A 2-Question Summative Score Correlates with the Maslach Burnout Inventory

Introduction: There is a high prevalence of burnout among emergency medicine (EM) residents. The Maslach Burnout Inventory - Human Services Survey (MBI-HSS) is a widely used tool to measure burnout. The objective of this study was to compare the MBI-HSS and a two-question tool to determine burnout in the EM resident population.Methods: Based on data from the 2017 National Emergency Medicine Resident Wellness Survey study, we determined the correlation between two single-item questions with their respective MBI subscales and the full MBI-HSS. We then compared a 2-Question Summative Score to the full MBI-HSS with respect to primary, more restrictive, and more inclusive definitions of burnout previously reported in the literature.Results: Of 1,522 residents who completed the survey 37.0% reported “I feel burned out from my work,” and 47.1% reported “I have become more callous toward people since I took this job” once a week or more (each item >3 on a scale of 0-6). A 2-Question Summative Score totaling >3 correlated most closely with the primary definition of burnout (Spearman’s rho 0.65 [95% confidence interval 0.62-0.68]). Using the summative score, 77.7% of residents were identified as burned out, compared to 76.1% using the full MBI-HSS, with a sensitivity and specificity of 93.6% and 73.0%, respectively.Conclusion: An abbreviated 2-Question Summative Score correlates well with the full MBI-HSS tool in assessing EM resident physician burnout and could be considered a rapid screening tool to identify at-risk residents experiencing burnout

A novel methodology based on hidden semi-Markov model for equipment health assessment

As one of the most important aspects of PHM in many application domains, health monitoring and management could maximize the equipment effectiveness within the allowed health ranges. This paper proposes a novel approach to assess the equipment health based on hidden semi-Markov model (HSMM), which is an extension of HMM and does not follow the unrealistic Markov chain assumption to provide more powerful modeling and analysis capability for real problems. With training the standard health state HSMM model by normal state data, the test data is inputted into the trained model in order to calculate the corresponding relative divergence, which is the deviation extent from the standard health state model. Then we can obtain the health index model for the equipment health monitoring and measurement. Moreover, the proposed HSMM based method is applied to the draught fan and showed to be effective

An investigation of the pattern and mechanism of comorbidity in patients with Hashimoto’s thyroiditis

ObjectiveThis study aimed to investigate comorbidity patterns and potential pathogenic mechanisms in patients with Hashimoto’s thyroiditis (HT).MethodsPatients with HT who visited the outpatient clinic of the Thyroid Department at Dongzhimen Hospital, Beijing University of Chinese Medicine, between June 2021 and December 2024 were included. Association rule analysis and logistic regression analysis were performed using SPSS 25.0 and SPSS Modeler 18.0 to identify comorbidity patterns. Disease targets were screened using the GeneCards database, and protein interaction networks for intersecting targets were constructed using STRING and Cytoscape. GO function and KEGG pathway enrichment analyses were performed with Metascape to uncover relevant targets and potential pathways associated with comorbidities in patients with HT.ResultsAmong 429 patients with HT, 348 had comorbidities, resulting in a comorbidity prevalence of 81.19%. Association rule analysis identified thyroid nodules (TN) as the core binary comorbidity. The combination of TN and hyperplasia of the mammary gland (HMG) was central to ternary comorbidities, while the trio of TN, HMG, and uterine leiomyomas (UL) characterized quaternary comorbidities. Being a woman and advancing age were associated with increased risk of comorbidities, whereas levothyroxine sodium (L-T4) therapy was linked to reduced risk. Core targets associated with comorbidity prediction included AKT1, TP53, EGFR, INS, and TNF. Key pathways involved were the cancer pathway and PI3K–Akt signaling pathway.ConclusionThe high prevalence of comorbidities in patients with HT warrants increased clinical attention within the medical community

An E3 ubiquitin-proteasome gene signature for predicting prognosis in patients with pancreatic cancer

Pancreatic cancer is the seventh leading cause of cancer death worldwide, which is demonstrated with remarkable resistance to radiotherapy and chemotherapy. The identification of prognosis signature and novel prognostic markers will facilitate patient stratification and an individualized precision therapy strategy. In this study, TCGA-PAAD was used to screen prognostic E3 ubiquitin ligases and establish prognostic signatures, and GEO database was used to verify the accuracy of prognostic signatures. Functional analysis, in vitro experiments and clinical cohort studies were used to analyze the function and prognostic efficacy of the target gene. An E3 ligase-based signature of 9 genes and the nomogram were developed, and the signature was proved to accurately predict the prognosis of patients with pancreatic cancer. WDR37 might be the most prognostic E3 ubiquitin ligase in pancreatic cancer, and the clinical cohort analyses suggested a tumor‐suppressive role. The results of functional analysis and in vitro experiments indicated that WDR37 may promote the degradation of TCP1 complex to inhibit tumor and improve immune cell infiltration. The E3 ligase-based signature accurately predicted the prognosis of patients with pancreatic cancer, so it can be used as a decision-making tool to guide the treatment of patients with pancreatic cancer. At the same time, WDR37, the main gene in E3PMP signature, can be used as the most prognostic E3 ubiquitin ligase in the treatment of pancreatic cancer

Comparison of recurrence patterns between patients with thoracic esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy and postoperative adjuvant chemoradiotherapy

PurposeTo compare the recurrence patterns and survival outcomes between patients with esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemoradiotherapy (NCRT) and adjuvant chemoradiotherapy (ACRT).MethodsWe retrospectively analyzed 267 patients with locally advanced ESCC who received treatment at Sichuan Cancer Hospital and Institute (Chengdu, China) between January 2018 and December 2020. Based on different treatment protocols, the patients were divided into two groups: NCRT (n=181) and ACRT (n=86). After propensity score matching, each group included 74 patients. This study compared the recurrence types, sites, frequencies, and timing, as well as overall survival (OS), disease-free survival (DFS), and prognostic risk factors between the two groups.ResultsThe recurrence rates in the NCRT and ACRT groups were 59.5% (44/74) and 33.8% (25/74), respectively; the difference was statistically significant (P=0.002). Recurrences primarily occurred within 2 years following esophagectomy. The ACRT group had a higher 3-year OS rate than the NCRT group (67.8% versus [vs.] 50.6%, respectively; P=0.019). In the subgroup of patients with local recurrence, the 3-year OS rate was higher in the NCRT group compared to the ACRT group (53.8% vs. 0%, respectively; P=0.029). In terms of DFS, the ACRT group exhibited better results than the NCRT group (P<0.001). Multivariate analysis revealed that pathological N staging was an independent risk factor affecting the OS prognosis of patients in the NCRT group. Margin status and pathological T staging were identified as independent risk factors influencing OS in the ACRT group, while sex and treatment regimen were independent risk factors affecting DFS in patients with postoperative pathological lymph node positivity.ConclusionThere was significant difference in the OS and DFS prognosis of patients with ESCC treated with NCRT and ACRT. Recurrence primarily occurs within 2 years following esophagectomy. The recurrence rate was higher in the NCRT group compared to the ACRT group. Patients with early recurrence had a poorer survival prognosis compared to those with late recurrence. Pathological N staging was identified as an independent risk factor affecting OS in the NCRT group. Furthermore, margin status and pathological T staging were independent risk factors influencing OS in the ACRT group

Incorporation of a hinge domain improves the expansion of chimeric antigen receptor T cells

© 2017 The Author(s). Background: Multiple iterations of chimeric antigen receptors (CARs) have been developed, mainly focusing on intracellular signaling modules. However, the effect of non-signaling extracellular modules on the expansion and therapeutic efficacy of CARs remains largely undefined. Methods: We generated two versions of CAR vectors, with or without a hinge domain, targeting CD19, mesothelin, PSCA, MUC1, and HER2, respectively. Then, we systematically compared the effect of the hinge domains on the growth kinetics, cytokine production, and cytotoxicity of CAR T cells in vitro and in vivo. Results: During in vitro culture period, the percentages and absolute numbers of T cells expressing the CARs containing a hinge domain continuously increased, mainly through the promotion of CD4+ CAR T cell expansion, regardless of the single-chain variable fragment (scFv). In vitro migration assay showed that the hinges enhanced CAR T cells migratory capacity. The T cells expressing anti-CD19 CARs with or without a hinge had similar antitumor capacities in vivo, whereas the T cells expressing anti-mesothelin CARs containing a hinge domain showed enhanced antitumor activities. Conclusions: Hence, our results demonstrate that a hinge contributes to CAR T cell expansion and is capable of increasing the antitumor efficacy of some specific CAR T cells. Our results suggest potential novel strategies in CAR vector design.Link_to_subscribed_fulltex

Global burden of cardiovascular diseases and risk factors, 1990-2019 : Update from the GBD 2019 Study

Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability. This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019. GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019. Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019. The global trends for disability-adjusted life years (DALYs) and years of life lost also increased significantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period. The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019. The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019. Cardiovascular diseases remain the leading cause of disease burden in the world. CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high-income countries. There is an urgent need to focus on implementing existing cost-effective policies and interventions if the world is to meet the targets for Sustainable Development Goal 3 and achieve a 30% reduction in premature mortality due to noncommunicable diseases

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions