Chronic obstructive pulmonary disease (COPD) affects approximately 480 million individuals globally and is projected to reach 600 million by 2050, representing a substantial burden on healthcare systems and patient quality of life. Pulmonary rehabilitation is a cornerstone intervention for COPD management, delivering clinically meaningful improvements in exercise capacity, health-related quality of life and dyspnoea. Despite strong guideline recommendations and established efficacy, only 2%–4% of eligible patients with COPD access traditional centre-based pulmonary rehabilitation due to geographical barriers, transportation difficulties, scheduling conflicts and limited healthcare resources. Digital health technologies offer promising alternatives to overcome these access barriers while potentially maintaining therapeutic benefits. Various digital delivery models have emerged, including video-based telerehabilitation, virtual reality platforms, mobile health applications and web-based programmes. However, their comparative effectiveness remains unclear, limiting evidence-based clinical decision making. This systematic review and network meta-analysis will aim to compare and rank the effectiveness and safety of different digital health delivery models for pulmonary rehabilitation in patients with COPD, providing evidence to inform optimal intervention selection in clinical practice.

We will conduct a systematic review and Bayesian network meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Network Meta-Analyses guidelines. Comprehensive searches will be performed across five electronic databases (PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, CINAHL) from inception to January 2026, without language restrictions. Eligible studies will include randomised controlled trials comparing digital health delivery models for pulmonary rehabilitation in adults with COPD. Digital health interventions will be categorised into four distinct delivery models: video-based telerehabilitation, virtual reality rehabilitation, mobile health rehabilitation and web-based platform rehabilitation. Interventions combining multiple modalities will be categorised according to the predominant component based on intervention frequency, duration and primary therapeutic mechanism. Two independent reviewers will perform study selection, data extraction and risk of bias assessment using the Cochrane Risk of Bias 2 tool. The primary outcome will be change in 6 min walk distance. Key secondary outcomes will include disease-specific quality of life measures, dyspnoea severity, hospitalisation rates, exacerbation frequency, intervention adherence and adverse events. A Bayesian random-effects network meta-analysis will be conducted, calculating mean differences or ORs with 95% credible intervals. Treatment rankings will be estimated using surface under the cumulative ranking curve probabilities. Evidence certainty will be assessed using the Confidence in Network Meta-Analysis framework. Planned subgroup analyses will explore potential effect modifiers including disease severity, intervention duration, supervision mode and technological features.

As this systematic review will use data from previously published studies, formal ethical approval is not required. Findings will be disseminated through peer-reviewed publication, presentations at relevant scientific conferences and communication to healthcare providers, policymakers and patient advocacy organisations.

CRD420251268701.

This community-led research study protocol emphasises placing black youth impacted by the legal system, their families and their communities at the forefront of substance use treatment development research and decision-making. The study, the Cultural Adaptation of a Substance Use Treatment (CAST) Project, challenges traditional top-down approaches to treatment creation, advocating for a grassroots model that centres community knowledge, values and active participation.

The CAST project is a US-based mixed-methods study with an exploratory design that examines the impact of racial discrimination on substance use in black youth impacted by the legal system. The study participants are black youth impacted by the legal system (N=15), parents of black youth impacted by the legal system (N=10) and community members who serve black youth (N=10) (total N=35 study participants). Study participants from each group (youth, parents and community members) will participate in three separate focus groups, respectively, to provide feedback on the culturally responsive content needed to best support black youth impacted by the legal system around substance use and mental health. The eight-step Assess, Decision, Adaptation, Production, Topical Expert, Integration, Training, Testing framework will be used as a guide to inform adaptations to the Motivational Enhancement Therapy and Cognitive Behavioural Therapy (MET/CBT12) for black youth impacted by the legal system. Once the cultural adaptation process has been completed, the study will conclude with an open feasibility and accessibility trial of the culturally adapted MET/CBT12 manual. The primary outcomes of this study are the feasibility and acceptability of the culturally adapted manual, measured by treatment attendance and participant feedback. Secondary outcomes include reductions in substance use and discrimination distress, and improvements in mental health symptoms.

This study was approved by the Institutional Review Board (IRB) at the University of California, San Francisco (IRB Protocol Number: 23-40126). All study procedures will be conducted in accordance with the ethical standards outlined by the institutional review board. The results from this study will be shared through peer-reviewed publications, academic conferences, community forums and policy briefs to support broader implementation of culturally adapted adolescent substance use interventions that address discrimination-related stress and substance use among black individuals impacted by the legal system.

NCT06003725.

To evaluate the prognostic significance of tumour deposit (TD) across different N stages in patients with stage III colon cancer and to develop and validate a novel N staging system that incorporates TD count to improve prediction of cancer-specific survival (CSS).

Retrospective cohort study based on population-based data and external validation.

Secondary and tertiary care settings; data from the SEER database, a population-based cancer registry capturing cancer incidence and survival information (USA, 2010–2017); and a single-centre validation cohort from South China (2015–2019).

A total of 8739 stage III colon cancer patients from the SEER database who underwent curative surgery were included; 1335 (15.3%) had TD. Patients with

The outcome was cancer-specific survival (CSS). The prognostic impact of tumour deposit (TD) and the comparative performance of the novel N staging system versus the AJCC system were evaluated using the Fine-Gray competing risks model, time-dependent area under the curve (AUC) and Brier score.

TD was independently associated with poorer CSS: 1 TD (SHR=1.23, 95% CI 1.04 to 1.47, p=0.017), 2–3 TDs (SHR=1.36, 95% CI 1.17 to 1.58, p3 TDs (SHR=2.02, 95% CI 1.73 to 2.35, pet al, TDs were converted to metastatic lymph nodes (mLNs) using the following weighting: 1 TD=3 mLNs (N1c), 1 TD=2 mLNs (N1) and 1 TD=1 mLN (N2). The novel N staging system stratified patients as nN1a (1 nLN), nN1b (2–3 nLNs), nN2a (4–6 nLNs) and nN2b (≥7 nLNs). This approach showed improved prognostic accuracy compared with AJCC N staging: 3-year AUC (0.623 vs 0.614) and Brier score (0.151 vs 0.157, p

TD significantly worsens prognosis in stage III colon cancer, particularly in lower N stages. Incorporating TD counts into the N staging system with different weightings based on N stage enhances prognostic accuracy and risk stratification within stage III disease, particularly for the heterogeneous AJC N1c category. This novel staging system provides better prognostic value and more accurate treatment guidance and should be considered for broader clinical use, subject to further (eg, prospective) validation.

Acute pain following pulmonary surgery can affect the recovery process of patients. The use of intrathecal morphine (ITM) injections offers a long-lasting analgesic effect, but its clinical application remains controversial. This study aims to investigate the impact of combining bupivacaine with ITM injections on the quality of postoperative recovery in patients who have undergone pulmonary surgery.

This multicentre, randomised, double-blind, controlled trial will enrol 254 patients undergoing elective lung surgery, who will be randomly assigned in a 1:1 ratio to either group IT (receiving an intrathecal injection of 3 mg bupivacaine and 0.25 mg morphine before general anaesthesia induction) or the control group (C group). The primary outcome includes postoperative recovery quality on day 1 (quality of recovery, QoR-15), with secondary outcomes encompassing postoperative recovery quality on days 2 and 3 (QoR-15), pain scores within 72 hours postoperatively, analgesic rescue, intraoperative haemodynamic parameters, opioid consumption, postoperative adverse reactions, recovery metrics, complications, chronic pain incidence and sleep quality.

The results will be disseminated through peer-reviewed publications. This study protocol (V.2.0, 30 October 2024) involves human participants and has been approved by the Ethics Committee of Affiliated Hospital of Yangzhou University (number 2024-08-02-2), Taicang Hospital Affiliated to Soochow University (number 2025 SR-041) and Yichang Central People’s Hospital (number 2024-513-02). Each individual who agrees to participate in the research will provide written informed consent after the objectives and procedures of this study are explained to them.

ChiCTR2400092935. Registered on 26 November 2024.

To assess the acceptability and adoption of multiparameter point-of-care testing (POCT) devices for the diagnosis and management of non-communicable diseases (NCDs) at the primary healthcare level in a resource-limited region of Peru.

Qualitative case-control process evaluation.

Eight primary healthcare facilities in northern Peru, including both urban and rural centres, where routine chronic care and laboratory services are provided.

Sixty-three participants: 36 patients, 12 laboratory technicians, 10 healthcare professionals and five facility heads. Eligible patients were ≥18 years, residing in the catchment area, with or without prior NCD diagnoses. Healthcare workers, including physicians, nurses, laboratory staff and facility managers.

Multiparameter POCT devices were installed in four intervention facilities, accompanied by staff training and community awareness activities, while four control facilities continued with conventional laboratory diagnostics.

Primary outcome: perceptions of patients and healthcare workers regarding the acceptability and adoption of POCT devices. Secondary outcomes: identification of facilitators and barriers to implementation, including infrastructure, supply chains and training gaps.

(1) Individuals: POCT was valued for speed and comfort, but concerns over accuracy were mentioned. (2) Intervention characteristics: laboratory staff valued POCT’s practicality in emergencies, but noted limitations in handling multiple samples. (3) Outer setting: urban centres outperformed rural facilities, with more staff and longer operating hours. (4) Inner setting: calibration gaps impacted POCT and conventional test reliability, requiring quality control and training. (5) Process: clear staff communication boosted patient confidence in POCT, but inconsistent training could lead to reliability doubts.

Multiparameter POCT devices show promise for enhancing NCD care in resource-limited primary healthcare settings, particularly in rural areas. However, their sustainability depends on broader health system reforms, including reliable supply chains, expanded training and stronger quality assurance mechanisms. Further research should examine strategies for embedding POCT within national regulatory and policy frameworks.

This study aimed to investigate the association between smoking behaviours during early pregnancy and the risk and severity of gestational diabetes mellitus (GDM), with a particular focus on smoking status, smoking intensity and secondhand smoke exposure.

Secondary analysis of prospectively collected cohort data.

Multi-centre study conducted in South Korea (Korean Pregnancy Outcome Study) between March 2013 and January 2017.

From 4537 pregnant women initially enrolled, 3457 singleton pregnancies were included after excluding cases with transfer, loss to follow-up, twin pregnancies, miscarriages and pre-existing diabetes mellitus. All participants were women of Korean ethnicity.

Primary outcome was GDM and its subtypes (A1GDM: diet-controlled; A2GDM: insulin-requiring). Secondary outcomes were associations with active smoking (before pregnancy and during early pregnancy), smoking intensity dose–response relationships (pack-years) and secondhand smoke exposure among never-smokers.

Among 3457 participants, 231 women (6.7%) were diagnosed with GDM (198 A1GDM, 33 A2GDM). Active smoking before pregnancy (adjusted OR (aOR) 3.98, 95% CI 1.58 to 9.30) and during early pregnancy (aOR 9.90, 95% CI 2.97 to 29.45) were significantly associated with A2GDM, while no significant association was observed with A1GDM. A clear dose-response relationship was observed, with smoking intensity >4 pack-years markedly increasing A2GDM risk (aOR 20.68, 95% CI 6.75 to 59.39). Detailed pack-year analysis showed 4–6 pack-years (aOR 20.57, 95% CI 5.80 to 65.46) and >6 pack-years (aOR 25.98, 95% CI 3.21 to 146.45). Among never-smokers, secondhand smoke exposure showed a borderline association with overall GDM risk (aOR 1.33, 95% CI 0.98 to 1.81).

Maternal active smoking before and during early pregnancy, as well as higher smoking intensity, was associated with an increased risk of pharmacologically treated GDM (A2GDM). Although secondhand smoke exposure did not reach statistical significance, the trend suggested a potential association with GDM risk among never-smokers. These findings provide important evidence for public health strategies for prenatal care, as smoking cessation and environmental smoke avoidance during prenatal and early antenatal care in women reduce the risk of gestational diabetes.

Sugemalimab plus chemotherapy significantly prolonged progression-free survival and overall survival in patients with advanced oesophageal squamous-cell carcinoma (ESCC). However, considering the high cost of sugemalimab, we evaluated the cost-effectiveness of sugemalimab plus chemotherapy in the first-line treatment for advanced ESCC.

A partitioned survival model with a 3-week cycle length and the lifetime time horizon was constructed to assess the cost-effectiveness of sugemalimab plus chemotherapy versus placebo plus chemotherapy as first-line treatment for advanced ESCC. The key survival data, drug costs, and utility values were obtained from the GEMSTONE-304 trial, YAOZHI database and the published literature. Total costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were measured. One-way and probabilistic sensitivity analyses were performed to evaluate the uncertainty and model stability. In addition, subgroup and scenario analyses were conducted.

The Chinese healthcare system perspective.

A hypothetical Chinese cohort of patients with unresectable, locally advanced, recurrent or metastatic ESCC.

Sugemalimab plus chemotherapy versus chemotherapy.

Costs, QALYs, ICERs.

Compared with the placebo plus chemotherapy, the sugemalimab plus chemotherapy provided an additional 0.36 QALYs, with an incremental cost of $44 376.88. The result of ICER was $119 400.69/QALY, which was significantly higher than the willingness-to-pay (WTP) threshold of three times per capita gross domestic product ($38 024.68/QALY) in 2023. Sensitivity analysis revealed that the cost of sugemalimab, the discount rate and the utility values were the most influential parameters on the base-case analysis results. Subgroup analyses showed that programmed cell death - ligand 1 subgroup ICERs exhibited dose-dependent efficacy: the ICERs for sugemalimab plus chemotherapy versus placebo plus chemotherapy were $138 739.23/QALY and $108 051.81/QALY in advanced ESCC patients with 1 ≤ combined positive score (CPS)

From a Chinese healthcare system perspective, sugemalimab plus chemotherapy as first-line treatment for advanced ESCC might not be a cost-effective treatment option at the WTP threshold of $38 024.68/QALY.

Hypertension represents a major public health challenge globally, with a rising prevalence in China. This study aims to explore the factors shaping blood pressure (BP) control among hypertensive patients managed in community health centres (CHCs), with a particular emphasis on the association with age.

This was a population-based, observational study that used healthcare records from CHC in Shenzhen, covering the period from 1 January 2000 to 8 October 2024. Univariate and multivariate logistic regression analyses were employed to assess the independent associations of various factors with BP control rate. Additionally, the study evaluated the relationship between age and BP control across six distinct age subgroups.

The study included 1 073 914 participants who met the eligibility criteria, with 955 415 (88.97%) patients achieving BP control. The median baseline age was 55.9 (IQR 18–109) years. Individuals aged 45 years and above demonstrated better BP control rates (46–55, OR 1.053, 95% CI 1.020 to 1.087; 56–65, OR 1.246, 95% CI 1.205 to 1.289; 66–75, OR 2.183, 95% CI 2.103 to 2.265; >75, OR 2.159, 95% CI 2.060 to 2.262). Among young adults aged 18–35 years, increasing age was consistently associated with poorer BP control across most subgroups. For the middle-aged groups (36–45 and 46–65 years), age had little impact on BP control. In the 66–75 years age range, older age was linked to better BP control in some groups.

The association between age and BP control varied across age groups. Hypertension management strategies should be tailored to address the unique needs of different age groups, geographical regions and targeted populations.

Type 2 diabetes mellitus has been associated with an increased risk of cognitive decline and dementia, with patients being 1.5–2 times more likely to develop these conditions. While both sodium-glucose co-transporter 2 (SGLT2) inhibitors and thiazolidinediones (TZDs) have shown potential neuroprotective effects in previous studies, their comparative effectiveness for preventing neurodegenerative outcomes has not been established. This study aimed to compare the risk of stroke, dementia and Alzheimer’s disease (AD) between patients treated with SGLT2 inhibitors and those treated with TZDs.

Multicentre, retrospective, observational, new-user, active-comparator cohort study.

Electronic health record-based databases from 11 secondary and tertiary institutions in South Korea from 1 January 2014 to 31 July 2025. The study period began in 2014, following the post-marketing surveillance initiation of SGLT2 inhibitors in Korea (November 2013), to ensure adequate drug availability and clinical adoption.

Patients aged 40 years or older who were newly prescribed either SGLT2 inhibitors or TZDs without prior exposure.

Propensity score matching (1:1) was performed using sex as the primary covariate due to data availability constraints in the Observational Medical Outcomes Partnership Common Data Model framework. The HRs with 95% CIs were measured via Cox regression analysis.

The study analysed 24 172 matched pairs for stroke outcomes (40 483 person-years in the SGLT2 inhibitor group and 39 363 person-years in the TZD group), 25 111 matched pairs for dementia (41 924 person-years in the SGLT2 inhibitor group and 40 726 person-years in the TZD group) and 25 237 matched pairs for AD (42 139 person-years in the SGLT2 inhibitor group and 40 895 person-years in the TZD group) across 11 participating hospitals. After a 1:1 propensity score matching, the SGLT2 inhibitors showed no significant difference in stroke risk (HR 1.18, 95% CI 0.62 to 2.23, p=0.62), while having significant reductions in dementia risk (HR 0.66, 95% CI 0.45 to 0.98, p=0.04) and AD risk (HR 0.54, 95% CI 0.35 to 0.83, p=0.005). Moreover, these protective effects for neurodegenerative outcomes were shown to be consistent across multiple hospital sites.

SGLT2 inhibitors are associated with a reduced risk of dementia and AD compared with TZDs in patients aged 40 years or older with type 2 diabetes and have neutral effects on stroke risk. These findings confirm the potential selective neuroprotective benefits of SGLT2 inhibitors for neurodegenerative outcomes, which may inform therapeutic decision-making for diabetic patients at risk of cognitive decline.

The WHO Package of Essential Non-communicable Diseases Interventions (WHO PEN) provides a core set of measures to prevent, detect and manage non-communicable diseases (NCDs) in low-resource settings. Many countries have adopted WHO PEN to strengthen primary healthcare, yet there is limited consolidated evidence on what components have been implemented and how WHO PEN has been implemented across different contexts. Understanding both the ‘what’ (disease modules, intervention activities, tools) and the ‘how’ (strategies, approaches, target populations and contextual factors) is crucial to assess the short-term to medium-term effects on health system readiness, provider performance, patient outcomes and long-term population health impact.

This protocol outlines a systematic review that will be updated as new evidence emerges and additional countries adopt or adapt WHO PEN. It represents the first systematic review focused on the implementation of the multifaceted interventions under WHO PEN. Findings will support efforts to sustain and scale up NCD interventions at the primary healthcare level and inform future updates of WHO PEN and related WHO guidance.

We will search PubMed, Web of Science, Cochrane Library and Google Scholar for studies published up to June 2025, supplemented by grey literature and reference checking.

The review will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. Given the complexity, the review will be conducted in two stages. Stage 1 consists of an overview of review, mapping of existing review and evidence and guiding deeper inquiry of stage 2. Stage 2 will conduct a mixed-methods systematic review of the primary studies, forming the main output of this protocol.

Ethics approval is not required. The protocol and findings will be disseminated through peer-reviewed publications, webinars and conferences.

CRD420251064835.

To explore the current context in which maternal influenza vaccination (MIV) is delivered in Kuwait and to identify determinants influencing its provision and uptake from the perspectives of preventive medicine professionals (PMPs), including policymakers.

Qualitative semistructured interviews were conducted with purposely selected PMPs including policymakers. Interview questions were obtained from the Tailoring Immunization Programme for improving MIV in Europe.

PMPs from six governmental regions of Kuwait, including hospitals and associated polyclinics. Data collection was conducted between March and June 2022.

A total of 10 participants reflected diverse professional and population contexts, including Kuwaiti and non-Kuwaiti professionals working in rural and urban settings. Cell sampling was used to ensure representation across key roles involved in MIV delivery, including policymakers, vaccination campaign managers and campaign implementers.

Thematic analysis identified four overarching themes: barriers, facilitators, influences on MIV uptake and suggested interventions. Key barriers included limited knowledge among pregnant women and healthcare providers (HCPs), lack of prioritisation of pregnant women within vaccination programmes, shortage of vaccine supply and the COVID-19 pandemic. Facilitators and influential factors included the presence of vaccination champions, targeted health promotion activities and the availability of a Ministry of Health (MoH) hotline for addressing concerns and system-level accessibility and digital facilitation of MIV uptake. Suggested interventions emphasised strengthening HCP education through continuous training aligned with clear national policies and guidelines.

This study highlights the need for clear national policies and clinical guidelines to support consistent MIV provision, alongside ongoing education for HCPs in Kuwait to strengthen MIV recommendation. Future research should include obstetricians, given their central role in antenatal care, to ensure MIV strategies are clinically grounded and integrated into routine maternity services.

This study investigated perinatal depressive symptoms among pregnant and postpartum Filipino women.

Cross-sectional survey.

The Philippines.

Participants were recruited online and face-to-face from maternal care facilities.

Perinatal depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS) score, with prevalence calculated based on ≥13 cut-off, indicating clinically significant symptoms of depression. Patterns of depressive symptoms were examined by demographics, perinatal time period and other obstetric information using adjusted regression coefficients (ab) and risk ratios (aRR).

A total of 856 women participated in the study, comprising 356 pregnant and 500 postpartum women. EPDS scores were, on average, similar between pregnant (14.4) and postpartum women (14.1). Using the locally validated cut-off of ≥13 revealed that 69.1% of pregnant and 62.0% of postpartum women reported clinically significant depressive symptoms. Consistent EPDS scores and prevalence were observed across pregnancy trimesters and within 12 months postpartum and beyond. Women who received adequate prenatal care were less likely to experience antenatal (ab=–1.59, 95% CI –3.13 to –0.05) and postpartum (ab=–1.30, 95% CI –2.48 to –0.12) depressive symptoms. Postpartum EPDS scores and depressive symptom prevalence (EPDS score ≥13) were higher among 18–24-year olds (ab=1.96, 95% CI 0.30 to 3.61; aRR=1.23, 95% CI 1.03 to 1.47) and single mothers (ab=3.46, 95% CI 0.22 to 6.71; aRR=1.42, 95% CI 1.07 to 1.90), compared with older and married mothers, respectively.

At least 60% Filipino mothers experienced clinically significant perinatal depressive symptoms, which exceeds the established global average of 25%. Younger and single postpartum women were at greater risk, while pregnant and postpartum women who attended adequate prenatal visits were less likely to report depressive symptoms. Our study underscores the need for further research to uncover the true burden of poor perinatal mental health and calls for targeted early interventions and integrative public health strategies to support at-risk mothers, particularly those from socially disadvantaged backgrounds.