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Background Assessing medication adherence is crucial in chronic obstructive pulmonary disease (COPD) management to prevent exacerbations. However, it is unclear whether this association between adherence and exacerbations is influenced by the adherence assessment methods or thresholds used. Electronic healthcare databases are valuable to study exacerbations and adherence in real life. We aimed to systematically review the literature to identify adherence assessment methods and thresholds used in healthcare databases when investigating the association between medication adherence and COPD exacerbations and to meta-analyse the associated effect sizes.Method MEDLINE, Web of Science and Embase were searched for peer-reviewed articles, written in English, published up to 10 October 2022 (PROSPERO: CRD42022363449). Two reviewers independently conducted screening for inclusion and performed data extraction. A qualitative approach described the adherence assessment methods and thresholds used. A quantitative approach (meta-analysis using random effects model) estimated the association between adherence and the risk of COPD exacerbations.Results Eight studies were included in the systematic review of which five studies were included in the meta-analysis. The medication possession ratio (MPR) and the proportion of days covered (PDC) were the adherence assessment methods used and 0.80 was always used as threshold to differentiate good from poor adherence. Adherence and exacerbations were mostly measured over the same time period. Poor adherence (MPR or PDC

ABSTRACT: Objectives: Elderly become more susceptible to lower respiratory tract infections, resulting in antibiotic prescriptions. Immunoglobulins (Ig) play an important role in host defense and protection against infections. Therefore, we aimed to investigate whether lower Ig levels are a risk factor for antibiotic use in the general elderly population. Methods: After exclusion of current antibiotic users, Cox proportional-hazards regression models were performed to investigate the effect of stable serum IgM, IgG and IgA levels on time to first antibiotic prescription within the Rotterdam Study. Regression models were adjusted for age, sex, body mass index, smoking status and diabetes. We introduced quadratic terms and additionally categorized Igs to explore and quantify potential non-linearity of the association. The restricted cubic splines technique was used to plot the natural log of the hazard across Ig level. Results: In total, 8,639 participants were included (mean age 64 years, 57% female, medium follow-up 3.2 years). No significant association between IgM and time to antibiotic prescription was observed. IgG and IgA levels (in g/L) showed a U-shaped relationship with time to antibiotic prescription (linear IgG HR 0.959, 95% CI 0.930–0.989; quadratic IgG² HR 1.002, 95% CI 1.000–1.003; linear IgA HR 0.949, 95% CI 0.910–0.990; quadratic IgA² HR 1.009, 95% CI 1.004–1.013). Conclusion: Both low and high IgG and IgA levels were associated with a higher incidence of antibiotic prescriptions in stable middle-aged and older individuals. Increased awareness for the potential increased infection risk when persons have low or high Ig levels, even within the reference ranges, is needed.

Abstract Background Skin cancer is a leading form of cancer in Belgium. Prevention of skin cancer by community pharmacists can play a role in increasing awareness and promoting sun protection. However, which persons could be reached by community pharmacists for skin cancer awareness in Belgium and whether this increased awareness is associated with increased sun protection and early detection remains unclear. Methods Demographics of approached persons in Flemish community pharmacies during the months of May-June 2022 and the content of the skin cancer counseling were retrieved from the pharmacy database. Sunscreen purchases and dermatologist visits were evaluated up to 180 days after the skin cancer counseling. Results Community pharmacists provided skin cancer counseling to a broad population of visitors (n = 822, 69% females, median age of 59 years Q1-Q3: 44–71 years). During the campaign, 822 visitors received a leaflet with skin cancer prevalence and sunscreen importance. On top of that, 335 visitors (41%) received additional counseling: skin type sensitivity was checked for 198 visitors (24%), typical characteristics of melanoma were discussed with 100 visitors (12%) and 37 visitors (5%) were referred to a physician for further information or concerns regarding a skin spot. Overall, one out of three visitors purchased sunscreen on the day of the counseling (33%, increasing up to 38% after 180 days). Among people under 20 years, this was even higher (51%). Additional counseling increased the likelihood of a dermatologist visit within 180 days (OR = 1.80; 95%CI: 1.12–2.88). Conclusions By providing skin cancer counseling in Belgian community pharmacies, a broad range of citizens was reached and triggered to purchase sunscreen, often on the same day as the counseling. Notably, young people were likely to purchase sunscreen. Citizens receiving additional counseling were more likely to visit a dermatologist within 180 days.

Background The determinants and health outcomes of lung function trajectories in adults among the general population are poorly understood. We aimed to identify and characterise clusters of lung function trajectories in adults aged ≥45 years. Methods Gaussian finite-mixture modelling was applied to baseline and annualised change of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio z-scores in participants of the Rotterdam Study, a prospective population-based cohort study, with repeated spirometry (n=3884; mean±sd age 64.7±8.9 years). Longitudinal outcomes were all-cause mortality, respiratory outcomes (symptoms, COPD (FEV1/FVC

Background Asthma exacerbations reflect disease severity, affect morbidity and mortality, and may lead to declining lung function. Inflammatory endotypes (e.g. T2-high (eosinophilic)) may play a key role in asthma exacerbations. We aimed to assess whether genetic susceptibility underlies asthma exacerbation risk and additionally tested for an interaction between genetic variants and eosinophilia on exacerbation risk. Methods UK Biobank data were used to perform a genome-wide association study of individuals with asthma and at least one exacerbation compared to individuals with asthma and no history of exacerbations. Individuals with asthma were identified using self-reported data, hospitalisation data and general practitioner records. Exacerbations were identified as either asthma-related hospitalisation, general practitioner record of asthma exacerbation or an oral corticosteroid burst prescription. A logistic regression model adjusted for age, sex, smoking status and genetic ancestry via principal components was used to assess the association between genetic variants and asthma exacerbations. We sought replication for suggestive associations (p

Introduction Current treatments for pain in breast cancer survivors (BCSs) are mostly biomedically focused rather than biopsychosocially driven. However, 22% of BCSs with pain are experiencing perceived injustice, which is a known predictor for adverse pain outcomes and opioid prescription due to increased maladaptive pain behaviour. Educational interventions such as pain neuroscience education (PNE) are suggested to target perceived injustice. In addition, motivational interviewing can be an effective behavioural change technique. This trial aims to examine whether perceived injustice-targeted PNE with the integration of motivational interviewing is superior to biomedically focused pain education in reducing pain after 12 months in BCS with perceived injustice and pain. In addition, improvements in quality of life, perceived injustice and opioid use are evaluated, and a cost-effectiveness analysis will finally result in a recommendation concerning the use of perceived injustice-targeted PNE in BCSs with perceived injustice and pain.Methods and analysis This two-arm multicentre randomised controlled trial will recruit female BCS (n=156) with pain and perceived injustice. Participants will be randomly assigned to perceived injustice-targeted PNE or biomedically focused pain education in each centre. Both interventions include an online session, an information leaflet and three one-to-one sessions. The primary outcome (pain), secondary outcomes (quality of life, perceived injustice and outcomes for cost-effectiveness analysis) and explanatory outcomes (pain phenotyping, sleep, fatigue and cognitive-emotional factors) will be assessed at baseline and at 0, 6, 12 and 24 months postintervention using self-reported questionnaires online. Treatment effects over time will be evaluated using linear mixed model analyses. Additionally, a cost-utility analysis will be done from a healthcare payer and societal perspective.Ethics and dissemination The ethical agreement was obtained from the Main Ethics Committee (B.U.N.1432020000068) at the University Hospital Brussels and all other participating hospitals. Study results will be disseminated through presentations, conferences, social media, press and journals.Trial registration number NCT04730154.

Background The prevalence and clinical profile of asthma with airflow obstruction (AO) remain uncertain. We aimed to phenotype AO in population- and clinic-based cohorts.Methods This cross-sectional multicohort study included adults ≥50 years from nine CADSET cohorts with spirometry data (N=69 789). AO was defined as ever diagnosed asthma with pre-BD or post-BD FEV1/FVC 300 cells/µL), although only significant in population-based cohorts. Compared with asthma-only, AO patients were more often men, current smokers, with a lower BMI, had less often obesity and had more often chronic bronchitis. Compared with COPD-only, AO patients were younger, less often current smokers and had less pack-years. In the general population, AO patients had a higher risk of coronary artery disease than asthma-only and COPD-only (OR=2.09 (95% CI 1.26 to 3.47) and OR=1.89 (95% CI 1.10 to 3.24), respectively) and of depression (OR=1.41 (95% CI 1.19 to 1.67)), osteoporosis (OR=2.30 (95% CI 1.43 to 3.72)) and gastro-oesophageal reflux disease (OR=1.68 (95% CI 1.06 to 2.68)) than COPD-only, independent of age, sex, smoking status and BMI.Conclusions AO is a relatively prevalent respiratory phenotype associated with more dyspnoea and a higher risk of coronary artery disease and elevated blood eosinophil counts in the general population compared with both asthma-only and COPD-only.

The aim of the present research is to investigate the development of left and right dislocation in child French through a corpus study of three children until age 2;7 from the corpus of Lyon (Demuth & Tremblay, 2008). We extracted a total of 704 dislocations and analysed their syntactic properties. We show that (i) right dislocations are more frequent than left dislocations and (ii) left dislocations are significantly more complete than right dislocations (fewer omissions of verbs or pronouns). We compare these results to the hypothesis of Freudenthal, Pine, Jones & Gobet (2015, 2016) according to which some properties of child language can be explained by a learning mechanism from the right edge of the sentences from the input. We will show that this hypothesis can explain the general trend found in our data, but it is not sufficient to account for the entire development of dislocation in French.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with variable mortality risk. The aim of our investigation was to validate a simple clinical algorithm for long-term mortality previously proposed by Burgel et al. in 2017. Subjects with COPD from two cohorts, the Swedish PRAXIS study (n = 784, mean age (standard deviation (SD)) 64.0 years (7.5), 42% males) and the Rotterdam Study (n = 735, mean age (SD) 72 years (9.2), 57% males), were included. Five clinical clusters were derived from baseline data on age, body mass index, dyspnoea grade, pulmonary function and comorbidity (cardiovascular disease/diabetes). Cox models were used to study associations with 9-year mortality. The distribution of clinical clusters (1–5) was 29%/45%/8%/6%/12% in the PRAXIS study and 23%/26%/36%/0%/15% in the Rotterdam Study. The cumulative proportion of deaths at the 9-year follow-up was highest in clusters 1 (65%) and 4 (72%), and lowest in cluster 5 (10%) in the PRAXIS study. In the Rotterdam Study, cluster 1 (44%) had the highest cumulative mortality and cluster 5 (5%) the lowest. Compared with cluster 5, the meta-analysed age- and sex-adjusted hazard ratio (95% confidence interval) for cluster 1 was 6.37 (3.94–10.32) and those for clusters 2 and 3 were 2.61 (1.58–4.32) and 3.06 (1.82–5.13), respectively. Burgel’s clinical clusters can be used to predict long-term mortality risk. Clusters 1 and 4 are associated with the poorest prognosis, cluster 5 with the best prognosis and clusters 2 and 3 with intermediate prognosis in two independent cohorts from Sweden and the Netherlands. Supplemental data for this article is available online at https://doi.org/10.1080/15412555.2022.2039608 .

Background: The Global Initiative for Chronic Obstructive Lung Disease 2023 report recommends medication adherence assessment in COPD as an action item. Healthcare databases provide opportunities for objective assessments; however, multiple methods exist. We aimed to systematically review the literature to describe existing methods to assess adherence in COPD in healthcare databases and to evaluate the reporting of influencing variables. Method: We searched MEDLINE, Web of Science and Embase for peer-reviewed articles evaluating adherence to COPD medication in electronic databases, written in English, published up to 11 October 2022 (PROSPERO identifier CRD42022363449). Two reviewers independently conducted screening for inclusion and performed data extraction. Methods to assess initiation (dispensing of medication after prescribing), implementation (extent of use over a specific time period) and/or persistence (time from initiation to discontinuation) were listed descriptively. Each included study was evaluated for reporting variables with an impact on adherence assessment: inpatient stays, drug substitution, dose switching and early refills. Results: 160 studies were included, of which four assessed initiation, 135 implementation and 45 persistence. Overall, one method was used to measure initiation, 43 methods for implementation and seven methods for persistence. Most of the included implementation studies reported medication possession ratio, proportion of days covered and/or an alteration of these methods. Only 11% of the included studies mentioned the potential impact of the evaluated variables. Conclusion: Variations in adherence assessment methods are common. Attention to transparency, reporting of variables with an impact on adherence assessment and rationale for choosing an adherence cut-off or treatment gap is recommended.

Background Sarcopenia is characterised by two major phenotypic components: low handgrip strength (HGS) and appendicular skeletal muscle index (ASMI). Oral corticosteroid (OCS) use is an important medication for acute respiratory exacerbations in patients with COPD and asthma. However, the association of OCS and sarcopenia components in older people is largely unexplored. The aim of this study was to examine the association between OCS use and HGS or ASMI in the general population and explore interactions with chronic airway diseases. Methods From the population-based Rotterdam Study, 5054 participants (age 69.0±8.8 years; 56% females) were included in the cross-sectional analysis and 1324 in the longitudinal analysis. Associations between OCS and muscle strength and mass were analysed using linear regression models adjusted for age, sex, fat %, height, kidney function, smoking and comorbidities. Results At baseline, ever-OCS users had lower handgrip strength (β= −0.48, 95% CI −0.84– −0.12) than never-OCS users, with cumulative frequency (≥10 OCS prescriptions)-dependent effects (β= −1.25, 95% CI −2.16– −0.33). COPD ever-OCS users, but not asthma, had lower handgrip strength (β= −0.98, 95% CI −1.91– −0.06) and lower lean mass (β= −0.14, 95% CI −0.27– −0.01) than never-OCS users. After 5.6 years of follow-up in those free of sarcopenia traits at baseline, COPD ever-OCS users developed lower handgrip strength (β= −1.64, 95% CI −2.87– −0.40) with frequency (β= −3.64, 95% CI −6.57– −0.72) and duration (β= −1.51, 95% CI −2.87– −0.15) association compared to never-OCS users. Conclusions OCS use is associated with a decline in handgrip strength in people with COPD in a cumulative frequency and duration-dependent manner. Routine muscle examination may be necessary for patients with COPD.

Background: Data on non-vitamin K antagonist oral anticoagulant (NOAC) use in patients with atrial fibrillation (AF) and a history of falls are limited. Therefore, we investigated the impact of a history of falls on AF-related outcomes, and the benefit-risk profiles of NOACs in patients with a history of falls. Methods: Using Belgian nationwide data, AF patients initiating anticoagulation between 2013 and 2019 were included. Previous falls that occurred ≤ 1 year before anticoagulant initiation were identified. Results: Among 254,478 AF patients, 18,947 (7.4%) subjects had a history of falls, which was associated with higher risks of all-cause mortality (adjusted hazard ratio (aHR) 1.11, 95%CI (1.06–1.15)), major bleeding (aHR 1.07, 95%CI (1.01–1.14)), intracranial bleeding (aHR 1.30, 95%CI (1.16–1.47)) and new falls (aHR 1.63, 95%CI (1.55–1.71)), but not with thromboembolism. Among subjects with a history of falls, NOACs were associated with lower risks of stroke or systemic embolism (aHR 0.70, 95%CI (0.57–0.87)), ischemic stroke (aHR 0.59, 95%CI (0.45–0.77)) and all-cause mortality (aHR 0.83, 95%CI (0.75–0.92)) compared to vitamin K antagonists (VKAs), while major, intracranial, and gastrointestinal bleeding risks were not significantly different. Major bleeding risks were significantly lower with apixaban (aHR 0.77, 95%CI (0.63–0.94)), but similar with other NOACs compared to VKAs. Apixaban was associated with lower major bleeding risks compared to dabigatran (aHR 0.78, 95%CI (0.62–0.98)), rivaroxaban (aHR 0.78, 95%CI (0.68–0.91)) and edoxaban (aHR 0.74, 95%CI (0.59–0.92)), but mortality risks were higher compared to dabigatran and edoxaban. Conclusions: A history of falls was an independent predictor of bleeding and death. NOACs had better benefit-risk profiles than VKAs in patients with a history of falls, especially apixaban.

Abstract Background Personalized medicine is an emerging field, aiming to improve the safety and efficacy of pharmacotherapy. The field’s implementation in clinical care is steadily increasing. Pharmacogenomics are one example of personalized approaches in the clinic and direct-to-consumer (DTC) pharmacogenomic tests have become publicly available. We aimed to assess public opinion on pharmacogenomic research and testing to foster integration within Belgian health care. Methods A cross-sectional survey was created and disseminated online, focusing on the citizen perspective. Participants’ willingness to engage in pharmacogenomic research was the primary outcome. In addition, their awareness, understanding, expectations and overall acceptance towards pharmacogenomic testing was investigated. Results A total of 156 participants (54.5% aged between 18 and 30 years, 45.5% > 30 years; 73.1% females) completed the survey. Half ever experienced side effects (46.2%) and treatment failure (52.6%). Up to 45.5% (n = 71) were willing to participate in pharmacogenomics research, and the majority (78.8%) were convinced that pharmacogenomic tests could help doctors to prescribe them the right medications. Additionally, 76.3% (n = 118) supported a partial reimbursement of pharmacogenomics tests. A minority (5.1%, n = 8) of participants showed interest in DTC tests, and 15.4% (n = 24) expressed privacy concerns regarding pharmacogenomics testing. Participants preferred their healthcare professionals’ to perform the test and access their data, but refused commercial providers. Conclusion Overall, participants showed a positive attitude towards precision medicine and pharmacogenomics research. Our findings may help guiding future pharmacogenomic implementation initiatives to optimize drug use by using pharmacogenomic information integrated within health care.

Rationale: Research suggests that respiratory and cardiovascular drugs can ameliorate the rate of lung function decline. Objectives: To investigate the impact of respiratory and cardiovascular pharmacotherapy on lung function trajectories in the general population. Methods: Repeated spirometry was performed in the Rotterdam Study, a population-based cohort of adults aged ⩾45 years. Exposure to long-acting β2-agonists (LABAs), long-acting muscarinic antagonists, inhaled corticosteroids (ICS), cardioselective β-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and statins was quantified from pharmacy records to account for therapy adherence. Propensity score matching and multinomial logistic regression were performed to model medication effects on lung function trajectories, which were previously identified on the basis of forced expiratory volume in 1 second and forced vital capacity patterns. Models were also stratified by genetic variation in each drug target. Results: Among 3,783 individuals, 2,974 (78.6%) were classified as normal lung function decliners, 432 (11.4%) as rapid decliners, and 377 (10.0%) as improvers. Exposure to LABA (odds ratio [OR], 1.09 [95% confidence interval (CI), 1.03–1.16] per 10% increase in exposure), ICS (OR, 1.08 [95% CI, 1.02–1.14]), and statins (OR, 1.04 [95% CI, 1.02–1.06]) significantly increased the odds of being an improver compared with a normal decliner. β1-Blocker use was associated with higher odds of being a rapid decliner (OR, 1.04 [95% CI, 1.00–1.09]), which was driven by incident users. Pharmacogenetic analysis suggests that the effects of LABA, ICS, and β1-blockers are dependent on genetic variation in their drug targets. Conclusions: Our study suggests that LABA, ICS, and statins may favorably modulate lung function trajectories in adults, whereas initiation of β1-blockers was associated with rapid lung function decline. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common malignancy among women worldwide, and advances in early detection and treatment have significantly increased survival rates. However, people living beyond breast cancer often suffer from late sequelae, negatively impacting their quality of life. Prehabilitation, focusing on the period prior to surgery, is a unique opportunity to enhance oncology care by preparing patients for the upcoming oncological treatment and rehabilitation. This article provides a clinical perspective on a patient-centered teleprehabilitation program tailored to individuals undergoing primary breast cancer surgery. The proposed multimodal program includes three key components: patient education, stress management, and physical activity promotion. Additionally, motivational interviewing is used to tailor counseling to individual needs. The proposed approach aims to bridge the gap between diagnosis and oncological treatment and provides a holistic preparation for surgery and postoperative rehabilitation in breast cancer patients. The aim of this preparation pertains to improving mental and physical resilience. By integrating current evidence and patient-centered practices, this article highlights the potential for teleprehabilitation to transform clinical care for breast cancer patients, addressing both logistical challenges and holistic well-being. [ABSTRACT FROM AUTHOR]

Introduction Pain is a prevalent side effect seen in breast cancer survivors (BCS). Psychological factors are known role players in pain mechanisms. Both pain and psychological factors contribute to or interact with healthcare use (HCU). However, the association between psychological factors and HCU has never been investigated in BCS with pain, which is the aim of the present study. Methods Belgian BCS with pain (n  = 122) were assessed via the Medical Consumption Questionnaire, the Injustice Experienced Questionnaire, the Pain Catastrophizing Scale, the Pain Vigilance and Awareness Questionnaire, the Brief Illness Perceptions Questionnaire, and the Depression, Anxiety, and Stress Scale. Associations were analyzed with logistic and Poisson regressions. Results Opioid use was related to more catastrophizing and less psychological distress. Psychotropic drug use was related to more psychological distress. Endocrine therapy was related to less vigilance and awareness. Psychological distress was related to all types of healthcare provider (HCP) visits, with psychological distress negatively related to physiotherapy, psychology, and other primary HCP visits, and positively related to visiting a general practitioner or secondary HCP. Catastrophizing was related to more visiting behavior to a primary HCP, except to a general practitioner. Perceived injustice was related to more general practitioner and other primary HCP visits but to fewer psychology visits. Illness perceptions were related only to visiting other primary HCPs. Vigilance and awareness were related to more psychologist and secondary HCP visits. Conclusion Our findings underscore the complex interplay between HCU and psychological factors in BCS with pain. Psychological distress was overall the most important psychological factor related to HCU, whether catastrophizing and perceived injustice were the most relevant related to HCP visits. [ABSTRACT FROM AUTHOR]

Dans des dictionnaires et des études linguistiques, les lexèmes plurifonctionnels justement et exactement sont souvent associés l’un à l’autre au niveau de leur signification. En effet, justement et exactement présentent tous les deux des emplois d’adverbe de manière, d’adverbe focalisateur et d’adverbe de phrase, où leur fonctionnement discursif est similaire. Cependant, au niveau du comportement syntaxique des deux adverbes, la question de leur degré de similarité reste ouverte: à notre connaissance, il n’existe pas de mesure quantitative de la fréquence des lexèmes dans les différentes positions de la phrase ou du tour de parole. Dans la présente étude, nous comblerons cette lacune en analysant la position de justement et exactement aux différents niveaux du discours dans un corpus de français parlé, le CFPP2000. Plus spécifiquement, nous observerons la position des deux lexèmes dans le tour de parole, la fréquence de l’emploi absolu vs non-absolu et la position syntaxique par rapport au groupe verbal à l’intérieur des phrases verbales. Cette analyse nous permettra de montrer que justement et exactement présentent des différences significatives au niveau de leur position syntaxique. Dans une dernière étape, nous démontrerons à l’aide d’une analyse des emplois discursifs de justement et d’exactement que les différences observées sur le plan syntaxique peuvent s’expliquer par des dissemblances au niveau de leurs emplois discursifs, dans la mesure où la position syntaxique de chacun des lexèmes est significativement corrélée avec son emploi discursif. De cette manière, notre étude apporte une nouvelle perspective à l’analyse de la position syntaxique des adverbes plurifonctionnels.

Background: Although non-vitamin K antagonist oral anticoagulants (NOACs) are recommended over vitamin K antagonists (VKAs) in atrial fibrillation (AF) management, direct long-term head-to-head comparisons are lacking. Therefore, their risk-benefit profiles were investigated compared to VKAs and between NOACs.Methods: AF patients initiating anticoagulation between 2013–2019 were identified in Belgian nationwide data. Inverse probability of treatment weighted Cox regression was used to investigate effectiveness and safety outcomes and were additionally stratified by NOAC dose.Results: Among 254,478 AF patients (328,796 person-years of follow-up), NOACs were associated with significantly lower risks of stroke or systemic embolism (stroke/SE) (hazard ratio (HR) 0.68, 95% confidence interval (CI) (0.64–0.72)), all-cause mortality (HR 0.76, 95%CI (0.74–0.79)), major or clinically relevant non-major bleeding (MB/CRNMB) (HR 0.94, 95%CI (0.91–0.98)) and intracranial hemorrhage (HR 0.73, 95%CI (0.66–0.79)), but non-significantly different risks of myocardial infarction, gastrointestinal and urogenital bleeding compared to VKAs. Despite similar stroke/SE risks, dabigatran and apixaban were associated with significantly lower MB/CRNMB risks compared to rivaroxaban (HR 0.86, 95%CI (0.83–0.90); HR 0.86, 95%CI (0.83–0.89), respectively) and edoxaban (HR 0.91, 95%CI (0.83–0.99); HR 0.86, 95%CI (0.81–0.91), respectively), and apixaban with significantly lower major bleeding risks compared to dabigatran (HR 0.86, 95%CI (0.80–0.92)) and edoxaban (HR 0.79, 95%CI (0.72–0.86)). However, higher mortality risks were observed in some risk groups including with apixaban in patients with diabetes or concomitantly using digoxin compared to dabigatran and edoxaban, respectively.Conclusion: NOACs had better long-term risk-benefit profiles than VKAs. While effectiveness was comparable, apixaban was overall associated with a more favorable safety profile followed by dabigatran.