Large Effectiveness Trial Research Articles

P29: Prolonged Intermittent Theta-Burst Stimulation of the Left Dorsolateral Prefrontal Cortex for Older Adults with Treatment-Resistant Depression: Effectiveness and Safety

Objective:Treatment-resistant depression (TRD) is not uncommon in older people. Brain stimulation, such as 4-6 weeks of repetitive transcranial magnetic stimulation (rTMS) or theta burst stimulation (TBS) targeting the left dorsolateral prefrontal cortex, has been evidenced as an essential intervention for adult TRD and also documented in the current international treatment guideline. In 2018, Taiwan Food and Drug Administration cleared the rTMS as a treatment option for TRD and now rTMS is still a treatment at their own expense in Taiwan. Additionally, prolonged intermittent TBS (piTBS) protocol has been proven its similar antidepressant efficacy as standard 4-6 weeks rTMS/iTBS in adult TRD, but in a shorter treatment course of 2 weeks. For older adults with depression, 4-6 weeks of treatment course may burden their caregiver due to their limited ambulation and transportation ability. However, hitherto there was no study to investigate the antidepressant efficacy of left-sided prefrontal piTBS in treating older TRD.Methods:A chart review was performed at a single Taiwan hospital from 2018 to 2020. 17-items Hamilton Depression Rating Scale (HDRS-17) was measured before and after the piTBS intervention. Maudsley Staging Method was used for the depression treatment refractoriness.Results:We identified 23 old adults with TRD (mean [SD] age, 66.0[5.2]; 78% female) who underwent 10-20 sessions of daily piTBS (1800 pulses/session; 10sessions, n=18, 15sessions,n=4, 20session,n=1). On continuous outcomes, mean(SD) HDRS-17 total scores improved from 20.5(6.62) to 11.8(7.7) after receiving piTBS intervention. The mean percent improvement of HDRS-17 was 46.0%±29.4%. Dichotomous outcomes showed response rate of 43.5% and remission rate of 34.8%. No seizures or other serious adverse events were noted, and no premature discontinuation was noted.Conclusion:This study is the largest study demonstrating the piTBS protocol provides a comparable reduction in depression symptoms in older adults with TRD, similar to the effectiveness in adult TRD and the efficacy of standard sequential bilateral rTMS/iTBS in older TRD in the FOUR-D trial. Regarding desirable efficiency and effectiveness, piTBS may be an optimal form of rTMS in treating older adults with TRD. Further large comparative effectiveness trials with standard iTBS or high-frequency rTMS in this population are warranted.

0365 The Effectiveness of Digital Cognitive Behavioral Therapy for Insomnia, Fatigue, and Quality of Life in Cancer Patients

Abstract Introduction The emotional, psychological and financial challenges of a cancer diagnosis profoundly affect patients and contribute to sleep difficulties. Insomnia affects 31%-54% of those newly diagnosed or undergoing treatment, and persists up to 5 years after treatment for cancer. Cognitive behavioral therapy (CBT) for insomnia is effective for sleep and insomnia outcomes, with no difference in outcomes for in-person or self-help CBT. Trials of digital CBT (dCBT) have recruited breast cancer survivors from Denmark and past pilot work did not identify statistically significant effects for fatigue and quality of life in US cancer survivors with insomnia. This study examined the effectiveness of a fully automated digital therapeutic (Sleepio) for improving insomnia, fatigue, and quality of life in patients with cancer from the US, UK, and Australia. Methods This is a secondary analysis of participants (n=70) with insomnia who self-reported a cancer diagnosis before randomization in a large effectiveness trial of dCBT for insomnia. Participants were randomized to receive either dCBT or a sleep hygiene education control. Insomnia (SCI-8), fatigue (FFS), and global health-related quality of life (PROMIS-10) were evaluated at baseline, 8-weeks post treatment and 24-weeks follow-up. Effect estimates are mean group differences, adjusted for baseline scores estimated using regression models. Results Digital CBT was superior to control for reducing symptoms of insomnia and fatigue at both post-treatment and follow-up (all p< 0.05). For the dCBT group, global PROMIS-10 scores were improved, although not significantly, at post-treatment (p=0.076), but were significantly higher at follow-up (p< 0.05). Conclusion Digital CBT was effective for reducing symptoms of insomnia and fatigue in patients with cancer and results were maintained after five and a half months. Significant improvements in global health-related quality of life scores at follow-up suggest effects extend beyond improvements to sleep. Findings may benefit patients with cancer as dCBT may provide scalable access to an effective treatment without contraindications. Further research is needed to understand the mechanisms and value of improving sleep in those with cancer and sleep difficulty. Support (if any) Big Health Inc.

Feasibility pilot trial for the Trajectories of Recovery after Intravenous propofol versus inhaled VolatilE anesthesia (THRIVE) pragmatic randomised controlled trial

IntroductionMillions of patients receive general anaesthesia for surgery annually. Crucial gaps in evidence exist regarding which technique, propofol total intravenous anaesthesia (TIVA) or inhaled volatile anaesthesia (INVA), yields superior patient...

Quality-adjusted life years for digital cognitive behavioural therapy for insomnia (Sleepio): a secondary analysis.

Insomnia is common, and difficulty with daytime functioning is a core symptom. Studies show cognitive behavioural therapy (CBT) improves functioning, but evidence is needed on its value for money. Quality-adjusted life years (QALYs), capturing length and quality of life, provide a standard metric by which to judge whether a treatment is worth its cost. Studies have found QALY gains with therapist-delivered and therapist-guided CBT, but most have not reached statistical significance. Estimates of QALY gains with fully automated digital CBT (dCBT) for insomnia are lacking. To assess whether dCBT (Sleepio) for insomnia is associated with gains in QALYs compared with a sleep hygiene education control. A secondary analysis of a large effectiveness trial of 1711 participants from the UK, US, and Australia. EQ-5D scores, the National Institute for Health and Care Excellence's (NICE's) preferred measure of health-related quality of life (HRQoL), were predicted (mapped) from the 10-item Patient-Reported Outcomes Measurement Information System (PROMIS-10) Global Health scores and used to determine QALYs from baseline to 24 weeks (controlled), and to 48 weeks (uncontrolled). At week 24, QALYs were significantly higher for the dCBT group, with mean QALYs 0.375 and 0.362 in the dCBT and control groups, respectively. The mean difference was 0.014 (95% confidence interval [CI] = 0.008 to 0.019), and this difference was maintained over the 48-week study period (0.026, 95% CI = 0.016 to 0.036). The difference of 0.026 QALYs is equivalent to 9.5 days in perfect health. Sleepio is associated with statistically significant gains in QALYs over time compared with control. Findings may be used to power future studies and inform cost-effectiveness analyses of automated dCBT for insomnia scaled to a population level.

Is cognitive behaviour therapy applicable to individuals diagnosed with bipolar depression or suboptimal mood stabilizer treatment: a secondary analysis of a large pragmatic effectiveness trial

BackgroundEfficacy trials of medications and/or psychological interventions for bipolar disorders (BD) aim to recruit homogenous samples of patients who are euthymic and such populations show high levels of adherence to the treatments offered. This study describes a secondary analysis of a large-scale multi-centre pragmatic effectiveness randomized controlled trial (RCT) of cognitive behaviour therapy plus treatment as usual (CBT) or treatment as usual alone (TAU) and explores outcomes in individuals who were: (i) recruited in depressive episodes, or (ii) receiving suboptimal doses of or no mood stabilizers (MS).MethodsData were extract on two separate subsamples (out of 253 RCT participants). Sample 1 comprised 67 individuals in a depressive episode (CBT: 34; TAU: 33); Sample 2 comprised 39 individuals receiving suboptimal MS treatment (CBT: 19; TAU: 20). Survival analyses (adjusted for confounding variables) were used to explore recovery in Sample 1 and relapse in Sample 2.ResultsIn Sample 1 (individuals with depression), Cox proportional hazards regression model revealed that the median time to recovery was significantly shorter in the CBT group (10 weeks; 95% confidence intervals (CI) 8, 17) compared to the TAU group (17 weeks; 95% CI 9, 30) [Adjusted Hazard Ratio (HR) 1.89; 95% CI 1.04, 3.4; p < 0.035]. In Sample 2 (suboptimal MS), the median time to any relapse was significantly longer in the CBT group compared to the TAU group (~ 35 versus ~ 20 weeks; Adjusted HR 2.01; 95% CI 1.01, 3.96; p < 0.05) with the difference in survival time to first depressive relapse also reaching statistical significance (X2 = 14.23, df 6, p 0.027).ConclusionsAdjunctive use of CBT appears to have benefits for individuals diagnosed with BD who are highly representative of the patients seen in routine clinical practice, but often excluded from efficacy RCTs. However, as this is a secondary analysis of 42% of the original RCT sample, it is important to replicate these findings in independent larger scale studies specifically designed for purpose.

Delivering language intervention at scale: promises and pitfalls

BackgroundThere is now substantial evidence that language interventions delivered to small groups can be effective for improving language skills and hence strengthening the foundation for formal schooling. However, there are remaining challenges when delivering such interventions in naturalistic environments at scale.MethodWe reflect on three randomised trials designed to evaluate the impact of an early years language programme, prior to the implementation of a large effectiveness trial, delivered in partnership with speech and language professionals. We consider findings within a framework from implementation science.ResultsWe found that, in contrast to policy‐led interventions for reading and mathematics, language interventions are not prioritised in mainstream settings. Aside from this, other obstacles to delivery were the time taken to prepare and to timetable sessions, lack of communication about the requirements of delivery and the need for language screening. Crucial to success was the support from the class teacher of teaching assistants delivering the intervention. However, feedback was largely positive from most stakeholders, and the intervention was found to have a positive impact on children's language with preliminary evidence for effects on behaviour and on reading comprehension.ConclusionsWhile many educators recognise the importance of language for communication, the benefits of oral language interventions are only recently becoming prioritised by policy‐makers. We propose that challenges to successful delivery and adoption of evidence‐based language interventions in mainstream settings can be remedied through better communication with stakeholders and collaboration between researchers and professional colleagues including senior leaders, teachers, teaching assistants, speech and language therapists and psychologists. It is imperative to take account of issues of implementation when designing an intervention and to do this successfully is a multidisciplinary enterprise.

The Natural History of Advanced Chronic Liver Disease Defined by Transient Elastography

The clinical course of cirrhosis does not follow a predictable trajectory. Transient elastography (TE) is commonly used in clinical practice to diagnose liver fibrosis and increasingly to risk stratify patients. The aim of this study was to assess the natural history of advanced chronic liver disease (ACLD) defined by TE using electronic health record (EHR) data in a multistate framework. TE data were collected between 2008 and 2019. Patients with a liver stiffness measurement (LSM) >10 kPa were included. Disease and procedure code information held in EHR was analyzed. Clinical events including decompensation, hepatocellular carcinoma (HCC), and death were identified. Outcomes were described in a multistate model using flexible parametric survival methods including LSM and the albumin bilirubin (ALBI) score. Three thousand and twenty eight patients were included. Median follow up was 3.1 years. LSM and ALBI were associated with the development of varices and decompensation, and ALBI, age, sex, and viral liver disease were associated with the development of HCC from the compensated state. The cumulative incidence of HCC before decompensation was low for patients with alcohol-related liver disease (3.8%) and nonalcoholic fatty liver disease (1.3%) at 5 years after TE. Importantly, death was predicted to occur before decompensation or HCC in most cases. Liver stiffness, ALBI score, and disease etiology are each associated with outcomes in a large contemporary cohort with ACLD. EHR data can be used to define clinical progression in these patients, facilitating large clinical effectiveness trials and cost-effectiveness analyses.

Process evaluation of the TeleClinical Care pilot study

Abstract Background A novel smartphone app-based model of care (TeleClinical Care – TCC) for patients with acute coronary syndrome (ACS) and heart failure (HF) was evaluated in a two-site, pilot randomised control trial of 164 participants in Australia. The trial demonstrated improvements in readmission rates, cardiac rehabilitation completion and medication compliance for participants in the intervention arm. Purpose A process evaluation was designed with the aims of identifying contextual factors and mechanisms that influenced the results of the trial, as well as identifying methods of improving site and participant recruitment and the delivery of the intervention, for a planned larger effectiveness trial of over 1000 patients across the state of New South Wales (TCC-Cardiac). Methods Multiple data sources were used in this mixed-methods process evaluation including interviews with four TCC team members, three general practitioners and three cardiologists. Cardiac rehabilitation completion (CR) rates, heart failure outreach service (HFOS) referrals and cardiologist follow-up appointments were audited. A patient questionnaire was also analysed for evidence of improved self-care as a mechanism of benefit of the TCC app. Results Several factors were identified that influenced the success of the trial. Rates of HFOS referral and cardiologist follow-up were high in both arms, and were not significantly different. Team members were largely positive towards their introduction into the trial, but highlighted several factors that could be optimised for the TCC-Cardiac trial, namely streamlining of the enrolment process and improving the reach of the trial, by maximising the screening of potential participants. In their interviews, the GPs and cardiologists viewed the intervention favourably in regard to potential benefit of closely monitoring, and responding to abnormalities in their patients. Several factors were suggested to be optimised prior to the commencement of TCC-Cardiac, such as additional workload and delineation of which party was responsible for alert management. Several patients commented on improved self-management as a result of TCC participation. Discussion The TCC trial was successful with the results likely influenced by high rates of follow-up from HFOS and cardiologists. Improved self-care likely drove several benefits including higher engagement with cardiac rehabilitation. The conduct and delivery TCC-Cardiac will be improved by extending recruitment to patients in non-cardiac wards, ensuring team members have adequate time (&amp;gt;15 hours per week) to optimise recruitment, establishing the responsibilities of GPs and cardiologists as part of the model and provision of summary data to them. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Prince of Wales Hospital

Implementing Attachment-Based Family Therapy for Depressed and Suicidal Adolescents and Young Adults in LGBTQ+ Services.

Background: Suicide is a serious public health problem for LGBTQ+ adolescents and young adults. Attachment-based family therapy (ABFT) is one of the few suicide treatment models that has been tested with this population. The challenge remains in how to implement ABFT into the ecology of LGBTQ+ service settings. Aims: In this study, we tested the feasibility, acceptability, and preliminary effectiveness of ABFT in LGBTQ+ community settings. Method: Ten participants were enrolled in 16 weeks of ABFT across three LGBTQ+ organizations. Feasibility (treatment completion) and acceptability (Working Alliance Inventory [WAI]; opinions about treatment [OAT]) were measured for youth and caregivers. Depression and suicide outcomes were assessed for nine participants. Results: ABFT was demonstrated to be both feasible and acceptable. All participants completed treatment, and there were no dropouts. Adolescents/young adults and their caregivers reported high WAI and adequate OAT scores throughout treatment. There was a significant decrease in suicidal ideation (β = -12.16, t(10) = -3.14, p < .01). Decreases in depression, however, were not significant (β = -1.83, t(9.11) = -0.88, p = .40). Limitations: The small sample limits our ability to estimate treatment effectiveness. A larger effectiveness trial is warranted. Conclusion: ABFT is a promising treatment for LGBTQ+ service settings.

Postoperative continuous positive airway pressure to prevent pneumonia, re-intubation, and death after major abdominal surgery (PRISM): a multicentre, open-label, randomised, phase 3 trial

Respiratory complications are an important cause of postoperative morbidity. We aimed to investigate whether continuous positive airway pressure (CPAP) administered immediately after major abdominal surgery could prevent postoperative morbidity. PRISM was an open-label, randomised, phase 3 trial done at 70 hospitals across six countries. Patients aged 50 years or older who were undergoing elective major open abdominal surgery were randomly assigned (1:1) to receive CPAP within 4 h of the end of surgery or usual postoperative care. Patients were randomly assigned using a computer-generated minimisation algorithm with inbuilt concealment. The primary outcome was a composite of pneumonia, endotracheal re-intubation, or death within 30 days after randomisation, assessed in the intention-to-treat population. Safety was assessed in all patients who received CPAP. The trial is registered with the ISRCTN registry, ISRCTN56012545. Between Feb 8, 2016, and Nov 11, 2019, 4806 patients were randomly assigned (2405 to the CPAP group and 2401 to the usual care group), of whom 4793 were included in the primary analysis (2396 in the CPAP group and 2397 in the usual care group). 195 (8·1%) of 2396 patients in the CPAP group and 197 (8·2%) of 2397 patients in the usual care group met the composite primary outcome (adjusted odds ratio 1·01 [95% CI 0·81-1·24]; p=0·95). 200 (8·9%) of 2241 patients in the CPAP group had adverse events. The most common adverse events were claustrophobia (78 [3·5%] of 2241 patients), oronasal dryness (43 [1·9%]), excessive air leak (36 [1·6%]), vomiting (26 [1·2%]), and pain (24 [1·1%]). There were two serious adverse events: one patient had significant hearing loss and one patient had obstruction of their venous catheter caused by a CPAP hood, which resulted in transient haemodynamic instability. In this large clinical effectiveness trial, CPAP did not reduce the incidence of pneumonia, endotracheal re-intubation, or death after major abdominal surgery. Although CPAP has an important role in the treatment of respiratory failure after surgery, routine use of prophylactic post-operative CPAP is not recommended. National Institute for Health Research, Barts Charity, Intersurgical, Association of Anaesthetists, and Sapienza Università di Roma.

Addressing the mental health needs of adolescents in South African communities: a protocol for a feasibility randomized controlled trial

BackgroundLike many low- and middle-income countries, almost half of the proportion of the South African population is under the age of 25. Given the peak age of onset for most mental health problems is in adolescence, it is vital that adolescents have access to mental health counselling. There are several initiatives to increase access to mental health counselling in South Africa, primarily through the integration of counselling for common mental disorders (CMD) into primary health care services, but adolescents (15–18 years of age) generally do not utilize these services. To address this gap, we will undertake a study to explore the feasibility of conducting a trial of the effectiveness of a community-based mental health counselling intervention for adolescents at-risk for a CMD.MethodsThe study is a feasibility trial of the ASPIRE intervention, a four-session blended multi-component counselling intervention adapted for South African adolescents at risk for depression and alcohol use disorders. We will enrol 100 adolescents from community settings and randomly assign them to the ASPIRE intervention or a comparison condition. Feasibility measures, such as rates of recruitment, consent to participate in the trial and retention, will be calculated. Qualitative interviews with participants and counsellors will explore the acceptability of the intervention. The primary outcomes for a subsequent trial would be reductions in symptoms of depression and days of heavy drinking which will be measured at baseline, 6 weeks, and 3 months post-randomization.DiscussionThis feasibility trial using a mixed-methods design will allow us to determine whether we can move forward to a larger effectiveness trial of the ASPIRE intervention.Trial registrationThe trial is registered with the Pan African Clinical Trials Registry (PACTR20200352214510). Registered 28 February 2020—retrospectively registered, https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=9795

Effects of the Active Choices Program on Self-Managed Physical Activity and Social Connectedness in Australian Defence Force Veterans: Protocol for a Cluster-Randomized Trial.

BackgroundA stepped-down program is one in which clients transition from the care of a health professional to self-managed care. Very little is known about the effectiveness of stepped-down physical activity (PA) programs for military service veterans.ObjectiveThis study will test Active Choices, a stepped-down behavioral support program designed to help Australian Defence Force veterans and their dependents who are clients of the Department of Veterans’ Affairs, transition from treatment by an exercise physiologist or physiotherapist to self-managed PA.MethodsThe study is a parallel-group, randomized trial, with city-based exercise physiology or physiotherapy practices that recruit eligible Department of Veterans’ Affairs clients assigned to Active Choices or a comparison program. The study aims to recruit 52 participants (26 in each group). The Active Choices program will consist of 2 face-to-face (Weeks 1, 12) and 2 telephone (Weeks 4 and 8) consultations. During these sessions, the participant and Active Choices consultant will utilize an evidence-based resource booklet to review the key benefits of an active lifestyle, build an action plan for PA preferences, set and review goals, self-monitor progress relative to set goals, and discuss strategies to overcome PA barriers. Linking participants to local PA communities to overcome social isolation will be a program priority. The comparison program will consist of 2 consultations (Weeks 1 and 12) and use fewer behavioral support strategies (education, self-monitoring, and action planning only) than Active Choices. Outcome measures will be administered at baseline, end-intervention (12 weeks), and follow-up (24 weeks) to assess changes in moderate intensity self-managed PA, psychological well-being, and social connectedness. We will also measure health service utilization and costs as well as PA choices across the intervention period. End-intervention interviews will capture participant experiences.ResultsDue to the impacts of the COVID-19 pandemic on human research activities in Australia, participant recruitment will commence when it is safe and feasible to do so.ConclusionsFindings will provide valuable pilot data to support up-scaling of the program and larger effectiveness trials with regional and rural as well as city-based Australian Defence Force veterans and their dependents.Trial RegistrationAustralian and New Zealand Clinical Trials Registry (ANZCTR): ACTRN12620000559910; https://www.anzctr.org.au/ACTRN12620000559910.aspxInternational Registered Report Identifier (IRRID)PRR1-10.2196/21911

Cost-effectiveness of out-of-hospital continuous positive airway pressure for acute respiratory failure: decision analytic modelling using data from a feasibility trial

BackgroundStandard prehospital management for Acute respiratory failure (ARF) involves controlled oxygen therapy. Continuous positive airway pressure (CPAP) is a potentially beneficial alternative treatment, however, it is uncertain whether this could improve outcomes and provide value for money. This study aimed to evaluate the cost-effectiveness of prehospital CPAP in ARF.MethodsA cost-utility economic evaluation was performed using a probabilistic decision tree model synthesising available evidence. The model consisted of a hypothetical cohort of patients in a representative ambulance service with undifferentiated ARF, receiving standard oxygen therapy or prehospital CPAP. Costs and quality adjusted life years (QALYs) were estimated using methods recommended by NICE.ResultsIn the base case analysis, using CPAP effectiveness estimates form the ACUTE trial, the mean expected costs of standard care and prehospital CPAP were £15,201 and £14,850 respectively and the corresponding mean expected QALYs were 1.190 and 1.128, respectively. The mean ICER estimated as standard oxygen therapy compared to prehospital CPAP was £5685 per QALY which indicated that standard oxygen therapy strategy was likely to be cost-effective at a threshold of £20,000 per QALY (67% probability). The scenario analysis, using effectiveness estimates from an updated meta-analysis, suggested that prehospital CPAP was more effective (mean incremental QALYs of 0.157), but also more expensive (mean incremental costs of £1522), than standard care. The mean ICER, estimated as prehospital CPAP compared to standard care, was £9712 per QALY. At the £20,000 per QALY prehospital CPAP was highly likely to be the most cost-effective strategy (94%).ConclusionsCost-effectiveness of prehospital CPAP depends upon the estimate of effectiveness. When based on a small pragmatic feasibility trial, standard oxygen therapy is cost-effective. When based on meta-analysis of heterogeneous trials, CPAP is cost-effective. Value of information analyses support commissioning of a large pragmatic effectiveness trial, providing feasibility and plausibility conditions are met.

Specific Anti-hostility Effects of Atypical Antipsychotics in Persons with Schizophrenia: From Clozapine to Cariprazine.

After participating in this activity, learners should be better able to:• Evaluate the anti-hostility effects of available atypical antipsychotic agents. In addition to hallucinations and delusions, persons with schizophrenia may exhibit hostility. In clinical trials of antipsychotics, hostility is routinely measured as part of rating scales such as the Brief Psychiatric Rating Scale or Positive and Negative Syndrome Scale. The availability of the atypical antipsychotic clozapine in 1989 led to the observation that it is possible to have a treatment effect on hostility that is independent of the treatment effect on hallucinations or delusions, and independent of general sedative effects. The data supporting this notion of a specific anti-hostility effect are the most robust for clozapine as the data include specifically designed randomized, controlled clinical trials. A specific anti-hostility effect is also observable to various degrees with most of the other atypical antipsychotics, as evidenced in post hoc analyses of clinical trials originally conducted for regulatory purposes, supplemented by post hoc analyses of large effectiveness trials. The generalizability of these studies, however, may be limited. Participants in these trials were not selected for aggressive and hostile behavior. Some of the studies also excluded patients with substance use disorders. The latter is particularly important because alcohol and substance use are well known to increase risk for hostility and aggression. Nevertheless, the repeated demonstrations of the specificity of an anti-hostility effect (in terms of statistical independence of effects on other positive symptoms and of sedation) are of potential clinical importance.

Young Adults Have Worse Outcomes Than Older Adults: Secondary Analysis of a Medication Trial for Opioid Use Disorder

PurposeYoung adults are disproportionately affected by the current opioid crisis. Although medications for opioid use disorder are broadly effective, with reductions in morbidity and mortality, the particular effectiveness of medications for opioid use disorder among young adults is less well understood. MethodsThis secondary analysis compared young adults (aged 18–25 years) with older adults (aged ≥26 years) in a large comparative effectiveness trial (“XBOT”) that randomized subjects to extended-release naltrexone or sublingual buprenorphine–naloxone for 6 months. Opioid relapse was defined by opioid use over four consecutive weeks or seven consecutive days, using urine testing and self-report. ResultsAmong subjects in the intention-to-treat sample (n = 570, all randomized participants), a main effect of age group was found, with higher relapse rates among young adults (70.3%) compared with older adults (58.2%), with an odds ratio of 1.72 (95% confidence interval = 1.08–2.70), p = .02. In the per-protocol sample (n = 474, only participants who started medication), relapse rates were higher among young adults (66.3%) compared with older adults (50.8%), with an odds ratio of 1.91 (95% confidence interval = 1.19–3.06). Among the intention-to-treat sample, survival analysis revealed a significant time-by-age group interaction (p = .01) with more relapse over time in young adults. No significant interactions between age and medication group were detected. ConclusionsYoung adults have increased rates of relapse compared with older adults, perhaps because of vulnerabilities that increase their risk for treatment dropout and medication nonadherence, regardless of medication assignment. These results suggest that specialized, developmentally informed interventions may be needed to improve retention and successful treatment of opioid use disorder among young adults.

0683 CPAP Adherence Relative To Sleep Duration And Sleep Period In Different Study Populations

Abstract Introduction CPAP is intended for use during sleep to alleviate disordered breathing. Most patients who use CPAP do so for only a portion of their sleep period, although anecdotally it is known that some also use CPAP while awake. We compared the unusually high levels of CPAP adherence found in a recent study of patients with Overlap Syndrome to a VA clinical population and to participants from the APPLES study. Methods CPAP adherence levels were taken from three sources: (1) The O2VERLAP Study, a large comparative effectiveness trial that used two different methods of providing information and support to current CPAP users diagnosed with both OSA and COPD. (2) Combined data from the four most recent clinical CPAP trials conducted at VA San Diego Healthcare System. (3) The APPLES study. Total sample sizes were 332, 957, and 405, respectively. Total sleep time (TST) and total sleep period (TSP) were assessed via the Pittsburgh Sleep Quality Index (PSQI) for (1) and (2) and via polysomnography for (3). Results Mean CPAP use, TST, and TSP for each source were: (1) 6.7, 6.8, &amp; 8.1; (2) 4.0, 6.1, &amp; 7.5; (3) 4.5, 6.6, &amp; 8.0. We examined the ratios of adherence over either TST or TSP, and the ratios for each source were: (1) 98% &amp; 83%; (2) 66% &amp; 55%; (3) 68% &amp; 56%. Conclusion This comparison demonstrates that unlike many CPAP users who tend to use therapy for only a fraction of time spent asleep, patients with COPD and OSA exhibit higher levels of adherence which often exceed sleep time and may be obtaining additional benefits from CPAP use during non-sleep periods. More research is needed both to improve CPAP delivery and support for patients who are using CPAP sub optimally and to understand the factors that account for the heightened levels of CPAP adherence in COPD. Support PPRND #1507-31666; IIR 02-275; IIR 07-163; IIR 12-069; PULM-028-12F.

0696 The O2VERLAP Study: High Cpap Use Levels Found In Overlap Syndrome (OSA And COPD) Patients

Abstract Introduction CPAP therapy is prescribed to help manage disordered breathing during sleep time periods. Most users, especially those with non-severe obstructive sleep apnea (OSA), use it only for some portion of their sleep period. Patients with Overlap Syndrome have both OSA and chronic obstructive pulmonary disease (COPD). While there has been some research on CPAP use levels in this patient population, there has been little indication that they use CPAP any differently than those with OSA only. Methods The O2VERLAP Study was a large comparative effectiveness trial enrolling people with COPD and OSA and using two different methods of providing information and support to current users of CPAP therapy. The study utilized an electronic national recruitment strategy and 332 participants were enrolled. CPAP data from the 12-week study period was analyzed. The Pittsburgh Sleep Quality Index was used to determine both estimated total sleep period (TSP) and total sleep time (TST). Because participants were all current users of CPAP, data from the total sample was combined and used. The percentage of TST and TSP that CPAP was used was calculated as CPAP use divided by either TST or TSP. Results The mean TST was 6.8 hours, TSP was 8.1 hours, and CPAP use was 6.7 hours. CPAP was used during 98.5% of the TST and during 82.7% of the TSP. Over 35% of the sample used CPAP at a level that was equal to or greater than their total sleep period. Conclusion Most OSA study populations use CPAP for some fraction of their night’s sleep. This COPD/OSA study population used CPAP to a markedly high level, including over one-third of the sample (n=~100) who used CPAP more than their self-reported sleep period. Further research on the extent and reasons for non-sleep period (i.e., daytime) CPAP use in COPD patients is warranted. Support PPRND #1507-31666.

Understanding and managing pelvic girdle pain from a person-centred biopsychosocial perspective

IntroductionClinicians need support to effectively implement a biopsychosocial approach to people with pelvic girdle pain disorders. PurposeA practical clinical framework aligned with a contemporary biopsychosocial approach is provided to help guide clinician's management of pelvic girdle pain. This approach is consistent with current pain science which helps to explain potential mechanistic links with co/multi-morbid conditions related to pelvic girdle pain. Further, this approach also aligns with the Common-Sense Model of Illness and provides insight into how an individual's illness perceptions can influence their emotional and behavioural response to their pain disorder. Communication is critical to supporting recovery and facilitating behaviour change within the biopsychosocial context and in this context, the patient interview is central to exploring the multidimensional nature of a persons' presentation. Focusing the biopsychosocial framework on targeted cognitive-functional therapy as a key component of care can help an individual with pelvic girdle pain make sense of their pain, build confidence and self-efficacy and facilitate positive behaviour and lifestyle change. There is growing evidence of the efficacy for this broader integrative approach, although large scale effectiveness trials are still needed. An in-depth case study provides guidance for clinicians, showing ‘how to’ implement these concepts into their own practice within a coherent practical framework. ImplicationsThis framework can give clinicians more confidence in understanding and managing pelvic girdle pain. The framework provides practical strategies to assist clinicians with implementation; assisting the transition from knowing to doing in an evidence-informed manner that resonates with real world practice.

Collaborative care model for treatment of persistent symptoms after concussion among youth (CARE4PCS-II): Study protocol for a randomized, controlled trial

BackgroundCurrently, there is limited evidence to guide intervention and service delivery coordination for youth who suffer a concussion and subsequently experience persistent post-concussive symptoms (PCS) (Lumba-Brown et al. JAMA Pediatr 172(11):e182853, 2018; Lumba-Brown A et al. JAMA Pediatr 172(11):e182847, 2018). We have developed a collaborative care intervention with embedded cognitive-behavioral therapy, care management, and stepped-up psychotropic medication consultation to address persistent PCS and related psychological comorbidities. The CARE4PCS-II study was designed to assess whether adolescents with persistent symptoms after sports-related concussion will demonstrate better outcomes when receiving this collaborative care intervention compared to a usual care (control) condition.Methods/designThis investigation is a randomized comparative effectiveness trial to receive intervention (collaborative care) or control (usual care). Two hundred sports-injured male and female adolescents aged 11–18 years with three or more post-concussive symptoms that persist for at least 1 month but less than 9 months after injury will be recruited and randomized into the study. The trial focuses on the effects of the intervention on post-concussive, depressive, and anxiety symptoms measured 3, 6, and 12 months after baseline.DiscussionThe CARE4PCS II study is a large comparative effectiveness trial targeting symptomatic improvements in sports injured adolescents after concussion. The study is unique in its adaptation of the collaborative care model to a broad spectrum of primary care, sports medicine, and school settings. The investigation incorporates novel elements such as the delivery of CBT through HIPAA complaint video conferenceing technology and has excellent widespread dissemination potential should effectiveness be demonstrated.Trial registrationClinicalTrials.gov, NCT03034720. Registered on January 27, 2017.

Controlling faecal incontinence in women by performing anal exercises with biofeedback or loperamide: a randomised clinical trial

Well designed, large comparative effectiveness trials assessing the efficacy of primary interventions for faecal incontinence are few in number. The objectives of this study were to compare different combinations of anorectal manometry-assisted biofeedback, loperamide, education, and oral placebo. In this randomised factorial trial, participants were recruited from eight clinical sites in the USA. Women with at least one episode of faecal incontinence per month in the past 3 months were randomly assigned 0·5:1:1:1 to one of four groups: oral placebo plus education only, placebo plus anorectal manometry-assisted biofeedback, loperamide plus education only, and loperamide plus anorectal manometry-assisted biofeedback. Participants received 2 mg per day of loperamide or oral placebo with the option of dose escalation or reduction. Women assigned to biofeedback received six visits, including strength and sensory biofeedback training. All participants received a standardised faecal incontinence patient education pamphlet and were followed for 24 weeks after starting treatment. The primary endpoint was change in St Mark's (Vaizey) faecal incontinence severity score between baseline and 24 weeks, analysed by intention-to-treat using general linear mixed modelling. Investigators, interviewers, and outcome evaluators were masked to biofeedback assignment. Participants and all study staff other than the research pharmacist were masked to medication assignment. Randomisation took place within the electronic data capture system, was stratified by site using randomly permuted blocks (block size 7), and the sizes of the blocks and the allocation sequence were known only to the data coordinating centre. This trial is registered with ClinicalTrials.gov, number NCT02008565. Between April 1, 2014, and Sept 30, 2015, 377 women were enrolled, of whom 300 were randomly assigned to placebo plus education (n=42), placebo plus biofeedback (n=84), loperamide plus education (n=88), and the combined intervention of loperamide plus biofeedback (n=86). At 24 weeks, there were no differences between loperamide versus placebo (model estimated score change -1·5 points, 95% CI -3·4 to 0·4, p=0·12), biofeedback versus education (-0·7 points, -2·6 to 1·2, p=0·47), and loperamide and biofeedback versus placebo and biofeedback (-1·9 points, -4·1 to 0·3, p=0·092) or versus loperamide plus education (-1·1 points, -3·4 to 1·1, p=0·33). Constipation was the most common grade 3 or higher adverse event and was reported by two (2%) of 86 participants in the loperamide and biofeedback group and two (2%) of 88 in the loperamide plus education group. The percentage of participants with any serious adverse events did not differ between the treatment groups. Only one serious adverse event was considered related to treatment (small bowel obstruction in the placebo and biofeedback group). In women with normal stool consistency and faecal incontinence bothersome enough to seek treatment, we were unable to find evidence against the null hypotheses that loperamide is equivalent to placebo, that anal exercises with biofeedback is equivalent to an educational pamphlet, and that loperamide and biofeedback are equivalent to oral placebo and biofeedback or loperamide plus an educational pamphlet. Because these are common first-line treatments for faecal incontinence, clinicians could consider combining loperamide, anal manometry-assisted biofeedback, and a standard educational pamphlet, but this is likely to result in only negligible improvement over individual therapies and patients should be counselled regarding possible constipation. Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health Office of Research on Women's Health.