Significant Reduction In Risk Research Articles

Survival and fracture risk with radium-223 therapy in metastatic castrate-resistant prostate cancer (mCRPC): A real-world analysis.

50 Background: Radium-223 is a life-prolonging radionuclide therapy for men with bone-predominant metastatic castrate-resistant prostate cancer (mCRPC). It accumulates at sites of high bone turnover with emerging evidence suggesting use of radium-223 increases risk of pathologic fractures. Bone-protective agents (BPAs) reduce skeletal-related events including pathologic fractures in men with mCRPC. We evaluated real-world outcomes of patients treated with radium-223, including the effect of BPA use on pathologic fracture risk. Methods: This was a single institution retrospective cohort study that included patients with mCRPC treated with radium-223 in Manitoba, Canada from 2014 to 2021. Outcomes of interest included incidence of pathologic fracture, pain response, alkaline phosphatase (ALP) response, and overall survival. Kaplan-Meier method was used for time to event outcomes and multivariable Cox regression models were used to adjust for covariates. Results: We identified 92 patients who received radium-223 for mCRPC (Table). Thirty patients (33%) completed 6 cycles of radium-223. Documented pain relief occurred in 39% of patients. For those with elevated ALP at baseline (n = 46), 57% had at least 30% reduction in total ALP. PSA reduction occurred in 29% with 11% having at least 30% reduction in PSA. Median overall survival (OS) was 9.4 months (95% CI 5.8 to 15.9). Of those who did not receive concurrent BPA, 26% developed a pathologic fracture, compared to 3% who received concurrent BPA during a median follow up of 8.1 months. BPA use was associated with significant delay in time to pathologic fracture (median not reached vs. 15.9 months; HR = 0.20, 95% CI: 0.05 – 0.76, p < 0.05) after adjusting for number of bone metastases and corticosteroid use. Conclusions: In this real-world study, concurrent BPA use was associated with significant reduction in risk of pathologic fractures in mCRPC patients receiving radium-223. BPA administration should be considered for patients receiving radium-223. [Table: see text]

Abstract 135: Efficacy and Safety of PCSK9 Inhibitors for Stroke Prevention: Systematic Review and Meta-Analysis

Objective: Investigate the efficacy and safety of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) on stroke prevention. Background: PCSK9i reduce low-density lipoprotein cholesterol (LDL-Chol) and lipoprotein a (LpA) levels. Their efficacy in reducing the risk of major cardiovascular events has been shown in multiple randomized clinical trials (RCT). However, clinical equipoise remains on the magnitude and mechanisms by which PCSK9i decrease the risk of stroke. Methods: We performed a systematic search of biomedical databases from inception to July 15, 2023, to identify RCTs that investigated the efficacy of PCSK9i versus placebo for major cardiovascular event prevention. The primary outcome was total stroke. The safety outcome was the risk of adverse neurological events, as defined by each trial. Effect size was represented by risk ratio (RR), and analysis was done using random-effects meta-analysis. Heterogeneity was assessed by I 2 and Cochrane Q statistics. Meta-regression analyses were performed to assess the association between LDL-Chol and LpA reduction and stroke risk. Results: Overall, 19 studies with 92,786 patients were included. The quality of the evidence was moderate and heterogeneity for all comparisons was low ( I 2 <25%). The mean age was 60.1 years for the PCSK9i group and 59.6 years for the placebo group, with a mean follow-up time of 60.1 weeks. PCSK9i reduced the LDL-Chol levels by 11% and LpA levels by 8%. PCSK9i were associated with a significant reduction in stroke risk (RR 0.71, 95% CI 0.62-0.81, I 2 =0%), without an increase in mortality (RR 0.94, 95% CI 0.85-1.05, I 2 =0%). The risk of adverse neurological events was similar between groups (RR 1.02, 95% CI 0.88-1.18, I 2 =0%). In meta-regression analyses, the stroke risk was not associated with the magnitude of the effect of PCSK9i on LDL-Chol (LDL Chol β=-0.01, 95% CI=-0.03-0.01) and LpA (β=-0.01, 95% CI=-0.06-0.03) levels. Conclusions: PCSK9i significantly reduced the stroke risk, without increasing mortality or the risk of adverse neurological events. Our findings also suggest that the beneficial effect of PCSK9i on stroke risk is mediated by LDL-Chol- and LpA-independent mechanisms.

Puget Sound sediment cleanup remedy effectiveness retrospective.

The monitoring of completed large-scale sediment remediation projects has revealed mixed effectiveness at reducing risks, thus highlighting uncertainties regarding whether and which remedial measures are necessary to achieve protective goals. To support valid statements about changes over time and the overall effectiveness of sediment remedial action, robust pre- and postremediation monitoring is required with sufficient time points, reference sites, and biological metrics. The five completed Puget Sound sediment remediation case studies reviewed here (Bellingham Bay, St. Paul Waterway, Eagle Harbor, Hylebos Waterway, and Sinclair Inlet) employed particularly robust remedy effectiveness monitoring programs that spanned decades, revealing common lessons for improving remediation outcomes. First, although sediment remediation can play an important role in reducing contaminant exposure in areas with higher sediment concentrations, at lower levels, sediment links with fish tissue concentrations diminish. As water column exposure from diverse sources becomes predominant, remediating sediments with lower concentrations yields proportionately less risk reduction. Second, timely monitoring of effective source controls achieving substantial (i.e., >80%) contaminant source load reductions as well as large-scale capping projects have revealed rapid changes in Puget Sound surface sediment concentrations and biological recovery metrics with an average recovery half-time of 1.6 ± 0.8 years. The weight of evidence suggests that natural recovery of Puget Sound surface sediments is significantly accelerated by exchange across the sediment-water interface from benthic organism feeding behaviors, porewater flux, and tide-generated currents. As a result, effective source controls in Puget Sound have rapidly improved surface sediment quality and achieved more significant risk reductions than broadscale sediment remediation. Going forward, comprehensive Puget Sound source control efforts that incorporate robust monitoring in an adaptive management framework are the best way to achieve protective remediation objectives. These lessons may apply more broadly across similar complex urban aquatic ecosystems. Integr Environ Assess Manag 2024;00:1-11. © 2024 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Associations between Plasma Tocopherols and Lung Cancer Risk: Results from the Southern Community Cohort Study.

Despite the various anticancer activities of tocopherols, little is known about tocopherols associated with lung cancer risk among low-income African Americans (AA) and European Americans (EA) who are disproportionately affected by the disease. We conducted a nested case-control study that included 209 incident lung cancer cases and 406 matched controls within the Southern Community Cohort Study. Using biospecimens collected at cohort enrollment, plasma levels of α-, β/γ-, δ-, and total-tocopherols were measured by high-performance liquid chromatography with photodiode array detection. Conditional logistic regression was used to estimate ORs and 95% confidence intervals (CI) for lung cancer risk after adjusting for potential confounders. Stratified analyses were also conducted. Plasma levels of total-tocopherols were inversely associated with lung cancer risk overall [OR (95% CI) for the highest vs. lowest tertile = 0.51 (0.30-0.90)]. The inverse association remained significant among EAs [0.20 (0.06-0.65)], men [0.43 (0.21-0.90)], current smokers [0.49 (0.26-0.93)], and cases diagnosed within 2 years of blood draw [0.36 (0.15-0.86)], though we did not find a significant risk reduction among AAs [0.75 (0.39-1.45)]. Notably, we found significant interactions between α-tocopherol and race after controlling the FDR to correct for multiple comparisons (Pinteraction = 0.02). Our results indicate that plasma total-tocopherols are inversely associated with lung cancer risk, but the association may differ across specific isomeric forms of tocopherols, race, or other individuals' characteristics. Further large-scale studies are warranted to confirm our findings. Recommendations on tocopherols for lung cancer prevention should take isomers, race, and smoking behaviors into consideration.

P665 Statins use and the risk of colorectal cancer in patients with inflammatory bowel disease: A Systematic review and meta-analysis

Abstract Background Statin use has been linked to a reduced risk of advanced colorectal adenomas; however, its association with colitis-associated dysplasia and cancer is not well-defined. We aimed to perform a systematic review and meta-analysis to assess the pooled association of statin exposure with dysplasia and colorectal cancer in patients with inflammatory bowel disease (IBD). Methods We searched MEDLINE, EMBASE, and the COCHRANE library to identify full text articles analyzing the risk of CRC or dysplasia development based on statin use in patients with IBD. A meta-analysis was performed using a random-effects model to pool estimates and report hazard ratios [HRs] or odds ratios [ORs], following the data format specified in the individual studies. Results A total of 4 studies were identified as eligible for the meta-analysis. In the analysis of studies presented with time-to-event outcomes, statin use was associated with a statistically significant reduction in risk of colorectal cancer (HR 0.76, 95% confidence interval [CI] 0.61-0.95, P=0.016). Meanwhile, in the analysis of non-time-to-event study results, statin use was associated with a trend towards lower colorectal cancer risk (OR 0.28, 95% CI 0.07-1.10, P=0.068). Conclusion Statin use appears to be associated with a reduced risk of colorectal cancer in patients with inflammatory bowel disease. Statins may serve as potential chemopreventive agents for long-standing IBD patients, and further large-scale prospective studies will be needed to confirm its potential benefit.

Rivaroxaban and Dabigatran: prospects for use in the management of heart failure

Scientific articles examine the effectiveness and pharmacokinetics of two oral anticoagulants, dabigatran and rivaroxaban, in the context of treating atrial fibrillation and chronic heart failure. Dabigatran, as a direct thrombin inhibitor, influences the thrombin zone and fibrinogen, preventing fibrin formation. Rivaroxaban, as a selective factor Xa inhibitor, blocks factor X activation. Both medications demonstrate high bioavailability and plasma protein binding. Studies on the efficacy of rivaroxaban in atherosclerosis and low-dose rivaroxaban in chronic heart failure did not reveal statistically significant reductions in cardiovascular risk. The findings emphasize the importance of further research and an individualized approach to selecting anticoagulants for optimal management of patients with diverse cardiovascular conditions.

Development of an Improved LASER-Resistant Endotracheal Tube.

Surgical fires, particularly within Otolaryngology, remain a surprisingly frequent and devastating complication of laser-related surgery in the oropharynx and airway; Current estimates suggest anywhere from 200 to 600 surgical fires per year in the United States, with 20%-30% of these occurring as a complication of laser surgery and 90%-95% of these occurring in the head and neck region. Unfortunately, the complications of laser surgery in the airway may include respiratory failure, airway burns with stenosis, and may result in mortality. The most commonly utilized endotracheal tube for protection against inadvertent laser strikes, the Laser-Shield II tube (Medtronic), was removed from the commercial marketplace in 2016 after cases of airway fires were reported as a result of feature deficiencies in the product (FDA MAUDE Database review). Since the demise of the Laser-Shield II tube, alternatives such as the Mallinckrodt laser tube and handmade reinforced tubes have been utilized, although shortcomings in design and features have made these options less appealing to practicing Otolaryngologists. Creating a laser-safe endotracheal tube is critical for safe upper airway surgery. This paper evaluates new technologies, materials, and technical innovations in endotracheal tubes that may advance patient safety in laser-assisted Otolaryngology procedures. This paper evaluates new technologies, materials, and technical innovations in endotracheal tubes that may advance patient safety in laser-assisted Otolaryngology procedures. First, this article reviews the background of laser surgery in Otolaryngology and the consequent risk of surgical fire with resultant development of laser-resistant endotracheal tubes and commercial availability. Next, a review of claims and national database review of product failures related to previous laser-resistant endotracheal tubes is performed through the FDA MAUDE database. This includes an evaluation of cases: review of techniques in laser airway surgery including spontaneous ventilation, decreased O2 concentration, currently available endotracheal tubes including "handmade" fixes for perceived safety risks, and determination of failure points for previous laser-resistant endotracheal tubes. Third, the paper reviews the requested features of an "ideal" laser-resistant endotracheal tube. Finally, the paper reviews failure testing from an initial, unsuccessful attempt at material development and the consequent development of alternative technologies that address failure points from previous endotracheal tubes and addresses requested features with a detailed analysis of FDA-approval required testing. Extensive lab testing of the new tube predicts a significant reduction of risk in vivo with inability to perforate the shaft or cuff of the tubes under standard working conditions. While no iteration of a laser-resistant endotracheal tube is entirely laser safe, advances in technology can improve the safety profile of these devices. The new tube contains a double cuff, a soft and flexible shaft to minimize laryngeal insertion trauma, a smooth external surface, a tight-to-shaft balloon, and methylene blue dye in the cuff to alert the user to inadvertent penetration. These characteristics were the most requested by laryngologists in the development of a new laser-resistant tube. The newest endotracheal tube brings the features most requested by Otolaryngologists in a laser-resistant tube, and improves the safety profile over previous tubes. Development of a new endotracheal tube represents an advancement in safety for the Otolaryngologist in laser airway surgery. Understanding the previous history and the science behind surgical fire formation is essential in advancing safety for patients in the future. N/A Laryngoscope, 134:S1-S12, 2024.

Tiotropium reduces clinically important deterioration in patients with mild-to-moderate chronic obstructive pulmonary disease: A post hoc analysis of the Tie-COPD study

BackgroundClinically important deterioration (CID) is a composite endpoint used to holistically assess the complex progression of chronic obstructive pulmonary disease (COPD). Tiotropium improves lung function and reduces the rate of COPD exacerbations in patients with COPD of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1 (mild) or 2 (moderate). However, whether tiotropium reduces CID risk in patients with mild-to-moderate COPD remains unclear. MethodsThis was a post hoc analysis of the 24-month Tie-COPD study comparing 18 μg tiotropium with placebo in patients with mild-to-moderate COPD. CID was defined as a decrease of ≥100 mL in trough forced expiratory volume in 1 s, an increase of ≥2 unit in COPD Assessment Test (CAT) score, or moderate-to-severe exacerbation. The time to the first occurrence of one of these events was recorded as the time to the first CID. Subgroup analyses were conducted among patients stratified by CAT score, modified Medical Research Council (mMRC) dyspnea score, and GOLD stage at baseline. ResultsOf the 841 randomized patients, 771 were included in the full analysis set. Overall, 643 patients (83.4 %) experienced at least one CID event. Tiotropium significantly reduced the CID risk and delayed the time to first CID compared with placebo (adjusted hazard ratio = 0.58, 95 % confidence interval = 0.49–0.68, P < 0.001). Significant reductions in CID risk were also observed in various subgroups, including patients with a CAT score <10, mMRC score <2, and mild COPD. ConclusionsTiotropium reduced CID risk in patients with mild-to-moderate COPD, even in patients with fewer respiratory symptoms or mild disease, which highlights tiotropium's effectiveness in treating COPD patients with mild disease. Trial registrationThis study is registered at ClinicalTrials.gov (Tie-COPD, NCT01455129).

Meta-Analysis of Randomized Trials: Efficacy and Safety of Colchicine for Secondary Prevention of Cardiovascular Disease.

Colchicine has shown potential cardioprotective effects owing to its broad anti-inflammatory properties. We performed a meta-analysis to assess its safety and efficacy in secondary prevention in patients with established coronary artery disease (CAD). We searched Ovid Healthstar, MEDLINE, and Embase (inception to May 2022) for randomized controlled trials (RCTs) evaluating the cardiovascular effects of colchicine compared with placebo or usual care in patients with CAD. Study-level data on efficacy and safety outcomes were pooled using the Peto method. The primary outcome was the composite of cardiovascular (CV) death, myocardial infarction (MI), or stroke. A total of 8 RCTs were included with a follow-up duration of ≥1 month, comprising a total of 12,151 patients. Compared with placebo or usual care, colchicine was associated with a significant risk reduction in the primary outcome (odds ratio (OR) 0.70, 95% CI 0.60 to 0.83, P < 0.0001; I2 = 52%). Risks of MI (OR 0.75, 95% CI 0.62 to 0.91, P = 0.003; I2 = 33%), stroke (OR 0.47, 95% CI 0.30 to 0.74, P = 0.001; I2 = 0%), and unplanned coronary revascularization (OR 0.67, 95% CI 0.55 to 0.82, P = 0.0001; I2 = 58%) were all reduced in the colchicine group. Rates of CV and all-cause mortality did not differ between the two groups, but there was an increase in noncardiac deaths with colchicine (OR 1.54, 95% CI 1.10 to 2.15, P = 0.01; I2 = 51%). The occurrence of all other adverse events was similar between the two groups, including GI reactions (OR 1.06, 95% CI 0.94 to 1.20, P = 0.35; I2 = 42%) and infections (OR 1.04, 95% CI 0.84 to 1.28, P = 0.74; I2 = 53%). Colchicine therapy may reduce the risk of future cardiovascular events in patients with established CAD; however, there remains a concern about non-CV mortality. Further trials are underway that will shed light on non-CV mortality and colchicine NCT03048825, and NCT02898610.

A Delirium Prevention and Management Initiative: Implementing a Best Practice Recommendation for the NICU.

Medically complex infants experiencing NICU stays can be difficult to manage, exhibiting refractory agitation, disengagement, or both-all signs of delirium, which can present in a hypoactive, hyperactive, or mixed form. Though documented in other settings, delirium is under-recognized in NICUs. Pediatric studies show that a high percentage of patients with delirium are under the age of 12 months. Delirium is associated with increased ventilation days, hospital days, and costs. It negatively affects neurodevelopment and social interaction. Studies show that pediatric nurses are unprepared to recognize delirium. Our nurse-led multidisciplinary group created a best practice recommendation (BPR) focused on detecting delirium and minimizing risk through thoughtful sedation management, promotion of sleep hygiene and mobility, and facilitation of meaningful caregiver presence. Occasionally, medications, including melatonin and risperidone, are helpful. In 2019, we introduced this BPR to reduce delirium risk in our NICU. Practice changes tied to this initiative correlate with a significant reduction in delirium scores and risk including exposure to deliriogenic medications. A multidisciplinary care bundle correlates with decreased delirium screening scores in NICU patients.

Relationship between sex differences in drinking, smoking, and exercising and the incidence of malignancies and medical procedures: a cross-sectional study of 21,916 participants in China.

Objectives: The unresolved issue of the relationship between sex differences in tea, coffee, and beverage consumption and malignancy risk prompted our study in 2022. Methods: Logistic proportional hazards models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) in our investigation of the associations between cancer risk and tea, coffee, and beverage consumption. Results: Our findings revealed that frequent consumption of white tea significantly reduced the occurrence of malignant tumours, but this effect was detected only in the fully adjusted model for males (OR: 0.736, 95% CI: 0.095-5.704). The amount of sugar added to coffee was associated with an increased risk of malignancy in a dose-dependent manner (P for trend = 0.001), with significance observed for both men (P for trend = 0.049) and women (P for trend = 0.005) in the final model. Notably, individuals who consumed more than 2100 ml of sugary beverages daily had a statistically significant reduction in malignancy risk (OR: 0.219, 95% CI: 0.052-0.917). Interestingly, the intake of sugary beverages had a protective effect on cancer incidence, with a significant effect on males (P for trend = 0.031) but not females (P for trend = 0.096) in the final model. Conclusions: Our study highlights the substantial impact of regular white tea consumption on reducing the risk of malignant tumours in males. This study first reported that the potential protective effect of consuming sugary beverages is predominantly observed in males, and a correlation between the amount of sugar added to coffee and a heightened risk of malignancy.

Omega-3 Fatty Acid Therapy: A Review of Study Design Flaws, Quality, and Composition

There is marked heterogeneity in the clinical response to omega-3 fatty acid therapy with many authors documenting futility in large-scale trials, secondary re-analysis, and meta-analysis. The question of failure in the context of omega-3 therapy is multifactorial and complicated by the observation that fish intake has been broadly linked to significant risk reductions across a range of conditions. The question that remains is how can we resolve the discrepancy between pre-clinical evidence and epidemiology, which dually emphasize the benefit of omega-3 therapy against the limited success of large-scale clinical trials and smaller scale clinical studies that do not consistently report benefit and may even report harm, especially as it pertains to atrial fibrillation. We present three primary considerations that may clarify the supposed failures of omega-3 therapy: 1) correction for omega-3:omega-6 ratio and competition, 2) variation in the fatty acid composition and quality of omega-3 products, and 3) fundamental concerns pertaining to the omega-3 vehicle and its impact on omega-3 metabolism. While the predominant source of omega-3 therapy is supplements, they are typically not regulated prior to market like drugs and have significant variability in fatty acid composition, vehicle, oxidation, and quality control. Further, the individual response to omega-3 therapy is likely variable and dependent on ambient dietary conditions and inherited differences in endogenous desaturase activity, which has infrequently been accounted for in large studies. The net effect of these concerns should engender pharmaceutical and consumer companies alike to consider 1) refining trial design and 2) consider the role of oxidation in the failure of omega-3 products.

A Meta-analysis on the Comparison of Carbetocin Versus Oxytocin on Additional Uterotonic Use, Incidence of Postpartum Hemorrhage, and Need for Blood Transfusion after Cesarean Section under Neuraxial Anesthesia

ABSTRACT Postpartum hemorrhage (PPH) remains to be the leading cause of maternal deaths worldwide. The first-line treatment in its prevention is the administration of uterotonics before the delivery of the placenta. Recently, a newer synthetic analog has been developed – carbetocin. With its introduction, new questions arise as to which is more effective in preventing PPH. Four major electronic databases were searched for randomized controlled trials comparing carbetocin and oxytocin in terms of additional uterotonic use, incidence of PPH, and need for blood transfusion. Only randomized controlled studies involving pregnant women undergoing cesarean section under regional anesthesia were included. Outcomes included are the need for additional uterotonic use, the incidence of PPH, and the need for blood transfusion. Of the three outcomes, carbetocin was found to show statistically significant protection against the need for additional uterotonic administration and the need for blood transfusion. Results showed that carbetocin provided a statistically significant risk reduction for the need for additional uterotonics (risk ratio [RR] = 0.53, 95% confidence interval [CI] 0.46–0.81, P &lt; 0.00001) and need for blood transfusion (RR = 0.34, 95% CI 0.19–0.62, P = 0.0004). Need for additional uterotonics and for blood transfusion was found to be almost twice (1/0.53 = 1.88) and almost thrice (1/0.34 = 2.94) as likely, respectively, to occur in the oxytocin group versus the carbetocin group. Reduction of PPH pointed toward carbetocin providing greater protection against it, but it was found not to be statistically significant (RR = 0.85, 95% CI 0.56–1.28, P = 0.43).

AHA Life's Essential 8 and new-onset CKD: a prospective cohort study from the UK Biobank.

The AHA has recently introduced a novel metric, Life's Essential 8, to assess cardiovascular health (CVH). Nevertheless, the association between varying levels of LE8 and the propensity for CKD is still unclear from a large prospective cohort. Our objective is to meticulously examine the relationship between LE8 and its associated susceptibilities to CKD. A total of 251,825 participants free of CKD from the UK Biobank were included. Cardiovascular health was scored using LE8 and categorized as low, moderate, and high. Cox proportional hazard models were employed to evaluate the associations of LE8 scores with new-onset CKD. The genetic risk score for CKD was calculated by a weighted method. Over a median follow-up of 12.8years, we meticulously documented 10,124 incident cases of CKD. Remarkably, an increased LE8 score correlated with a significant reduction of risk in new-onset CKD (high LE8 score vs. low LE8 score: HR = 0.300, 95% CI 0.270-0.330, p < 0.001; median LE8 score vs. low LE8 score: HR = 0.531, 95% CI 0.487-0.580, p < 0.001). This strong LE8-CKD association remained robust in extensive subgroup assessments and sensitivity analysis. Additionally, these noteworthy associations between LE8 scores and CKD remained unaffected by genetic predispositions to CKD. An elevated degree of CVH, as delineated by the discerning metric LE8, exhibited a pronounced and statistically significant correlation with a marked reduction in the likelihood of CKD occurrence.

Comparison of GLP-1 Receptor Agonists and Other Glucose-Lowering Agents on Cardiovascular Outcomes in Individuals with Type 2 Diabetes and Obesity: A Spanish Real-World Population-Based Study

AimsAssess the impact of glucagon-like peptide receptor agonists (GLP-1RA) compared to other glucose-lowering agents on cardiovascular outcomes in individuals with type 2 diabetes and obesity in a Spanish metropolitan area MethodsA retrospective population-based type 2 diabetes cohort was identified from the Valencia Clinic-Malvarrosa Department electronic databases (2014-2019). Study groups included GLP-1RA, sodium-glucose co-transporter-2 inhibitors (SGLT2i), Insulin, and Miscellany (other glucose-lowering agents). 1:1:1:1 propensity score matching was conducted. The primary outcome was a composite of major adverse cardiovascular events (4-point MACE) comprising myocardial infarction, stroke, all-cause mortality, and heart failure. Secondary outcomes included individual 4-point MACE components. Hazard ratios were estimated using Cox regression analyses against the Miscellany group. ResultsFrom 26,944 subjects, 1,848 adults were selected per group. GLP-1RA did not show a significant reduction in 4-point MACE risk (HR 1.05 [95%CI 0.82-1.34]). SGLT2i significantly reduced the risk of heart failure (HR 0.16 [95%CI 0.05-0.54]) and atrial fibrillation (HR 0.58, [95%CI 0.35-0.95]). The Insulin group exhibited a higher risk for 4-point MACE and most individual outcomes compared to GLP-1RA and SGLT2i. ConclusionsOur findings do not provide evidence of a reduced cardiovascular risk, as assessed by 4-point MACE, with GLP-1RA. In contrast, SGLT2i demonstrated protective effects against heart failure and atrial fibrillation.

Large-scale data reveal disparate associations between leisure time physical activity patterns and mental health

BackgroundLeisure time physical activity (LTPA) is known to be associated with a lower risk for mental health burden, while whether the underlying mechanisms vary across populations is unknown. We aimed to explore the disparate associations between LTPA and mental health based on large-scale data.MethodsIn this study, we analyzed data including 711,759 individuals aged 15 years or above from the latest four rounds (2003, 2008, 2013, and 2018) of the National Health Service Survey (NHSS) in China. We used multiple logistic regression models adjusted for potential confounders to investigate associations between LTPA and mental health in the total population and subgroups by measuring a diverse set of activity frequencies, intensities, and types. To examine the dose-response associations between total activity volume and mental health, we conducted restricted cubic splines to investigate possible nonlinearity.ResultsLTPA was associated with remarkably lower self-reported mental health burden (OR 0.56, 95% CI 0.54–0.58). The dose-response relationship between total activity volume and mental health was highly nonlinear (p < 0.001), presenting L-shaped with first 1200 metabolic equivalents of task (METs)-min/week for significant risk reduction (OR 0.58, 95% CI 0.56–0.60). Notably, merely exercising 3–5 times per week with moderate swimming was significantly associated with lower mental health burden among younger people, while the association was strongly large in older adults aged 60 years or above doing 55-min moderate apparatus exercise at least six times a week.ConclusionsIn a large Chinese sample, LTPA was meaningfully and disparately associated with mental health burden across different people. Policy targeted at prompting activity may be effective for reducing mental health burden, but importantly, tailored strategies are needed based on population contexts.

Protective Effects Against Dementia Undergo Different Statin Type, Intensity, and Cumulative Dose in Older Adult Type 2 Diabetes Mellitus Patients

ObjectivesThis study investigated the relationship between statin use and dementia risk in older adults with type 2 diabetes (T2DM). It also assessed the impact of various statin types, dosage intensity, and cumulative doses on dementia risk. DesignEmploying the inverse probability of treatment weighting (IPTW) Cox hazards model, this research explored the influence of statin utilization on dementia incidence. Setting and ParticipantsThe study included older adult T2DM patients aged 60 years or older who received statins (case group) and those who did not (control group) during the follow-up period. MethodsThe IPTW Cox hazards model quantified the association between statin use and dementia incidence. Subgroup analyses investigated different statin types, usage intensity, and cumulative dose–dependent relationships with dementia risk, measured by adjusted hazard ratios (aHRs) with corresponding 95% CIs. ResultsStatin users experienced a significant reduction in dementia risk (aHR: 0.47, 95% CI: 0.46-0.48). Subgroup analysis using IPTW Cox regression revealed varying dementia incidence reductions among users of different statin types, with aHRs (95% CIs) ranging from 0.09 to 0.69. Multivariate analyses unveiled a dose-dependent relationship, showing reduced dementia incidence based on cumulative defined daily doses (cDDDs) per year. The corresponding aHRs (95% CIs) were 0.20 to 0.72 across quartiles 4 to 1 of cDDD-years, with a significant trend (P < .001). The optimal daily statin use was 0.88 defined daily doses (DDDs), associated with the lowest dementia risk. Conclusions and ImplicationsStatins significantly reduced dementia risk in older adult T2DM patients. Higher cumulative defined daily doses (cDDD-years) were linked to more substantial risk reductions. This research underscores the clinical benefits of statin use in preventing dementia in this population and calls for further investigation into the underlying mechanisms. It also raises the possibility of influencing policy decisions to manage dementia risk in this vulnerable group.

Coronectomy? A case report following coronectomy of a ‘high-risk’ mandibular third molar

Background The surgical removal of mandibular third molar (M3M) is a common procedure performed by oral and maxillofacial surgeons, oral surgeons, and general dental practitioners. Apart from risks such as pain, swelling, bruising, bleeding, trismus, alveolar osteitis, post-op infection, and damage to adjacent structures which are common to all surgical extractions, M3M removal includes the risk of permanent or temporary damage to the inferior alveolar nerve (IAN) or the lingual nerve. IAN damage can significantly impact the quality of life due to altered sensation of the lip and chin area. As such, the alternative surgical option of coronectomy, which is the sectioning of the crown from the tooth and deliberate retention of the roots, can be offered to high-risk cases to avoid IAN damage. Case presentation 36-year-old female was diagnosed with recurrent pericoronitis of her left M3M. Her left M3M was partially erupted and horizontally impacted with bulbous roots that were in close proximity to the IAN. Due to a higher risk of IAN damage, she underwent a coronectomy procedure of her left M3M instead of a complete removal. She experienced typical post-operative pain and swelling but no other complications such as altered nerve sensation were reported. The surgical site was healed with full mucosal coverage after 12 weeks. Conclusion Coronectomy provides a viable alternative surgical option to removal for mandibular third molars that are at high risk of IAN damage. This is due to the significant reduction of risk of IAN damage and low incidence of failure.

Real-world progression in the survival of de novo Metastatic prostate cancer over the past decade

BackgroundThe impact of evolving treatment strategies for metastatic prostate cancer (mPCa) on real-world survival is not well understood. We analyzed changes in mPCa survival over the past decade and discussed the potential driving factors behind these changes. MethodsOur study involved 43,228 mPCa patients (2004–2020) from the SEER database, divided into 4 diagnostic periods. We used a multivariate Cox proportional hazards model to evaluate diagnostic periods' influence on overall mortality (OM) and prostate cancer-specific mortality (PSM), and calculated relative median survival improvements between adjacent periods. Subgroup analyses based on age and distant metastasis sites were conducted. ResultsPatients diagnosed in 2016 to 2020 experienced significantly reduced mortality risk compared to those in 2004 to 2007 (HR 0.64 for OM, HR 0.62 for CSM, both P < 0.001). The study period witnessed an absolute improvement in median overall survival (OS) and prostate cancer-specific survival (PCSS), 17 months (54.8%) and 25 months (67.6%) respectively. The most rapid relative survival improvement occurred post-2016, with a 29.7% increase in median OS and a 37.8% increase in PCSS compared to 2012 to 2015. There was a significant reduction in mortality risk throughout the study period in both age groups (age <75 and ≥75), but absolute survival gains were smaller in the older group (24 months [68.6%] vs. 8 months [32%] for OS, 36 months [90.0%] vs. 11 months [33.3%] for PCSS), with lower relative survival improvements after 2016 (37.2% vs. 17.9% for OS, 49% vs. 22.2% for PCSS). All metastasis site subgroups (except M1a) exhibited a significant reduction in mortality risk (all P < 0.001). Absolute survival improvements were 58 months (134.9%) for M1a, 16 months (50.0%) for M1b, and 17 months (54.8%) for M1c. ConclusionThe survival of mPCa have significantly improved over the past decade, although the progress is slower in elderly patients. Investigating the underlying reasons for survival differences among various patient profiles can further refine mPCa treatment strategies.

Predictive Value of Methicillin-Resistant Staphylococcus aureus Nasal Swab PCR Assay for MRSA Infection in Critically Ill Pediatric Patients.

Critically ill pediatric patients are frequently initiated methicillin-resistant Staphylococcus aureus (MRSA) active antibiotics during infection evaluation even though MRSA infections are rare in many patient populations. The MRSA nasal swab polymerase chain reaction assay (MRSA-NS-PCR) is a test that has been shown to have a high negative predictive value (NPV) for MRSA infection in adults. This study evaluated the diagnostic test characteristics of the MRSA-NS-PCR in predicting the presence of MRSA infection in critically ill pediatric patients. A retrospective cohort study was performed in a 44-bed pediatric intensive care unit (PICU) between 2013 and 2017. 3860 pediatric patients (54% male, median age 4 years [IQR 1-11 years]) admitted to the PICU who met pediatric systemic inflammatory response syndrome (pSIRS) criteria, were screened with a MRSA-NS-PCR, and had cultures obtained within seven days of MRSA-NS-PCR collection were included. Predictive values and post-test probabilities of the MRSA-NS-PCR for MRSA infection were calculated. MRSA-NS-PCR was positive in 8.6% of patients. MRSA infection was identified in 40 patients, equaling an incidence rate of 2 per 1000 patient days. The MRSA-NS-PCR demonstrated a positive predictive value (PPV) of 9.7%, a NPV of 99.8%, and a post-test probability for a negative test of 0.2% for MRSA infection. The MRSA-NS-PCR has a poor PPV but a high NPV for MRSA infection in PICU patients when the incidence of MRSA infection is low. Creation of protocols to guide antimicrobial selection based on MRSA-NS-PCR results may lead to improved antimicrobial stewardship and significant risk reduction.