Oral anticoagulants and cognitive impairment in patients with atrial fibrillation: A systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: This systematic review assesses the likelihood of developing dementia and cognitive impairment in patients with atrial fibrillation (AF) receiving non-vitamin K antagonist oral anticoagulants (NOACs) as opposed to vitamin K antagonists (VKAs). METHODS: We performed a systematic review with meta-analysis and trial sequential analysis (TSA), which encompassed both randomized controlled trials (RCTs) and observational studies. The objective was to assess the impact of NOACs and VKAs on the incidence of dementia in individuals diagnosed with AF. RESULTS: Out of 1914 studies that were screened, 31 studies were included in the final analysis, which consisted of nine RCTs or their subsequent post-hoc analyses, in addition to 22 observational studies. The meta-analysis shows that NOACs were associated with a decreased probability of developing dementia of any cause [Rate Ratio (RR): 0.88; 95 % confidence interval (95 % CI): 0.82-0.94], especially in patients below the age of 75 (RR: 0.78; 95 % CI: 0.73-0.84). Consistent patterns were observed across all forms of dementia and cognitive function decline. The overall evidence indicates notable variability in the outcome with a moderate-to-low degree of certainty. The TSA suggests that the total sample size of the included trials (155,647 patients) was significantly smaller than the required information size of 784,692 patients to discern the true effect of NOAC versus VKA in terms of reducing dementia risk. CONCLUSION: NOACs may reduce the likelihood of developing dementia in patients with AF, particularly in those under the age of 75. This review highlights the urgent necessity for thorough research to determine the efficacy of NOACs in safeguarding cognitive health.

The Clinical Benefits of Antiresorptive Agents in Patients with Primary Breast Cancer Receiving Adjuvant Endocrine Therapy: A Systematic Review with Pairwise and Network Meta-analysis.

CONTEXT: Clinical trials have investigated the role of antiresorptive agents, including bisphosphonates and denosumab, in patients with primary breast cancer receiving adjuvant endocrine therapy, aiming for better bone protection and/or improving survival. OBJECTIVE: To summarize the clinical effects of antiresorptive agents in patients with early breast cancer receiving endocrine therapy. METHODS: We systematically reviewed and synthesized the clinical benefits and harms of antiresorptive agents in patients with early breast cancer receiving endocrine therapy by calculating the risk ratios (RRs). RESULTS: In the pooled meta-analysis, antiresorptive agents had significant clinical benefits on disease recurrence (RR 0.78, 95% CI 0.67-0.90) and locoregional recurrence (RR 0.69, 95% CI 0.49-0.95) in patients with breast cancer receiving endocrine therapy. Early use of antiresorptive agents has a beneficial effect on secondary endocrine therapy resistance instead of primary resistance. Safety analysis revealed that potential risk for osteonecrosis of the jaw (ONJ, RR 3.29, 95% CI 1.12-9.68) with antiresorptive agents; however, there is an insignificant difference in arthralgia. The subgroup analyses revealed that intervention with bisphosphonates might have profound clinical benefits, but also increased the occurrence of ONJ. A network meta-analysis further supported the clinical effects of early antiresorptive agent use compared with delayed use or placebo. CONCLUSION: Using antiresorptive agents early in patients with breast cancer receiving adjuvant endocrine therapy may provide additional benefits in risk reduction of recurrence, but there is a potential risk of ONJ.

130/80 mmHg as a unifying hypertension threshold for office brachial, office central, and ambulatory daytime brachial blood pressure.

The present study investigated the prognostic values for office brachial (OB), office central (OC), and ambulatory daytime brachial (AmDB) hypertension, as defined by a unifying threshold of 130/80 mmHg, and the incremental value of either OC or AmDB hypertension to OB hypertension. A total of 1219 community residents without receiving anti-hypertensive treatment (671 men and 548 women, aged ≥ 30 years old) from central Taiwan and Kinmen islands had OB, OC, and AmDB blood pressure measurements during a cardiovascular survey conducted in 1992-1993. OB hypertension, OC hypertension, and AmDB hypertension were all defined in retrospect at the threshold of 130/80 mmHg. They were followed up for nonfatal and fatal cardiovascular events until December 31, 2017, by linking the baseline database to the National Health Insurance Research dataset and the National Death Registry. During a follow-up of 25 612.5 person-years (Average event-free time: 21.0 years), there were 368 fatal and nonfatal cardiovascular events. In multivariable analyses, OB hypertension, OC hypertension, and AmDB hypertension had similar hazard ratios for cardiovascular events [2.03, 95% confidence interval: 1.47-2.80]; 1.92 (1.47-2.51); and 1.79 (1.41-2.29), respectively. Using OB normotension as the reference, either the concordant OB and OC hypertension [2.24 (1.61-3.12)], or the concordant OB and AmDB hypertension [2.52 (1.80-3.54)] was significantly associated with cardiovascular events. Moreover, OB hypertension plus AmDB normotension was also significantly associated with increased risk for cardiovascular events. We concluded that OB hypertension, OC hypertension, and AmDB hypertension defined by a unifying threshold of 130/80 mmHg may provide similar estimates of long-term risk for cardiovascular events. Cross-classification analyses suggest that addition of OC hypertension or AmDB hypertension may improve the prognostic value of OB hypertension.

Improvement of clinical outcomes in patients undergoing peritoneal dialysis using hydroxymethylglutaryl-CoA reductase inhibitors: A systematic review and meta-analysis.

BACKGROUND: It is unclear whether hydroxymethylglutaryl-CoA reductase inhibitor (statin) therapy decreases the risk of mortality and cardiovascular disease (CVD) in patients undergoing peritoneal dialysis (PD). METHODS: We performed a literature search of PubMed, Cochrane Library, Embase, and other databases for research publications up to June 2022. The outcomes of interest were fatal and nonfatal CVDs, all-cause mortality, and changes in the biochemical profiles. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled and synthesized using a random-effects model. The certainty of the evidence was determined using Grading of Recommendations, Assessment, Development, and Evaluation. RESULTS: Nine studies, including 2,933 patients undergoing PD, were included. Among them, three studies, including 2,099 patients, reported all-cause mortality, and three, including 1,571 patients, reported CVDs. In these patients, pooling results of two observational studies (very low-certainty evidence) showed that statin therapy significantly reduced CVDs (HR = 0.67; 95% CI = 0.54-0.84; p = 0.0004). Moreover, statin therapy was associated with significantly reduced low-density lipoprotein cholesterol, total cholesterol, and C-reactive protein levels (very low certainty of evidence). However, the effects of statin therapy on triglyceride, high-density lipoprotein, and albumin levels were not statistically significant. CONCLUSION: Although statin therapy was associated with significantly reduced low-density lipoprotein cholesterol, total cholesterol, and C-reactive protein levels, the probable beneficial effect of statins on CVD risk in patients undergoing PD could not be concluded firmly. Additional high-quality studies are required to assess the potential beneficial effects of statin therapy in PD patients.

Optimal stroke preventive strategy for patients aged 80 years or older with atrial fibrillation: a systematic review with traditional and network meta-analysis.

BACKGROUND: An optimal antithrombotic strategy for patients aged 80 years or older with atrial fibrillation (AF) remains elusive. OBJECTIVE: Using a systematic review with traditional and network meta-analysis, we investigated outcomes in AF patients ≥80 years treated with different antithrombotic strategies. METHODS: We searched eligible randomised controlled trials (RCTs) and observational studies from MEDLINE, EMBASE, Cochrane Library and Web of Science databases from inception to 16 December 2021. Research comparing treatment outcomes of novel oral anticoagulants (NOACs), aspirin, vitamin K antagonists (VKAs) or no oral anticoagulant/placebo therapy in patients ≥80 years with AF were included. Outcomes were stroke or systemic embolism (SSE), major bleeding, all-cause mortality, intracranial bleeding (ICH) and gastrointestinal bleeding. Traditional and network meta-analyses were performed. Net clinical benefit integrating SSE and major bleeding was calculated. RESULTS: Fifty-three studies were identified for analysis. In the meta-analysis of RCTs, risk of SSE (risk ratio [RR]: 0.82; 95% confidence interval [CI]: 0.73-0.99) and ICH (RR: 0.38; 95% CI: 0.28-0.52) was significantly reduced when NOACs were compared with VKAs. Network meta-analysis of RCTs demonstrated that edoxaban (P-score: 0.8976) and apixaban (P-score: 0.8528) outperformed other antithrombotic therapies by showing a lower major bleeding risk and better net clinical benefit. Both traditional and network meta-analyses from RCTs combining with observational studies showed consistent results. CONCLUSIONS: In patients aged 80 years or older with AF, NOACs have better outcomes than VKAs regarding efficacy and safety profiles. Edoxaban and apixaban may be preferred treatment options since they are safer than other antithrombotic strategies.

Implementing a flipped classroom model in an evidence-based medicine curriculum for pre-clinical medical students: evaluating learning effectiveness through prospective propensity score-matched cohorts.

BACKGROUND: In a flipped classroom (FC) model, blended learning is used to increase student engagement and learning by having students finish their readings at home and work on problem-solving with tutors during class time. Evidence-based medicine (EBM) integrates clinical experience and patient values with the best evidence-based research to inform clinical decisions. To implement a FC and EBM, students require sufficient information acquisition and problem-solving skills. Therefore, a FC is regarded as an excellent teaching model for tutoring EBM skills. However, the effectiveness of a FC for teaching EBM competency has not been rigorously investigated in pre-clinical educational programs. In this study, we used an innovative FC model in a pre-clinical EBM teaching program. METHODS: FC's teaching was compared with a traditional teaching model by using an assessment framework of prospective propensity score matching, which reduced the potential difference in basic characteristics between the two groups of students on 1:1 ratio. For the outcome assessments of EBM competency, we used an analysis of covariance and multivariate linear regression analysis to investigate comparative effectiveness between the two teaching models. A total of 90 students were prospectively enrolled and assigned to the experimental or control group using 1:1 propensity matching. RESULTS: Compared with traditional teaching methods, the FC model was associated with better learning outcomes for the EBM competency categories of Ask, Acquire, Appraise, and Apply for both written and oral tests at the end of the course (all p-values< 0.001). In particular, the "appraise" skill for the written test (6.87 ± 2.20) vs. (1.47 ± 1.74), p < 0.001), and the "apply" skill for the oral test (7.34 ± 0.80 vs. 3.97 ± 1.24, p < 0.001) had the biggest difference between the two groups. CONCLUSIONS: After adjusting for a number of potential confunding factors, our study findings support the effectiveness of applying an FC teaching model to cultivate medical students' EBM literacy.

Evaluating Teaching Effectiveness of Medical Humanities in an Integrated Clerkship Program by a Novel Prospective Propensity Score Matching Framework.

BACKGROUND: This study aims to rigorously compare the effectiveness of the educational programs of a new integrated clinical clerkship in medicine (3 months) and surgery (3 months) at a cancer center with the conventional subspecialty-based rotations at a tertiary teaching hospital, by this prospective, pre-post comparative method. METHODS: Between 2013-2016, we compared 69 students who had selected the integrated clerkship that emphasized clinical competency and medical humanities training with 138 matched peers who had completed conventional clerkships during the same period. Outcome measures for medical humanities included empathy, patient-centeredness, and other values and skills related to holistic health care professionalism by introducing prospective propensity score matching (PSM). RESULTS: At baseline, no significant between-group differences existed. At the completion of the core clerkships, students receiving the integrative clerkship had significantly higher scores on the Patient-Practitioner Orientation Scale (PPOS) and the Professionalism Climate in Clinical Teaching Environment (PCI), and similar Jefferson Scale of Physician Empathy Student Version (JSPE) scores, as compared with the comparison group. We also found that the students in this program did not perform worse than those in the traditional internship group in the comprehensive and formative OSCE medical clinical skills test. CONCLUSIONS: Our study develops an empirical basis for rigorous evaluation to design medical education to improve the medical humanities values and skills of interns. Features of the new integrated clerkship program that we developed include substantial participation by the students in patient-centered in-hospital culture, as well as reflection, discussion, and feedback on actual clinical cases.

Risk of work-related injury in workers with obstructive sleep apnea: A systematic review and meta-analysis.

The objective of this study is to elucidate the relationship between obstructive sleep apnea (OSA) and the risk of work-related injuries (WRIs), synthesize the latest clinical evidence and conduct a systematic review and meta-analysis adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA 2020). Observational studies published before April 2020 in PubMed, Cochrane library, PsycINFO, Scopus, Google Scholar and Web of Science were included. Random-effects Mantel-Haenszel meta-analysis was performed. A total of 15 studies with 21,507 participants were included. Prespecified subgroup analyses based on study design and the characteristics of the enrollees were conducted. Overall, workers with OSA had 1.64-fold increased odds of being involved in WRIs compared to their counterparts (OR = 1.64, 95% CI = 1.24-2.16, p = 0.0005). In addition to the professional drivers that have been studied in the past, such a trend also existed in the general working population (OR = 1.68, 95% CI = 1.14-2.49, p = 0.01). We also found that workers with excessive daytime sleepiness (Epworth Sleepiness Scale score >10) had a 1.68-fold increased risk of WRIs compared to those with lower ESS scores (OR = 1.68, 95% CI = 1.22-2.30, p = 0.002). This study verified that OSA workers had a higher risk of WRIs, and such correlations do not show obvious differences in subgroups with different sample sizes, OSA diagnosis methods, job types or definitions of WRI. Based on the association between OSA and WRIs identified in our study, further studies investigating the protective effects of early identification and management of OSA on WRIs are warranted.

The prognostic significance of the alterations of pulmonary hemodynamics in patients with pulmonary arterial hypertension: a meta-regression analysis of randomized controlled trials.

BACKGROUND: Hemodynamic assessment in patients with pulmonary arterial hypertension (PAH) is essential for risk stratification and pharmacological management. However, the prognostic value of the hemodynamic changes after treatment is less well established. OBJECTIVES: We investigated the prognostic impacts of the changes in hemodynamic indices, including mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), right atrial pressure (RAP), and cardiac output index (CI). We conducted this systematic review with meta-regression analysis on existing clinical trials. METHODS: We searched and identified all relevant randomized controlled trials from multiple databases. An analogous R2 index was used to quantify the proportion of variance explained by each predictor in the association with PAH patients' prognosis. A total of 21 trials and 3306 individuals were enrolled. RESULTS: The changes in mPAP, PVR, RAP, and CI were all significantly associated with the change in 6MWD (∆6MWD). The change in mPAP was with the highest explanatory power for ∆6MWD (R2 analog = 0.740). Additionally, the changes in mPAP, PVR, and CI were independently predictive of adverse clinical events. The change in mPAP had the highest explanatory power for the clinical events (R2 analog = 0.911). Furthermore, the change in PVR was with the highest explanatory power for total mortality of PAH patients (R2 analog = 0.612). CONCLUSION: Hemodynamic changes after treatment, including mPAP, PVR, CI, and RAP, were significantly associated with adverse clinical events or mortality in treated PAH patients. It is recommended that further studies be conducted to evaluate the changes in hemodynamic indices to guide drug titration. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019125157.

Vascular complications of diabetes: natural history and corresponding risks of dementia in a national cohort of adults with diabetes.

AIMS: This study aimed to determine the trajectory of diabetic vascular diseases and to investigate the association between vascular diseases and dementia. METHODS: We included adults aged ≥ 50 years with newly diagnosed type 2 diabetes (n = 173,118) from 2001 to 2005 who were followed-up until December 31, 2013 in the Taiwan's National Health Insurance Research Database. Multivariable Cox regression models were constructed to estimate hazard ratios (HRs) and confidence limits (CLs) for all-cause dementia in relation to the number, types, and occurrence patterns of vascular disease. RESULTS: Within 1 year of diabetes diagnosis, 26.3% of adults developed their first vascular disease. During the 1,864,279 person-years of follow-up, 17,426 adults had all-cause dementia, corresponding to an incidence of 97.9 cases/10,000 person-years in 127,718 adults with at least one vascular disease and 67.5 cases/10,000 person-years in 45,400 adults without vascular diseases. Across all age groups, adults who subsequently developed a vascular disease in two one-year windows since diabetes diagnosis had the highest incidence of all-cause dementia. In comparison with adults without vascular diseases, HR for all-cause dementia was 1.99 (CL: 1.92-2.07) for those with one vascular disease only; 2.04 (CL: 1.98-2.13) for two or more vascular diseases; 3.56 (CL: 3.44-3.70) for stroke only; and 2.06 (CL: 1.99-2.14) for neuropathy alone. Similar associations were also observed with a smaller magnitude for adults with nephropathy, retinopathy, cardiovascular disease, or peripheral arterial disease. CONCLUSIONS: Patients with diabetes-related complications, particularly stroke and neuropathy, and those with rapidly developed vascular diseases appeared to have a high risk of dementia.

A preliminary evaluation of psychological stress amongst workers in Taiwan: a cross-sectional survey.

BACKGROUND: Stress and psychological disorders have been assigned increasing significance in the field of occupational health. Based on Japan's psychiatric disability occupational disease recognition regulation, Taiwan's Council of Labor Affairs announced "Evaluation Guidelines for psychiatric diseases induced by work-related stress" in 2009. This evaluation tool was designed to assess the source and intensity of work-related and non-work-related mental stress, and references existing Japanese guidelines. However, empirical data from workers in various sectors in Taiwan are still required to validate the utility of the guidelines. METHODS: This study recruited 2319 workers from the manufacturing, service, and public administration sectors to participate in a survey between 2010 and 2011. The survey included questions regarding participants' demographic characteristics, job type or attributes, a life event stress intensity evaluation Table (35 work-related and 23 non-work-related items on a scale of 1-10). The Chinese version of the Copenhagen Burnout Inventory (C-CBI) and Chinese Health Questionnaire (CHQ-12) were also included to explore associations between work-related/non-work-related stress and health outcomes. RESULTS: Analyses of survey results showed events relating to employment security (e.g., "company bankruptcy" and "being fired or forced to retire" scores; mean stress intensity scores both 6.18) were the cause of the highest intensity work-related stress. Within different demographic/job type categories, women had higher stress intensity scores for most items than men (greatest difference in "sexual harassment in the workplace" score). Furthermore, executive class workers generally experienced more psychological stress than blue-collar workers (greatest difference in "serious injury or disease due to work" score). Results from regression analysis supported the observation that employees' burnout and work-related stress was more significant than non-work-related stress. Moreover, work-related/non-work-related stress intensity levels both had significant negative predictive effects on mental health. CONCLUSIONS: Regarding policy, this study provides empirical evidence and practical suggestions for establishing a psychological stress intensity database of workers under specific social contexts in a newly industrialized East Asian country. Such a database can be employed to help identify workers with work-related psychological disorders. Additionally, this study also provides a point of reference for enterprises to prioritize agendas when developing employee stress management and support protocols.

Exploring the public-private and company size differences in employees' work characteristics and burnout: data analysis of a nationwide survey in Taiwan.

Distinct differences exist between public-private sector organizations with respect to the market environment and operational objectives; furthermore, among private sector businesses, organizational structures and work conditions often vary between large- and small-sized companies. Despite these obvious structural distinctions, however, sectoral differences in employees' psychosocial risks and burnout status in national level have rarely been systematically investigated. Based on 2013 national employee survey data, 15,000 full-time employees were studied. Sector types were classified into "public," "private enterprise-large (LE)," and "private enterprise-small and medium (SME);" based on the definition of SMEs by Taiwan Ministry of Economic Affairs, and the associations of sector types with self-reported burnout status (measured by the Chinese version of Copenhagen Burnout Inventory) were examined, taking into account other work characteristics and job instability indicators. Significantly longer working hours and higher perceived job insecurity were found among private sector employees than their public sector counterparts. With further consideration of company size, greater dissatisfaction of job control and career prospect were found among SME employees than the other two sector type workers. This study explores the pattern of public-private differences in work conditions and employees' stress-related problems to have policy implications for supporting mechanism for disadvantaged workers in private sectors.

Active job, healthy job? Occupational stress and depression among hospital physicians in Taiwan.

This study assessed the levels and association of occupational stress and depression rate among physicians, and to compare physicians' occupational stress with that of Taiwanese employees in other occupations. The subjects were physicians employed at 14 participating regional hospitals in the Around Taiwan Health Care Alliance. Self-administered questionnaires capturing data on demographics, occupational characteristics, occupational stress measured using Job Content Questionnaire (C-JCQ), and health status measured using Taiwanese Depression Questionnaire (TDQ) were sent to eligible physicians. Results revealed that the depression rate (13.3%) was higher than that found in the general population (3.7%) of Taiwan. The mean scores of the JCQ dimensions "work demands" and "job control" were both much higher than those in most occupations in Taiwan. Higher depression scores were found in subjects with higher work demands, 8-10 d of being on duty per month, and more frequent alcohol consumption, while lower depression scores were found in subjects working in the east Taiwan area, with higher job control and with greater workplace social support. On the other hand, gender, smoking, and working hour were not independently correlated with depression, but the interaction of gender and job control also had an independent effect on depression. This study suggests that job stress plays an important role in depression in physicians; it is necessary to pay attention to physicians at high risk of depression, as well as their work environments, for early detection and intervention.

Social patterns of pay systems and their associations with psychosocial job characteristics and burnout among paid employees in Taiwan.

Today, performance-based pay systems, also known as variable pay systems, are commonly implemented in workplaces as a business strategy to improve workers' performance and reduce labor costs. However, their impact on workers' job stress and stress-related health outcomes has rarely been investigated. By utilizing data from a nationally representative sample of paid employees in Taiwan, we examined the distribution of variable pay systems across socio-demographic categories and employment sectors. We also examined the associations of pay systems with psychosocial job characteristics (assessed by Karasek's Demand-Control model) and self-reported burnout status (measured by the Chinese version of the Copenhagen Burnout Inventory). A total of 8906 men and 6382 women aged 25-65 years were studied, and pay systems were classified into three categories, i.e., fixed salary, performance-based pay (with a basic salary), and piece-rated or time-based pay (without a basic salary). Results indicated that in men, 57% of employees were given a fixed salary, 24% were given a performance-based pay, and 19% were remunerated through a piece-rated or time-based pay. In women, the distributions of the 3 pay systems were 64%, 20% and 15%, respectively. Among the three pay systems, employees earning through a performance-based pay were found to have the longest working hours, highest level of job control, and highest percentage of workers who perceived high stress at work. Those remunerated through a piece-rated/time-based pay were found to have the lowest job control, shortest working hours, highest job insecurity, lowest potential for career growth, and lowest job satisfaction. The results of multivariate regression analyses showed that employees earning through performance-based and piece-rated pay systems showed higher scores for personal burnout and work-related burnout, as compared to those who were given fixed salaries, after adjusting for age, education, marital status, employment grade, job characteristics, and family care workloads. As variable pay systems have gained in popularity, findings from this study call for more attention on the tradeoff between the widely discussed management advantages of such pay systems and the health burden they place on employees.

Psychometric properties of the Chinese version of Copenhagen burnout inventory among employees in two companies in Taiwan.

This study examined the psychometric properties of two selected scales--'personal burnout' and 'work-related burnout'--from the Chinese version of the Copenhagen Burnout Inventory (C-CBI) in 384 employees from two companies in Taiwan. A self-administered questionnaire was used that included the two C-CBI scales, the scales of mental health, vitality and general health from the Short Form 36 (SF-36), perceived level of job stress, job satisfaction, working hours, as well as measures for psychological job demands, job control, work-related social support, and over-commitment to work. Both the C-CBI personal burnout scale and work-related burnout scale had high internal consistency and were correlated well with other health, job characteristics, and perception of work measures;furthermore, exploratory factor analysis extracted two empirical factors. However, the two C-CBI scales were highly correlated in the present population and appeared to measure overlapping concepts. Some comments and suggestions were raised for further improvement.