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BACKGROUND: Major depressive disorder (MDD) is a highly prevalent condition with a substantial incidence of relapse or treatment resistance. A subset of patients show evidence of low-grade inflammation, with these patients having a higher likelihood of more severe or difficult to treat courses of illness. Anti-inflammatory treatment of MDD has been investigated with mixed results, and no known studies have included assessments beyond cessation of the anti-inflammatory agent, meaning it remains unknown if any benefit from treatment persists. The objective of the present study was to investigate treatment outcomes up to 29 weeks post-cessation of celecoxib or placebo augmentation of an antidepressant, and how concentrations of selected inflammatory markers change over the same period. METHODS: The PREDDICT parallel-group, randomised, double-blind, placebo-controlled trial (University of Adelaide, Australia) ran from December 2017 to April 2020. Participants with MDD were stratified into normal range or elevated inflammation strata according to screening concentrations of high sensitivity C-reactive protein (hsCRP). Participants were randomised to treatment with vortioxetine and celecoxib or vortioxetine and placebo for six weeks, and vortioxetine alone for an additional 29 weeks (35 total weeks). Following a previous publication of results from the six-week RCT phase, exploratory analyses were performed on Montgomery-Åsberg Depression Rating Scale (MADRS) scores, response and remission outcomes, and selected peripheral inflammatory markers across the entire study duration up to week 35. RESULTS: Participants retained at each observation were baseline N=119, week 2 N=115, week 4 N=103, week 6 N=104, week 8 N=98, week 22 N=81, and week 35 N=60. Those in the elevated hsCRP celecoxib-augmented group had a statistically significantly greater reduction in MADRS score from baseline to week 35 compared to all other groups, demonstrating the greatest clinical improvement long-term, despite no group or strata differences at preceding time points. Response and remission outcomes did not differ by treatment group or hsCRP strata at any time point. Changes in hsCRP between baseline and week 35 and Tumour Necrosis Factor-α (TNF-α) concentrations between baseline and week 6 and baseline and week 35 were statistically significantly associated with MADRS scores observed at week 6 and week 35 respectively, with reducing TNF-α concentrations associated with reducing MADRS scores and vice versa in each case. A post-hoc stratification of the participant cohort by baseline TNF-α concentrations led to significant prediction by the derived strata on clinical response at weeks 6, 8 and 35, with participants with elevated baseline TNF-α less likely to achieve clinical response. INTERPRETATION: The present analysis suggests for the first time a possible longer-term clinical benefit of celecoxib augmentation of vortioxetine in inflammation-associated MDD treatment. However, further research is needed to confirm the finding and to ascertain the reason for such a delayed effect. Furthermore, the trial suggests that TNF-α may have a stronger relationship with anti-inflammatory MDD treatment outcomes than hsCRP, and should be investigated further for potential predictive utility. CLINICAL TRIALS REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12617000527369p. Registered on 11 April 2017, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12617000527369p.

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AIM: To assess the impact of digital picture books on preoperative anxiety, pain and sleep quality in young children undergoing cardiac catheterisation and the anxiety of their family caregivers. DESIGN: A randomised, single-blinded, two-arm, parallel-group controlled trial. METHODS: Participants are young children aged 2-7 years with congenital heart disease scheduled for cardiac catheterisation and their family caregivers. They were enrolled at Fujian Medical University Union Hospital between September 2022 and July 2023. They were randomised to either a control group receiving usual care or an intervention group receiving digital picture book sessions. Anxiety and pain levels were assessed using standardised scales, and sleep quality was measured using actigraphy. RESULTS: The study included 64 pairs of young children and family caregivers. Digital picture books significantly reduced preoperative anxiety and bandage removal pain in children and anxiety in family caregivers. However, there was no statistical difference in sleep quality between the intervention group and the control group. CONCLUSIONS: Digital picture books prove to be an effective intervention for reducing anxiety and pain in paediatric cardiac catheterisation patients and anxiety of their family caregivers. The intervention did not affect sleep quality, suggesting the need for additional strategies to address this aspect of the hospital experience. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: This study demonstrated the effectiveness of digitally illustrated books in reducing preoperative anxiety and pain in young children and anxiety in family caregivers. Digital picture books offer a creative and engaging way to help children and their families cope with the stress and anxiety associated with medical procedures. Further research in this area may lead to the development of more innovative and effective interventions for paediatric patients and their family caregivers. IMPACT: The study's impact lies in its innovative approach to addressing the psychological and emotional challenges faced by young children and their family caregivers during the stressful experience of cardiac catheterisation. By demonstrating the efficacy of digital picture books in significantly reducing preoperative anxiety and postoperative pain, the research presents a non-pharmacological, accessible and engaging intervention that can be seamlessly integrated into existing healthcare practices. The findings have the potential to transform paediatric care by offering a safe, developmentally appropriate and cost-effective method to support the emotional well-being of children and their families, thereby enhancing the overall patient experience and clinical outcomes. Moreover, the study's emphasis on family caregiver involvement underscores the importance of a holistic approach to care that considers the needs of both the patient and their support system. PATIENT OR PUBLIC CONTRIBUTION: Children and their family caregivers were invited to provide valuable input which has been critical to the development of the intervention. The participant information sheet and consent form, as well as the consent/recruitment process, were reviewed by a consumer advisor advocate from the pilot study. REPORTING METHOD: CONSORT. TRIAL REGISTRATION: Chinese clinical trial registry: ChiCTR2200063973. Registered on 22 September 2022, https://www.chictr.org.cn/showproj.html?proj=132833.

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BACKGROUND AND OBJECTIVE: Randomised data on patient-reported outcomes (PROs) for stereotactic body radiotherapy (SBRT) and prostatectomy in localised prostate cancer are lacking. PACE-A compared patient-reported health-related quality of life after SBRT with that after prostatectomy. METHODS: PACE is a phase 3 open-label, randomised controlled trial. PACE-A randomised men with low- to intermediate-risk localised prostate cancer to SBRT or prostatectomy (1:1). Androgen deprivation therapy (ADT) was not permitted. The coprimary outcomes were the Expanded Prostate Index Composite (EPIC-26) number of absorbent urinary pads required daily and bowel domain score at 2 yr. The secondary endpoints were clinician-reported toxicity, sexual functioning, and other PROs. KEY FINDINGS AND LIMITATIONS: In total, 123 men were randomised (60 undergoing prostatectomy and 63 SBRT) from August 2012 to February 2022. The median follow-up time was 60.7 mo. The median age was 65.5 yr and the median prostate-specific antigen (PSA) value 7.9 ng/ml; 92% had National Comprehensive Cancer Network (NCCN) intermediate-risk disease. Fifty participants received prostatectomy and 60 received SBRT. At 2 yr, 16/32 (50%) prostatectomy and three of 46 (6.5%) SBRT participants used one or more urinary pads daily (p < 0.001; 15 and two, respectively, used one pad daily); the estimated difference was 43% (95% confidence interval [CI]: 25%, 62%). At 2 yr, bowel scores were better for prostatectomy (median [interquartile range] 100 [100-100]) than for SBRT (87.5 [79.2-100]; p < 0.001), with an estimated mean difference of 8.9 between these (95% CI: 4.2, 13.7); sexual scores were worse for prostatectomy (18 [13.8-40.3]) than for SBRT (62.5 [32.0-87.5]). The limitations were slow recruitment and incomplete 2-yr PRO response rates. CONCLUSIONS AND CLINICAL IMPLICATIONS: SBRT was associated with less patient-reported urinary incontinence and sexual dysfunction, and slightly more bowel bother than prostatectomy. These randomised data should inform treatment decision-making for patients with localised, intermediate-risk prostate cancer.

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BACKGROUND & AIMS: Malnutrition is prevalent among hospitalised patients, and increases the morbidity, mortality, and medical costs; yet nutritional assessments on admission are not routine. This study assessed the clinical and economic benefits of using an artificial intelligence (AI)-based rapid nutritional diagnostic system for routine nutritional screening of hospitalised patients. METHODS: A nationwide multicentre randomised controlled trial was conducted at 11 centres in 10 provinces. Hospitalised patients were randomised to either receive an assessment using an AI-based rapid nutritional diagnostic system as part of routine care (experimental group), or not (control group). The overall medical resource costs were calculated for each participant and a decision-tree was generated based on an intention-to-treat analysis to analyse the cost-effectiveness of various treatment modalities. Subgroup analyses were performed according to clinical characteristics and a probabilistic sensitivity analysis was performed to evaluate the influence of parameter variations on the incremental cost-effectiveness ratio (ICER). RESULTS: In total, 5763 patients participated in the study, 2830 in the experimental arm and 2933 in the control arm. The experimental arm had a significantly higher cure rate than the control arm (23.24% versus 20.18%; p = 0.005). The experimental arm incurred an incremental cost of 276.52 CNY, leading to an additional 3.06 cures, yielding an ICER of 90.37 CNY. Sensitivity analysis revealed that the decision-tree model was relatively stable. CONCLUSION: The integration of the AI-based rapid nutritional diagnostic system into routine inpatient care substantially enhanced the cure rate among hospitalised patients and was cost-effective. REGISTRATION: NCT04776070 (https://clinicaltrials.gov/study/NCT04776070).

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BACKGROUND: Experimental studies of wound healing often use survival analysis and time to event outcomes or differences in wound area at a specific time point. However, these methods do not use a potentially large number of observations made over the course of a trial and may be inefficient. A model-based approach can leverage all trial data, but there is little guidance on appropriate models and functional forms to describe wound healing. METHODS: We derive a general statistical model and review a wide range of plausible mathematical models to describe wound healing. We identify a range of possible derived estimands and their derivation from the models. Using data from a trial of an intervention to promote ulcer healing in patients affected by leprosy that included three measurement methods repeated across the course of the study, we compare the goodness-of-fit of the models using a range of methods and estimate treatment effects and healing rate functions with the best-fitting models. RESULTS: Overall, we included 5,581 ulcer measurements of 1,578 unique images from 130 patients. We examined the performance of a range of models. The square root, log square root, and log quadratic models were the best fitting models across all outcome measurement methods. The estimated treatment effects magnitude and sign varied by time post-randomisation, model type, and outcome type, but across all models there was little evidence of effectiveness. The estimated effects were significantly more precise than non-parametric alternatives. For example, estimated differences from the three outcome measurements at 42-days post-randomisation were - 0.01 cm2 (-0.77, 0.74), -0.44 cm2 (-1.64, 0.76), and 0.11 cm2 (-0.87, 1.08) using a non-parametric method versus - 0.03 cm2 (-0.14, 0.06), 0.06 cm2 (-0.05, 0.17), and 0.03 cm2 (-0.07, 0.17) using a square-root model. CONCLUSIONS: Model-based analyses can dramatically improve the precision of estimates but care must be taken to carefully compare and select the best fitting models. The (log) square-root model is strongly recommended reflecting advice from a century ago.

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BACKGROUND: Mental health settings are increasingly using co-facilitation of educational group interventions in collaboration with patient partners and service users. However, despite promising results, limited information is available regarding the feasibility and satisfaction levels of these programmes among adults newly diagnosed with attention-deficit hyperactivity/impulsivity disorder (ADHD). Hence, this study aimed to determine the feasibility, acceptability, and preliminary effects of a user co-facilitated psychoeducational group programme for adults diagnosed with ADHD. METHODS: This feasibility proof-of-concept randomised controlled trial recruited outpatients from a Norwegian community mental health centre. Outpatients randomised to the intervention group (IG) received a psychoeducational programme supplementing Treatment As Usual (TAU), while the control group received TAU. Feasibility was determined by the acceptance rate, adherence rate, and dropout rate. Acceptability was measured with the Client Satisfaction Questionnaire and a 3-item scale measuring satisfaction with the received information. To test the preliminary effects, self-efficacy, symptom severity, and quality of life were measured at baseline and pre- and post-intervention. RESULTS: Feasibility was demonstrated; most of the patients were willing to enrol, participants attended 82% of the psychoeducational programme, and only 13% dropped out of the study. The between-group analyses revealed that the IG reported significantly greater mean satisfaction than the CG. Moreover, the intervention group was more satisfied with the information they received during the psychoeducational programme. Concerning the preliminary effects, the linear mixed model showed improvement in quality of life (the subscale relationship); however, other patient-reported outcomes did not show improvements. CONCLUSIONS: This proof-of-concept randomised controlled trial supports the feasibility and acceptability of the user co-facilitated psychoeducational programme for patients newly diagnosed with ADHD in an outpatient setting. While preliminary findings indicate promise in enhancing patient-reported outcomes, a larger study is warranted to assess the intervention's effectiveness rigorously. TRIAL REGISTRATION: NCT03425, 09/11/2017.

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AIMS/HYPOTHESIS: We conducted the largest and longest clinical trial comparing a whole-food, plant-based intervention with standard medical care (SMC) in individuals with type 2 diabetes. METHODS: We randomised (parallel-arm; computerised 1:1 randomisation ratio) 169 adults aged 18-75 years with type 2 diabetes in the Marshall Islands to an intensive whole-food, plant-based intervention with moderate exercise (PB+Ex) or SMC for 24 weeks. The PB+Ex intervention included 12 weeks of meals, exercise sessions and group classes. Primary outcomes were glycaemic control (HbA1c, glucose, insulin and HOMA-IR) and glucose-lowering medication use. Secondary outcomes included lipids, blood pressure, heart rate and C-reactive protein. Only lab analysts were blinded. RESULTS: Compared with SMC (n=90 randomised; n=70 analysed), the PB+Ex (n=79 randomised; n=66 analysed) intervention decreased HbA1c by an additional 14 mmol/mol (1.3%) at week 12 (-22 vs -7 mmol/mol [-2.0% vs -0.7%]; p<0.0001) and 8 mmol/mol (0.7%) at week 24 (-16 vs -8 mmol/mol [-1.4% vs -0.7%]; p=0.01). Concomitantly, 63% of medicated PB+Ex participants reduced their glucose-lowering medications (vs 24%; p=0.006), and 23% of PB+Ex participants with a baseline HbA1c <75 mmol/mol (<9%) achieved remission. Additionally, the PB+Ex intervention reduced weight (-2.7 kg; p<0.0001), C-reactive protein (-11 nmol/l; p=0.005) and cardiovascular medication use compared with SMC. At intermediate timepoints, it improved glucose, insulin, HOMA-IR, cholesterol, triglycerides and heart rate, but not at week 24. CONCLUSIONS/INTERPRETATION: A whole-food, plant-based lifestyle intervention was more effective for improving glycaemic control than SMC. It also reduced the need for diabetes and cardiovascular medications and induced diabetes remission in some participants. Therefore, it is an effective, evidence-based lifestyle option for individuals with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03862963 FUNDING: This research was funded by the Department of the Army (W81XWH-05-1-0547). CJH received support through a National Institutes of Health Predoctoral T32 Obesity Fellowship (T32 HL105349).

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BACKGROUND: Findings from the MAVIDOS trial demonstrated a positive effect of gestational cholecalciferol supplementation on offspring bone mineral density (BMD) at age 4 years. Demonstrating persistence of this effect is important to understanding whether maternal vitamin D supplementation could be a useful public health strategy to improving bone health. OBJECTIVE: We investigated whether gestational vitamin D supplementation increases offspring BMD at 6-7 years in an exploratory post-hoc analysis of an existing trial. METHODS: In the MAVIDOS randomised controlled trial, pregnant females <14 weeks' gestation with a singleton pregnancy and serum 25-hydroxyvitamin D [25(OH)D] 25-100nmol/l at three UK hospitals (Southampton, Sheffield and Oxford) were randomised to either 1000 IU/day cholecalciferol or placebo from 14-17 weeks gestation until delivery. Offspring born at term to participants recruited in Southampton were invited to the childhood follow-up at 4 and 6-7 years. The children had a dual-energy X-ray absorptiometry (DXA, Hologic discovery) scan of whole-body-less-head (WBLH) and lumbar spine, from which bone area [BA], bone mineral content [BMC], BMD and bone mineral apparent density [BMAD]) were derived. Linear regression was used to compare the two groups adjusting for age, sex, height, weight, duration of consumption of human milk and vitamin D use at 6-7 years. RESULTS: 454 children were followed up at age 6-7 years, of whom 447 had a usable DXA scan. Gestational cholecalciferol supplementation resulted in higher WBLH BMC (0.15 SD, 95%CI 0.04, 0.26), BMD (0.18 SD, 95%CI 0.06,0.31), BMAD (0.18 SD, 95%CI 0.04,0.32) and lean mass (0.09 SD, 95%CI 0.00,0.17) compared to placebo. The effect of pregnancy cholecalciferol on bone outcomes was similar at ages 4 and 6-7 years. CONCLUSIONS AND RELEVANCE: Supplementation with cholecalciferol 1000 IU/day during pregnancy resulted in greater offspring BMD and lean mass in mid-childhood versus placebo in this exploratory post-hoc analysis. These findings suggest that pregnancy vitamin D supplementation may be an important population health strategy to improve bone health. TRIAL REGISTRATION: ISRCTN:82927713 https://doi.org/10.1186/ISRCTN82927713; EUDRACT:2007-001716-23 https://www.clinicaltrialsregister.eu/ctr-search/trial/2007-001716-23/results.

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AIMS: To evaluate the effect of dignity therapy on dignity, anxiety, depression and overall quality of life for people with burns. DESIGN: A single-blind, double-arm, parallel randomised controlled study. METHODS: The Patient Dignity Scale, Hospital Anxiety and Depression Scale, and Burn-Specific Health Scale-Short were employed to assess the dignity, anxiety, depression and overall quality of life for people with burns. These outcome indicators were measured and analysed at baseline, 2-, 4- and 8-week follow-up. The generalised estimating equations were used to analyse the effect of the intervention during each time point. RESULTS: A total of 99 participants were recruited (50 in the intervention group and 49 in the control group), with a high retention rate of 97 participants (94.95%) completing the 8-week follow-up. All outcome measurement tools met the feasibility criteria related to completeness and responsiveness over time. Dignity was the primary outcome measure, with anxiety, depression and quality of life serving as secondary outcome measures. At the 8-week post-intervention, participants in the intervention group demonstrated a statistically significant decrease in dignity and anxiety and depression, and a statistically significant increase in burn-specific health. CONCLUSIONS: Dignity therapy can effectively reduce the loss of dignity, anxiety and depression, and improve the quality of life for people with burns. This study has a positive impact on burn dignity nursing practice and provides healthcare professionals with a novel approach to help people with burns return to normal social life with dignity. IMPLICATIONS FOR THE PROFESSION: It is important to develop patient-centred care for burns with dignity. Focusing on developing a rational understanding of non-discriminatory dignity care practices among clinical providers and to develop dignity-oriented clinical care practices on the wards. IMPACT: This study validated the feasibility of implementing dignity therapy for people with burns. Dignity therapy is effective in reducing the degree of dignity impairment, reducing anxiety and depressive symptoms, and enhancing the quality of life for people with burns. Our findings can help healthcare professionals to provide personalised dignity care throughout the patient's journey to facilitate a dignified reintegration into society and life for people with burns. REPORTING METHOD: This randomised controlled trial used the CONSORT guidelines. PATIENT OR PUBLIC CONTRIBUTION: No patients or members of the public participated in the study design, data analysis or interpretation. CLINICAL TRIALS: This study has been registered in the Chinese Clinical Trial Registry registration number: ChiCTR2200065145, 29 October 2022.

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BACKGROUND: Prematurity remains one of the main causes of neonatal morbidity and mortality. Approximately two thirds of preterm births are spontaneous, i.e. secondary to preterm labour, preterm prelabour rupture of membranes (PPROM) or cervical insufficiency. Etiologically, the vaginal microbiome plays an important role in spontaneous preterm birth (sPTB). Vaginal dysbiosis and bacterial vaginosis are well-known risk factors for ascending lower genital tract infections and sPTB, while a Lactobacillus crispatus-dominated vaginal microbiome is associated with term deliveries. Synbiotics may help to achieve and/or maintain a normal, Lactobacillus-dominated vaginal microbiome. METHODS: We will perform a multi-centre, double-blind, randomised, placebo-controlled trial. Women aged 18 years or older with a singleton pregnancy are eligible for inclusion at 80/7-106/7 weeks gestational age if they have one or more of the following risk factors for sPTB: previous sPTB at 240/7-356/7 weeks, prior PPROM before 360/7 weeks, or spontaneous pregnancy loss at 140/7-236/7 weeks of gestation. Exclusion criteria are multiple gestation, cervix conisation, inflammatory bowel disease, uterine anomaly, and the use of pro-/pre-/synbiotics. Patients will be randomised to oral synbiotics or placebo, starting before 11 weeks of gestation until delivery. The oral synbiotic consists of eight Lactobacillus species (including L. crispatus) and prebiotics. The primary outcome is the gestational age at delivery. Vaginal microbiome analysis once per trimester (at approximately 9, 20, and 30 weeks) and delivery will be performed using metataxonomic sequencing (16S rRNA gene) and microbial culture. Secondary outcomes include PPROM, the use of antibiotics, antenatal admission information, and neonatal outcomes. DISCUSSION: This study will evaluate the effect of oral synbiotics on the vaginal microbiome during pregnancy in a high-risk population and correlate the microbial changes with the gestational age at delivery and relevant pregnancy outcomes. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05966649. Registered on April 5, 2024.

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BACKGROUND: It is unknown whether ultra-early physiotherapy commenced during neonatal intensive care unit admission is of value for optimising developmental outcomes in preterm/term infants at high-risk of cerebral palsy or motor-delay. AIMS: To determine whether ultra-early parent-administered physiotherapy to preterm/term high- risk infants commenced at earliest from 34-weeks post menstrual age, improves motor outcomes at 16-weeks corrected age (CA) compared to usual care. METHODS: Single-blind randomised controlled pilot study with 30 infant participants. The primary outcome was the Alberta Infant Motor Scale (AIMS) total score at 16-weeks CA. Secondary outcomes included (i) parent Depression Anxiety and Stress Score and Parent Perceptions Survey at 16-weeks CA; and (ii) Bayley Scales of Infant Development at 12-months CA. RESULTS: There were no clinically worthwhile effects at 16-weeks CA on the AIMS (mean between-group difference, 95% CI: -0.2, -2.4 to 2.0) or most secondary outcomes. However, the parents' "perception of treatment effectiveness" and "perception of change" favoured the experimental group. CONCLUSIONS: In this pilot trial, there was no clinically worthwhile effect of ultra-early parent-administered physiotherapy over usual care on the AIMS. However, the intervention was feasible for infants, acceptable to parents and parents perceived a benefit of treatment. Whilst this trial did not demonstrate treatment effectiveness using the AIMS, these findings should be interpreted cautiously because of the small sample size, the low responsivity of the AIMS to change in motor performance and the heterogeneity of the participants. Therefore, the intervention should not be abandoned on the basis of this trial, but rather further evaluated in a larger trial that addresses some of the learnings from this one.

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Purpose Video laryngoscopes were being used more often in cases of potentially difficult airways. The Karl Storz video stylet offered clear advantages over conventional laryngoscopes for patients with cervical spine fractures. This study aimed to compare the performance of the C-MAC video laryngoscope with the new Karl Storz video stylet in patients with simulated cervical fracture injuries. Material and methods The study, approved by the Board of Studies and the Ethical Committee of Jawaharlal Nehru Medical College and Hospital in Aligarh, involved 50 patients undergoing operative procedures under general anaesthesia. It was a prospective randomised controlled study on patients aged 20-60, weighing 30-80 kg, and classified as American Society of Anesthesiologists (ASA) Grades I and II, admitted for elective operative procedures. Patients were randomly assigned to two groups for intubation using different devices: the control group (N = 25) was intubated with the C-MAC (Mac blade) video laryngoscope (CM), and the study group (N = 25) was intubated with the Karl Storz video stylet (VS). The anaesthetic procedure involved a detailed pre-anesthetic check-up for all patients, including a medical history review, physical examination, and necessary tests based on age. Standard monitoring and pre-medication were administered uniformly. Anesthesia was induced and intubation was attempted using appropriate devices, following manual stabilisation of the neck. Parameters such as intubation attempts, time taken, failures, hemodynamic changes, and complications were recorded throughout the procedure. If intubation was unsuccessful, alternative measures were taken, and the operative procedure proceeded. Results The intubation success rates were compared between the two groups, CM and VS. In the CM group, all 25 patients (100%) were successfully intubated on the first attempt, while in the VS group, 23 patients (92%) were successfully intubated on the first attempt, and two patients (8%) required two attempts. The difference in the distribution of the number of attempts between the two groups was not statistically significant (p = 0.4915). The mean intubation time in the CM group was 27.24 ± 2.16 seconds, while in the VS group, the mean intubation time was significantly longer at 30.84 ± 6.81 seconds, with a statistically significant difference (p = 0.0105). Adjustment manoeuvres were required in only 4% of patients in the CM group compared to 0% in the VS group, although this difference was not statistically significant. The occurrence of blood on the device during intubation was recorded, and the distribution of patients with blood on the device among the two groups did not show a statistically significant difference (p = 0.617). Conclusion This study compared the effectiveness of two intubation devices. The C-MAC video laryngoscope showed a significantly higher rate of first-attempt successful intubations and required fewer attempts compared to the Karl Storz video stylet. The C-MAC also had shorter intubation times compared to the Karl Storz device. However, the Karl Storz video stylet demonstrated comparable performance to the C-MAC video laryngoscope in clinical settings, with both devices having similar safety profiles and minimal complications.

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Background and objective: There is currently no self-management package designed to meet the needs of people with pulmonary fibrosis (PF). This study evaluated the feasibility and acceptability of a PF-specific self-management package. Methods: Adults with PF were randomly allocated (1:1) to either receive the self-management package with healthcare professional (HCP) support or standardised PF information. Primary outcomes were feasibility and acceptability of the intervention. Secondary outcomes included health-related quality of life, self-efficacy, breathlessness, daily steps, use of PF-related treatments, and healthcare utilisation. Participants' experiences of using the package were explored using qualitative interviews. Results: Thirty participants were included. Recruitment rate was 91% and 100% of those recruited were randomised. Eighty-seven percent of participants who received the package read ≥1 module and set a goal. Secondary outcomes were feasible to collect with high assessment completion rates (87%). Most participants reported the package was easy to use and enhanced knowledge, but suggested some improvements, while HCP support was highly valued. Conclusion: A PF-specific self-management package was feasible to deliver and requires further testing in a trial powered to detect changes in clinical outcomes. Innovation: This is the first self-management package designed specifically for people with PF, informed by patient experience and expert consensus.

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INTRODUCTION: Midfoot osteoarthritis (OA) is a painful and disabling condition. Arch contouring foot orthoses have been recommended for midfoot OA, yet there is no high-quality evidence from randomised controlled trials to support their use. This clinical trial aims to evaluate the efficacy of arch contouring foot orthoses for midfoot OA. METHODS: This will be a parallel-group randomised controlled superiority trial. One-hundred and forty community-dwelling people with painful midfoot OA will be randomised to receive either arch contouring foot orthoses or flat sham inserts. Outcome measures will be obtained at baseline, 4, 8 and 12 weeks; the primary endpoint for assessing efficacy being 12 weeks. The primary outcome measure will be average midfoot pain whilst walking over the last 7 days on an 11-point numerical rating scale. Secondary outcome measures include function (walking/standing subscale of the Manchester-Oxford Foot Questionnaire), participants' perception of overall treatment effect (self-reported global rating of change on a 15-point Likert scale), physical activity (Incidental and Planned Exercise Questionnaire), general health-related quality of life (Short Form-12 Version® 2.0), use of co-interventions and adverse events. DISCUSSION: This trial will evaluate the efficacy of arch contouring foot orthoses for relieving pain and improving function, physical activity and health-related quality of life in people with midfoot OA. The findings will provide high-quality evidence as to whether arch contouring foot orthoses are efficacious and will help to inform clinical guidelines about the use of foot orthoses for midfoot OA. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry (ACTRN12623000953639).

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BACKGROUND: The World Health Organization's (WHO) Mental Health Gap Action Programme (mhGAP) is a validated intervention that can be provided by non-specialised healthcare workers to individuals with unhealthy alcohol use. However, it typically requires several in-person sessions at a health facility, which may limit its feasibility and effectiveness in remote settings. This trial compares mhGAP-Standard, a 4 to 6 in-person session intervention, to mhGAP-Remote, a 1 in-person session intervention followed by 8 week of short message service (SMS) in Lesotho. We hypothesise that mhGAP-Remote is superior to mhGAP-Standard in reducing alcohol use (as detailed by the primary and secondary outcomes below). METHODS: This is a two-arm randomised open-label multicentre superiority trial. Participants allocated to mhGAP-Standard receive 4 in-person sessions using motivational interviewing, identifying triggers, and alternative behaviours, with the option of two additional booster sessions. Participants in the mhGAP-Remote arm receive 1 in-person session covering the same content, followed by standardised SMSs over 8 weeks that reinforce intervention content. Non-specialist providers deliver the intervention and receive weekly supervision. Adults (Nplanned = 248) attending participating health facilities for any reason and who meet criteria for unhealthy alcohol use based on the Alcohol Use Disorders Identification Test ([AUDIT] score ≥ 6 for women, ≥ 8 for men) are individually randomised to the two arms (1:1 allocation, stratified by participant sex and age (≥ 50 vs < 50 years old). Follow-up assessments occur at 8, 20, and 32 weeks post-randomisation. The primary outcome is change in self-reported alcohol use (continuous AUDIT score), from baseline to 8 weeks follow-up. Change in the AUDIT from baseline to 20 and 32 weeks follow-up is a secondary outcome. Change in the biomarker phosphatidylethanol (secondary), liver enzyme values in serum (exploratory), and HIV viral load (for people with HIV only; exploratory) are also evaluated from baseline throughout the entire follow-up period. A linear regression model will be conducted for the primary analysis, adjusted for the stratification factors. Three a priori sensitivity analyses for the primary outcome are planned based on per protocol treatment attendance, recovery from unhealthy alcohol use, and clinically significant and reliable change. DISCUSSION: This trial will provide insight into feasibility and effectiveness of a shortened and primarily SMS supported version of mhGAP, which is especially relevant for settings where regular clinic attendance is a major barrier. TRIAL REGISTRATION: clinicaltrials.gov NCT05925270 . Approved on June 29th, 2023.

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OBJECTIVE: This study aims to systematically evaluate the efficacy of probiotics in treating minimum hepatic encephalopathy (MHE). METHODS: A systematic search was conducted across three major databases: PubMed, China National Knowledge Infrastructure and Wanfang. The search period spanned from the inception of each database to 9 March 2023. The objective was to identify all randomised controlled trials (RCTs) examining the efficacy of probiotic preparations in treating MHE. The search terms included 'probiotics' along with other clinically relevant terms to comprehensively capture all pertinent studies. RESULTS: A total of 18 RCTs were included. The meta-analysis showed that probiotic treatment outperformed control groups in reducing blood ammonia levels (standard mean difference [MD] = -2.68, 95% confidence interval [CI]: -3.90 to -1.46, p < .0001), improving the remission rate of MHE (risk ratio [RR] = 2.79, 95% CI: 1.23-6.35, p = .01) and lowering alanine aminotransferase levels (MD = -11.10, 95% CI: -16.17 to -6.03, p < .0001). It also significantly reduced the Model for End-Stage Liver Disease scores (MD = -2.55, 95% CI: -3.56 to -1.54, p < .00001) and the incidence of MHE (RR = .18, 95% CI: .09-.34, p < .00001). CONCLUSION: Our study demonstrates that probiotics effectively improve blood ammonia levels, liver function and cognitive function in patients with MHE. They significantly enhance the remission rate of MHE and effectively reduce its incidence, providing solid new evidence for treating MHE with probiotics.

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Background: Young adults represent a third of the United Kingdom prison population and are at risk of poor health outcomes, including drug and alcohol misuse, self-harm and suicide. Court diversion interventions aim to reduce the negative consequences of criminal sanctions and address the root causes of offending. However, evidence of their effectiveness has not yet been established. The Gateway programme, issued as a conditional caution, aimed to improve the life chances of young adults committing low-level offences. Participants agreed not to reoffend during the 16-week caution and, following a needs assessment, received individual support from a Gateway navigator and attended two workshops encouraging analysis of own behaviour and its consequences. Objective: To evaluate the effectiveness and cost-effectiveness of Gateway in relation to health and well-being of participants compared to usual process (court summons or a different conditional caution). Design, setting and participants: Pragmatic, multisite, parallel-group, superiority randomised controlled trial with two 6-month internal pilots and a target sample size of 334. Randomisation between Gateway and usual process was on a 1 : 1 basis. Four Hampshire Constabulary sites recruited 18- to 24-year-old residents of Hampshire and Isle of Wight who were questioned for an eligible low-level offence. Semistructured interviews were also held with a sample of Gateway programme participants, staff and police study recruiters. Main outcome measures: Primary outcome was the Warwick-Edinburgh Mental Wellbeing Scale score at 12 months. Secondary outcomes included health status, alcohol and drug use, recidivism and resource use. Results: Recruitment commenced in October 2019 and the trial stopped in April 2021. A total of 191 participants were recruited, with 109 randomised to Gateway and 82 to usual process. Due to an initial overestimation of potentially eligible young people and low retention rates, recruitment targets were adjusted, and a range of mitigating measures introduced. Although recruitment broadly met study progression criteria [35/50 (70%) Pilot 1: 64/74 (86%) Pilot 2], retention was low throughout (overall: data collected at week 4 was 50%: at week 16 it was 50%: 1-year 37%). Low retention was multifactorial, with one of the main barriers being difficulties contacting participants. It was therefore not possible to complete the randomised controlled trial or the health economics analyses. Qualitative interviews held with 58 individuals yielded rare insights into the benefits and limitations of this type of intervention, as well as barriers and facilitators in relation to recruitment in this setting. Limitations: Despite close collaboration with the police to address recruitment and consent issues, expansion of the inclusion criteria and recruitment area and introducing other measures, the researchers were unable to collect sufficient data within an acceptable timeframe. Conclusions: The Gateway study was a unique endeavour to gather evidence for a potentially life-changing intervention for an underserved population. The experience gained indicates that randomised controlled trials of interventions, with a health-related outcome, are possible in this setting but point towards the need for conservative recruitment and retention estimates in this target population. Other study designs should be considered. The qualitative evaluation provided a range of valuable lessons for those seeking to design similar interventions or conduct research in similar settings. Study registration: This study is registered as ISRCTN11888938. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR award ref: 16/122/20) and is published in full in Public Health Research; Vol. 12, No. 7. See the NIHR Funding and Awards website for further award information.

Young adults who commit low-level offences often have many health and social needs, making them vulnerable to physical and mental health problems. The Gateway programme was a conditional caution developed to address the underlying causes of low-level offending in young people aged 18­24 years and hence improve their life chances. In Gateway, a mentor assessed the young person's needs and supported them, signposting to healthcare, housing or other services as required. The young people also participated in two workshops, analysing the causes and consequences of their behaviour. To find out if Gateway improved health and reoffending rates, a group of those who received a Gateway conditional caution were compared with a group of those receiving a court summons or a different conditional caution. Of the 191 participants recruited to the study, 109 were randomised to Gateway and 82 to the usual process. However, the researchers had significant difficulties getting hold of the study participants on the phone and they were unable to collect enough information from them to be able to say whether Gateway worked. The researchers introduced various changes to overcome this, but in the end had to stop the study early. As part of the study, the researchers interviewed 28 Gateway programme participants, 17 Gateway project staff and 13 police officers and staff who had been recruiting into the study. From the interviews the study discovered the perceived benefits of Gateway, how programmes like this could be improved and which factors helped or got in the way of doing research in the police setting. The Gateway study aimed to provide evidence for a potentially life-changing intervention for vulnerable young adults. Although it proved impossible to complete the study, the lessons learnt from running it should help colleagues design similar programmes or plan research studies with similar populations or in similar settings.

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Background: Children whose parents have anxiety problems are at increased risk of developing anxiety themselves. Parenting behaviors are a contributing factor to intergenerational transmission. Interventions which seek to limit anxiogenic parenting behaviors have shown potential in reducing anxiety in offspring but are not widely accessible. This prevention trial aimed to establish the effectiveness of an unguided modular online intervention for highly anxious parents in preventing anxiety in their children. Methods: A parallel group, block-randomised controlled trial of unblinded participants in a 1:1 ratio was conducted to compare efficacy of the online course compared to a no-intervention control. The intervention comprised 8 modules, of approximately 20 min each, and participants progressed through the course at their own pace. The study was conducted entirely online with a self-referred UK-based community sample of parents (child 2-11 years) with substantial anxiety. The primary outcome measure was change in parent-reported child anxiety, as measured by the Spence Children's Anxiety Scale-Parent Report (SCAS-P) or Spence Pre-School Anxiety Scale-Parent Report (Preschool SCAS). Secondary outcomes were child internalising, externalising, and attentional symptoms (Pediatric Symptom Checklist), and parent anxiety (SCARED-Adult). Analyses using complete case analysis following intention to treat principles investigated intervention effects at 6 months (primary analysis) and additionally at 9 to 25-months' follow-up. Trial registration: ClinicalTrials.GovNCT04755933, https://clinicaltrials.gov/ct2/show/NCT04755933. Findings: 1811 participants (intervention = 900; control = 911; 92.7% (1677/1810) female; 85.3% (1535/1800) White-British; 66.8% (1201/1799) university educated). Participant retention (based on primary outcome completion) at T2 (6-months post consent) was 67.6% overall (n = 1224) and substantially lower in the intervention arm 57.3% ((516/900) control = 77.8% (708/910)). Child anxiety was lower in the intervention group compared to control at 6-month follow-up (adjusted effect size estimate -0.15 (95% CI: -0.23 to -0.08, p < 0.001). There was very strong evidence that those in the intervention arm had lowered child anxiety (standardised SCAS score) compared to the control arm, with an effect size (Cohen's d) of -0.16 (95% CI: -0.23 to -0.08, p < 0.001). The difference in standardised Spence Child Anxiety Scale score between the arms was -0.15 standard deviations. On the original scales for SCAS-P (0-114) and Preschool SCAS (0-112), this corresponds to a reduction of -2.38 (95% CI: -3.59 to -1.16) and -2.68 (95% CI: -4.05 to -1.31), respectively. No reported harms. Interpretation: A clinically unsupported online intervention designed for parents with high levels of anxiety is effective in reducing anxiety and internalising symptoms in their children, and also anxiety in parents. Given the low resource intensity of this intervention, and the positive effects reported here, these findings suggest it has promise in limiting the intergenerational transmission of severe anxiety. Funding: This work was supported by Kavli Trust (grant 38/19).

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OBJECTIVE: Diabetic foot ulcers (DFUs) present a significant global health challenge, resulting in high morbidity and economic costs. Current available treatments often fail to achieve satisfactory healing rates, highlighting the need for novel therapies. This study evaluated the safety and efficacy of a novel autologous whole blood clot (AWBC)-a blood-based, biodegradable provisional matrix-in conjunction with standard of care (SoC) when compared to SoC alone in the treatment of hard-to-heal DFUs. METHOD: A multicentre, prospective, blinded assessor, randomised controlled trial was conducted at 16 sites across the US, South Africa and Turkey. A cohort of patients with hard-to-heal DFUs was enrolled and randomised to either the AWBC group or the control group. The primary endpoint was complete wound closure at 12 weeks, while secondary endpoints included time to heal and percentage area reduction (PAR) at four and eight weeks. Data were analysed using both intention-to-treat (ITT) and per-protocol (PP) populations. RESULTS: The cohort included 119 patients. AWBC treatment resulted in a significantly higher healing rate compared to the control in both ITT (41% versus 15%, respectively; p=0.002) and PP populations (51% versus 18%, respectively; p=0.0075). AWBC treatment also resulted in a shorter mean time to heal and higher durability of wound closure. Safety analysis showed a similar incidence of adverse events (AEs) between groups, with no device-related AEs. CONCLUSION: The AWBC system, by modulating the wound microenvironment and providing a functional extracellular matrix, offered a promising new approach to treating hard-to-heal DFUs, demonstrating superior healing outcomes compared to SoC alone in this study.

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