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.

Chronic dyspnoea is a prevalent symptom, and primary care is ideally placed to identify and manage it. However, chronic dyspnoea is under-reported by patients and can be a diagnostic dilemma for practitioners. A fully automated system of patient screening, coupled with a clinical decision support system (CDSS) that uses a validated and evidence-based dyspnoea algorithm, may improve detection, diagnosis and management of the condition. There is currently no CDSS validated for chronic dyspnoea diagnosis and management in primary care in Australia. The objectives of this study are to assess the clinical impact of a CDSS for chronic dyspnoea in primary care. We hypothesise that the use of the CDSS will lead to a clinically significant improvement in patient-reported dyspnoea scores, reduced time to diagnosis and healthcare costs at 12 months compared with standard care.

The BREATHE study is an open-label, cluster-randomised controlled trial of standard of care compared with a CDSS. General practices (n=40) in metropolitan, regional/rural and rural/remote settings will be recruited and randomised equally to pre-screening for chronic dyspnoea and usual standard-of-care management or pre-screening and CDSS-guided management. The CDSS includes an algorithm derived from a robust data and clinical knowledge model and incorporates evidence-based recommendations for the assessment and management of chronic dyspnoea. It is integrated into general practice medical software systems, fitting in the workflow of general practitioners (GPs). Eligible patients will be ≥18 years old and will have previously consented to receive SMS communication from their practice. In-scope patients will receive an automated text message prior to their GP appointment and will be screened for chronic dyspnoea (≥4 weeks). Patients identified with chronic dyspnoea will be invited to participate in the BREATHE study and followed up for 12 months. The primary outcome is improvement in the Dyspnoea-12 (D-12) score from baseline to 12 months, measured by the Dyspnoea-12 (D-12) questionnaire. Secondary outcomes include disease-specific questionnaires to assess changes in clinical outcomes, time to final diagnosis, quality of life, healthcare utilisation and costs incurred to patients.

The trial is registered at ANZCTR (ACTRN12624001451594). ANZCTR is a primary registry that meets the requirements of the ICMJE and is listed on the ICTRP Registry Network.

The study protocol has been approved by the University of New South Wales Human Research Ethics Committee (HREC) (iRECS6645) and complies with the National Health and Medical Research Council ethical guidelines. Participating practices and each GP will provide written, informed consent. All patients being screened will provide electronic informed consent. Results of the study will be disseminated through various forums, including peer-reviewed publications and presentation at national and international conferences. Following the study, participating practices will be provided with a summary of the findings of the study, together with a full copy of any publications and a plain language statement for participants, which will be made available in the practice reception area.

Crohn’s disease (CD) and ulcerative colitis (UC) are chronic, inflammatory bowel diseases (IBDs) of unknown origin, affecting the gastrointestinal tract and often causing extraintestinal symptoms. Conventional treatments (eg, glucocorticosteroids, immunomodulators) and targeted advanced treatments, including anti-TNFα, antibodies to p40 subunit of IL-12/23, antibodies to p19 subunit of IL-23, anti-α4β7 integrin, Janus kinase inhibitors (JAKis) and sphingosine-1-phosphate receptor (S1PR) modulators, do not achieve sustained responses for all patients, leaving significant unmet therapeutic needs.

This prospective, multi-centre observational study will follow a cohort of 240 patients across multiple study centres within NHS trusts in the UK who are initiating or switching biologics, specifically anti-TNFα and anti-α4β7 integrin for UC, and anti-TNFα, antibodies to p40 subunit of IL-12/2 and JAKi for CD. Through comprehensive profiling of immunological, transcriptional, microbiome, genetic and proteomic markers at baseline, week 12, and week 52, this study aims to uncover non-invasive biomarkers that predict response to these drug classes, ultimately advancing personalised medicine in IBD.

Ethical approval for the Nottingham/AstraZeneca study was granted by the West of Scotland Research Ethics Committee. Recruitment began in December 2022 and is currently ongoing at 10 NHS Trust sites across the UK. Study findings will be disseminated by publication in peer-reviewed journals and presentations at relevant national and international conferences.

Post-traumatic stress disorder (PTSD) constitutes a significant anxiety disorder that exerts substantial societal and familial impacts, while concurrently imposing an additional as well as a substantial burden on the healthcare system. Beyond the direct expenses incurred in its treatment, PTSD also gives rise to broader economic costs. The details of these costs in the UK are currently, we believe, unknown.

Our methodology was developed collaboratively with a collaborative advisory group of clinicians, patients, carers and other stakeholders. A comprehensive search strategy was devised to identify articles, including systematic reviews evaluating the economic costs linked to PTSD. We adhered to the National Institute for Health and Care Excellence checklist for economic evaluations. After applying our search strategy, the selected included papers were analysed to identify various cost categories contributing to the economic burden of PTSD.

PubMed, PsycInfo, PTSDpubs, EMBASE and Google Scholar were searched from January 1990 until January 2023; the search was revised and re-run in September 2024.

The articles must have been published originally in English and include a detailed evaluation of costs related to PTSD.

Two independent reviewers used standardised methods to search, screen and code included papers. After applying our search strategy, selected included papers were analysed to identify various cost categories contributing to the economic burden of PTSD. Detailed information on per-contact and per-session costs of healthcare variables was obtained at 2020/2021 prices. Additionally, with the advisory group, we ensured the validity of frequencies and unit cost figures associated with variables linked to PTSD. Further, indirect socio-economic costs arising from PTSD were computed.

By extrapolating from cost components identified, our findings indicate an average annual cost exceeding £14 780 per person. Given current 2020/2021 prevalence rates, this translates to an annual societal burden of £40 billion, a figure that does not encompass the many additional financial burdens stemming from PTSD, such as poor or inconsistent employment. This figure does not include the myriad intangible costs ranging from reduced quality of life to suicidality and countless other issues a person may suffer from as a result of PTSD. Finally, this number does not capture the breadth of impact, as it is difficult to quantify how the families, communities and social systems are adversely affected (both financially and otherwise) by the condition.

The economic and societal burden of PTSD in the UK is far greater than what extant research and common understanding indicate, as there is minimal awareness and information relating to indirect costs or ancillary effects such as discrimination, joblessness, substance use and other comorbidities. Ultimately, we found that there exists, conservatively, an annual excess societal burden of £40 billion, or approximately £14 780 per person. We demonstrated that PTSD is a significantly larger burden on society and individuals than estimated and that we are gravely underquantifying the cost of this increasingly prevalent condition.