Causal and Associational Language in Observational Health Research: A Systematic Evaluation.

We estimated the degree to which language used in the high-profile medical/public health/epidemiology literature implied causality using language linking exposures to outcomes and action recommendations; examined disconnects between language and recommendations; identified the most common linking phrases; and estimated how strongly linking phrases imply causality. We searched for and screened 1,170 articles from 18 high-profile journals (65 per journal) published from 2010-2019. Based on written framing and systematic guidance, 3 reviewers rated the degree of causality implied in abstracts and full text for exposure/outcome linking language and action recommendations. Reviewers rated the causal implication of exposure/outcome linking language as none (no causal implication) in 13.8%, weak in 34.2%, moderate in 33.2%, and strong in 18.7% of abstracts. The implied causality of action recommendations was higher than the implied causality of linking sentences for 44.5% or commensurate for 40.3% of articles. The most common linking word in abstracts was "associate" (45.7%). Reviewers' ratings of linking word roots were highly heterogeneous; over half of reviewers rated "association" as having at least some causal implication. This research undercuts the assumption that avoiding "causal" words leads to clarity of interpretation in medical research.

The effectiveness of digital interventions for increasing physical activity in individuals of low socioeconomic status: a systematic review and meta-analysis.

BACKGROUND: Digital technologies such as wearables, websites and mobile applications are increasingly used in interventions targeting physical activity (PA). Increasing access to such technologies makes an attractive prospect for helping individuals of low socioeconomic status (SES) in becoming more active and healthier. However, little is known about their effectiveness in such populations. The aim of this systematic review was to explore whether digital interventions were effective in promoting PA in low SES populations, whether interventions are of equal benefit to higher SES individuals and whether the number or type of behaviour change techniques (BCTs) used in digital PA interventions was associated with intervention effects. METHODS: A systematic search strategy was used to identify eligible studies from MEDLINE, Embase, PsycINFO, Web of Science, Scopus and The Cochrane Library, published between January 1990 and March 2020. Randomised controlled trials, using digital technology as the primary intervention tool, and a control group that did not receive any digital technology-based intervention were included, provided they had a measure of PA as an outcome. Lastly, studies that did not have any measure of SES were excluded from the review. Risk of Bias was assessed using the Cochrane Risk of Bias tool version 2. RESULTS: Of the 14,589 records initially identified, 19 studies were included in the final meta-analysis. Using random-effects models, in low SES there was a standardised mean difference (SMD (95%CI)) in PA between intervention and control groups of 0.06 (- 0.08,0.20). In high SES the SMD was 0.34 (0.22,0.45). Heterogeneity was modest in both low (I2 = 0.18) and high (I2 = 0) SES groups. The studies used a range of digital technologies and BCTs in their interventions, but the main findings were consistent across all of the sub-group analyses (digital interventions with a PA only focus, country, chronic disease, and duration of intervention) and there was no association with the number or type of BCTs. DISCUSSION: Digital interventions targeting PA do not show equivalent efficacy for people of low and high SES. For people of low SES, there is no evidence that digital PA interventions are effective, irrespective of the behaviour change techniques used. In contrast, the same interventions in high SES participants do indicate effectiveness. To reduce inequalities and improve effectiveness, future development of digital interventions aimed at improving PA must make more effort to meet the needs of low SES people within the target population.

Antibiotic Prescribing for Acute Respiratory Tract Infections 12 Months After Communication and CRP Training: A Randomized Trial.

PURPOSE: C-reactive-protein (CRP) is useful for diagnosis of lower respiratory tract infections (RTIs). A large international trial documented that Internet-based training in CRP point-of-care testing, in enhanced communication skills, or both reduced antibiotic prescribing at 3 months, with risk ratios (RRs) of 0.68, 0.53, 0.38, respectively. We report the longer-term impact in this trial. METHODS: A total of 246 general practices in 6 countries were cluster-randomized to usual care, Internet-based training on CRP point-of-care testing, Internet-based training on enhanced communication skills and interactive booklet, or both interventions combined. The main outcome was antibiotic prescribing for RTIs after 12 months. RESULTS: Of 228 practices providing 3-month data, 74% provided 12-month data, with no demonstrable attrition bias. Between 3 months and 12 months, prescribing for RTIs decreased with usual care (from 58% to 51%), but increased with CRP training (from 35% to 43%) and with both interventions combined (from 32% to 45%); at 12 months, the adjusted RRs compared with usual care were 0.75 (95% CI, 0.51-1.00) and 0.70 (95% CI, 0.49-0.93), respectively. Between 3 months and 12 months, the reduction in prescribing with communication training was maintained (41% and 40%, with an RR at 12 months of 0.70 [95% CI, 0.49-0.94]). Although materials were provided for free, clinicians seldom used booklets and rarely used CRP point-of-care testing. Communication training, but not CRP training, remained efficacious for reducing prescribing for lower RTIs (RR = 0.7195% CI, 0.45-0.99, and RR = 0.76; 95% CI, 0.47-1.06, respectively), whereas both remained efficacious for reducing prescribing for upper RTIs (RR = 0.60; 95% CI, 0.37-0.94, and RR = 0.58; 95% CI, 0.36-0.92, respectively). CONCLUSIONS: Internet-based training in enhanced communication skills remains effective in the longer term for reducing antibiotic prescribing. The early improvement seen with CRP training wanes, and this training becomes ineffective for lower RTIs, the only current indication for using CRP testing.

Acceptability and Feasibility of Implementing Accelorometry-Based Activity Monitors and a Linked Web Portal in an Exercise Referral Scheme: Feasibility Randomized Controlled Trial.

BACKGROUND: Exercise referral schemes (ERSs) are recommended for patients with health conditions or risk factors. Evidence points to the initial effectiveness and cost-effectiveness of such schemes for increasing physical activity, but effects often diminish over time. Techniques such as goal setting, self-monitoring, and personalized feedback may support motivation for physical activity and maintenance of effects. Wearable technologies could provide an opportunity to integrate motivational techniques into exercise schemes. However, little is known about acceptability to exercise referral populations or implementation feasibility within exercise referral services. OBJECTIVE: To determine the feasibility and acceptability of implementing an activity-monitoring device within the Welsh National ERS to inform a decision on whether and how to proceed to an effectiveness trial. METHODS: We conducted a feasability randomized controlled trial with embedded mixed-methods process evaluation and an exploratory economic analysis. Adults (N=156) were randomized to intervention (plus usual practice; n=88) or usual practice only (n=68). Usual practice was a 16-week structured exercise program. The intervention group additionally received an accelerometry-based activity monitor (MyWellnessKey) and associated Web platform (MyWellnessCloud). The primary outcomes were predefined progression criteria assessing acceptability and feasibility of the intervention and proposed evaluation. Postal questionnaires were completed at baseline (time 0:T0), 16 weeks (T1), and 12 months after T0 (T2). Routine data were accessed at the same time-points. A subsample of intervention participants and scheme staff were interviewed following the initiation of intervention delivery and at T2. RESULTS: Participants were on average aged 56.6 (SD 16.3) years and mostly female (101/156, 64.7%) and white (150/156, 96.2%). Only 2 of 5 progression criteria were met; recruitment and randomization methods were acceptable to participants, and contamination was low. However, recruitment and retention rates (11.3% and 67.3%, respectively) fell substantially short of target criteria (20% and 80%, respectively), and disproportionally recruited from the least deprived quintile. Only 57.4% of intervention participants reported receipt of the intervention (below the 80% progression threshold). Less than half reported the intervention to be acceptable at T2. Participant and staff interviews revealed barriers to intervention delivery and engagement related to the device design as well as context-specific technological challenges, all of which made it difficult to integrate the technology into the service. Routinely collected health economic measures had substantial missing data, suggesting that other methods for collecting these should be used in future. CONCLUSIONS: To our knowledge, this is the first study to evaluate short- and long-term feasibility and acceptability of integrating wearable technologies into community-based ERSs. The findings highlight device- and context-specific barriers to doing this in routine practice, with typical exercise referral populations. Key criteria for progression to a full-scale evaluation were not met. TRIAL REGISTRATION: ISRCTN Registry ISRCTN85785652; http://www.isrctn.com/ISRCTN85785652.

Pragmatic RAndomised controlled trial of a trauma-focused guided self-help Programme versus InDividual trauma-focused cognitive Behavioural therapy for post-traumatic stress disorder (RAPID): trial protocol.

BACKGROUND: There is good evidence that trauma-focused therapies for Post-Traumatic Stress Disorder are effective. However, they are not always feasible to deliver due a shortage of trained therapists and demands on the patient. An online trauma-focused Guided Self-Help (GSH) programme which could overcome these barriers has shown promise in a pilot study. This study will be the first to evaluate GSH against standard face-to-face therapy to assess its suitability for use in the NHS. METHODS: The study is a large-scale multi-centre pragmatic randomised controlled non-inferiority trial, with assessors masked to treatment allocation. One hundred and ninety-two participants will be randomly allocated to receive either face-to-face trauma-focused cognitive behaviour therapy (TFCBT) or trauma-focused online guided self-help (GSH). The primary outcome will be the severity of symptoms of PTSD over the previous week as measured by the Clinician Administered PTSD Scale for DSM5 (CAPS-5) at 16 weeks post-randomisation. Secondary outcome measures include PTSD symptoms over the previous month as measured by the CAPS-5 at 52 weeks plus the Impact of Event Scale - revised (IES-R), Work and Social Adjustment Scale (WSAS), Patient Health Questionnaire-9 (PHQ-9), General Anxiety Disorder-7 (GAD-7), Alcohol Use Disorders Test (AUDIT-O), Multidimensional Scale for Perceived Social Support (MSPSS), short Post-Traumatic Cognitions Inventory (PTCI), Insomnia Severity Index (ISI) and General Self Efficacy Scale (GSES) measured at 16 and 52 weeks post-randomisation. Changes in health-related quality of life will be measured by the EQ-5D and the level of healthcare resource utilisation for health economic analysis will be determined by an amended version of the Client Socio-Demographic and Service Receipt Inventory European Version. The Client Satisfaction Questionnaire (CSQ) will be collected at 16 weeks post-randomisation to evaluate treatment satisfaction. DISCUSSION: This study will be the first to compare online GSH with usual face-to-face therapy for PTSD. The strengths are that it will test a rigorously developed intervention in a real world setting to inform NHS commissioning. The potential challenges of delivering such a pragmatic study may include participant recruitment, retention and adherence, therapist retention, and fidelity of intervention delivery. TRIAL REGISTRATION: ISRCTN13697710 registered on 20/12/2016.

Prevalence and correlates of resistance training skill competence in adolescents.

The aim of this study is to examine the prevalence and correlates of adolescents' resistance training (RT) skill competence. Participants were 548 adolescents (14.1 ± 0.5 years) from 16 schools in New South Wales, Australia. RT skills were assessed using the Resistance Training Skills Battery. Demographics, BMI, muscular fitness, perceived strength, RT self-efficacy, and motivation for RT were also assessed. The proportion demonstrating "competence" and "near competence" in each of the six RT skills were calculated and sex differences explored. Associations between the combined RT skill score and potential correlates were examined using multi-level linear mixed models. Overall, the prevalence of competence was low (range = 3.3% to 27.9%). Females outperformed males on the squat, lunge and overhead press, whereas males performed better on the push-up (p < .05). Significant associations were seen for a number of correlates, which largely differed by sex. Muscular fitness was moderately and positively associated with RT skills among both males (ß = 0.34, 95%CIs = 0.23 to 0.46) and females (ß = 0.36, 95%CIs = 0.23 to 0.48). Our findings support a link between RT skills and muscular fitness. Other associations were statistically significant but small in magnitude, and should therefore be interpreted cautiously.

Development and Delivery of a Physical Activity Intervention for People With Huntington Disease: Facilitating Translation to Clinical Practice.

BACKGROUND AND PURPOSE: We studied the development and delivery of a 14-week complex physical activity intervention for people with Huntington disease, where detailed information about the intervention was fully embedded in the trial design process. METHODS: Intervention Development: The intervention was developed through a series of focus groups. The findings from the focus groups informed the development of a logic model for the physical activity intervention that was broadly consistent with the framework of self-determination theory. Intervention Delivery: Key components underpinning the delivery of the intervention were implemented including a defined coach training program and intervention fidelity assessment methods. Training of coaches (physical therapists, occupational therapists, research nurses, and exercise trainers) was delivered via group and 1:1 training sessions using a detailed coach's manual, and with ongoing support via video calls, and e-mail communication as needed. Detailed documentation was provided to determine costs of intervention development and coach training. RESULTS: Intervention delivery coaches at 8 sites across the United Kingdom participated in the face-to-face training. Self-report checklists completed by each of the coaches indicated that all components of the intervention were delivered in accordance with the protocol. Mean (standard deviation) intervention fidelity scores (n = 15), as measured using a purpose-developed rating scale, was 11 (2.4) (out of 16 possible points). Coaches' perceptions of intervention fidelity were similarly high. The total cost of developing the intervention and providing training was £30,773 ($47,042 USD). DISCUSSION AND CONCLUSIONS: An important consideration in promoting translation of clinical research into practice is the ability to convey the detailed components of how the intervention was delivered to facilitate replication if the results are favorable. This report presents an illustrative example of a physical activity intervention, including the development and the training required to deliver it. This approach has the potential to facilitate reproducibility, evidence synthesis, and implementation in clinical practice.Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A122).

Oral fumaric acid esters for psoriasis.

BACKGROUND: Psoriasis is a chronic inflammatory skin condition that can markedly reduce life quality. Several systemic therapies exist for moderate to severe psoriasis, including oral fumaric acid esters (FAE). These contain dimethyl fumarate (DMF), the main active ingredient, and monoethyl fumarate. FAE are licensed for psoriasis in Germany but used off-licence in many countries. OBJECTIVES: To assess the effects and safety of oral fumaric acid esters for psoriasis. SEARCH METHODS: We searched the following databases up to 7 May 2015: the Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library (Issue 4, 2015), MEDLINE (from 1946), EMBASE (from 1974), and LILACS (from 1982). We searched five trials registers and checked the reference lists of included and excluded studies for further references to relevant randomised controlled trials. We handsearched six conference proceedings that were not already included in the Cochrane Skin Group Specialised Register. SELECTION CRITERIA: Randomised controlled trials (RCTs) of FAE, including DMF monotherapy, in individuals of any age and sex with a clinical diagnosis of psoriasis. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. Primary outcomes were improvement in Psoriasis Area and Severity Index (PASI) score and the proportion of participants discontinuing treatment due to adverse effects. MAIN RESULTS: We included 6 studies (2 full reports, 2 abstracts, 1 brief communication, and 1 letter), with a total of 544 participants. Risk of bias was unclear in several studies because of insufficient reporting. Five studies compared FAE with placebo, and one study compared FAE with methotrexate. All studies reported data at 12 to 16 weeks, and we identified no longer-term studies. When FAE were compared with placebo, we could not perform meta-analysis for the primary outcome of PASI score because the three studies that assessed this outcome reported the data differently, although all studies reported a significant reduction in PASI scores with FAE. Only 1 small study designed for psoriatic arthritis reported on the other primary outcome of participants discontinuing treatment due to adverse effects (2 of 13 participants on FAE compared with none of the 14 participants on placebo; risk ratio (RR) 5.36, 95% confidence interval (CI) 0.28 to 102.1; 27 participants; very low-quality evidence). However, these findings are uncertain due to indirectness and a very wide confidence interval. Two studies, containing 247 participants and both only reported as abstracts, allowed meta-analysis for PASI 50, which showed superiority of FAE over placebo (RR 4.55, 95% CI 2.80 to 7.40; low-quality evidence), with a combined PASI 50 of 64% in those given FAE compared with a PASI 50 of 14% for those on placebo, representing a number needed to treat to benefit of 2. The same studies reported more participants achieving PASI 75 with FAE, but we did not pool the data because of significant heterogeneity; none of the studies measured PASI 90. One study reported significant improvement in participants' quality of life (QoL) with FAE, measured with Skindex-29. However, we could not compute the mean difference because of insufficient reporting in the abstract. More participants experienced adverse effects, mainly gastrointestinal disturbance and flushing, on FAE (RR 4.72, 95% CI 2.45 to 9.08; 1 study, 99 participants; moderate-quality evidence), affecting 76% of participants given FAE and 16% of the placebo group (representing a number needed to treat to harm of 2). The other studies reported similar findings or did not report adverse effects fully.One study of 54 participants compared methotrexate (MTX) with FAE. PASI score at follow-up showed superiority of MTX (mean Difference (MD) 3.80, 95% CI 0.68 to 6.92; 51 participants; very low-quality evidence), but the difference was not significant after adjustment for baseline disease severity. The difference between groups for the proportion of participants who discontinued treatment due to adverse effects was uncertain because of imprecision (RR 0.19, 95% CI 0.02 to 1.53; 1 study, 51 participants; very low-quality evidence). Overall, the number of participants experiencing common nuisance adverse effects was not significantly different between the 2 groups, with 89% of the FAE group affected compared with 100% of the MTX group (RR 0.89, 95% CI 0.77 to 1.03; 54 participants; very low-quality evidence). Flushing was more frequent in those on FAE, with 13 out of 27 participants affected compared with 2 out of 27 given MTX. There was no significant difference in the number of participants who attained PASI 50, 75, and 90 in the 2 groups (very low-quality evidence) whereas this study did not measure the effect of treatments on QoL. The included studies reported no serious adverse effects of FAE and were too small and of limited duration to provide evidence about rare or delayed effects. AUTHORS' CONCLUSIONS: Evidence suggests that FAE are superior to placebo and possibly similar in efficacy to MTX for psoriasis; however, the evidence provided in this review was limited, and it must be noted that four out of six included studies were abstracts or brief reports, restricting study reporting. FAE are associated with nuisance adverse effects, including flushing and gastrointestinal disturbance, but short-term studies reported no serious adverse effects.

Socio-economic inequalities in the breadth of internet use before and during the COVID-19 pandemic among older adults in England.

Understanding digital exclusion in older adults during the COVID-19 pandemic could help tailor responses to future outbreaks. This cohort study used data from older adults aged 60+ years in England who participated in wave nine (2018/2019) of the main English Longitudinal Study of Ageing (ELSA) survey, and/or wave one of the ELSA COVID-19 sub-study (June/July 2020). Using latent class analysis and latent transition analysis, we aimed to identify distinct subgroups of older adults characterised by different patterns of internet use pre- and intra-pandemic, explore the extent to which individuals remained in the same subgroup or transitioned to a different subgroup during the COVID-19 pandemic, and examine longitudinal associations of socio-economic factors (education, occupational class, and wealth) with latent class membership. Preliminary tests showed that the types of internet activities differed between men and women; therefore, subsequent analyses were stratified by biological sex. Three clusters (low, medium, and high) were identified in male participants at both timepoints. Among female participants, three clusters were distinguished pre-pandemic and two (low versus high) during the pandemic. The latent classes were characterised by participants' breadth of internet use. Higher education, occupational class, and wealth were associated with greater odds of membership in the medium and/or high classes, versus the low class, in men and women. A high degree of stability in latent class membership was observed over time. However, men experienced a stark decrease in online health information-seeking. Our results highlight that inequality regarding the range of functional and social opportunities provided by the internet prevailed during the pandemic. Policymakers should ensure that digital access and upskilling initiatives are equitable for all.

Borderline personality traits are differently associated with postpartum psychosis and postpartum depression episodes in women with bipolar disorder.

BACKGROUND: Women with bipolar disorder have approximately 40 %-50 % chance of having a perinatal bipolar recurrence. Knowing the factors associated will be beneficial for the prediction and prevention of episodes. We aim to establish if borderline personality disorder traits, as measured by the BEST (Borderline Evaluation of Severity over Time) scale, are associated with perinatal psychiatric outcomes. METHODS: We recruited women with bipolar disorder as part of the BDRN (Bipolar Disorder Research Network) study. Women were interviewed and we collected their demographic and clinical information. Participants subsequently completed the BEST questionnaire. We analysed the association of BEST scores with lifetime presence/absence of perinatal bipolar relapse and, employing multinomial logistic regression, with different subtypes of perinatal outcomes: postpartum psychosis; postpartum depression, and other episodes. RESULTS: In our sample of 807, although there was no significant association between the BEST total score and perinatal episodes as a whole (adjustedOR 1.01 CI95% [0.99, 1.03], p = 0.204), we found significant differing associations with different subtypes of episodes. Women scoring highly on BEST were less likely to experience a postpartum psychotic episode (RRR 0.96 CI95% [0.94, 0.99], p = 0.005) but more likely to experience a non-psychotic depressive episode (RRR 1.03 CI95% [1.01, 1.05], p = 0.007) than no relapse. LIMITATIONS: This study is limited by its cross-sectional design and self-report nature of BEST. CONCLUSIONS: In women with bipolar disorder, borderline traits differentiate the risk of postpartum depression and postpartum psychosis, emphasise the importance of considering risk factors for these perinatal episodes separately, and may help individualise the risk for women in the perinatal period.

Exploring the effect of case management in homelessness per components: A systematic review of effectiveness and implementation, with meta-analysis and thematic synthesis.

Background: Adequate housing is a basic human right. The many millions of people experiencing homelessness (PEH) have a lower life expectancy and more physical and mental health problems. Practical and effective interventions to provide appropriate housing are a public health priority. Objectives: To summarise the best available evidence relating to the components of case-management interventions for PEH via a mixed methods review that explored both the effectiveness of interventions and factors that may influence its impact. Search Methods: We searched 10 bibliographic databases from 1990 to March 2021. We also included studies from Campbell Collaboration Evidence and Gap Maps and searched 28 web sites. Reference lists of included papers and systematic reviews were examined and experts contacted for additional studies. Selection Criteria: We included all randomised and non-randomised study designs exploring case management interventions where a comparison group was used. The primary outcome of interest was homelessness. Secondary outcomes included health, wellbeing, employment and costs. We also included all studies where data were collected on views and experiences that may impact on implementation. Data Collection and Analysis: We assessed risk of bias using tools developed by the Campbell Collaboration. We conducted meta-analyses of the intervention studies where possible and carried out a framework synthesis of a set of implementation studies identified by purposive sampling to represent the most 'rich' and 'thick' data. Main Results: We included 64 intervention studies and 41 implementation studies. The evidence base was dominated by studies from the USA and Canada. Participants were largely (though not exclusively) people who were literally homeless, that is, living on the streets or in shelters, and who had additional support needs. Many studies were assessed as having a medium or high risk of bias. However, there was some consistency in outcomes across studies that improved confidence in the main findings. Case Management and Housing Outcomes: Case management of any description was superior to usual care for homelessness outcomes (standardised mean difference [SMD] = -0.51 [95% confidence interval [CI]: -0.71, -0.30]; p < 0.01). For studies included in the meta-analyses, Housing First had the largest observed impact, followed by Assertive Community Treatment, Critical Time Intervention and Intensive Case Management. The only statistically significant difference was between Housing First and Intensive Case Management (SMD = -0.6 [-1.1, -0.1]; p = 0.03) at ≥12 months. There was not enough evidence to compare the above approaches with standard case management within the meta-analyses. A narrative comparison across all studies was inconclusive, though suggestive of a trend in favour of more intensive approaches. Case Management and Mental Health Outcomes: The overall evidence suggested that case management of any description was not more or less effective compared to usual care for an individual's mental health (SMD = 0.02 [-0.15, 0.18]; p = 0.817). Case Management and Other Outcomes: Based on meta-analyses, case management was superior to usual care for capability and wellbeing outcomes up to 1 year (an improvement of around one-third of an SMD; p < 0.01) but was not statistically significantly different for substance use outcomes, physical health, and employment. Case Management Components: For homelessness outcomes, there was a non-significant trend for benefits to be greater in the medium term (≤3 years) compared to long term (>3 years) (SMD = -0.64 [-1.04, -0.24] vs. -0.27 [-0.53, 0]; p = 0.16) and for in-person meetings in comparison to mixed (in-person and remote) approaches (SMD = -0.73 [-1.25,-0.21]) versus -0.26 [-0.5,-0.02]; p = 0.13). There was no evidence from meta-analyses to suggest that an individual case manager led to better outcomes then a team, and interventions with no dedicated case manager may have better outcomes than those with a named case manager (SMD = -0.36 [-0.55, -0.18] vs. -1.00 [-2.00, 0.00]; p = 0.02). There was not enough evidence from meta-analysis to assess whether the case manager should have a professional qualification, or if frequency of contact, case manager availability or conditionality (barriers due to conditions attached to service provision) influenced outcomes. However, the main theme from implementation studies concerned barriers where conditions were attached to services. Characteristics of Persons Experiencing Homelessness: No conclusions could be drawn from meta-analysis other than a trend for greater reductions in homelessness for persons with high complexity of need (two or more support needs in addition to homelessness) as compared to those with medium complexity of need (one additional support need); effect sizes were SMD = -0.61 [-0.91, -0.31] versus -0.36 [-0.68, -0.05]; p = 0.3. The Broader Context of Delivery of Case Management Programmes: Other major themes from the implementation studies included the importance of interagency partnership; provision for non-housing support and training needs of PEH (such as independent living skills), intensive community support following the move to new housing; emotional support and training needs of case managers; and an emphasis on housing safety, security and choice. Cost Effectiveness: The 12 studies with cost data provided contrasting results and no clear conclusions. Some case management costs may be largely off-set by reductions in the use of other services. Cost estimates from three North American studies were $45-52 for each additional day housed. Authors' Conclusions: Case management interventions improve housing outcomes for PEH with one or more additional support needs, with more intense interventions leading to greater benefits. Those with greater support needs may gain greater benefit. There is also evidence for improvements to capabilities and wellbeing. Current approaches do not appear to lead to mental health benefits. In terms of case management components, there is evidence in support of a team approach and in-person meetings and, from the implementation evidence, that conditions associated with service provision should be minimised. The approach within Housing First could explain the finding that overall benefits may be greater than for other types of case management. Four of its principles were identified as key themes within the implementation studies: No conditionality, offer choice, provide an individualised approach and support community building. Recommendations for further research include an expansion of the research base outside North America and further exploration of case management components and intervention cost-effectiveness.

Pragmatic randomised controlled trial of guided self-help versus individual cognitive behavioural therapy with a trauma focus for post-traumatic stress disorder (RAPID).

Background: Guided self-help has been shown to be effective for other mental conditions and, if effective for post-traumatic stress disorder, would offer a time-efficient and accessible treatment option, with the potential to reduce waiting times and costs. Objective: To determine if trauma-focused guided self-help is non-inferior to individual, face-to-face cognitive-behavioural therapy with a trauma focus for mild to moderate post-traumatic stress disorder to a single traumatic event. Design: Multicentre pragmatic randomised controlled non-inferiority trial with economic evaluation to determine cost-effectiveness and nested process evaluation to assess fidelity and adherence, dose and factors that influence outcome (including context, acceptability, facilitators and barriers, measured qualitatively). Participants were randomised in a 1 : 1 ratio. The primary analysis was intention to treat using multilevel analysis of covariance. Setting: Primary and secondary mental health settings across the United Kingdom's National Health Service. Participants: One hundred and ninety-six adults with a primary diagnosis of mild to moderate post-traumatic stress disorder were randomised with 82% retention at 16 weeks and 71% at 52 weeks. Nineteen participants and ten therapists were interviewed for the process evaluation. Interventions: Up to 12 face-to-face, manualised, individual cognitive-behavioural therapy with a trauma focus sessions, each lasting 60-90 minutes, or to guided self-help using Spring, an eight-step online guided self-help programme based on cognitive-behavioural therapy with a trauma focus, with up to five face-to-face meetings of up to 3 hours in total and four brief telephone calls or e-mail contacts between sessions. Main outcome measures: Primary outcome: the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, at 16 weeks post-randomisation. Secondary outcomes: included severity of post-traumatic stress disorder symptoms at 52 weeks, and functioning, symptoms of depression, symptoms of anxiety, alcohol use and perceived social support at both 16 and 52 weeks post-randomisation. Those assessing outcomes were blinded to group assignment. Results: Non-inferiority was demonstrated at the primary end point of 16 weeks on the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [mean difference 1.01 (one-sided 95% CI -∞ to 3.90, non-inferiority p = 0.012)]. Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, score improvements of over 60% in both groups were maintained at 52 weeks but the non-inferiority results were inconclusive in favour of cognitive-behavioural therapy with a trauma focus at this timepoint [mean difference 3.20 (one-sided 95% confidence interval -∞ to 6.00, non-inferiority p = 0.15)]. Guided self-help using Spring was not shown to be more cost-effective than face-to-face cognitive-behavioural therapy with a trauma focus although there was no significant difference in accruing quality-adjusted life-years, incremental quality-adjusted life-years -0.04 (95% confidence interval -0.10 to 0.01) and guided self-help using Spring was significantly cheaper to deliver [£277 (95% confidence interval £253 to £301) vs. £729 (95% CI £671 to £788)]. Guided self-help using Spring appeared to be acceptable and well tolerated by participants. No important adverse events or side effects were identified. Limitations: The results are not generalisable to people with post-traumatic stress disorder to more than one traumatic event. Conclusions: Guided self-help using Spring for mild to moderate post-traumatic stress disorder to a single traumatic event appears to be non-inferior to individual face-to-face cognitive-behavioural therapy with a trauma focus and the results suggest it should be considered a first-line treatment for people with this condition. Future work: Work is now needed to determine how best to effectively disseminate and implement guided self-help using Spring at scale. Trial registration: This trial is registered as ISRCTN13697710. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/192/97) and is published in full in Health Technology Assessment; Vol. 27, No. 26. See the NIHR Funding and Awards website for further award information.

Post-traumatic stress disorder is a common, disabling condition that can occur following major traumatic events. Typical symptoms include distressing reliving, avoidance of reminders and feeling a current sense of threat. First-choice treatments for post-traumatic stress disorder are individual, face-to-face talking treatments, of 12­16 hours duration, including cognitive behavioural therapy with a trauma focus. If equally effective treatments could be developed that take less time and can be largely undertaken in a flexible manner at home, this would improve accessibility, reduce waiting times and hence the burden of disease. RAPID was a randomised controlled trial using a web-based programme called Spring. The aim was to determine if trauma-focused guided self-help provided a faster and cheaper treatment for post-traumatic stress disorder than first-choice face-to-face therapy, while being equally effective. Guided self-help using Spring is delivered through eight steps. A therapist provides a 1-hour introductory meeting followed by four further, fortnightly sessions of 30 minutes each and four brief (around 5 minutes) telephone calls or e-mail contacts between sessions. At each session, the therapist reviews progress and guides the client through the programme, offering continued support, monitoring, motivation and problem-solving. One hundred and ninety-six people with post-traumatic stress disorder to a single traumatic event took part in the study. Guided self-help using Spring was found to be equally effective to first-choice face-to-face therapy at reducing post-traumatic stress disorder symptoms at 16 weeks. Very noticeable improvements were maintained at 52 weeks post-randomisation in both groups, when most results were inconclusive but in favour of face-to-face therapy. Guided self-help using Spring was significantly cheaper to deliver and appeared to be well-tolerated. It is noteworthy that not everyone benefitted from guided self-help using Spring, highlighting the importance of considering it on a person-by-person basis, and personalising interventions. But, the RAPID trial has demonstrated that guided self-help using Spring provides a low-intensity treatment option for people with post-traumatic stress disorder that is ready to be implemented in the National Health Service.

A Therapeutic Vibrating Insole Device for Postural Instability in Older People with Type 2 Diabetes: A Randomized Control Study.

INTRODUCTION: Frail older people with diabetes often present with or develop walking impairments, in part due to lower-limb sensory-motor neuropathy. Several studies suggest a possible improvement of balance control using somatosensory stimulation. We undertook a novel randomized control trial, the aim of which was to observe whether use of this device for 1 month improves walking speed as measured in the 10-m fast walking speed test standardized to body size at month 1 (M1) (FWS). Secondary outcomes were the differences between intervention (VS) and control (C) in the 10-m normal walking speed test, step length, short physical performance battery, timed up and go test, and posturographic measures. METHODS: Subjects were aged ≥ 70 years and had had type 2 diabetes for at least 2 years. The intervention (VS) at home consisted of 22-min daily vibrating sequences with noise intensity set at 90% of the tactile threshold for each foot. The same device was used in group C but noise was set to 0. Compliance was retrieved from the device. RESULTS: Among 56 subjects, 27 were in the VS group and 29 in the C group; 35 subjects were frail, 15 were prefrail ,and 6 were non-frail. Bilateral neuropathy was present in 17 subjects. More than half of sessions were done in 36 subjects with no discernible difference according to intervention. At M1 there were no discernible differences in FWS between the groups [VS: 0.96 (0.53) cm s-1 cm-1, C: 0.94 (0.47) cm s-1 cm-1]. There were also no discernible differences in other outcomes, irrespective of the presence of bilateral neuropathy. CONCLUSION: In a cohort of frail, prefrail, or non-frail older subjects with diabetes, a 1-month intervention using a vibrating insole device did not alter measures of walking speed and related measures. Larger studies with longer term and different stimulation protocols are required to test this hypothesis more fully.

PROTOCOL: Exploring the effect of case management in homelessness per components: A systematic review of effectiveness and implementation, with meta-analysis and thematic synthesis.

This is the protocol for a Campbell review. The objectives are as follows: To carry out a mixed methods review to summarise current evidence relating to the components of case-management interventions for people experiencing homelessness.

Physical activity and exercise outcomes in Huntington's disease (PACE-HD): results of a 12-month trial-within-cohort feasibility study of a physical activity intervention in people with Huntington's disease.

INTRODUCTION: While physical activity (PA) is recognized as important in Huntington's disease (HD) disease management, there has been no long-term evaluation undertaken. We aimed to evaluate the feasibility of a nested (within cohort) randomized controlled trial (RCT) of a physical therapist-led PA intervention. METHODS: Participants were recruited from six HD specialist centers participating in the Enroll-HD cohort study in Germany, Spain and U.S. Assessments were completed at baseline and 12 months and linked to Enroll-HD cohort data. Participants at three sites (cohort) received no contact between baseline and 12 month assessments. Participants at three additional sites (RCT) were randomized to PA intervention or control group. The intervention consisted of 18 sessions delivered over 12 months; control group participants received no intervention, however both groups completed monthly exercise/falls diaries and 6-month assessments. RESULTS: 274 participants were screened, 204 met inclusion criteria and 116 were enrolled (59 in cohort; 57 in RCT). Retention rates at 12-months were 84.7% (cohort) and 79.0% (RCT). Data completeness at baseline ranged from 42.3 to 100% and at 12-months 19.2-85.2%. In the RCT, there was 80.5% adherence, high intervention fidelity, and similar adverse events between groups. There were differences in fitness, walking endurance and self-reported PA at 12 months favoring the intervention group, with data completeness >60%. Participants in the cohort had motor and functional decline at rates comparable to previous studies. CONCLUSION: Predefined progression criteria indicating feasibility were met. PACE-HD lays the groundwork for a future, fully-powered within cohort trial, but approaches to ensure data completeness must be considered. CLINICALTRIALS: GOV: NCT03344601.

Guided, internet based, cognitive behavioural therapy for post-traumatic stress disorder: pragmatic, multicentre, randomised controlled non-inferiority trial (RAPID).

OBJECTIVE: To determine if guided internet based cognitive behavioural therapy with a trauma focus (CBT-TF) is non-inferior to individual face-to-face CBT-TF for mild to moderate post-traumatic stress disorder (PTSD) to one traumatic event. DESIGN: Pragmatic, multicentre, randomised controlled non-inferiority trial (RAPID). SETTING: Primary and secondary mental health settings across the UK's NHS. PARTICIPANTS: 196 adults with a primary diagnosis of mild to moderate PTSD were randomised in a 1:1 ratio to one of two interventions, with 82% retention at 16 weeks and 71% retention at 52 weeks. 19 participants and 10 therapists were purposively sampled and interviewed for evaluation of the process. INTERVENTIONS: Up to 12 face-to-face, manual based, individual CBT-TF sessions, each lasting 60-90 minutes; or guided internet based CBT-TF with an eight step online programme, with up to three hours of contact with a therapist and four brief telephone calls or email contacts between sessions. MAIN OUTCOME MEASURES: Primary outcome was the Clinician Administered PTSD Scale for DSM-5 (CAPS-5) at 16 weeks after randomisation (diagnosis of PTSD based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, DSM-5). Secondary outcomes included severity of PTSD symptoms at 52 weeks, and functioning, symptoms of depression and anxiety, use of alcohol, and perceived social support at 16 and 52 weeks after randomisation. RESULTS: Non-inferiority was found at the primary endpoint of 16 weeks on the CAPS-5 (mean difference 1.01, one sided 95% confidence interval -∞ to 3.90, non-inferiority P=0.012). Improvements in CAPS-5 score of more than 60% in the two groups were maintained at 52 weeks, but the non-inferiority results were inconclusive in favour of face-to-face CBT-TF at this time point (3.20, -∞ to 6.00, P=0.15). Guided internet based CBT-TF was significantly (P<0.001) cheaper than face-to-face CBT-TF and seemed to be acceptable and well tolerated by participants. The main themes of the qualitative analysis were facilitators and barriers to engagement with guided internet based CBT-TF, treatment outcomes, and considerations for its future implementation. CONCLUSIONS: Guided internet based CBT-TF for mild to moderate PTSD to one traumatic event was non-inferior to individual face-to-face CBT-TF and should be considered a first line treatment for people with this condition. TRIAL REGISTRATION: ISRCTN13697710.

Can wearable technology be used to approximate cardiopulmonary exercise testing metrics?

BACKGROUND: Consumer wrist-worn wearable activity monitors are widely available, low cost and are able to provide a direct measurement of several markers of physical activity. Despite this, there is limited data on their use in perioperative risk prediction. We explored whether these wearables could accurately approximate metrics (anaerobic threshold, peak oxygen uptake and peak work) derived using formalised cardiopulmonary exercise testing (CPET) in patients undergoing high-risk surgery. METHODS: Patients scheduled for major elective intra-abdominal surgery and undergoing CPET were included. Physical activity levels were estimated through direct measures (step count, floors climbed and total distance travelled) obtained through continuous wear of a wrist worn activity monitor (Garmin Vivosmart HR+) for 7 days prior to surgery and self-report through completion of the short International Physical Activity Questionnaire (IPAQ). Correlations and receiver operating characteristic (ROC) curve analysis explored the relationships between parameters provided by CPET and physical activity. DEVICE SELECTION: Our choice of consumer wearable device was made to maximise feasibility outcomes for this study. The Garmin Vivosmart HR+ had the longest battery life and best waterproof characteristics of the available low-cost devices. RESULTS: Of 55 patients invited to participate, 49 (mean age 65.3 ± 13.6 years; 32 males) were enrolled; 37 provided complete wearable data for analyses and 36 patients provided full IPAQ data. Floors climbed, total steps and total travelled as measured by the wearable device all showed moderate correlation with CPET parameters of peak oxygen uptake (peak VO2) (R = 0.57 (CI 0.29-0.76), R = 0.59 (CI 0.31-0.77) and R = 0.62 (CI 0.35-0.79) respectively), anaerobic threshold (R = 0.37 (CI 0.01-0.64), R = 0.39 (CI 0.04-0.66) and R = 0.42 (CI 0.07-0.68) respectively) and peak work (R = 0.56 (CI 0.27-0.75), R = 0.48 (CI 0.17-0.70) and R = 0.50 (CI 0.2-0.72) respectively). Receiver operator curve (ROC) analysis for direct and self-reported measures of 7-day physical activity could accurately approximate the ventilatory equivalent for carbon dioxide (VE/VCO2) and the anaerobic threshold. The area under these curves was 0.89 for VE/VCO2 and 0.91 for the anaerobic threshold. For peak VO2 and peak work, models fitted using just the wearable data were 0.93 for peak VO2 and 1.00 for peak work. CONCLUSIONS: Data recorded by the wearable device was able to consistently approximate CPET results, both with and without the addition of patient reported activity measures via IPAQ scores. This highlights the potential utility of wearable devices in formal assessment of physical functioning and suggests they could play a larger role in pre-operative risk assessment. ETHICS: This study entitled "uSing wearable TEchnology to Predict perioperative high-riSk patient outcomes (STEPS)" gained favourable ethical opinion on 24 January 2017 from the Welsh Research Ethics Committee 3 reference number 17/WA/0006. It was registered on ClinicalTrials.gov with identifier NCT03328039.

Whole transcriptome in silico screening implicates cardiovascular and infectious disease in the mechanism of action underlying atypical antipsychotic side effects.

BACKGROUND: Stroke/thromboembolic events, infections, and death are all significantly increased by antipsychotics in dementia but little is known about why they can be harmful. Using a novel application of a drug repurposing paradigm, we aimed to identify potential mechanisms underlying adverse events. METHODS: Whole transcriptome signatures were generated for SH-SY5Y cells treated with amisulpride, risperidone, and volinanserin using RNA sequencing. Bioinformatic analysis was performed that scored the association between antipsychotic signatures and expression data from 415,252 samples in the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) repository. RESULTS: Atherosclerosis, venous thromboembolism, and influenza NCBI GEO-derived samples scored positively against antipsychotic signatures. Pathways enriched in antipsychotic signatures were linked to the cardiovascular and immune systems (eg, brain derived neurotrophic factor [BDNF], platelet derived growth factor receptor [PDGFR]-beta, tumor necrosis factor [TNF], transforming growth factor [TGF]-beta, selenoamino acid metabolism, and influenza infection). CONCLUSIONS: These findings for the first time mechanistically link antipsychotics to specific cardiovascular and infectious diseases which are known side effects of their use in dementia, providing new information to explain related adverse events.

Physical activity assessment by accelerometry in people with heart failure.

BACKGROUND: International guidelines for physical activity recommend at least 150 min per week of moderate-to-vigorous physical activity (MVPA) for adults, including those with cardiac disease. There is yet to be consensus on the most appropriate way to categorise raw accelerometer data into behaviourally relevant metrics such as intensity, especially in chronic disease populations. Therefore the aim of this study was to estimate acceleration values corresponding to inactivity and MVPA during daily living activities of patients with heart failure (HF), via calibration with oxygen consumption (VO2) and to compare these values to previously published, commonly applied PA intensity thresholds which are based on healthy adults. METHODS: Twenty-two adults with HF (mean age 71 ± 14 years) undertook a range of daily living activities (including laying down, sitting, standing and walking) whilst measuring PA via wrist- and hip-worn accelerometers and VO2 via indirect calorimetry. Raw accelerometer output was used to compute PA in units of milligravity (mg). Energy expenditure across each of the activities was converted into measured METs (VO2/resting metabolic rate) and standard METs (VO2/3.5 ml/kg/min). PA energy costs were also compared with predicted METs in the compendium of physical activities. Location specific activity intensity thresholds were established via multilevel mixed effects linear regression and receiver operator characteristic curve analysis. A leave-one-out method was used to cross-validate the thresholds. RESULTS: Accelerometer values corresponding with intensity thresholds for inactivity (< 1.5METs) and MVPA (≥3.0METs) were > 50% lower than previously published intensity thresholds for both wrists and waist accelerometers (inactivity: 16.7 to 18.6 mg versus 45.8 mg; MVPA: 43.1 to 49.0 mg versus 93.2 to 100 mg). Measured METs were higher than both standard METs (34-35%) and predicted METs (45-105%) across all standing and walking activities. CONCLUSION: HF specific accelerometer intensity thresholds for inactivity and MVPA are lower than previously published thresholds based on healthy adults, due to lower resting metabolic rate and greater energy expenditure during daily living activities for HF patients. TRIAL REGISTRATION: Clinical trials.gov NCT03659877, retrospectively registered on September 6th 2018.

An app-, web- and social support-based weight loss intervention for adults with obesity: the 'HelpMeDoIt!' feasibility randomised controlled trial.

BACKGROUND: Social support has an important role in successful weight loss. The aim of this study was to assess the feasibility and acceptability of an app-, web- and social support-based intervention in supporting adults with obesity to achieve weight loss. METHODS: The intervention and evaluation methods were tested in a feasibility randomised controlled trial. Adults in the Greater Glasgow and Clyde Health Board area of Scotland with a body mass index ≥ 30 kg/m2 were recruited and randomised 2:1 (intervention to control). The feasibility and acceptability of the intervention and trial methods were assessed against pre-specified progression criteria, via process, economic and outcome evaluation. Three primary outcomes were explored: BMI, diet and physical activity, as well as a number of secondary outcomes. The intervention group had access to the HelpMeDoIt! intervention for 12 months. This encouraged them to (i) set goals, (ii) monitor progress and (iii) harness social support by inviting 'helpers' from their existing social network. The control group received a healthy lifestyle leaflet. RESULTS: One hundred and nine participants were recruited, with 84 participants (77%) followed-up at 12 months. The intervention and trial methods were feasible and acceptable. Participants and helpers were generally positive. Of the 54 (74%) participants who downloaded the app, 48 (89%) used it. Interview data indicated that HelpMeDoIt! promoted social support from existing social networks to support weight loss. This support was often given outside of the app.Outcomes were compared using linear regression models, with randomised group, the baseline measurement of the outcome, age and gender as predictor variables. These analyses were exploratory and underpowered to detect effects. However, all pre-specified primary outcome effects (BMI, diet and physical activity) had wide confidence intervals and were therefore consistent with clinically relevant benefits. Objective physical activity measures perhaps showed most potential (daily step count (p = 0.098; 1187 steps [- 180, 2555])) and sedentary time (p = 0.022; - 60.8 min [- 110.5, - 11.0]). However, these outcomes were poorly completed. CONCLUSIONS: The study demonstrated that a novel social support intervention involving support from participants' close social networks, delivered via app and website, has potential to promote weight loss and is feasible and acceptable. TRIAL REGISTRATION: ISRCTN, ISRCTN85615983. Registered 25 September 2014.