Significant Reduction In Risk Research Articles

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.

The Prognosis and Outcomes of Acutely Ill Patients Admitted to “Hospital-at-home” Programs Versus Patients with Similar Attributes Admitted to Internal Hospital Wards

Hospital-at-home programs have shown clinical and economic benefits globally but are still in the early stages in Israel for acute care. This study evaluated hospital-at-home units’ clinical, safety, and economic outcomes compared to internal wards. The study assesses hospital-at-home units’ clinical, safety, and economic outcomes versus internal wards for acutely ill patients. This retrospective matched cohort study assessed the impact of at-home hospitalization on patient survival. Patients admitted from the emergency room to at-home hospitalization were matched 2:1 with patients admitted to internal wards based on demographic and clinical characteristics using propensity score matching. The primary outcome was the rate of readmissions at 30 days. After matching, 645 individuals were included: 215 in the hospital-at-home group and 430 in the control group. Baseline characteristics were well-balanced. After 30 days, 6 individuals in the study group and 38 in the control group had died. The study group’s overall mortality rate was significantly lower (2.79% vs 8.84%, p = .0043). The hazard ratio for the control group compared to the study group was 1.907 (95% CI 1.227-2.963), indicating a 90% increased risk of death. The primary outcome of readmissions at 30 days did not differ significantly between groups. Secondary outcomes showed substantially lower healthcare resource use in the study group. Hospital-at-home units are a safe alternative to internal wards, offering significant mortality risk reduction and lower healthcare resource use. These findings support the feasibility of implementing hospital-at-home units for acute care in Israel.

Prevention of Recurrent Spontaneous Preterm Delivery Using Probiotics (Clostridium butyricum, Enterococcus faecium, and Bacillus subtilis; PPP Trial): Protocol for a Prospective, Single-Arm, Nonblinded, Multicenter Trial

Background The rate of recurrent spontaneous preterm delivery (sPTD) ranges between 27% and 34% and is 22.3% in Japan. Although it currently remains unclear whether probiotics prevent sPTD, retrospective studies recently reported a reduction in the rate of recurrent sPTD with the administration of probiotics including Clostridium spp., which induce regulatory T cells that play an important role in maintaining pregnancy. Objective The objective of this trial is to evaluate the preventative effects of available oral probiotics, including Clostridium butyricum, on recurrent sPTD. Methods This is a prospective, single-arm, nonblinded, multicenter trial in Japan. The sample size required for this trial is 345 pregnant women with a history of sPTD, considering a clinically significant reduction in the relative risk of 30% (risk ratio=0.7). The primary endpoint is the rate of recurrent sPTD at <37 weeks of gestation. The secondary endpoints are the rate of sPTD at <34 weeks of gestation, the rate of recurrent sPTD at <28 weeks of gestation, the ratio of intestinal Clostridium spp. (detected by next-generation sequencing), and bacterial vaginosis (using the Nugent score). Results The trial procedures were approved by the Clinical Research Review Board of Toyama University Hospital (SCR2020008) on March 31, 2021. The trial was registered on the Japan Registry of Clinical Trial website on April 28, 2021. Recruitment began on May 1, 2021, and the trial is estimated to finish on March 31, 2025. Conclusions The findings will clarify the rate of recurrent sPTD following probiotic administration including Clostridium butyricum. Outcomes from this trial will inform clinical practice and guide future randomized controlled trials. Trial Registration Japan Registry of Clinical Trials jRCTs041210014; https://jrct.niph.go.jp/latest-detail/jRCTs041210014 International Registered Report Identifier (IRRID) DERR1-10.2196/59928

Predictors of relapse risk and treatment response in AQP4-IgG positive and seronegative NMOSD: A multicentre study

BackgroundNeuromyelitis optica spectrum disorder (NMOSD) can be categorised into aquaporin-4 antibody (AQP4-IgG) NMOSD or seronegative NMOSD. While our knowledge of AQP4-IgG NMOSD has evolved significantly in the past decade, seronegative...

Optimal Pair Matching Combined with Machine Learning Predicts a Significant Reduction in Myocardial Infarction Risk in African Americans Following Omega-3 Fatty Acid Supplementation.

Conflicting clinical trial results on omega-3 highly unsaturated fatty acids (n-3 HUFA) have prompted uncertainty about their cardioprotective effects. While the VITAL trial found no overall cardiovascular benefit from n-3 HUFA supplementation, its substantial African American (AfAm) enrollment provided a unique opportunity to explore racial differences in response to n-3 HUFA supplementation. The current observational study aimed to simulate randomized clinical trial (RCT) conditions by matching 3766 AfAm and 15,553 non-Hispanic White (NHW) individuals from the VITAL trial utilizing propensity score matching to address the limitations related to differences in confounding variables between the two groups. Within matched groups (3766 AfAm and 3766 NHW), n-3 HUFA supplementation's impact on myocardial infarction (MI), stroke, and cardiovascular disease (CVD) mortality was assessed. A weighted decision tree analysis revealed belonging to the n-3 supplementation group as the most significant predictor of MI among AfAm but not NHW. Further logistic regression using the LASSO method and bootstrap estimation of standard errors indicated n-3 supplementation significantly lowered MI risk in AfAm (OR 0.17, 95% CI [0.048, 0.60]), with no such effect in NHW. This study underscores the critical need for future RCT to explore racial disparities in MI risk associated with n-3 HUFA supplementation and highlights potential causal differences between supplementation health outcomes in AfAm versus NHW populations.

Apolipoprotein A-I Infusions and Cardiovascular Outcomes in Acute Myocardial Infarction According to Baseline LDL-Cholesterol Levels: The AEGIS-II Trial.

In the AEGIS-II trial (NCT03473223), CSL112, a human apolipoprotein A1 derived from plasma that increases cholesterol efflux capacity, did not significantly reduce the risk of the primary endpoint through 90 days versus placebo after acute myocardial infarction (MI). Nevertheless, given the well-established relationship between higher low-density lipoprotein cholesterol (LDL-C) and plaque burden, as well as greater risk reductions seen with PCSK9 inhibitors in patients with baseline LDL-C ≥100 mg/dL on statin therapy, the efficacy of CSL112 may be influenced by baseline LDL-C. Overall, 18,219 patients with acute MI, multivessel coronary artery disease, and additional risk factors were randomized to either four weekly infusions of 6 g CSL112 or placebo. This exploratory post-hoc analysis evaluated cardiovascular outcomes by baseline LDL-C in patients prescribed guideline-directed statin therapy at the time of randomization (n=15,731). As baseline LDL-C increased, risk of the primary endpoint at 90 days lowered in those treated with CSL112 compared with placebo. In patients with LDL-C ≥100 mg/dL at randomization, there was a significant risk reduction of cardiovascular death, MI, or stroke in the CSL112 vs. placebo group at 90, 180, and 365 days (hazard ratio 0.69 [0.53-0.90], 0.71 [0.57-0.88], and 0.78 [0.65-0.93]). In contrast, there was no difference between treatment groups among those with LDL-C <100 mg/dL at baseline. In this population, treatment with CSL112 compared to placebo was associated with a significantly lower risk of recurrent cardiovascular events among patients with a baseline LDL-C ≥100 mg/dL. Further studies need to confirm that CSL112 efficacy is influenced by baseline LDL-C.

Impact of metabolic bariatric surgery on outcomes and the 10-year risk of major adverse cardiovascular events during a 7-year period: a retrospective cohort study.

Metabolic bariatric surgery offers enduring weight reduction and alleviation of obesity-related comorbidities, including dyslipidemia, diabetes, hypertension, and major adverse cardiovascular events (MACE). Long-term data on one-anastomosis gastric bypass (OAGB) and single-anastomosis duodenal-jejunal bypass with sleeve gastrectomy (SADJB-SG) is lacking, necessitating this investigation. In this multicenter prospectively-collected retrospective observational study, 830 adult Taiwanese patients (682 OAGB, 148 SADJB-SG) who underwent surgery from 1 January 2011 to 31 December 2017, were initially identified. Following protocol, 224 patients (177 OAGB, 47 SADJB-SG) with complete follow-up data at various intervals up to 3 years after surgery were included in the final analysis. The study's primary focus is to evaluate the long-term safety, efficacy, and durability of OAGB and SADJB-SG in promoting weight loss and diabetes remission. Additionally, changes in 10-year and lifetime risks of MACE before and 3-year after surgery are assessed using Taiwan MACE risk prediction model and the China-PAR project model. SADJB-SG patients exhibit higher diabetes prevalence, lower BMI, and more severe diabetes compared to OAGB. Both groups demonstrate significant improvements in BMI, diabetes, hypertension, and dyslipidemia three years after surgery, with the most substantial improvements occurring in the second year. The Taiwan MACE risk model reveals a significant reduction in 10-year MACE and stroke risks for both groups. The China-PAR project model indicates a synchronized reduction in atherosclerotic cardiovascular disease 10-year and lifetime risk in both OAGB and SADJB-SG groups. OAGB and SADJB-SG exhibit sustained improvements in weight reduction and obesity-related comorbidities over 3 years after surgery. Notably, both procedures contribute to a substantial reduction in 10-year MACE, stroke, and atherosclerotic cardiovascular disease risks. These findings underscore the efficacy of OAGB and SADJB-SG in the context of metabolic bariatric surgery.

Age and Menopausal Status in Idiopathic Subglottic Stenosis.

To evaluate the impact of age on disease recurrence in idiopathic subglottic stenosis (iSGS) patients. This was a retrospective chart review of iSGS patients treated with laser wedge excision. Patients did not have prior surgery. Survival rates free of recurrence were estimated using the Kaplan-Meier methods, and associations were evaluated using Cox Proportional Hazards models. Eighty-five female patients were included in the study. Most patients (68%) were postmenopausal, had first period at or before 13 years of age, had at least one full-term pregnancy (82%), were not undergoing hormone replacement therapy (93%), were not using hormonal birth control (88%), and were either partially or completely compliant with triple therapy regime (80%). There was a statistically significant average reduction in risk of recurrence of 5% for every additional year of age (p < 0.0001). When compared to patients older than 65 years of age, patients less than 35 were nearly 10 times more likely to recur (p = 0.002), and patients 55-65 and 45-55 years of age were 8 and 5 times more likely to recur, respectively (p = 0.003 and 0.009). Additionally, females on birth control showed decreased risk of recurrence of 74% compared with their counterparts (p = 0.04). This is the first study to demonstrate an inverse relationship between age and disease recurrence in patients with iSGS following surgery. Using age as a surrogate for menopausal status, these results suggest that increased age and/or birth control provide a protective effect through decreased recurrence rates, possibly mediated by decreased estrogen levels. 4 Laryngoscope, 2024.

Exploring the role of interleukin-6 receptor blockade in epilepsy and associated neuropsychiatric conditions through a mendelian randomization study

BACKGROUND The interplay between inflammation, immune dysregulation, and the onset of neurological disorders, including epilepsy, has become increasingly recognized. Interleukin (IL)-6, a pro-inflammatory cytokine, is suspected to not only mediate traditional inflammatory pathways but also contribute to neuroinflammatory responses that could underpin neuropsychiatric symptoms and broader psychiatric disorders in epilepsy patients. The role of IL-6 receptor (IL6R ) blockade presents an intriguing target for therapeutic intervention due to its potential to attenuate these processes. AIM To explore the potential of IL6R blockade in reducing the risk of epilepsy and investigate whether this pathway might also influence associated psychiatric and neuropsychiatric conditions due to neuroinflammation. METHODS Mendelian randomization (MR) analysis employing single nucleotide polymorphisms (SNPs) in the vicinity of the IL6R gene (total individuals = 408225) was used to evaluate the putative causal relationship between IL6R blockade and epilepsy (total cases/controls = 12891/312803), focal epilepsy (cases/controls = 7526/399290), and generalized epilepsy (cases/controls = 1413/399287). SNP weights were determined by their effect on C-reactive protein (CRP) levels and integrated using inverse variance-weighted meta-analysis as surrogates for IL6R effects. To address potential outlier and pleiotropic influences, sensitivity analyses were conducted employing a variety of MR methods under different modeling assumptions. RESULTS The genetic simulation targeting IL6R blockade revealed a modest but significant reduction in overall epilepsy risk [inverse variance weighting: Odds ratio (OR): 0.827; 95% confidence interval (CI): 0.685-1.000; P = 0.05]. Subtype analysis showed variability, with no significant effect observed in generalized, focal, or specific childhood and juvenile epilepsy forms. Beyond the primary inflammatory marker CRP, the findings also suggested potential non-inflammatory pathways mediated by IL-6 signaling contributing to the neurobiological landscape of epilepsy, hinting at possible links to neuroinflammation, psychiatric symptoms, and associated mental disorders. CONCLUSION The investigation underscored a tentative causal relationship between IL6R blockade and decreased epilepsy incidence, likely mediated via complex neuroinflammatory pathways. These results encouraged further in-depth studies involving larger cohorts and multifaceted psychiatric assessments to corroborate these findings and more thoroughly delineate the neuro-psychiatric implications of IL-6 signaling in epilepsy. The exploration of IL6R blockade could herald a novel therapeutic avenue not just for seizure management but also for addressing the broader psychiatric and cognitive disturbances often associated with epilepsy.

Beyond breast cancer: role of selective estrogen receptor modulators in reducing systemic malignancies: evidence from population-based data

Background Raloxifene and bazedoxifene are selective estrogen receptor modulators (SERMs) used to prevent and treat osteoporosis in postmenopausal women. Raloxifene is also known for its preventive effect against invasive breast cancer; however, its effect on other cancer types is unclear. This study investigated the incidence of various cancers in osteoporosis patients receiving SERM therapy to determine its association with the risk of developing specific cancer types. Methods This retrospective cohort study examined the association between SERM use and the incidence of cervical, endometrial, ovarian, and colorectal cancers in postmenopausal women using data from the Korean National Health Insurance Service. Propensity score matching ensured group comparability by analyzing 95,513 participants. Cox proportional hazard models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the cancer risk associated with SERM therapy, differentiating between the effects of raloxifene and bazedoxifene. Results SERM therapy was associated with a reduced risk of cervical (adjusted HR = 0.47, 95% CI = 0.31–0.71), ovarian (adjusted HR = 0.61, 95% CI = 0.42–0.88), and colorectal cancer (adjusted HR = 0.49, 95% CI = 0.42–0.57). No significant risk reduction was observed for endometrial cancer (adjusted HR = 1.05, 95% CI = 0.70–1.59). A comparison between raloxifene and bazedoxifene revealed no significant differences in their cancer prevention effects. Conclusion SERM therapy administration is associated with a decreased incidence of cervical, ovarian, and colorectal cancers. Notably, the effects of raloxifene and bazedoxifene were consistent. Further investigations are crucial to elucidate the mechanisms underlying these observations and their clinical implications.

Transformation of p-arsanilic acid by dissolved Mn(III) and enhanced arsenic removal: Mechanism, toxicity and performance in complicated water matrices

Dissolved Mn(III), as a potent one-electron transfer oxidant, is ubiquitous in natural waters and sediments and actively involved in the transformation of organics in biogeochemical processes and water treatment. However, the important role of Mn(III) has long been overlooked because of its short life. This study was the first to investigate the performance of Mn(III) in organoarsenic transformation and to highlight the environmental implications. Both homogeneous and heterogeneous Mn(III)-based systems were effective to remove p-arsanilic acid (p-ASA, 15 μM) with degradation efficiency approaching 40.4 %–98.3 %. Two degradation pathways of p-ASA were proposed, in which As-C bond and amino group were vulnerable sites to Mn(III) attack, leading to the formation of more toxic arsenate (As(V)) and nitarsone. Through transforming organoarsenic to inorganic arsenic species, the removal efficiency of total arsenic and dissolved organics were enhanced to 65.1 %–95.5 % and 16.6 %–36.6 %, respectively, by post-treatment of coagulation or adsorption, accompanied with significant reduction of cytotoxicity and environmental risks. Particularly, polymeric ferric sulfate and granular activated alumina showed superior performance in the total As removal. Moreover, oxidation efficiency of Mn(III) was hardly affected by common cations and anions (e.g., Ca2+, Mg2+, NH4+, NO3ˉ, SO4ˉ), halide ions (e.g., Clˉ, Brˉ) and natural organic matter, showing high robustness for organoarsenic removal under complicated water matrices. Overall, this study shed light on the significance of Mn(III) to the fate of organoarsenics in manganese-rich environments, and demonstrated the promising potential of Mn(III)-based strategies to achieve targeted decontamination in water/wastewater purification.

The Importance of Geographic Proximity of Convalescent Plasma Donors.

Donor-recipient proximity emerged as an important factor influencing the efficacy of COVID-19 convalescent plasma (CCP) treatment during the early stages of the COVID-19 pandemic. This relationship was uncovered while analyzing data collected in the collaborative Expanded Access Program (EAP) for CCP at Mayo Clinic, a project aimed to establish protocols for CCP use amid the uncertainty of the novel disease. Analysis of data from nearly 28,000 patients revealed a significant reduction in risk of 30-day mortality for those receiving near-sourced plasma when compared to those receiving distantly sourced plasma [pooled relative risk, 0.73 (95% CI 0.67-0.80)], prompting adjustments in treatment protocols at selected institutions, and highlighting the importance of proximity in optimizing CCP outcomes. Despite its significance, subsequent studies of CCP effectiveness in COVID-19 have often overlooked donor-recipient proximity. Our findings emphasize the importance of donor-recipient proximity in CCP treatment in the current pandemic, and we discuss potential methods for improving CCP efficacy in future pandemics. Our recommendations include prioritizing virus genotyping for vulnerable patients, establishing a robust testing infrastructure, and collecting additional donor data to enhance plasma selection. This chapter underscores the importance of comprehensive data collection and sharing to navigate the evolving landscape of newly emerging infectious diseases.

Reduced Risk of Cardiovascular Diseases after Bariatric Surgery Based on the New PREVENT Equations.

We applied the novel Predicting Risk of Cardiovascular Disease EVENTs (PREVENT) equations to evaluate cardiovascular-kidney-metabolic (CKM) health and estimated CVD risk, including heart failure (HF), after bariatric surgery. Among 7804 patients (20-79 years) undergoing bariatric surgery at Vanderbilt University Medical Center during 1999-2022, CVD risk factors at pre-surgery, 1-year, and 2-year post-surgery were extracted from electronic health records. The 10- and 30-year risks of total CVD, atherosclerotic CVD (ASCVD), coronary heart disease (CHD), stroke, and HF were estimated for patients without a history of CVD or its subtypes at each time point, using the social deprivation index-enhanced PREVENT equations. Paired t-tests or McNemar tests were used to compare pre- with post-surgery CKM health and CVD risk. Two-sample t-tests were used to compare CVD risk reduction between patient subgroups defined by age, sex, race, operation type, weight loss, and history of diabetes, hypertension, and dyslipidemia. CKM health was significantly improved after surgery with lower systolic blood pressure, non-high-density-lipoprotein cholesterol (non-HDL), and diabetes prevalence, but higher HDL and estimated glomerular filtration rate (eGFR). The 10-year total CVD risk decreased from 6.51% at pre-surgery to 4.81% and 5.08% at 1- and 2-year post-surgery (relative reduction: 25.9% and 16.8%), respectively. Significant risk reductions were seen for all CVD subtypes (i.e., ASCVD, CHD, stroke, and HF), with the largest reduction for HF (relative reduction: 55.7% and 44.8% at 1- and 2-year post-surgery, respectively). Younger age, White race, >30% weight loss, diabetes history, and no dyslipidemia history were associated with greater HF risk reductions. Similar results were found for the 30-year risk estimates. Bariatric surgery significantly improves CKM health and reduces estimated CVD risk, particularly HF, by 45-56% within 1-2 years post-surgery. HF risk reduction may vary by patient's demographics, weight loss, and disease history, which warrants further research.

Vegan versus meat-based dog food: Guardian-reported health outcomes in 2,536 dogs, after controlling for canine demographic factors

To compare health outcomes between dogs fed meat and vegan diets, we surveyed 2,536 dog guardians who provided data and opinions about dogs fed conventional meat (1,370 = 54 %), raw meat (830 = 33 %) or vegan (336 = 13 %) diets for at least one year. We examined seven general indicators of illness: increased numbers of veterinary visits, medication use, progression onto a therapeutic diet after initial maintenance on a vegan or meat-based diet, reported veterinary assessment of being unwell, reported veterinary assessment and guardian opinion of increased illness severity, and number of health disorders per unwell dog. We also considered the prevalence of 22 specific health disorders, based on reported veterinary assessments. In each dietary group the proportions of dogs considered to have suffered from health disorders were: conventional meat – 49 %, raw meat – 43 % and vegan – 36 %. Probabilities of suffering from a disorder respectively appeared highest in dogs fed conventional meat for 11 disorders, raw meat for eight disorders, and vegan diets for three disorders. We conducted regression analyses to control for differences in medically-relevant canine demographic variables, including age, sex, neutering status, breed size and unusually high exercise levels. Dogs fed vegan diets had the best health outcomes. This trend was clear and consistent, with dogs fed vegan diets usually having substantial and statistically significant decreases in risks of these seven general indicators of illness. These ranged from 14.4 % to 51.3 % compared to dogs fed conventional meat-based diets. For six specific disorders, vegan diets were associated with statistically significant risk reductions of 50 %–61 % compared to dogs fed conventional meat. After pooling our results with related studies published to date, vegan dog food was consistently associated with lowered risks of multiple specific health disorders. No health disorder was consistently more prevalent in dogs fed vegan diets.

Heart Failure Events After Long-term Continuous Screening for Atrial Fibrillation: Results From the Randomized LOOP Study.

Mounting evidence indicates that even device-detected subclinical atrial fibrillation is associated with a higher risk of heart failure (HF). However, the potential impact of atrial fibrillation screening on HF remains unknown. The LOOP Study (Atrial Fibrillation detected by Continuous ECG Monitoring using Implantable Loop Recorder to prevent Stroke in High-risk Individuals) evaluated the effects of atrial fibrillation screening on stroke prevention using an implantable loop recorder (ILR) versus usual care in older individuals with additional stroke risk factors. In this secondary analysis, we explored the following HF end points: (1) HF event or cardiovascular death; (2) HF event; (3) event with HF with reduced ejection fraction (HFrEF); and (4) HFrEF event or cardiovascular death. Outcomes were assessed in a Cox model both as time-to-first events and as total (first and recurrent) events analyzed using the Andersen-and-Gill method. Of 6004 participants (mean age 74.7 and 52.7% men), 1501 were randomized to ILR screening and 4503 to the control group. In total, 77 (5.1%) in the ILR group versus 295 (6.6%) in the control group experienced the primary outcome of an HF event or cardiovascular death. Compared with usual care, ILR screening was associated with a nonsignificant reduction in the primary outcome for the time-to-first event analysis (hazard ratio, 0.78 [95% CI, 0.61-1.01]) and the total event analysis (hazard ratio, 0.77 [95% CI, 0.59-1.01]). Similar results were obtained for the HF event. A significant risk reduction in total events was observed in the ILR group for the composite of HFrEF event or cardiovascular death and for HFrEF event (hazard ratio, 0.74 [95% CI, 0.56-0.98] and 0.65 [95% CI, 0.44-0.97], respectively). In an older population with additional stroke risk factors, ILR screening for atrial fibrillation tended to be associated with a lower rate of total HF events and cardiovascular death, particularly those related to HFrEF. These findings should be considered hypothesis-generating and warrant further investigation. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02036450.

Comparison of Absolute and Relative Grip Strength to Predict Incidence of Diabetes Mellitus in Korea: A Prospective Cohort Study.

Background: This study aimed to investigate the association between absolute grip strength (AGS), relative grip strength (RGS) levels, and the risk of developing diabetes in middle-aged adults, utilizing longitudinal data. Methods: A total of 1935 participants, 51-81 years of age, were engaged in surveys both in 2017-2018 and during the subsequent follow-up survey in 2019-2020. Diabetes diagnosis and treatment were the criteria for categorizing individuals as "diabetic." Grip strength was measured using the JAMA-5030J1 equipment (SAEHAN, Korea), and AGS and RGS were also categorized into tertiles by gender. A proportional hazards Cox regression model was used to evaluate the relationship among AGS, RGS, and the risk of developing diabetes. Subsequently, we computed the hazard ratio (HR) and 95% confidence interval (95% CI) for the risk of developing diabetes. Results: After adjusting for various confounding variables, a significant reduction in diabetes risk was observed in the high grip strength group, adjusted for body mass index (RGS1) and body weight (RGS2), compared with the low RGS1 and RGS2 groups (RGS1 HR = 0.54, 95% CI = 0.36-0.80; RGS2 HR = 0.50, 95% CI = 0.34-0.73). However, there were no significant associations between AGS and diabetes risk. Furthermore, significant differences in the relationship among AGS, RGS levels, and the risk of developing diabetes were found across gender and insulin resistance levels. Conclusion: This study underscores the importance of RGS levels in predicting the incidence of diabetes, with AGS, RGS1, and RGS2 emerging as significant predictive indicators for assessing diabetes risk.

The Physical Activity Guidelines and Diabetes-Related Mortality: National Health and Nutrition Examination Survey 1999-2006.

Background: Previous studies have indicated an inverse relationship between aerobic physical activity (PA) and risk of diabetes-related mortality (DRM). However, the contribution of aerobic PA across multiple domains, while also considering the contribution of muscle-strengthening activity (MSA), in reduction of risk for DRM has yet to be examined. Purpose: The aim of this study is to examine the individual and combined associations of aerobic PA and MSA with DRM. Methods: The study sample (n = 13,350) included adult (20-79 years of age) participants from the 1999 to 2006 National Health and Nutrition Examination Survey. PA was categorized into 6 categories based around the 2018 PA guidelines: category 1 (inactive), category 2 (insufficient aerobic PA and no MSA), category 3 [active (aerobic) and no MSA], category 4 (no aerobic PA and sufficient MSA), category 5 (insufficient aerobic PA and sufficient MSA), and category 6 (meeting both recommendations). The dependent variable in this study was DRM, which includes those who had diabetes as the primary cause of death as well as those with diabetes listed as an underlying cause of death. Cox proportional hazards models were used for all analyses. Results: Following adjustment for covariates, significant risk reductions for DRM were found only in category 3 (HR = 0.57; 95% confidence interval: 0.37-0.88). Conclusions: Results suggest that meeting the aerobic PA guidelines significantly reduces the risk for DRM. Those meeting versus not meeting the MSA guidelines seem to have no difference in risk for DRM independent of aerobic PA.

Climate change versus Mediterranean diet: A hazardous struggle for the women's heart

Climate change impacts food systems, causing nutritional deficiencies and increasing cardiovascular diseases (CVD). Regulatory frameworks like the European Farm-to-Fork Strategy aim to mitigate these effects, but current EU food safety regulations inadequately address health risks from poor diet quality and contaminants.Climate change adversely affects food quality, such as nutrient depletion in crops due to higher CO2 levels, leading to diets that promote chronic diseases, including CVD. Women, because of their roles in food production and their unique physiological responses to nutrients, face distinct vulnerabilities. This review explores the interplay between climate change, diet, and cardiovascular health in women. The review highlights that sustainable diets, particularly the Mediterranean diet, offer health benefits and lower environmental impacts but are threatened by climate change-induced disruptions. Women's adherence to the Mediterranean diet is linked to significant reductions in CVD risk, though sex-specific responses need further research.Resilient agricultural practices, efficient water management, and climate-smart farming are essential to mitigate climate change's negative impacts on food security. Socio-cultural factors influencing women's dietary habits, such as traditional roles and societal pressures, further complicate the picture.Effective interventions must be tailored to women, emphasizing education, community support, policy changes, and media campaigns promoting healthy eating. Collaborative approaches involving policymakers, health professionals, and the agricultural sector are crucial for developing solutions that protect public health and promote sustainability.Addressing the multifaceted challenges posed by climate change to food quality and cardiovascular health in women underscores the need for integrated strategies that ensure food security, enhance diet quality, and mitigate environmental impacts.

Revisiting the concept of bout: associations of moderate-to-vigorous physical activity sessions and non-sessions with mortality

IntroductionCurrent physical activity guidelines recommend 150 min of moderate-to-vigorous physical activity (MVPA) for health benefits, regardless of the pattern of MVPA. However, MVPA that occurs in sessions (MVPA-S) may have different health implications compared to MVPA that is not accumulated in sessions (MVPA-nonS). This study aimed to investigate the associations of MVPA-S and MVPA-nonS with mortality.MethodsWe conducted a cohort study of the National Health and Nutrition Examination Survey 2003–2006 (n = 5,658) with accelerometer-measured physical activity at baseline and mortality followed through December 31, 2019. A session was defined as a time window of 30 min or longer where the average intensity was at or above 2020 counts/minute. MVPA accumulated within such sessions was quantified as MVPA-S, while MVPA accumulated outside the sessions was quantified as MVPA-nonS. We examined the joint association of MVPA-S and MVPA-nonS by classifying the participants into four groups (both < 75 min/week [referent], MVPA-S ≥ 75 and MVPA-nonS < 75, MVPA-S < 75 and MVPA-nonS ≥ 75, and both ≥ 75). We used 75 min as the cut-point because it is half of the guideline-recommended MVPA volume where a strong MVPA-mortality association has been observed in previous studies, and because it was close to the median of MVPA-nonS (75 min/week was the 54th percentile), allowing a sufficient sample size in each group for testing statistical significance. The hazard ratios and 95% confidence intervals were estimated with adjustment for important confounders.ResultsDuring 13.9 years of follow-up (74,988 person-years), there were 1,424 deaths, out of which 472 were related to cardiovascular diseases (CVD). Compared to the referent combination (both < 75), the hazard ratios in the other three combinations were 0.48 (0.33–0.69), 0.85 (0.71–1.01), and 0.45 (0.30–0.67) for all-cause mortality; and were 0.34 (0.17–0.70), 0.96 (0.69–1.33), and 0.40 (0.17–0.90) for CVD mortality, respectively. Results were largely consistent in the spline-based models, age- and sex-stratified analyses, complete-case analysis, competing risk analysis, and the analysis excluding deaths within two years of follow-up.ConclusionIn conclusion, MVPA accumulated in sessions that lasted at least 30 min was associated with significant reductions in all-cause and CVD-specific mortality risks. The health implications of MVPA that were not accumulated in such sessions warrant further investigation.

Mental Health Diagnoses and Suicidality Among Transgender Youth in Hospital Settings.

Purpose: The purpose of this analysis is to: 1) describe the most common mental health diagnoses in the emergency department (ED) and inpatient hospital settings among transgender and gender diverse (TGD) youth vs. matched controls and 2) evaluate if a gender-affirming hormone therapy (GAHT) or gonadotropin-releasing hormone agonist (GnRHa) prescription decreased the risk of suicidality within these settings. Methods: Using the PEDSnet dataset (years 2009-2019), TGD youth aged 8-18 (n = 3414, with a median age at last visit of 16.2 [14.4, 17.7] years, were propensity-score matched to controls (n = 13,628, age 16.6 [14.2, 18.3] years). Relative risks of the most common mental health diagnoses within ED and inpatient settings were calculated for TGD youth compared with controls. Recurrent time-to-event analysis was used to examine whether GAHT or GnRHa attenuated the risk of suicidality among subsamples of TGD youth. Results: TGD youth had a higher relative risk (95% confidence interval [CI]) of mental health diagnoses and suicidality in the ED (5.46 [4.71-6.33]) and inpatient settings (6.61 [5.28-8.28]) than matched controls. TGD youth prescribed GAHT had a 43.6% lower risk of suicidality (hazard ratio [HR] = 0.564 [95% CI 0.36-0.89]) compared with those never prescribed GAHT during our study period or before GAHT initiation. TGD youth who were prescribed GnRHa therapy had a nonstatistically significant reduction in ED or inpatient suicidality diagnoses compared with those never prescribed GnRHa (HR = 0.79 [0.47-1.31]). Conclusion: Although risk of mental health diagnoses and suicidality in ED and inpatient settings was high among TGD youth, a GAHT prescription was associated with a significant reduction in suicidality risk.