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Highlights • Refusal rate of nurses to influenza vaccine reduced during the pandemic. • A low acceptance level and high hesitancy level to COVID vaccination was observed. • A strong association between COVID-19 and influenza vaccine acceptance was found. • Major concern of nurses about the COVID-19 vaccine was its efficacy and safety., Background Maintaining health of healthcare workers with vaccination is a major component of pandemic preparedness and acceptance of vaccinations is essential to its success. This study aimed to examine impact of the coronavirus disease 2019 (COVID-19) pandemic on change of influenza vaccination acceptance and identify factors associated with acceptance of potential COVID-19 vaccination. Method A cross-sectional self-administered anonymous questionnaire survey was conducted among nurses in Hong Kong, China during 26 February and 31 March 2020. Their previous acceptance of influenza vaccination and intentions to accept influenza and COVID-19 vaccination were collected. Their relationship with work-related and other factors were examined using multiple multinomial logistic regressions. Results Responses from 806 participants were retrieved. More nurses changed from vaccination refusal to hesitancy or acceptance than those changed from acceptance to vaccination hesitancy or refusal (15.5% vs 6.8% among all participants, P

Background: The role of late gadolinium enhancement (LGE) in cardiac MRI (CMR) as prognostic marker in non-ischemic dilated cardiomyopathy (NIDCM) is evolving. Objective: To study the effect of LGE in the prognosis of NIDCM patients. Methods: 112 consecutive NIDCM patients, who underwent CMR, were prospectively followed up for 745 ± 320 days. Primary end point was occurrence of MACE {composite of all-cause mortality, resuscitated cardiac arrest, sustained ventricular tachycardia (VT)/appropriate ICD shock, heart failure (HF) hospitalization}. Results: LGE was present in 44 out of 112 patients (39%). The primary end point (MACE) was significantly higher in LGE + ve group compared to the LGE –ve group (72.7% vs. 29.4%; p 14% of LV predicted MACE with 90.6% sensitivity and 86% specificity. HR of LGE extent >14% of LV for MACE is 6.12; p 14% of LV volume were strongest predictor of MACE. Conclusion: LGE and its extent >14% predicts adverse cardiac events in NIDCM irrespective of LVEF and LGE location, pattern or distribution. This study emphasises the role of CMR in risk stratification of NIDCM patients and guiding therapy.

Background Ovarian cancer is the fifth leading cause of cancer mortality in UK women. Ovarian cancer survival varies by disease stage at diagnosis, but evidence is mixed on the effect of tumour histological type (histotype) and other factors. Methods 1.3 million UK women completed a detailed health questionnaire in 1996–2001 and were followed for incident cancers and deaths via linkage to national databases. Using Cox regression models, we estimated adjusted relative risks (RRs) of death from ovarian cancer, by stage at diagnosis, tumour histotype, and 16 other personal characteristics of the women. Results During 17.7 years’ average follow-up, 13,222 women were diagnosed with ovarian cancer, and 8697 of them died from the disease. Stage at diagnosis was a major determinant of survival (stage IV vs I, RR=10.54, 95% CI: 9.16–12.13). Histotype remained a significant predictor after adjustment for stage and other factors, but associations varied over the follow-up period. Histotype-specific survival was worse for high-grade than low-grade tumours. Survival appeared worse with older age at diagnosis (per 5 years: RR=1.19, 95% CI: 1.15–1.22), higher BMI (per 5-unit increase: RR=1.06, 95% CI: 1.02–1.11), and smoking (current vs never: RR=1.17, 95% CI: 1.07–1.27), but there was little association with 13 other pre-diagnostic reproductive, anthropometric, and lifestyle factors. Conclusion Stage at diagnosis is a strong predictor of ovarian cancer survival, but tumour histotype and grade remain predictors of survival even after adjustment for stage and other factors, contributing further evidence of biological dissimilarity between the ovarian cancer histotypes. Obesity and smoking represent potentially-modifiable determinants of survival, but the stronger association with stage suggests that improving earlier diagnosis would have a greater impact on increasing ovarian cancer survival., Highlights • This study investigated ovarian cancer survival in a cohort of 1.3 million UK women. • After 18 years of follow-up, the study included 13,222 incident ovarian cancers. • Stage, age and histotype were significantly associated with ovarian cancer survival. • Survival was also worse with higher BMI and smoking, but with less impact than stage.

Background Early mobilization on a tilt table with stepping versus standard care may be beneficial for patients with severe brain injury, but data from randomized clinical trials are lacking. This detailed statistical analysis plan describes the analyses of data collected in a randomized clinical feasibility trial for early mobilization by head-up tilt with stepping versus standard care after severe traumatic brain injury. Methods Primary feasibility outcomes are the proportion of included participants who were randomized out of all screened patients; the proportion of participants allocated to the experimental intervention who received at least 60% of the planned exercise sessions; and safety outcomes such as adverse events and reactions and serious adverse events and reactions. Exploratory clinical outcomes are suspected unexpected serious adverse reactions; and functional outcomes as assessed by the Coma Recovery Scale-Revised at four weeks; Early Functional Ability Scale and Functional Independence Measure at three months. The description includes the statistical analysis plan, including the use of multiple imputations and Trial Sequential Analysis.

Graphical abstract Flowchart of the method to explore the association between the type of WS and malaria infection among children under five years across sub-Saharan Africa., Current efforts for the prevention of malaria have resulted in notable reductions in the global malaria burden; however, they are not enough. Good hygiene is universally considered one of the most efficacious and straightforward measures to prevent disease transmission. This work analyzed whether improved drinking water and sanitation (WS) conditions were associated with a decreased risk of malaria infection. Data were acquired through surveys published between 2006 and 2018 from the Demographic and Health Program in sub-Saharan Africa (SSA). Multiple logistic regression was used for each national survey to identify the associations between WS conditions and malaria infection diagnosed by microscopy or a malaria rapid diagnostic test (RDT) among children (0–59 months), with adjustments for age, gender, indoor residual spraying (IRS), insecticide-treated net (ITN) use, house quality, and the mother’s highest educational level. Individual nationally representative survey odds ratios (ORs) were combined to obtain a summary OR using a random-effects meta-analysis. Among the 247,440 included children, 18.8% and 24.2% were positive for malaria infection based on microscopy and RDT results, respectively. Across all surveys, both unprotected water and no facility users were associated with increased malaria risks (unprotected water: aOR 1.17, 95% CI 1.07–1.27, P = 0.001; no facilities: aOR 1.35, 95% CI 1.24–1.47, P

Highlights • We examined virus interference in a Department of Defense dependent population. • Vaccinated personnel did not have significant odds of respiratory illnesses. • Vaccinated personnel were protected against influenza. • Odds of virus interference by vaccination varied for individual respiratory viruses., Purpose Receiving influenza vaccination may increase the risk of other respiratory viruses, a phenomenon known as virus interference. Test-negative study designs are often utilized to calculate influenza vaccine effectiveness. The virus interference phenomenon goes against the basic assumption of the test-negative vaccine effectiveness study that vaccination does not change the risk of infection with other respiratory illness, thus potentially biasing vaccine effectiveness results in the positive direction. This study aimed to investigate virus interference by comparing respiratory virus status among Department of Defense personnel based on their influenza vaccination status. Furthermore, individual respiratory viruses and their association with influenza vaccination were examined. Results We compared vaccination status of 2880 people with non-influenza respiratory viruses to 3240 people with pan-negative results. Comparing vaccinated to non-vaccinated patients, the adjusted odds ratio for non-flu viruses was 0.97 (95% confidence interval (CI): 0.86, 1.09; p = 0.60). Additionally, the vaccination status of 3349 cases of influenza were compared to three different control groups: all controls (N = 6120), non-influenza positive controls (N = 2880), and pan-negative controls (N = 3240). The adjusted ORs for the comparisons among the three control groups did not vary much (range: 0.46–0.51). Conclusions Receipt of influenza vaccination was not associated with virus interference among our population. Examining virus interference by specific respiratory viruses showed mixed results. Vaccine derived virus interference was significantly associated with coronavirus and human metapneumovirus; however, significant protection with vaccination was associated not only with most influenza viruses, but also parainfluenza, RSV, and non-influenza virus coinfections.

Highlights • More patients with chronic hepatitis B (CHB) are surviving into old age. • The late-life health-related quality of life (HRQoL) they might experience remains unclear. • We repeatedly assessed HRQoL in a cohort of older adults with CHB over five years. • The HRQoL changes older CHB patients might experience were delineated. • Extrahepatic organ/system abnormalities were associated with changes in HRQoL., Despite the increasing health burden of chronic hepatitis B (CHB) in aging populations, little is known about the course of health-related quality of life (HRQoL) changes. We aimed to assess individual-level longitudinal HRQoL changes in elderly patients with CHB and to examine their correlates. A prospective 5.1 years-cohort study was conducted in community-dwelling adults aged 55 years with hepatitis B surface antigen-positive. Participants underwent serial measurement of HRQoL using the short-form (12) health survey version 2. Of 503 participants, 82.7% remained in good physical health throughout the study period, whereas 9.1% had declining physical health and 8.2% were in poor physical health. We likewise identified three trajectories of mental health changes (“good mental health” [86.9%], “declining mental health” [6.8%], and “poor mental health” [6.4%]). Three baseline characteristics were independently associated with a lower likelihood of remaining physically or mentally healthy: sarcopenic obesity (odds ratio [OR] with 95% confidence interval [95% CI] of 7.5 [2.8–20.5] for poor physical health, 3.1 [1.1–8.4] for declining physical health, 4.3 [1.4–13.0] for poor mental health), a higher number of metabolic abnormalities (OR [95% CI] of 3.6 [1.6–8.0] for poor physical health) and depressed mood (OR [95% CI] of 21.7 [5.8–81.0] for poor physical health, 5.3 [1.4–19.9] for declining physical health, 83.1 [19.7–350.2] for poor mental health, 13.6 [2.9–64.8] for declining mental health). In conclusion, in a cohort of elderly patients with CHB, we demonstrated the heterogeneity and nonlinearity of HRQoL changes and their associations with variations in specific extrahepatic organs/systems.

The risk factors for severe COVID-19 beyond older age and certain underlying health conditions are largely unknown. Recent studies suggested that long-term environmental exposures may be important determinants of severe COVID-19. However, very few environmental factors have been studied, often separately, without considering the totality of the external environment (i.e., the external exposome). We conducted an external exposome-wide association study (ExWAS) using the nationwide county-level COVID-19 mortality data in the contiguous US. A total of 337 variables characterizing the external exposome from 8 data sources were integrated, harmonized, and spatiotemporally linked to each county. A two-phase procedure was used: (1) in Phase 1, a random 50:50 split divided the data into a discovery set and a replication set, and associations between COVID-19 mortality and individual factors were examined using mixed-effect negative binomial regression models, with multiple comparisons addressed, and (2) in Phase 2, a multivariable regression model including all variables that are significant from both the discovery and replication sets in Phase 1 was fitted. A total of 13 and 22 variables were significant in the discovery and replication sets in Phase 1, respectively. All the 4 variables that were significant in both sets in Phase 1 remained statistically significant in Phase 2, including two air toxicants (i.e., nitrogen dioxide or NO2, and benzidine), one vacant land measure, and one food environment measure. This is the first external exposome study of COVID-19 mortality. It confirmed some of the previously reported environmental factors associated with COVID-19 mortality, but also generated unexpected predictors that may warrant more focused evaluation., Graphical abstract Unlabelled Image, Highlights • The first external exposome study of COVID-19 mortality • Confirmed some previously reported associations • Generated unexpected predictors that may warrant more focused evaluation

Introduction A more structured role of radiographers is advisable to speed up the management of patients with suspected COVID-19. The purpose of our study was to evaluate the diagnostic performance of radiographers in the detection of COVID-19 pneumonia on chest CT using CO-RADS descriptors. Methods CT images of patients who underwent RT-PCR and chest CT due to COVID-19 suspicion between March and July 2020 were analysed retrospectively. Six readers, including two radiologists, two highly experienced radiographers and two less experienced radiographers, independently scored each CT using the CO-RADS lexicon. ROC curves were used to investigate diagnostic accuracy, and Fleiss’κ statistics to evaluate inter-rater agreement. Results 714 patients (419 men; 295 women; mean age: 64 years ±19SD) were evaluated. CO-RADS> 3 was identified as optimal diagnostic threshold. Highly experienced radiographers achieved an average sensitivity of 58.7% (95%CI: 52.5–64.7), an average specificity of 81.8% (95%CI: 77.9–85.2), and a mean AUC of 0.72 (95%CI: 0.68–0.75). Among less experienced radiographers, an average sensitivity of 56.3% (95%CI: 50.1–62.2) and an average specificity of 81.5% (95%CI: 77.6–84.9) were observed, with a mean AUC of 0.71 (95%CI: 0.68–0.74). Consultant radiologists achieved an average sensitivity of 60.0% (95%CI: 53.7–65.8), an average specificity of 81.7% (95%CI: 77.8–85.1), and a mean AUC of 0.73 (95%CI: 0.70–0.77). Conclusion Radiographers can adequately recognise the classic appearances of COVID-19 on CT, as described by the CO-RADS assessment scheme, in a way comparable to expert radiologists. Implications for practice Radiographers, as the first healthcare professionals to evaluate CT images in patients with suspected SARS-CoV-2 infection, could diagnose COVID-19 pneumonia by means of a categorical reporting scheme at CT in a reliable way, hence playing a primary role in the early management of these patients.

Objective To determine immediate performance measures for short-term, multicomponent cardiac rehabilitation (CR) in clinical routine in patients of working age, taking into account cardiovascular risk factors, physical performance, social medicine, and subjective health parameters and to explore the underlying dimensionality. Design Prospective observational multicenter register study in 12 rehabilitation centers throughout Germany. Setting Comprehensive 3-week CR. Participants Patients (N=1586) ≤65 years of age (mean 53.8±7.3y, 77.1% men) in CR (May 2017-May 2018). Interventions Not applicable. Main Outcome Measures Feasibility, defined by data availability for ≥85% of patients (CR admission and discharge), and modifiability based on pre-post comparison (statistical significance, with P value

Background The multi-morbid burden and use of systemic immunosuppressants in people with psoriasis may confer greater risk of adverse COVID-19 outcomes but data are limited. Objective Characterize the course of COVID-19 in psoriasis and identify factors associated with hospitalization. Methods Clinicians reported psoriasis patients with confirmed/suspected COVID-19 via an international registry, PsoProtect. Multiple logistic regression assessed the association between clinical/demographic characteristics and hospitalization. A separate patient-facing registry characterized risk-mitigating behaviours. Results Of 374 clinician-reported patients from 25 countries, 71% were receiving a biologic, 18% a non-biologic and 10% no systemic treatment for psoriasis. 348 (93%) fully recovered from COVID-19, 77 (21%) were hospitalized and nine (2%) died. Increased hospitalization risk was associated with older age (multivariable-adjusted OR 1.59 per 10 years, 95% CI 1.19-2.13), male sex (OR 2.51, 95% CI 1.23-5.12), non-white ethnicity (OR 3.15, 95% CI 1.24-8.03) and comorbid chronic lung disease (OR 3.87, 95% CI 1.52-9.83). Hospitalization was more frequent in patients using non-biologic systemic therapy than biologics (OR 2.84, 95% CI 1.31-6.18). No significant differences were found between biologic classes. Independent patient-reported data (n=1,626 across 48 countries) suggested lower levels of social isolation in individuals receiving non-biologic systemic therapy compared to biologics (OR 0.68, 95% CI 0.50-0.94). Conclusion In this international moderate-severe psoriasis case series, biologics use was associated with lower risk of COVID-19-related hospitalization than non-biologic systemic therapies, however further investigation is warranted due to potential selection bias and unmeasured confounding. Established risk factors (being older, male, non-white ethnicity, comorbidities) were associated with higher hospitalization rates. Clinical Implications We identify risk factors for COVID-19-related hospitalization in psoriasis patients, including older age, male sex, non-white ethnicity and comorbidities. Use of biologics was associated with lower hospitalization risk than non-biologic systemic therapies., Capsule summary: In this global registry-based study, risk factors for COVID-19-related hospitalization in psoriasis patients were older age, male sex, non-white ethnicity and comorbidities. Use of biologics was associated with lower hospitalization risk than non-biologic systemic treatment.

Objective To investigate the efficacy of fall hazards identification programs when compared to no intervention or other fall prevention programs on number of falls, falls incidence, and identifying fall hazards in community-dwelling adults. Data Sources CINAHL, PubMed, EMBASE, Scopus, and PsychINFO were used to identify articles. Study Selection Studies were selected to compare fall hazards identification programs to a control group. Studies were eligible if they were randomized controlled trials and enrolled adults older than 50 years with the incidence rate of falls as an outcome. Data Extraction Study or authors, year, sample characteristics, intervention or comparison groups, number of falls, and number of hazards identified in the intervention and control groups, and follow-up were extracted. The risk of bias assessment was performed using the Cochrane Risk of Bias tool. Quality was evaluated with Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach per outcome. Data Synthesis A total of 8 studies (N=8) and 5177 participants were included. There was a high risk of bias across the studies mostly due to improper blinding of personnel of the outcome assessor. Pooled estimate effects from 5 studies assessing the incidence rate of falls from 3019 individuals indicated no difference between fall hazards identification programs and control (incidence rate ratio=0.98; 95% confidence interval, 0.87-1.10). Conclusions The current study suggests that there may be a benefit for fall hazards programs in reducing incident falls. However, because of a moderate GRADE rating, more large-scale studies with a higher number of falls events and more consistent control groups are required to determine the true effect.

PURPOSE: To examine the performance of radiologists in differentiating COVID-19 from non-COVID-19 atypical pneumonia and to perform an analysis of CT patterns in a study cohort including viral, fungal and atypical bacterial pathogens. METHODS: Patients with positive RT-PCR tests for COVID-19 pneumonia (n = 90) and non-COVID-19 atypical pneumonia (n = 294) were retrospectively included. Five radiologists, blinded to the pathogen test results, assessed the CT scans and classified them as COVID-19 or non-COVID-19 pneumonia. For both groups specific CT features were recorded and a multivariate logistic regression model was used to calculate their ability to predict COVID-19 pneumonia. RESULTS: The radiologists differentiated between COVID-19 and non-COVID-19 pneumonia with an overall accuracy, sensitivity, and specificity of 88% ± 4 (SD), 79% ± 6 (SD), and 90% ± 6 (SD), respectively. The percentage of correct ratings was lower in the early and late stage of COVID-19 pneumonia compared to the progressive and peak stage (68 and 71% vs 85 and 89%). The variables associated with the most increased risk of COVID-19 pneumonia were band like subpleural opacities (OR 5.55, p

Background Emerging evidence indicates that small nucleolar RNAs (snoRNAs) play a central role in oncogenesis. Herein, we systematically evaluated expression profiles of snoRNAs in colorectal cancer (CRC) and investigated their clinical and functional role in this malignancy. Methods We compared expression levels of snoRNAs between cancer and normal tissues using publicly available datasets and identified the most differentially expressed and commonly upregulated snoRNAs in CRC. These results were examined in 489 colorectal tissues to assess their clinical significance, followed by a series of in vitro and in vivo experiments to evaluate the functional role of candidate snoRNAs. Results Using multiple RNA profiling datasets, we identified consistent overexpression of SNORA21 in CRC. In the clinical validation cohorts, the expression level of SNORA21 was upregulated in colorectal adenomas and cancers. Furthermore, elevated SNORA21 emerged as an independent factor for predicting poor survival. Both in vitro and in vivo experiments revealed that CRISPR/Cas9-mediated inhibition of SNORA21 expression resulted in decreased cell proliferation and invasion through modulation of multiple cancer related pathways. Conclusions We systematically identified SNORA21 as a key oncogenic snoRNA in CRC, which plays an important role in cancer progression, and might serve as an important prognostic biomarker in CRC., Highlights • Systematic and comprehensive analysis revealed that SNORA21 was significantly upregulated in CRC. • Elevated SNONA21 expression was related to metastasis and predicted poor prognosis in CRC patients. • SNORA21 is a promising cancer prognostic biomarker and a potential therapeutic target in CRC. Emerging evidence indicates that small nucleolar RNAs (snoRNAs) might play a central role in oncogenesis; however, the clinical significance and functional roles of snoRNAs in colorectal cancer (CRC) remain unclear. Herein, using multiple publicly available datasets, we systematically assessed expression profiles of snoRNAs in CRC and elucidated that the high expression of SNORA21 was associated with distant metastasis and poor overall survival. A series of in vitro and in vivo experiments revealed oncogenic role for SNORA21. Our findings indicate that SNORA21 is a promising cancer prognostic biomarker and a potential therapeutic target in CRC.

Background Cancer stem cell (CSC) epithelial cell adhesion molecule (Ep-CAM) is frequently expressed in colorectal cancer (CRC). However, the clinical significance of Ep-CAM expression in CRC is not clear. This study evaluated whether Ep-CAM provided valuable insight as a molecular biomarker for CRC diagnosis and prognosis and the potential of Ep-CAM as a novel therapeutic target in CRC. Methods Publications were selected online using electronic databases. The pooled odds ratios (ORs) or hazard ratios (HRs) with their 95% confidence intervals (95% CIs), and the combined sensitivity, specificity, and area under the curve (AUC) were calculated and summarized. Results Eleven eligible articles published in English involving 4561 cases were analyzed in this study. Ep-CAM expression was significantly higher in CRC compared with normal controls, and its overexpression was negatively linked to tumor differentiation, tumor stage, vascular invasion, depth of tumor invasion, lymph node metastasis, distant metastasis, and tumor budding in CRC patients. The loss of Ep-CAM expression positively correlated with these characteristics. Multivariate analysis of loss of Ep-CAM expression correlated with a poor prognosis in disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS). The pooled sensitivity, specificity and AUC values of Ep-CAM expression in patients with CRC vs. normal controls were 0.93, 0.90, and 0.94, respectively. Conclusions The present findings suggest that Ep-CAM expression may be associated with CRC carcinogenesis, while the loss of Ep-CAM expression is correlated with the progression, metastasis, and poor prognosis of CRC. Ep-CAM expression may be a useful biomarker for the clinical diagnosis of CRC., Highlights • Cancer stem cell (CSC) epithelial cell adhesion molecule (Ep-CAM) expression may correlate with CRC tumorigenesis. • Frequent overexpression of Ep-CAM was a favorable factor for CRC progression and metastasis. • Loss of Ep-CAM expression correlated with the progression, metastasis, and poor prognosis of patients with CRC. • Ep-CAM expression may be a potential marker for the detection of CRC. Ep-CAM expression was reported in CRC, but no clear direction for the diagnostic and prognostic effects of Ep-CAM expression was documented in patients with CRC. We performed a systematic meta-analysis of the existing evidence to determine the clinical significance of Ep-CAM expression in CRC. The findings indicated that Ep-CAM expression was associated with CRC risk. Frequent overexpression of Ep-CAM correlated with a decreased risk of CRC progression and metastasis, and loss of Ep-CAM expression played an important role in CRC progression, metastasis and prognosis. The detection of Ep-CAM expression may be a promising biomarker in diagnosing CRC.

Methylation of the RAS association domain family protein 1A (RASSF1A) promoter has been observed in nasopharyngeal carcinoma (NPC). This study investigated the correlation of RASSF1A promoter methylation with clinicopathological features and its utility as a diagnostic biomarker in NPC. A total of 926 patients with NPC and 495 non-tumor controls were analyzed in this study. RASSF1A promoter methylation was notably higher in NPC compared with non-tumor tissue, brushing and blood samples. RASSF1A promoter methylation was associated with clinical stage, lymph node status, distant metastasis, and T classification of patients with NPC, although it was not linked to age and sex. The pooled sensitivity, specificity, and AUC (area under the curve) of RASSF1A promoter methylation were determined in NPC samples vs. non-tumor samples (tissue: sensitivity = 0.72, specificity = 0.99, AUC = 0.98; brushing: sensitivity = 0.56, specificity = 1.00, AUC = 0.94; blood: sensitivity = 0.11, specificity = 0.98, AUC = 0.97). Our findings show that RASSF1A promoter methylation may be correlated with the development, progression and metastasis of NPC. RASSF1A promoter methylation is a promising noninvasive biomarker for the diagnosis of NPC from tissue and brushing samples., Highlights • RASSF1A promoter methylation was correlated with nasopharyngeal carcinoma (NPC) in tissue, brushing, and blood samples. • RASSF1A promoter methylation was linked to an unfavorable prognosis for patients with NPC. • The detection of RASSF1A promoter methylation in tissue and brushing samples could be used as a noninvasive biomarker for the diagnosis of NPC. The RASSF1A promoter is methylated in NPC. However, the clinical effects of RASSF1A promoter methylation in NPC are not clear. Our research shows that RASSF1A promoter methylation in NPC was significantly higher than in non-tumor tissue, brushing and blood samples. RASSF1A promoter methylation was correlated with clinical stage, lymph node status, distant metastasis, and T classification in patients with NPC. RASSF1A promoter methylation was effective for diagnoses of NPC based on tissue and brushing samples. Our work contributes to a better understanding of the potential diagnostic and prognostic values of RASSF1A promoter methylation in NPC.

EBioMedicine 52, 102647 (2020). doi:10.1016/j.ebiom.2020.102647, Published by Elsevier, Amsterdam [u.a.]

Objective/background Associations between exposure to effort-reward imbalance at work (eg, high time pressure/low appreciation) and risk of sleep disturbances have been reported, but the direction of the effect is unclear. The present study investigated changes in effort-reward imbalance and risk of concomitant and subsequent onset of sleep disturbances. Methods Participants with sleep disturbances at baseline were excluded. We included participants from a population-based cohort in Denmark (n = 8,464, 53.6% women, mean age = 46.6 years), with three repeated measurements (2012 (T0); 2014 (T1); 2016 (T2)). Changes in effort-reward imbalance (T0-T1) were categorized into ‘increase’, ‘decrease’ and ‘no change’. Self-reported sleep disturbances (difficulties initiating or maintaining sleep, non-restorative sleep, daytime tiredness) were dichotomized (presence versus absence). We regressed concomitant (T1) and subsequent (T2) sleep disturbances on changes in effort-reward imbalance (T0-T1) and calculated odds ratios (OR) and 95% confidence intervals, adjusted for sex, age, education and cohabitation. Results At follow-up, 8.4% (T1) and 12.5% (T2) reported onset of sleep disturbances. Increased effort-reward imbalance was associated with concomitant sleep disturbances (T1) (OR = 3.16, 2.56–3.81), whereas decreased effort-reward imbalance was not (OR = 1.22, 0.91–1.63). There was no association between increased effort-reward imbalance and subsequent sleep disturbances (T2) (OR = 1.00, 0.74–1.37). Results were similar for men and women. Conclusions Increased effort-reward imbalance was associated with a three-fold higher risk of concomitant onset of sleep disturbances at two-year follow-up, but not subsequent onset of sleep disturbances at four-year follow-up, indicating that changes in effort-reward imbalance have immediate rather than delayed effects on sleep impairment. It is possible that the results from the two-year follow-up were to some extent affected by reverse causality., Highlights • Psychosocial work stressors are discussed as risk factors for sleep disturbances. • Working conditions in which efforts exceeds rewards may elicit stress. • We studied the effect of changes in stressors on sleep in a large nationwide cohort. • Effort-reward imbalance was associated with 3-fold higher risk of sleep disturbances. • Changes in stressors had immediate rather than delayed effects on sleep impairment.

Objective: To identify patient characteristics on admission and daily events during hospitalization that could influence older medical inpatients walking activity during hospitalization. Design: A cohort study. Setting: Acute hospitalized care. Participants: Premorbidly mobile, nonsurgical, nonelective inpatients (50% women) aged ≥65 years (N=154), with an anticipated ≥3-day inpatient stay were recruited consecutively within 48 hours of hospital admission. Of the 227 patients screened, 69 did not meet study criteria and 4 refused. Interventions: Not applicable. Main Outcome Measures: Age, comorbidities (Cumulative Illness Rating Scale), cognitive status (6-item Cognitive Impairment Test), falls history and efficacy (Falls Efficacy Scale-International), physical performance (short physical performance battery), and medications were recorded within 2 days of admission. Walking activity (step count) was recorded for 7 days or until discharge. Daily events (procedures, falls, fear of falling, ordered bedrest, devices or treatments that hindered walking [eg, intravenous fluids, wall-mounted oxygen therapy], patient- and nurse-reported medial status, fatigue, sleep quality, physiotherapy, or occupational therapy intervention) were measured on concurrent weekdays. Their associations with daily (log) step count were estimated using linear mixed-effects models, adjusted for patient-characteristics measured at admission. Results: Approximately half of the variability in step count was described at the within-patient level. Multivariable models suggested positive associations with Wednesdays (+25% in step count; 95% confidence interval, 4-53), admission physical performance (+15%, 8-22), improving medical status (+33%, 7-64), negative associations with devices or treatments that hinder walking (−29%, −9 to −44), and instructed bedrest (−69%, −55 to −79). Conclusion: Day-to-day step count fluctuated, suggesting considerable scope for intervention. Devices or treatments that hinder walking should be reviewed daily and walking activity should become a clinical priority. Admission physical performance may identify vulnerable patients. Keywords: Accelerometry, Aged, Hospitalization, Mobility limitation, Rehabilitation, Walking

Objective: To assess the reliability, validity, and the psychometric properties of the Spanish version of the Functional Rating Index (Sp-FRI) in a preliminary cohort of patients with low back pain (LBP). Design: Prospective observational multicenter study. Setting: Outpatient physical therapy clinics and units from public and private settings. Participants: Patients with LBP (N=22; 52.5±12.5y) entered the study. Interventions: The translation and cross-cultural adaptation were performed following international guidelines through a 5-step procedure. Main Outcome Measures: The Sp-FRI was administered along with the Spanish version of Roland-Morris Disability Questionnaire (Sp-RMDQ) and numeric pain rating scale (NPRS) index. Preliminary testing included readability, comprehensibility, ceiling and floor effects, reliability, and validity. Statistical analysis was based on the Fernandez-Huerta index, and the calculation of Cronbach alpha, intraclass correlation coefficient (ICC), and Spearmanś correlation coefficient, respectively. All patients completed the Sp-FRI again after 1-2 days to assess its test-retest reliability. Results: None of the participants requested clarification of any of the items at the time of completion. The test-retest reliability of the FRI score was substantial (ICC 0.77). Cronbach alpha was 0.859. Spearman correlation coefficient between Sp-FRI and Sp-RMDQ was 0.66; P

Highlights • Use and adoption of health information technology advances quality in patient care. • Healthcare systems need tools to enhance primary prevention at the point-of-care. • Providers and patients have shared accountability for population health metrics.

Background: Clinical efficacy of balloon pulmonary angioplasty (BPA) to the patients with non-operable chronic thromboembolic pulmonary hypertension (CTEPH) for improving pulmonary hemodynamics and exercise tolerance has been reported in these several years. However, reperfusion pulmonary injury (RPI) remains to be a major complication of BPA to overcome. This study elucidated the local predictor of RPI. Methods: Twenty-eight consecutive patients with non-operable CTEPH underwent BPA for lesions in the segmental or sub-segmental vessels. Pre- and post-BPA pulmonary arterial pressures at proximal (Pp) and distal (Pd) to the stenosis were measured by a 0.014-in. pressure wire. Positive or negative RPI was evaluated by chest computed tomography in each re-perfused segment separately 4 h after BPA. Results: Pressure measurements pre- and post-BPA were obtained from 110 lesions, where Pd and pressure ratio (Pd/Pp) increased after BPA in all lesions. Among them, RPI was observed in 49 lesions (44.5%). In the RPI-positive lesions, post-BPA Pd and post-BPA Pd/Pp were higher compared with the RPI-negative lesions. Multivariate logistic analysis revealed that the post-BPA Pd was independently associated with RPI incidence. Receiver operating characteristic curve analysis demonstrated the best cut-off value of 19.5 mm Hg for post-BPA Pd to predict RPI. Conclusions: High reperfusion pressure after BPA could be a predictor of RPI. Monitoring local pressure during BPA procedure may have a potential to reduce the incidence of RPI.

Background: Relieving malignant biliary obstruction improves quality of life and permits chemotherapy. Outcomes of endoscopic retrograde cholangio-pancratography(ERCP) in inoperable malignant biliary obstruction have been examined in a national cohort to establish factors associated with poor outcomes. Methods: Hospital Episode Statistics include diagnostic and procedural data for all NHS hospital attendances in England. Patients from 2006 to 2017 with a Hepaticopancreaticobiliary (HPB) malignancy who had undergone ERCP were studied. Patients undergoing a potentially curative operation were excluded. Associations between demographics, co-morbidities, unit ERCP volume and mortality were examined by logistic regression. Findings: 39,702 patients were included; 49.4% were male; median age was 75 (IQR 66–88)years. Pancreatic cancer was the most common tumour (63.9%). Mortality was 4.1%, 9.7% and 19.1% for 7-day, in hospital and 30-day respectively. On multivariable analysis: men (OR 1.20(95%CI 1.14–1.26), p < 0.001); increasing age quintile 78–83(1.73(1.59–1.89), p < 0.001), >83(2.70(2.48–2.94),p < 0.001); most deprived quintile (1.21(1.11–1.32), p < 0.001); increasing co-morbidity score >20(3.36(2.94–3.84),p < 0.001); small bowel malignancy (1.45(1.22–1.72), p < 0.001), intrahepatic biliary malignancy(1.10(1.03–1.17), p = 0.005) and year of ERCP 2006/07 (1.37(1.22–1.55), p < 0.001) were associated with increased 30-day mortality. Extrahepatic biliary tree cancers (0.67(0.61–0.73), p318 annually, 0.91(0.84–0.98), p = 0.01) and high volume of ERCP for malignant obstruction (>40 annually (0.91(0.85–0.98), p = 0.014) were negatively associated with 30-day mortality. Patients were less likely to require a second ERCP in high volume providers (>318, 8.0%) compared to low volume ((

Objective To clarify the association of rs11196218 polymorphism in transcription factor 7-like 2 (TCF7L2) and type 2 diabetes mellitus (T2DM) in Asian population by a case–control study and meta-analysis. Methods In the case–control study, 1842 patients with T2DM and 7777 normal glucose-tolerant controls in the Henan province of China were genotyped for rs11196218 in TCF7L2 by PCR–ligase detection reaction. We used allele, co-dominant, dominant and recessive models to evaluate the risk association and performed a meta-analysis of the results of different genetic models in previous studies and the current study. Results The AG genotype of rs11196218 was associated with risk of T2DM in the Henan population (odds ratio 1.37, 95% confidence interval 1.06–1.78), and dominant model showed marginal significant association (1.28, 0.99–1.67). Meta-analysis of 10 studies revealed the dominant model associated with T2DM in the overall population (1.20, 1.05–1.36). When stratified by region (southern and northern China and Japan), both the AG genotype and the dominant model were associated with risk of T2DM in southern Chinese (1.31, 1.03–1.66; 1.27, 1.01–1.60, respectively). Conclusion The rs11196218 polymorphism in TCF7L2 is associated with risk of T2DM in Asian population.

Background There is a persistent gap in the health of Aboriginal Victorians compared with non-Aboriginal Victorians, where Aboriginal Victorians have poorer health. Currently, the most commonly touted explanation for this gap revolves around health behaviours known as ‘lifestyle risk factors’. Yet the gap in health is similarly matched by persistent gaps in social and economic outcomes that reflect past and ongoing discrimination of Aboriginal peoples across Australia. Perceived racism has been implicated as a key determinant of the gap in health between Indigenous and non-Indigenous peoples across the world. We sought to determine the contribution of perceived racism to the gap in health and how this compared with the contribution of lifestyle risk factors and other determinants of health such as socioeconomic status. Methods We combined data from 2011, 2012 and 2014 Victorian Population Health Surveys (VPHS) to obtain a sample size of 33,833 Victorian adults, including 387 Aboriginal adults. The VPHS is a population-representative, cross-sectional, computer-assisted telephone interview survey conducted annually. Using logistic regression, poor self-reported health status was the dependent variable and Aboriginal status was the primary independent variable of interest. Secondary independent variables included age, sex, perceived racism, socioeconomic status, and lifestyle risk factors. Results Aboriginal Victorians were almost twice as likely as non-Aboriginal Victorians to report poor health; OR=1.9 (95% confidence interval; 1.3–2.6). Perceived racism explained 34% of the gap in self-reported health status between Aboriginal and non-Aboriginal Victorians, followed by: smoking (32%), unhealthy bodyweight (20%), socioeconomic status (15%), excessive consumption of alcohol (13%), and abstinence from alcohol consumption (13%). In contrast, physical inactivity made no contribution. Together, perceived racism and smoking explained 58% of the gap, while all secondary independent variables explained 82% of the gap. Conclusions Perceived racism may be an independent health risk factor that explains more than a third of the health gap between Aboriginal and non-Aboriginal Victorians; equivalent in strength to smoking. The recognised failure of the Australian government’s Closing the Gap strategy may be due in part to the failure to consider other determinants of the health gap beyond the lifestyle risk factors, namely racism, which may act to damage health through multiple pathways at multiple points along the causal chain., Highlights • Aboriginal Victorians have poorer health than their non-Aboriginal counterparts. • Racism explained more than a third of the gap in self-reported health status. • Racism may be a health risk factor that is equivalent in strength to smoking. • Racism and smoking explained 58% of the gap in self-reported health status. • The failure of policies to reduce the health gap may be due to not addressing racism.

Objective To determine whether exposures to infectious illness during childhood involving the CNS or elsewhere is associated with adult schizophrenia or other psychoses. Method Systematic review and meta-analysis of published literature identified by electronic and manual search meeting three inclusion criteria: population-base, objective assessment of childhood infection at the individual level, standard definition of adult psychotic outcomes. We calculated risk ratio for all CNS infection, and separately for viral and bacterial infection in relation to non-affective psychosis and schizophrenia, which was combined in meta-analysis. Results Seven studies were included. Meta-analysis involving 2424 cases and over 1.2 million controls showed CNS viral infection was associated with nearly two-fold increased risk of adult non-affective psychosis (risk ratio 1.70; 95% CI 1.13–2.55; p = 0.01). There was no significant heterogeneity between studies (p = 0.26; I2 = 20%). Separate meta-analysis involving 1035 cases and over 1.2 million controls suggested all childhood CNS infections, particularly viral infections, may be associated with nearly two-fold risk of adult schizophrenia. However, there was evidence of some heterogeneity between these studies (p = 0.07; I2 = 70%). CNS bacterial infections were not associated with risk of psychosis. Data on childhood infections with no obvious involvement of the CNS is insufficient. Conclusions These findings indicate childhood CNS viral infections increase the risk of adult psychotic illness. Possible mechanisms may include both direct effects of pathogens, and the effects of inflammatory response on the developing brain.

Objectives Many hospitals cannot afford an hCG assay on a central lab analyzer and turn to point of care testing (POCT) solutions. The Radiometer AQT90 FLEX is a small benchtop immunoareement between the AQT90 and comparator methods for samples with hCG ssay analyzer for use in the laboratory or at the patient bedside. This study evaluated the analytical performance of the AQT90's βhCG assay. Methods Precision was assessed using whole blood patient samples and two levels of quality control. Linearity was assessed by dilution of a high hCG plasma sample. Carryover and hook effect were assessed using high and low hCG samples. Method comparisons were done against Abbott i-STAT Total βhCG, Beckman Coulter Total βhCG (5th IS), and Roche hCG+β. Sample concentrations ranged from20 IU/L, biases were apparent against all three comparator assays (i-STAT: +20%, Roche: +30%, Beckman: +5 to 15%). At ≤20 IU/L, the acceptability of agreement varied according to TAE specifications. Concordance between AQT90 and comparator assays using 5 IU/L as the medical decision level ranged from 69% to 81%. Conclusions Overall, the AQT90 hCG assay performed well and would be suitable for smaller suburban or rural hospitals. Some limitations have been noted and should be kept in mind during clinical testing., Highlights • Analytical evaluation of the Radiometer AQT90 FLEX βhCG assay. • Most of Radiometer's claims and TAE criteria met by the AQT90. • Clinically significant differences with comparators at high concentrations. • Clinically insignificant differences with comparators at low concentrations. • Suitable for use at smaller suburban or rural hospitals for hCG testing.

Background Maternal mood symptoms have been associated with psychiatric disorders in children. This study aimed to assess critical periods when maternal symptoms would be more deleterious. Methods Cohort of 4231 births followed-up in the city of Pelotas, Brazil. Mood symptoms during pregnancy were self-reported by mothers at perinatal interview; and at 3-months postpartum, mothers answered the Self-Reporting Questionnaire. Psychiatric disorders in 6-year-old children were evaluated through the Development and Well-Being Assessment instrument. Odds ratios with 95% confidence intervals (95% CI) were calculated by logistic regression. Results Prevalence of mood symptoms in pregnancy was 24.6% (23.2–26.0%) and at three months postpartum 22.5% (21.1–23.9%). Prevalence of mental disorders in children was 13.3% (12.2–14.4%). After adjustment for confounders children of mothers with mood symptoms during pregnancy were 82% more likely of presenting psychiatric disorders than children of mothers that did not (1.82; 1.48–2.25); and the chance of having mental disorders among children whose mothers had positive SRQ-20 at three months postpartum was 87% greater than the observed among children whose mothers had it negative (1.87; 1.50–2.33). Limitations Because maternal anxiety/depression may interfere with interpretation of the child behavior, child׳s mental health being obtained by interviewing the mother is a limitation of this study. Lack of information on other risk factors may have lead to residual confounding on the effect of maternal mood symptoms at three months postpartum. Conclusions Children of mothers presenting mood symptoms during pregnancy and in the first months postpartum are more likely to present psychiatric disorders at 6 years of age.