Conservative management versus invasive management of significant traumatic pneumothoraces in the emergency department (the CoMiTED trial): a study protocol for a randomised non-inferiority trial.

INTRODUCTION: Traumatic pneumothoraces are present in one of five victims of severe trauma. Current guidelines advise chest drain insertion for most traumatic pneumothoraces, although very small pneumothoraces can be managed with observation at the treating clinician's discretion. There remains a large proportion of patients in whom there is clinical uncertainty as to whether an immediate chest drain is required, with no robust evidence to inform practice. Chest drains carry a high risk of complications such as bleeding and infection. The default to invasive treatment may be causing potentially avoidable pain, distress and complications. We are evaluating the clinical and cost-effectiveness of an initial conservative approach to the management of patients with traumatic pneumothoraces. METHODS AND ANALYSIS: The CoMiTED (Conservative Management in Traumatic Pneumothoraces in the Emergency Department) trial is a multicentre, pragmatic parallel group, individually randomised controlled non-inferiority trial to establish whether initial conservative management of significant traumatic pneumothoraces is non-inferior to invasive management in terms of subsequent emergency pleural interventions, complications, pain, breathlessness and quality of life. We aim to recruit 750 patients from at least 40 UK National Health Service hospitals. Patients allocated to the control (invasive management) group will have a chest drain inserted in the emergency department. For those in the intervention (initial conservative management) group, the treating clinician will be advised to manage the participant without chest drain insertion and undertake observation. The primary outcome is a binary measure of the need for one or more subsequent emergency pleural interventions within 30 days of randomisation. Secondary outcomes include complications, cost-effectiveness, patient-reported quality of life and patient and clinician views of the two treatment options; participants are followed up for 6 months. ETHICS AND DISSEMINATION: This trial received approval from the Wales Research Ethics Committee 4 (reference: 22/WA/0118) and the Health Research Authority. Results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ISRCTN35574247.

Colonoscopy findings after increasing two-stool faecal immunochemical test (FIT) cut-off: Cross-sectional analysis of the SCREESCO randomized trial.

BACKGROUND: We determined the impact of an increased two-stool faecal immunochemical test (FIT) cut-off on colonoscopy positivity and relative sensitivity and specificity in the randomized controlled screening trial screening of Swedish colons conducted in Sweden. METHODS: We performed a cross-sectional analysis of participants in the FIT arm that performed FIT between March 2014 and 2020 within the study registered with ClinicalTrials.gov, NCT02078804, who had a faecal haemoglobin concentration of at least 10 µg/g in at least one of two stool samples and who underwent a colonoscopy (n = 3841). For each increase in cut-off, we computed the positive predictive value (PPV), numbers needed to scope (NNS), sensitivity and specificity for finding colorectal cancer (CRC) and advanced neoplasia (AN; advanced adenoma or CRC) relative to cut-off 10 µg/g. RESULTS: The PPV for AN increased from 23.0% (95% confidence intervals [CI]: 22.3%-23.6%) at cut-off 10 µg/g to 28.8% (95% CI: 27.8%-29.7%) and 33.1% (95% CI: 31.9%-34.4%) at cut-offs 20 and 40 µg/g, respectively, whereas the NNS to find a CRC correspondingly decreased from 41 to 27 and 19. The PPV for AN was higher in men than women at each cut-off, for example 31.5% (95% CI: 30.1%-32.8%) in men and 25.6% (95% CI: 24.3%-27.0%) in women at 20 µg/g. The relative sensitivity and relative specificity were similar in men and women at each cut-off. CONCLUSION: A low cut-off of around 20-40 µg/g allows detection and removal of many AN compared to 10 µg/g while reducing the number of colonoscopies in both men and women.

Rapid respiratory microbiological point-of-care-testing and antibiotic prescribing in primary care: Protocol for the RAPID-TEST randomised controlled trial.

BACKGROUND: Antibiotics are prescribed for over 50% of respiratory tract infections in primary care, despite good evidence of there being no benefit to the patient, and evidence of over prescribing driving microbial resistance. The high treatment rates are attributed to uncertainty regarding microbiological cause and clinical prognosis. Point-of-care-tests have been proposed as potential antibiotic stewardship tools, with some providing microbiological results in 15 minutes. However, there is little research on their impact on antibiotic use and clinical outcomes in primary care. METHODS: This is a multi-centre, individually randomised controlled trial with mixed-methods investigation of microbial, behavioural and antibiotic mechanisms on outcomes in patients aged 12 months and over presenting to primary care in the UK with a suspected respiratory tract infection, where the clinician and/or patient thinks antibiotic treatment may be, or is, necessary. Once consented, all participants are asked to provide a combined nose and throat swab sample and randomised to have a rapid microbiological point-of-care-test or no point-of-care-test. For intervention patients, clinicians review the result of the test, before contacting the patient to finalise treatment. Treatment decisions are made as per usual care in control group patients. The primary outcome is whether an antibiotic is prescribed at this point. All swab samples are sent to the central laboratory for further testing. Patients are asked to complete a diary to record the severity and duration of symptoms until resolution or day 28, and questionnaires at 2 months about their beliefs and intention to consult for similar future illnesses. Primary care medical records are also reviewed at 6-months to collect further infection consultations, antibiotic prescribing and hospital admissions. The trial aims to recruit 514 patients to achieve 90% power with 5% significance to detect a 15% absolute reduction in antibiotic prescribing. Qualitative interviews are being conducted with approximately 20 clinicians and 30 participants to understand any changes in beliefs and behaviour resulting from the point-of-care-test and generate attributes for clinician and patient discrete choice experiments. DISCUSSION: This trial will provide evidence of efficacy, acceptability and mechanisms of action of a rapid microbiological point-of-care test on antibiotic prescribing and patient symptoms in primary care. TRIAL REGISTRATION: ISRCTN16039192, prospectively registered on 08/11/2022.

Prostate-Specific Antigen Screening and 15-Year Prostate Cancer Mortality: A Secondary Analysis of the CAP Randomized Clinical Trial.

Importance: The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) reported no effect of prostate-specific antigen (PSA) screening on prostate cancer mortality at a median 10-year follow-up (primary outcome), but the long-term effects of PSA screening on prostate cancer mortality remain unclear. Objective: To evaluate the effect of a single invitation for PSA screening on prostate cancer-specific mortality at a median 15-year follow-up compared with no invitation for screening. Design, Setting, and Participants: This secondary analysis of the CAP randomized clinical trial included men aged 50 to 69 years identified at 573 primary care practices in England and Wales. Primary care practices were randomized between September 25, 2001, and August 24, 2007, and men were enrolled between January 8, 2002, and January 20, 2009. Follow-up was completed on March 31, 2021. Intervention: Men received a single invitation for a PSA screening test with subsequent diagnostic tests if the PSA level was 3.0 ng/mL or higher. The control group received standard practice (no invitation). Main Outcomes and Measures: The primary outcome was reported previously. Of 8 prespecified secondary outcomes, results of 4 were reported previously. The 4 remaining prespecified secondary outcomes at 15-year follow-up were prostate cancer-specific mortality, all-cause mortality, and prostate cancer stage and Gleason grade at diagnosis. Results: Of 415 357 eligible men (mean [SD] age, 59.0 [5.6] years), 98% were included in these analyses. Overall, 12 013 and 12 958 men with a prostate cancer diagnosis were in the intervention and control groups, respectively (15-year cumulative risk, 7.08% [95% CI, 6.95%-7.21%] and 6.94% [95% CI, 6.82%-7.06%], respectively). At a median 15-year follow-up, 1199 men in the intervention group (0.69% [95% CI, 0.65%-0.73%]) and 1451 men in the control group (0.78% [95% CI, 0.73%-0.82%]) died of prostate cancer (rate ratio [RR], 0.92 [95% CI, 0.85-0.99]; P = .03). Compared with the control, the PSA screening intervention increased detection of low-grade (Gleason score [GS] ≤6: 2.2% vs 1.6%; P < .001) and localized (T1/T2: 3.6% vs 3.1%; P < .001) disease but not intermediate (GS of 7), high-grade (GS ≥8), locally advanced (T3), or distally advanced (T4/N1/M1) tumors. There were 45 084 all-cause deaths in the intervention group (23.2% [95% CI, 23.0%-23.4%]) and 50 336 deaths in the control group (23.3% [95% CI, 23.1%-23.5%]) (RR, 0.97 [95% CI, 0.94-1.01]; P = .11). Eight of the prostate cancer deaths in the intervention group (0.7%) and 7 deaths in the control group (0.5%) were related to a diagnostic biopsy or prostate cancer treatment. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, a single invitation for PSA screening compared with standard practice without routine screening reduced prostate cancer deaths at a median follow-up of 15 years. However, the absolute reduction in deaths was small. Trial Registration: isrctn.org Identifier: ISRCTN92187251.

Graded exercise therapy compared to activity management for paediatric chronic fatigue syndrome/myalgic encephalomyelitis: pragmatic randomized controlled trial.

The MAGENTA pragmatic parallel groups randomized controlled trial compared graded exercise therapy (GET) with activity management (AM) in treating paediatric myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS). Children aged 8-17 years with mild/moderate ME/CFS and presenting to NHS specialist paediatric services were allocated at random to either individualised flexible treatment focussing on physical activity (GET, 123 participants) or on managing cognitive, school and social activity (AM, 118 participants) delivered by NHS therapists. The primary outcome was the self-reported short-form 36 physical function subscale (SF-36-PFS) after 6 months, with higher scores indicating better functioning. After 6 months, data were available for 201 (83%) participants who received a mean of 3.9 (GET) or 4.6 (AM) treatment sessions. Comparing participants with measured outcomes in their allocated groups, the mean SF-36-PFS score changed from 54.8 (standard deviation 23.7) to 55.7 (23.3) for GET and from 55.5 (23.1) to 57.7 (26.0) for AM giving an adjusted difference in means of -2.02 (95% confidence interval -7.75, 2.70). One hundred thirty-five participants completed the mean SF-36-PFS at 12 months, and whilst further improvement was observed, the difference between the study groups remained consistent with chance. The two study groups showed similar changes on most of the secondary outcome measures: Chalder Fatigue, Hospital Anxiety and Depression Scale: Depression, proportion of full-time school attended, a visual analogue pain scale, participant-rated change and accelerometer measured physical activity, whether at the 6-month or 12-month assessment. There was an isolated finding of some evidence of an improvement in anxiety in those allocated to GET, as measured by the Hospital Anxiety and Depression Scale at 6 months, with the 12-month assessment, and the Spence Children's Anxiety scale being aligned with that finding. There was weak evidence of a greater risk of deterioration with GET (27%) than with AM (17%; p = 0.069). At conventional UK cost per QALY thresholds, the probability that GET is more cost-effective than AM ranged from 18 to 21%. Whilst completion of the SF-36-PFS, Chalder Fatigue Scale and EQ-5D-Y was good at the 6-month assessment point, it was less satisfactory for other measures, and for all measures at the 12-month assessment.  Conclusion: There was no evidence that GET was more effective or cost-effective than AM in this setting, with very limited improvement in either study group evident by the 6-month or 12-month assessment points.  Trial registration: The study protocol was registered at www.isrctn.com (3rd September 2015; ISRCTN 23962803) before the start of enrolment to the initial feasibility phase.

The role of endoscopist adenoma detection rate in in sex differences in colonoscopy findings: cross-sectional analysis of the SCREESCO randomized controlled trial.

BACKGROUND: Fewer adenomas are detected at colonoscopy in women compared to men and failure to detect adenomas and sessile serrated polyps is associated with an increased risk of post-colonoscopy colorectal cancer. The aim of this study was to investigate whether this was in part due to the greater difficulty of conducting colonoscopy in women, with the difference being more apparent in colonoscopies conducted by less skilled endoscopists. MATERIAL AND METHODS: Cross-sectional exploratory analysis of data on 16,551 individuals undergoing a primary colonoscopy (PCOL group) or colonoscopy after positive faecal immunochemical test (FIT group) within the randomized controlled trial SCREESCO. Endoscopist adenoma detection rate (ADR; low or high) was determined based on each endoscopist's colonoscopies performed in SCREESCO. In each study group, the relationship between the sex difference in colonoscopy outcome and endoscopist ADR was assessed using multiplicative interaction tests. RESULTS: Endoscopists performed equally many colonoscopies in men and women (median 52% men). There were no signs of effect modification of the risk ratio of any finding (men vs women) by endoscopist ADR in the PCOL group (p = 0.33) or the FIT group (p = 0.30). The proportion of incomplete index colonoscopies was lower in men than in women in both groups and there was no effect modification by endoscopist ADR in either the PCOL group (p = 0.41) or the FIT group (p = 0.96). CONCLUSIONS: This study provides no evidence that endoscopist skill measured by ADR underlies the sex difference in adenoma detection at colonoscopy. This study has trial number NCT02078804 and is registered with ClinicalTrials.gov.

HepFREEPak: protocol for a multi-centre, prospective observational study examining efficacy and impact of current therapies for the treatment of hepatitis C in Pakistan and reporting resistance to antiviral drugs: study protocol.

BACKGROUND: Pakistan has one of the highest burdens of Hepatitis C virus (HCV) infection globally. To achieve the World Health Organization's goals for HCV elimination, there is a need for substantial scale-up in testing, treatment, and a reduction in new infections. Data on the population impact of scaling up treatment is not available in Pakistan, nor is there reliable data on the incidence of infection/reinfection. This project will fill this gap by providing important empirical data on the incidence of infection (primary and reinfection) in Pakistan. Then, by using this data in epidemic models, the study will determine whether response rates achieved with affordable therapies (sofosbuvir plus daclatasvir) will be sufficient to eliminate HCV in Pakistan. METHODS: This prospective multi-centre cohort study will screen 25,000 individuals for HCV antibody (Ab) and RNA (if Ab-positive) at various centers in Pakistan- Karachi (Sindh) and Punjab, providing estimates of the disease prevalence. HCV positive patients will be treated with sofosbuvir and daclatasvir for 12-weeks, (extended to 24-weeks in those with cirrhosis) and the proportion responding to this first-line treatment estimated. Patients who test HCV Ab negative will be recalled 12 months later to test for new HCV infections, providing estimates of the incidence rate. Patients diagnosed with HCV (~ 4,000) will be treated and tested for Sustained Virological Response (SVR). Questionnaires to assess risk factors, productivity, health care usage and quality of life will be completed at both the initial screening and at 12-month follow-up, allowing mathematical modelling and economic analysis to assess the current treatment strategies. Viral resistance will be analysed and patients who have successfully completed treatment will be retested 12 months later to estimate the rate of re-infection. CONCLUSION: The HepFREEPak study will provide evidence on the efficacy of available and widely used treatment options in Pakistan. It will also provide data on the incidence rate of primary infections and re-infections. Data on incidence risk factors will allow us to model and incorporate heterogeneity of risk and how that affects screening and treatment strategies. These data will identify any gaps in current test-and-treat programs to achieve HCV elimination in Pakistan. STUDY REGISTRATION: This study was registered on clinicaltrials.gov (NCT04943588) on June 29, 2021.

Outcomes of Cochlear implantation in early-deafened patients with Waardenburg syndrome: A systematic review and narrative synthesis.

Objective: This systematic review aims to establish the expected hearing and speech outcomes following cochlear implantation (CI) in patients with profound congenital deafness secondary to Waardenburg syndrome (WS). Methods: A systematic review of the literature and narrative synthesis was performed in accordance with the PRISMA statement. Databases searched: Medline, Pubmed, Embase, Web of Science, Cochrane Collection, and ClinicalTrials.gov. No limits were placed on language or year of publication. Results: Searches identified 186 abstracts and full texts. Of these, 16 studies met inclusion criteria reporting outcomes in 179 patients and at least 194 implants. Hearing outcomes of those receiving cochlear implantation were generally good. Five studies included genetic analysis of one or more of the participants. A total of 11 peri/post-operative complications were reported. The methodological quality of included studies was modest, mainly comprising noncontrolled case series with small cohort size. All studies were OCEBM grade III-IV. Conclusion: Cochlear implantation in congenitally deafened children with Waardenburg Syndrome is a well-established intervention as a method of auditory rehabilitation. Due to the uncommon nature of the condition, there is a lack of large-scale high-quality studies examining the use of cochlear implantation in this patient group. However, overall outcomes following implantation are positive with the majority of patients demonstrating improved audiometry, speech perception and speech intelligibility supporting its use in appropriately selected cases.

Investigating the factors associated with meaningful improvement on the SF-36-PFS and exploring the appropriateness of this measure for young people with ME/CFS accessing an NHS specialist service: a prospective cohort study.

OBJECTIVES: Paediatric myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is relatively common and disabling, but little is known about the factors associated with outcome. We aimed to describe the number and characteristics of young people reaching the 10-point minimal clinically important difference (MCID) of SF-36-Physical Function Subscale (SF-36-PFS) and to investigate factors associated with reaching the MCID. DESIGN: Prospective observational cohort study. SETTING: A specialist UK National Health Service ME/CFS service, Southwest England; recruitment between March 2014 and August 2015. PARTICIPANTS: 193 eligible patients with ME/CFS aged 8-17 years reported baseline data. 124 (65%) and 121 (63%) with outcome data at 6 and 12 months, respectively. OUTCOME MEASURES: SF-36-PFS (primary outcome). Chalder Fatigue Questionnaire, school attendance, visual analogue pain scale, Hospital Anxiety and Depression Scale, Spence Young People Anxiety Scale, Clinical Global Impression scale and EQ-5D-Y (secondary). RESULTS: At 6 months 48/120 (40%) had reached the MCID for SF-36-PFS. This had increased to 63/117 (54%) at 12 months. On the Clinical Global Impressions, 77% and 79% reported feeling either a little better, much better or very much better. Those with worse SF-36-PFS at baseline assessment were more likely to achieve the MCID for SF-36-PFS at 6 months (odds ratio 0.97, 95% confidence interval 0.96 to 0.99, p value 0.003), but there was weaker evidence of effect at 12 months (OR 0.98, 95% CI 0.97 to 1.00, p value 0.038). No other factors at baseline were associated with the odds of reaching the MCID at 6 months. However, at 12 months, there was strong evidence of an effect of pain on MCID (OR 0.97, 95% CI 0.95 to 0.99, p value 0.001) and SF-36-PFS on MCID (OR 0.96, 95% CI 0.94 to 0.98, p value 0.001). CONCLUSIONS: 40% and 54% of young people reached the MCID at 6 and 12 months, respectively. No factors at assessment (other than SF-36-PFS at 6 months, and pain and SF-36-PFS at 12 months) are associated with MCID of SF-36-PFS at either 6 or 12 months. Further work is needed to explore the most appropriate outcome measure for capturing clinical meaningful improvement for young people with ME/CFS.

Protocol to evaluate the effectiveness and cost-effectiveness of an environmental nutrition and physical activity intervention in nurseries (Nutrition and Physical Activity Self Assessment for Child Care - NAP SACC UK): a multicentre cluster randomised controlled trial.

BACKGROUND: One in seven UK children have obesity when starting school, with higher prevalence associated with deprivation. Most pre-school children do not meet UK recommendations for physical activity and nutrition. Formal childcare settings provide opportunities to deliver interventions to improve nutritional quality and physical activity to the majority of 3-4-year-olds. The nutrition and physical activity self-assessment for childcare (NAP SACC) intervention has demonstrated effectiveness in the USA with high acceptability in the UK. The study aims to evaluate the effectiveness and cost-effectiveness of the NAP SACC UK intervention to increase physical activity, reduce sedentary time and improve nutritional intake. METHODS: Multi-centre cluster RCT with process and economic evaluation. Participants are children aged 2 years or over, attending UK early years settings (nurseries) for ≥ 12 h/week or ≥ 15 h/week during term time and their parents, and staff at participating nurseries. The 12-month intervention involves nursery managers working with a Partner (public health practitioner) to self-assess policies and practices relating to physical activity and nutrition; nursery staff attending one physical activity and one nutrition training workshop and setting goals to be achieved within 6 months. The Partner provides support and reviews progress. Nursery staff receive a further workshop and new goals are set, with Partner support for a further 6 months. The comparator is usual practice. Up to 56 nurseries will be stratified by area and randomly allocated to intervention or comparator arm with minimisation of differences in level of deprivation. PRIMARY OUTCOMES: accelerometer-assessed mean total activity time on nursery days and average total energy (kcal) intake per eating occasion of lunch and morning/afternoon snacks consumed within nurseries. SECONDARY OUTCOMES: accelerometer-assessed mean daily minutes of moderate-to-vigorous physical activity and sedentary time per nursery day, total physical activity on nursery days compared to non-nursery days, average serving size of lunch and morning/afternoon snacks in nursery per day, average percentage of core and non-core food in lunch and morning/afternoon snacks, zBMI, proportion of children who are overweight/obese and child quality-of-life. A process evaluation will examine fidelity, acceptability, sustainability and context. An economic evaluation will compare costs and consequences from the perspective of the local government, nursery and parents. TRIAL REGISTRATION: ISRCTN33134697, 31/10/2019.

Suicide Rates in High-Risk High-Harm Perpetrators of Domestic Abuse in England and Wales.

Background A limited amount of research indicates a high prevalence of mental illness in perpetrators of domestic abuse (DA). Aims Estimate the suicide rate in high-risk high-harm perpetrators of DA. Method We utilized data collected as part of Drive, which supports and challenges perpetrators of DA to reduce their harmful behaviors. Using routine anonymized data, we established a cohort of clients (n = 3,475) who were referred via Multi-Agency Risk Assessment Conferences to the service and were followed up during service engagement. Results Most clients were male (92%) and White British (76%) with a median age of 32 years (IQI 27-39). There were 10 male suicide deaths recorded with an estimated male suicide rate of 461 per 100,000 person years (95% CI 248, 856). Limitations Analysis was restricted to those referred to the service and a specific group of perpetrators, limiting the generalizability to all perpetrators of DA. Conclusion The suicide rate in this high-risk high-harm DA perpetrator group is significantly higher than many other high-risk groups. Improving their mental health and outcomes is imperative to reduce the suicide deaths in this group and therefore reduce the impact such deaths would have on the victims of abuse.

Isotopic-based evidence for reduced benthic contributions to fish after a whole-lake addition of nanosilver.

Silver nanoparticles (AgNPs) are added as antibacterial and anti-odor agents to a wide range of textiles, with high potential for release into aquatic environments via domestic wastewater. Previous work demonstrating the negative impacts of AgNP exposure on periphyton production suggests benthic primary production could be reduced in aquatic ecosystems impacted by AgNP discharge. To evaluate the potential for AgNPs to alter benthic-pelagic coupling in aquatic ecosystems, tissue-stable isotope ratios of carbon and nitrogen from northern pike (Esox lucius) and yellow perch (Perca flavescens) were measured before, during, and after the addition of AgNPs to a whole-lake ecosystem, and compared to those collected from a nearby reference lake. A shift in carbon isotope ratios toward more negative values was observed in both P. flavescens and E. lucius collected from the lake where AgNPs were added, with no shift in similar magnitude observed in E. lucius from the reference lake. Consequently, Bayesian estimates of benthic energy consumed decreased by 32% for P. flavescens and by 40% for E. lucius collected after AgNP additions relative to pre-addition estimates, greater in magnitude or opposite in direction of trends observed in our reference lake. Analyses suggest no changes in fish nitrogen isotope ratios related to AgNP additions. We hypothesize that the observed reduction in littoral energy use of fish reported here is a response to AgNP settling in littoral benthic habitats-the main habitat in lakes supporting periphyton-as AgNP has been shown elsewhere to significantly reduce the rates of periphyton production. Further, our study highlights the need to broaden the scope of risk assessments for AgNPs and other emerging contaminants prone to settling to consider habitat-specific impacts on resource utilization by organisms after their release into aquatic ecosystems.

Participant retention in paediatric randomised controlled trials published in six major journals 2015-2019: systematic review and meta-analysis.

BACKGROUND: The factors which influence participant retention in paediatric randomised controlled trials are under-researched. Retention may be more challenging due to child developmental stages, involving additional participants, and proxy-reporting of outcomes. This systematic review and meta-analysis explores the factors which may influence retention in paediatric trials. METHODS: Using the MEDLINE database, paediatric randomised controlled trials published between 2015 and 2019 were identified from six general and specialist high-impact factor medical journals. The review outcome was participant retention for each reviewed trial's primary outcome. Context (e.g. population, disease) and design (e.g. length of trial) factors were extracted. Retention was examined for each context and design factor in turn, with evidence for an association being determined by a univariate random-effects meta-regression analysis. RESULTS: Ninety-four trials were included, and the median total retention was 0.92 (inter-quartile range 0.83 to 0.98). Higher estimates of retention were seen for trials with five or more follow-up assessments before the primary outcome, those less than 6 months between randomisation and primary outcome, and those that used an inactive data collection method. Trials involving children aged 11 and over had the higher estimated retention compared with those involving younger children. Those trials which did not involve other participants also had higher retention, than those where they were involved. There was also evidence that a trial which used an active or placebo control treatment had higher estimated retention, than treatment-as-usual. Retention increased if at least one engagement method was used. Unlike reviews of trials including all ages of participants, we did not find any association between retention and the number of treatment groups, size of trial, or type of treatment. CONCLUSIONS: Published paediatric RCTs rarely report the use of specific modifiable factors that improve retention. Including multiple, regular follow-ups with participants before the primary outcome may reduce attrition. Retention may be highest when the primary outcome is collected up to 6 months after a participant is recruited. Our findings suggest that qualitative research into improving retention when trials involve multiple participants such as young people, and their caregivers or teachers would be worthwhile. Those designing paediatric trials also need to consider the use of appropriate engagement methods. RESEARCH ON RESEARCH (ROR) REGISTRY: https://ror-hub.org/study/2561.

Protocol to evaluate the effectiveness and cost-effectiveness of an environmental nutrition and physical activity intervention in nurseries (Nutrition and Physical Activity Self Assessment for Child Care - NAP SACC UK): a multicentre cluster randomised controlled trial.

Background One in seven UK children have obesity when starting school, with higher prevalence associated with deprivation. Most pre-school children do not meet UK recommendations for physical activity and nutrition. Formal childcare settings provide opportunities to deliver interventions to improve nutritional quality and physical activity to the majority of 3-4-year-olds. The nutrition and physical activity self-assessment for childcare (NAP SACC) intervention has demonstrated effectiveness in the USA with high acceptability in the UK. The study aims to evaluate the effectiveness and cost-effectiveness of the NAP SACC UK intervention to increase physical activity, reduce sedentary time and improve nutritional intake. Methods Multi-centre cluster RCT with process and economic evaluation. Participants are children aged 2 years or over, attending UK early years settings (nurseries) for ≥ 12 hours/week or ≥ 15 hours/week during term time and their parents, and staff at participating nurseries. The 12-month intervention involves nursery managers working with a Partner (public health practitioner) to self-assess policies and practices relating to physical activity and nutrition; nursery staff attending one physical activity and one nutrition training workshop and setting goals to be achieved within six months. The Partner provides support and reviews progress. Nursery staff receive a further workshop and new goals are set, with Partner support for a further six months. The comparator is usual practice. Up to 56 nurseries will be stratified by area and randomly allocated to intervention or comparator arm with minimisation of differences in level of deprivation. PRIMARY OUTCOMES: accelerometer-assessed mean total activity time on nursery days and average total energy (kcal) intake per eating occasion of lunch and morning/afternoon snacks consumed within nurseries. SECONDARY OUTCOMES: accelerometer-assessed mean daily minutes of moderate-to-vigorous physical activity and sedentary time per nursery day, total physical activity on nursery days compared to non-nursery days, average serving size of lunch and morning/afternoon snacks in nursery per day, average percentage of core and non-core food in lunch and morning/afternoon snacks, zBMI, proportion of children who are overweight/obese and child quality-of-life. A process evaluation will examine fidelity, acceptability, sustainability and context. An economic evaluation will compare costs and consequences from the perspective of the local government, nursery and parents. TRIAL REGISTRATION: ISRCTN33134697.

Fifteen-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer.

BACKGROUND: Between 1999 and 2009 in the United Kingdom, 82,429 men between 50 and 69 years of age received a prostate-specific antigen (PSA) test. Localized prostate cancer was diagnosed in 2664 men. Of these men, 1643 were enrolled in a trial to evaluate the effectiveness of treatments, with 545 randomly assigned to receive active monitoring, 553 to undergo prostatectomy, and 545 to undergo radiotherapy. METHODS: At a median follow-up of 15 years (range, 11 to 21), we compared the results in this population with respect to death from prostate cancer (the primary outcome) and death from any cause, metastases, disease progression, and initiation of long-term androgen-deprivation therapy (secondary outcomes). RESULTS: Follow-up was complete for 1610 patients (98%). A risk-stratification analysis showed that more than one third of the men had intermediate or high-risk disease at diagnosis. Death from prostate cancer occurred in 45 men (2.7%): 17 (3.1%) in the active-monitoring group, 12 (2.2%) in the prostatectomy group, and 16 (2.9%) in the radiotherapy group (P = 0.53 for the overall comparison). Death from any cause occurred in 356 men (21.7%), with similar numbers in all three groups. Metastases developed in 51 men (9.4%) in the active-monitoring group, in 26 (4.7%) in the prostatectomy group, and in 27 (5.0%) in the radiotherapy group. Long-term androgen-deprivation therapy was initiated in 69 men (12.7%), 40 (7.2%), and 42 (7.7%), respectively; clinical progression occurred in 141 men (25.9%), 58 (10.5%), and 60 (11.0%), respectively. In the active-monitoring group, 133 men (24.4%) were alive without any prostate cancer treatment at the end of follow-up. No differential effects on cancer-specific mortality were noted in relation to the baseline PSA level, tumor stage or grade, or risk-stratification score. No treatment complications were reported after the 10-year analysis. CONCLUSIONS: After 15 years of follow-up, prostate cancer-specific mortality was low regardless of the treatment assigned. Thus, the choice of therapy involves weighing trade-offs between benefits and harms associated with treatments for localized prostate cancer. (Funded by the National Institute for Health and Care Research; ProtecT Current Controlled Trials number, ISRCTN20141297; ClinicalTrials.gov number, NCT02044172.).

Proactive and Integrated Management and Empowerment in Parkinson's Disease protocol for a randomised controlled trial (PRIME-UK) to evaluate a new model of care.

BACKGROUND: People living with Parkinson's disease experience progressive motor and non-motor symptoms, which negatively impact on health-related quality of life and can lead to an increased risk of hospitalisation. It is increasingly recognised that the current care models are not suitable for the needs of people with parkinsonism whose care needs evolve and change as the disease progresses. This trial aims to evaluate whether a complex and innovative model of integrated care will increase an individual's ability to achieve their personal goals, have a positive impact on health and symptom burden and be more cost-effective when compared with usual care. METHODS: This is a single-centre, randomised controlled trial where people with parkinsonism and their informal caregivers are randomised into one of two groups: either PRIME Parkinson multi-component model of care or usual care. Adults ≥18 years with a diagnosis of parkinsonism, able to provide informed consent or the availability of a close friend or relative to act as a personal consultee if capacity to do so is absent and living in the trial geographical area are eligible. Up to three caregivers per patient can also take part, must be ≥18 years, provide informal, unpaid care and able to give informed consent. The primary outcome measure is goal attainment, as measured using the Bangor Goal Setting Interview. The duration of enrolment is 24 months. The total recruitment target is n=214, and the main analyses will be intention to treat. DISCUSSION: This trial tests whether a novel model of care improves health and disease-related metrics including goal attainment and decreases hospitalisations whilst being more cost-effective than the current usual care. Subject to successful implementation of this intervention within one centre, the PRIME Parkinson model of care could then be evaluated within a cluster-randomised trial at multiple centres.

The Impact of the COVID-19 Pandemic and Lockdowns on Self-Poisoning and Suicide in Sri Lanka: An Interrupted Time Series Analysis.

Evidence from high-income countries suggests that the impact of COVID-19 on suicide and self-harm has been limited, but evidence from low- and middle-income countries is lacking. Using data from a hospital-based self-poisoning register (January 2019-December 2021) and data from national records (2016-2021) of suicide in Sri Lanka, we aimed to assess the impact of the pandemic on both self-poisoning and suicide. We examined changes in admissions for self-poisoning and suicide using interrupted time series (ITS) analysis. For the self-poisoning hospital admission ITS models, we defined the lockdown periods as follows: (i) pre-lockdown: 01/01/2019-19/03/2020; (ii) first lockdown: 20/03/2020-27/06/2020; (iii) post-first lockdown: 28/06/2020-11/05/2021; (iv) second lockdown: 12/05/2021-21/06/2021; and (v) post-second lockdown: 22/06/2021-31/12/2021. For suicide, we defined the intervention according to the pandemic period. We found that during lockdown periods, there was a reduction in hospital admissions for self-poisoning, with evidence that admission following self-poisoning remained lower during the pandemic than would be expected based on pre-pandemic trends. In contrast, there was no evidence that the rate of suicide in the pandemic period differed from that which would be expected. As the long-term socioeconomic impacts of the pandemic are realised, it will be important to track rates of self-harm and suicide in LMICs to inform prevention.

Acceptability of integrating smoking cessation treatment into routine care for people with mental illness: A qualitative study.

INTRODUCTION: Improving Access to Psychological Therapies (IAPTs) Services could offer smoking cessation treatment to improve physical and psychological outcomes for service users, but it currently does not. This study aimed to understand participants' views and experiences of receiving a novel smoking cessation intervention as part of the ESCAPE trial (intEgrating Smoking Cessation treatment As part of usual Psychological care for dEpression and anxiety). We used the Capability, Opportunity and Motivation Model of Behaviour (COM-B) to understand the (i) acceptability of the integrated smoking cessation treatment, (ii) views of psychological well-being practitioners' (PWPs) ability to deliver the smoking cessation treatment and (iii) positive and negative impacts of smoking cessation treatment. METHODS: This was a qualitative study embedded within a feasibility randomized-controlled trial (ESCAPE) in primary care services in the United Kingdom (IAPT). Thirty-six participants (53% female) from both usual care and intervention arms of the ESCAPE trial, including both quitters and nonquitters, were interviewed using semi-structured interviews. Data were analysed using a framework approach to thematic analysis, using the COM-B as a theoretical frame. RESULTS: Psychological Capability: Integrated smoking cessation treatment was acceptable and encouraged participants to reflect on their mental health. Some participants found it difficult to understand nicotine withdrawal symptoms. MOTIVATION: Participants were open to change during the event of presenting to IAPT. Some described being motivated to take part in the intervention by curiosity, to see whether quitting smoking would help their mental health. Physical Opportunity: IAPT has a natural infrastructure for supporting integrated treatment, but there were some barriers such as session duration and interventions feeling segmented. Social Opportunity: Participants viewed PWPs as having good interpersonal skills to deliver a smoking cessation intervention. CONCLUSION: People with common mental illness generally accepted integrated smoking cessation and mental health treatment. Smoking cessation treatment fits well within IAPT's structure; however, there are barriers to implementation. PATIENT OR PUBLIC CONTRIBUTION: Before data collection, we consulted with people with lived experience of smoking and/or mental illness and lay public members regarding the aims, design and interview schedules. After analysis, two people with lived experience of smoking and mental illness individually gave feedback on the final themes and quotes.

Compounds of wastewater origin in remote upland lakes in Ireland.

It is well established that persistent organic pollutants are transported long distances in the atmosphere and deposited into aquatic and terrestrial ecosystems in remote areas, including high altitude lakes. The objective of this research was to evaluate whether compounds of wastewater origin were present in four remote upland headwater lakes in Ireland that primarily receive loadings from atmospheric deposition. Using Polar Organic Chemical Integrative Samplers (POCIS) deployed in the lakes for 60 to 68 days, seven compounds were detected at levels that could be quantified but 25 of the target compounds were not detected. The detected compounds included the cannabinoid metabolite, tetrahydrocannabinol carboxylate (THC-COOH), codeine, acetaminophen (paracetamol), ibuprofen, and the artificial sweeteners, sucralose, and saccharin, which were all present at concentrations estimated to be < 125 ng/L. Caffeine was also present in the lakes at estimated concentrations between 213 and 1320 ng/L. Cocaine and tramadol were detected in POCIS deployed in some of the lakes, but at levels below the limits of quantitation. The highest concentrations of the target analytes were detected in two lakes located in the eastern part of Ireland. These data are consistent with regional atmospheric transport of these compounds originating from wastewater treatment plants in Ireland. However, contaminants from wastewater treatment plants in the United Kingdom may also be a source in these upland lakes that are located far from emissions of urban pollution.

Patient-Reported Outcomes 12 Years after Localized Prostate Cancer Treatment.

BACKGROUND: Long-term patient-reported outcomes are needed to inform treatment decisions for localized prostate cancer. METHODS: Patient-reported outcomes of 1643 randomly assigned participants in the ProtecT (Prostate Testing for Cancer and Treatment) trial were evaluated to assess the functional and quality-of-life impacts of prostatectomy, radiotherapy with neoadjuvant androgen deprivation, and active monitoring. This article focuses on the outcomes of the randomly assigned participants from 7 to 12 years using mixed effects linear and logistic models. RESULTS: Response rates exceeded 80% for most measures. Among the randomized groups over 7 to 12 years, generic quality-of-life scores were similar. Among those in the prostatectomy group, urinary leakage requiring pads occurred in 18 to 24% of patients over 7 to 12 years, compared with 9 to 11% in the active monitoring group and 3 to 8% in the radiotherapy group. In the prostatectomy group, 18% reported erections sufficient for intercourse at 7 years, compared with 30% in the active monitoring and 27% in the radiotherapy groups; all converged to low levels of potency by year 12. Nocturia (voiding at least twice per night) occurred in 34% in the prostatectomy group compared with 48% in the radiotherapy group and 47% in the active monitoring group at 12 years. Fecal leakage affected 12% in the radiotherapy group compared with 6% in the other groups by year 12. The active monitoring group experienced gradual age-related declines in sexual and urinary function, avoiding radical treatment effects unless they changed management. CONCLUSIONS: ProtecT provides robust evidence about continued impacts of treatments in the long term. These data allow patients newly diagnosed with localized prostate cancer and their clinicians to assess the trade-offs between treatment harms and benefits and enable better informed and prudent treatment decisions. (Funded by the UK National Institute for Health and Care Research Health Technology Assessment Programme projects 96/20/06 and 96/20/99; ISRCTN number, ISRCTN20141297; ClinicalTrials.gov number, NCT02044172.)