCAS-P) were completed by the caregivers. The preschool anxiety scale was used to measure anxiety in children aged 2.5-6.9 years. Results: The mean age was 8.72 ± 3.66 years, 52.4% were males and 65.4% were transfusion-dependent patients. Almost 60% of children were aware of the pandemic and 60.3% had blood transfusion difficulties. Males had lower anxiety levels than females (p < 0.001), and transfusion-dependent patients had lower anxiety levels than patients receiving chemotherapy (p < 0.001). Children who were aware of the COVID-19 pandemic had lower anxiety levels than those who were not (p = 0.006), while those suffering from fewer clinic days had higher anxiety levels (p = 0.02). Anxiety significantly reduced the three HRQoL domains (p < 0.001). Summary/Conclusion: The present study demonstrated the degree of anxiety and HRQoL affection during the COVID-19 pandemic in children with chronic hematological/oncological diseases and malignancies. The anxiety score was highest in patients receiving chemotherapy, while the HRQoL was lowest in patients with bleeding/coagulation disorders. These findings help a better understanding of the psychological impact of the pandemic on the studied group as a crucial step in guiding policies and interventions to maintain their psychological wellbeing.
Care of the Patient With Abnormal Liver Test Results
Authors: Ashley N. Tran, Joseph K. Lim
Journal: Annals of Internal Medicine (2021)

Liver tests are commonly performed in primary care and may signal the presence of acute or chronic liver disease. Abnormal results are defined by standardized rather than individual laboratory thresholds and must be interpreted in the context of a patient's history and examination. The pattern and severity of liver injury may provide clues about the cause of disease and should guide diagnostic evaluation with serologic testing and liver imaging. A systematic, stepwise approach to the evaluation and management of abnormal liver test results is recommended to optimize high-value care.
High Congenital Syphilis Case Counts among U.S. Infants Born in 2020
Authors: Virginia B. Bowen, Robert McDonald, Jeremy A. Grey, Anne Kimball, Elizabeth A. Torrone
Journal: New England Journal of Medicine (2021)

Congenital Syphilis in U.S. Infants Born in 2020 As of July 29, 2021, a total of 2022 cases of congenital syphilis were reported to the Centers for Disease Control and Prevention, already surpassin...
Inflation-Adjusted Trends in Medicare Reimbursement for Common Dermatologic Procedures, 2007-2021
Authors: Rishabh S. Mazmudar, Anjani Sheth, Raghav Tripathi, Jeremy S. Bordeaux, Jeffrey F. Scott
Journal: JAMA Dermatology (2021)

Medicare enrollment, dermatologist utilization of Medicare, and dermatologic procedural volume have all increased over time. Despite this, there are limited studies evaluating changes in Medicare reimbursement within dermatology.To identify trends in Medicare reimbursement for 46 common dermatologic procedures from 2007 to 2021.In this cross-sectional study, reimbursement data were obtained from the Centers for Medicare & Medicaid Services Physician Fee Schedule for commonly used dermatologic Current Procedural Terminology (CPT) codes from 2007 to 2021. The CPT codes in several major dermatologic categories were analyzed, including skin biopsy, shave removal, benign/premalignant/malignant destruction, benign/malignant excision, Mohs micrographic surgery, simple/intermediate/complex repair, flap, graft, and laser/phototherapy. All procedure prices were adjusted for inflation to January 2021 dollar value.The primary outcomes were percentage changes and cumulative annual growth rates of pricing for each dermatologic procedure.From 2007 to 2021, there was a mean decrease in dermatologic procedure reimbursement of -4.8% after adjusting for inflation. Mean inflation-adjusted changes in reimbursements during this time period significantly varied by procedure type, including skin biopsy (+30.3%), shave removal (+24.5%), benign/premalignant/malignant destruction (-7.5%), Mohs micrographic surgery (-14.4%), benign/malignant excision (-3.9%), simple/intermediate/complex repair (-9.9%), flap repair (-14.1%), graft repair (-12.0%), and laser/phototherapy (-6.6%; P < .001). Changes in reimbursement did not vary by anatomical risk categories.The findings of this cross-sectional analysis suggest that changes in Medicare reimbursement can have several downstream effects, including concomitant private insurance changes and decreased patient access. Future adjustments in reimbursement should balance high-value care with sustainable pricing to optimize patient access.
Correlation Between National Institutes of Health Funding for Pediatric Research and Pediatric Disease Burden in the US
Authors: Chris A. Rees, Michael C. Monuteaux, Vendela Herdell, Eric W. Fleegler, Florence T. Bourgeois
Journal: JAMA Pediatrics (2021)

The US National Institutes of Health (NIH) is the largest government funding source for biomedical research globally. Burden of disease is one of the factors considered by the NIH in making funding allocations, though it is not known how funding patterns are associated with disease burden for pediatric conditions.To determine the correlation between NIH funding and disease burden across pediatric conditions.This cross-sectional study evaluates NIH grants funding pediatric research from 2015 to 2018 in the US. Pediatric grants were classified according to disease categories studied. Disease burden for each category was determined using measures from the Institute of Health Metrics and Evaluation and hospitalization data from the 2016 Kids' Inpatient Database.Correlation between NIH funding and pediatric disease burden using Spearman rank order coefficients and predicted amounts of disease-specific funding based on disease burden estimated from linear regression models.This study analyzed 14 060 disease-specific pediatric grants awarded by the NIH from 2015 to 2018 in the US. Annual funding for disease categories ranged from $0 to $382 849 631. Funding for pediatric research was correlated with pediatric disability-adjusted life-years (DALYs), deaths, years lived with disability, and years of life lost (r, 0.56-0.63; P < 0.001 for all measures). There was also a correlation between funding and hospital-based metrics, including hospital days, number of hospital admissions, and hospital charges (r, 0.67-0.69; P < .001 for all measures). Eight disease categories received greater than $500 million more than predicted levels relative to DALYs, while 5 disease categories were funded more than $50 million less than predicted levels. Based on predicted levels of funding, congenital birth defects; endocrine, metabolic, blood, and immune disorders; and HIV/AIDS were the most overfunded categories relative to DALYs and hospital days. Conditions identified as most underfunded differed depending on use of DALYs or hospital days in estimating predicted funding levels.NIH funding for pediatric research was correlated with pediatric disease burden in the US with variable correlation based on the disease metric applied. There was substantial overfunding and underfunding of certain conditions. Ongoing evaluation of pediatric funding patterns using a complementary set of disease measures may help inform and prioritize pediatric research funding.
Effect of radiotherapy on survival in patients with resected non-pancreatic periampullary malignancies: Analysis using the surveillance, epidemiology, and end results (SEER) registry data
Authors: Hsiang-Hsuan Yu, Ya-Yu Tsai, Richard Schulick, Joseph Herman
Journal: Cancer Research (2007)

5060  Purpose:  Patients with resected non-pancreatic periampullary malignancies often undergo adjuvant radiotherapy, but evidence from prospective studies is lacking. We evaluated the effect of radiotherapy on survival in patients with non-metastatic non-pancreatic periampullary cancers who underwent cancer directed surgery using the Surveillance, Epidemiology, and End Results (SEER) registry.  Methods:   A total of 1564 patients with resected carcinoma of the ampulla (C24.0), extrahepatic bile duct (C24.1), and duodenum (C17.0) were identified from the SEER registry between1988 and 2003. Periampullary lymphoma, sarcoma, carcinoid, and endocrinoma were excluded. Overall survival (OS) and cancer-specific survival (CSS) were analyzed by the Kaplan-Meier method. Multivariate analysis was performed with Cox regression.  Results:   Radiotherapy was administered in 412 (26%) of these patients; 94% in the adjuvant setting. The proportions of patients who received radiotherapy were as follows: 181/789 (22.9%) for ampullary primary, 157/422 (37.2%) for extrahepatic bile duct cancer, and 73/353 (21.0%) for cancer of the duodenum. Patients who received radiotherapy were more likely to have higher stage disease, nodal involvement, poorly differentiated grade, but had a younger age at diagnosis. For all patients, survival analysis demonstrated that radiotherapy did not improve OS when compared to no radiotherapy (2-year and 5-year OS: 51% vs. 59% and 28% vs. 38%, respectively, p=0.062) and adversely affected CSS (2-year and 5-year CSS: 63% vs. 73% and 42% vs. 56%, respectively, p= 0.0003).  Multivariate analysis showed that radiotherapy did not affect OS (HR=0.96, 95% CI = 0.82-1.13) or CSS (HR=1.02, 95% CI = 0.84-1.25). Higher T stage, nodal involvement, and age greater than 60 were associated with poorer OS and CSS. In addition to these factors, poorly differentiated grade was also significantly associated with decreased CSS. Multivariate analysis by primary sites showed that radiotherapy improved OS but not CSS in patients with ampullary cancer; radiotherapy had no significant effect on OS or CSS in patients with cancers of the extrahepatic bile duct or duodenum.  Conclusion:   Radiotherapy is not associated with improved OS or CSS in patients with resected non-pancreatic periampullary malignancies in this population-based registry. Patients with adverse clinicopathological characteristics and younger age at diagnosis were more likely to receive adjuvant radiotherapy.
Low-pressure endoscopy using the gel immersion method facilitates endoscopic variceal ligation of ruptured esophageal varices
Authors: Hiromi Sekiguchi, Tomonori Yano, Shinnosuke Tokoro, Mizuho Iida, Shigeo Tano, Alan Kawarai Lefor, Hironori Yamamoto
Journal: Endoscopy (2021)

Although endoscopic variceal ligation (EVL) is a standard procedure in the management of acute variceal bleeding [1], it is often difficult to secure the visual field because the lumen is filled with fresh blood and the injected water rapidly mixes with blood. For previously treated varices, it may also be difficult to adequately aspirate fibrotic varices into the banding cap.