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Air pollution represents a critical public health crisis in Bangladesh, driven by rapid industrialization, urbanization, and widespread emissions from brick kilns, traffic, and biomass burning. Elevated levels of fine particulate matter and toxic gases across both urban and rural regions contributes to significant reductions in life expectancy and escalating respiratory disease burdens. Therefore, the present review aims to examine the role of fine/ultrafine particulate matter and hazardous gases in respiratory health outcomes among the Bangladeshi population to synthesize evidence that can inform public health policy. We included 42 studies to obtain data related to the fine/ultrafine particulate matter and hazardous gases and their impact on respiratory health in Bangladesh from scientific databases including PubMed, Google Scholar, Scopus, Directory of Open Access Journals, Web of Science, EMBASE, and the Cochrane Library between 2013 and 2025 (last 12 years). Findings indicated that PM2.5 concentrations in major cities such as Dhaka, Chattogram, and Khulna exceed WHO guidelines by 8 to 18 times, with consistent hotspots linked to industrial zones, brick kilns, transportation, and seasonal biomass burning. These pollutants are strongly associated with increased prevalence of asthma, chronic obstructive pulmonary disease, bronchitis, acute respiratory infections, and hospital admissions, particularly among children, the elderly, and occupational groups. The discussion underscores severe monitoring gaps in peri-urban and rural areas, where exposure remains under-characterized despite comparable pollution levels. The findings of the present review indicates that the urgent regulatory enforcement, enhanced air quality monitoring, and targeted public health interventions are essential to mitigate respiratory health risks and reduce the nationwide burden of air pollution in Bangladesh. Furthermore, comprehensive geological and environmental monitoring studies are required across all districts to fully characterize exposure and guide effective public health interventions.

The accumulation of antibiotic fermentation residue (AFR) and pharmaceutical waste salt (WS) poses a severe disposal challenge. Herein, we report a WS-assisted co-pyrolysis strategy is proposed to convert these hazardous waste streams into an active material for hexavalent chromium (Cr(VI)) reduction. During pretreatment, the intrinsic osmotic stress of WS disrupts AFR microbial cells in AFR, thereby promoting deep dehydration. The subsequent thermal process effectively degrades residual antibiotics and antibiotic resistance genes. During co-pyrolysis, the inherent NaCl in WS acts as a mineral-phase regulator. The salt matrix promotes pore development in the carbon matrix, forming a hierarchical pore architecture. Concurrently, the salt matrix converts calcium-rich components into Ca5(PO4)3OH. These Ca5(PO4)3OH domains enrich CrO42- near Fe-containing redox sites, where Fe-mediated electron transfer drives the aqueous reduction of Cr(VI) to Cr(III). The synthesized composite achieves more than 90% reduction of low-concentration Cr(VI). Economic evaluation confirms the financial feasibility of this integrated protocol when avoided hazardous-waste disposal costs are considered. This integrated upcycling strategy mitigates pharmaceutical solid waste while producing functional biochar for environmental remediation.

Evidence on the clinical utility of baseline human epididymis protein 4 levels and their kinetics in recurrent ovarian cancer remains limited. This study evaluated longitudinal human epididymis protein 4 dynamics in real-world patients treated with platinum-based chemotherapy, aiming to determine the prognostic significance of human epididymis protein 4 kinetic parameters compared with CA125 response and established prognostic factors for progression-free and overall survival. This retrospective analysis included 220 patients with recurrent epithelial ovarian cancer treated with second-line platinum-based chemotherapy between 2000 and 2020. Four mathematical models were tested to describe human epididymis protein 4 kinetics, with model selection based on goodness of fit, visual predictive checks, and prognostic performance. The prognostic value of the most informative human epididymis protein 4 kinetic parameter (the modeled residual human epididymis protein 4 level), was assessed in univariable and multi-variable analyses. Among the 93 assessable patients, no clear associations were observed between baseline human epididymis protein 4 levels and disease characteristics. Longitudinal human epididymis protein 4 kinetics differed from those of CA125 and showed an initial decline followed by a plateau at approximately 40 days. The best-fitting model was a mono-exponential decline incorporating the modeled residual human epididymis protein 4 parameter, which was subsequently evaluated as a prognostic factor. Baseline human epididymis protein 4 levels lacked prognostic significance for progression-free or overall survival. In contrast, a higher modeled residual human epididymis protein 4 level was significantly associated with shorter progression-free and overall survival in univariable analyses (residual human epididymis protein 4 &#x2265;median vs <median; median progression-free survival: 7.2 vs 12.6 months, p =.002; median overall survival: 16.5 vs 34.9 months; p =.001) and in multi-variable models (overall survival: hazard ratio 2.65; 95% confidence interval 1.23 to 5.71, p =.012) alongside CA125 response. In this study, we identified residual HE4 levels in patients treated with second-line platinum-based chemotherapy as an independent dynamic marker of overall survival, with higher levels indicating poorer outcomes and potential chemoresistance.

There is little evidence on health and care service utilisation among those identified as needing palliative care. We aimed to quantify the uptake of services across health and care systems in the last year of life before non-sudden death, by GP palliative care registration. Multi-state models were used to evaluate pathways of service utilisation in the last year of life using population-scale linked administrative and health data for Welsh residents who died of non-sudden causes between 2014 and 2023. Cox regression models, adjusted for age, sex, rurality, area-level deprivation and GP palliative care registration were used to estimate hazards between settings, including emergency, elective and other hospital admissions, homes, care homes (with and without nursing), and death. In total, 1.8 million transitions were modelled for 267,199 individuals. Of those, 27.7% of individuals were registered for palliative care. Men, most-deprived communities, Asian ethnic groups and those living alone were under-represented on the GP palliative care register. 90.3% of emergency admissions were from home. Palliative care registered individuals had a 23% (HR 1.23 [95% CI 1.22-1.25]) increased rate of emergency admissions from home compared with unregistered. Emergency admissions from care homes with and without nursing were 17% (HR 0.83 [95% CI 0.80-0.86]) and 18% (HR 0.82 [95% CI 0.79-0.85]) lower for palliative care registered compared with unregistered residents. Health service utilisation varied significantly by GP palliative care status. Targeted identification of individuals eligible for palliative care, and additional support at home could improve whole-system outcomes.

Socioeconomic status (SES) strongly predicts survival in the Netherlands: those in the top 10% of the income distribution live about eight years longer than those in the bottom 10%. Evidence suggests these inequalities have widened over the twentieth century, although the underlying mechanisms remain unclear. One proposed explanation is that rising intergenerational mobility has altered the composition of socioeconomic groups, concentrating characteristics associated with poor health within groups with low SES. This study provides one of the first empirical tests of this hypothesis. We examine whether intergenerational social mobility influences age and cause of death in the Netherlands, by linking historical and contemporary population registers. Ancestors are identified in the Historical Sample of the Netherlands (observed 1883-2010), and descendants are identified in the System of Social-Statistical Datasets (observed 1994-2024). Our analytical sample includes 60,369 individuals from 37,495 families who survived to at least age 40 and are linked to at least one ancestor. We use Cox proportional hazards models for all-cause mortality and competing risks models for cause-specific mortality. Key predictors are ancestors' occupational status and a categorical measure of descendants' social mobility. Preliminary results show that the proportion of individuals with high SES in both childhood and adulthood increased across cohorts. These individuals experienced the lowest mortality risk. Those who remained low SES had the highest risk, despite declining in number. Upwardly mobile individuals experienced intermediate risks. Overall, mortality inequities widened over time, suggesting intergenerational mobility contributes to the growing social gradient in survival.

Cancer remains the second most prevalent cause of death in the United States, claiming 605,213 lives in 2021, surpassing COVID-19 deaths. The cancer mortality rate continued to decline between 2019 and 2020, dropping by 1.5%, marking a significant 33% decrease since 1991. This ongoing improvement primarily mirrors advances in treatment, allowing patients to achieve clinical remission and recovery. Now, a cancer patient is simultaneously exposed to the risk of primary cancer as well as other risks, such as other cancer(s) or other diseases, leading to a competing risks scenario. Analysis of survival data under competing risks and the presence of cured patients have been extensively studied individually, but there is limited work in the current literature that models the possibility of cure from one risk in the presence of competing risks. Moreover, such a model should allow for the possibility of cure from the cause-specific risk of the primary cancer; however, the overall survival probability should eventually approach zero, thereby incorporating the prevalent belief of eventual failure with certainty. We propose a novel unified competing risks cure model, based on the cause-specific hazard approach, that satisfies the aforementioned desired properties. The conditions required to establish model identifiability are studied in detail. To find the maximum likelihood estimates of the model parameters, a computationally efficient expectation maximization algorithm is developed. An extensive simulation study is carried out to demonstrate the performance of the proposed model and estimation method under different parameter settings and in the presence of multiple competing risks. Finally, an application is illustrated using breast cancer data from the SEER cancer database.

Aging out of the care system strongly predicts later homelessness, yet little is known about how levels of contact with children's social care influence youth homelessness, or whether risk peaks at particular ages. We conducted a population-wide, retrospective cohort study of individuals born January 1995-December 1997, alive and resident in Northern Ireland during follow-up (July 2011-October 2022; aged 16-28 years). Homelessness data from the Northern Ireland Housing Executive were linked to social services, administrative, and health records. Cox proportional hazards models estimated age-specific hazard ratios (HRs) for homelessness risk from age 16, comparing young people with prior social care contact ("child in need" or "child in care") to those without, adjusting for sex, area deprivation, settlement band, and mental ill health. The cohort included 90,260 individuals contributing 869,524 person-years. More than half (54.6%) of those presenting as homeless had a history of children's social care contact. Care experienced individuals faced the highest risk at age 18 (HRadj = 29.11, 95% CI 25.33-33.45), while risk among those with a child in need history peaked at age 17 (HRadj = 8.10, 95% CI 7.13-9.21), relative to peers with no social care history. Young people with a history of social care contact are markedly overrepresented among the homeless population. The transition to adulthood (ages 17-18-years) is a critical period of vulnerability, underscoring the need for targeted interventions and enhanced support so social care experienced young people can enter adulthood without homelessness.

Our study identifies industrial subsectors in Canada where a few facilities are responsible for the majority of PM2.5 and PM2.5 precursor emissions and investigates whether these facilities are disproportionately sited near structurally marginalized socio-demographic groups, indicating the existence of "double disproportionalities." We find that disproportionality in emissions exists across pollutants and subsectors. Patterns of disproportionate facility siting differ between urban and rural settings. Facility siting from "Oil and Gas Extraction" disproportionately affects more marginalized groups in urban areas, while "mining and quarrying" affects more groups in rural areas. Urban Indigenous populations are highly affected by disproportionate siting patterns for both all emitters and high emitters. Different patterns emerge when considering clusters of industrial facilities: Low-income and Black populations are more likely to reside in proximity to multiple emitting facilities. Our results support the existence of double disproportionalities for some sectors and highlight the need for research on cumulative environmental hazards.

Proteinuria is a key marker in IgA nephropathy (IgAN). However, long-term thresholds and significance of early changes in proteinuria remains unclear in US populations. Retrospective cohort study of 745 adult patients with IgA nephropathy from the TriNetX US network (2015-2023). The baseline Time-average proteinuria (TAP) were calculated and categorized as <500, 500-1,000, 1,000-2,000, and >2,000 mg/g. Starting 1 year post diagnosis, the composite kidney failure outcome (sustained eGFR &#x2264;15 mL/min/1.73 m2, sustained >40% eGFR decline, initiation of dialysis, or all-cause mortality) was evaluated. Associations with baseline TAP and changes in TAP at first-year were evaluated using Kaplan-Meier analysis and multivariable Cox proportional hazard models. Out of 745 patients (mean age 43.5 [&#xb1;16] years, 58% male, 68% White), a composite outcome occurred in 175 (23.5%) of patients over a median follow-up of 5.4 years (IQR: 3.2-7.2). Survival analysis showed 13.8% of patients with TAP <500 mg/g remained at risk of kidney failure by 8 years. Compared to TAP <500 mg/g, adjusted hazard ratios were significantly higher for TAP 1,000-2,000 mg/g (aHR 2.84; 95% CI: 1.66-4.85) and TAP >2,000 mg/g (aHR 5.68; 95% CI: 3.45-9.36); whereas TAP 500-1,000 mg/g was not significant after adjustment (aHR 1.69; 95% CI: 0.96-2.97). Higher baseline eGFR and white race were associated with better outcomes. Among 389 patients with follow up TAP data at the first-year observation period, each one-category reduction in TAP was associated with &#x223c;40% lower risk of composite outcome, and &#x2265;30% and &#x2265;50% proteinuria reductions were associated with 62% and 66% lower risk of composite outcome, respectively. In US adults with IgA nephropathy, baseline proteinuria exceeding 1,000 mg/g identifies a high-risk group. Early proteinuria reductions - either by category (TAP) or percentage (&#x2265;30-50%) - strongly predict improved outcomes. This study supports use of proteinuria as a modifiable, treat-to-target surrogate for prognosis and treatment monitoring.

Biologic augmentation with bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP) has been used in conjunction with hip decompression (HD) for the treatment of pre-collapse osteonecrosis (ON) of the femoral head. This study reports a concise minimum 10-year follow-up of a previously published prospective cohort of patients who had corticosteroid-induced ON treated with HD augmented with BMAC and PRP. There were 21 patients (34 hips) who had pre-collapse corticosteroid-associated ON who underwent HD combined with BMAC and PRP. Their mean age and body mass index at surgery were 43 years (range, 22 to 66) and 31 (range, 22 to 41), respectively. Survivorship free from femoral head collapse and conversion to total hip arthroplasty (THA) was assessed using Kaplan-Meier analysis. Risk factors for failure were evaluated using Cox regression analyses. Functional outcomes were assessed using the Harris Hip Score (HHS). At a mean follow-up of 11 years (range, 10 to 13), survivorship free from conversion to THA was 62%. Indications for conversion included femoral head collapse (n = 5), persistent pain without collapse (n = 5), and progression of osteoarthritis (n = 2). Patients who had low preoperative Kerboul angles (KA) (grades 1 to 2) demonstrated 11-year survivorship of 91% free from collapse and 66% free from THA, whereas those who had high KA (grades 3 to 4) demonstrated survivorship of 40% for both outcomes (P = 0.0004 and P = 0.083, respectively). High preoperative KA independently increased the risk of femoral head collapse (hazard ratio (HR) 13.2; P = 0.005). In hips not converted to THA, mean HHS improved from 58 preoperatively to 86 at final follow-up (P < 0.0001). There were no additional conversions to THA beyond the previously reported mean 7-year follow-up. At a minimum of 10 years, HD augmented with BMAC and PRP resulted in sustained hip preservation in patients who had corticosteroid-induced osteonecrosis. Lesion size, as defined by the KA, remains the most important predictor of longer-term success.

The risk of secondary cancers in breast cancer survivors remains a significant concern. This study aimed to evaluate the association between treatment modalities and the time to development of secondary cancers in patients after mastectomy or breast-conserving therapy (BCT). A retrospective analysis was conducted on 6590 patients from 2 centres (Poznan and Gorzow, Poland) treated for breast cancer between 2017 and 2022. A total of 149 patients from this group developed secondary cancer. Data included demographic and clinical characteristics, treatment types (chemotherapy, hormonotherapy, radiotherapy), and subtypes of primary breast cancer (luminal, triple negative, HER2 positive). Statistical methods included Kaplan-Meier analysis, Cox proportional hazards models, and &#x3c7;2 tests. The median time to secondary cancer detection was significantly shorter in patients with TNBC/HER2+ subtypes (2.8 years) compared to luminal subtypes (6.1 years; p = 0.024). TNBC/HER2+ subtypes were associated with a 1.9-fold increased risk of secondary cancers (HR = 1.93; p = 0.048). No significant association was found between treatment type and the occurrence of secondary cancers (p > 0.05). However, combined therapies (e.g. chemotherapy + hormonotherapy) showed a trend toward reduced risk (HR = 0.53; p = 0.061). The most common secondary cancers were gastrointestinal malignancies (27%) and gynaecological cancers (15%). The subtype of primary breast cancer significantly influences the time to secondary cancer development, with TNBC/HER2+ patients at higher risk. Treatment modalities did not significantly affect secondary cancer risk, but combined therapies may offer protective effects. These findings highlight the need for tailored surveillance strategies based on tumour biology.

Record linkage enables research using data from multiple sources but can introduce linkage errors-missed matches and false matches-that may bias downstream analyses. Evidence on their impact has not been systematically synthesized to inform linkage practice or statistical adjustment. Objective: To synthesize published evidence on the impact of record linkage errors on downstream analyses in health and social science research. A comprehensive literature search was conducted in Embase. Reference list scanning and supplemental hand searching were used to identify additional relevant studies not captured in the systematic search. The systematic search identified 228 articles. Title and abstract screening yielded 47 articles for full-text review, of which seven met the inclusion criteria. Two additional articles were identified through reference list scanning and four through hand searching, resulting in 13 included publications. Eleven studies (85%) reported that linkage errors had a considerable impact on study findings, specifically on Cox proportional hazards ratios (n&#x2009;=&#x2009;5), logistic regression odds ratios (n&#x2009;=&#x2009;2), and rates or ratios (n&#x2009;=&#x2009;4). False matches were shown to reduce estimated effect sizes, whereas missed matches increased standard errors, reducing the precision of estimates, and introduced sampling error by disproportionately excluding certain population subgroups. Evidence suggests that data linkage errors can substantially affect research findings across analytical methods. These findings highlight the importance of accurate linkage processes, appropriate statistical adjustment for residual linkage error, and transparent reporting practices to support assessment of linkage quality and potential sources of bias.

Postpartum hypertension (PPHTN) drives severe maternal morbidity in women with hypertensive disorders of pregnancy (HDP). The uncharacterized effect of labor epidural analgesia (LEA) on postpartum blood pressure trajectories may explain its protective association with severe maternal morbidity. We aim to investigate whether LEA exposure is associated with a delayed onset of PPHTN during hospitalization in women with HDP. We conducted a retrospective cohort study of women with HDP from 2018 to 2023. Participants were categorized based on LEA duration, with non-recipients assigned a duration of zero. An optimal LEA duration cut-off was identified using the maximally selected log-rank statistic to facilitate group comparison. The primary outcome was in-hospital PPHTN, defined as &#x2265;2 postpartum blood pressure measurement meeting standard hypertensive criteria. Time-to-event analyses were performed using Kaplan-Meier estimates and the Log rank test. Multivariable Cox regression with DAG-guided covariate selection was used to adjust for potential confounders. Secondary outcomes included postpartum antihypertensive treatment patterns, specifically combination therapy use and daily labetalol dose. Three prespecified sensitivity analyses assessed the robustness of results. Of 1,069 women included in the final analysis, 823 (77.0%) received LEA. Longer LEA duration was significantly associated with a reduced hazard of PPHTN (HR = 0.96 per hour; 95% CI: 0.93-0.98; P = 0.002). The optimal duration cut-off for discriminating PPHTN risk was 3.5&#xa0;hours. Women with LEA duration >3.5&#xa0;hours had lower in-hospital PPHTN incidence, a longer median time to onset, and reduced postpartum antihypertensive requirements, including lower rates of combination therapy and labetalol dosing, while nifedipine use was similar between groups. After multivariable adjustment, LEA >3.5&#xa0;hours was independently associated with a reduced risk of PPHTN (HR = 0.72; 95% CI: 0.58-0.88; P = 0.001). Sensitivity analyses yielded consistent results in women not requiring postpartum antihypertensive therapy and across gestational hypertension and pre-eclampsia subgroups. In the cause-specific Cox model, LEA >3.5&#xa0;hours was associated with a lower hazard of PPHTN, consistent with the primary model. Among women receiving postpartum antihypertensives, LEA duration was not significantly associated with PPHTN risk but was linked to lower labetalol doses. Longer LEA duration was associated with a reduced risk of postpartum hypertension and lower antihypertensive use in women with HDP. These observational findings indicate that prolonged analgesia may be associated with improved postpartum hemodynamic stability, suggesting consideration for its continuation in eligible patients; prospective studies are needed to confirm causality and guide clinical practice.

Advances in genomic techniques have great potential to accelerate the development of the microalgal sector and to address key challenges related to upscaling. Genetically modified microalgae (GMM) can exhibit enhanced biomass productivity, increased accumulation of valuable biocompounds, or express other beneficial traits compared to their non-modified counterparts. However, the application of GMM and their associated cultivation methods may lead to unintentional release, potentially affecting adjacent ecosystems. Here we apply a problem formulation approach to support the environmental risk assessment of novel GMM relative to their wild-type counterparts. We focus on potential effects on ecosystem services provided by natural microalgae communities. We present plausible pathways to harm through which GMM could exert adverse effects and formulate relevant research questions to evaluate the likelihood of each step within these pathways. Existing knowledge on the hazards associated with invasiveness, gene transfer and toxicity of GMM is compiled and discussed. Together, these elements provide a practical framework for identifying relevant hazards and guiding data generation to support environmental risk assessments of GMM.

Sleep disturbance is a core feature of affective and neurodegenerative disorders. This study tracks long-term sleep disturbance trajectories and their links to incident Alzheimer's disease (AD) and longitudinal clinical and pathological changes. A total of 774 non-demented participants from the ADNI cohort were included. Sleep disturbance (NPI sleep item) trajectories over 8 years were identified via group-based trajectory modeling. Cox proportional hazards regression was used to estimate the risk of incident AD. Linear mixed-effects models were used to assess longitudinal changes in cognition, structural magnetic resonance imaging, amyloid-&#x3b2; positron emission tomography (A&#x3b2;-PET), fluorodeoxyglucose (FDG)-PET, and cerebrospinal fluid (CSF) biomarkers. Three trajectories emerged: "Low-stable" (37.2%), "High-peaked" (21.0%), and "Moderate-increasing" (41.8%). Compared to those without sleep disturbance, a significantly elevated risk of incident AD was associated with "High-peaked" (hazard ratio [HR]&#x202f;=&#x202f;3.28; 95% confidence interval [CI] = 1.89-5.70; p&#x202f;<&#x202f;0.001) and "Moderate-increasing" trajectories (HR&#x202f;=&#x202f;2.13; 95% CI = 1.28-3.53; p&#x202f;=&#x202f;0.003) but not with the "Low-stable" trajectory (p&#x202f;=&#x202f;0.888). Participants with "High-peaked" trajectory exhibited faster declines in cognition (MMSE, memory, executive function) (p&#x202f;<&#x202f;0.050) and a steeper reduction in CSF A&#x3b2;1-42 levels (p&#x202f;=&#x202f;0.038) than those with non-sleep disturbance. However, there were no significant differences between groups in the rates of hippocampal, entorhinal, or middle temporal atrophy, global A&#x3b2;-PET burden, or FDG-PET changes (p&#x202f;>&#x202f;0.050). "High-peaked" and "Moderate-increasing" sleep trajectories predict higher AD risk, faster cognitive decline, and faster A&#x3b2;1-42 reduction. Long-term monitoring of sleep behaviors is essential for identifying and stratifying individuals at high risk for AD.

Understanding the longer-term health impacts of SARS-CoV-2 infection is essential for informing public health policy. While earlier studies suggested increased diabetes risk after infection, evidence for the Omicron period and the modifying effect of vaccination remains limited and inconsistent. A matched cohort study was conducted using a large-scale linked asset covering over 90% of the Australian population, integrating COVID-19 notifications with demographic information and administrative health records. Individuals aged &#x2265;16 years diagnosed with COVID-19 between 15 December 2021 and 31 December 2022 were matched 1:1 to those without COVID-19 by age, sex, and COVID-19 vaccine recency. Cox-models were used to estimate the association between COVID-19 and initiation of diabetes treatment, adjusting for relevant demographic and health-related factors. Negative control outcomes were assessed. Among 5,736,501 matched pairs followed for a median of 200 days, 45,816 initiated diabetes treatment. Compared to those without COVID-19, individuals with COVID-19 had a 14% higher risk of subsequently initiating diabetes treatment (aHR 1.14 [95%CI 1.12; 1.17]), with the highest risk observed among those hospitalised due to COVID-19 (aHR 2.52 [95%CI 2.23; 2.84]). The risk was also higher for individuals with &#x2264;2 COVID-19 vaccine doses compared to those boosted within the last 90 days (aHR of 1.22 [95%CI 1.18; 1.25] vs 1.08 [95%CI 1.04; 1.12]). We found an increased risk of diabetes following SARS-CoV-2 infection during the Omicron dominant period and a protective effect of COVID-19 vaccination. However, the findings should be interpreted with caution considering the potential for unmeasured confounding.

This study aims to investigate the association between domestic water hardness and the risk of severe metabolic dysfunction-associated steatotic liver disease (MASLD) and to assess the potential modifying role of genetic susceptibility. The UK Biobank is a prospective cohort study that recruited over 500,000 participants across the United Kingdom between 2006 and 2010. Domestic water hardness was assessed based on calcium carbonate (CaCO3) concentration. Severe MASLD was defined using ICD-10 codes and death registry data. A polygenic risk score (PRS) for severe MASLD was constructed using 61 single nucleotide polymorphisms (SNPs) and divided into tertiles (low, intermediate, high risk). Cox proportional hazards regression models and restricted cubic spline analyses were employed. A total of 7039 incident severe MASLD cases (1.5%) were documented during a mean 13.8-year follow-up. Compared to water hardness <&#x2009;100 mg/L, individuals with domestic water hardness of 100-200&#x2009;mg/L were associated with a 22% lower risk of severe MASLD (HR 0.78, 95% CI 0.72-0.86), while water hardness >&#x2009;200&#x2009;mg/L was associated with an 11% higher risk (HR 1.11, 95% CI 1.05-1.16). A non-linear relationship was observed between water hardness and severe MASLD incidence (p for non-linear <&#x2009;0.001). The association did not significantly differ across strata of genetic susceptibility (p-interaction >&#x2009;0.05). The study revealed a U-shaped relationship between water hardness and severe MASLD, which was robust to genetic risk. An optimal water hardness range (100-200&#x2009;mg/L) may serve as a modifiable environmental factor for the prevention of severe MASLD.

The C-reactive protein-albumin-lymphocyte (CALLY) index represents a novel composite biomarker integrating inflammatory, nutritional, and immune parameters. We aimed to examine the relationship between CALLY index and chronic kidney disease (CKD) prevalence. This cross-sectional analysis utilized data from the National Health and Nutrition Examination Survey. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 and/or urinary albumin-to-creatinine ratio (UACR) &#x2265; 30 mg/g. Multivariable logistic regression and restricted cubic spline (RCS) analyses assessed the relationship between CALLY index and CKD risk. Among CKD patients, Cox proportional hazards models evaluated associations of the CALLY index with all-cause and cardiovascular mortality. Among the 26 996 participants, 4997 individuals were diagnosed with CKD. Participants with CKD demonstrated lower CALLY index values compared to those without CKD. Multivariable logistic regression indicated that, compared to the lowest quartile, the highest quartile showed 29.5% reduced CKD risk (OR = 0.705, 95% CI: 0.589-0.845, p < 0.001). The RCS model demonstrated a significant L-shaped association between CALLY index and CKD prevalence. Among CKD patients, higher CALLY index significantly predicted better survival outcomes for both all-cause and cardiovascular mortality. The CALLY index demonstrates inverse associations with CKD risk and mortality, suggesting its potential utility as a comprehensive biomarker for CKD risk stratification and prognosis assessment.

Patients receiving voriconazole often have insufficient hepatic reserve, making it difficult to stratify the risk of severe hepatotoxicity using therapeutic drug monitoring (TDM) alone. This multicenter study aimed to evaluate whether the albumin-bilirubin (ALBI) score can stratify the risk of hepatotoxicity in patients undergoing TDM. This multicenter, retrospective cohort study included 608 patients. The primary outcome was voriconazole-induced hepatotoxicity. The cumulative risk of hepatotoxicity was evaluated using a Gray's test between ALBI score &#x2265;-2.0 or <-2.0, and a landmark approach was applied as a sensitivity analysis. The Fine-Gray test was performed, and independent risk factors were used for decision tree analysis. The cumulative risk of hepatotoxicity was significantly higher in the ALBI score &#x2265;-2.0 group than that in the ALBI score <-2.0 group (p&#x202f;=&#x202f;0.006), and this trend was confirmed in a sensitivity analysis. The Fine-Gray model revealed that the ALBI score &#x2265;-2.0 (subdistribution hazard ratio, 1.951; 95% confidence interval, 1.135-3.355; p&#x202f;=&#x202f;0.016) was an independent risk factor. In the decision tree model, the development of hepatotoxicity was lowest (6.5%, 12/186) in patients with ALBI score <-2.0 and voriconazole trough concentration (Cmin) <4.0 &#x3bc;g/mL, whereas that in patients with ALBI score &#x2265;-2.0 and Cmin &#x2265;4.0 &#x3bc;g/mL was highest at 18% (27/153), with an accuracy of 88.3%. The present study demonstrated that combining an ALBI score &#x2265;-2.0 with the Cmin of voriconazole allows risk stratification for voriconazole-induced hepatotoxicity with high accuracy, and this model may provide a practical risk stratification tool.