Undertaking Studies Within A Trial to evaluate recruitment and retention strategies for randomised controlled trials: lessons learnt from the PROMETHEUS research programme.

Background: Randomised controlled trials ('trials') are susceptible to poor participant recruitment and retention. Studies Within A Trial are the strongest methods for testing the effectiveness of strategies to improve recruitment and retention. However, relatively few of these have been conducted. Objectives: PROMoting THE Use of Studies Within A Trial aimed to facilitate at least 25 Studies Within A Trial evaluating recruitment or retention strategies. We share our experience of delivering the PROMoting THE Use of Studies Within A Trial programme, and the lessons learnt for undertaking randomised Studies Within A Trial. Design: A network of 10 Clinical Trials Units and 1 primary care research centre committed to conducting randomised controlled Studies Within A Trial of recruitment and/or retention strategies was established. Promising recruitment and retention strategies were identified from various sources including Cochrane systematic reviews, the Study Within A Trial Repository, and existing prioritisation exercises, which were reviewed by patient and public members to create an initial priority list of seven recruitment and eight retention interventions. Host trial teams could apply for funding and receive support from the PROMoting THE Use of Studies Within A Trial team to undertake Studies Within A Trial. We also tested the feasibility of undertaking co-ordinated Studies Within A Trial, across multiple host trials simultaneously. Setting: Clinical trials unit-based trials recruiting or following up participants in any setting in the United Kingdom were eligible. Participants: Clinical trials unit-based teams undertaking trials in any clinical context in the United Kingdom. Interventions: Funding of up to £5000 and support from the PROMoting THE Use of Studies Within A Trial team to design, implement and report Studies Within A Trial. Main outcome measures: Number of host trials funded. Results: Forty-two Studies Within A Trial were funded (31 host trials), across 12 Clinical Trials Units. The mean cost of a Study Within A Trial was £3535. Twelve Studies Within A Trial tested the same strategy across multiple host trials using a co-ordinated Study Within A Trial design, and four used a factorial design. Two recruitment and five retention strategies were evaluated in more than one host trial. PROMoting THE Use of Studies Within A Trial will add 18% more Studies Within A Trial to the Cochrane systematic review of recruitment strategies, and 79% more Studies Within A Trial to the Cochrane review of retention strategies. For retention, we found that pre-notifying participants by card, letter or e-mail before sending questionnaires was effective, as was the use of pens, and sending personalised text messages to improve questionnaire response. We highlight key lessons learnt to guide others planning Studies Within A Trial, including involving patient and public involvement partners; prioritising and selecting strategies to evaluate and elements to consider when designing a Study Within A Trial; obtaining governance approvals; implementing Studies Within A Trial, including individual and co-ordinated Studies Within A Trials; and reporting Study Within A Trials. Limitations: The COVID-19 pandemic negatively impacted five Studies Within A Trial, being either delayed (n = 2) or prematurely terminated (n = 3). Conclusions: PROMoting THE Use of Studies Within A Trial significantly increased the evidence base for recruitment and retention strategies. When provided with both funding and practical support, host trial teams successfully implemented Studies Within A Trial. Future work: Future research should identify and target gaps in the evidence base, including widening Study Within A Trial uptake, undertaking more complex Studies Within A Trial and translating Study Within A Trial evidence into practice. Study registration: All Studies Within A Trial in the PROMoting THE Use of Studies Within A Trial programme had to be registered with the Northern Ireland Network for Trials Methodology Research Study Within A Trial Repository. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/55/80) and is published in full in Health Technology Assessment; Vol. 28, No. 2. See the NIHR Funding and Awards website for further award information.

A Study Within A Trial is a research study nested inside a larger 'host trial', promoting the use of Studies Within A Trial aimed to do Study Within A Trial routine practice in clinical trial units by funding and supporting at least 25 Studies Within A Trial. The best way to test health and social care treatments is to do a randomised controlled trial ('trial'), where some patients get the treatment being tested and some do not. The results of different groups are compared to see if the treatment improves care. Recruiting patients and keeping them involved in trials is often very difficult. Research teams often do not know how best to recruit and keep patients engaged as the methods have not been tested to see if they work. The best way to test these methods is by doing a Study Within A Trial. We test a programme of Studies Within A Trial for recruiting and keeping patients engaged in trials. Trial teams were able to apply for funding of up to £5000 and receive support from Promoting the use of Study Within A Trial team to do Studies Within A Trial. We used our experience of doing Studies Within A Trial to outline lessons learnt for doing Studies Within A Trial. We funded 42 Studies Within A Trial and gave teams necessary advice to do them. We significantly increased the knowledge for both recruitment and retention strategies, and found 'pre-notifying' before sending questionnaires, sending pens and personalised text messages were all effective for increasing responses by participants. We tested Studies Within A Trial across several different trials at the same time to find out more quickly whether their methods worked. We highlight key lessons learnt to guide others doing Studies Within A Trial, including involving patient partners; picking the right strategy to test; getting ethical approvals; how to do and report Studies Within A Trial. Promoting the use of studies within a trial was successful and supported more Studies Within A Trial than planned. We hope our experience will support those doing Studies Within A Trial in the future.

Intermittently scanned continuous glucose monitoring in adults with type 1 diabetes: A subgroup analysis from the FLASH-UK study.

AIMS: The FLASH-UK trial showed lower HbA1c with intermittently scanned continuous glucose monitoring (isCGM), as compared with self monitoring of blood glucose (SMBG), in adults with type 1 diabetes and HbA1c ≥58 mmol/mol (≥7.5%). Here, we present results from the pre-specified subgroup analysis for the 24-week HbA1c (primary outcome) and selected sensor-based secondary outcomes. METHODS: This was a multi-centre, parallel-design, randomised controlled trial. The difference in treatment effect between subgroups (baseline HbA1c [≤75 vs. >75 mmol/mol] [≤9.0 vs >9.0%], treatment modality [pump vs injections], prior participation in structured education, age, educational level, impaired awareness of hypoglycaemia, deprivation index quintile sex, ethnic group and Patient Health Questionnaire-9 [PHQ-9] detected depression category) were evaluated. RESULTS: One hundred fifty-six participants (females 44%, mean [SD] baseline HbA1c 71 [9] mmol/mol 8.6 [0.8%], age 44 [15]) were randomly assigned, in a 1:1 ratio to isCGM (n = 78) or SMBG (n = 78). The mean (SD) baseline HbA1c (%) was 8.7 (0.9) in the isCGM group and 8.5 (0.8) in the SMBG group, lowering to 7.9 (0.8) versus 8.3 (0.9), respectively, at 24 weeks (adjusted mean difference -0.5, 95% confidence interval [CI] -0.7 to -0.3; p < 0.001]. For HbA1c, there was no impact of treatment modality, prior participation in structured education, deprivation index quintile, sex or baseline depression category. The between-group difference in HbA1c was larger for younger people (a reduction of 2.7 [95% CI 0.3-5.0; p = 0.028] mmol/mol for every additional 15 years of age). Those with HbA1c 76-97 mmol/mol (>9.0%-11.0%) had a marginally non-significant higher reduction in HbA1c of 8.4 mmol/mol (3.3-13.5) compared to 3.1 (0.3-6.0) in those with HbA1c 58-75 mmol/mol (p = 0.08). For 'Time in range' (% 3.9-10 mmol/L), the difference was larger for those with at least a bachelor's degree. For 'Time below range' (% <3.9 mmol/L), the difference was larger for those using injections, older people and those with less than bachelor's degree. CONCLUSIONS: Intermittently scanned continuous glucose monitoring is generally effective across a range of baseline characteristics.

Estimating the cost-effectiveness of intermittently scanned continuous glucose monitoring in adults with type 1 diabetes in England.

OBJECTIVE: We previously showed that intermittently scanned continuous glucose monitoring (isCGM) reduces HbA1c at 24 weeks compared with self-monitoring of blood glucose with finger pricking (SMBG) in adults with type 1 diabetes and high HbA1c levels (58-97 mmol/mol [7.5%-11%]). We aim to assess the economic impact of isCGM compared with SMBG. METHODS: Participant-level baseline and follow-up health status (EQ-5D-5L) and within-trial healthcare resource-use data were collected. Quality-adjusted life-years (QALYs) were derived at 24 weeks, adjusting for baseline EQ-5D-5L. Participant-level costs were generated. Using the IQVIA CORE Diabetes Model, economic analysis was performed from the National Health Service perspective over a lifetime horizon, discounted at 3.5%. RESULTS: Within-trial EQ-5D-5L showed non-significant adjusted incremental QALY gain of 0.006 (95% CI: -0.007 to 0.019) for isCGM compared with SMBG and an adjusted cost increase of £548 (95% CI: 381-714) per participant. The lifetime projected incremental cost (95% CI) of isCGM was £1954 (-5108 to 8904) with an incremental QALY (95% CI) gain of 0.436 (0.195-0.652) resulting in an incremental cost-per-QALY of £4477. In all subgroups, isCGM had an incremental cost-per-QALY better than £20,000 compared with SMBG; for people with baseline HbA1c >75 mmol/mol (9.0%), it was cost-saving. Sensitivity analysis suggested that isCGM remains cost-effective if its effectiveness lasts for at least 7 years. CONCLUSION: While isCGM is associated with increased short-term costs, compared with SMBG, its benefits in lowering HbA1c will lead to sufficient long-term health-gains and cost-savings to justify costs, so long as the effect lasts into the medium term.

An Artificial Therapist (Manage Your Life Online) to Support the Mental Health of Youth: Co-Design and Case Series.

BACKGROUND: The prevalence of child and adolescent mental health issues is increasing faster than the number of services available, leading to a shortfall. Mental health chatbots are a highly scalable method to address this gap. Manage Your Life Online (MYLO) is an artificially intelligent chatbot that emulates the method of levels therapy. Method of levels is a therapy that uses curious questioning to support the sustained awareness and exploration of current problems. OBJECTIVE: This study aimed to assess the feasibility and acceptability of a co-designed interface for MYLO in young people aged 16 to 24 years with mental health problems. METHODS: An iterative co-design phase occurred over 4 months, in which feedback was elicited from a group of young people (n=7) with lived experiences of mental health issues. This resulted in the development of a progressive web application version of MYLO that could be used on mobile phones. We conducted a case series to assess the feasibility and acceptability of MYLO in 13 young people over 2 weeks. During this time, the participants tested MYLO and completed surveys including clinical outcomes and acceptability measures. We then conducted focus groups and interviews and used thematic analysis to obtain feedback on MYLO and identify recommendations for further improvements. RESULTS: Most participants were positive about their experience of using MYLO and would recommend MYLO to others. The participants enjoyed the simplicity of the interface, found it easy to use, and rated it as acceptable using the System Usability Scale. Inspection of the use data found evidence that MYLO can learn and adapt its questioning in response to user input. We found a large effect size for the decrease in participants' problem-related distress and a medium effect size for the increase in their self-reported tendency to resolve goal conflicts (the proposed mechanism of change) in the testing phase. Some patients also experienced a reliable change in their clinical outcome measures over the 2 weeks. CONCLUSIONS: We established the feasibility and acceptability of MYLO. The initial outcomes suggest that MYLO has the potential to support the mental health of young people and help them resolve their own problems. We aim to establish whether the use of MYLO leads to a meaningful reduction in participants' symptoms of depression and anxiety and whether these are maintained over time by conducting a randomized controlled evaluation trial.

Intermittently Scanned Continuous Glucose Monitoring for Type 1 Diabetes.

BACKGROUND: In persons with type 1 diabetes and high glycated hemoglobin levels, the benefits of intermittently scanned continuous glucose monitoring with optional alarms for high and low blood glucose levels are uncertain. METHODS: In a parallel-group, multicenter, randomized, controlled trial involving participants with type 1 diabetes and glycated hemoglobin levels between 7.5% and 11.0%, we investigated the efficacy of intermittently scanned continuous glucose monitoring as compared with participant monitoring of blood glucose levels with fingerstick testing. The primary outcome was the glycated hemoglobin level at 24 weeks, analyzed according to the intention-to-treat principle. Key secondary outcomes included sensor data, participant-reported outcome measures, and safety. RESULTS: A total of 156 participants were randomly assigned, in a 1:1 ratio, to undergo intermittently scanned continuous glucose monitoring (the intervention group, 78 participants) or to monitor their own blood glucose levels with fingerstick testing (the usual-care group, 78 participants). At baseline, the mean (±SD) age of the participants was 44±15 years, and the mean duration of diabetes was 21±13 years; 44% of the participants were women. The mean baseline glycated hemoglobin level was 8.7±0.9% in the intervention group and 8.5±0.8% in the usual-care group; these levels decreased to 7.9±0.8% and 8.3±0.9%, respectively, at 24 weeks (adjusted mean between-group difference, -0.5 percentage points; 95% confidence interval [CI], -0.7 to -0.3; P<0.001). The time per day that the glucose level was in the target range was 9.0 percentage points (95% CI, 4.7 to 13.3) higher or 130 minutes (95% CI, 68 to 192) longer in the intervention group than in the usual-care group, and the time spent in a hypoglycemic state (blood glucose level, <70 mg per deciliter [<3.9 mmol per liter]) was 3.0 percentage points (95% CI, 1.4 to 4.5) lower or 43 minutes (95% CI, 20 to 65) shorter in the intervention group. Two participants in the usual-care group had an episode of severe hypoglycemia, and 1 participant in the intervention group had a skin reaction to the sensor. CONCLUSIONS: Among participants with type 1 diabetes and high glycated hemoglobin levels, the use of intermittently scanned continuous glucose monitoring with optional alarms for high and low blood glucose levels resulted in significantly lower glycated hemoglobin levels than levels monitored by fingerstick testing. (Funded by Diabetes UK and others; FLASH-UK ClinicalTrials.gov number, NCT03815006.).

Delivering motivational interviewing early post stroke: standardisation of the intervention.

BACKGROUND: We applied Motivational Interviewing (MI) techniques, early after stroke, to facilitate psychological adjustment to life post-stroke. In our trial, MI-plus-usual-care increased the likelihood of normal mood at 3-months post-stroke, compared to usual-care alone. Whilst appropriate training, manuals, and supervision may increase adherence to core principles of this complex intervention, unintended variability in implementation inevitably remains. We aimed to explore the impact of variability on participant outcome. METHODS: Using our trial data (411 participants), we explored variation in MI delivery, examining: therapist characteristics (stroke care expertise/knowledge, psychology training); MI content (fidelity to MI techniques assessed with Motivational Interviewing Treatment Integrity code, describing therapist behaviours as MI-consistent, MI-neutral or MI-inconsistent); and MI dose (number/duration of sessions). RESULTS: The four MI therapists (two nurses/two psychologists) had varying expertise and MI delivery. Across therapists, mean average session duration ranged 29.5-47.8 min. The percentage of participants completing the per-protocol four sessions ranged 47%-74%. These variations were not related to participant outcome. There were uniformly high frequencies (>99%) of MI-consistent and MI-neutral interactions, and low frequencies (<1%) of MI-inconsistent interactions. CONCLUSIONS: Variation in therapist characteristics and MI dose did not affect participant outcome. These may have been tolerated due to high fidelity to MI principles.IMPLICATIONS FOR REHABILITATIONMotivational Interviewing (MI) can help reduce depression in stroke survivors when delivered early after stroke.The effectiveness of our MI intervention depends on the delivery of high quality MI; in particular, interactions with low levels of MI-inconsistency, and high global MI ratings, ideally delivered over more than one session, each lasting at least 30 minutes.Provided high quality MI is being delivered, the intervention can still have a beneficial effect on participant outcome, even with flexibility and variation in therapist characteristics, and duration and number of sessions, which may be inevitable in a clinical context.

Identification of factors associated with stillbirth in Zimbabwe - a cross sectional study.

INTRODUCTION: 98% of the 2.6 million stillbirths per annum occur in low and middle income countries. However, understanding of risk factors for stillbirth in these settings is incomplete, hampering efforts to develop effective strategies to prevent deaths. METHODS: A cross-sectional study of eligible women on the postnatal ward at Mpilo Hospital, Zimbabwe was undertaken between 01/08/2018 and 31/03/2019 (n = 1779). Data were collected from birth records for maternal characteristics, obstetric and past medical history, antenatal care and pregnancy outcome. A directed acyclic graph was constructed with multivariable logistic regression performed to fit the corresponding model specification to data comprising singleton pregnancies, excluding neonatal deaths (n = 1734), using multiple imputation for missing data. Where possible, findings were validated against all women with births recorded in the hospital birth register (n = 1847). RESULTS: Risk factors for stillbirth included: previous stillbirth (29/1691 (2%) of livebirths and 39/43 (91%) of stillbirths, adjusted Odds Ratio (aOR) 2628.9, 95% CI 342.8 to 20,163.0), antenatal care (aOR 44.49 no antenatal care vs. > 4 antenatal care visits, 95% CI 6.80 to 291.19), maternal medical complications (aOR 7.33, 95% CI 1.99 to 26.92) and season of birth (Cold season vs. Mild aOR 14.29, 95% CI 3.09 to 66.08; Hot season vs. Mild aOR 3.39, 95% CI 0.86 to 13.27). Women who had recurrent stillbirth had a lower educational and health status (18.2% had no education vs. 10.0%) and were less likely to receive antenatal care (20.5% had no antenatal care vs. 6.6%) than women without recurrent stillbirth. CONCLUSION: The increased risk in women who have a history of stillbirth is a novel finding in Low and Middle Income Countries (LMICs) and is in agreement with findings from High Income Countries (HICs), although the estimated effect size is much greater (OR in HICs ~ 5). Developing antenatal care for this group of women offers an important opportunity for stillbirth prevention.

Predictors of recognition of out of hospital cardiac arrest by emergency medical services call handlers in England: a mixed methods diagnostic accuracy study.

BACKGROUND: The aim of this study was to identify key indicator symptoms and patient factors associated with correct out of hospital cardiac arrest (OHCA) dispatch allocation. In previous studies, from 3% to 62% of OHCAs are not recognised by Emergency Medical Service call handlers, resulting in delayed arrival at scene. METHODS: Retrospective, mixed methods study including all suspected or confirmed OHCA patients transferred to one acute hospital from its associated regional Emergency Medical Service in England from 1/7/2013 to 30/6/2014. Emergency Medical Service and hospital data, including voice recordings of EMS calls, were analysed to identify predictors of recognition of OHCA by call handlers. Logistic regression was used to explore the role of the most frequently occurring (key) indicator symptoms and characteristics in predicting a correct dispatch for patients with OHCA. RESULTS: A total of 39,136 dispatches were made which resulted in transfer to the hospital within the study period, including 184 patients with OHCA. The use of the term 'Unconscious' plus one or more of symptoms 'Not breathing/Ineffective breathing/Noisy breathing' occurred in 79.8% of all OHCAs, but only 72.8% of OHCAs were correctly dispatched as such. 'Not breathing' was associated with recognition of OHCA by call handlers (Odds Ratio (OR) 3.76). The presence of key indicator symptoms 'Breathing' (OR 0.29), 'Reduced or fluctuating level of consciousness' (OR 0.24), abnormal pulse/heart rate (OR 0.26) and the characteristic 'Female patient' (OR 0.40) were associated with lack of recognition of OHCA by call handlers (p-values < 0.05). CONCLUSIONS: There is a small proportion of calls in which cardiac arrest indicators are described but the call is not dispatched as such. Stricter adherence to dispatch protocols may improve call handlers' OHCA recognition. The existing dispatch protocol would not be improved by the addition of further terms as this would be at the expense of dispatch specificity.

Repetitive task training for improving functional ability after stroke.

BACKGROUND: Repetitive task training (RTT) involves the active practice of task-specific motor activities and is a component of current therapy approaches in stroke rehabilitation. OBJECTIVES: Primary objective: To determine if RTT improves upper limb function/reach and lower limb function/balance in adults after stroke. Secondary objectives: 1) To determine the effect of RTT on secondary outcome measures including activities of daily living, global motor function, quality of life/health status and adverse events. 2) To determine the factors that could influence primary and secondary outcome measures, including the effect of 'dose' of task practice; type of task (whole therapy, mixed or single task); timing of the intervention and type of intervention. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (4 March 2016); the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 5: 1 October 2006 to 24 June 2016); MEDLINE (1 October 2006 to 8 March 2016); Embase (1 October 2006 to 8 March 2016); CINAHL (2006 to 23 June 2016); AMED (2006 to 21 June 2016) and SPORTSDiscus (2006 to 21 June 2016). SELECTION CRITERIA: Randomised/quasi-randomised trials in adults after stroke, where the intervention was an active motor sequence performed repetitively within a single training session, aimed towards a clear functional goal. DATA COLLECTION AND ANALYSIS: Two review authors independently screened abstracts, extracted data and appraised trials. We determined the quality of evidence within each study and outcome group using the Cochrane 'Risk of bias' tool and GRADE (Grades of Recommendation, Assessment, Development and Evaluation) criteria. We did not assess follow-up outcome data using GRADE. We contacted trial authors for additional information. MAIN RESULTS: We included 33 trials with 36 intervention-control pairs and 1853 participants. The risk of bias present in many studies was unclear due to poor reporting; the evidence has therefore been rated 'moderate' or 'low' when using the GRADE system. There is low-quality evidence that RTT improves arm function (standardised mean difference (SMD) 0.25, 95% confidence interval (CI) 0.01 to 0.49; 11 studies, number of participants analysed = 749), hand function (SMD 0.25, 95% CI 0.00 to 0.51; eight studies, number of participants analysed = 619), and lower limb functional measures (SMD 0.29, 95% CI 0.10 to 0.48; five trials, number of participants analysed = 419). There is moderate-quality evidence that RTT improves walking distance (mean difference (MD) 34.80, 95% CI 18.19 to 51.41; nine studies, number of participants analysed = 610) and functional ambulation (SMD 0.35, 95% CI 0.04 to 0.66; eight studies, number of participants analysed = 525). We found significant differences between groups for both upper-limb (SMD 0.92, 95% CI 0.58 to 1.26; three studies, number of participants analysed = 153) and lower-limb (SMD 0.34, 95% CI 0.16 to 0.52; eight studies, number of participants analysed = 471) outcomes up to six months post treatment but not after six months. Effects were not modified by intervention type, dosage of task practice or time since stroke for upper or lower limb. There was insufficient evidence to be certain about the risk of adverse events. AUTHORS' CONCLUSIONS: There is low- to moderate-quality evidence that RTT improves upper and lower limb function; improvements were sustained up to six months post treatment. Further research should focus on the type and amount of training, including ways of measuring the number of repetitions actually performed by participants. The definition of RTT will need revisiting prior to further updates of this review in order to ensure it remains clinically meaningful and distinguishable from other interventions.

Assessing fidelity to treatment delivery in the ICONS (Identifying Continence OptioNs after Stroke) cluster randomised feasibility trial.

BACKGROUND: The implementation of strategies to monitor and enhance treatment fidelity is of paramount importance in trials of complex interventions. A recent framework published by the National Institutes of Health Behavior Change Consortium recommends addressing five areas of treatment fidelity, one of which is delivery of treatment. This study aimed to explore fidelity to treatment delivery of the ICONS intervention (a systematic voiding programme [SVP]). This included exploring the feasibility of a method to assess fidelity to treatment delivery and collecting preliminary evidence of the level of fidelity to SVP delivery in order to inform strategies for improving fidelity in a future trial. METHODS: Delivery of treatment was recorded by nurses through completion of daily clinical logs, which included: a voiding interval, proposed voiding times and actual voiding times. The a priori method for assessment of fidelity - comparing actual voiding times with proposed voiding times - was trialled on a small amount of data. Due to errors in documentation of the voiding intervals and proposed voiding times it was not possible to assess fidelity directly as planned. A new method was devised, which included identification of 'key quality indicators'. RESULTS: This new approach to assessing fidelity used key quality indicators based upon presence of the data needed to make the comparison between proposed and actual voiding times. The proportion of clinical logs with correct documentation of voiding intervals and proposed voiding times was less than 40 %. For clinical logs with correct documentation, an actual voiding time within 30 min of the proposed voiding time was identified on approximately 55 % of occasions. CONCLUSIONS: Lessons learnt from this study have implications for the future ICONS definitive trial and for other trials of complex interventions. Implementation of a complex intervention may often deviate from what is intended. While careful consideration should be given to the best method of fidelity assessment, an iterative approach allowing flexibility to adapt pre-planned methods is recommended within feasibility trials. As fidelity to treatment delivery in the ICONS feasibility trial appeared to be relatively low, more attention to implementation strategies will be required in the definitive trial. TRIAL REGISTRATION: Identifier: ISRCTN08609907 ; date registered: 07/07/2010.

Identifying continence options after stroke (ICONS): a cluster randomised controlled feasibility trial.

BACKGROUND: Urinary incontinence (UI) affects half of patients hospitalised after stroke and is often poorly managed. Cochrane systematic reviews have shown some positive impact of conservative interventions (such as bladder training) in reducing UI, but their effectiveness has not been demonstrated with stroke patients. METHODS: We conducted a cluster randomised controlled feasibility trial of a systematic voiding programme (SVP) for the management of UI after stroke. Stroke services were randomised to receive SVP (n = 4), SVP plus supported implementation (SVP+, n = 4), or usual care (UC, n = 4).Feasibility outcomes were participant recruitment and retention. The main effectiveness outcome was presence or absence of UI at six and 12 weeks post-stroke. Additional effectiveness outcomes included were the effect of the intervention on different types of UI, continence status at discharge, UI severity, functional ability, quality of life, and death. RESULTS: It was possible to recruit patients (413; 164 SVP, 125 SVP+, and 124 UC) and participant retention was acceptable (85% and 88% at six and 12 weeks, respectively). There was no suggestion of a beneficial effect on the main outcome at six (SVP versus UC: odds ratio (OR) 0.94, 95% CI: 0.46 to 1.94; SVP+ versus UC: OR: 0.62, 95% CI: 0.28 to 1.37) or 12 weeks (SVP versus UC: OR: 1.02, 95% CI: 0.54 to 1.93; SVP+ versus UC: OR: 1.06, 95% CI: 0.54 to 2.09).No secondary outcomes showed a strong suggestion of clinically meaningful improvement in SVP and/or SVP+ arms relative to UC at six or 12 weeks. However, at 12 weeks both intervention arms had higher estimated odds of continence than UC for patients with urge incontinence. CONCLUSIONS: The trial has met feasibility outcomes of participant recruitment and retention. It was not powered to demonstrate effectiveness, but there is some evidence of a potential reduction in the odds of specific types of incontinence. A full trial should now be considered. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN08609907, date of registration: 7 July 2010.

Correlations between night eating, sleep quality, and excessive daytime sleepiness in a severely obese UK population.

OBJECTIVE: The relationships between night eating, poor sleep quality, and obesity-related comorbidity in a severely obese UK clinic population is unknown. We used validated tools to identify prevalence and to explore this relationship. METHODS: Consecutive consenting clinic attendees completed the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Score (ESS), and Night Eating Questionnaire (NEQ) to identify sleep quality, excessive daytime sleepiness (EDS) (a surrogate marker for suspected obstructive sleep apnea [OSA]), and night eating, respectively. Proportions of individuals above and below tool cutoff points were compared. Pearson product moment correlation coefficients examined relationships between total scores. RESULTS: Reported prevalence from 144 participants (mean body mass index [BMI] 46.9 [9.5] kg/m(2); age 44.6 [12.1]years; 68% women) had poor sleep quality (73.0%), suspected OSA (30.8%), and night-eating behavior (2.8%). The strongest correlation between PSQI and NEQ scores (r=0.54; P<.001) was undiminished after controlling for EDS. Although significantly correlated, PSQI and ESS scores (r=0.31; P<.001) reduced after controlling for night eating (r=0.21; P=.02). Correlation between NEQ and ESS scores (r=0.26; P=.002) was smaller and nonsignificant after controlling for sleep quality (r=0.12; P=.18). CONCLUSIONS: Poor sleep quality is common in severe obesity, though night eating is rare. The association between poor sleep quality and night eating is not influenced by the presence of EDS.

Illustrating problems faced by stroke researchers: a review of cluster-randomized controlled trials.

The cluster-randomized controlled trial is a design increasingly used in prevention and health care evaluation studies and is highly relevant to stroke research. However, there are methodological issues that make it complex to implement. These are not always fully appreciated, with reviews continuing to reveal deficiencies. We searched PUBMED and CENTRAL databases to March 31, 2011 for cluster-randomized controlled trials in stroke. Two investigators independently reviewed citations for eligibility and extracted data on key aspects of each trial. Fifteen trials met the eligibility criteria. No trial fully met CONSORT cluster-randomized controlled trial guidelines, although good design and reporting practice were usually present. Twelve trials included the term 'cluster-randomized' (or 'group-randomized') in the title, and 12 trials stated the intraclass correlation coefficient used to plan the number of clusters and cluster size. However, few provided a clear, evidence-based justification for the choice of intraclass correlation coefficient, and only two-thirds reported the intraclass correlation coefficient for primary outcomes. Several trials appeared underpowered because of problems in determining an appropriate sample size, defining appropriate clusters, and recruiting and retaining clusters and patients. Cluster-randomized controlled trials are difficult to design and perform due to the combination of methodological and practical difficulties. It is important that further improvements are made to reporting cluster-randomized trials and intraclass correlation coefficients should be estimated using a standardized approach and reported consistently; this would be beneficial for stroke researchers when designing future cluster-randomized trials.

Postal and face-to-face administration of stroke outcome measures: can mixed modes be used?

BACKGROUND AND PURPOSE: Different modes of administration are used to collect stroke outcomes, even within the same study, potentially leading to different results. We investigated the effect of administration mode (postal questionnaire; face-to-face interview) on self-reports of activities of daily living and mood. METHODS: The study was nested within a poststroke motivational interviewing trial. Activities of daily living (Barthel; Nottingham Extended) and mood (General Health Questionnaire; Yale) were collected at 3 and 12 months via postal questionnaire. Participants were approached to respond again via face-to-face interview. Paired t tests (McNemar test) and intraclass correlation coefficients (Cohen κ) were used, with 95% CI, to compare scores (items). RESULTS: Forty-four participants consented. Only Barthel scores were significantly different; they were 1.0 (95% CI, 0.5-1.6) higher face-to-face. The intraclass correlation coefficient for the Barthel was 0.90; for the other scales it was between 0.83 and 0.87. The Yale κ was 0.72. CONCLUSIONS: Modes of administration might be used interchangeably, albeit in conjunction with corrections for the Barthel.

One-lung ventilation in infants and small children: blood gas values.

PURPOSE: We investigated one-lung ventilation (OLV) in pediatric patients under 10 kg. The feasibility of OLV using either Arndt endobronchial blocker (AEB) or mainstem intubation technique is analyzed. Arterial blood gases (ABG) monitored throughout the procedures are presented. METHODS: Following IRB approval, a retrospective chart review was conducted on 9 patients ≤6 months of age and 2 patients ≥12 months of age undergoing lung resections or aortic coarctations. For right thoracotomy, a conventional, cuffed, endotracheal tube (ETT) was inserted and guided into the left mainstem bronchus with a bronchoscope and the left lung was ventilated. For left thoracotomy, an AEB was inserted into the trachea 2 cm past the vocal cords and an ETT was placed through the cords adjacent to the blockers (extraluminal). A bronchoscope was then inserted through the ETT to visualize and manipulate the blocker into the left mainstem bronchus. The blocker cuff was inflated slowly under direct vision while the ETT continued to ventilate the right, dependent lung. ABG values were collected intraoperatively in all cases. RESULTS: One-lung ventilation could be accomplished within 15 min in all cases, and lung isolation was successful in all patients. All patients were extubated within 12 h of surgery and had an uneventful recovery. ABG values revealed modest arterial acidosis and hypercarbia and mild acute ventilatory insufficiency. CONCLUSION: The use of extraluminal AEB or mainstem intubation for OLV can be successfully completed in infants weighing less than 10 kg. OLV may induce acute respiratory pathology; therefore we recommend routine intraoperative ABG monitoring for pediatric patients.

The 12-month effects of early motivational interviewing after acute stroke: a randomized controlled trial.

BACKGROUND AND PURPOSE: The purpose of this study was to determine whether motivational interviewing (MI), a patient-centered counseling technique, can benefit patients' mood and mortality poststroke. METHODS: This was a single-center, open, randomized, controlled trial. The setting was a hospital with a stroke unit. Four hundred eleven consecutive patients on the stroke register were >18 years old, not known to be moving out-of-area postdischarge, not receiving psychiatric or clinical psychology intervention, and were without severe cognitive or communication problems preventing participation in interviews. All patients received usual stroke care. Patients in the intervention group also received 4 individual, weekly sessions of MI. The primary outcome was the proportion of patients with normal mood measured by the 28-item General Health Questionnaire (normal <5; low ≥5) using a mailed questionnaire at 12 months poststroke. RESULTS: At 12-month follow-up (including imputed data), 37.7% patients in the control group and 48.0% patients in the intervention group had normal mood. Twenty-five (12.8%) of 195 patients in the control group and 13 (6.5%) of 199 patients in the intervention group had died. A significant benefit of motivational interviewing over usual stroke care was found for mood (P=0.020; OR, 1.66; 95% CI, 1.08 to 2.55) and mortality (P=0.035; OR, 2.14; 95% CI, 1.06 to 4.38). CONCLUSIONS: Results suggest that motivational interviewing improves patients' mood and reduces mortality 12 months poststroke. CLINICAL TRIAL REGISTRATION: URL: www.controlled-trials.com. Unique identifier: ISRCTN54465472.

Motivational interviewing early after acute stroke: a randomized, controlled trial.

BACKGROUND AND PURPOSE: The purpose of this study was to determine whether motivational interviewing, a patient-centered counseling technique, can benefit patients' mood 3 months after stroke. METHODS: A single-center, open, randomized, controlled trial was conducted at a single hospital with a stroke unit. Subjects consisted of 411 consecutive patients on the stroke register who were over 18 years of age and who did not have severe cognitive and communication problems that would prevent them from taking part in an interview; were not known to be moving out of the area after discharge; and were not already receiving psychiatric or clinical psychology intervention. All patients received usual stroke care. Patients in the intervention group received 4 individual, weekly sessions of motivational interviewing with a trained therapist in addition to usual stroke care. The primary outcome was the proportion of patients with normal mood at 3 months poststroke measured by the 28-item General Health Questionnaire (normal, <5; low > or=5) using a mailed questionnaire. RESULTS: Eighty-one of 207 (39.1%) patients in the control group and 100 of 204 (49.0%) patients in the intervention group had normal mood at follow up. A significant benefit of motivational interviewing over usual stroke care (OR: 1.60, 95% CI: 1.04 to 2.46, P=0.03) was found. CONCLUSIONS: Our results suggest motivational interviewing leads to an improvement in patients' mood 3 months after stroke.