Evaluate tofacitinib efficacy, safety and persistence by sex in rheumatoid arthritis (RA).

Post hoc analyses using data from phase III placebo-controlled randomised controlled trials (ORAL Scan, ORAL Sync and ORAL Standard).

ORAL Scan, ORAL Sync and ORAL Standard were global, multicentre trials conducted across 111, 114 and 115 sites, respectively.

The trials enrolled adults with active RA and prior inadequate response to methotrexate (ORAL Scan/ORAL Standard) or ≥1 conventional synthetic or biologic disease-modifying antirheumatic drug (ORAL Sync). Post hoc analyses included 2265 patients (1870 female and 395 male).

Patients received tofacitinib 5 mg or 10 mg two times a day, adalimumab or placebo.

Efficacy outcomes to month 12 included American College of Rheumatology (ACR)20, 50 and 70 responses, Disease Activity Score in 28 joints (DAS28) (erythrocyte sedimentation rate (ESR))-defined low disease activity (LDA) and remission, DAS28 (C reactive protein (CRP)) ≤3.2 and

At baseline, female patients had similar DAS28(CRP and ESR), slightly higher HAQ-DI and lower FACIT-F scores versus male patients (n=395). ORs for active treatments (tofacitinib and adalimumab) versus placebo were generally >1 for ACR20, 50 and 70 responses, DAS28(CRP) ≤3.2 and

In post hoc analyses, tofacitinib was efficacious across both sexes, with higher responses in males observed particularly for more stringent composite endpoints and patient-reported outcomes. Findings are generally consistent with studies of other advanced RA therapies. Safety and persistence were similar across sexes. Interpretation is limited by the small proportion of male patients (

NCT00847613, NCT00856544, NCT00853385, NCT00661661 and NCT00413699.

Several antibiotic stewardship interventions have been proven effective and safe for reducing the high number of antibiotic prescriptions in late preterm and term neonates at risk of early-onset sepsis (EOS). For successful translation of EOS interventions to clinical practice, implementation strategies should be employed targeting stakeholders. The primary aim of this study is to assess the impact of implementing an antibiotic stewardship bundle, including the EOS calculator, procalcitonin-guided therapy and intravenous-to-oral switch therapy on antibiotic exposure for EOS in Dutch secondary hospitals. Secondary aims are to examine additional clinical outcomes and implementation outcomes.

We will conduct a multicentre, prospective implementation study with interrupted time series and before-after analyses at the paediatric or specialised neonatal departments of 11 Dutch secondary hospitals and their surrounding neonatal care networks. A multimodal implementation strategy, designed using Implementation Mapping, is employed to facilitate implementation. The study population is twofold: (1) neonates born at 34 weeks of gestation or later with suspected EOS that will receive intervention-related care and (2) paediatricians, paediatric residents, neonatal nurses, maternity nurses and parents who are the focus of the implementation strategies. The primary outcome is days of antibiotic therapy per 1000 live-born neonates, which will be evaluated using interrupted time series analysis as well as before-after comparison. Secondary clinical outcomes will be assessed by comparing clinical data from the 12 months pre-implementation and post implementation. Implementation outcomes are adoption, fidelity, feasibility and acceptability of the interventions and fidelity and appropriateness of the implementation strategies. Implementation outcomes will be assessed using both qualitative and quantitative methods, including surveys, individual interviews and focus group interviews. A mixed-methods approach will be used to integrate clinical and implementation outcomes.

The Medical Ethics Committee United (MEC-U) declared (reference: W24.132) that this study does not fall under the Dutch Medical Research Involving Human Subjects Act (WMO). Subsequently, ethical approval was granted by the Scientific Committee of the Franciscus Hospital (T110). The scientific committees of all participating sites adopted this decision and granted permission for local conduct of the study. As electronic health record data are sampled retrospectively and anonymously, a waiver of consent was given to collect these data. Informed consent will be obtained from participants completing surveys or taking part in interviews and focus group discussions. The findings will be disseminated through journal publications and conference presentations. Furthermore, practice and policy recommendations will be collaboratively developed with partner organisations.

NCT06845332.

Globally, more than 700 000 people commit suicide annually. In Sweden, the yearly incidence ranges between 1000 and 1500 people, which is higher than the global average. The aim of this study is to estimate the economic burden related to indirect costs that suicide has imposed on Swedish society between 2010 and 2019.

National population-based cross-sectional study.

All suicides in Sweden between 2010 and 2019, using data from the Swedish National Cause of Death Registry.

Indirect costs associated with suicides, estimated using the human capital approach, including productivity loss over 1-year and lifetime horizons.

Between 2010 and 2019, 1406 to 1591 suicides occurred annually in Sweden, resulting in approximately 26 500 productive life years lost each year. In 2019, the productivity loss due to suicides was estimated at 44 million over a 1-year horizon and 935 million over a lifetime horizon. The corresponding per-person costs were 37 000 and 778 000, respectively.

This study provides valuable insights into the economic burden of suicide on Swedish society. It underlines the potential economic benefits of effective suicide prevention, aligning with previous research highlighting the substantial returns—both monetary and in terms of human well-being—that successful prevention strategies can yield.

Although poor mental health among young people has been increasing in the past decades, many young people are reluctant to use traditional mental healthcare. To cater to the needs of young people, various youth-friendly treatment options have been developed. These include the youth-friendly health service (YFHS) standards put forth by the WHO in 2012 and the integrated youth services (IYS) for mental health developed in certain countries globally. However, no synthesis of the effect of these services on youth mental health has been conducted. The aim of the proposed study is to conduct a systematic review of the effect of mental health treatments conducted within YFHS and IYS clinics. The primary research question is what effect mental health interventions given at ‘youth-friendly’ clinics for treating mental health, such as IYS and YFHS, have on the mental health and quality of life (QoL) of young people?

A preliminary search for other reviews on the topic was conducted during the first half of 2024, after which a protocol of the present study was registered in PROSPERO. In May 2024, a search was carried out in the PubMed, PsycINFO, CINAHL and Web of Science databases, which gave references for 12 738 papers to be screened for inclusion in the review, and a follow-up search was carried out in April 2025, yielding a further 2182 references. For inclusion, studies must have participants between 12 and 25 years of age; interventions be given at clinics designed to be ‘youth-friendly’ or given at an IYS; control condition, if any, consisting of standard care or waiting list; outcomes must be mental health symptomology or QoL. To be included, studies must be published from 2012 and onwards. Screening of titles and abstracts in the initial search was carried out independently by two reviewers. Screening of studies found in the follow-up search and in the reference lists of included articles will be carried out in the same way. Data analysis of the initial search was conducted in the latter half of 2024, while final data analysis including the results from the follow-up search is ongoing. The Cochrane risk of bias assessment tools will be used to assess bias of included articles, and certainty of the evidence will be evaluated according to the GRADE methodology. A meta-analysis of the results will be performed if a sufficient amount of homogenous data is found; otherwise, a synthesis without meta-analysis will be conducted.

The proposed review may form a valuable synthesis of the state of the art of treatment options catering to young people. Investigating the effectiveness of YFHS or IYS in treating young people’s mental health may inform future directions for development and research. The present study does not need ethical approval, since only previously published, ethically approved data are used in the current study. The findings of the study will be disseminated through submissions to peer-reviewed journals and international conferences, as well as disseminated within the Swedish YFHS community.

ID nr CRD42024528687.

The majority of people globally who have undergone limb amputations are living in low- and middle-income countries. For those with lower-limb amputations, ambulatory mobility with a prosthesis is considered a key factor for achieving independent living; however, little is known of determinants of mobility for prosthesis users in low- to middle-income countries. In this study, we sought to assess levels of self-reported mobility in Cambodian prosthesis users and to identify determinants associated with their ambulant mobility.

Cross-sectional survey.

Three secondary care centres located in urban and rural Cambodia.

Adults receiving prosthetic services for a major lower-limb amputation.

The Khmer version of the LCI-5 and the mobility dimension of the EuroQol five-dimensional five levels (EQ-5D-5L) were used as dependent variables, while personal, physical, psychological and social determinants served as independent variables. Associations were assessed using hierarchical and ordinal regression analyses.

347 participants completed the survey. Determinants that were negatively associated with mobility outcomes were as follows: being female, having an amputation due to dysvascular complications, using an above-knee prosthesis and reporting higher levels of psychological distress. Social determinants did not appear to have any major association with mobility outcomes.

Findings highlight the multidimensional nature of mobility and suggest that future interventions may benefit from targeting female prosthesis users and those with diabetes or vascular disease. Mental health interventions addressing symptoms of anxiety and depression may also contribute to improved mobility outcomes. Social determinants explored in the study were not associated with significant changes in mobility scores. This may be due to high overall levels of mobility, a relatively homogenous group or failure to identify context-specific variables that impact on mobility outcomes.