Research on the impact of smoking behaviour across generations has primarily focused on grandmaternal smoking during pregnancy. However, the broader multigenerational effects of smoking behaviour, notably through environmental and behavioural pathways, remain underexplored. This study evaluated previous studies on the possibility of transgenerational transmission, rather than in utero transmission, regarding the effects of grandparental smoking behaviour on offspring’s development outcomes.
This study is a systematic review with qualitative evidence synthesis.
A comprehensive search was conducted across multiple online databases, including PubMed, EBSCOhost, Web of Science and Scopus. To ensure a broad scope of relevant studies, publication dates, study locations and language were restricted to English only.
After duplicates were removed, 3916 articles remained from the 4133 identified articles. Based on the predefined eligibility criteria, 38 articles were selected for full-text assessment. The selection process involved multiple reviewers, with disagreements resolved through consensus.
Multiple reviewers independently extracted data using a standardised protocol. The Joanna Briggs Institute critical appraisal tool was used to assess the quality of the included studies, with inter-rater reliability tests indicating moderate-to-high agreement. Extracted data included study design, participant demographics, exposure details and measured outcomes.
This systematic review included seven studies because of heterogeneity in reported outcomes and effect measures. Three independent reviewers extracted data using a standardised coding sheet. The synthesis compared methodologies, identified gaps, key findings and conclusions across studies.
Seven included articles examined grandchildren’s behaviour, such as hyperactivity disorder, oppositional defiant disorder and conduct problems, body composition and IQ concerning grandparents’ smoking habits. Most studies used robust statistical methods; two included parental factors as mediators. The synthesis of results indicated that the associations were primarily indirect. Key findings revealed that grandparents’ smoking status was significantly associated with their grandchildren’s physical and cognitive outcomes. Furthermore, the reviewed studies demonstrated sex-specific transgenerational effects of ancestral smoking on grandchildren’s health, with stronger effects often observed in male descendants.
This review highlights the methods and findings of previous studies on the potential transgenerational transmissions through which grandparents’ smoking behaviour may influence grandchildren’s behavioural, physical and cognitive development. Although the findings emphasise the importance of environmental and behavioural factors, further research is needed to address existing gaps and clarify mechanisms.
This systematic review protocol was registered in the PROSPERO database under registration number CRD42024571725.
The incidence of anal carcinoma is increasing, with the current gold standard treatment being chemoradiotherapy. There is currently a wide range in the radiotherapy dose used internationally which may lead to overtreatment of early-stage disease and potential undertreatment of locally advanced disease.
PLATO is an integrated umbrella trial protocol which consists of three trials focused on assessing risk-adapted use of adjuvant low-dose chemoradiotherapy in anal margin tumours (ACT3), reduced-dose chemoradiotherapy in early anal carcinoma (ACT4) and dose-escalated chemoradiotherapy in locally advanced anal carcinoma (ACT5), given with standard concurrent chemotherapy.
The primary endpoints of PLATO are locoregional failure (LRF)-free rate for ACT3 and ACT4 and LRF-free survival for ACT5. Secondary objectives include acute and late toxicities, colostomy-free survival and patient-reported outcome measures. ACT3 will recruit 90 participants: participants with removed anal tumours with margins ≤1 mm will receive lower dose chemoradiotherapy, while participants with anal tumours with margins >1 mm will be observed. ACT4 will recruit 162 participants, randomised on a 1:2 basis to receive either standard-dose intensity modulated radiotherapy (IMRT) in combination with chemotherapy or reduced-dose IMRT in combination with chemotherapy. ACT5 will recruit 459 participants, randomised on a 1:1:1 basis to receive either standard-dose IMRT in combination with chemotherapy, or one of two increased-dose experimental arms of IMRT with synchronous integrated boost in combination with chemotherapy.
This study has been approved by Yorkshire & The Humber – Bradford Leeds Research Ethics Committee (ref: 16/YH/0157, IRAS: 204585), July 2016. Results will be disseminated via national and international conferences, peer-reviewed journal articles and social media. A plain English report will be shared with the study participants, patients’ organisations and media.
Children with medical complexity (CMC) are a subset of children with special healthcare needs, defined by high healthcare utilisation, severe single or multisystem organ dysfunction, and in many cases, reliance on medical technology. In the emergency care setting, known challenges for this population include poor quality of care, avoidable admissions and high caregiver and provider burden. While experts and professional societies recommend emergency care planning tools to address these concerns, evidence to support effectiveness and implementation of such tools is lacking. Through a human-centred design approach, we recently engaged key partners to create and optimise an emergency care action plan (ECAP) for infants with medical complexity. Here, we describe the protocol for a pilot type 1 hybrid effectiveness-implementation randomised controlled trial (RCT) for infants with medical complexity aimed to evaluate ECAP effectiveness and implementation.
Infants with medical complexity and their caregivers will be randomly assigned to the intervention group (ECAP) or control group (standard care) in a pilot type 1 hybrid effectiveness-implementation RCT. The primary outcome is number of inpatient hospital days for infant participants. Additional effectiveness outcomes include perceived avoidance of emergency department (ED) visits, healthcare costs, caregiver stress and self-efficacy. Preliminary implementation outcomes include acceptability, feasibility, appropriateness and usability, as well as contextual barriers and facilitators to reach, adoption and implementation. Key partners, including caregivers of CMC and healthcare providers, will be engaged throughout the implementation of the ECAP and execution of the trial.
This study was approved by the University of Vermont Institutional Review Board (STUDY00002937). Findings will be disseminated through peer-reviewed publications, conference presentations, and focus groups and interviews with key stakeholders.
Artificial intelligence (AI) has the potential to revolutionise healthcare delivery, particularly in the domain of emergency medicine. With the rise of telemedicine and virtual care, AI-powered tools could assist in triage, diagnosis and treatment recommendations for patients seeking emergency care remotely. This systematic review aims to synthesise the current state of research on AI applications in virtual emergency care, identify key challenges and opportunities and provide recommendations for future research and implementation.
We will conduct a comprehensive search of multiple electronic databases (PubMed, Web of Science, Embase, CINAHL, MEDLINE, The Cochrane Library, Scopus) from each database’s inception to March 2025. The search will include terms related to AI, machine learning, deep learning, virtual care, telemedicine and emergency medicine. We will include original research articles, conference proceedings and preprints that describe the development, validation or implementation of AI models for virtual emergency care. Two reviewers will independently screen titles and abstracts, review full texts, extract data and assess risk of bias using the PROBAST (Prediction model Risk Of Bias ASsessment Tool) tool for prediction model studies, Cochrane Risk-of-Bias tool for randomised trials for randomised trials and Risk Of Bias In Non-randomised Studies of Interventions for non-randomised studies. Data synthesis will involve a narrative review of included studies, summarising key findings, methodological approaches and implications for practice and research. The results will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
No ethical approval is required for this systematic review as it will use only published data. The findings will be disseminated through publication in a peer-reviewed journal, presentations at relevant conferences and engagement with clinicians, health system leaders, policymakers and researchers. This review will provide a timely and comprehensive overview of the applications of AI in virtual emergency care to inform evidence-based guidelines, policies and practices for leveraging these technologies to enhance access, quality and efficiency of emergency care delivery.
CRD42025648202.
In Bangladesh, evidence on the long-term trajectory of adolescents' sexual and reproductive health (SRH) remains limited, largely due to the lack of longitudinal data to assess the changes over time. To address this gap, the Advancing Sexual and Reproductive Health and Rights (AdSEARCH) project of International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) set up an adolescent cohort study aimed at documenting changes in SRH knowledge, attitudes and practices, and identifying the factors affecting these changes. This article presents the baseline sociodemographic and SRH characteristics of this cohort as a pathway for future analyses.
This cohort study included 2713 adolescents from the Baliakandi Health and Demographic Surveillance System run by icddr,b. The cohort covered three age groups from girls and boys, giving a total of five cohorts: girls aged 12, 14 and 16 years; and boys aged 14 and 16 years. A total of seven rounds of data had been collected at 4-month intervals over 2-years follow-up period.
The majority of adolescents were attending school (90%), and school dropouts were higher among boys. Around 17% of the respondents were involved in income-generating activities, which were mostly boys. Among girls, the mean age of menarche was 12.2 years. Overall, 6% of adolescents had major depressive disorder, with prevalence increasing with age. Gender differences were evident regarding knowledge about conception and contraception. Egalitarian attitudes towards social norms and gender roles were found higher among girls (52%) compared to boys (11%). The majority of adolescents reported experiencing social/verbal bullying (43%), followed by physical violence (38%) and cyberbullying (4%).
This article presents the baseline findings only. A series of papers is in the pipeline for submission to different peer-reviewed journals. The findings from this study will be used to support data-driven policy formulation for future adolescent health programmes.
Although as many as 92% of survivors of physical intimate partner violence (IPV) report impacts to the head and/or non-fatal strangulation (NFS) that raise clinical suspicion of brain injury (BI), there are no evidence-based methods to document and characterise BI in this vulnerable population, limited clinical practice guidelines and insufficient understanding about long-term risks for conditions including Alzheimer’s Disease and Related Dementias (ADRD). This leaves most survivors of IPV-caused BI (IPV-BI), overwhelmingly women, without adequate access to medical care and support, safe housing, back-to-school/work accommodations or follow-up care for long-term neurocognitive health. Although traumatic brain injury (TBI) is an established ADRD risk factor, little is known about the attributable risk of ADRD due to IPV-BI, particularly in women.
Our overarching objectives are to (1) use plasma biomarkers as novel tools to assist clinicians to improve diagnosis of IPV-BI at the acute, subacute and chronic stages in a manner sensitive to the needs of this vulnerable population and (2) raise awareness of the importance of considering IPV-BI as a potential ADRD risk factor. A prospective observational study funded by the US Department of Defense (HT9425-24-1-0462), Brain Canada (6200) and the Canadian Institutes of Health Research (523320-NWT-CAAA-37499) leverages collaborative research at multiple clinical sites in British Columbia to maximise equity, diversity and inclusion among participants, with a target enrolment of n=600 participants.
The Advocates, Academics, Survivors and Clinicians to END Intimate Partner Violence Biomarkers study, which is predicated on pre-specified research questions, represents one of the most significant community-based studies on plasma biomarkers affected by an IPV-BI incident. Of particular significance is the fact our study uses robust biomarker approaches being applied in the TBI and ADRD fields to determine how the biomarker profile after IPV-BI compares to typical TBI and the early stage of neurodegenerative disorders.
This study was approved by the University of British Columbia Clinical Research Ethics Board (H24-01990, H22-02241 and H16-02792) and the Island Health Research Ethics Board (H22-03510). Upon publication of primary papers, de-identified data and biospecimens will be made widely available, including the US Federal Interagency Traumatic Brain Injury Research (FITBIR) federated database. Our data and integrated knowledge translation activities with persons with lived experience of IPV-BI and those working in the healthcare sector will be synthesised into co-designed and implemented knowledge tools to improve outcomes for survivors of IPV-BI.
Ischaemia reperfusion injury (IRI) is inevitable in kidney transplantation and negatively affects patient and graft outcomes. Anaesthetic conditioning (AC) refers to the use of anaesthetic agents to mitigate IRI. AC is particularly associated with volatile anaesthetic (VA) agents and to a lesser extent to intravenous agents like propofol. VA like sevoflurane interferes with many of the processes underlying IRI and exerts renal protective properties in various models of injury and inflammation. We hypothesise that a sevoflurane-based anaesthesia is able to induce AC and thereby reduce post-transplant renal injury, reflected in improved graft and patient outcome, compared with a propofol-based anaesthesia in transplant recipients of a deceased donor kidney.
Investigator-initiated, multicentre, randomised, controlled and prospective clinical trial with two parallel groups. The study will include 488 kidney transplant recipients from donation after brain death (DBD) or donation after circulatory death (DCD) donors. Participants are randomised in a 1:1 design to a sevoflurane (intervention) or propofol (control) group. The primary endpoint is the incidence of delayed graft function in recipients of DCD and DBD donor kidneys and/or 1-year biopsy-proven and treated acute rejection. Secondary endpoints include functional delayed graft function defined as failure of serum creatinine levels to decrease by at least 10% per day for three consecutive days; primary non-function is defined as a permanent lack of function of the allograft; length of hospital stay and postoperative complications of all kinds, estimated glomerular filtration rate at 1 week and 3 and 12 months calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula; readmissions at 3 and 12 months, graft survival and all-cause mortality at 12 months.
The study is approved by the local ethical committees and national data security agencies. Results are expected to be published in 2025.
Peer support in youth mental health settings holds promise as a developmentally appropriate and impactful initiative; however, research exploring implementation remains limited. To advance the field and strengthen future implementation efforts, the aim of the present study was to generate new understandings about how non-peer service providers working alongside youth peer support workers experience the peer support role in youth mental health settings.
Guided by interpretive description and tenets of a research community partnership model, semi-structured interviews were conducted with non-peer service providers (n=11) across three integrated youth services centres in British Columbia, Canada, from August to December 2020. Data were analysed inductively using a constant comparative approach to identify and construct themes.
Participants emphasised integration and supervision of youth peer support workers as essential for successful peer programming within integrated youth services, highlighting three interconnected themes: defining supervisory roles, envisioning role clarity and capacity and governance of youth peer support services.
Integrated youth services initiatives and peer-led agencies can play key roles—both directly and indirectly—to strengthen the governance and infrastructure of youth peer support.
Progressive supranuclear palsy (PSP) is a devastating neurodegenerative disease characterised by cognitive, behavioural and motor problems. Motor symptoms are highly disabling, while cognitive and behavioural changes have a major impact on carer burden, quality of life and prognosis. Apathy and impulsivity are very common, often coexistent in PSP, and negatively predict survival. In preclinical models and other diseases, apathy and impulsivity are associated with noradrenergic deficits, which can be severe in PSP.
Noradrenaline for Progressive Supranuclear Palsy Syndromes trial is a randomised, double-blind, placebo-controlled, crossover design, Phase IIb clinical trial to evaluate the efficacy and safety of oral atomoxetine for the treatment of cognitive and behavioural changes in PSP. Participants receive atomoxetine 40 mg (10 mg/mL oral solution) once daily or a matched placebo solution, in random order, each for 8 weeks. An ‘informant’, who knows the patient with PSP well, is co-recruited to complete some of the trial outcome measures. Participants remain in the trial for 22 weeks after randomisation. The primary objectives are to assess (1) safety and tolerability and (2) efficacy versus placebo on challenging behaviours as reported in a subscale of the Cambridge Behavioural Inventory. Secondary and exploratory measures relate to cognition, the PSP Rating Scale, mood and potential baseline predictors of individual response to atomoxetine computed from imaging, genetic and cognitive measures at baseline.
The trial was approved by the South Central-Oxford B Research Ethics Committee (REC) and the Medicines and Healthcare products Regulatory Agency (REC reference: 20/SC/0416). Dissemination will include publication in peer-reviewed journals, presentations at academic and public conferences and engagement with patients, the public, policymakers and practitioners.
ISRCTN99462035; DOI:
International consensus guidelines support the initial administration of 30 mL/kg of intravenous fluids for haemodynamic resuscitation of newly diagnosed septic shock. Practice variation exists between the volume of fluids administered and timing of vasopressor commencement. The optimal approach in patients with septic shock is uncertain.
Australasian Resuscitation In Sepsis Evaluation: FLUid or vasopressors In emergency Department Sepsis is a 1000-participant multicentre, randomised, open-label, parallel group clinical trial conducted in patients with septic shock presenting to the emergency department in participating sites in Australia, New Zealand and Ireland. Participants are randomised (1:1) to either restricted fluids and early vasopressors or a larger initial intravenous fluid volume and later vasopressors. The primary outcome is days alive and out of hospital at day 90 postrandomisation. Secondary outcomes are all-cause mortality at day 90, time from randomisation until death (to day 90), days alive and at home at day 90 and ventilator-free, vasopressor-free and renal replacement-free days to day 28 postrandomisation and death or disability at 6-month and 12-month postrandomisation. Health-related quality of life will be assessed at day 180 and 12 months following randomisation.
The study was approved by Northern Sydney Local Health District Human Research Ethics Committee (HREC2020/ETH02874) on 21 January 2021. Patients will be enrolled under a waiver of prior consent. The patient or next-of-kin (or equivalent according to local jurisdiction) is approached at the first available opportunity and given a trial information sheet. According to local approvals, the patient or next-of-kin chooses to either continue in the trial or opt-out/decline continued participation. Results will be disseminated in peer-reviewed journals and presented at academic conferences.
To explore neonatal survival by type of neonatal complications at birth and referral pattern for these complications by place of delivery.
Bihar, India.
Women aged 15–49 years who had given live birth between July 2020 and June 2021.
Prevalence of neonatal complications at birth, referral pattern by complication and neonatal deaths by type of complication.
Data were available for 6767 (81.8%) newborns including 717 neonatal deaths. The prevalence of at least one neonatal complication at birth was reported for 32.9% (95% CI 32.4 to 33.4) newborns, with the most common complications including difficulty in breathing (21.9%), high fever (20.7%), low birth weight (12.5%) and jaundice (13.2%). A total of 578 (26.6%; 95% CI 25.8 to 27.4) neonates with complications at birth were referred to another health provider, predominantly to private sector (68.1%, 93% and 78.7% from public facility, private facility and home). The complications with high referrals included meconium aspiration syndrome (64.1%; 95% CI: 61.1 to 67.1), inability to pass urine (54.7%; 95% CI: 42.1 to 67.2), difficulty in suckling (49.7%; 95% CI: 46.9 to 52.5), cold to touch (48.5%; 95% CI: 43.5 to 53.6), inability to cry (47.2%; 95% CI: 44.2 to 50.1), pneumonia (45.6%; 95% CI: 42.0 to 49.1), difficulty in breathing (44.0%; 95% CI: 42.5 to 45.6) and lethargy (43.5%; 95% CI: 38.4 to 48.6). Referrals were linked to higher neonatal deaths, in particular, among neonates born at home and referred for complications (84.7%; p
With one-third of the neonates reported to have complications at birth and those referred more likely to die, critical gaps in addressing neonatal complications at birth and improvement in the referral services are urgently needed to reduce neonatal mortality.
Psychotic disorders are more prevalent among minority ethnic groups in the UK. However, there is no research on how the British Sikh community understands and seeks help for psychosis. The way in which a community understands the nature, causes and treatment of psychosis can impact their duration of untreated psychosis, treatment pathways, experience and engagement with mental health services, and outcomes.
To explore the lay understandings of psychosis and associated help-seeking within the Sikh community in England, and how family, religion and culture influence these perspectives
An exploratory qualitative design, consisting of online semistructured interviews across the UK.
30 participants, 11 men and 19 women, ages ranged from 19 to 69, who identified as Sikh.
Thematic analysis revealed several common themes, including a lack of awareness and knowledge of psychosis, variety of causal beliefs held about psychosis, professional help-seeking being encouraged, religious practices regarded as helpful coping mechanisms, supernatural beliefs influencing alternative help-seeking, strong negative perceptions towards psychosis and general mental illness, the significant role of family and community, and conflicting religious and cultural beliefs.
Participants showed limited understanding of psychosis and mental illnesses, accompanied by widespread negative perceptions, potentially delaying help-seeking. Increasing awareness may prompt earlier help-seeking, enhancing outcomes and diminishing stigma.
To assess the relation of exposure to cement dust and heavy metal (aluminium, cadmium and lead) exposures to pulmonary function among male cement plant workers. The study also aimed to evaluate dose–response relationships and prevalence and severity of respiratory symptoms among exposure categories compared with a control group.
Cross-sectional study.
Secondary-level occupational health clinic in Ankara, Türkiye.
461 male non-smoking cement plant employees were included in total. Participants were categorised into packaging (n=101), milling (n=162) and office unexposed workers (n=198). Inclusion criteria were more than 70% work history in the cement industry and exclusion of pre-existing respiratory disease and missing data from the participants.
Not applicable.
Pulmonary function tests (forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC and peak expiratory flow (PEF)) and urinary, cadmium and blood lead concentrations were measured. Lung function impairment was the primary outcome measure; secondary outcomes included metal exposure—pulmonary measure correlations.
Significant negative correlations existed between FEV1 and urine aluminium (r=–0.622, p
Occupational cement dust and heavy metal exposure is closely linked to impaired pulmonary function in cement plant employees, particularly those who work in higher exposure jobs. The implications are robust endorsement of targeted monitoring and preventive interventions. Long-term longitudinal research is necessary to identify long-term outcome and efficacy of exposure reduction approaches.