Significant Reduction In Risk Research Articles

Mobile Apps for the Personal Safety of At-Risk Children and Youth: Scoping Review.

Personal safety is a widespread public health issue that affects people of all demographics. There is a growing interest in the use of mobile apps for enhancing personal safety, particularly for children and youth at risk, who are among the most vulnerable groups in society. This study aims to explore what is known about the use of mobile apps for personal safety among children and youth identified to be "at risk." A scoping review following published methodological guidelines was conducted. In total, 5 databases (Scopus, SocINDEX, PsycINFO, Compendex, and Inspec Archive) were searched for relevant scholarly articles published between January 2005 and October 2023. The gray literature was searched using Google and Google Scholar search engines. The results were reported using the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines. For summarizing the features and users' experiences of the apps, a published framework for evaluating the quality of mobile health apps for youth was used. A total of 1986 articles were identified, and 41 (2.1%) were included in the review. Nine personal safety apps were captured and categorized into 4 groups based on the goals of the apps, as follows: dating and sexual violence prevention (n=4, 44% of apps), bullying and school violence prevention (n=2, 22% of apps), self-harm and suicide prevention (n=2, 22% of apps), and homeless youth support (n=1, 11% of apps). Of the 41 articles, 25 (61%) provided data solely on app descriptions and features, while the remaining 16 (39%) articles provided data on app evaluations and descriptions. Outcomes focused on app engagement, users' experiences, and effectiveness. Four articles reported on app use, 3 (75%) of which reported relatively high app use. Data on users' experience were obtained from 13 studies. In general, participants found the app features to be easy to use and useful as educational resources and personal safety tools. Most of the views were positive. Negative perceptions included redundancy of app features and a lack of usefulness. Five apps were evaluated for effectiveness (n=2, 40% dating and sexual violence prevention; n=2, 40% self-harm and suicide prevention; and n=1, 20% bullying and school violence prevention) and were all associated with a statistically significant reduction (P=.001 to .048) in harm or risk to participants at the 95% CI. Although many personal safety apps are available, few studies have specifically evaluated those designed for youth. However, the evidence suggests that mobile safety apps generally appear to be beneficial for reducing harm to at-risk children and youth without any associated adverse events. Recommendations for future research have been made to strengthen the evidence and increase the availability of effective personal safety apps for children and youth.

Efficacy and Safety of Direct Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation and Liver Cirrhosis.

Comparing direct oral anticoagulants (DOACs) and warfarin's efficacy and safety in patients with nonvalvular atrial fibrillation (AF) and liver cirrhosis (LC). Evidence of the pharmacodynamics of DOACs is limited in patients with AF and LC. A retrospective cohort study was conducted in the largest hospital system in Taiwan, involving patients with AF and LC for the years 2012 to 2021. Hazards of thromboembolic events (ischemic stroke, transient ischemic attack, and systemic embolism), intracranial hemorrhage, gastrointestinal, major bleeding, and all-cause mortality were investigated with a new-user, active comparator design. Inverse probability of treatment weighting was applied to balance potential confounders between treatment groups. In total, 478 DOAC users and 247 warfarin users were included. DOACs and warfarin demonstrated similar trends in preventing thromboembolic events, namely ischemic stroke [adjusted hazard ratio (aHR), 1.05 (95% CI: 0.42-2.61)], transient ischemic attack [aHR, 1.36 (95% CI: 0.18-10.31)], and systemic embolism [aHR, 0.49 (95% CI: 0.14-1.70)]. DOAC use was associated with a similar risk of intracranial hemorrhage [aHR, 0.65 (95% CI: 0.26-1.59)] and gastrointestinal bleeding [aHR, 0.64 (95% CI: 0.39-1.03)], a decreased risk of major bleeding [aHR, 0.64 (95% CI: 0.42-0.99)], and a reduction in mortality [aHR, 0.73 (95% CI: 0.54-0.99)]. DOAC users exhibited a significant reduction in major bleeding risk in patients with Child-Pugh class A (aHR, 0.48; 95% CI: 0.33-0.70). DOACs showed potential safety advantages over warfarin for patients with nonvalvular AF and LC, particularly in reducing major bleeding risk in those with Child-Pugh class A.

Smoking Cessation and Incident Cardiovascular Disease

The association between smoking cessation and cardiovascular disease (CVD) risk in relation to cumulative smoking exposure remains poorly understood. To evaluate the associations among smoking cessation, lifetime smoking burden, and CVD risk according to the number of years elapsed after smoking cessation. This retrospective cohort study of the Korean National Health Insurance Service database investigated smoking duration and intensity between January 2006 and December 2008. Participants were categorized by self-reported smoking habits as current, ex-, or never-smokers. Smoking records were updated every 2 years until December 2019, with participants whose smoking status changed or whose smoking status was unclear excluded. Data analysis was performed between June and December 2022. Time-updated self-reported smoking status, years since quitting, and cumulative smoking amount (pack-years [PY]). The primary outcome was incidence and hazard ratio of CVD (composite of cardiovascular death, myocardial infarction, stroke, and heart failure). Overall, 5 391 231 participants (39.9% male; mean [SD] age, 45.8 [14.7] years; 853 756 [15.8%] current smokers, 104 604 [1.9%] ex-smokers, and 4 432 871 [82.2%] never smokers) were followed up for a mean (SD) of 4.2 (4.4) years. The median (IQR) baseline cumulative smoking amounts were 14.0 (7.5-20.0) PY in current smokers and 10.5 (5.3-20.0) PY in ex-smokers. The median (IQR) duration of smoking cessation was 4 (2-8) years for ex-smokers. Regardless of continued smoking, a dose-dependent association was evident between smoking and incident CVD. Compared with current smokers, ex-smokers with a lifetime smoking burden of less than 8 PY (light ex-smokers) experienced a significant reduction in CVD risk within 10 years of cessation, with a CVD risk similar to that of never-smokers. Conversely, ex-smokers with at least 8 PY (heavy ex-smokers) exhibited a slower decline in CVD risk than light ex-smokers, requiring more than 25 years for the residual CVD risk to disappear. In this cohort study, smoking and CVD risk exhibited a dose-dependent association, with light ex-smokers having a CVD risk similar to that of never-smokers relatively soon after smoking cessation. For heavy ex-smokers, greater than 25 years might be required for the residual CVD risk to align with that of never-smokers.

Construction and Validation of a Prognostic Prediction Model for Gastric Mucinous Adenocarcinoma Based on the SEER Database

This study focused on the development and validation of a prognostic model to predict overall survival (OS) in patients with gastric mucinous adenocarcinoma (GMA), utilizing data from the SEER database. A cohort of 537 GMA patients was analyzed to identify factors affecting survival, using both univariate and multivariate Cox regression analyses on demographic and clinicopathological variables. The analysis led to the creation of a nomogram model. Findings revealed that TNM staging and the administration of radiotherapy or chemotherapy were significant factors impacting survival outcomes. Specifically, patients at stages T4, N3, and M1 faced a notably higher mortality risk, while those who received radiotherapy and chemotherapy experienced a significant reduction in mortality risk. The model's performance, as indicated by C-indices of 0.73 in the training set and 0.66 in the validation set, suggests robust predictive capability. The area under the curve (AUC) analysis confirmed high accuracy in predicting 1-year, 3-year, and 5-year survival rates, and calibration curves displayed strong agreement between predicted and actual outcomes. Decision curve analysis (DCA) demonstrated that the model exhibited significant clinical utility across various thresholds. Overall, this study presents a reliable prognostic tool for individualized risk stratification and clinical treatment in GMA patients. Future work should focus on enhancing the model by incorporating molecular biological data to increase its predictive accuracy and applicability.

Long-Term Benefits and Safety of Statins in Patients with Kidney Failure: A Target Trial Emulation Study.

Patients with kidney failure are at elevated risk of cardiovascular diseases. Although statins were commonly used to mitigate cardiovascular disease risk among the population with high risk, the evidence for initiating statin therapy among patients with kidney failure remains inconclusive. This study aimed to investigate the long-term benefits and risks associated with statin therapy in patients with kidney failure. Using territory-wide public electronic health records in Hong Kong, 3,019 statin-eligible individuals with kidney failure and elevated LDL cholesterol ≥ 100 mg/dL from Jan 2008 to Dec 2015 were included for analysis. The framework of target trial emulation was adopted to investigate the risk of the major cardiovascular diseases (i.e., a composite of myocardial infarction, heart failure and stroke), all-cause mortality, as well as the major adverse events (i.e., myopathies and liver dysfunction) between statin initiators and statin non-initiators. The pooled logistic model was used to obtain the hazard ratio (HRs) for the outcomes of interest in both intention-to-treat (ITT) analysis and per-protocol (PP) analysis. Significant risk reduction associated with statin therapy (HR [95%CI]) was observed for major cardiovascular diseases (ITT: 0.78 [0.62, 0.98]; PP: 0.66 [0.50, 0.87]) and all-cause mortality (ITT: 0.80 [0.68, 0.95]; PP: 0.60 [0.48, 0.76]). The standardised 5-year and 10-year absolute risk reduction in per-protocol analysis was 7% (3%, 11%) and 11% (4%, 18%), respectively. No significant risks for the major adverse events were observed. Statin therapy was associated with lower risks of cardiovascular diseases and all-cause mortality in patients with kidney failure without a higher risk of major adverse events.

The impact of daily step count with mobile health apps on clinical outcomes among general population

Abstract Background/Introduction Numerous studies have investigated the correlation between daily step count and the reduction of all-cause mortality and cardiovascular events. However, the optimal daily step count for the general population remains controversial. Purpose This study aims to assess cardiovascular risk based on individual step counts using a large cohort that includes step count data from mHealth Apps (Kencom), health checkups databases, and Japanese insurance claims databases. Methods We analyzed data from 85,204 users registered with Kencom between January 2016 and September 2021. The mean step count during one year before and after baseline data collection was used to define each individual's step count. We divided participants into low (N=45,539) and high (N=39,665) step count groups based on their mean step counts. Additionally, we categorized users into five groups based on their step counts (<4000; 4000-5999; 6000-7999; 8000-9999; and ≥10000) to evaluate cardiovascular events. The primary outcome was the occurrence of cardiovascular events, including myocardial infarction, stroke, angina pectoris, heart failure, and atrial fibrillation, as classified by the International Classification of Diseases and Related Health Problems, 10th Revision (ICD-10). The cumulative incidence was estimated over 5 years. Results The high step count group was generally younger and predominantly male. No significant differences in cardiovascular risk factors such as hypertension, dyslipidemia, diabetes mellitus, and current smoking status were found between the two groups. Stratifying baseline characteristics by step count revealed significant differences among the five groups, with the exception of sex. The cumulative incidence of cardiovascular events was significantly lower in the high step count group compared to the low step count group (6.5% vs. 7.5%, log-rank P=0.005, Figure 1). After adjusting for confounding factors, the risk reduction of the high step count group remained significant (HR: 0.92, 95% CI: 0.87-0.98, P=0.005). Among the five step count groups, the incidence of primary outcome significantly differed, with only Group 5 (≥10000 steps) showing a significant reduction in the risk of cardiovascular events compared to Group 1 (<4000 steps) after adjustment (HR: 0.87, 95% CI: 0.77-0.99, P=0.03). Subgroup analyses based on sex indicated that the risk reduction was significant in males in Group 5 but not in females. Conclusion The risk of cardiovascular events was higher in the low step count group compared to the high step count group. After adjusting for confounders, only the highest step count group (≥10,000 steps/day) showed a significant reduction in cardiovascular event risk compared to the lowest step count group.

The comparison of short-term dual antiplatelet therapy versus standard dual antiplatelet therapy in elderly patients with coronary artery disease who underwent percutaneous coronary intervention

Abstract Introduction Elderly patients are likely to have more underlying risk factors for bleeding and the bleeding risk increases with age although dual anti-platelet therapy (DAPT) is mandatory for patients who underwent percutaneous coronary intervention (PCI) for prevention of ischemic events. Therefore, elderly patients aged 75 or older are included as minor criteria for high bleeding risk, as defined by the Academic Research Consortium for High Bleeding Risk criteria. However, only limited data have been investigated of optimal duration of DAPT for patients aged 75 or older. Purpose The aim of this study is to evaluate optimal DAPT duration for elderly patients aged 75 and older. Methods We selected 1,571 patients aged 75 and older with coronary artery disease (CAD) from the pooled database among the 5 randomized controlled trials related to DAPT duration after PCI. DAPT was consisted of clopidogrel or ticagrelor in addition to aspirin. Short-term DAPT duration was defined as 1 to 3months, and standard DAPT duration was defined as 6 to 12months after PCI. Primary outcomes were net clinical adverse outcomes (NACE), composite of major cardiovascular and cerebrovascular adverse outcomes (MACCE) and TIMI major bleeding at 1 year. The inversed probability of treatment weighting (IPTW) analysis was performed to minimize selection bias effects of pooled database. Results The NACE was not significantly different between the short-term DAPT group (3.9%) and standard DAPT group (7.6%) (HR: 0.69, 95% CI: 0.46-1.04; p=0.076) (Figure A). Moreover, MACCE was not different in both groups. However, the significant reduction of bleeding risk was observed in short-term DAPT group (1.4%) than standard DAPT group (3.4%) (hazard ratio (HR): 0.40, 95% confidential interval (CI): 0.19-0.83; p=0.015) (Figure B). These results were consistent after multivariable Cox regression analysis and IPTW analysis. Conclusions Short-term DAPT duration (1 to 3months) was found to be superior to standard DAPT duration (6 to 12months) in terms of bleeding outcomes without the increased ischemic outcomes in patients aged 75 or older with CAD who underwent PCI.

Favorable impact of FFRCT on myocardial revascularization outcomes: results from an observational real-world registry

Abstract Background Based on excellent clinical outcomes data, coronary computed tomography angiography (CCTA)-derived fractional flow reserve (FFRCT) is endorsed by guidelines to diagnose obstructive coronary artery disease (OCAD)(1). Dedicated outcome analyses in revascularized patients are essential to assess the additional value of FFRCT in revascularization. Purpose To assess the impact of FFRCT use on the postprocedural myocardial injury (PMI) and long-term outcomes of patients with OCAD undergoing myocardial revascularization. Methods Patients with suspected OCAD on CCTA (at least one stenosis of >50% in any vessel) were included from a 2013-2021 tertiary hospital registry. Propensity score adjusted Cox- regression and logistic regression analysis were used to assess the impact of FFRCT on the outcomes of OCAD patients post-revascularization. PMI was defined as cardiac troponin (cTn)>5 times the 99th percentile URL for percutaneous coronary intervention (PCI) and cTn>10 times the 99th percentile URL for coronary artery bypass graft (CABG) (2). Major adverse cardiovascular events (MACE) comprised all – cause mortality, acute myocardial infarction (AMI), stroke, hospitalization for heart failure (HHF) and new revascularization. Results From a registry of 7541 patients, suspected CCTA - derived OCAD was reported in 1601 cases. 559 OCAD patients were revascularized: 386(69.05%) by PCI, 166(29.7%) by CABG and 7(1.25%) by PCI and CABG. FFRCT was performed in 252(45.1%) patients. During a follow-up of 4.4±2.2 years, MACE occurred in 137(24.5%) patients: 43(7.7%) died, 21(3.8%) patients were hospitalized for AMI, 14(2.5%) patients had a stroke, 12 (2.1%) patients had HHF and 77(13.8%) patients had a new revascularization. Survival analysis indicated significant differences in MACE and all-cause mortality–rates between FFRCT use and no FFRCT use (log- rank p = 0.033 and 0.004, Fig 1). Multivariable propensity–adjusted Cox–regression analysis showed a non–significant trend towards reduced MACE risk by using FFRCT (HR 0.736, 95% CI 0.513-1.055, P=0.095) and a significant reduction in all-cause mortality risk (HR 0.476, 95% CI 0.230–0.985, P=0.046). Sub-analysis in the PCI and CABG groups showed no significant association between FFRCT and MACE. Among the 477 patients with available cTn values, 203 (42.5%) had PMI. In the CABG group, FFRCT use correlated with low PMI incidence (5.3% vs. 15.6%, p=0.044). However, multivariable Cox regression analysis revealed no significant association between FFRCT use and PMI(Fig 2). Conclusion This observational designed study reveals for the first time that FFRCT reduces post-myocardial revascularization MACE, primarily driven by reduced all-cause mortality. No clear reduction of PMI was observed suggesting that FFRCT value extends beyond procedural enhancements. Although derived from a large real-world registry, these promising observations need to be confirmed by randomized studies.Figure 1Figure 2

A Review of Lifestyle Interventions in Weight Loss Programs for Community-Based Psychiatric Patients

Abstract Background Psychiatric patients face aggravated physical health issues and reduced life expectancy, primarily due to premature cardiovascular diseases. The intricate relationship between lifestyle factors, illness, and psychotropic medications contributes to this phenomenon. The focus of this research is to evaluate weight management interventions for individuals with Severe Mental Disorders through a comprehensive scoping review, focusing on diverse study designs, outcomes, and their clinical implications. Methods 20 studies were analyzed to understand the effectiveness of interventions and characteristics, such as duration, delivery, and professional involvement. Assessment criteria included weight modifications, BMI changes, and metabolic measures like blood pressure and lipid profiles. Results The total number of participants included in the 20 studies evaluated was 3886. All trials included individuals of all genders. The studies included patients with a weighted mean age of 44.37 (SD = 4.72) and a mean BMI of 34.7 kg/m2 (SD = 3.56). Varied interventions, mostly conducted in the US, showed promising weight reduction and cardiovascular risk management results among psychiatric patients. However, disparate methods used in the studies hindered the evaluation of outcomes. The studies which yielded more interesting results included Gaughran F. et al, 2017 who showed improvements in HDL cholesterol and metabolic indicators, (HR 0.085; 95% CI:0.007-0.16), and Bartels S. et al, 2015 who reported that 51% of participants achieved clinically significant reduction in overall cardiovascular risk. Conclusions Although interventions displayed potential benefits for beneficiaries, the lack of standardized protocols and non-uniform endpoints poses challenges in effectively addressing weight-related concerns in psychiatric patients. Clear guidelines and standardized assessments are necessary to implement psychiatric patients’ weight management interventions. Key messages • The health issues and reduced life expectancy of psychiatric patients is a major health burden. The mean BMI of 34.7 kg/m2, indicating a prevalence of Obese individuals needs to be addressed. • Psychotropic medications are associated with increase in weight. More effort in increasing awareness and including mandatory nutritional educational classes when prescribing these drugs is needed.

The effects of angiotensin receptor-neprilysin inhibitors on clinical outcomes in heart failure with mildly reduced or preserved ejection fraction: real-world evidence from the CCA Database-HF Center

Abstract Background Recent clinical trials have demonstrated the potential efficacy and safety of angiotensin receptor-neprilysin inhibitors (ARNI) in patients with heart failure (HF) with mildly reduced or preserved ejection fraction. Nevertheless, the generalizability of these findings in real-world clinical settings remains to be determined. We aimed to compare the real-world effectiveness of ARNI versus angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB)on clinical outcomes in HF patients with mildly reduced or preserved ejection fraction. Methods Patient-level data was derived from the China Cardiovascular Association Database-HF Center Registry. We included exclusively a subpopulation of HF patients with left ventricular ejection fraction (LVEF) >40% and comorbid with hypertension. Patients prescripted with ARNI at discharge and sustaining to ARNI therapy during follow-up were categorized as the ARNI group, while those maintaining the usage of ACEI/ARB after discharge were designated as the ACEI/ARB group. In complete cases, the primary endpoint of all-cause mortality at one year was assessed by the 1:1 propensity score matching (PSM) method. Results In all HF patients with LVEF >40% comorbid with hypertension, the usage of ARNI has increased from 0.9% in 2017 to 37.2% in 2021. A total of 3348 patients in the ARNI group and 7688 patients in the ACEI/ARB group were identified for comparative effectiveness. After 1:1 PSM, 5482 patients were included in the primary analysis, with 2741 patients in each treatment arm. The proportion of patients receiving higher dosages of ARNI (200mg/d and 400mg/d) was 20.9%, 26.6%, 29.2%, and 30.3% at discharge, 1-month, 3-month, and 1-year, respectively. Over the 1-year follow-up, ARNI was associated with a 20% relative reduction in all-cause death compared to the ACEI/ARB therapy (10.5% vs. 12.9%, adjusted hazard ratio [HR], 0.80 [95% CI, 0.69-0.94], P=0.005). The absolute risk difference in all-cause death between ARNI and ACEI/ARB arms was 2.88 per 100 patient-years (incidence rate difference, -2.88 [95% CI, -4.86 to -0.9]). Cardiovascular death also tended to decrease in the ARNI group but with missed statistical significance (4.5% vs. 4.9%, adjusted HR, 0.89 [95% CI, 0.70-1.14], P=0.373). Treatment benefits were more significant in those with LVEF between 40-50% (adjusted HR, 0.62 [95% CI, 0.48-0.79]), 50-60% (adjusted HR, 0.85 [95% CI, 0.68-1.06]), but not observed in HF patients with LVEF>60% (adjusted HR, 1.80 [95% CI, 1.08-2.98]; Pinteraction<0.001). Conclusion In real-world clinical settings, treatment with ARNI was associated with a significant relative risk reduction in all-cause mortality compared with ACEI/ARB in HF patients with mildly reduced or preserved LVEF. The cardiovascular benefit was concentrated in patients with LVEF ≤60%.

Dynamic recommendation for anticoagulant treatment in patients with atrial fibrillation using deep reinforcement learning method

Abstract Background Recent evidence suggests that the guideline-directed anticoagulant therapy for atrial fibrillation (AF) remains controversial. Widely-used CHA2DS2-VASc score is solely based on limited traditional cardiovascular risk factors, omitting AF characteristics and other markers of thromboembolic risk. A more efficient, safer and more personalized anticoagulant approach is warranted. Purpose To develop a data-driven deep reinforcement learning (DRL) model for guiding dynamic anticoagulant treatment in AF patients to improve cardiovascular outcomes. Methods Participants of this study were enrolled from the multicentred China Atrial Fibrillation (China-AF) Registry between August 2011 and December 2022, who were with regular follow-up every 6 months. We excluded patients on warfarin at baseline due to its declining usage trend in non-valvular AF patients in China. The DRL model was trained in 70% randomly selected patients for optimal dynamic decision-making, and then subsequently tested in the remaining 30%. Data of sociodemographic characteristics, AF characteristics, medical history, lifestyle factors, laboratory examination, and medications were input for model training. Concordance rate between DRL model’s recommendations and physicians’ actual decisions of non-vitamin-K-antagonist oral anticoagulant (NOAC) prescription among all visits before censoring was calculated for each patient. Primary outcome was the composite of cardiovascular death, ischemic stroke, transient ischemic attack or systemic embolism (SSE), and major bleeding. Shapley additive explanation analysis ranked the most important factors affecting decision-making of the DRL model. Results A total of 20068 patients (mean age: 63.0±12.0 years; 36.2% female) were randomly divided into a training cohort of 14050 patients and a testing cohort of 6018 patients. The model’s NOAC recommendations were mostly affected by age, prior NOAC prescription, body mass index, hypertension history and prior statin prescription (Figure 1). Patients with concordance rates of 50.1%-75% and 75.1%-100% had significant risk reductions for the primary outcome (adjusted HR =0.63; 95% CI, 0.46-0.85; P = 0.003 and adjusted HR =0.59; 95% CI, 0.46-0.75; P <0.001, respectively), compared to those with a concordance rate of 0-25%. Similar results were observed for all-cause death, cardiovascular death and SSE outcomes, that patients with the highest concordance rate had a significant lower risk, compared to those with the lowest concordance rate. There was a nonsignificant but similar trend with regard to major bleeding events (Figure 2). Conclusions This modelling study suggests that a data-driven DRL model might provide more efficient, safer and more personalized anticoagulant suggestions, potentially assisting physicians in clinical practice.

Modern heart failure treatment is superior to conventional treatment across the left ventricular ejection spectrum: Real-life data from the Swedish Heart Failure Registry 2013-2020

Abstract Background Heart failure (HF) is a clinical syndrome characterized by high mortality and morbidity. In 2016, Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), was recommended as a new treatment option for HF in patients with HFrEF. In the 2021 European Society of Cardiology guidelines for treatment of HFrEF patients Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were introduced because they demonstrated significantly reduced HF events or cardiovascular (CV) mortality. Since ARNI and SGLT2i were introduced to treat HF, its therapeutic regimen has modernized from previous treatment with beta-blocker (BB) and angiotensin-converting enzyme inhibitor (ACEi)/angiotensin II receptor blocker (ARB) with mineralocorticoid receptor antagonist (MRA) as added-on in HF with reduced ejection fraction (HFrEF). Purpose This study is aimed to compare effectiveness of modern therapy including ARNI and SGLT2i with conventional heart failure treatment. Conventional HF treatment includes (BB, ACEi/ARB, with or without MRA) and modern heart failure treatment (BB, ACEi/ARB, MRA, SGLT2i or BB, ARNI, MRA with/without SGLT2i) in real-world. Methods This observational study (2013-2020), using the Swedish HF Registry, involved 20,849 HF patients. Patients received either conventional (BB, ACEi/ARB, with/without MRA, n=20,140) or modern (BB, ACEi/ARB, MRA, SGLT2i or BB, ARNI, MRA with/without SGLT2i, n=709) treatment at the index visit. The endpoints were all-cause and cardiovascular (CV) mortality. Results Modern HF therapy was associated with a significant 28% reduction in all-cause mortality compared to conventional HF treatment (adjusted HR [aHR]: 0.72 (95% CI 0.54 - 0.96), p=0.024), and had 33% reduced all-cause mortality (aHR: 0.67 (95% CI 0.48 - 0.94), p=0.019) within 2 years of index registration. Similarly, modern HF therapy was associated with a significant 62% reduction in CV mortality compared to conventional HF treatment (aHR: 0.38 (95% CI 0.21 - 0.68), p=0.0013). In addition, we found a 58% reduced CV mortality (aHR 0.42 (95% CI 0.22 - 0.79), p=0.0067) within 2 years of index registration. In the propensity score 1:1 matched cohort in which ARNI was included in the matching procedure, i.e., no ARNI was used in any of the two treatment groups and the effect of SGLT2i was the target assessment. The results were associated with a statistically significant risk reduction of 42% in all-cause mortality in the modern HF treatment group compared to the conventional treatment group (aHR: 0.58 (95% CI 0.36 - 0.94), p=0.028), and a 49% (aHR: 0.51 (95% CI 0.29 - 0.89), p=0.018) risk reduction within 2 years of index registration. Conclusion This study demonstrates that modern HF therapy in a real-world Swedish HF population is associated with a statistically significant risk reduction in all-cause and CV mortality, regardless of EF, sex, age, eGFR, and etiology of HF compared to conventional HF therapy.Central Illustration

Real-world clinical and economic outcomes from rapid start antiretroviral therapy in HIV: systematic review and meta-analysis.

We aimed to synthesize clinical and economic outcomes of rapid start versus non-rapid antiretroviral therapy (ART) in people with HIV (PWH) in real-world settings. A search was conducted in PubMed, Embase, Web of Science, and ProQuest from January 2017 to January 2023, supplementing a previous search by Ford et.al, 2018. Observational studies investigating clinical or economic outcomes of rapid start ART versus non-rapid ART in PWH were included. Clinical outcomes were mortality, loss-to-follow-up (LTFU), and viral suppression. Economic outcomes were Incremental cost-effectiveness ratio (ICER) values and per patient per month (PPPM) costs. Meta-analyses using random-effects models were performed for clinical outcomes, while qualitative syntheses were conducted for economic outcomes. The quality of clinical and economic studies was assessed. Sixty-two studies were included. The pooled adjusted risk ratio (aRR) for mortality demonstrated a significant reduction in risk of mortality among participants who received rapid start ART compared to non-rapid ART (0.80, 95%CI, 0.65-0.98). For LTFU at 6 and 12 months, the pooled aRR showed increased LTFU for rapid start ART (1.33, 95%CI, 1.15-1.55 and 1.18, 95%CI, 0.74-1.89 respectively). All cost-effectiveness studies reported cost-saving or cost-effective findings. The PPPM costs of rapid start ART across the first 36 months of treatment were consistently lower than non-rapid ART. Rapid ART is associated with reduced mortality and is cost-effective compared to non-rapid ART in real-world settings. Clinicians and policymakers should consider these findings to facilitate rapid start of ART in PWH. Further research on LTFU in PWH is needed.

The impact of education level on all-cause mortality in patients with atrial fibrillation

The association of socioeconomic status with cardiovascular morbidity and mortality is well known, but data on the influence of education level on mortality in individuals with atrial fibrillation (AF) are scarce. We investigated education level as a predictor of all-cause mortality in patients diagnosed with AF. This retrospective cohort study used a database created from several Swedish nationwide registries to identify all patients hospitalized with a diagnosis of AF hospitalized from 1995 to 2008. Education level was categorized as primary, secondary, and academic. All-cause mortality risk was estimated in subpopulations defined by the Charlson Comorbidity Index and several comorbidities. A total of 272,182 patients (56% male; mean age 72 ± 10 years) were followed for five years. Cox regression models showed a reduction in all-cause mortality risk with increased education level. Hazard ratios (HR) relative to primary education remained significant after stratification and adjustment for several confounders: secondary education HR = 0.88; 95% CI: 0.86–0.89; P < 0.001; academic education HR = 0.70; 95% CI: 0.67–0.72; P < 0.001. Subpopulation analyses confirmed a significant reduction in relative risk with higher education level. Targeted screening and education programs could be effective in reducing mortality in AF patients with fewer years of formal education.

Evaluation of Return to Military Activities after Combining Anterior Cruciate Ligament Reconstruction with Modified Lateral Extra-articular Tenodesis Versus Anterior Cruciate Ligament Reconstruction Alone in Primary Anterior Cruciate Ligament Tear in Soldiers. A Randomized Comparative Study

Abstract Background: This study aimed to assess the clinical result, complications, failure rate, and return to resuming military duty of a single-stage anterior cruciate ligament reconstruction (ACLR) procedure utilizing quadrupled semitendinosus tendon graft joint with modified lateral extra-articular tenodesis (LET). This study evaluates the potential impact of combined modified LET with ACLR versus ACLR alone on the rate of return to high-impact military activities, which we call return to sports (RTSs), and the subsequent rate of the anterior cruciate ligament (ACL) graft failure. Materials and Methods: A total of 198 soldiers with primary ACL tears with a high-grade pivot test (grade 3) were included and randomized using the simple randomized method and divided into two groups. A consecutive cohort of military personnel with an isolated ACL tear undergoing ACLR with modified LET (group A, n = 116) and ACLR alone (group B, n = 82) were analyzed between 2016 and 2021. Both groups were followed up for a minimum of 2 years. Soldiers underwent a survey evaluating knee function (knee injury and osteoarthritis outcome score [KOOS]), RTS criteria (RTS type), symptoms (International Knee Documentation Committee [IKDC] subjective), activity level (Tegner score), and fear of movement (Tampa Scale of Kinesiophobia-11) to assess psychological readiness for sport participation. Results: Among these, a mean age of 32 ± 2.93 years underwent primary ACLR with modified LET (n = 116) or without LET (n = 82) procedure. A total of 31 soldiers (15.6%) experienced ACL graft failure, including 26 (31.7%) reconstructions without LET and 5 (4.3%) with LET. Combined with LET during primary ACLR, it lowered the risk of graft failure by 2.8 times. Multivariable analysis revealed a significant reduction in graft rupture risk (relative risk = 0.325, P = 0.029) associated with LET compared to ACLR alone after adjusting for age, anthropometric factors, and tibial slopes. 105 out of 113 (90.5%) soldiers were able to return to military duty in group A (combined ACLR with modified LET), whereas 51 of 81 (62.9%) of the soldiers who underwent ACLR alone (group B) returned to military duty (P = 0.05). Conclusion: At 24 months postoperatively, combined ACLR plus LET showed a significantly higher RTS rate than ACLR alone. The combined ACLR with the modified LET group also showed a lower failure rate than the ACLR alone group. No marked differences were observed in KOOS sub-scores, IKDCsubjective, and Tegner activity scores.

Role of PCSK9 Inhibitors in Venous Thromboembolism: Current Evidence and Unmet Clinical Needs.

Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have recently emerged as promising therapeutic agents for lowering low-density lipoprotein cholesterol and reducing the risk of cardiovascular events. Moreover, preliminary evidence from randomized controlled trials (RCTs) suggests that PCSK9i may also offer beneficial effects for patients following venous thromboembolism (VTE), with the most significant reductions in risk appearing over time, particularly beyond the first year of treatment. However, there is a lack of randomized controlled data supporting their efficacy and safety in conjunction with standard anticoagulation therapy. This article aims to critically evaluate the existing evidence for the use of PCSK9i as a complementary therapy for VTE risk reduction, while also identifying unmet clinical and research needs and proposing potential strategies to address these knowledge gaps.

Antibiotics for surgical site infections in patients undergoing orthognathic surgery.

PubMed, Embase, Web of Science and Scopus. Randomized Controlled Trials (RCTs) for patients undergoing orthognathic surgery of any type, which evaluated surgical site infections (SSI) in either: long-term (at least 2 days) post-surgical antibiotic dosing versus short term (one day) post-surgical dosing for the same drug; or Orthognathic surgery patients administered a post-surgical single-day antibiotic versus a singular pre-operative dosing of any antibiotic in the post-surgical phase. Singe-arm studies, retrospective studies, unpublished data, studies which were not peer-reviewed, editorials and trials not dealing with patients undergoing orthognathic surgery specifically were not included. Data for the publication year, primary author name, location of the study, antibiotic type, antibiotic protocol with its type, dosing and timing, sample size, protocol of the control group, male gender, age, diagnosis and rates of SSIs were extracted from the included studies. Pooled rates of SSIs were utilized to produce risk ratio (RR). A total of eleven RCTs met the inclusion criteria. As per the meta-analysis, post-orthognathic surgery SSI risk was reduced significantly as a result of long-term prophylactic antibiotic usage when compared to short-term utilization. Further, the meta-analysis demonstrated that there was a significant reduction of SSI risk in patients on a single day prophylactic antibiotic regimen in comparison to those on a single preoperative antibiotic dose. The study observed that long-term (2-7 days) prophylactic antibiotics reduce SSI risk when compared to antibiotic administration over a single day. In turn, it was also found that the latter was of greater benefit over a pre-operative single antibiotic dosage.

Effectiveness of a fixed combination of empagliflozin with metformin in reduction of cardiovascular risk in patients with uncontrolled arterial hypertension and decompensated type 2 diabetes mellitus

Objective is to study the effectiveness of a fixed combination of empagliflozin and metformin in reducing cardiovascular risk in patients with uncontrolled arterial hypertension (AH) and decompensated type 2 diabetes mellitus (DM). Materials and methods. 36 patients with uncontrolled AH and decompensated type 2 diabetes mellitus aged 45 to 60 were examined. Before inclusion in the study, all patients received standard antihypertensive (angiotensin‑converting enzyme (ACE) inhibitor or angiotensin‑II receptor blocker (ARB) in combination with a calcium channel blocker and a thiazide‑like diuretic), glucose‑lowering (metformin) and hypolipidemic (atorvastatin) therapy. However, target levels of blood pressure (BP), glycated haemoglobin (HbA1c) and lipids were not achieved. After the initial examination, all patients were prescribed a fixed combination of empagliflozin and metformin at a dose of 12.5 mg/1000 mg 1—2 times a day, and antihypertensive and hypolipidemic therapy was continued. Re‑examination was carried out after 20 weeks. In the work, a statistical analysis of the obtained data was carried out using standard methods using Microsoft Excel 7.0 and SPSS 19.0 application packages. Results. The transfer of the examined patients from previous ineffective hypoglycemic therapy to a fixed combination of empagliflozin with metformin against the background of standard antihypertensive and hypolipidemic therapy made it possible to achieve the target levels of HbA1c in 69% of patients and target BP levels in 64%. The frequency of reaching target BP levels in the subgroup of patients who received ARB was significantly higher than in the subgroup of patients who received ACE inhibitors. The specified therapy contributed to a significant reduction in body weight, reaching the target levels of low‑density lipoprotein cholesterol (LDL‑C) and non‑high‑density lipoprotein cholesterol (Non‑HDL‑C) in more than a third of patients, and reducing the severity of albuminuria in some patients. The tested therapy, in general, led to reduction in cardiovascular risk and did not cause side effects that could lead to discontinuation of treatment. Conclusions. The fixed combination of empagliflozin with metformin against the background of standard antihypertensive and hypolipidemic therapy in patients with uncontrolled hypertension and decompensated type 2 diabetes mellitus contributed to the achievement in the vast majority of patients of the target levels of HbA1c in the blood and BP levels, reduced body weight, positive changes in lipid metabolism and kidney function, and demonstrated the possibility of a significant reduction in cardiovascular risk. A more pronounced decrease in BP was detected in the case of a fixed combination of empagliflozin and metformin with ARB compared to ACE inhibitors in this category of patients.

Correlation between fruit consumption and 10-year all-cause mortality in patients with dyslipidemia.

Consuming fruit provides health benefits. Reportedly, increased fruit consumption reduces the risks of hypertension and cardiovascular disease. However, existing studies have not clarified the effect of fruit consumption on mortality risk in patients with dyslipidemia. This study aimed to assess the correlation between the consumption of different types of fruits and all-cause mortality in patients with dyslipidemia. A total of 2,184 patients with dyslipidemia were included in this study, and trends in the correlation between the frequency of consumption of different types of fruits and the 10-year all-cause mortality risk in patients with dyslipidemia were analyzed by smoothed curve fitting, Cox regression, and Kaplan-Meier curve analysis. Subgroup analysis and interaction test were applied to analyze the stability of the effect of apple consumption on 10-year all-cause mortality in patients with dyslipidemia. Smoothed curve fitting and Cox regression analyses revealed a significant reduction in the 10-year all-cause mortality risk in patients with dyslipidemia who consumed apples 3-4 times/week (hazard ratio [HR] = 0.61, 95% confidence interval [CI]: 0.43-0.87, p = 0.007) and in those who consumed bananas 3-4 times/week (HR = 0.71, 95% CI: 0.52-0.98, p = 0.039), with a more pronounced effect in patients who consumed both apples and bananas (HR = 0.55, 95% CI: 0.30-0.99, p = 0.045). Other fruits did not exhibit similar effects. Consuming apples or bananas 3-4 times/week significantly improved the 10-year survival rate in patients with dyslipidemia, and the effect was even more profound in patients who consumed both fruits.

The impact of green tax system on idiosyncratic risk: evidence from China’s environmental protection tax law

ABSTRACT China’s enactment of the Environmental Protection Tax (EPT) Law is a pivotal milestone in the transition towards a green tax system; however, its impact on enterprises capital market performance remains unclear. We adopt a difference-in-differences approach to investigate the influence of green taxation on the idiosyncratic risk of listed companies. The findings reveal a significant reduction in idiosyncratic risk for heavily polluting enterprises following the introduction of the EPT Law, thus suggesting that green taxation contributes to firms’ enhanced capital market performance. This effect acts through environmental, social, and governance performance and is more pronounced for firms with a stronger resource base.