Pharmaceutical manufacturers routinely launch high-cost, specialty medicines, including biologics and biosimilars, with an accompanying patient support program (PSP). PSPs offer patients financial support, case management and clinical services to facilitate access to the promoted medicine. Because these programs are proprietary, there is little publicly available information, thus, this study aimed to generate in-depth understandings of the patient, health system and policy-level implications of relying on manufacturer PSPs for affordable access to high-cost medicines.

Qualitative, critical ethnographic study conducted from November 2023 to April 2025. We conducted an interpretive, thematic analysis, triangulating fieldnotes (40 hours observations at public events), semistructured in-depth interview transcripts (n=48 interviews with 52 participants) and documents (ie, policies, media, reports).

This study examined direct experiences with manufacturer PSPs across Canada. PSPs have proliferated in Canada as the universal public health insurance scheme does not cover outpatient prescription drugs or infusion services.

A purposive sample of 52 participants with direct experience of pharmaceutical industry PSPs, including patients prescribed specialty medicines, clinicians, pharmaceutical industry and PSP provider employees, payers and policymakers.

Manufacturer PSPs are the default pathway for people to afford and access high-cost specialty and biologic prescription medicines in Canada. Though they are the only care pathway available, participants experienced support as variably helpful, stressful and superfluous; variable over time and across patients’ experiences; and available at the discretion of the PSP. Across participants, four core themes were identified: (1) patients are required to engage with PSPs in exchange for access; (2) outsourcing supports for access to medicines gives rise to a parallel, private health system, generating additional health system complexity; (3) programs are inherently designed for physicians, thus adoption is prioritised over access; and (4) this results in calculated policy trade-offs and health system and patient risks when depending on manufacturer PSPs for affordable access to medicines.

Patients and health systems are precariously dependent on manufacturers to afford and access high-cost, specialty medicines. As a parallel, private care system, there remains little transparency nor patient accountability, with access at the discretion of manufacturers through physician intermediaries. Thus, reliance on pharmaceutical industry resources for affordable access to medicines may incur greater costs for patients and health systems in the longer term. Policymakers need to consider how to design patient-centred, equitable, accountable systems that ensure affordable access to important medicines.

Doxycycline as post-exposure prophylaxis (doxy-PEP) has emerged as an efficacious strategy to reduce Chlamydia trachomatis (C. trachomatis), Neisseria gonorrhoeae (N. gonorrhoeae) and syphilis (sexually transmitted infections (STIs)) among gay, bisexual and other men who have sex with men (GBM). There is a need to identify prescribing criteria that maximise the number of STIs averted while minimising excessive use.

In this prospective longitudinal cohort study with repeated measures and biobehavioural data collection, participants completed a questionnaire and tested for STIs at each visit.

Community-based, population-level study conducted in three large Canadian cities between February 2017 and July 2023.

2449 GBM were recruited through respondent-driven sampling (RDS); 1998 had ≥1 follow-up visit, contributing 7551 person-years of observation. Eligible participants were aged ≥16 years, cis- or transgender men, reported sex with another man in the past 6 months and resided in Montreal, Toronto or Vancouver.

Adjusted rate ratios (aRR) of STIs, accounting for RDS recruitment, loss to follow-up and confounding were estimated using generalised estimating equations (GEE) Poisson regression. For identified STI risk factors, the proportions of STIs averted through doxy-PEP prescription (based on the efficacy of doxy-PEP for each bacterial STI) and the number needed to treat (NNT) for 1 year to avert one STI, assuming 100% adherence, were calculated.

Among 1998 participants, the combined incidence rate of any C. trachomatis, N. gonorrhoeae and syphilis infection was 29.5 (95%CI 27.3 to 31.9) per 100 person-years. STI risk factors that had the most impact as doxy-PEP criteria were history of any of the three STIs in the past 12 months (P12M) (aRR=2.0, 95% CI 1.8 to 2.2, 36% STI averted, NNT=2.1); ≥10 male sexual partners in the past 6 months (P6M) (aRR=3.8, 95% CI 3.0 to 4.9, 41% STI averted, NNT=2.4); HIV-pre-exposure prophylaxis (PrEP) use P6M (aRR=1.7, 95% CI 1.5 to 2.0, 29% STI averted, NNT=2.5); use of any chemsex-related substance P6M (aRR=1.2, 95% CI 1.1 to 1.4, 28% STI averted, NNT=2.6); and group sex event attendance P6M (aRR=1.2, 95% CI 1.1 to 1.3, 27% STI averted, NNT=2.3). Reporting≥10 male sex partners P6M represented the most useful criterion for syphilis prevention (52% syphilis infections averted, NNT=20). Prescribing doxy-PEP to GBM having any of the following STI risk factors, namely, ≥1 bacterial STI P12M, ≥10 male sex partners P6M, or HIV-PrEP use P6M, would substantially increase the proportion of all STI diagnoses potentially averted (60%) with minimal increase of the NNT (2.7).

This work informs on the impact of various doxy-PEP clinical prescribing criteria and demonstrates the benefit of focusing on any of the following three criteria: ≥1 bacterial STI P12M, ≥10 male sex partners P6M or HIV-PrEP use P6M.

Diabetic foot ulceration represents a prevalent, persistent and resource-intensive complication of diabetes. These ulcers are slow to heal, prone to recurrence and impose a substantial burden on both patients and healthcare providers. The reducing the impact of diabetic foot ulcers (REDUCE) intervention has been designed as a multifaceted approach targeting psychological and behavioural determinants linked to diabetic foot ulcer (DFU) outcomes. Following a successful pilot trial, the REDUCE trial has been designed as a pragmatic, multicentre randomised trial to compare the effectiveness and cost-effectiveness of the REDUCE intervention plus usual care versus usual care alone in reducing recurrence in people with healed DFUs. Additionally, there is an embedded process evaluation and two sub-studies which will be carried out alongside the main trial.

Adults over 18 years of age, with a recently healed DFU and two lower limbs, will be identified from around 30 specialist multidisciplinary diabetic foot clinics at participating National Health Service Trusts in the UK. Patients with active Charcot neuro-osteoarthropathy, active DFU or ulcers healed for more than 12 weeks will be excluded. We will aim to recruit 544 participants (1:1 randomisation). The primary outcome for this trial will be total ulcer-free days with limbs intact (ie, without amputation) between randomisation and the end of follow-up (18 months post-randomisation). Secondary outcomes include time to re-ulceration, total number of ulcers, amputation, quality of life (EQ-5D-5L), Patient Health Questionnaire-9, Nottingham Assessment of Functional Footcare, ICEpop capability measure for adults and resource use. As part of the process evaluation, up to 20 REDUCE intervention patient-participants will be interviewed, and the healthcare professionals delivering the intervention will also be interviewed. An assessment of intervention fidelity will also be carried out.

Ethics approval was granted by Wales 3 Research Ethics Committee (REC reference 22/WA/0053) on 16 March 2022. The findings will be presented at relevant conferences and disseminated via peer-reviewed research publications and to relevant stakeholders.

ISRCTN15570706.

Frostbite is a common reason for emergency department (ED) presentations in Canada. Iloprost, a prostacyclin analogue, has been investigated to reduce the risk of amputation with its use expanding. Two Canadian cities implemented iloprost over different times leading to a practice variation that allowed for treatment comparison. Our objective is to evaluate the effectiveness of iloprost compared with non-iloprost treatment. Secondary objectives include assessing the impact of iloprost dosage and homelessness.

A retrospective cohort study was conducted on adult severe frostbite cases presenting to EDs in Calgary and Edmonton between November 2021 and April 2024. Data were abstracted from clinical databases and analysed for demographic and injury characteristics, treatment and amputation outcomes.

Of 1812 total ED encounters for frostbite, 257 patients with grades 2–4 extremity frostbite were included for analysis. Logistic regression found that overall patients receiving iloprost were associated with reduced likelihood of any amputation (OR=0.49, 95% CI 0.25 to 0.96) and fewer digit amputations (p

Iloprost infusion was associated with a reduction in amputation rates in grade 3 and 4 frostbite with the greatest association seen in grade 3 cases. Greater iloprost dosage was associated with improved digit salvage. Homelessness was associated with delayed ED presentation.

Clinical practice guidelines support evidence-based care and aim to reduce unwarranted variation in healthcare. Despite evidence that guideline-adherent physiotherapy is associated with reduced healthcare utilisation, adherence among physiotherapists remains inconsistent. This scoping review aimed to synthesise evidence on determinants of guideline adherence and implementation strategies in physiotherapy and to identify research gaps relevant to guideline implementation.

Scoping review.

MEDLINE (PubMed), EMBASE, the Cochrane Library, PEDro and CINAHL were searched from database inception to July 2023 and updated in July 2025. Grey literature sources, including Grey Literature Report, OpenGrey and Web of Science Conference Proceedings, were also searched. Reference lists of included studies were screened.

Studies were eligible if they examined determinants of guideline adherence and/or implementation strategies in physiotherapy. Studies involving physiotherapists across all clinical fields and settings were included. Only studies published in English or German were considered.

Determinants were analysed using qualitative content analysis and mapped to the Consolidated Framework for Implementation Research (CFIR). Implementation strategies were summarised using Proctor’s reporting recommendations.

Fifty-eight studies were included: 29 examined determinants, 25 implementation strategies and four both. Determinants were identified across all CFIR domains, with most relating to the Inner Setting and Characteristics of Individuals. Implementation strategies primarily targeted individual-level change, such as education, reminders and feedback, whereas few addressed system-level factors, including organisational leadership or reimbursement structures.

Guideline implementation in physiotherapy is shaped by determinants across individual, organisational and system levels, yet current strategies predominantly focus on individual clinicians. This individual-level focus may contribute to the responsibilisation of clinicians for care quality, while organisational and system-level strategies that have shown promise in other fields remain underutilised in physiotherapy. Future implementation initiatives should adopt broader, system-oriented approaches to enhance long-term implementation success.

Open Science Framework (https://osf.io/g5cpt/).

Patients who consult their GP about psychological complaints, such as feeling anxious or depressed, are often initially given a psychological symptom diagnosis. However, it remains unclear whether these symptoms will develop into psychiatric conditions, which is crucial for informing patients about their prognosis and guiding GPs in their management.

To explore the course of psychological symptom diagnoses and compare GPs’ management strategies for (a) psychological symptom diagnoses that persisted for more than a year and (b) those that changed into psychiatric conditions during the first year of care.

We performed a retrospective cohort study using the Family-Medicine Network database. We included all episodes of care (EoC) that started with a psychological symptom diagnosis between 2008 and 2021. We performed negative binomial analyses and logistic regression analyses to compare management strategies and number of contacts between EoC that changed into psychiatric conditions and persistent psychological symptoms (>1 year) during the first year of care.

Out of the 14 633 EoC that started with a psychological symptom diagnosis, 79.4% resolved within 1 year, 12.8% persisted as psychological symptoms and 7.8% changed into psychiatric conditions. In EoC that changed into psychiatric conditions, as compared with EoC that persisted as psychological symptoms, we observed a significantly higher number of contacts with the GP (RR=1.76, 95% CI 1.63 to 1.91) as well as an increased total number of interventions (RR=1.71, 95% CI 1.58 to 1.84).

Most psychological symptoms remain for only a short period of time and only a few persist or change into psychiatric conditions. Future research should investigate the factors that influence patients’ decisions to seek further help from their GPs as well as those that contribute to the transition from psychological symptom diagnoses to a psychiatric condition.

To assess access to child-appropriate medicines in Albanian community pharmacies by applying a child-adapted version of sustainable development goal (SDG) indicator 3.b.3.

Cross-sectional survey.

Community pharmacies providing primary care medicines in six urban areas in Albania.

Thirty community pharmacies were surveyed. Two predefined baskets of child-appropriate essential medicines were assessed: 24 medicines for children aged 1–59 months and 25 medicines for children aged 5–12 years. Medicines were selected from these child-adapted SDG 3.b.3 medicine baskets proposed at an international level and then matched to paediatric formulations registered nationally for application to Albania.

Individual facility scores by age group and medicine type (originator brands (OBs) vs lowest-priced generics (LPGs)), as well as sensitivity analyses using alternative affordability thresholds.

The SDG 3.b.3 indicator score was 0%, as no surveyed facility reached the 80% access threshold. Mean facility scores were 42.6% for medicines intended for children aged 1–59 months and 29.6% for those aged 5–12 years, indicating poorer access for older children. Scores for OBs were particularly low (11.8% and 13.6%, respectively), reflecting reliance on LPGs. In younger children, ibuprofen and hydroxycobalamin showed 0% availability, while in school-aged children, paracetamol, propranolol and budesonide were absent across surveyed facilities; benzylpenicillin was absent in both age groups, whereas ceftriaxone was consistently available in both. Although all surveyed medicines were affordable, limited availability remained the primary barrier to access.

Application of the child-adapted SDG indicator 3.b.3 in Albania highlights substantial gaps in access to essential paediatric medicines in private community pharmacies, driven primarily by poor availability rather than affordability. The findings underscore the need for targeted supply-side policies. This study demonstrates the complementary value of composite SDG indicators and medicine-specific availability measures in monitoring progress toward universal health coverage for children.

Although important learnings come from traditionally designed large prospective asthma cohorts, highly restrictive inclusion and exclusion criteria limit generalisability to clinical practice. Moreover, small sample sizes for important disease subtypes, narrow scope of clinical data collection and limited biomarker assessments reduce the power of some studies to detect important and diverse longitudinal disease courses. The Real-world and Genomic data-based Asthma Insights through Network Analysis (REGAIN) study takes a novel approach to asthma cohort development by employing a pragmatic definition of asthma and simplified study procedures for biospecimen and data collection. REGAIN will produce a large scale, real-world, longitudinal clinical and molecular description of asthma powered to characterise and compare clinically relevant asthma subtypes. This design will provide insights on distinct longitudinal trajectories of disease, predictors of response to therapies and likelihood of clinical remission, all of which should help guide asthma management.

REGAIN is a clinical observational retrospective and prospective cohort study designed to determine large scale, real-world longitudinal clinical and molecular descriptions of asthma according to types of treatment, level of asthma control and inflammatory biology based on clinical biomarkers. Key questions include predictors of change in asthma control as well as timing and durability of clinical remission on biological therapy. To complement these clinical insights, REGAIN will produce one of the largest multiscale data sets in asthma that will include demographic and clinical features, inflammatory biomarkers, responses to therapy with inhaled steroids and other inhaled controllers with or without asthma biologics, and serial airway epithelium and peripheral blood transcriptomics and proteomics. REGAIN targets enrolment of 780 participants with asthma fitting one of five prespecified asthma subtypes with the aim of better characterising under-studied groups and allowing comparative analyses to elucidate important differential therapeutic responses and clinical trajectories. We target enrolment of 400 healthy controls to provide a healthy state molecular description of the tissues sampled in REGAIN participants with asthma. Participants with asthma are followed prospectively for 18 months with assessment of longitudinal clinical status including prospective clinical data collection, integration of electronic medical record data and serial biospecimen collection at 6 and 18 months. Participants with asthma starting treatment with asthma biologics undergo additional clinical assessment and biospecimen sampling at 3 months to track early clinical and molecular response to therapy. Healthy participants without asthma are evaluated cross-sectionally on enrolment without longitudinal follow-up in order to compare molecular profiles for airway epithelium and blood. An optional study component for participants with asthma employs a mobile phone application, digital inhaler monitors and home digital peak flow measurements and contributes data on real-time medication use, serial lung function and geolocated environmental data relevant to asthma.

The REGAIN protocol and all amendments were approved by The Icahn School of Medicine at Mount Sinai Program for Protection of Human Subjects (PPHS19-0358), and all participants provided written informed consent. Enrolment began in November 2019 and was completed in February 2024. Results will be presented at local, national and international meetings, and results will be submitted to peer-reviewed journals for consideration for publication.

NCT06623435.

The length of hospital stay for patients with physical illnesses is longer for those with mental health comorbidity, particularly in the presence of severe physical multimorbidity. Integrating psychosocial risk screening at hospital admission, with a subsequent care pathway, could address psychosomatic and social care needs early and reduce length of stay. However, implementation may be hindered by organisational factors such as increased staff workload and timely integration into existing processes. In addition, patient factors such as low acceptance of screening and follow-up may affect uptake. This pilot study aims to assess the feasibility of implementing this integrated approach to screening and follow-up in preparation for a confirmatory trial.

The present study is a single centre, randomised feasibility study conducted on a pilot ward. Patients will be enrolled and assigned to the intervention or the control group. Only the intervention group will receive tablet-based psychosocial risk screening conducted by ward physicians or medical students in their practical year. If the psychosomatic screening is positive and the patient agrees, he or she is referred to the psychosomatic consultation service. If the social service screening is positive, the patient will be seen by a social worker. The main objective of this study is to assess the feasibility of conducting a full-sized confirmatory trial. An informed consent rate of 30% of eligible patients is set as the feasibility criterion. A study period of 4 months is planned for the feasibility study. The feasibility study will be analysed using descriptive statistics.

The study protocol was approved by the Ethics Committee of the Medical Faculty of Heidelberg University (S-301/2024) on 24 May 2024. The results of this feasibility study will be published in a peer-reviewed journal.

NCT06651164.

To translate and culturally adapt six self-report measures for depression, anxiety, post-traumatic stress disorder (PTSD) and somatic symptom disorder into Hindi and determine their diagnostic accuracy against a diagnostic clinical interview.

Cross-sectional validation study.

Rural Kangra, Himachal Pradesh, northern India.

480 perinatal (pregnant or within 12 months postpartum) and non-perinatal (not currently pregnant and not given birth within 12 months) women at one tertiary hospital and district-level Anganwadi (community health) centres.

Symptom endorsement; and discriminant validity, sensitivity, specificity, positive and negative predictive values and area under the receiver operating characteristic curve (AUROC) of the Kessler Scale of Psychological Distress (K10), Patient Health Questionnaire (PHQ9), Edinburgh Postnatal Depression Scale (EPDS), Generalised Anxiety Disorder Scale (GAD7), Perinatal Anxiety Screening Scale (PASS), PTSD Checklist (PCL-5) and Scale for the Assessment of Somatic Symptoms (SASS).

Complete data were available for 443 participants. Tiredness and body weakness were the most commonly endorsed symptoms among participants with common mental disorders. Among perinatal participants, the AUROC was highest for the GAD7 (0.88, 95% CI 0.79 to 0.96) and SASS (0.84, 95% CI 0.71 to 0.96). Among non-perinatal participants, the AUROC was highest for the SASS (0.92, 95% CI 0.88 to 0.97) and PHQ9 (0.91, 95% CI 0.86 to 0.96).

Measures which assess for fatigue, tiredness and somatic symptoms may help to identify women experiencing common mental disorders in this setting. Small numbers of participants with clinically diagnosed mental disorders in our sample mean results must be interpreted cautiously.

NCT05485701.

Patients in intensive care units (ICUs) and their families face existential physical, psychosocial and spiritual distress. Integrating palliative care (PC) into ICU care may benefit patients, relatives and ICU clinicians. Prior PC studies have shown a reduction in ICU length of stay (LOS) and distressing symptoms without altering overall mortality. A shorter ICU LOS may alleviate the burden for patients and relatives and help optimise the use of limited intensive care resources. PC in the ICU, however, remains underused, partly due to limited access and knowledge of ICU clinicians. Also, robust data regarding the effectiveness and cost-effectiveness of PC treatment in the ICU are scarce. We established the ‘enhancing palliative care in ICUs’ (EPIC) study to implement a system-based harmonised practice model across European ICUs. The aim is to investigate if early integration of PC via telemedicine, clinician education and bedside tools is effective and cost-effective, ultimately benefiting patients, relatives and ICU clinicians.

This multicentre, controlled, cluster-randomised, non-blinded stepped-wedge design trial with crossover phase aims to recruit around 2,000 patients from five European countries. All adult patients admitted to participating ICUs—with an ICU LOS exceeding 72 hours, where cancer is not the primary cause of critical illness, and who are not expected to die within the next 24 hours—are screened for the need for specialised PC based on the attending physician’s judgement. This judgement is triggered by the presence of one or more of the following: (1) significant disagreement among ICU team members and/or relatives about the appropriateness of current ICU treatment, (2) considerations of limiting life-sustaining therapy or (3) the anticipation that a specialised PC consultation may benefit the patient, their relatives or the ICU team. Patients identified as needing specialised PC and their relatives are then enrolled after obtaining written informed consent.

The complex intervention consists of (a) a blended-learning programme to foster knowledge and attitude about PC among ICU clinicians, (b) bedside tools, including a checklist to identify patients in need of PC and a factsheet and (c) standardised telemedical consultations from trained EPIC interventionists. Patient and relative follow-up is conducted 3 months post-ICU discharge. Outcomes include clinical measures (including ICU LOS (primary outcome), severity of critical illness, invasive treatments and health-related quality of life), economic endpoints (resource use, costs, cost–consequence situation, cost-effectiveness), ICU clinician burnout and distress, and patient and family perception about the quality of symptom management, care and communication. Endpoint analyses will employ generalised linear mixed models, accounting for the clustered data structure and stepped wedge design.

EPIC complies with the Declaration of Helsinki and has been approved by all local ethics committees. A decision-making structure is established to ensure trial procedures are carried out according to Good Clinical Practice. Study findings will be published in peer-reviewed journals and communicated to participants, healthcare professionals and the public. Sets of anonymised study data will be made available following Findable, Accessible, Interoperable, and Reusable principles.

NCT06605079.

Transgender and gender-diverse individuals often face significant barriers to accessing gender-affirming care, such as hormones and/or surgery, leading to poorer mental health, lower quality of life, and higher rates of substance use and suicidal ideation. Vaginoplasty, the most commonly sought genital gender-affirming surgery (GGAS), is desired by over half of all trans women but has been performed in only a minority. This is due largely to limited surgeon availability and long wait times. Peer support has been shown to improve health outcomes and reduce stigma in marginalised populations, including trans communities, but has never been studied for efficacy during the perioperative period of GGAS. Building on priorities identified by multi-stakeholder engagement from the Transgender & Non-Binary Surgery Allied Research Collective, the Support for Transgender and Nonbinary Individuals Seeking Vaginoplasty (STRIVE) study aims to evaluate the efficacy of a centralised peer support and education intervention for patients seeking vaginoplasty, addressing a critical gap in perioperative care.

The STRIVE Study is a pragmatic, multi-site randomised controlled trial enrolling trans adults seeking full depth vaginoplasty. Participants are randomised to one of two arms; enhanced usual care, or a facilitated group intervention. The primary outcome is coping self-efficacy at 6 months, with a secondary outcome of surgical readiness. Primary analysis uses an intention-to-treat approach with linear mixed effects modelling, adjusting for selected baseline values and site. The feasibility evaluation data collected via qualitative interviews will be analysed thematically.

Approvals were granted by the primary site’s Institutional Review Board on 10 May 2024 (STUDY00026957). The trial was registered on 24 May 2024. Results will be published in open access journals and made available to community members in plain language formats.

NCT06436560.

Pulmonary embolism (PE) is a potentially fatal condition requiring timely diagnosis and treatment. CT pulmonary angiography (CTPA) is the gold standard for diagnosis and indicates PE severity through radiological markers of right heart strain. However, accurate interpretation and communication of these findings is often suboptimal in real-world practice. Artificial intelligence (AI) could alleviate pressure on radiology services by supporting PE identification, risk stratification and worklist prioritisation. Before widespread adoption, AI tools must be rigorously validated for diagnostic accuracy, safety and clinical impact.

This pragmatic single-centre, non-randomised quasi-experimental study will evaluate the diagnostic accuracy, feasibility, and clinical-cost impact of AI-assisted PE detection and risk stratification using AIDOC and IMBIO software. We will recruit two consecutive cohorts of adult patients undergoing CTPAs for suspected PE: a comparator cohort (12 months pre-AI implementation) and an intervention cohort (12 months post-AI implementation). AI will be applied retrospectively to the comparator cohort, while in the intervention cohort, radiologists will have contemporaneous access to the AI’s interpretation of CTPA images.

A subset of retrospective scans, both PE-positive and PE-negative, will undergo expert thoracic radiologist review to establish a reference standard. Data on patient demographics, clinical management and outcomes will be collected. Clinical management pathways and patient outcomes will be compared between cohorts to assess AI’s influence on acute PE management. Health economic modelling will assess the cost-effectiveness of integrating AI technology within the diagnostic workflow of acute PE.

This study was approved by the UK Healthcare Research authority (IRAS 311735, 10 May 2023). Ethical approval was granted by West of Scotland Research Ethics Service (23/WS/0067, 3 May 2023). Results will be shared with stakeholders, presented at national and international conferences, and published in open-access peer-reviewed journals.

NCT06093217.

The management of active patients with symptomatic knee osteoarthritis (KnOA) who are too young for total knee arthroplasty poses a specific challenge to clinicians. Research studies show that improving quadriceps muscle strength improves pain and function; however, aspects of the disease render it difficult for patients to achieve and maintain improvements. Recombinant human growth hormone (rHGH) is shown to increase the magnitude and duration of muscle growth when combined with exercise treatment in adult populations. Hence, rHGH combined with physical therapy may provide meaningful benefits in the treatment of KnOA.

This is a single-centre, double-blind, randomised trial to pilot a future Phase III trial from 2025 to 2028. Participants are aged 18–60 with clinical and radiographic evidence of isolated degenerative arthritis of the knee (patellofemoral or tibiofemoral). The investigational product is rHGH (Saizen (somatropin of rDNA origin, EMD Serono)) and a saline placebo. Participants will deliver the solution via subcutaneous injection area once per day at a dose of 0.5 mg HGH per body surface area (0.5 mg/m²) for 6 weeks, alongside participation in a lower limb strengthening programme developed by rehabilitation specialists. 17 participants will be recruited into each study arm.

The primary outcomes are feasibility (compliance with the study drug regimen for the 6-week administration period and enrolment rate) and safety (the proportion of minor and major adverse events between groups). The primary endpoint for these outcomes will be at 6 weeks. The secondary outcomes are knee extension strength, knee flexion strength, radiographic arthritis progression, thigh muscle circumference, MRI-measured quadriceps muscle volume and patient-reported outcome measures (Knee Osteoarthritis Outcome Score (KOOS), SF-20 and Tegner). The primary endpoint for these outcomes will be at 12 weeks, and the final endpoint will be 24 months, where final radiographic (X-ray) assessment will take place.

The primary outcome of compliance will be a calculation of mean compliance between groups, which can be analysed as a t-test after the treatment period. A two-sample, two-sided t-test will compare the clinical (secondary) outcome of greatest interest: knee extension strength at baseline versus week 6 compared between treatment groups. Other secondary outcomes will be compared using a simple linear mixed-effects model. The ² test will be used to determine whether the number of participants who made meaningful changes was different between groups. The null hypotheses are that the rHGH and placebo groups will have no difference in compliance rates, safety events, knee extension strength at 12 weeks and arthritis grade progression at 24 months.

This study has been approved by the Sunnybrook Research Institute Research and Ethics Board (#6427) and received a no-objection letter from Health Canada Clinical Trials. The primary sponsor is the Sunnybrook Centre for Clinical Trial Studies (CCTS). The findings of this study will be published in a peer-reviewed journal and presented at orthopaedic conferences.

NCT07036003.

Mothers’ mental health and life satisfaction may have been negatively affected due to challenges during the COVID-19 pandemic. Given the risk of future crises, knowledge of possible mitigating factors in this population is essential. This study aims to examine whether the pandemic affected the level of protective factors such as social support, physical activity and employment situation, and how these factors are associated with mental distress and life satisfaction.

Longitudinal cohort study.

Primary outcomes were mental distress (measured by the eight-item version of the Hopkins Symptom Checklist) and life satisfaction (measured by the Satisfaction With Life Scale). As the first step, we investigated changes in the levels of social support (defined by the number and frequency of social contact), physical activity (average hours of physical activity during a week), employment situation (actively working vs sick leave or unemployed), alcohol consumption (measured by the Alcohol Use Disorders Identification Test-Consumption) and relationship satisfaction (measured by the five-item version of the Relationship Satisfaction Scale).

We analysed data from two waves of the Norwegian Mother, Father and Child Cohort Study (n=~18 000 mothers); one pre-pandemic wave and one wave where half of the sample responded after the onset of the pandemic, with pandemic exposure being defined by questionnaire response timing rather than cohort recruitment. To assess changes in protective factors over time and pandemic exposure, we used difference-in-differences analyses and regression discontinuity design. Associations between protective factors with mental distress and life satisfaction, and possible moderation by pandemic exposure, were investigated using multiple regression models with interaction terms adjusted for potential confounders.

Apart from physical activity, which declined less across time in the pandemic group (B=0.09, 99% CI 0.05 to 0.12), protective factors did not change during the pandemic. Social support, employment situation and relationship satisfaction were associated with mental distress and life satisfaction, whereas physical activity showed a unique relationship with mental distress. Most associations were similar across pandemic exposure groups, except employment situation which appeared to have a stronger protective effect in the pandemic group (β=–0.12, 99% CI –0.24 to –0.00).

Changes over time in self-reported levels of protective factors were generally consistent among mothers independent of the pandemic. These factors appear to play an equally important role for mental distress and life satisfaction both under ordinary circumstances and during public health crises. Our findings enhance the understanding of how potential protective factors among mothers are associated with mental distress and life satisfaction in the context of a global stressor. Future studies should investigate additional mitigating factors that may be particularly relevant during global crises and explore the causal relationship between protective factors, mental health and life satisfaction.