Two-by-two factorial randomised study within a trial (SWAT) to evaluate strategies for follow-up in a randomised prevention trial

BackgroundFailure to collect outcome data in randomised trials can result in bias and loss of statistical power. Further evaluations of strategies to increase retention are required. We assessed the effectiveness of two strategies for retention in a randomised prevention trial using a two-by-two factorial randomised study within a trial (SWAT).MethodsParents of babies included in the host trial were randomised to (1) short message service (SMS) notification prior to sending questionnaires at 3, 6, 12 and 18 months versus no SMS notification and (2) a £10 voucher sent with the invitation letter for the primary follow-up visit at 24 months or given at the visit. The two co-primary outcomes were collection of host trial (1) questionnaire data at interim follow-up times and (2) primary outcome at 24 months during a home/clinic visit with a research nurse.ResultsBetween November 2014 and November 2016, 1394 participants were randomised: 350 to no SMS + voucher at visit, 345 to SMS + voucher at visit, 352 to no SMS + voucher before visit and 347 to SMS + voucher before visit. Overall questionnaire data was collected at interim follow-up times for 75% in both the group allocated to the prior SMS notification and the group allocated to no SMS notification (odds ratio (OR) SMS versus none 1.02, 95% CI 0.83 to 1.25). Host trial primary outcome data was collected at a visit for 557 (80%) allocated to the voucher before the visit in the invitation letter and for 566 (81%) whose parents were allocated to receive the voucher at the visit (OR before versus at visit 0.89, 95% CI 0.69 to 1.17).ConclusionThere was no evidence of a difference in retention according to SMS notification or voucher timing. Future synthesis of SWAT results is required to be able to detect small but important incremental effects of retention strategies

Health related quality of life in individuals at high risk of chronic liver disease: Impact of a community diagnostic pathway

Objectives: There is a lack of understanding of health related quality of life (HRQoL) in chronic liver disease (CLD). With the rising prevalence of alcohol and obesity driven CLD, and the increasing ability to screen for fibrosis, it is important to understand the impact of the diagnostic process for patients.Study design: Prospective cohort studyMethods: A cohort study conducted utilising the Nottingham Adult Liver Disease Stratification Pathway, UK. All patients referred as high risk for CLD (due to metabolic, alcohol or abnormal liver enzymes) completed the EQ-5D before diagnosis and at three and 12 months after. HRQoL was investigated by domain, CLD severity (transient elastography) and temporally.Results: 493 patients participated with 300 (60.9%) completing at least one follow-up HRQoL assessment.Pre-diagnosis the median (IQR) utility index was 0.75 (0.61-0.85) and visual analogue scale was 75/100 (60-90). The median utility index was significantly lower amongst those with advanced liver disease compared to those without at all time points (baseline 0.68 vs 0.77, three-months 0.65 vs 0.79, 12-months 0.69 vs 0.84, all

Uncertainty about cellulitis and unmet patient information needs: a mixed methods study in primary and secondary care

Background: Cellulitis is a painful infection of the skin and underlying tissues, commonly affecting the lower leg: approximately a third of people experience recurrence. Patients’ ability to recover from cellulitis or prevent recurrence is likely to be influenced by their understanding of the condition.Aim: To explore patients’ perceptions of cellulitis and their information needs.Design and Setting: Mixed methods study comprising semi‐structured, face‐to‐face interviews and a cross‐sectional survey, recruiting through primary care, secondary care and advertising.Methods: Adults aged 18 or over with a history of cellulitis were invited to take part in a survey, qualitative interview, or both.Results: Thirty interviews were conducted between August 2016 and July 2017. Qualitative data highlighted: (1) low awareness of cellulitis prior to first episode, 2) uncertainty around the time of diagnosis, 3) concern/surprise at the severity of cellulitis, 4) perceived insufficient information provision. People were surprised they had never heard of cellulitis and that they had not received advice or leaflets giving self‐care information. Some sought information from the internet and found this confusing. Two hundred and forty surveys were completed (response rate 17%). These showed that, while many participants had received information on the treatment of cellulitis (60.0%, n=144), they often reported receiving no information about causes (60.8%, n=146) or prevention of recurrence (73.3%, n=176).Conclusions: There is a need to provide information for people with cellulitis, particularly around (1) the name of their condition, (2) managing acute episodes and (3) reducing risk of recurrences

Long-term oral prednisolone exposure in primary care for bullous pemphigoid: population-based study

Background: Oral prednisolone is the mainstay treatment for bullous pemphigoid, an autoimmune blistering skin disorder affecting older people. Treatment with moderate-to-high doses is often initiated in secondary care, but then continued in primary care. Aim: To describe long-term oral prednisolone prescribing in UK primary care for adults with bullous pemphigoid from 1998 to 2017. Design and setting: A prospective cohort study using routinely collected data from the Clinical Practice Research Datalink, a primary care database containing the healthcare records for over 17 million people in the UK. Method: Oral prednisolone exposure was characterised in terms of the proportion of individuals with incident bullous pemphigoid prescribed oral prednisolone following their diagnosis, and the duration and dose of prednisolone. Results: In total, 2312 (69.6%) of 3322 people with bullous pemphigoid were prescribed oral prednisolone in primary care. The median duration of exposure was 10.6 months (interquartile range [IQR] 3.4–24.0). Of prednisolone users, 71.5% were continuously exposed for >3 months, 39.7% for >1 year, 14.7% for >3 years, 5.0% for >5 years, and 1.7% for >10 years. The median cumulative dose was 2974 mg (IQR 1059–6456). Maximum daily doses were ≥10 mg/day in 74.4% of prednisolone users, ≥20 mg/day in 40.7%, ≥30 mg/day in 18.2%, ≥40 mg/day in 6.6%, ≥50 mg/day in 3.8%, and ≥60 mg/day in 1.9%. Conclusion: A high proportion of people with incident bullous pemphigoid are treated with oral prednisolone in UK primary care. Action is required by primary and second care services to encourage use of steroid-sparing alternatives and, where switching is not possible, ensure prophylactic treatments and proactive monitoring of potential side effects are in place

Safety of topical corticosteroids in atopic eczema:an umbrella review

Objective: An umbrella review summarising all safety data from systematic reviews of topical corticosteroids (TCS) in adults and children with atopic eczema .Methods: Embase, MEDLINE, PubMed, Cochrane Database of Systematic Reviews and the Centre of Evidence Based Dermatology map of eczema systematic reviews searched until 7th November 2018 and Epistemonikos until 2nd March 2021. Reviews were included if they assessed safety of TCS in atopic eczema and searched >1 database using a reproducible search strategy. Review quality assessed using AMSTAR-2. PROSPERO registration: CRD42018079409. Results: 38 systematic reviews included, 34 low/critically low quality. Treatment and follow-up usually short (2-4 weeks). Key findings: TCS versus emollient/vehicle: No meta-analyses identified for skin-thinning. Two 2-week randomised controlled trials (RCTs) found no significant increased risk with very potent TCS (0/196 TCS vs 0/33 vehicle in children and 6/109 TCS vs 2/50 vehicle, age unknown). Biochemical adrenal suppression (cortisol) was 3.8% (95% CI 2.4%-5.8%) in a meta-analysis of 11 uncontrolled observational studies (any potency TCS, 522 children). Effects reversed when treatment ceased. TCS versus topical calcineurin inhibitors (TCIs): Meta-analysis showed higher relative risk of skin-thinning with TCS (RR 4.86, 95% CI 1.06-22.28, n=4128, four RCTs, including one 5-year RCT). Eight cases in 2068 participants, 7 using potent TCS. No evidence of growth suppression.Once daily versus more frequent TCS: No meta-analyses identified. No skin-thinning in one RCT (3 weeks potent TCS, n=94) or biochemical adrenal suppression in two RCTs (up to 2 weeks very potent/moderate TCS, n=129).TCS twice/week to prevent flares (‘weekend therapy’) versus vehicle: No meta-analyses identified. No evidence of skin-thinning in five RCTs. One RCT found biochemical adrenal suppression (2/44 children, potent TCS).Conclusions: We found no evidence of harm when TCS used intermittently “as required” to treat flares or “weekend therapy” to prevent flares. However, long-term safety data was limited

Investing in updating: how do conclusions change when Cochrane systematic reviews are updated?

BACKGROUND: Cochrane systematic reviews aim to provide readers with the most up-to-date evidence on the effects of healthcare interventions. The policy of updating Cochrane reviews every two years consumes valuable time and resources and may not be appropriate for all reviews. The objective of this study was to examine the effect of updating Cochrane systematic reviews over a four year period. METHODS: This descriptive study examined all completed systematic reviews in the Cochrane Database of Systematic Reviews (CDSR) Issue 2, 1998. The latest version of each of these reviews was then identified in CDSR Issue 2, 2002 and changes in the review were described. For reviews that were updated within this time period and had additional studies, we determined whether their conclusion had changed and if there were factors that were predictive of this change. RESULTS: A total of 377 complete reviews were published in CDSR Issue 2, 1998. In Issue 2, 2002, 14 of these reviews were withdrawn and one was split, leaving 362 reviews to examine for the purpose of this study. Of these reviews, 254 (70%) were updated. Of these updated reviews, 23 (9%) had a change in conclusion. Both an increase in precision and a change in statistical significance of the primary outcome were predictive of a change in conclusion of the review. CONCLUSION: The concerns around a lack of updating for some reviews may not be justified considering the small proportion of updated reviews that resulted in a changed conclusion. A priority-setting approach to the updating of Cochrane systematic reviews may be more appropriate than a time-based approach. Updating all reviews as frequently as every two years may not be necessary, however some reviews may need to be updated more often than every two years

Different strategies for using topical corticosteroids in people with eczema

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To establish the effectiveness and safety of different ways of using topical corticosteroids in people with eczema

What are the main inefficiencies in trial conduct : a survey of UKCRC registered clinical trials units in the UK

BACKGROUND: The UK Clinical Research Collaboration (UKCRC) registered Clinical Trials Units (CTUs) Network aims to support high-quality, efficient and sustainable clinical trials research in the UK. To better understand the challenges in efficient trial conduct, and to help prioritise tackling these challenges, we surveyed CTU staff. The aim was to identify important inefficiencies during two key stages of the trial conduct life cycle: (i) from grant award to first participant, (ii) from first participant to reporting of final results. METHODS: Respondents were asked to list their top three inefficiencies from grant award to recruitment of the first participant, and from recruitment of the first participant to publication of results. Free text space allowed respondents to explain why they thought these were important. The survey was constructed using SurveyMonkey and circulated to the 45 registered CTUs in May 2013. Respondents were asked to name their unit and job title, but were otherwise anonymous. Free-text responses were coded into broad categories. RESULTS: There were 43 respondents from 25 CTUs. The top inefficiency between grant award and recruitment of first participant was reported as obtaining research and development (R&D) approvals by 23 respondents (53%), contracts by 22 (51%), and other approvals by 13 (30%). The top inefficiency from recruitment of first participant to publication of results was failure to meet recruitment targets, reported by 19 (44%) respondents. A common comment was that this reflected overoptimistic or inaccurate estimates of recruitment at site. Data management, including case report form design and delays in resolving data queries with sites, was reported as an important inefficiency by 11 (26%) respondents, and preparation and submission for publication by 9 (21%). CONCLUSIONS: Recommendations for improving the efficiency of trial conduct within the CTUs network include: further reducing unnecessary bureaucracy in approvals and contracting; improving training for site staff; realistic recruitment targets and appropriate feasibility; developing training across the network; improving the working relationships between chief investigators and units; encouraging funders to release sufficient funding to allow prompt recruitment of trial staff; and encouraging more research into how to improve the efficiency and quality of trial conduct

Cyclospora infection linked to travel to Mexico, June to September 2015.

Cyclospora cayetanensis was identified in 176 returned travellers from the Riviera Maya region of Mexico between 1 June and 22 September 2015; 79 in the United Kingdom (UK) and 97 in Canada. UK cases completed a food exposure questionnaire. This increase in reported Cyclospora cases highlights risks of gastrointestinal infections through travelling, limitations in Cyclospora surveillance and the need for improved hygiene in the production of food consumed in holiday resorts