Current guideline-recommended antibiotic treatment durations for ventilator-associated pneumonia (VAP) are largely standardised, with limited consideration of individual patient characteristics, pathogens or clinical context. This one-size-fits-all approach risks both overtreatment—promoting antimicrobial resistance and adverse drug events—as well as undertreatment, increasing the likelihood of pneumonia recurrence and sepsis-related complications. There is a critical need for VAP-specific biomarkers to enable individualised treatment strategies. The Ventilator-associated pneumonia Biomarker Evaluation (VIBE) study aims to identify a dynamic alveolar biomarker signature associated with treatment response, with the goal of informing personalised antibiotic duration in future clinical trials.

VIBE is a prospective, observational, case-cohort study of 125 adult patients with VAP in Michigan Medicine University Hospital intensive care units. Study subjects will undergo non-bronchoscopic bronchoalveolar lavage on the day of VAP diagnosis (Day 1) and then on Days 3 and 5. Alveolar biomarkers (quantitative respiratory culture bioburden, alveolar neutrophil percentage and pathogen genomic load assessed via BioFire FilmArray polymerase chain reaction) will be assessed. An expert panel of intensivists, blinded to biomarker data, will adjudicate each patient’s Day 10 outcome as VAP clinical cure (control) or treatment failure (case). Absolute biomarker levels and mean-fold changes in biomarker levels will be compared between groups. Data will be used to derive a composite temporal alveolar biomarker signature predictive of VAP treatment failure.

Ethical approval was obtained from the University of Michigan Institutional Review Board (IRB #HUM00251780). Informed consent will be obtained from all study participants or their legally authorised representatives. Findings will be disseminated through peer-reviewed publications, conferences and feedback into clinical guidelines committees.

To assess the feasibility of conducting a definitive randomised controlled trial (RCT) to test the clinical and cost-effectiveness of a tailored exercise intervention compared with usual care for people aged 80 years and older with hip and/or knee osteoarthritis (OA) and comorbidities.

Two-arm, parallel-design, multicentre, pragmatic, feasibility RCT.

Four National Health Service outpatient physiotherapy services across England.

Adults aged 80 years and over with clinical hip and/or knee OA and ≥1 comorbidity.

Participants were randomised 1:1 via a central web-based system to be offered: (1) a 12-week tailored exercise programme or (2) usual care. Participants and outcome assessors were not blinded to treatment allocation.

(1) Ability to screen and recruit participants; (2) retention of participants at 14-week follow-up; (3) intervention fidelity (proportion of participants who received ≥4 intervention sessions as per protocol) and (4) participant engagement (assessed by home exercise adherence).

Between 12 May 2022 and 26 January 2023, 133 potential participants were screened, of whom 94 were eligible. The main reasons for ineligibility were symptoms not consistent with hip or knee OA (10/39, 25.6%) or already having had a physiotherapy appointment (8/39, 20.5%). 51 of 94 (54%) eligible participants were recruited. Participants had a mean age of 84 years (SD 3.5), 31 (60.8%) were female and 96.1% reported their ethnicity as White British (n=49/51). 45 of 51 participants (88%) provided outcome data at the 14-week follow-up time point. Four or more intervention sessions were attended by 13/25 (52%) participants. Home exercise log completion declined over time: 6/23 participants (26.1%) returned completed exercise logs for all 12 weeks. The median number of days home exercises were recorded each week was 5 (range 0–7).

This study demonstrated that a definitive trial would be feasible. Before proceeding, modifications to ensure recruitment of a diverse population and intervention fidelity should be addressed.

ISRCTN75983430.

Palmoplantar pustulosis (PPP) is a rare, debilitating inflammatory skin disease involving painful pustules on the palms and soles. Janus kinase (JAK) inhibitors target pathways relevant to PPP disease biology but also confer a risk of major adverse cardiovascular events and malignancy in certain ‘at risk’ individuals; this includes those with PPP given prevalent smoking and cardiovascular risk factors in the PPP population. The feasibility of JAK inhibitor therapy for PPP requires assessment prior to a randomised controlled trial evaluation of drug efficacy and safety for this indication.

The ‘Janus kinase inhibitors in palmoplantar pustulosis: a mixed-methods feasibility’ trial is an open-label, single-centre, single-arm, mixed-methods feasibility trial of JAK inhibition in PPP (REC reference: 24/NE/0147; ISRCTN61751241). Participants (n=20) will receive 8 weeks of treatment with the JAK inhibitor upadacitinib (‘Rinvoq’, 30 mg, once daily). Qualitative semistructured interviews (up to n=40) will be undertaken with trial participants, trial decliners and healthcare professionals. The primary outcome will be a composite assessment of feasibility across three domains: recruitment, adherence and acceptability, using a mixed-methods analysis approach. Secondary objectives include the identification of trial recruitment optimisation strategies, using the ‘Quintet Recruitment Intervention’, and the generation of an indication of effect size on disease severity (measured using the Palmoplantar Pustulosis Psoriasis Area and Severity Index) to inform future sample size calculations. Historic placebo control data from the Anakinra for Pustular Psoriasis: Response in a Controlled Trial (National Institute of Health and Social Care reference: 13/50/17; Research Ethics Commitee reference: 16/LO/0436) will be used as the effect size comparator. Study recruitment will be undertaken over a 24-month period, commencing in November 2024.

This study has been approved by the Newcastle North Tyneside 2 Research Ethics Committee, 24/NE/0132. Our findings will inform the feasibility of a future adequately powered RCT evaluating the efficacy of JAK inhibitor therapy in PPP.

ISRCTN61751241.

Musculoskeletal injury (MSKI) is the leading cause of medical downgrading and discharge within the UK military, with lower limb MSKI having the greatest incidence, negatively impacting operational readiness. Pain is a primary limiting factor to rehabilitation progress following MSKI. Heavy-load resistance training (RT; ie, loads >70% 1-repetition maximum) is traditionally used but may be contraindicated due to pain, potentially prolonging recovery and leading to failure of essential physical employment standards for UK military personnel. Low-load RT with blood flow restriction (BFR) can promote favourable morphological and physiological adaption, as well as elicit hypoalgesia in healthy and clinical populations (eg, post-operative), and has proven a viable option in military rehabilitation settings. The acceptability and tolerance of higher relative BFR pressures in persistent pain populations are unknown due to the complexity of presentation and the perception of discomfort experienced during BFR exercise. Greater relative pressures (ie, 80% limb occlusion pressure (LOP)) elicit a greater hypoalgesic response in pain-free individuals, but greater perceived discomfort which may not be tolerated in persistent pain populations. However, lower relative pressure (ie, 40% LOP) has elicited hypoalgesia in pain-free individuals, which therefore may be more clinically acceptable and tolerated in persistent pain populations. The primary aim of both randomised controlled trials (RCT) is to investigate the efficacy and acceptability of using high-frequency, low-load BFR-RT in UK military personnel with lower limb MSKI where persistent pain is the primary limiting factor for progression.

The presented protocol is a two-phase RCT based within a military rehabilitation setting. Phase One is a 1-week RCT to determine the most efficacious and acceptable BFR-RT protocol (7x BFR-RT sessions over 5 days at 40% or 80% LOP; n=28). Phase Two is a 3-week RCT comparing the most clinically acceptable BFR pressure, determined by Phase One (21x BFR-RT sessions over 15 days; n=26) to usual care within UK Defence Rehabilitation residential rehabilitation practices. Outcomes will be recorded at baseline, daily and following completion of the intervention. The primary outcome will be the brief pain inventory. Secondary outcomes include blood biomarkers for inflammation and pain (Phase Two only), injury-specific outcome measures, lower extremity function scale, objective measures of muscle strength and neuromuscular performance, and pressure pain threshold testing.

The study is approved by the Ministry of Defence Research Ethics Committee (2318/MODREC/24) and Northumbria University. All study findings will be published in scientific peer-reviewed journals and presented at relevant scientific conferences.

Registered with Clinical Trials. The registration numbers are as follows: NCT06621914 (Phase One) and NCT06621953 (Phase Two).