Lung cancer in never-smokers represents a distinct clinical and biologic entity. However, its epidemiologic characteristics remain incompletely described in the Middle East. To characterize lung cancer in never-smokers and compare it with ever-smokers in a multicenter Saudi cohort. Retrospective multicenter cohort study. Three tertiary-care centers of King Faisal Specialist Hospital & Research Centre system in Saudi Arabia. Adults with histologically confirmed primary lung cancer diagnosed between January 2020 and December 2024 were classified as never- or ever-smokers. Carcinoid tumors were excluded from the comparative analysis. Demographic, histologic, stage, and molecular characteristics were compared. Multivariable logistic regression identified factors independently associated with never-smoker status. Clinical, histologic, stage, and molecular differences between never-smokers and ever-smokers expressed as crude and adjusted odds ratios (95% confidence interval). 301 patients reviewed; 253 in the primary analytic cohort (92 never-smokers, 161 ever-smokers). Among 280 patients with available smoking history, 253 were included after excluding 27 carcinoid tumors (92 never-smokers [36%] and 161 ever-smokers [63.6%]). Never-smokers were mostly females (64/92 (70%) vs 12/161 (7.5%); P<.001) and younger than ever-smokers [mean age 59.2 (standard deviation 13.5) vs 62.3 (11.1) years; P=.065]. Adenocarcinoma predominated among never-smokers (81/92 (88%) vs 108/161 (67.1%); P<.001). Among patients tested, Epidermal growth factor receptor (EGFR) mutations(34/86 (39.5%) vs 12/128 (9.4%); P<.001) and Anaplastic lymphoma kinase (ALK) rearrangements [17/86 (20%) vs 9/128 (7.0%); P=.01] were significantly more frequent in never-smokers, whereas KRAS alterations were more common in ever-smokers [6/86 (7%) vs 21/128 (16.4%); P=.068]. Stage III-IV disease was common in both groups (70% vs 72%; P=.783). In multivariable analysis, female sex [adjusted odds ratio (OR) 31.9, 95% CI 14.2-71.6; P<.001] and adenocarcinoma histology (adjusted OR 5.3, 95% CI 2.0-14.2; P<.001) were independently associated with never-smoker status. In this multi-center Saudi cohort, more than one-third of lung cancers occurred in never-smokers, characterized by female predominance, adenocarcinoma histology, and frequent EGFR and ALK alterations. These findings support comprehensive molecular testing regardless of smoking history and underscore the need for strategies to improve early recognition of lung cancer in never-smokers. Retrospective design, incomplete molecular testing, tertiary-referral setting, and potential misclassification of smoking exposure, including unrecorded waterpipe and electronic-cigarette use.
It is important to investigate whether declines in smoking initiation with age are less pronounced among people with mental health problems than among those without. If smoking is used to cope with new mental health symptoms, initiation may occur at older ages in this group. Using cross-sectional data from 29 845 adults aged 16-45 in Great Britain (surveyed October 2020-June 2023), we examined whether associations between age and i) ever smoking prevalence and ii) length of abstinence (among those who quit >1 year ago; n = 4315) differed by past-month psychological distress or history of a mental health condition (MHC). Approximately half of those reporting distress (46.5% [95%CI = 45.5-47.5]) or history of a MHC (52.2% [51.1-53.2]) had ever smoked, compared with one-third of those without (35.1% [34.2-35.9] and 32.6% [31.8-33.4], respectively). Ever smoking prevalence was higher among those with mental health problems across all ages and increased more steeply between ages 16-25 among those reporting distress before plateauing. Among former smokers, mean abstinence was shorter with distress (6.8 [SD = 5.5]) or history of a MHC (7.1 [5.6]) than without (8.0 [5.9] and 7.9 [5.9], respectively), though age-related increases in abstinence duration were similar. Ever smoking prevalence was consistently higher in people with mental health problems and may have increased more steeply in early adulthood among those with past-month distress. Age-related abstinence patterns were similar, but those with mental health problems had shorter average abstinence durations. Patterns may reflect higher initiation rates earlier in life and greater relapse, rather than later initiation. Smoking prevention and cessation efforts in Great Britain should prioritize people with mental health problems, among whom smoking remains more prevalent and durations of abstinence are shorter. The concentration of smoking initiation before age 30 underscores the importance of interventions during young adulthood, and the potential for the smoke-free generation policy to reduce the burden of smoking in this priority group.
Concerns about albumin causing respiratory failure in patients with hepatorenal syndrome-acute kidney injury (HRS-AKI) have caused unease with excess albumin use in these patients. To assess the outcomes of patients with HRS-AKI who received varying daily albumin doses. Retrospective study of inpatients with HRS-AKI between Jan 2020 and Apr 2023 collected clinical and laboratory data, AKI treatment, and hospital course with 6-month follow-up. 3 groups of patients such as no albumin, standard albumin (≤ 50 g/day), and high albumin (> 50 g/day) were compared. 159 AKI episodes were diagnosed in 149 patients (age 60 ± 11 years; male: 63%; MELD-Na: 29 ± 7). 16 AKI episodes received no albumin. Standard and high albumin patients had higher MELD score (p = 0.007) and higher Child-Pugh score (p = 0.057) compared to no albumin group. Standard albumin patients received 40 ± 10 g/day for 6.3 ± 6.5 days, versus 66 ± 14 g/day for 8.5 ± 6.7 days (p < 0.001 and p = 0.055, respectively) in high albumin group. 44 of 54 AKI episodes in high albumin patients had infection as an AKI precipitant (p < 0.001), 67% had stage 3 AKI (p = 0.002 vs. the other 2 groups) with peak creatinine at 403 ± 173 µmol/L, associated with higher rate of AKI progression (p = 0.01), with similar duration of hospital stay compared to the other 2 groups. Respiratory failure occurred in 2 patients in each albumin group related to pneumonia and aspiration. Survival at 6 months was not significantly reduced in the albumin groups (p = 0.141). Patients with severe liver dysfunction with HRS-AKI triggered by infection receiving more than recommended albumin dose did not have a more adverse outcome compared to standard albumin dose.
Chronic obstructive pulmonary disease (COPD) increases cardiovascular disease risk. Coronary artery calcification (CAC) predicts cardiovascular events and mortality in COPD. We hypothesized that plasma proteins linked to pulmonary phenotypes mediate CAC burden. Pulmonary function, emphysema, airway wall thickening, Agatston CAC scores (inverse normal transformed), and relative abundance of 1305 plasma proteins (log-transformed) were assessed in 989 Phase 1 COPDGene (Genetic Epidemiology of COPD) participants. Proteins associated with both pulmonary phenotypes (FEV1[forced expiratory volume in 1 second]%predicted, FVC [forced vital capacity], FEV1/FVC, emphysema, airway wall thickness, wall area percentage) and CAC (false discovery rate P≤0.20) were evaluated using multivariable mediation. Model adjustments included sex, age, race, body mass index, smoking, comorbidities, and medications. Adjustment for pulmonary artery-to-aortic diameter ratio-a marker of pulmonary vascular pressure-was also explored. The95% bootstrap CIs that excluded zero were considered significant. FEV1%predicted (P=0.026) and FEV1/FVC (P=0.010) were associated with CAC. After adjusting for FEV1, visual emphysema, and visual airway wall thickening remained associated with CAC. Five proteins (TSP2 [thrombospondin-2], renin, MMP-7 [matrix metalloproteinase-7], ERBB1 [epidermal growth factor receptor], MIC-1 [macrophage inhibitory cytokine-1]) mediated the FEV1%predicted and CAC association. All except MIC-1 mediated FEV1/FVC and CAC. All except renin mediated quantitative airway wall thickness or wall area percentage and CAC. Additionally, α2-antiplasmin (alpha-2 antiplasmin) mediated airway wall thickness and CAC. ERBB1 mediated visual paraseptal emphysema and CAC. Pulmonary artery-to-aortic diameter ratio adjustment reduced or eliminated some mediation effects. ERBB1 remained an independent mediator across multiple phenotypes. Six plasma proteins mediated associations between COPD phenotypes and CAC burden. These effects were partially influenced by pulmonary artery-to-aortic diameter ratio A, suggesting shared molecular pathways linking lung dysfunction to cardiovascular risk in COPD.
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Nonattendance can substantially decrease the effectiveness of existing and potential future population-based screening programmes for (prostate) cancer. We evaluated the long-term association between nonattendance and prostate cancer-specific mortality (PCSM) in the European Randomised Study of Screening for Prostate Cancer (ERSPC), with up to 20 yr of follow-up. This secondary analysis included 161 380 men aged 55-69 yr randomised to receive invitations for Prostate-specific antigen-based (PSA)-based screening (n = 72 460, screening arm [SA]) or to the control arm (CA) (n = 88,920) across seven ERSPC centres. Within the SA, men were classified as screening never-attenders (no attendance at any screening round) or screening ever-attenders (attended at least one screening round). The primary endpoint was PCSM. Cumulative incidence of PCSM was calculated using competing risk analysis, accounting for death from other causes as a competing event. Poisson regression was used to estimate rate ratios (RR) of cumulative PCSM between three groups: screening never-attenders, ever-attenders, and CA. Of the 72 460 men in the SA, 12,401 (17%) were defined as never-attenders. At 20 yr, the cumulative PCSM was 1.4% (95% confidence interval [CI], 1.2-1.6) among never-attenders, 1.2% (95% CI, 1.2-1.3) in the CA, and 1.0% (95% CI, 0.9-1.0) in ever-attenders. For PCSM, we observed an RR of 1.39 (95% CI, 1.2-1.6; p < 0.001) for never-attenders compared to the CA, while for ever-attenders compared to the CA, we observed an RR of 0.77 (95% CI, 0.69-0.85; p < 0.001). Data on determinants of attendance are lacking. Men randomised to the SA but who never attended had higher observed PCSM than men in the CA who were not offered screening. Conversely, men in the SA who attended screening had lower observed PCSM than men in the CA, with a larger observed difference than that reported in prior intention-to-screen analyses. Trial registration: ISRCTN49127736.
Study the treatment gap of guideline-indicated therapies in people with T2D and atherosclerotic cardiovascular disease (ASCVD) or heart failure (HF) or chronic kidney disease (CKD). We extracted prescription history from 2005 to 2025 from a national dataset, a community-based health system, and an academic center. We assessed treatment gap (current and ever) within four subgroups defined using American Diabetes Association Standards of Care indications for SGLT2i and GLP-1RA use. We identified 6,951,624 people in the national dataset, 58,390 people at the community-based health system, and 15,235 people at the academic center. The current treatment gaps among people with ASCVD (without HF or CKD) were 72%, 67%, and 49%; with ASCVD and HF or CKD3 were 73%, 71%, and 55%; with CKD3 or HF without ASCVD were 75%, 71%, and 65%; with CKD4/5 were 87%, 89%, and 74% within the national dataset, community-based health system, and academic health system, respectively. The ever-prescription rates ranged from 23% to 39%, 30%-47%, 42%-64% within the national dataset, community-based health system, and academic center, respectively. Over half the population never received an indicated cardio-kidney protective prescription, and two-thirds lack a current prescription. These gaps were substantial across all systems; however, lowest at the academic center.
The association between electronic cigarette (e-cigarette) use and Barrett's esophagus (BE) is still unclear. While traditional, combustible cigarette smoking is a known risk factor for BE, growing evidence on e-cigarette exposure has raised concerns about potential esophageal injury. Our aim is to evaluate the relationship between e-cigarette use and BE in a large and diverse population. We conducted a cross-sectional analysis using the All of Us Research Program to examine the association between e-cigarette use and BE. Adults aged 18 years or older with an ICD-10 diagnosis of BE (K22.7) were included. E-cigarette exposure was categorized as (1) ever vs. never use, (2) former vs. current vs. never use, and (3) dual use (concurrent e-cigarette and traditional cigarette smoking). Covariates including demographics, BMI, smoking status, alcohol use, GERD, hiatal hernia, diabetes, NSAID use, education, income, employment, and insurance status, were obtained. Multivariable logistic regression estimated adjusted odds ratios (AORs) with 95% confidence intervals. Among the 328,022 individuals studied, 29,343 (9%) reported e-cigarette use. E-cigarette users were younger and had lower rates of diabetes and GERD. After adjusting for relevant factors, we found that ever e-cigarette use was associated with higher odds of BE (OR 1.21, 95% CI 1.06-1.39). When we stratified by patterns of use, current e-cigarette use was significantly associated with BE (OR 1.46, 95% CI 1.15-1.83), whereas former use was not (OR 1.12, 95% CI 0.96-1.31). Individuals who were dual users also had increased odds of BE (OR 1.22, 95% CI 1.05-1.41). As expected, smoking, older age, hiatal hernia, and GERD remained strong predictors across all models, with GERD showing the strongest relationship. In this large national cohort, current and dual e-cigarette use were associated with increased odds of BE after adjustment for established risk factors, including GERD and combustible cigarette smoking. These findings suggest that e-cigarette use may represent a modifiable and underrecognized contributor to esophageal mucosal injury. Prospective longitudinal studies are needed to establish causality and clarify the mechanisms underlying this association.
Once known as a toxic gas, hydrogen sulfide (H2S) is now making its way into many therapeutic applications. Similar to its other fellow endogenous gasotransmitters, nitric oxide and carbon monoxide, H2S is a small gas with a short half-life, making it extremely capable of penetrating through cell membranes quite easily and fast via gas exchange. This fundamental small molecule possesses many physiological and pathological functions and is found in almost every mammalian system, such as the cardiovascular system, the integumentary/skin system, the neural system, the gastrointestinal tract system, and the skeletal system. As a therapeutic, the gas can modulate biological pathways, maintain homeostasis under physiological conditions, and mediate several pathological processes, thereby supporting cardioprotective applications. Due to the ever-increasing cardiovascular complications, especially concerning myocardial infarction and atherosclerosis, more and more patients are suffering from heart failure, and in some cases, this results in death. To remedy the progression of cardiovascular complications and cardiovascular disease burden as a whole, H2S has emerged as a potential candidate to mediate this problem. This review will specifically focus on the therapeutic potential of H2S-releasing platforms tailored to aid in cardiovascular applications.
Hormone replacement therapy (HRT) is widely prescribed for the management of hormone deficiency, particularly during menopause, yet its causal effects on human brain structure remain incompletely understood. Observational studies have reported heterogeneous associations, underscoring the need for robust causal inference. We applied an integrated causal framework combining two-sample Mendelian Randomization (MR) and Double Machine Learning (DML) to evaluate the effects of four HRT-related exposures-age at initiation, age at cessation, ever-use of HRT, and a composite medication-based phenotype-on 1366 brain imaging-derived phenotypes from the UK Biobank. Genetic instruments were derived from large-scale GWAS summary statistics, and causal estimates were validated using non-parametric DML models with cross-fitting and performance evaluation. Genetic instruments for age at HRT initiation, age at cessation, and ever-use of HRT were strong (median F-statistics 16.29-36.66). MR analyses identified a causal association between later initiation of HRT and lower orientation dispersion in the right inferior cerebellar peduncle (ubm-a-542; primary finding, no pleiotropy detected). An additional association with the left tapetum FA (ubm-a-243) was identified but exhibited significant directional horizontal pleiotropy (MR-Egger intercept P = 0.001) and is excluded from primary conclusions (Supplementary Note S2). Later cessation of HRT was associated with increased cortical thickness in the left middle occipital gyrus, reduced surface area in the left frontopolar cortex, and increased orientation dispersion in the splenium of the corpus callosum. Ever-use of HRT was causally linked to larger volumes of the right inferior frontal gyrus and right nucleus accumbens. These associations were corroborated by independent DML validation, which provided causally debiased estimates robust to high-dimensional confounding. Results for ukb-b-8080 (median F = 1.45) are provided in Supplementary Note S1 only; weak-instrument bias precludes causal inference. This study provides genetic-instrument-based and machine-learning-validated evidence for causal associations between HRT exposure-particularly its timing and lifetime use-and specific features of human brain structure, including white-matter microarchitecture, cortical thickness, and regional brain volume. These findings are FDR-controlled within exposures and independently replicated by DML, but require replication in external neuroimaging GWAS cohorts to establish definitive causal conclusions. They highlight the neurobiological relevance of sex steroid exposure and inform future research on brain aging and personalized hormone-based interventions.
SUMMARYFor single-celled organisms, the cell envelope is the thin barrier between life and death, responding dynamically to both the ever-expanding self and the ever-changing environment. Failure to balance these responses can lead to disastrous consequences, such as lysis. In gram-negative bacteria, the cell envelope is tripartite, consisting of two lipid bilayers with the periplasm, an aqueous space containing the thin peptidoglycan sacculus, between them. The outer of these lipid bilayers-aptly called the outer membrane-is asymmetric, bearing phospholipids on the inner leaflet and lipopolysaccharide (LPS) on the outer leaflet. Surface-exposed, highly immunoreactive, and essential to nearly all tested gram-negative bacteria, the overall architecture of LPS is largely conserved, but its modifications are subject to a myriad of variations. LPS has been studied extensively for its roles in pathogenesis and immunobiology and as a target of potential novel antibiotics. However, LPS exists in both free-living and pathogenic bacteria, suggesting it plays a critical role in bacterial physiology independent of the host. This aspect of LPS biology and its contribution to overall gram-negative cell physiology remains an area of active investigation. Addressing this gap, here we describe recent work detailing the essential contributions of LPS to bacterial physiology: particularly its role in cell envelope rigidity, its contributions to outer membrane capacity and fluidity, and the mechanisms integrating LPS synthesis into diverse aspects of cell envelope biogenesis during growth and division. We end with a discussion of the subset of gram-negative organisms that survive-either naturally or through genetic manipulation-in the absence of LPS and the adaptations that make this possible.
Unintended pregnancy is a key marker of unmet sexual and reproductive health needs, yet quantitative evidence among female sex workers (FSWs) in Sri Lanka is scarce. We conducted a cross-sectional respondent-driven sampling survey among 551 FSWs aged 18-49 years in Colombo from March to June 2025. Using Gile's successive sampling estimator, we generated respondent-driven sampling-weighted prevalence estimates and described pregnancy awareness, testing, and mitigating actions taken following pregnancy recognition among this sample. We conducted multivariate logistic regressions to identify women-level correlates of ever unintended pregnancy. Pregnancy-level prevalence was contextualized against six Sri Lankan non-sex worker studies using meta-analysis. Most participants had ever been pregnant (88.5 percent). Among ever-pregnant women, 51.1 percent reported at least one unintended pregnancy, and 39.8 percent of 1,225 lifetime pregnancies were unintended. Around two-thirds of FSWs recognized their most recent pregnancy by four weeks' gestation, but routine pregnancy testing was uncommon (11.3 percent), 44.8 percent reported no preventive measure at their most recent unintended pregnancy, and the pregnancy-accounting cascade indicated important downstream consequences. The risk of unintended pregnancy was found to be more clustered among women initiating paid sex before age 19 and those with higher parity. Pregnancy-level unintended pregnancy exceeded pooled non-sex worker estimates by about 11-13 percentage points. Taken together, the findings point to missed opportunities at both the pregnancy recognition and preventive response stages of the pathway. These findings support targeted sexual and reproductive health programs for FSWs in Colombo that prioritize routine and outreach-based pregnancy testing, rapid access to acceptable contraceptive options, and focused support for women entering sex work early, those with repeated pregnancies, and those who took no preventive measures at unintended conception.
Higher future time perspective (FTP), or how much individuals consider the long-term outcomes of their present actions, is associated with more attempts to quit smoking. Nicotine vaping products are less harmful than smoking and may aid cessation, but perceptions about their harm relative to smoking vary. This study examined whether FTP predicts vaping initiation (ever tried vaping), among adults who smoke, and whether this relationship depends on perceived harm. Data were drawn from the 2020 and 2022 International Tobacco Control Four Country Smoking and Vaping Surveys. The sample included 853 adults aged 18 years or older who smoked, had never vaped at baseline, and provided outcome data at follow-up. Binary logistic regression examined whether FTP predicted vaping initiation and any moderating role of perceived harm (less versus equally or more harmful than smoking). Multinomial logistic regression examined whether FTP predicted current (versus past or never) vaping at follow-up. Higher FTP significantly increased odds of vaping initiation among older adults, especially those over 55 (OR = 3.93, 95 % CI [1.39, 11.13], p = 0.01). Perceived harm was not a significant moderator but, independently, those perceiving vaping as less harmful than smoking were more likely to initiate vaping (OR = 2.12, 95 % CI [1.40, 3.21], p < 0.001). Those who changed to believing it was less harmful by follow-up were the most likely to be currently vaping at follow-up (p < 0.001). Among adults who smoke, those older in age with higher FTP and all who perceived vaping as less harmful than smoking, were more likely to initiate vaping.
To systematically review the evidence on the association between occupational exposure to pesticides and the risk of amyotrophic lateral sclerosis (ALS). A systematic search, conducted in eight bibliographic databases for publications between 1990 and 2025, identified observational studies estimating the risk of ALS after occupational pesticide exposure. Study quality was assessed using the WHO Risk of Bias (RoB) assessment instrument for systematic reviews, with the ROBINS-E (RoB in non-randomised studies of exposure) tool domains of bias. Pooled risk estimates were produced using random-effects models with restricted maximum likelihood, heterogeneity was assessed with I² statistics, and meta-regressions and publication bias explored with funnel plots and Egger's test. Eight case-control studies (1734 cases) were retained for meta-analysis from 767 initially screened articles. 'Ever' occupational exposure to pesticides was associated with an increased risk of ALS (n=6 studies, pooled OR (pOR)=1.6; 95% CI 1.1, 2.2; I²=57%), for combined sexes. The risk for exposure to herbicides was slightly greater (pOR=1.7, I2=0.0%) than for exposure to insecticides or fungicides (pORs=1.6, I2=0.0%). Based on three studies, ever exposure to high levels of pesticides was associated with a higher risk (pOR=2.7; 95% CI=1.4, 5.0) than exposure to low levels (pOR=1.9; 95% CI=1.0, 3.7). Self-reported exposure assessment methods and older publication dates (<2015) were statistically significant predictors of the effect size. Despite the small number of studies and some heterogeneity, our results add to the evidence suggesting that occupational exposure to pesticides may increase the risk of ALS.
The incidence of stroke at younger ages appears to be increasing, whilst it is falling at older ages. We aimed to determine the current trend and how it might have changed during and after the COVID-19 pandemic. We identified first-ever stroke events in adults in England between 1st April 2018 and 31st March 2024 through record-linkage with multiple overlapping sources including primary care, hospital admission, death certificate, and records from a stroke specific national audit. Standardised age-specific (age < 55 versus ≥ 55 years) stroke incidence was calculated and compared using incidence rate ratio (IRR) during three time periods (pre COVID-19 pandemic: 2018-2020; COVID-19 pandemic: 2020-2022 and post COVID-19 pandemic: 2022-2024). We quantified the age-specific divergence using the Relative Temporal Rate Ratio (RTTR). Diagnosis and treatment of modifiable stroke risk factors (hypertension, diabetes, atrial fibrillation, and hyperlipidaemia) before and after the stroke were also compared across the study periods. Analyses were stratified by sex, ethnicity, deprivation, regions, and stroke subtypes. 643,885 incident strokes were included (2018-2020: 206,290; 2020-2022: 211,420; and 2022-2024: 226,175). At age < 55 years, there was a significant increase of stroke incidence during the pandemic (2020-2022 versus 2018-2020: IRR = 1.07, 95%CI [1.05,1.09], p < 0.001), which was consistent by sex, ethnicity, deprivation, stroke subtype and region, and was most prominent for ethnic minority groups (Black: IRR = 1.13, 95%CI [1.05,1.21], p = 0.0005; Asian: IRR = 1.26, 95%CI [1.20,1.33], p < 0.001). This trend continued after the pandemic (2022-2024 vs. 2020-2022: IRR = 1.04, 95%CI [1.02,1.06], p < 0.001). On the contrary, stroke incidence at age ≥ 55 remained stable during the pandemic (IRR = 0.99, 95%CI [0.99,1.00], p = 0.06), and increased afterwards (IRR = 1.04, 95%CI [1.03,1.04], p < 0.001). Consequently, the age divergence in stroke incidence with a less favourable trend at younger ages widened significantly during the pandemic (RTTR = 1.07, 95%CI 1[1.05,1.08], p < 0.001) and remained unchanged since (RTTR = 0.99, 95%CI [0.97,1.00], p = 0.11). Prevalence of modifiable stroke risk factors remained largely unchanged during and after the pandemic for both age groups. However, there was a significant increase in the frequency of undiagnosed premorbid hypertension and diabetes at age < 55 years during the pandemic (hypertension RR = 1.07, 95%CI [1.02-1.13]; diabetes RR = 1.22, 95%CI [1.08-1.37]). Again, this trend was most prominent for ethnic minority groups and has not improved after the pandemic. A key limitation was the use of routinely collected data, which lacked granularity to explore potential mechanisms. There was an increase in stroke incidence at younger ages, with no increase at older ages, especially for ethnic minority groups, during and after the COVID-19 pandemic. This coincided with worsening in risk factor identification and diagnosis in primary care, highlighting missed opportunities that need to be urgently addressed.
Biologic prophylaxis is used to prevent postoperative recurrence (POR) of Crohn's disease (CD) in high-risk patients who have undergone ileocolonic resection (ICR). There are limited data to guide clinicians' choice of prophylactic biologic class to prevent POR in patients previously exposed to biologics. We aimed to determine if reutilizing a prophylactic biologic class is associated with lower risk of POR in patients preoperatively exposed to biologics. Adult CD patients who underwent ICR between 2009 and 2020 and were ever preoperatively exposed to biologics were included. Composite POR, including endoscopic (Rutgeerts ≥ i2b) and/or radiographic recurrence, was compared between patients who: received no prophylaxis, reutilized prophylaxis, or received a new class of prophylaxis (≤3 months from ICR) using Kaplan-Meier analysis. A multivariate Cox proportional hazards regression model was utilized to compare the 3 groups along with clinically established risk factors. A total of 635 biologic-exposed patients (≥2 biologics: 46%) who postoperatively received no prophylactic biologic (63.8%), who reutilized prophylactic biologic (30.7%), or who received a new class of prophylactic biologic (5.5%) were included. On multivariable analysis, no biologic prophylaxis was associated with a higher risk of recurrence (adjusted hazard ratio, 1.33; 95% confidence interval, 1.01-1.74; P = .04), and new biologic prophylaxis (adjusted hazard ratio, 1.50; 95% confidence interval, 0.89-2.53; P = .13) was associated with a similar risk of recurrence when compared with reutilization. Recurrence-free survival was similar among the 3 groups (P = .08); however, in patients undergoing their first ICR (P = .026) and in patients previously exposed only to anti-tumor necrosis factor agents (P = .051), the reutilization group demonstrated longer recurrence-free survival. Reutilization of biologic classes can be a valid strategy to prevent postoperative CD recurrence.
Interstitial lung disease in Sjögren disease (SjD-ILD) is a clinically relevant and potentially progressive complication, yet treatment remains empirical and poorly supported by evidence. This multicentre observational study across three European expert centres (Oslo, Zurich, and Vienna) included patients with SjD-ILD who were diagnosed between 1997 and 2025, fulfilled the 2016 ACR/EULAR SjD criteria and had ILD confirmed by high-resolution computed tomography (HRCT). Treatment patterns and pulmonary function were analysed across four predefined calendar periods (≤2006, 2007-2011, 2012-2016, ≥2017). Outcomes included therapeutic patterns, factors associated with treatment, longitudinal changes in pulmonary function and mortality. ILD progression and improvement were defined as absolute forced vital capacity (FVC) change (≥5% or ≥10%) over 12 ± 3 and 24 ± 3 months, and by 5-year all-cause mortality. Comparisons across periods used trend tests, and logistic regression was applied to identify factors associated with treatment. We involved people with lived experience in the study design and implementation. Among 191 patients with SjD-ILD (mean age 59.9 ± 13.6 years, 81% females), 122 (63.9%) ever received immunosuppressive therapy, increasing from 52.4% before 2006 to 71.3% after 2017 (p = 0.03). Glucocorticoids were used in 81 patients (42.4%), rituximab in 48 (25.1%), azathioprine in 33 (17.3%), and mycophenolate-mofetil in 32 (16.8%). Patients with higher dyspnoea severity (OR 3.34, 95% CI 1.43-7.80) and FVC<70% predicted (OR 3.48, 95% CI 1.54-7.90) were more likely to be treated. Lymphocytic interstitial pneumonia was treated less frequently than non-specific interstitial pneumonia (OR 0.40, 95% CI 0.18-0.90). Over time, ILD progression remained largely unchanged, while ILD improvement (≥5% FVC increase) increased from 2.9% to 11.9% (p = 0.03). Over a mean follow-up of five years, 9 patients (4.8%) died, with no significant changes in mortality rates over time. Management of SjD-ILD has evolved towards broader and more consistent use of immunosuppressive therapy. However, a substantial proportion of patients remained untreated, and treatment was more frequently initiated in patients with greater symptom burden and impaired lung function, which emphasises the need for earlier and evidence-based intervention strategies.
To address the critical challenge of the scarcity of low-cost wide-bandgap polymer donor materials, we have developed a novel ester-substituted benzotrithiophene acceptor unit. The incorporation of an ester group into the benzotrithiophene structure induces a fundamental transformation, shifting it from an electron-donating entity to a weakly electron-withdrawing one. Leveraging this innovation, we synthesized a new low-cost wide-bandgap polymer donor material, namely BLZ-20, by using the ester-functionalized benzotrithiophene as the acceptor unit, benzodithiophene (BDT) as the donor unit, and 3-alkylthiophene as the π-bridge. BLZ-20 exhibits excellent solution-processability and unique temperature-dependent aggregation properties. Building on these advantageous characteristics, the BLZ-20:L8-BO blend film exhibits a well-defined nanofiber network structure that not only promotes efficient exciton dissociation and charge transport but also effectively reduces nonradiative losses. The BLZ-20:L8-BO-based binary organic solar cell (OSC) has achieved a remarkable power conversion efficiency (PCE) of 20.13%, setting a new industry-wide benchmark for OSCs. Furthermore, the BLZ-20:L8-BO:BTP-eC9-based ternary OSC has attained an even more impressive PCE of 20.55%, ranking among the highest-performing OSCs ever reported. Our research findings unequivocally demonstrate that the wide-bandgap polymer BLZ-20, derived from benzotrithiophene, is a cost-effective and high-performance donor material. It offers significant potential for advancing the practical application of OSCs.
We sought to synthesize and evaluate evidence for the overuse of vascular diagnostic imaging tests and procedures in high-income countries as they may be overused in asymptomatic, minimally symptomatic, and/or high-risk patients with limited life expectancy. After protocol registration (CRD42021257490), we searched MEDLINE, EMBASE, and Evidence-Based Medicine Reviews (January 1st, 2010-May 14th, 2025) for English-language studies that reported the incidence/prevalence of overuse of vascular diagnostic imaging tests and/or procedures in high-income countries; adjusted predictors of overuse; or adjusted associations between overuse and outcomes. Three investigators independently reviewed titles/abstracts and full-texts, extracted data, and assessed risk of bias. Data were pooled using random-effects models. GRADE was used to assess estimate certainty. Among 11,748 citations, we included 14 studies (n=16,706,904 patients) that examined two unique vascular diagnostic imaging tests and eight unique procedures. The most frequently overused vascular imaging tests included carotid (pooled-cumulative incidence=19%; 95% confidence interval [CI]=10-30%; moderate-certainty) and venous duplex (cumulative incidence=46%; 95% CI=43-48%; moderate-certainty). The most frequently overused vascular procedures included renal artery angioplasty (pooled-cumulative incidence=92%; 95% CI=85-97%; low-certainty) and inferior vena cava filter placement (pooled-cumulative incidence=72%; 95% CI=0-100%; low-certainty). Adjusted-risk factors for carotid duplex overuse included increasing age and higher median neighborhood income quartile. Adjusted risk factors for overuse of endovascular intervention for claudication included ever smoking and end-stage renal disease. Overuse was associated with increased healthcare costs in all studies examining this outcome. Overuse of vascular diagnostic imaging tests and procedures may be common in high-income countries and associated with increased healthcare costs. However, because the included studies had important limitations, our findings should be confirmed before methods to reduce the above overuse are developed.
More than 90% of the highest incidence rates of cervical cancer occur in sub-Saharan Africa region. However, this region has low uptake of cervical cancer screening compared to other World Health Organization (WHO) regions. Therefore, the current study aimed to show the geographical and regional variation and predictors of low uptake of cervical cancer screening among women aged 30-49 years in Tanzania. This study analyzed data from 2022 Tanzania Demographic and Health Survey and Malaria Indicator Survey (TDHS-MIS). The uptake of cervical cancer screening was the outcome variable which dichotomized into "Yes" for the women who reported a doctor or other healthcare provider ever tested her for cervical cancer otherwise it was coded "No." Besides, descriptive and geospatial analysis, the mixed-effect multilevel logistic regression analysis was performed to determine predictors of low uptake of cervical cancer screening. This study included a total of 6911 women between 30 and 49 years old, with the median age (interquartile range) of 38 (34-43) years. The overall uptake of cervical cancer in Tanzania remain low (12.2%). The geospatial analysis indicates the lowest uptake was observed in Southern (4.7%) and Central (5.9%). The random effect model revealed that the variation in uptake of cervical cancer screening, 26% was attributed to between clusters within regions or geographical zones differences [ICC = 0.26, 95%CI; 0.22-0.31]. Fixed effect model revealed that women with older ages, formal education, health insurance coverage, employed for cash, being in rich household, listen to radio, reading newspapers, magazines, or using the internet had higher odds of uptake cervical cancer screening than their counterparts. For realization of WHO target on elimination of cervical cancer by screening 70% of all eligible women age 30 and above by 2030, more efforts on addressing social determinants of health and provision of health education through mass media should be considered. Not applicable.