Trial Forge Guidance 4: a guideline for reporting the results of randomised Studies Within A Trial (SWATs).

BACKGROUND: Evidence to support decisions on trial processes is minimal. One way to generate this evidence is to use a Study Within A Trial (SWAT) to test trial processes or explore methodological uncertainties. SWAT evidence relies on replication to ensure sufficient power and broad applicability of findings. Prompt reporting is therefore essential; however, SWAT publications are often the first to be abandoned in the face of other time pressures. Reporting guidance for embedded methodology trials does exist but is not widely used. We sought therefore to build on these guidelines to develop a straightforward, concise reporting standard, which remains adherent to the CONSORT guideline. METHODS: An iterative process was used to develop the guideline. This included initial meetings with key stakeholders, development of an initial guideline, pilot testing of draft guidelines, further iteration and pilot testing, and finalisation of the guideline. RESULTS: We developed a reporting guideline applicable to randomised SWATs, including replications of previous evaluations. The guideline follows the Consolidated Standards for Reporting Trials (CONSORT) statement and provides example text to ensure ease and clarity of reporting across all domains. CONCLUSIONS: The SWAT reporting guideline will aid authors, reviewers, and journal editors to produce and review clear, structured reports of randomised SWATs, whilst also adhering to the CONSORT guideline. TRIAL REGISTRATION: EQUATOR Network - Guidelines Under Development ( https://www.equator-network.org/library/reporting-guidelines-under-development/reporting-guidelines-under-development-for-clinical-trials/#SWAT ). Registered on 25 March 2021.

The lived experience of severe mental illness and long-term conditions: a qualitative exploration of service user, carer, and healthcare professional perspectives on self-managing co-existing mental and physical conditions.

BACKGROUND: People with severe mental illness (SMI), such as schizophrenia, have higher rates of physical long-term conditions (LTCs), poorer health outcomes, and shorter life expectancy compared with the general population. Previous research exploring SMI and diabetes highlights that people with SMI experience barriers to self-management, a key component of care in long-term conditions; however, this has not been investigated in the context of other LTCs. The aim of this study was to explore the lived experience of co-existing SMI and LTCs for service users, carers, and healthcare professionals. METHODS: A qualitative study with people with SMI and LTCs, their carers, and healthcare professionals, using semi-structured interviews, focused observations, and focus groups across the UK. Forty-one interviews and five focus groups were conducted between December 2018 and April 2019. Transcripts were coded by two authors and analysed thematically. RESULTS: Three themes were identified, 1) the precarious nature of living with SMI, 2) the circularity of life with SMI and LTCs, and 3) the constellation of support for self-management. People with co-existing SMI and LTCs often experience substantial difficulties with self-management of their health due to the competing demands of their psychiatric symptoms and treatment, social circumstances, and access to support. Multiple long-term conditions add to the burden of self-management. Social support, alongside person-centred professional care, is a key facilitator for managing health. An integrated approach to both mental and physical healthcare was suggested to meet service user and carer needs. CONCLUSION: The demands of living with SMI present a substantial barrier to self-management for multiple co-existing LTCs. It is important that people with SMI can access person-centred, tailored support for their LTCs that takes into consideration individual circumstances and priorities.

Dietary protein and bone health across the life-course: an updated systematic review and meta-analysis over 40 years.

We undertook a systematic review and meta-analysis of published papers assessing dietary protein and bone health. We found little benefit of increasing protein intake for bone health in healthy adults but no indication of any detrimental effect, at least within the protein intakes of the populations studied. This systematic review and meta-analysis analysed the relationship between dietary protein and bone health across the life-course. The PubMed database was searched for all relevant human studies from the 1st January 1976 to 22nd January 2016, including all bone outcomes except calcium metabolism. The searches identified 127 papers for inclusion, including 74 correlational studies, 23 fracture or osteoporosis risk studies and 30 supplementation trials. Protein intake accounted for 0-4% of areal BMC and areal BMD variance in adults and 0-14% of areal BMC variance in children and adolescents. However, when confounder adjusted (5 studies) adult lumbar spine and femoral neck BMD associations were not statistically significant. There was no association between protein intake and relative risk (RR) of osteoporotic fractures for total (RR(random) = 0.94; 0.72 to 1.23, I2 = 32%), animal (RR (random) = 0.98; 0.76 to 1.27, I2 = 46%) or vegetable protein (RR (fixed) = 0.97 (0.89 to 1.09, I2 = 15%). In total protein supplementation studies, pooled effect sizes were not statistically significant for LSBMD (total n = 255, MD(fixed) = 0.04 g/cm2 (0.00 to 0.08, P = 0.07), I2 = 0%) or FNBMD (total n = 435, MD(random) = 0.01 g/cm2 (-0.03 to 0.05, P = 0.59), I2 = 68%). There appears to be little benefit of increasing protein intake for bone health in healthy adults but there is also clearly no indication of any detrimental effect, at least within the protein intakes of the populations studied (around 0.8-1.3 g/Kg/day). More studies are urgently required on the association between protein intake and bone health in children and adolescents.

Compliance effects in a randomised controlled trial of yoga for chronic low back pain: a methodological study.

STUDY DESIGN: Methodological study nested within a multicentre randomised controlled trial (RCT) of yoga plus usual general practitioner (GP) care vs usual GP care for chronic low back pain. OBJECTIVE: To explore the treatment effects of non-compliance using three approaches in an RCT evaluating yoga for low back pain. SUMMARY OF BACKGROUND DATA: A large multicentre RCT using intention-to-treat (ITT) analysis found that participants with chronic low back pain who were offered a 12-week progressive programme of yoga plus usual GP care had better back function than those offered usual GP care alone. However, ITT analysis can underestimate the effect of treatment in those who comply with treatment. As such, the data were analysed using other approaches to assess the problem of non-compliance. The main outcome measure was the self-reported Roland Morris Disability Questionnaire (RMDQ). METHODS: Complier average causal effect (CACE) analysis, per-protocol analysis and on-treatment analysis were conducted on the data of participants who were fully compliant, predefined as attendance of at least three of the first six sessions and at least three other sessions. The analysis was repeated for participants who had attended at least one yoga session (i.e. any compliance), which included participants who were fully compliant. Each approach was described, including strengths and weaknesses, and the results of the different approaches were compared with those of the ITT analysis. RESULTS: For the participants who were fully compliant (n=93, 60%), a larger beneficial treatment effect was seen using CACE analysis compared with per-protocol, on-treatment and ITT analyses at 3 and 12 months. The difference in mean change in RMDQ score between randomised groups was -3.30 [95% confidence interval (CI) -4.90 to -1.70, P<0.001] at 3 months and -2.23 (95% CI -3.93 to -0.53, P=0.010) at 12 months for CACE analysis, -3.12 (95% CI -4.26 to -1.98, P<0.001) at 3 months and -2.11 (95% CI -3.33 to -0.89, P=0.001) at 12 months for per-protocol analysis, and -2.91 (95% CI -4.06 to -1.76, P<0.001) at 3 months and -2.10 (95% CI -3.31 to -0.89, P=0.001) at 12 months for on-treatment analysis. For the participants who demonstrated any compliance (n=133, 85%), the results were generally consistent with the fully compliant group at 3 months, but the treatment effect was smaller. The difference in mean change in RMDQ score between randomised groups was -2.45 (95% CI -3.67 to -1.24) for CACE analysis, -2.30 (95% CI -3.43 to 1.17) for per-protocol analysis and -2.15 (95% CI -3.25 to -1.06) for on-treatment analysis, which was slightly less than that for ITT analysis. In contrast, at 12 months, per-protocol and on-treatment analyses showed a larger treatment effect compared with CACE and ITT analyses: per protocol analysis -1.86 (95% CI -3.02 to -0.71), on-treatment analysis -1.99 (95% CI -3.13 to -0.86) and CACE analysis -1.67 (95% CI -2.95 to -0.40). CONCLUSION: ITT analysis estimated a slightly smaller treatment effect in participants who complied with treatment. When examining compliance, CACE analysis is more rigorous than per-protocol and on-treatment analyses. Using CACE analysis, the treatment effect was larger in participants who complied with treatment compared with participants who were allocated to treatment, and the difference between ITT and CACE analyses for the fully compliant group at 3 months was small but clinically important. Per-protocol and on-treatment analyses may produce unreliable estimates when the effect of treatment is small. INTERNATIONAL STANDARD RANDOMISED TRIAL NUMBER REGISTER: ISRCTN 81079604.

Bilateral or unilateral cochlear implantation for deaf children: an observational study.

OBJECTIVE: Cochlear implantation in one ear (unilateral implantation) has been the standard treatment for severe-profound childhood deafness. We assessed whether cochlear implantation in both ears (bilateral implantation) is associated with better listening skills, higher health-related quality of life (health utility) and higher general quality of life (QOL) than unilateral implantation. DESIGN: Cross-sectional observational study. SETTING: University of York. PARTICIPANTS: Fifty severely-profoundly deaf and 56 normally-hearing children recruited via a charity, the UK National Health Service and schools. INTERVENTIONS: Thirty of the deaf children had received bilateral cochlear implants; 20 had unilateral cochlear implants. MAIN OUTCOME MEASURES: Performance measures of children's listening skills; parental-proxy valuations of the deaf children's health utility obtained with the Health Utilities Index Mark 3 and of their QOL obtained with a visual analogue scale. RESULTS: On average, bilaterally-implanted children performed significantly better than unilaterally implanted children on tests of sound localisation and speech perception in noise. After conservative imputation of missing data and while controlling for confounds, bilateral implantation was associated with increases of 18.5% in accuracy of sound localisation (95% CI 5.9 to 31.1) and of 3.7 dB in speech perception in noise (95% CI 0.9 to 6.5). Bilaterally-implanted children did not perform as well as normally-hearing children, on average. Bilaterally- and unilaterally-implanted children did not differ significantly in parental ratings of health utility (difference in medians 0.05, p>0.05) or QOL (difference in medians 0.01, p>0.05). CONCLUSIONS: Compared with unilateral cochlear implantation, bilateral implantation is associated with better listening skills in severely-profoundly deaf children.

Is it clinically and cost effective to screen for postnatal depression: a systematic review of controlled clinical trials and economic evidence.

BACKGROUND: Postnatal depression (PND) is a common mental health problem, which is associated with adverse consequences beyond the individual with depression. It is not known whether using formal methods to identify PND are clinically and cost effective in improving maternal and infant outcomes. OBJECTIVES: To evaluate the clinical and cost effectiveness of antenatal and postnatal identification of depressive symptoms. SEARCH STRATEGY: Twenty electronic databases were searched to retrieve English and non-English language articles published until February 2007. SELECTION CRITERIA: Randomised controlled trials or controlled trials comparing the use of formal methods to identify PND, with or without enhancement of care, or feedback of scores with not using formal methods to identify PND or usual care. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed studies for inclusion and extracted data. Results from the trials were combined to calculate odds ratios and 95% confidence intervals for dichotomous outcomes. MAIN RESULTS: Five studies were identified that compared formal use of a method to identify PND, with or without enhancement of care, or feedback of scores with not using a formal method or usual care. All of the studies used the Edinburgh Postnatal Depression Scale (EPDS) to identify women with PND. The results of the studies indicated beneficial effects of using the EPDS in reducing EPDS scores (OR = 0.61; 95% CI 0.48-0.76). AUTHOR'S CONCLUSIONS: Despite some apparent beneficial effects of using formal methods to identify PND, it is difficult to disentangle the effects of the screening component alone from interventions linked to a positive screen as some of the studies included enhancements of care and/or an intervention.