Purpose To determine if reuse of intermittent catheters is safe for the community management of long-term bladder emptying problems, this trial compared using a combination of reusable and single-use catheters (Mixed-use), to standard practice of single-use catheters only and examined the incidence of urinary tract infections (UTI). Design Open label, randomised, non-inferiority trial. Setting and participants Community-dwelling intermittent catheter users aged over 18 were invited to join the Trial by 234 general practices and five community nursing teams across the United Kingdom. The Trial was managed from two university-based trial centres (Southampton and Glasgow) from April 2021 to July 2024. Interventions Random assignment (1:1) using permuted block sequences via a web-based system to receive either Mixed-use (trial reusable catheters plus participants' own single-use catheters) or Single-use (participants' own single-use catheters) for 12 months. Treatment allocation was masked from microbiology assessors but not participants or researchers. Main outcome measures The primary outcome was at least one episode of microbiologically confirmed symptomatic UTI (any sign or symptom) with help-seeking or self-help over 12 months. The critical odds ratio for non-inferiority was 2·0. The primary analysis was on a per protocol basis. Secondary outcomes included antibiotic-use, quality of life and participant reported problems with catheterisation. Results 578 participants were randomly assigned to Mixed-use (n = 289) or Single-use (n = 289). The per protocol analysis comprised 171 participants in Mixed-use and 244 participants in Single-use. The primary outcome of at least one UTI episode over 12 months was met by 49 (28·7%) of 171 participants in Mixed-use and 84 (34·4%) of 244 participants in Single-use. Mixed-use was non-inferior to Single-use (unadjusted odds ratio (95% CI): 0·77 (0·50, 1·17)). Antibiotic use was 35% less in Mixed-use compared to Single-use (adjusted incidence rate ratio (95% CI): 0·65 (0·45, 0·95)). Catheter ‘sticking’ was significantly worse in Mixed-use compared to Single-use. Participants reused a median of 2·8 (interquartile range: 1·8, 3·9) times per day. Quality of life and adverse events were similar across both groups. Conclusions For the community management of long-term bladder emptying problems, the combined use of reusable and single-use catheters is as safe as using only single-use catheters for UTI and is associated with lower antibiotic use. Reusable catheters can be offered as a safe choice for intermittent catheter users. Trial registration ISRCTN 42028483, 05.09.2019. Trial commenced 19.02.2021.

Introduction Hypertensive disorders of pregnancy (HDP), including gestational hypertension and pre-eclampsia, affect approximately 10% of pregnancies worldwide and contribute significantly to fetal and maternal morbidity and mortality. Early identification of HDP would facilitate targeted surveillance and personalised care in order to mitigate the severity of complications and improve pregnancy outcomes. Uric acid is a marker of oxidative stress, inflammation and endothelial dysfunction, and has been proposed as a predictor of hypertensive disease. Salurate is a salivary uric acid test that has the potential to identify pregnant women at risk of developing HDP several weeks before clinical manifestation.Methods and analysis This is a prospective, multicentre, observational, cohort study with health economics evaluation. Women aged 16 and above, with a viable singleton pregnancy at <16 weeks gestation and a combined first trimester pre-eclampsia risk of >1:300 will be eligible for recruitment. Participants will perform weekly remote salivary uric acid testing from enrolment until the conclusion of pregnancy and upload results of colourimetric paper tests via a smartphone application. We will validate a predictive algorithm that analyses colour data from several consecutive samples to detect patterns that predict whether HDP is likely to occur. The primary outcome is test performance for the prediction of HDP. Secondary outcomes include adherence to sampling and test performance for predicting gestational diabetes, stillbirth and fetal growth restriction. Data on pregnancy outcomes will be collected from the medical notes, compared with the predictions made by the algorithm and subjected to statistical analysis.Ethics and dissemination Approval has been obtained from Cambridge East Research Ethics Committee (REC reference 24/EE/0123), Medicines and Healthcare products Regulatory Agency (CI/2024/0038/GB) and Health Research Authority (IRAS ID 337290). Results of the study will be published in peer-reviewed journals and presented at national and international conferences.Trial registration number ISRCTN17992452.Protocol version 4, 4 July 2024.

Introduction:Early rehabilitation of critically ill patients is challenging due to limited staff resources. This study assessed the feasibility of delivering a randomised controlled trial of physiotherapy assistants delivering early protocolised rehabilitation plus usual care compared with usual care. Methods:We conducted a randomised feasibility study in three U.K. mixed medical/surgical intensive care units. Eligible patients were intubated and ventilated <72 h, expected to be ventilated for a further 48 h, and functionally independent before ICU admission. Patients were randomised to protocolised early rehabilitation plus usual care or usual care. Feasibility outcomes were (i) recruitment of one to two patients/per month/site; (ii) >75% of patients commencing the intervention within 72 h of ventilation with >70% interventions delivered; and (iii) blinded outcome measures recorded at three-time points in >80% of patients. Results:The study delivery was compromised by the COVID-19 pandemic: 46 patients were enrolled, of which 22 were allocated to intervention. Feasibility outcomes: (i) recruitment of 0.9 patients/month/site, (ii) 90% of patients commenced interventions within 72 h of ventilation, with 166/264 (63%) of study interventions delivered: median total 22.5 min (IQR 15-35) of therapy per day in the usual care group and 45 min (IQR 25-70) in the intervention group, and (iii) the outcome assessments were performed at three-time points for 64% of survivors, 63% of which were blinded. Conclusion:While delivery of protocolised rehabilitation by physiotherapy assistants is feasible, the design of a future RCT needs to consider strategies to improve recruitment and complete blinded outcome assessments.

Introduction Evaluating the safety and acceptability of reusing catheters for intermittent catheterisation (IC) is one of the top 10 continence research priorities identified by the UK James Lind Alliance Priority Setting Partnership in 2008. There are an estimated 50 000 IC users in England and this number is rising. Globally, both single-use catheters (thrown away after use) and multi-use/reusable ones (cleaned between uses) are used. Using multi-use catheters as well as single-use ones (mixed-use) could bring benefits (eg, reducing plastic waste and patients never running out of catheters) and offer more choice to users. Evidence is needed that mixed-use is at least as safe and acceptable as using only single-use catheters.Methods The MultICath Trial is a non-inferiority randomised controlled trial involving 578 participants. The aim is to compare mixed-use catheter management with single-use catheter management over 12 months. Participants are randomised on a 1:1 basis to either mixed-use catheter management, which includes an evidence-based cleaning method for the multi-use catheters (intervention) or single-use catheter management (control). Following randomisation, participants are followed up for 12 months. The primary outcome is at least one episode of microbiologically confirmed symptomatic urinary tract infection with help-seeking or self-help behaviour over the 12-month follow-up period. Laboratory analysis of patient-initiated urine samples is blind. Secondary outcomes include antibiotic use, microhaematuria, visible blood on catheter/in urine, quality of life and health economics. A qualitative sub-study to examine participant experiences using mixed-use is included.Ethics and dissemination Ethical review was undertaken by South Central-Hampshire A Research Ethics Committee and favourable opinion was granted on 12 July 2019 (reference: 19/SC/0334). Written, informed consent to participate was obtained from all participants. Results will be disseminated in peer-reviewed publications, in the National Institute for Health and Care Research journal library and to participants and the public via a lay summary published on the trial website.Trial registration number ISRCTN42028483.

While non-operative treatment has emerged as an alternative to surgery for the treatment of uncomplicated acute appendicitis in children, comparative patient-centred outcomes are not well documented. We investigated these in a feasibility randomised trial. Of 57 randomised participants, data were available for 26. Compared with appendicectomy, children allocated to non-operative treatment reported higher short-term quality of life scores, shorter duration of requiring analgesia, more rapid return to normal activities and shorter parental absence from work. These preliminary data suggest differences exist in recovery profile and quality of life between these treatments that are important to measure in a larger RCT. Trial registration number is ISRCTN15830435 .

Introduction There remains a need for a non-invasive, low-cost and easily accessible way of identifying women at risk of developing hypertensive disorders in pregnancy. This study evaluated the predictive value of longitudinal salivary uric acid measurement. Material and methods Pregnant women (n = 137) from 20 weeks of gestation were recruited at St Richards Hospital, Chichester, UK, for this prospective cohort study. Weekly samples of salivary uric acid were analyzed until delivery. Information regarding pregnancy and labor were obtained from the patient's record after delivery. Independent t tests were used to compare mean levels of salivary uric acid in women with hypertensive complications and adverse fetal outcomes with women with normal pregnancies. Main outcome measures were preeclampsia, pregnancy-induced hypertension, spontaneous preterm delivery and small-for-gestational-age babies. Results From 21 weeks of gestation until delivery, levels of salivary uric acid increased significantly in women who subsequently developed preeclampsia and pregnancy-induced hypertension compared with women with normal pregnancies (preeclampsia-mean at gestational age 21-24, 95% confidence interval [95% CI] [mean (GA21-24)): 108 [63-185] vs 47 (39-55) mu mol/L; P = .005; pregnancy-induced hypertension-mean (GA21-24): 118 [54-258] vs 47 [39-55] mu mol/L; P = .004). In women who had spontaneous preterm delivery, salivary uric acid levels increased significantly from 29 to 32 weeks of gestation compared with women with normal pregnancies (mean (GA29-32): 112 (57-221) vs 59 (50-71) mu mol/L; P = .04). In women who had babies small-for-gestational-age <10th percentile and small-for-gestational-age <3rd percentile, differences in salivary uric acid levels were insignificant. Conclusions Elevated levels of salivary uric acid precede the onset of preeclampsia, pregnancy-induced hypertension and preterm delivery. Salivary uric acid may prove to be an early biomarker of hypertensive complications of pregnancy and spontaneous preterm delivery.

We conducted a health economic sub-study within a feasibility RCT comparing a non-operative treatment pathway as an alternative to appendicectomy for the treatment of uncomplicated acute appendicitis in children. The objectives were to understand and assess data collection tools and methods and to determine indicative costs and benefits assessing the feasibility of conducting a full economic evaluation within the definitive trial. We compared different methods of estimating treatment costs including micro-costing, hospital administrative data (PLICS) and health system (NHS) reference costs. We compared two different HRQoL instruments (CHU-9D and EQ-5D-5L) in terms of data completeness and sensitivity to change over time, including potential ceiling effects. We also explored how the timing of data collection and duration of the analysis could affect QALYs (Quality Adjusted Life Years) and the results of the cost-utility analysis (CUA) within the future RCT. Using a micro-costing approach, the total per treatment costs were in alignment with hospital administrative data (PLICS). Average health system reference cost data (macro-costing using NHS costs) could potentially underestimate these treatment costs, particularly for non-operative treatment. Costs incurred following hospital discharge in the primary care setting were minimal, and limited family borne costs were reported by parents/carers. While both HRQoL instruments performed relatively well, our results highlight the problem of ceiling effect and the importance of the timing of data collection and the duration of the analysis in any future assessment using QALYs and CUA. We highlighted the importance of obtaining accurate individual-patient cost data when conducting economic evaluations. Our results suggest that timing of data collection and duration of the assessment are important considerations when evaluating cost-effectiveness and reporting cost per QALY. Current Controlled Trials ISRCTN15830435.

BACKGROUND:The success of early dexamethasone therapy for hospitalised COVID-19 cases in treatment of Sars-CoV-2 infection may predominantly reflect its anti-inflammatory action against a hyperinflammation (HI) response. It is likely that there is substantial heterogeneity in HI responses in COVID-19. METHODS:Blood CRP, ferritin, neutrophil, lymphocyte and platelet counts were scored to assess HI (HI5) and combined with a validated measure of generalised medical deterioration (NEWS2) before day 2. Our primary outcome was 28 day mortality from early treatment with dexamethasone stratified by HI5-NEWS2 status. FINDINGS:Of 1265 patients, high risk of HI (high HI5-NEWS2) (n = 367, 29.0%) conferred a strikingly increased mortality (36.0% vs 7.8%; Age adjusted hazard ratio (aHR) 5.9; 95% CI 3.6-9.8, p<0.001) compared to the low risk group (n = 455, 36.0%). An intermediate risk group (n = 443, 35.0%) also showed significantly higher mortality than the low risk group (17.6% vs 7.8%), aHR 2.2, p = 0.005). Early dexamethasone treatment conferred a 50.0% reduction in mortality in the high risk group (36.0% to 18.0%, aHR 0.56, p = 0.007). The intermediate risk group showed a trend to reduction in mortality (17.8% to 10.3%, aHR 0.82, p = 0.46) which was not observed in the low risk group (7.8% to 9.2%, aHR 1.4, p = 0.31). INTERPRETATION:Higher HI5-NEWS2 scores measured at COVID-19 diagnosis, strongly associate with increased mortality at 28 days. Significant reduction in mortality with early dexamethasone treatment was only observed in the high risk group. Therefore, the HI5-NEWS2 score could be utilised to stratify randomised clinical trials to test whether intensified anti-inflammatory therapy would further benefit high risk patients and whether alternative approaches would benefit low risk groups. Considering its recognised morbidity, we suggest that early dexamethasone should not be routinely prescribed for HI5-NEWS2 low risk individuals with COVID-19 and clinicians should cautiously assess the risk benefit of this intervention in all cases.

Little is known about the distribution and determinants of pain at multiple sites in the neck and upper limb. To investigate the prevalence, pattern, and clustering of such pains and the association of extensive involvement with putative risk factors, we mailed a questionnaire to a community sample of 9696 working-aged adults. Age–sex specific prevalence rates for pain were estimated and the frequency of bilateral involvement, pairwise overlap at different sites, and extent to which reports clustered within individuals were explored. Associations of multi-site involvement with age, gender, psychological health, smoking, and employment status were assessed by logistic regression. Among 6038 responders, 2657 reported at least a day of neck or upper limb pain in the past 7 days, including 1843 whose symptoms rendered normal activities difficult or impossible. Pain was frequently bilateral or in the dominant arm. Significant associations were seen for pain at anatomically adjacent sites. Pain affecting every site considered (neck, shoulders, elbows, wrists/hands) was far more common than might be expected if each site were statistically independent (observed/expected ratio 8750). Being female, unemployed, a blue-collar worker, or a smoker were independent risk factors for such extensive pain, but the strongest association was with psychological ill-health (odds ratio for worst vs. best third of the SF-36 low vitality score, 30.3, 95% CI 7.1–129.0). Neck and upper limb pain commonly cluster, and frequently display symmetry and adjacent patterns of involvement. Extensive neck and upper limb pain is far more strongly associated with poor mental vitality than localised pain.

Introduction Physical rehabilitation delivered early following admission to the intensive care unit (ICU) has the potential to improve short-term and long-term outcomes. The use of supine cycling together with other rehabilitation techniques has potential as a method of introducing rehabilitation earlier in the patient journey. The aim of the study is to determine the feasibility of delivering the designed protocol of a randomised clinical trial comparing a protocolised early rehabilitation programme including cycling with usual care. This feasibility study will inform a larger multicentre study. Methods and analysis 90 acute care medical patients from two mixed medical-surgical ICUs will be recruited. We will include ventilated patients within 72 hours of initiation of mechanical ventilation and expected to be ventilated a further 48 hours or more. Patients will receive usual care or usual care plus two 30 min rehabilitation sessions 5days/week. Feasibility outcomes are (1) recruitment of one to two patients per month per site; (2) protocol fidelity with >75% of patients commencing interventions within 72 hours of mechanical ventilation, with >70% interventions delivered; and (3) blinded outcome measures recorded at three time points in >80% of patients. Secondary outcomes are (1) strength and function, the Physical Function ICU Test-scored measured on ICU discharge; (2) hospital length of stay; and (3) mental health and physical ability at 3 months using the WHO Disability Assessment Schedule 2. An economic analysis using hospital health services data reported with an embedded health economic study will collect and assess economic and quality of life data including the Hospital Anxiety and Depression Scales core, the Eurogol-5 Dimension-5 Level and the Impact of Event Score. Ethics and dissemination The study has ethical approval from the South Central Hampshire A Research Ethics Committee (19/SC/0016). All amendments will be approved by this committee. An independent trial monitoring committee is overseeing the study. Results will be made available to critical care survivors, their caregivers, the critical care societies and other researchers.

Background: Although non-operative treatment is known to be effective for the treatment of uncomplicated acute appendicitis in children, randomised trial data comparing important outcomes of non-operative treatment with those of appendicectomy are lacking. Objectives: The objectives were to ascertain the feasibility of conducting a multicentre randomised controlled trial comparing the clinical effectiveness and cost-effectiveness of a non-operative treatment pathway with appendicectomy for the treatment of uncomplicated acute appendicitis in children. Design: This was a mixed-methods study, which included a feasibility randomised controlled trial, embedded and parallel qualitative and survey studies, a parallel health economic feasibility study and the development of a core outcome set. Setting: This study was set in three specialist NHS paediatric surgical units in England. Participants: Children (aged 4–15 years) clinically diagnosed with uncomplicated acute appendicitis participated in the feasibility randomised controlled trial. Children, their families, recruiting clinicians and other health-care professionals involved in caring for children with appendicitis took part in the qualitative study. UK specialist paediatric surgeons took part in the survey. Specialist paediatric surgeons, adult general surgeons who treat children, and children and young people who previously had appendicitis, along with their families, took part in the development of the core outcome set. Interventions: Participants in the feasibility randomised controlled trial were randomised to a non-operative treatment pathway (broad-spectrum antibiotics and active observation) or appendicectomy. Main outcome measures: The primary outcome measure was the proportion of eligible patients recruited to the feasibility trial. Data sources: Data were sourced from NHS case notes, questionnaire responses, transcribed audio-recordings of recruitment discussions and qualitative interviews. Results: Overall, 50% (95% confidence interval 40% to 59%) of 115 eligible patients approached about the trial agreed to participate and were randomised. There was high acceptance of randomisation and good adherence to trial procedures and follow-up (follow-up rates of 89%, 85% and 85% at 6 weeks, 3 months and 6 months, respectively). More participants had perforated appendicitis than had been anticipated. Qualitative work enabled us to communicate about the trial effectively with patients and families, to design and deliver bespoke training to optimise recruitment and to understand how to optimise the design and delivery of a future trial. The health economic study indicated that the main cost drivers are the ward stay cost and the cost of the operation; it has also informed quality-of-life assessment methods for future work. A core outcome set for the treatment of uncomplicated acute appendicitis in children and young people was developed, containing 14 outcomes. There is adequate surgeon interest to justify proceeding to an effectiveness trial, with 51% of those surveyed expressing a willingness to recruit with an unchanged trial protocol. Limitations: Because the feasibility randomised controlled trial was performed in only three centres, successful recruitment across a larger number of sites cannot be guaranteed. However, the qualitative work has informed a bespoke training package to facilitate this. Although survey results suggest adequate clinician interest to make a larger trial possible, actual participation may differ, and equipoise may have changed over time. Conclusions: A future effectiveness trial is feasible, following limited additional preparation, to establish appropriate outcome measures and case identification. It is recommended to include a limited package of qualitative work to optimise recruitment, in particular at new centres. Future work: Prior to proceeding to an effectiveness trial, there is a need to develop a robust method for distinguishing children with uncomplicated acute appendicitis from those with more advanced appendicitis, and to reach agreement on a primary outcome measure and effect size that is acceptable to all stakeholder groups involved. Trial registration: Current Controlled Trials ISRCTN15830435. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 10. See the NIHR Journals Library website for further project information.

Background The success of early dexamethasone therapy for hospitalised COVID-19 cases in treatment of Sars-CoV-2 infection may predominantly reflect its anti-inflammatory action against a hyperinflammation (HI) response. It is likely that there is substantial heterogeneity in HI responses in COVID-19. Methods Blood CRP, ferritin, neutrophil, lymphocyte and platelet counts were scored to assess HI (HI5) and combined with a validated measure of generalised medical deterioration (NEWS2) before day 2. Our primary outcome was 28 day mortality from early treatment with dexamethasone stratified by HI5-NEWS2 status. Findings Of 1265 patients, high risk of HI (high HI5-NEWS2) (n=367, 29.0%) conferred a strikingly increased mortality (36.0% vs 7.8%; Age adjusted hazard ratio (aHR) 5.9; 95% CI 3.6-9.8, p<0.001) compared to the low risk group (n= 455, 36.0%). An intermediate risk group (n= 443, 35.0%) also showed significantly higher mortality than the low risk group (17.6% vs 7.8%), aHR 2.2, p=0.005). Early dexamethasone treatment conferred a 50.0% reduction in mortality in the high risk group (36.0% to 18.0%, aHR 0.56, p=0.007). The intermediate risk group showed a trend to reduction in mortality (17.8% to 10.3%, aHR 0.82, p=0.46) which was not observed in the low risk group (7.8% to 9.2%, aHR 1.4, p =0.31). Interpretation The HI5-NEWS2 measured at COVID-19 diagnosis, strongly predicts mortality at 28 days. Significant reduction in mortality with early dexamethasone treatment was only observed in the high risk group. Therefore, the HI5-NEWS2 score could be utilised to stratify randomised clinical trials to test whether intensified anti-inflammatory therapy would further benefit high risk patients and whether alternative approaches would benefit low risk groups. Considering its recognised morbidity, we suggest that early dexamethasone should not be routinely prescribed for HI5-NEWS2 low risk individuals with COVID-19 and clinicians should cautiously assess the risk benefit of this intervention. Funding No external funding.

ObjectiveTo establish the feasibility of a multicentre randomised controlled trial to assess the effectiveness and cost-effectiveness of a non-operative treatment pathway compared with appendicectomy in children with uncomplicated acute appendicitis.DesignFeasibility randomised controlled trial with embedded qualitative study to inform recruiter training to optimise recruitment and the design of a future definitive trial.SettingThree specialist paediatric surgery centres in the UK.PatientsChildren (aged 4–15 years) with a clinical diagnosis of uncomplicated acute appendicitis.InterventionsAppendicectomy or a non-operative treatment pathway (comprising broad-spectrum antibiotics and active observation).Main outcome measuresPrimary outcome measure was the proportion of eligible patients recruited. Secondary outcomes evaluated adherence to interventions, data collection during follow-up, safety of treatment pathways and clinical course.ResultsFifty per cent of eligible participants (95% CI 40 to 59) approached about the trial agreed to participate and were randomised. Repeated bespoke recruiter training was associated with an increase in recruitment rate over the course of the trial from 38% to 72%. There was high acceptance of randomisation, good patient and surgeon adherence to trial procedures and satisfactory completion of follow-up. Although more participants had perforated appendicitis than had been anticipated, treatment pathways were found to be safe and adverse event profiles acceptable.ConclusionRecruitment to a randomised controlled trial examining the effectiveness and cost-effectiveness of a non-operative treatment pathway compared with appendicectomy for the treatment of uncomplicated acute appendicitis in children is feasible.Trial registration numberNCT15830435.