Significant Increase In Risk Research Articles

Combined Methylphenidate and Selective Serotonin Reuptake Inhibitors in Adults With Attention-Deficit/Hyperactivity Disorder.

Depression is a common comorbidity of adult attention-deficit/hyperactivity disorder (ADHD), and the combination of methylphenidate and selective serotonin reuptake inhibitors (SSRIs) is a frequently prescribed treatment. However, there is limited clinical evidence on the safety of this medication combination in adults with ADHD. To evaluate the safety of administering a combination of SSRI and methylphenidate in adults with ADHD and comorbid depression. This cohort study obtained data from a nationwide claims database in South Korea from January 2016 to February 2021. Participants were adults aged 18 years or older with a diagnosis of ADHD and depressive disorder who were prescribed methylphenidate. Comparisons of 4 groups who received prescriptions were conducted: (1) SSRI plus methylphenidate (hereafter, SSRI) group vs methylphenidate-only group and (2) methylphenidate plus fluoxetine (hereafter, fluoxetine) group vs methylphenidate plus escitalopram (hereafter, escitalopram) group (compared to find a preferable treatment option). Data analysis was conducted between July and December 2023. New users of the methylphenidate and SSRI combination among adults with both ADHD and depressive disorder. A total of 17 primary and secondary outcomes, including neuropsychiatric and other events, were assessed, with respiratory tract infection used as a control outcome. Groups were matched at a 1:1 ratio using a propensity score to balance confounders. A Cox proportional hazards regression model was used to calculate hazard ratio (HRs) and 95% CIs. Subgroup analysis by sex and sensitivity analyses in varying epidemiologic settings were conducted. The study included 17 234 adults with ADHD (mean [SD] age at study entry, 29.4 [10.8] years; 9079 females [52.7%]). There was no difference in the risk of outcomes between the methylphenidate-only and SSRI groups, except for a lower risk of headache in the SSRI group (HR, 0.50; 95% CI, 0.24-0.99). In sensitivity analyses of fluoxetine vs escitalopram, the risk of hypertension (HR: 1:n matching, 0.26; 95% CI, 0.08-0.67) and hyperlipidemia (HR: 1:n matching, 0.23; 95% CI, 0.04-0.81) was lower in the fluoxetine group than in the escitalopram group. Results of this study revealed no significant increase in adverse event risk associated with use of SSRI plus methylphenidate vs methylphenidate alone in adults with ADHD and comorbid depression. Instead, the combination was associated with a lower risk of headache.

Screening of the most common cardiometabolic diseases based on risk factor assessment among military personnel

Objective — to assess the prevalence of major cardiometabolic diseases by identifying their risk factors and comparing them with metabolic disorders and stress indicators in military personnel. Materials and methods. The study included 74 male military personnel with an average age of 43.4 [31.4; 50.6] years. Among all the participants, the proportion of individuals with hypertension (HTN) was 51.4%, with dyslipidemia (DLP) — 75.7%, with metabolic­associated steatotic liver disease (MASLD) — 48.6%, and with overweight or obesity — 51.4%. The participants were divided into groups based on the number of cardiometabolic diseases: group 1 (comparison) consisted of military personnel without HTN, DLP, or MASLD (n=14, 18.9%), group 2 — personnel with 1—2 of the above­mentioned cardiometabolic diseases (n=32, 43.2%), and group 3 — military personnel with comorbid pathology, including HTN, DLP, and MASLD (n=28, 37.8%). All participants were assessed for anthropometric profile, traditional clinical and biochemical indicators. Stress indicators included dehydroepiandrosterone sulfate (DHEA­S), cortisol, and oxidative stress marker 8­OH­deoxyguanosine (8­OH­DG), which were measured in the blood using immunoassay methods. Results. Among military personnel with HTN, overweight/obesity was twice as common (p=0.003, χ2=9.110), MASLD was 3.3 times more frequent (p=0.0001, χ2=19.598), and DLP was 1.7 times more frequent (p=0.0001, χ2=15.418). Among military personnel with MASLD, overweight/obesity was observed three times more frequently (p=0.0001, χ2=19.598), and dyslipidemia was 1.6 times more common (p=0.0001, χ2=13.416). Personnel with more cardiometabolic diseases were significantly older (p=0.003). In group 3, 21.4% had a normal BMI, while in group 1, 28.6% were overweight or had obesity (p=0.001). The increase in the number of cardiometabolic diseases between groups was accompanied by a significant reduction in skeletal muscle percentage (p=0.039 for group 1 vs group 2; p=0.001 for group 1 vs group 3; p=0.001 for group 2 vs group 3). Military personnel in group 3 had significantly higher BMI, waist circumference (WC), total fat percentage, and lower skeletal muscle percentage compared to groups 1 and 2 (p=0.001 for all comparisons). The highest levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), uric acid (UA), and the lowest AST/ALT ratio were observed in group 3 compared to group 1 (p=0.002; p=0.0001; p=0.001; p=0.0001) and group 2 (p=0.0001; p=0.0001; p=0.0001; p=0.0001), respectively. Alkaline phosphatase levels were significantly lower in group 3 compared to group 1 (p=0.048). Lipid profile deterioration was observed with an increase in the number of cardiometabolic diseases: total cholesterol (TC), triglycerides (TG), very low­density lipoprotein cholesterol (VLDL­C), and low­density lipoprotein cholesterol (LDL­C) levels were significantly higher in group 3 compared to group 1 (p=0.0001; p=0.0001; p=0.0001; p=0.007) and group 2 (p=0.0001; p=0.024; p=0.002; p=0.005), respectively. In group 2, only TG (p=0.0001) and VLDL­C (p=0.0001) levels were higher compared to group 1. DHEA­S levels were significantly lower in group 3 compared to group 1 (p=0.019), but no differences in cortisol levels were found. 8­OH­DG levels were significantly lower in groups 2 (p=0.003) and 3 (p=0.019) compared to group 1. Correlation analysis revealed that stress hormone levels were inversely associated with WC (p=0.016), AST (p=0.004), ALT (p=0.021), total bilirubin (p=0.033), UA (p=0.002), glycated haemoglobin (HbA1с) (p=0.024), TC (p=0.002), TG (p=0.001), and VLDL­C (p=0.001). Conclusions. Cardiometabolic diseases are highly prevalent among military personnel, and comorbidity is a frequent phenomenon that contributes to a significant increase in cardiovascular risk and highlights the need for optimized preventive and therapeutic strategies. The increase in the number of cardiometabolic diseases is associated with older age, worsened anthropometric status, liver function tests, increased uric acid levels, and deteriorating lipid profile. DHEA­S can be considered a marker of chronic stress in individuals with cardiometabolic comorbidity. Monitoring and timely correction of WC, AST, ALT, total bilirubin, UA, HbA1с, TC, TG, and VLDL­C levels among military personnel are necessary, as these indicators are related to stress and can improve cardiometabolic disease prevention.

Incidence of intraocular inflammation and its risk factors in patients treated with brolucizumab: a nationwide cohort study

This study aimed to evaluate the incidence of clinically significant intraocular inflammation (csIOI) after treatment with intravitreal injection (IVI) of brolucizumab and identify csIOI risk factors. We categorized 60,966 South Korean patients from a nationwide population-based cohort into 4 groups: groups 1 (Ranibizumab), 2 (Aflibercept), 3 (Brolucizumab), and 4 (switched to brolucizumab). We used the Kaplan–Meier method to estimate the cumulative incidence of csIOI in each group and calculated the hazard ratios (HRs) and 95% confidence intervals (CIs). We constructed a multivariate model using forward selection methods to identify risk factors for csIOI. The cumulative incidence of csIOI within 180 days of the index date in groups 1, 2, 3, and 4 was 0.36% (67/18,537), 0.49% (186/37,951), 3.47% (38/1,095), and 3.69% (125/3,383), respectively. Multivariate analysis revealed a significant increase in csIOI risk in groups 3 (HR 11.08, 95% CI 7.42–16.53, P < 0.001) and 4 (HR 10.40, 95% CI 7.67–14.09, P < 0.001). History of retinal vascular occlusion (HR 1.56, 95% CI 1.01–2.40, P = 0.043) significantly increased csIOI risk after brolucizumab IVI treatment; female sex (HR 0.78, 95% CI 0.64–0.96, p = 0.020) and diabetes (HR 0.72, 95% CI 0.58–0.90, p = 0.004) decreased the risk. csIOI incidence was higher after brolucizumab IVI treatment than after ranibizumab and aflibercept IVI treatment. Retinal vein occlusion history, female sex, and diabetes are associated with csIOI after brolucizumab IVI treatment.

Association of four CTLA-4 gene polymorphisms with pemphigus risk: a systematic review, meta-analysis, and meta-regression.

This review aimed to summarize the existing data on the contribution of four single nucleotide polymorphisms (SNPs) in the cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) genes to pemphigus susceptibility. An electronic literature search for eligible studies among those published prior to 30 April 2024 was conducted through the PubMed, EMBASE, Web of Science, and Scopus databases. To minimize publication bias, an additional search was performed via the Google Scholar and Semantic Scholar search engines. Meta-analyses, together with subgroup analyses and meta-regressions, were performed for the following four CTLA-4 SNPs: rs231775, rs5742909, rs3087243, and rs733618. Combined analyses revealed a significant increase in pemphigus risk conferred by the CTLA-4 rs5742909*C and rs733618*C alleles. Conversely, there was no evidence of any significant association between the rs231775*G and rs3087243*G alleles and susceptibility to pemphigus. Subgroup analyses by ethnicity and pemphigus type (vulgaris or foliaceus) and meta-regressions did not reveal any significant difference. This meta-analysis suggested that two of the four investigated CTLA-4 SNPs were significantly associated with increased pemphigus risk.Registration: This review has been registered on PROSPERO: CRD42024550668; available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024550668.

Associations between polychlorinated biphenyls and cancer risk among type 2 diabetes: The modifying effects of lifestyle

A growing percentage of diabetes-related deaths has been attributed to cancer, with environmental factors playing important contributions. Thus, we studied the potential relationship between endocrine disruptors polychlorinated biphenyls (PCBs) and cancer risk in diabetes. We aimed to evaluate the association between serum seven indicator-PCB (PCB-28/52/101/118/138/153/180) levels and incident cancer, and further explore the possible modifying role of lifestyle. A total of 2806 type 2 diabetes mellitus (T2DM) cases were included from the Dongfeng-Tongji cohort at the baseline in 2008 and tracked until December 2018, and 320 incident cancers were identified during about 10-year follow-up. Cox proportional hazards models and competing risk regression models were used to reveal associations of baseline concentrations of PCBs with total cancer and specific cancer, respectively. Lifestyle score was determined by body mass index, waist circumference, physical activity, smoking, alcohol drinking, and diet. Each interquartile range (IQR) increment of non-dioxin-like PCBs (NDL-PCBs) generated an 8%–30% increase in cancer incidence. Individuals in the highest quartile for PCB-52, PCB-101, PCB-138, and lowly chlorinated PCBs had 1.44- to 1.68-fold higher cancer risk compared to those in the lowest quartile. Restricted cubic spline analyses and the quantile g-computation model showed similar results. Significant interactions were found between PCBs and fasting blood glucose or simplified insulin resistance assessment indicators. NDL-PCBs were positively and significantly associated with gastrointestinal cancer and respiratory cancer, especially with liver cancer, colorectal cancer, and lung cancer. Higher PCBs showed a significant increase in total cancer risk among participants with an unhealthy lifestyle, however, no associations were observed in those with a relatively healthy lifestyle (Pinteraction < 0.05). Our findings indicated an increased cancer risk associated with NDL-PCBs, highlighted the role of a healthy lifestyle in potentially reducing adverse impact, and provided preliminary data for environmental and public health interventions to alleviate the risk of cancer among diabetes.

Weathering the Storm: Unravelling the Influence of Climate Change Risk Exposure on Firms’ Human Capital Investment

AbstractBuilding on agency theory, this study examines the impact of climate change risks on corporate investment in human capital as a key factor of production. Using a sample of US listed firms for the period 1989–2017, we find that firms respond to the growing climate risks by enhancing efficiency in human capital investment, primarily through a reduction in over‐hiring, consistent with our conjecture that firms adopt more prudent and efficient recruitment strategies in reaction to higher climate risks. Cross‐sectional analyses suggest that such an improvement in human capital investment decisions is more salient for firms with poor corporate governance, less intellectual capital and facing greater industry competition and less pronounced for firms with more resilient assets against climate change. By exploiting two exogenous events that cause significant increases in climate risk as quasi‐natural experiments, we conduct difference‐in‐differences analyses and find consistent evidence that the firms engage in more efficient human capital investment in response to both the physical and regulatory risks of climate change. Collectively, despite the overwhelming negative impact of climate change, our study reveals that such risks can play a disciplinary role in promoting more efficient managerial decisions on human capital investment.

Impacts of Matrix Metalloproteinase-8 Genotypes, Smoking, Alcohol Drinking, and Helicobacter Pylori Infection on Gastric Cancer.

In gastric cancer (GCa) tissues, mRNA expression of matrix metalloproteinase-8 (MMP-8) is notably reduced compared to healthy tissues. Furthermore, abnormally low or elevated serum levels of MMP-8 have been linked to a significantly poor prognosis. The involvement of MMP-8 genotypes in susceptibility to GCa remains underexplored. We aimed to assess the influence of MMP-8 genotypes on GCa susceptibility and their potential interactions with smoking, alcohol consumption, and Helicobacter pylori (H. pylori) infection. The study utilized polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) to analyze MMP-8 rs11225395, rs34009635, and rs35866072 genotypes in 161 GCa patients and 483 controls. No statistically significant difference was detected in the distribution of genotypic (p for trend=0.3635) or allelic (p=0.1954) frequencies of MMP-8 rs11225395. Under a dominant model, combined CT+TT genotypes showed no association with GCa risk [odds ratio (OR)=0.77, 95% confidence interval (95%CI)=0.54-1.10, p=0.1852]. Similarly, no association was observed for MMP-8 rs34009635 or rs35866072. Importantly, individuals with the MMP-8 rs11225395 CC genotype demonstrated a significant increase in GCa risk when exposed to smoking (OR=4.04, 95%CI=2.28-7.16, p=0.0001), alcohol consumption (OR=2.83, 95%CI=1.64-4.89, p=0.0002), and H. pylori infection (OR=3.53, 95%CI=2.12-5.90, p=0.0001). The findings indicate that individuals carrying the MMP-8 rs11225395 CC genotype have increased susceptibility to GCa, especially when combined with risk factors, such as smoking, alcohol consumption, and H. pylori infection. These results suggest that MMP-8 genotype-based preventive strategies, including lifestyle alterations and targeted infection treatments, may be valuable in mitigating GCa development.

Multi-Scale Integrated Corrosion-Adjusted Seismic Fragility Framework for Critical Infrastructure Resilience

This study presents a novel framework for integrating corrosion effects into critical infrastructure seismic risk assessment, focusing on reinforced concrete (RC) structures. Unlike traditional seismic fragility curves, which often overlook time-dependent degradation such as corrosion, this methodology introduces an approach incorporating corrosion-induced degradation into seismic fragility curves. This framework combines time-dependent corrosion simulation with numerical modeling, using the finite–discrete element method (FDEM) to assess the reduction in structural capacity. These results are used to adjust the seismic fragility curves, capturing the increased vulnerability due to corrosion. A key novelty of this work is the development of a comprehensive risk assessment that merges the corrosion-adjusted fragility curves with seismic hazard data to estimate long-term seismic risk, introducing a cumulative risk ratio to quantify the total risk over the structure’s lifecycle. This framework is demonstrated through a case study of a one-story RC moment frame building, evaluating its seismic risk under various corrosion scenarios and locations. The simulation results showed a good fit, with a 3% to 14% difference between the case study and simulations up to 75 years. This fitness highlights the model’s accuracy in predicting structural degradation due to corrosion. Furthermore, the findings reveal a significant increase in seismic risk, particularly in moderate and intensive corrosion environments, by 59% and 100%, respectively. These insights emphasize the critical importance of incorporating corrosion effects into seismic risk assessments, offering a more accurate and effective strategy to enhance infrastructure resilience throughout its lifecycle.

Dietary inflammatory index and all-cause mortality in adults with COPD: a prospective cohort study from the NHANES 1999-2018.

Chronic inflammation is closely linked to Chronic Obstructive Pulmonary Disease (COPD); however, the impact of the Dietaryq Inflammatory Index (DII) on mortality among COPD patients remains uncertain. To assess the correlation between the DII and all-cause mortality in COPD patients using data from the National Health and Nutrition Examination Survey (NHANES). We conducted a retrospective cohort study on 1,820 COPD patients from the NHANES dataset (1999-2018). The influence of DII on mortality was evaluated using multivariate Cox regression, smoothing spline fitting, and threshold effect analysis. Additionally, Kaplan-Meier survival analysis was performed to compare survival curves among different DII groups. Subgroup analyses and E-values identified sensitive cohorts and assessed unmeasured confounding. Over an average follow-up of 91 months, multivariate Cox regression models revealed a significant positive correlation between DII scores and mortality risk, with each unit increase in DII associated with a 10% higher risk of death (HR: 1.10, 95% CI: 1.03-1.16; P = 0.002). Among the DII tertiles, individuals in the second tertile (T2: 1.23-2.94) experienced a 67% increase in mortality risk compared to those in the lowest tertile (T1: -5.28-1.23) (HR: 1.67, 95% CI: 1.26-2.21; p < 0.001). The third tertile (T3) did not show a statistically significant increase in mortality risk (HR: 1.30, 95% CI: 0.98-1.72; p=0.074). A restricted cubic spline analysis indicated a significant nonlinear association between DII and all-cause mortality (p = 0.021). Threshold effect analysis further revealed that below a DII of 2.19, there was a significant increase in all-cause mortality risk (HR = 1.19, 95% CI: 1.07-1.33; p = 0.002), while at or above this threshold, the risk increase was not statistically significant (HR=0.89, 95% CI: 0.68-1.15; p = 0.380). Kaplan-Meier analysis revealed significant differences in survival curves among DII tertiles (p < 0.001), with the lowest DII tertile showing the highest survival probability. Both subgroup and sensitivity analyses confirmed the robustness of these findings. DII is positively correlated with mortality risk in COPD patients, showing nonlinear characteristics and threshold effects, underscoring its prognostic value.

Foundational model aided automatic high-throughput drug screening using self-controlled cohort study.

Developing medicine from scratch to governmental authorization and detecting adverse drug reactions (ADR) have barely been economical, expeditious, and risk-averse investments. The availability of large-scale observational healthcare databases and the popularity of large language models offer an unparalleled opportunity to enable automatic high-throughput drug screening for both repurposing and pharmacovigilance. To demonstrate a general workflow for automatic high-throughput drug screening with the following advantages: (i) the association of various exposure on diseases can be estimated; (ii) both repurposing and pharmacovigilance are integrated; (iii) accurate exposure length for each prescription is parsed from clinical texts; (iv) intrinsic relationship between drugs and diseases are removed jointly by bioinformatic mapping and large language model - ChatGPT; (v) causal-wise interpretations for incidence rate contrasts are provided. Using a self-controlled cohort study design where subjects serve as their own control group, we tested the intention-to-treat association between medications on the incidence of diseases. Exposure length for each prescription is determined by parsing common dosages in English free text into a structured format. Exposure period starts from initial prescription to treatment discontinuation. A same exposure length preceding initial treatment is the control period. Clinical outcomes and categories are identified using existing phenotyping algorithms. Incident rate ratios (IRR) are tested using uniformly most powerful (UMP) unbiased tests. We assessed 3,444 medications on 276 diseases on 6,613,198 patients from the Clinical Practice Research Datalink (CPRD), an UK primary care electronic health records (EHR) spanning from 1987 to 2018. Due to the built-in selection bias of self-controlled cohort studies, ingredients-disease pairs confounded by deterministic medical relationships are removed by existing map from RxNorm and nonexistent maps by calling ChatGPT. A total of 16,901 drug-disease pairs reveals significant risk reduction, which can be considered as candidates for repurposing, while a total of 11,089 pairs showed significant risk increase, where drug safety might be of a concern instead. This work developed a data-driven, nonparametric, hypothesis generating, and automatic high-throughput workflow, which reveals the potential of natural language processing in pharmacoepidemiology. We demonstrate the paradigm to a large observational health dataset to help discover potential novel therapies and adverse drug effects. The framework of this study can be extended to other observational medical databases.

A meta-analysis of randomized controlled studies examining the effects of sodium-glucose co-transporter-2 inhibitors on peripheral artery disease and risk of amputations.

Sodium-glucose co-transporter-2 inhibitors (SGLT-2is) are used to maintain glycaemic control as well as for their beneficial cardiovascular and renal effects in diabetes patients. However, increased risk of amputation and peripheral artery disease (PAD) have been observed with the use of some SGLT-2is. A meta-analysis was conducted to understand the effect of SGLT-2is on amputation and PAD events using data from randomized controlled trials (RCT). A systematic literature review was conducted using Medline and Central databases for RCTs that involved the administration of SGLT-2is versus placebo/active comparators to diabetic patients. The primary outcome was amputation events and PAD. A random-effects model was used to calculate the pooled odds ratio, and subgroup analyses was performed. A total of 51 RCTs were included in the meta-analysis with data from 97 589 patients. Meta-analysis of the data showed that there was a significant increase in PAD risk (p = 0.04) but no significant increase in amputation risk with SGLT-2i use versus placebo/active comparators (p = 0.43). Subgroup analyses demonstrated no significant difference between SGLT-2i type, duration of treatment or patient risk factors on amputation or PAD incidence. However, length of drug treatment (> 100 weeks) was associated with a significant increase in both PAD and amputation risks in the SGLT-2i treatment groups. The results of the meta-analysis showed no significant association between SGLT-2i use and PAD and amputation risks in diabetic patients when used for shorter treatment durations.

Burden and Risk Factors of Cervical Spine Conditions in Military Aircrew From 1997 to 2015: A Retrospective Cohort Study.

Military aviators may have increased risk of cervical spine injuries because of exposure to supraphysiologic forces and vibration during dynamic flight. Aviator medical attrition impairs mission readiness, decreases operational capabilities, increases overall DoDcosts, and decreases retention of seasoned aviators. This study evaluated incidence and risk factors for cervical spine conditions in U.S. military aviators from 1997 to 2015. The Defense Medical Epidemiological Database was queried for aviators with a diagnosis of cervical spine conditions. Pertinent ICD-9 codes for cervical spine pathology were ascertained from U.S. Army, Air Force, and Naval Air Forces aeromedical references. Negative binomial regressions assessed sex, age, service, aircraft, and year on incidence of conditions. Rates were compared to non-aviator controls. The study was approved by the Institutional Review Board at the Naval Health Research Center (NHRC.2020.0205-NHSR). Incidence rates were 9.78 to 12.57/1,000 person-years for neck pain, 2.04 to 3.89/1,000 person-years for degenerative conditions without neurological involvement, and 0.94 to 1.36/1,000 person-years for degenerative conditions with neurological involvement. Aviation occupation (relative risk [RR] 1.41-2.05), female sex (RR 3.32-7.89), age over 40 (RR 2.39-4.62), and service in the Army or Marine Corps (RR 1.62-2.14) were risk factors. Military aviators had a statistically significant increase in risk of neck pain and medically disqualifying degenerative cervical spine conditions compared to non-aviator controls. Rates of neck pain increased in all aviators over the study epoch. Possible explanations could be related to the operational demands and the increased use of forward helmet-mounted display systems during the study period, a supposition that requires further investigation. There was no significant difference in rates of neck pain or degenerative cervical conditions between aircraft platforms (fighter/bomber, other fixed wing, and rotary wing). Female sex, age over 40 years, and Army/Marine Corps service were the greatest risk factors for neck pain and degenerative cervical spine conditions. Targeted prevention programs and expanded treatment modalities are necessary to reduce aviator attrition and Department of Defense cost burden.

Association Between Oral Anticoagulant Adherence and Serious Clinical Outcomes in Patients With Atrial Fibrillation: A Long-Term Retrospective Cohort Study.

Patients with atrial fibrillation are frequently nonadherent to oral anticoagulants (OACs) prescribed for stroke and systemic embolism (SSE) prevention. We quantified the relationship between OAC adherence and atrial fibrillation clinical outcomes using methods not previously applied to this problem. Retrospective observational cohort study of incident cases of atrial fibrillation from population-based administrative data over 23 years. The exposure of interest was proportion of days covered during 90 days before an event or end of follow-up. Cox proportional hazard models were used to evaluate time to first SSE and the composite of SSE, transient ischemic attack, or death and several secondary outcomes. A total of 44 172 patients were included with median follow-up of 6.7 years. For direct OACs (DOACs), each 10% decrease in adherence was associated with a 14% increased hazard of SSE and 5% increased hazard of SSE, transient ischemic attack, or death. For vitamin K antagonist (VKA) the corresponding increase in SSE hazard was 3%. Receiving DOAC or VKA was associated with primary outcome hazard reduction across most the proportion of days covered spectrum. Differences between VKA and DOAC were statistically significant for all efficacy outcomes and at most adherence levels. Even small reductions in OAC adherence in patients with atrial fibrillation were associated with significant increases in risk of stroke, with greater magnitudes for DOAC than VKA. DOAC recipients may be more vulnerable than VKA recipients to increased risk of stroke and death even with small reductions in adherence. The worsening efficacy outcomes associated with decreasing adherence occurred without the benefit of major bleeding reduction.

Acceleration of the Banking Sector and Economic Growth: Effectiveness of Economic Recovery Strategies Post-Covid-19

The banking sector around the world is under great pressure due to the current state of the Covid-19. This study investigates how Covid-19 impacts systemic risk in the banking sector across all types of banking lines affected by Covid-19. This study found that all banking lines experienced a significant increase in systemic risk among the types of banking that were sampled initially. By using spillover policies, it is also possible to identify institutions that are systemically important. The analysis was performed using Panel Data Regression, SVAR, and FEVD on individual bank data and macroeconomic data. The findings proved that government policies to drive the business cycle and MSME actors in the context of overcoming the impact of Covid-19, have not shown their effectiveness. This is indicated by the negative response of economic growth to the policies that have been issued. On the other hand, the performance of banking financial institutions also contributes to national economic growth. This is indicated by the sensitivity of the bank's internal variables in responding to national economic growth. Likewise, with the response to government policies and macroeconomic conditions. Therefore, there is a need for an acceleration policy in handling the current national economic recovery.Originality/Value: This paper focus on systematic risk in banking during COVID-19, use of advanced econometric techniques, evaluation of government policies, integration of bank performance and macroeconomic growth, and its assessment of policy effectiveness, and its implications for future economic recovery efforts.

A Bayesian network analysis of the probabilistic relationships between metabolically healthy obesity and cardiovascular disease risk under new diagnostic criteria.

The relationship between metabolically healthy obesity (MHO) and cardiovascular disease (CVD) risk remains debated. The critical point may be the lack of consensus on MHO's definition and diagnostic criteria. This study aimed to investigate the association of MHO status with arteriosclerosis-CVD (ASCVD) risk in Chinese under new diagnostic criteria. Participants aged 35-79 in the 2009 China Health and Nutrition Survey cohort were included. The 10-year ASCVD risk was predicted by the prediction for ASCVD risk in China, and participants with a predicted risk of ⩾ 10% were classified into the high-risk group. The Bayesian network (BN) models were constructed to characterize the multivariable probabilistic connections between metabolically obesity phenotypes and ASCVD risk. The 10-year ASCVD risk score and the proportion of individuals at ASCVD high risk were significantly different between metabolically obesity phenotypes (P< 0.001). BN reasoning results showed that MHO individuals were not significantly associated with a 10-year ASCVD risk. Among metabolically unhealthy individuals, the conditional probability of high ASCVD risk increased with the Body Mass Index (BMI), with the conditional probability of high ASCVD risk was 24.63% (95% CI: 22.81-26.55%), 32.97% (95% CI: 30.75-35.27%) and 40.2% (95% CI: 36.64-43.86%) for metabolically unhealthy normal weight (MUNW), metabolically healthy overweight weight (MHOW), and metabolically unhealthy obesity (MUO) group, respectively. Subgroup analysis showed that MHO individuals were at increased risk of CVD compared with metabolically healthy normal weight (MHNW) individuals only in females. These results showed that there was no significant increase in ASCVD risk of MHO phenotype based on the new diagnostic criteria, suggesting that MHO is in a relatively healthy state.

Timing of Direct Oral Anticoagulants Resumption Following Colorectal Endoscopic Submucosal Dissection: A Nationwide Study in Japan.

With the increasing use of direct oral anticoagulants (DOACs), managing these agents around endoscopic submucosal dissection (ESD) is crucial. However, due to the need for a large number of cases, studies examining the timing of resumption are lacking, resulting in varied recommendations across international guidelines. We aimed to perform a comparative study about the resumption timing of DOACs after colorectal ESD using a nationwide database in Japan. We conducted a retrospective cohort study on colorectal ESD using the Diagnosis Procedure Combination database from 2012 to 2023. Patients using anticoagulants other than DOACs were excluded, and only those who resumed DOACs within 3 days were included. From eligible patients, we divided them into early (the day after ESD) and delayed (2 to 3 days after ESD) resumption groups. We used inverse probability of treatment weighting (IPTW) to assess the delayed bleeding and thromboembolic events within 30 days. Delayed bleeding was defined as bleeding requiring endoscopic hemostasis or blood transfusion after ESD. Of 176,139 colorectal ESDs, 3,550 involved DOAC users, with 2,698 (76%) categorized as early resumption and 852 (24%) categorized as delayed resumption groups. After IPTW adjustment, the early resumption group did not significantly increase delayed bleeding compared to the delayed resumption group (OR, 1.05; 95% CI, 0.78-1.42; P = 0.73). However, it significantly reduced the risk of thromboembolic events (OR, 0.45; 95% CI, 0.25-0.82; P < 0.01). Resuming DOACs the day after colorectal ESD was associated with reduced thromboembolic events without significant increase in risk of delayed bleeding.

Role of chronic kidney disease and risk factors in preeclampsia

BackgroundOur goal was to identify what impact chronic kidney disease (CKD) and its associated risk factors, such as body mass index (BMI), diabetes and hypertension, have on preeclampsia and other adverse pregnancy outcomes in the CKD population. MethodsThis was a population-based cohort study of women with CKD who had a pregnancy from 2010 to 2022 (n = 95). At the time of the woman’s pregnancy, data was collected on demographics, clinical measures, BMI, CKD etiology and other renal parameters. Outcomes included preeclampsia, pre-term delivery, and low birth weight. ResultsPre-pregnancy BMI increased over time in patients with CKD, with a median (interquartile range) BMI of 25 (22–29) prior to 2016 and 29 (25–34) after 2016 (p = 0.01). There were significant trends of increasing age at delivery and decreasing pre-pregnancy estimated glomerular filtration rate (eGFR) by delivery year. Preeclampsia affected nearly half of pregnancies in this cohort. In multivariate analyses, BMI and chronic hypertension did not impact the odds of preeclampsia, preterm delivery or low birth weight, though a CKD etiology of diabetes (19/20 with type I diabetes), was associated with a significant increase in preeclampsia risk (odds ratio (OR) 7.41 (95 % CI 2.1–26.1)). Higher pre-pregnancy eGFR was associated with a lower odds of preterm delivery (OR 0.81 (95 % CI 0.67–0.98)) per 10 ml/min/1.73 m2). ConclusionPre-pregnancy BMI significantly increased over time, similar to the general population. While preeclampsia was common in CKD patients, outcomes were associated with eGFR and CKD etiology as opposed to BMI and chronic hypertension.

Efficacy of Prophylactic Cranial Irradiation in Early to Mid-stage Small Cell Lung Cancer Patients in the Era of Magnetic Resonance Imaging

BackgroundRecent advancements in magnetic resonance imaging (MRI) for staging have highlighted the critical question of the need for prophylactic cranial irradiation (PCI) in managing early to mid-stage small cell lung cancer (SCLC). This study assesses the impact of PCI on overall survival (OS) and intracranial control among patients with stage I-IIB SCLC. MethodsData from 148 stage I-IIB SCLC patients treated with thoracic radiation therapy (TRT) at two centers were examined. Patients were categorized based on PCI administration: 63 received PCI, while 85 did not. All underwent pretreatment MRI, achieving at least a partial response to therapy. A 1:1 propensity score matching analysis corrected for potential biases. ResultsPropensity scores were generated to 116 patients, considering patient demographics, disease progression, and treatment methods. Death was included as a competing risk. The 3-year brain metastases (BM) occurrence rate was significantly higher in patients who did not receive PCI (30.0%) compared to those who did (14.8%), however, the difference was not statistically significant (No PCI vs. PCI, hazard ratio [HR]: 2.08, 95% CI [0.93-4.55], P = .07). No significant effect of PCI on OS was observed [PCI vs. No PCI, HR: 0.80, 95% CI (0.45-1.43), P = .45]. A subgroup analysis of stage IIB patients showed a significant increase in BM risk and mortality for those not receiving PCI (No PCI vs. PCI, BM risk HR: 5.85, 95% CI: 1.83-18.87, P = .003; mortality HR: 2.78, 95% CI: 1.14-6.67, P = .02), with less pronounced effects in stages I-IIA. ConclusionWith modern MRI-based screening, PCI may markedly benefit stage IIB SCLC patients by reducing BM and improving OS after initial sensitive treatment. This benefit does not appear to extend to stage I-IIA patients.

Exploring depression risk among breast cancer survivors: A nationwide cohort study in South Korea.

19 Background: With advances in early diagnosis and treatment, the population of breast cancer survivors globally continues to grow. Depression among these survivors poses a significant concern for their long-term survivorship and overall quality of life. This study aims to investigate the incidence of depression among breast cancer survivors and identify associated risk factors. Methods: We used the National Health Insurance Service database of Korea from 2010 to 2016 and examined 59,340 breast cancer survivors and 1:2 age-matched individuals without breast cancer to investigate the incidence of depression. Cox proportional hazards regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI). The risk of depression was assessed based on age, categorizing individuals as under or over 50 years old. We conducted 1-year, 3-year, and 5-year lag sensitivity analysis to demonstrate changes in risk over time. The study identified risk factors for developing depression through multivariable Cox regression, and Kaplan-Meier analysis was conducted to illustrate the incidence probabilities of depression in breast cancer survivors. Results: Breast cancer survivors exhibited a 39% increased risk of depression compared to individuals without breast cancer, and those under the age of 50 years facing higher risk than their older counterparts (HR 1.64, 95% CI 1.58-1.70 and HR 1.23, 95% CI 1.20-1.27, respectively). Chemotherapy (anthracycline and taxane) and endocrine therapy (tamoxifen and aromatase inhibitor) emerged as potential risk factors for depression among breast cancer survivors. Sensitivity analysis revealed a decreasing trend in depression risk over time, particularly among survivors aged older than 50 years. Conclusions: This study highlights a significant increase in depression risk among breast cancer survivors, particularly those under 50 years old. Specific treatments such as chemotherapy and endocrine therapy were identified as potential risk factors. These findings emphasize the necessity for targeted interventions and support strategies to address the heightened risk of depression in breast cancer survivors, ultimately improving their long-term well-being and quality of life.

Effects of ambient heat exposure on risk of all-cause mortality in children younger than 5 years in Africa: a pooled time-series analysis

Reducing child mortality is a Sustainable Development Goal, and climate change constitutes numerous challenges for Africa. Previous research has shown an association between leading causes of child mortality and climate change. However, few studies have examined these effects in detail. We aimed to explore the effects of ambient heat on neonate, post-neonate, and child mortality rates. For this pooled time-series analysis, health data were obtained from the International Network for the Demographic Evaluation of Populations and Their Health (INDEPTH) Health and Demographic Surveillance System. We included data from 29 settlements from 13 countries across Africa, collected via monthly surveys from Jan 1, 1993, to Dec 31, 2016. Climate data were obtained from ERA5, collected from Jan 1, 1991, to Dec 31, 2019. We pooled these data for monthly mean daily maximum wet bulb globe temperature (WBGT) and downscaled to geolocations. Due to data heaping, we pooled our health data on a monthly temporal scale and a spatial scale into six different climate regions (ie, Sahel [ie, Burkina Faso and northern Ghana], Guinea [ie, southern Ghana, Côte d'Ivoire, and Nigeria], Senegal and The Gambia, eastern Africa [ie, Kenya, Malawi, Tanzania, Mozambique, and Uganda], South Africa, and Ethiopia). Our outcomes were neonate (ie, younger than 28 days), post-neonate (ie, aged 28 days to 1 year), and child (ie, older than 1 year and younger than 5 years) mortality. To assess the association between WBGT and monthly all-cause mortality, we used a time-series regression with a quasi-Poisson, polynomial-distributed lag model. Between Jan 1, 1993, and Dec 31, 2016, there were 44 909 deaths in children younger than 5 years across the 29 sites in the 13 African countries: 10 078 neonates, 14 141 post-neonates, and 20 690 children. We observed differences in the association of heat with neonate, post-neonate, and child mortality by study region. For example, for Ethiopia, the relative risk ratio of mortality at the 95th percentile compared with median heat exposure during the study period was 1·14 (95% CI 1·06-1·23) for neonates, 0·99 (0·90-1·07) for post-neonates, and 0·79 (0·73-0·87) for children. Across the whole year, there was a significant increase in the relative risk of increased mortality for children in eastern Africa (relative risk 1·27, 95% CI 1·19-1·36) and Senegal and The Gambia (1·11, 1·04-1·18). Our results show that the influence of extreme heat on mortality risk in children younger than 5 years varies by age group, region, and season. Future research should explore potentially informative ways to measure subtleties of heat stress and the factors contributing to vulnerability. EU Horizons as part of the Heat Indicators for Global Health (HIGH) Horizons project.