Smoking has been associated with lower risks of Parkinson disease (PD) in epidemiological studies, but the underlying mechanisms remain poorly elucidated.

To investigate the association of exhaled carbon monoxide (CO) with risk of PD.

This nationwide prospective cohort study leveraged data from the China Kadoorie Biobank across 10 geographically diverse areas in China. A total of 512 724 adults aged 30 to 79 years were recruited between June 2004 and July 2008. Prospective analyses were restricted to first events occurring between ages 40 and 94 years and before January 1, 2019. Data were analyzed from May 2025 to March 2026.

Self-reported smoking status and measured exhaled CO.

During approximately 12 years' follow-up, 1131 individuals with PD and 2949 with other neurodegenerative diseases were recorded through linkage to national death and disease registries and the health insurance system. Cox regression was used to estimate adjusted hazard ratios (HRs) for associations of smoking and, among individuals who never smoked, exhaled CO levels with PD, other neurodegenerative diseases, and several known smoking-related diseases. Covariates included sociodemographic characteristics, lifestyle factors, and other confounders (ie, solid fuel use and passive exposure to smoking).

Among the 512 701 participants included in the main analyses, the mean (SD) age was 52 (11) years and 302 041 (58.9%) were female. Overall, 156 650 male individuals (74.5%) and 9944 female individuals (3.3%) ever smoked regularly, with mean exhaled CO levels higher among those who regularly smoked (11.1 ppm) than those who never smoked (3.5 ppm), those who occasionally smoked (3.8 ppm), and those who formerly smoked regularly (3.7 ppm). Regular smoking was significantly associated with elevated risks of lung cancer, ischemic heart disease, stroke, and all-cause mortality but with lower risk of PD (adjusted HR, 0.70; 95% CI, 0.62-0.79). In individuals who never smoked, higher exhaled CO levels were associated with lower HRs of PD (n = 675) in a broadly dose-dependent manner (exhaled CO <2.0 ppm: 1.00 [95% CI, 0.85-1.18]; 2.0 to <3.0: 0.85 [95% CI, 0.73-0.99]; 3.0 to <5.0: 0.62 [95% CI, 0.53-0.73]; 5.0 to <11.5: 0.68 [95% CI, 0.56-0.83]; ≥11.5: 0.65 [95% CI, 0.45-0.92]; P for trend < .001) but were not associated with risks of smoking-related diseases or other neurodegenerative diseases. The associations with PD were more pronounced in female individuals who never smoked. Similar exhaled CO-PD associations were found in those who regularly smoked.

Among individuals who never smoked, higher exhaled CO levels were associated with lower PD risk. These findings demonstrate a potentially protective role of CO in PD etiology, which help explain the association between smoking and PD observed in this and other epidemiological studies and support ongoing clinical trials of CO in the treatment of PD.

As global smoking rates decline, Lung Cancer in Never-Smokers (LCINS) has emerged as a distinct and increasingly important clinical entity. However, its underlying pathogenesis remains poorly understood, highlighting the need to identify circulating molecular determinants and candidate biomarkers.

Genetic instruments for plasma proteins were obtained from pQTL datasets (Fenland study and UK Biobank Pharma Proteomics Project), while summary statistics for LCINS were sourced from TRICL-ILCCO. Two-sample Mendelian Randomization (MR) was performed using inverse-variance weighting as the primary approach, complemented by sensitivity analyses for heterogeneity (Cochran's Q), horizontal pleiotropy (MR-Egger intercept), and outlier detection (MR-PRESSO). Tissue-level validation was conducted using CPTAC proteomic data. Further analyses, including Bayesian colocalization, Protein-Protein Interaction (PPI) network construction, Gene Ontology (GO) enrichment, and mediation analysis, were applied to investigate shared genetic architecture, functional pathways, and immune-mediated mechanisms.

Among 543 cis-acting plasma proteins evaluated in the discovery phase, 35 exhibited evidence of association with LCINS risk, including 15 positively and 20 inversely associated proteins. After False Discovery Rate (FDR) correction, only genetically proxied plasma RARRES1 remained statistically significant (OR = 1.17, adjusted P = 2.72 × 10-5), and this finding was replicated in an independent cohort. Bayesian colocalization supported a shared causal variant (PPH4 = 0.83). Functional enrichment analyses implicated RARRES1-related networks in immune regulation and extracellular processes. Two-step MR mediation analysis nominated CD16-CD56 intensity on NKT cells as a potential immune-mediated pathway, accounting for an estimated 11.8% of the genetic effect.

This study prioritizes genetically proxied plasma RARRES1 as a candidate protein associated with LCINS risk and highlights CD16-CD56 intensity on NKT cells as a potential immune-related mechanism. These findings provide biologically plausible evidence supporting a role for RARRES1 in LCINS pathogenesis and its potential utility in biomarker development.

Genetically proxied plasma RARRES1 is associated with increased LCINS risk and may contribute to disease susceptibility through immune-related alterations involving NKT-cell phenotypes. RARRES1 represents a promising candidate for future mechanistic studies and blood-based diagnostic biomarker development in LCINS.

Echocardiography is a non-invasive technique for evaluating pulmonary thromboembolism (PTE), facilitating a dynamic assessment of cardiac structure, function, and hemodynamic alterations. It is critical in the auxiliary diagnosis, risk stratification, and prognosis assessment of acute PTE; monitoring the progression of chronic PTE; and conducting early screening for chronic thromboembolic pulmonary hypertension and evaluating right heart function in such cases. In current clinical practice in China, right heart echocardiographic assessment protocols for PTE are not standardized, resulting in image acquisition and interpretation variability. To address this challenge, our research group invited multidisciplinary specialists from relevant fields across China to engage in collaborative discussions. Based on a comprehensive review of both Chinese and international literature, and in alignment with the specific circumstances of clinical practice in China, the measurement methods, technical considerations, normal reference values, and clinical implications of each parameter used in echocardiographic assessment of the right heart for PTE were systematically summarized, and operational standards and recommendations suitable for the Chinese clinical setting were proposed. This document was developed on the basis of a systematic literature review and expert consensus.

Diabetes distress is common among adults with Type 1 diabetes (T1D) and is associated with poorer psychological and medical outcomes. While diabetes distress occurs across the lifespan, less is known about how its sources differ by age and how patient input can inform intervention development.

Using a user-centred design (UCD) approach, we conducted six virtual group sessions with adults with T1D to inform the development of a cognitive-behavioural intervention targeting diabetes distress. Participants included young adults aged 18-34 recruited from an academic medical centre and adults aged 35-64 recruited from a national patient advisory council. Sessions were audio-recorded, transcribed and analysed using a modified inductive qualitative approach.

Nineteen adults with T1D participated. Across age groups, participants identified shared domains of diabetes distress, including competing daily priorities, financial and insurance-related barriers, interpersonal relationships and healthcare system challenges. However, important age-related differences emerged. Young adults emphasized immediate disruptions to daily life, identity, competing priorities and technology-related burden, whereas adults aged 35-64 highlighted cumulative fatigue, fear of complications, caregiving responsibilities and long-term concerns related to healthcare access and financial sustainability.

Diabetes distress is a pervasive but age-contextualized experience among adults with T1D. Incorporating stakeholder perspectives revealed both shared and age-specific drivers of distress, supporting the need for life stage-responsive psychosocial interventions to address diabetes distress in adults with T1D.

Type 2 diabetes mellitus affects more than 500 million adults worldwide, yet up to 80% of related complications are preventable through evidence-based care. Clinical practice guidelines function as key prevention policy instruments; however, their implementation and integration into health systems vary substantially, with important implications for prevention access and health equity.

This study aimed to examine how national policy integration architecture within diabetes management guidelines influences access to preventive care and health equity across diverse health system contexts.

A comparative qualitative policy analysis evaluated national diabetes management guidelines from seven countries (United States, United Kingdom, Japan, India, Ghana, Colombia, Australia) using the Health Policy Triangle and Integration Continuum Framework. Guidelines were scored on integration strength (1 to 5 scale) across clinical, financial and administrative domains. Equity analysis examined financing barriers, workforce distribution and cultural adaptations. Inter-rater reliability testing achieved substantial agreement (Cohen's kappa 0.68).

All guidelines converged on evidence-based clinical content, yet integration scores varied threefold (range 2 to 5). High-integration systems (United Kingdom, Australia; scores 5) achieved prevention medication access rates exceeding 80% among eligible populations through unified financing and zero cost-sharing. Partial-integration systems (United States, India, Ghana; scores 2 to 3) showed 30% to 50% access despite comparable clinical recommendations. Integration strength correlated strongly with implementation effectiveness (Spearman ρ = 0.89, p < 0.01). Financing structure emerged as the primary equity determinant. Countries with fragmented payment systems preserved disparities despite equity language in guidelines.

Preventing diabetes complications at scale requires integrated health systems where financing, workforce, and monitoring align with guideline intent. Policy priorities should emphasise unified financing, elimination of cost-sharing for preventive therapies, and mandatory equity monitoring in quality frameworks.

The aim was to evaluate how treatment supplied in public oral health care services is associated with the prevalence and incidence of periodontitis.

The data for this study comprised patients aged 20 years or older who had visited publicly funded oral health care services in the Wellbeing Services County of North Karelia (Siun sote) during the years 2021-2022 (N = 50,469). These patients were retrospectively followed in the patient register starting from 2014. Associations of treatments received during the follow-up period (years 2014-2020) with ICD-10 diagnoses of chronic and acute periodontitis at follow-up (in 2021-2022) were analyzed by logistic regressions.

The prevalence of diagnoses of both chronic and acute periodontitis in 2021-2022 was quite low. The number of years of having received different treatments in 2014-2020 was associated with the odds of being diagnosed with periodontitis in 2021-2022. In the case of chronic periodontitis, an increasing number of years with preventive and restorative treatments was particularly associated with lower prevalence and incidence. Conversely, an increasing number of years with periodontal treatments and tooth extractions, in addition to earlier diagnosis, were associated with higher prevalence and incidence. For acute periodontitis, in contrast, an increasing number of years with preventive care among all participants and periodontal treatment in incident cases appeared to slightly increase the odds, whereas more years of examinations and tooth extractions were associated with reduced odds. In addition, smoking and diagnosis of diabetes mellitus were associated with higher odds of periodontitis diagnosis.

While the association of treatments was similar for prevalence and incidence, it differed between chronic and acute periodontitis, highlighting their distinct pathophysiological profiles. Although preventive care is offered less frequently than other treatments and often for reasons unrelated to periodontal health, it shows a positive impact in reducing the risk of chronic but not acute periodontitis.

Women with a history of adverse pregnancy outcomes (APOs), including gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), small for gestational age (SGA) offspring, preterm birth and placental abruption, are at increased risk of cardiovascular disease (CVD) and diabetes mellitus (DM) later in life. Physical inactivity is a risk factor for developing CVD and DM. Thus, for women with a history of APOs, it is particularly important to achieve recommended levels of physical activity (PA). The aim of this study was to investigate differences in PA levels among women with and without a history of APOs, using accelerometers to objectively measure PA levels.

This is a population-based cohort study. Women who participated in the fourth survey of Trøndelag health study (HUNT4) and were registered with one or more births in the Medical Birth Registry of Norway (MBRN) before participation, were included in the study. PA levels were objectively measured with two accelerometers worn by the participants for 3-7 consecutive days. Three different paces of walking, running and cycling were measured by the accelerometers and used to calculate our two outcomes: moderate-vigorous physical activity (MVPA) in metabolic equivalent of task (MET)-minutes/week and total PA in min/day. MVPA included moderate and fast walking, running and cycling, and total PA included additionally slow walking. We used linear and logistic regression to examine the associations between history of APOs and PA levels.

Among 3771 women, 868 (23.0%) had a history of one or more APOs. We found that women with a history of APOs had lower levels of PA. These differences diminished after accounting for postpartum general health and modifiable lifestyle factors. Among women with and without a history of APOs, respectively 17.7% and 15.9% did not achieve recommended levels of PA.

There were no significant associations between history of APOs and PA levels in the fully adjusted regression analyses. Nevertheless, almost every fifth woman (15.9-17.7%) did not achieve recommended levels of PA, and postpartum follow up of women with APOs aimed at increasing their PA is important to prevent CVD and DM later in life.

Painful diabetic neuropathy (PDN) is a common complication of diabetes that leads to significant co-morbidity. Emerging evidence suggests glycaemic variability may be linked to fluctuations in pain intensity. Hybrid closed loop (HCL) systems reduce glycaemic variability, raising the possibility that they may modify pain intensity. This study aims to evaluate the effects of HCL use on pain intensity in people with PDN.

PAINLESS is a two-centre, randomised cross-over study, recruiting 49 adults with type 1 diabetes and PDN. Each participant will complete two 12-week intervention periods in a randomised sequence (1:1): one with standard care including continuous glucose monitoring (CGM) and one with HCL using the Tandem t:slim X2 insulin pump with Control-IQ technology. The primary outcome is the change in 7-day average 24-hour pain intensity [rated on a numerical scale from 0-10 (NRS)] from baseline to the end of each 12-week intervention period as measured by daily pain diaries. Secondary outcomes include measures of pain trajectory/durability [responder rates (30% and 50% pain reduction in 7-day NRS), and the AUC for daily NRS scores], functional and quality of life outcomes [Short Form Health Survey (SF-36), and Short Form of the Brief Pain Inventory (BPI-MSF)], mood [Beck Depression Inventory (BDI)], health status [EQ-5D-5L], and global improvement [participant and clinician reported global impression of change]. Exploratory endpoints will harness neurophysiological assessments including Sudoscan, DPN-Check, Vagus and Vibrosense, and sleep and activity data from Withings devices. Statistical analyses will employ an intention-to-treat approach and mixed effect models.

24-month trial: 18 months recruitment/follow up, 6 months close-out, analyses and dissemination.

ISRCTN24233750.

Housing wealth can be leveraged to maintain economic security when expenses exceed income, allowing households flexibility when managing a new chronic disease diagnosis. We linked housing and electronic health record (EHR) data to examine how housing wealth and stability relate to type 2 diabetes (T2D) outcomes.

EHR data from patients diagnosed with T2D were linked to housing data (tenure, foreclosure, home equity, reverse mortgage, and loan-to-value ratio) using residential address. Multinomial logistic regression models were used to estimate associations between housing variables measured in the year before T2D diagnosis and glycemic control a year or more after T2D diagnosis.

Among 5810 patients with T2D and complete housing data, patients with more home equity [relative risk ratio (rrr)=0.52, 95% CI: 0.323-0.838, P<0.001] were less likely to experience HbA1c >9% 1 year after diagnosis, and owners who were actively extracting home equity through a reverse mortgage (rrr=2.137, 95% CI: 0.008-1.511, P=0.048) were also more likely to have HbA1c >9% compared with patients with HbA1c<6.5%. Homeowners were less likely than renters to experience HbA1c >9% (rrr=0.798, 95% CI: 0.672-0.948, P=0.010).

Patients diagnosed with T2D who had more housing wealth were less likely to experience challenges with glycemic control after diagnosis.

This mixed methods systematic review will aim to identify, synthesize, and integrate quantitative and qualitative evidence on the barriers and facilitators affecting the implementation of exercise therapy for patients with diabetic neuropathy.

Diabetic neuropathy is one of the most prevalent and debilitating complications of diabetes, often leading to impaired mobility, pain, reduced physical function, and diminished quality of life. Exercise therapy is widely recommended as a core component of management; however, its implementation in clinical and community settings remains inconsistent.

This review will include qualitative, quantitative, and mixed methods studies involving adults (≥18 years) with type 1 or type 2 diabetes mellitus and diabetic peripheral neuropathy. The review will consider evidence relating to barriers and facilitators influencing the implementation, uptake, adherence, or delivery of exercise therapy from multiple perspectives, including patient (eg, beliefs, motivation, health literacy), provider (eg, knowledge, attitudes, training), and health system (eg, accessibility, policies, financing, service delivery).

The review will follow the JBI methodology for mixed methods systematic reviews using a convergent integrated approach. The data will be extracted from databases and gray literature, including MEDLINE (Ovid), CINAHL (EBSCOhost), Embase (Ovid) Scopus, Cochrane CENTRAL, ProQuest Dissertations and Theses Global, the WHO International Clinical Trials Registry Platform (ICTRP), and Google Scholar. Two reviewers will independently extract data using a customized form, screen titles, abstracts, and full texts, and assess methodological quality. Qualitative data will be transformed into "qualitized" statements and integrated with quantitative findings. A single set of integrated findings will be developed using meta-aggregation and narrative integration techniques, resulting in synthesized statements and practical recommendations. The review will follow PRISMA reporting guidelines.

PROSPERO CRD420261284500.