Significant Reduction In Risk Research Articles

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...

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.

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.

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.

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.

Comparative effectiveness of warfarin management strategies: a systematic review and network meta-analysis

The management of warfarin therapy presents clinical challenges due to its narrow therapeutic index. We aimed to evaluate the comparative effectiveness of different management strategies in patients using warfarin. PubMed, Embase, Cochrane CENTRAL, CINAHL, and EBSCO Open Dissertation were searched from inception to 8 May 2024. Randomized controlled trials that compared the following interventions: patient self-management (PSM), patient self-testing (PST), anticoagulation management services (AMS), and usual care in patients prescribed warfarin for any indication were included. Risk ratios (RR) with 95% confidence interval (CI) were estimated using a random-effects model. Surface under the cumulative ranking curves (SUCRA) were used to rank different interventions. The certainty of evidence was assessed using the Confidence in Network Meta-Analysis (CINeMA) online platform. This study is registered with PROSPERO (CRD42023491978). Twenty-eight trials involving 8100 participants were included, with follow-up periods of 1-24 months. Mean warfarin dosages were 4.9-7.2mg/day. Only PSM showed a significant reduction of major TE risk compared with usual care (RR=0.41; 95% CI: 0.24, 0.71; I2=0.0%) with moderate certainty of evidence. The 97.6% SUCRA also supported the beneficial effects of PSM over other interventions. The combined direct and indirect evidence showed significantly higher TTR in PSM compared with usual care (MD=7.39; 95% CI: 2.39, 12.39), with very low certainty. However, direct evidence showed non-significant TTR improvement (MD=6.49; 95% CI:-3.09, 16.07, I2=96.1%). No differences across various strategies were observed in all-cause mortality, major bleeding, stroke, transient ischemic attack, and hospitalization. PSM reduces the risk of major TE events compared with usual care, tends to improve anticoagulation control, and should be considered where appropriate. Agency for Healthcare Research and Quality (grant ID 5R18HS027960).

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.

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 elderly 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 elderly population with 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.

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.

Assessment of flood risk in a coastal city considering multiple socio-economic vulnerability scenarios

Abstract. The Intergovernmental Panel on Climate Change stresses the importance of vulnerability and exposure along with hazard in defining flood risk. Therefore, a novel approach for flood risk quantification is proposed that evaluates the impact of various realistic socio-economic scenarios on risk reduction. The flood hazard is derived from a hydrodynamic flood modelling framework over Mumbai, India's highly flood-prone coastal megacity. The socio-economic vulnerability is assessed by a multivariate approach based on principal component analysis and data envelopment analysis. Finally, the flood risk is quantified and mapped by aggregating hazard and vulnerability for different socio-economic scenarios, also key indicators contributing to a significant reduction in vulnerability and risk are identified. This non-structural long-term flood risk management approach will benefit densely populated urban areas, especially in developing, and underdeveloped countries.

Fewer Dislocations After Total Hip Arthroplasty With Robotic Assistance or Fluoroscopic Guidance

BackgroundComputer navigation and robotic assistance may reduce total hip arthroplasty (THA) dislocations by improving the accuracy and precision of component positioning. We investigated dislocation rates for THAs using conventional techniques, robotic assistance, and computer navigation, while controlling for surgical approach, dual mobility (DM) use, and fluoroscopic guidance. MethodsWe reviewed 11,740 primary THAs performed between June 2016 and December 2022, including 5,873 conventional, 1,293 with robotic-arm assistance, and 4,574 with navigation. The approach was posterior in 6,580 (56.0%), anterior in 4,342 (37.0%), and lateral in 818 (7.0%). A DM was used in 10.4%. Fluoroscopy was used in 3,653 cases and only with the anterior approach. Multivariate analyses yielded odds ratios (OR) for dislocation and revision. Additional regression analyses for dislocation were performed for approach and DM. ResultsRaw dislocation rates were as follows: conventional 1.2%, robotic 0.4%, navigation 0.9%, anterior with fluoroscopy 0.4%, anterior without fluoroscopy 2.3%, posterior 1.3%, and lateral 0.5%. Upon multivariate analysis, use of robotics was found to be associated with significantly reduced dislocation risk compared to conventional (OR: 0.3), as did anterior (OR: 0.6) compared to posterior approach; navigation and lateral approach were not found to be associated with a significant reduction in risk. For the anterior approach, multivariate analysis demonstrated that fluoroscopy significantly reduced dislocation risk (OR: 0.1), while DM, robotics, and navigation were not significant. For the posterior approach, the dislocation risk was lower with robotics than with conventional (OR: 0.2); the use of navigation or DM did not demonstrate a significant reduction in risk. ConclusionsThe use of robotics was associated with a reduction in dislocations for this cohort overall. Further, fluoroscopy in the anterior approach and robotic assistance in the posterior approach were both associated with decreased dislocation risk. The role of imageless computer navigation and DM implants requires further study.

Comprehensive management of polypharmacy in older patients with diabetes

Background: Diabetes mellitus is a complex group of chronic metabolic conditions. The incidence of frailty, sarcopenia, geriatric syndrome, and multiple chronic conditions is high in older patients with diabetes, who often require multiple medications for optimal glucose control and treatment of associated chronic complications. Unfortunately, polypharmacy is associated with a high risk of adverse outcomes, such as hypoglycemia, drug-drug interactions, and an increased socioeconomic burden in older adults with diabetes.Current Concepts: Elderly patients with diabetes are at a high risk for polypharmacy and consequently, a high risk of adverse drug reactions. Polypharmacy is defined as the cumulative use of five or more medications. Comprehensive management and deprescribing are the most important approaches to reduce polypharmacy. Deprescription refers to reduction in or cessation of inappropriate medications.Discussion and Conclusion: Polypharmacy continues to increase the risk of morbidity and mortality among older adults with diabetes. A comprehensive polypharmacy management and deprescription plan is warranted for significant risk reduction in elderly patients with diabetes.

Non-diabetes status after diagnosis of impaired glucose tolerance and risk of long-term death and vascular complications: A post hoc analysis of the Da Qing Diabetes Prevention Outcome Study.

The association between years of non-diabetes status after diagnosis of impaired glucose tolerance (IGT) and the risk of long-term death and cardiovascular outcomes needed to be clarified. In this post hoc analysis, we included 540 individuals with IGT who participated in the original Da Qing Diabetes Prevention Study (DQDPS). In the DQDPS, all participants were diagnosed with IGT by a 75 g oral glucose tolerance test and randomized to intervention or control groups with a 6-year lifestyle intervention trial. After the completion of the trial, death, cardiovascular events, and microvascular complications were monitored over a 30-year follow-up. In this post hoc analysis, the Cox analysis assessed the extended risk of these outcomes in individuals who either remained non-diabetes status or progressed to diabetes at the end of 2, 4, and 6 years after diagnosis of IGT. In all participants, the difference in the cumulative incidence rate of the outcomes between the diabetes and non-diabetes group gradually increased over 30 years. Compared with the diabetes group, a significantly lower risk of all-cause death (hazard ratio [HR]: 0.74; 95% confidence interval [CI]: 0.57 to 0.97, p = 0.026), cardiovascular events (HR: 0.63; 95% CI: 0.49 to 0.82, p < 0.001), and microvascular complications (HR: 0.62; 95% CI: 0.45 to 0.86, p = 0.004) first emerged in individuals who remained non-diabetes at the 4 years visit, whereas the significant risk reduction in cardiovascular death was first observed at the end of 6 years (HR: 0.56; 95% CI: 0.39 to 0.81, p = 0.002) after adjustment for age, sex, smoking status, BMI, systolic blood pressure, blood glucose, total cholesterol, intervention, and medications (including insulin plus oral hypoglycaemics, antihypertensives, and lipid-lowering agents). The results in the original intervention group alone were similar to the whole group. The main limitations of our study are the limited number of participants and the sole ethnicity of the Chinese population. In this study, we observed that maintaining several years of non-diabetes status after IGT diagnosis was associated with a significant reduction in long-term risk of death and vascular complications, and for most of these outcomes, maintaining at least 4 years of non-diabetes status may be needed to achieve a significant risk reduction.

Quantifying microbial risk from drinking water production process under changing climate and socio-economic conditions

Consumption of drinking water containing pathogenic microorganisms may pose serious health risks from waterborne diseases. Quantifying such risks is essential for guiding interventions and policy decisions. Quantitative microbial risk assessment (QMRA) is a very useful method to estimate the public's risk of infection from disease-causing microorganisms in water sources. QMRA of drinking water production process is limited worldwide and so far no such QMRA study has been conducted in Bangladesh. Moreover, climate and socio-economic changes may impact waterborne pathogens and associated health risks, but to what extent remains unclear, because comprehensive QMRA by taking into account combined impact of climatic and socio-economic factors has never been done worldwide so far. In this study, the Swedish QMRA tool was applied to evaluate public health risk from drinking water production process in Dhaka, Bangladesh as a case study. At first, current risk was quantified, and then the potential future risk was projected by taking into account climate and socio-economic factors. The results revealed that the annual infection risks at the current (2020s) baseline condition were below the acceptable risk threshold 10–4 infections per person per year (as proposed by several USEPA scientists) for all three pathogens Salmonella, norovirus and Giardia. However, after extreme events with sewer overflow and agricultural runoff, norovirus violates the acceptable risk thresholds, and the risks for Salmonella and Giardia are in borderline. The selected sustainable future scenario showed some improvement in terms of annual infection risks, while the uncontrolled scenario resulted in substantially higher infection risks both in the near and far future compared to the current scenarios. Installment of a UV treatment step as an additional treatment barrier resulted in significant infection risk reduction. According to the sensitivity analysis results, socio-economic factors such as human population, livestock, and pathogen removal in wastewater were found to have greater influence on the infection risks, compared to climate change. The study can help policy makers and water managers to identify interventions to reduce the burden of disease on the population. The tool can be used to assess the health risk associated with drinking water production process in other areas of the world with similar characteristics.

Metformin in diabetes management: expanding benefits. Review

We have conducted a narrative review based on a structured search strategy, focusing on the effects of metformin on the progression of non‑diabetic hyperglycemia to clinical type 2 diabetes mellitus. The principal trials that demonstrated a significantly lower incidence of diabetes in at‑risk populations randomized to metformin (mostly with impaired glucose tolerance) were published mainly from 1999 to 2012. Metformin reduced the 3‑year risk of diabetes by ‑31% in the randomized phase of the Diabetes Prevention Program (DPP), vs.‑ 58% for intensive lifestyle intervention. Metformin was most effective in younger, heavier subjects. Diminishing but still significant reductions in diabetes risk for subjects originally randomized to these groups were present in the trial’s epidemiological follow‑up, the DPP Outcomes Study (DPPOS) at 10 years (‑18 and ‑34%, respectively), 15 years (‑18 and ‑27%), and 22 years (‑18 and ‑25%). Long‑term weight loss was also seen in both groups, with better maintenance under metformin. Subgroup analyses from the DPP/DPPOS have shed important light on the actions of metformin, including a greater effect in women with prior gestational diabetes, and a reduction in coronary artery calcium in men that might suggest a cardioprotective effect. Improvements in long‑term clinical outcomes with metformin in people with non‑diabetic hyperglycemia («prediabetes») have yet to be demonstrated, but cardiovascular and microvascular benefits were seen for those in the DPPOS who did not vs. did develop diabetes mellitus. Multiple health economic analyses suggest that either metformin or intensive lifestyle intervention is cost‑effective in a community setting. Long‑term diabetes prevention with metformin is feasible and is supported in influential guidelines for selected groups of subjects. Future research will demonstrate whether intervention with metformin in people with non‑diabetic hyperglycemia will improve long‑term clinical outcomes.

SGLT2i effect on atrial fibrillation: A network meta‐analysis of randomized controlled trials

AbstractIntroductionGliflozins are recommended as first‐line treatment in patients with heart failure and/or cardiovascular comorbidities and are demonstrated to reduce atrial fibrillation (AF) occurrence. However, it is not well known which gliflozin yields the larger cardioprotection in terms of AF occurrence reduction. Hence, we aimed to compare data regarding AF recurrence associated with different gliflozins.MethodsAn accurate search of online scientific libraries (from inception to June 1, 2023) was performed. Fifty‐nine studies were included in the meta‐analysis involving 108 026 patients, of whom 60 097 received gliflozins and 47 929 received placebo.ResultsGliflozins provided a statistically significant reduction of AF occurrence relative to standard of care therapy in the overall population (relative risks [RR]: 0.8880, 95% CI: [0.8059; 0.9784], p = .0164) and in patients with diabetes and cardiorenal diseases (RR: 0.8352, 95% CI: [0.7219; 0.9663], p = .0155). Dapagliflozin significantly decreased AF occurrence as compared to placebo (0.7259 [0.6337; 0.8316], p &lt; .0001) in the overall population, in patients with diabetes (RR: 0.2482, 95% CI: [0.0682; 0.9033], p = .0345), with diabetes associated with cardiorenal diseases (RR: 0.7192, 95% CI: [0.5679; 0.9110], p = .0063) and in the subanalysis including studies with follow‐up ≥1 year (RR: 0.7792, 95% CI: [0.6508; 0.9330], p = .0066). No significant differences in terms of AF protection were found among different gliflozins.ConclusionsDapagliflozin use was associated with significant reduction in AF risk as compared to placebo in overall population and patients with diabetes, whereas the use of other gliflozins did not significantly reduce AF occurrence.

Real-World Effectiveness and Safety of Tixagevimab-Cilgavimab: A Target Trial Emulation Study.

Immunocompromised individuals are at high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and subsequent severe or fatal coronavirus disease 2019 (COVID-19), yet they have suboptimal responses to mRNA and inactivated COVID-19 vaccines. The efficacy of tixagevimab-cilgavimab in reducing symptomatic SARS-CoV-2 infection was demonstrated in phase III clinical trials. Nevertheless, real-world data on the effectiveness and safety of tixagevimab-cilgavimab remain limited. The aim was to evaluate the effectiveness and safety of tixagevimab-cilgavimab among immunocompromised individuals. Adults who were immunocompromised or receiving immunosuppressive therapies were included in this target trial emulation using territory-wide electronic health records in Hong Kong. A sequential trial emulation approach was adopted to compare effectiveness and safety outcomes between individuals who received tixagevimab-cilgavimab and individuals who did not. A total of 746 tixagevimab-cilgavimab recipients and 2980 controls were included from 1 May 2022 to 30 November 2022. Tixagevimab-cilgavimab significantly reduced the risk of COVID-19 infection (hazard ratio [HR] 0.708, 95% confidence interval [CI] 0.527-0.951) during a median follow-up of 60 days. No significant difference was observed in the risk of COVID-19-related hospitalisation. Zero versus eight COVID-19 mortality cases and zero versus two severe COVID-19 cases were observed in tixagevimab-cilgavimab recipients and controls, respectively. Notably, significant risk reduction in COVID-19 infection was also observed among immunocompromised individuals who had been previously vaccinated with three or more doses of COVID-19 vaccine, or had no prior COVID-19 infection history. Tixagevimab-cilgavimab was effective in reducing COVID-19 infection among immunocompromised patients during the Omicron wave. Findings were consistent among individuals who previously received three or more doses of COVID-19 vaccine, or had no previous history of COVID-19 infection.