Automated Insulin Delivery in Women with Pregnancy Complicated by Type 1 Diabetes.

BACKGROUND: Hybrid closed-loop insulin therapy has shown promise for management of type 1 diabetes during pregnancy; however, its efficacy is unclear. METHODS: In this multicenter, controlled trial, we randomly assigned pregnant women with type 1 diabetes and a glycated hemoglobin level of at least 6.5% at nine sites in the United Kingdom to receive standard insulin therapy or hybrid closed-loop therapy, with both groups using continuous glucose monitoring. The primary outcome was the percentage of time in the pregnancy-specific target glucose range (63 to 140 mg per deciliter [3.5 to 7.8 mmol per liter]) as measured by continuous glucose monitoring from 16 weeks' gestation until delivery. Analyses were performed according to the intention-to-treat principle. Key secondary outcomes were the percentage of time spent in a hyperglycemic state (glucose level >140 mg per deciliter), overnight time in the target range, the glycated hemoglobin level, and safety events. RESULTS: A total of 124 participants with a mean (±SD) age of 31.1±5.3 years and a mean baseline glycated hemoglobin level of 7.7±1.2% underwent randomization. The mean percentage of time that the maternal glucose level was in the target range was 68.2±10.5% in the closed-loop group and 55.6±12.5% in the standard-care group (mean adjusted difference, 10.5 percentage points; 95% confidence interval [CI], 7.0 to 14.0; P<0.001). Results for the secondary outcomes were consistent with those of the primary outcome; participants in the closed-loop group spent less time in a hyperglycemic state than those in the standard-care group (difference, -10.2 percentage points; 95% CI, -13.8 to -6.6); had more overnight time in the target range (difference, 12.3 percentage points; 95% CI, 8.3 to 16.2), and had lower glycated hemoglobin levels (difference, -0.31 percentage points; 95% CI, -0.50 to -0.12). Little time was spent in a hypoglycemic state. No unanticipated safety problems associated with the use of closed-loop therapy during pregnancy occurred (6 instances of severe hypoglycemia, vs. 5 in the standard-care group; 1 instance of diabetic ketoacidosis in each group; and 12 device-related adverse events in the closed-loop group, 7 related to closed-loop therapy). CONCLUSIONS: Hybrid closed-loop therapy significantly improved maternal glycemic control during pregnancy complicated by type 1 diabetes. (Funded by the Efficacy and Mechanism Evaluation Program; AiDAPT ISRCTN Registry number, ISRCTN56898625.).

Effects of an increased financial incentive on follow-up in an online, automated smoking cessation trial: A randomised controlled Study Within a Trial (SWAT).

INTRODUCTION: Poor retention in clinical trials can impact on statistical power, reliability, validity and generalisability of findings and is a particular challenge in smoking cessation studies. In online trials with automated follow up mechanisms, poor response also increases resource-need for manual follow up. This study compared two financial incentives on response rates at 6 months follow up, in an online, automated smoking cessation feasibility trial of a cessation smartphone app (Quit Sense). METHODS: A study within a trial (SWAT), embedded within a host randomised controlled trial. Host trial participants were randomised 1:1 to receive either a £10 or £20 voucher incentive, for completing the 6-month questionnaire. Stratification for randomisation to the SWAT was by minimisation to ensure an even split of host trial arm participants, and by 6-week response rate. Outcome measures were: questionnaire completion rate, time to completion, number of completers requiring manual follow up and completeness of responses. RESULTS: 204 participants were randomised to the SWAT. The £20 and £10 incentives did not differ in completion rate at 6 months (79% versus 74%; p=0.362) but did reduce the proportion of participants requiring manual follow up (46% versus 62%; p=0.018) and the median completion time (7 days versus 15 days; p=0.008). Measure response completeness rates were higher among £20 incentive participants, though differences were small for the host trial's primary smoking outcome. CONCLUSIONS: Benefits to using relatively modest increases in incentive for online smoking cessation trials include more rapid completion of follow up questionnaires and reduced manual follow up. IMPLICATIONS: A modest increase in incentive (from £10 to £20) to promote the completion of follow up questionnaires in online smoking cessation trials may not increase overall response rates but could lead to more rapid data collection, a reduced need for manual follow-up and reduced missing data among those who initiate completing a questionnaire. Such an improvement may help to reduce bias, increase validity and generalisability, and improve statistical power in smoking cessation trials.

Alcohol Consumption and Measures of Sarcopenic Muscle Risk: Cross-Sectional and Prospective Associations Within the UK Biobank Study.

Alcohol intake is a major modifiable risk factor for many diseases. Alcohol can also damage skeletal muscle health during ageing which in turn increases risk of sarcopenia, frailty and falls but this relationship is understudied. The aim of this study was to model the relationship between a full range of alcohol consumption and components of sarcopenic risk, skeletal muscle mass and function, in middle-aged and younger older-aged men and women. A cross-sectional analyses was undertaken of 196,561 white participants from the UK Biobank with longitudinal analysis also in 12,298 of these participants, with outcome measures for the latter repeated after around four years. For the cross-sectional analysis fractional polynomial curves were fitted in models of measures of skeletal muscle mass, appendicular lean mass/body mass index (ALM/BMI), fat-free mass as a percentage of body weight (FFM%) and grip strength, all predicted from alcohol consumption with models fitted for men and women separately. Alcohol consumption at baseline was based on the mean of up to five dietary recalls, typically over 16 months. Linear regression was used for longitudinal analyses to model the effects of alcohol consumption groups on these measures. All models were adjusted for covariates. In the cross-sectional analysis, modelled values of the muscle mass measures all showed a peak at medium levels of alcohol consumption and a steep decline with increasing alcohol consumption. Modelled differences in muscle mass from zero consumption of alcohol to 160 g/d ranged from 3.6 to 4.9% for ALM/BMI for men and women, respectively, and 3.6 to 6.1% for FFM%. Grip strength consistently increased with alcohol consumption. No association between alcohol consumption and muscle measures were seen in the longitudinal results. Our results suggest that higher levels of alcohol consumption could have detrimental effects on muscle mass in middle- and older-aged men and women.

An Automated, Online Feasibility Randomized Controlled Trial of a Just-In-Time Adaptive Intervention for Smoking Cessation (Quit Sense).

INTRODUCTION: Learned smoking cues from a smoker's environment are a major cause of lapse and relapse. Quit Sense, a theory-guided Just-In-Time Adaptive Intervention smartphone app, aims to help smokers learn about their situational smoking cues and provide in-the-moment support to help manage these when quitting. METHODS: A two-arm feasibility randomized controlled trial (N = 209) to estimate parameters to inform a definitive evaluation. Smoker's willing to make a quit attempt were recruited using online paid-for adverts and randomized to "usual care" (text message referral to NHS SmokeFree website) or "usual care" plus a text message invitation to install Quit Sense. Procedures, excluding manual follow-up for nonresponders, were automated. Follow-up at 6 weeks and 6 months included feasibility, intervention engagement, smoking-related, and economic outcomes. Abstinence was verified using cotinine assessment from posted saliva samples. RESULTS: Self-reported smoking outcome completion rates at 6 months were 77% (95% CI 71%, 82%), viable saliva sample return rate was 39% (95% CI 24%, 54%), and health economic data 70% (95% CI 64%, 77%). Among Quit Sense participants, 75% (95% CI 67%, 83%) installed the app and set a quit date and, of those, 51% engaged for more than one week. The 6-month biochemically verified sustained abstinence rate (anticipated primary outcome for definitive trial), was 11.5% (12/104) among Quit Sense participants and 2.9% (3/105) for usual care (adjusted odds ratio = 4.57, 95% CIs 1.23, 16.94). No evidence of between-group differences in hypothesized mechanisms of action was found. CONCLUSIONS: Evaluation feasibility was demonstrated alongside evidence supporting the effectiveness potential of Quit Sense. IMPLICATIONS: Running a primarily automated trial to initially evaluate Quit Sense was feasible, resulting in modest recruitment costs and researcher time, and high trial engagement. When invited, as part of trial participation, to install a smoking cessation app, most participants are likely to do so, and, for those using Quit Sense, an estimated one-half will engage with it for more than 1 week. Evidence that Quit Sense may increase verified abstinence at 6-month follow-up, relative to usual care, was generated, although low saliva return rates to verify smoking status contributed to considerable imprecision in the effect size estimate.

Psychiatric inpatient admissions and discharges of people with intellectual disabilities: A time series analysis of English national data.

BACKGROUND: We examined whether a series of variables were related to the number of psychiatric inpatients using publicly available data about English psychiatric bed utilisation and NHS workforce. METHOD: Using linear regression, with auto-regressive errors, we examined relationships between variables over time using data from December 2013 to March 2021. RESULTS: Over time, the number of inpatients reduced by either 6.58 or 8.07 per month depending upon the dataset utilised, and the number of community nurses and community nursing support staff reduced by 7.43 and 2.14 nurses per month, respectively. Increasing numbers of consultant psychiatrists were associated with fewer inpatients over time. More care and treatment reviews (CTRs) were associated with more admissions over time, while more post-admission CTRs were associated with increased discharges over time. CONCLUSIONS: Future studies should examine whether psychiatric bed utilisation elsewhere within the NHS by people with intellectual disabilities has increased.

Study of mirtazapine for agitated behaviours in dementia (SYMBAD): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Agitation is common in people with dementia and negatively affects the quality of life of both people with dementia and carers. Non-drug patient-centred care is the first-line treatment, but there is a need for other treatment when this care is not effective. Current evidence is sparse on safer and effective alternatives to antipsychotics. We assessed the efficacy and safety of mirtazapine, an antidepressant prescribed for agitation in dementia. METHODS: This parallel-group, double-blind, placebo-controlled trial-the Study of Mirtazapine for Agitated Behaviours in Dementia trial (SYMBAD)-was done in 26 UK centres. Participants had probable or possible Alzheimer's disease, agitation unresponsive to non-drug treatment, and a Cohen-Mansfield Agitation Inventory (CMAI) score of 45 or more. They were randomly assigned (1:1) to receive either mirtazapine (titrated to 45 mg) or placebo. The primary outcome was reduction in CMAI score at 12 weeks. This trial is registered with ClinicalTrials.gov, NCT03031184, and ISRCTN17411897. FINDINGS: Between Jan 26, 2017, and March 6, 2020, 204 participants were recruited and randomised. Mean CMAI scores at 12 weeks were not significantly different between participants receiving mirtazapine and participants receiving placebo (adjusted mean difference -1·74, 95% CI -7·17 to 3·69; p=0·53). The number of controls with adverse events (65 [64%] of 102 controls) was similar to that in the mirtazapine group (67 [66%] of 102 participants receiving mirtazapine). However, there were more deaths in the mirtazapine group (n=7) by week 16 than in the control group (n=1), with post-hoc analysis suggesting this difference was of marginal statistical significance (p=0·065). INTERPRETATION: This trial found no benefit of mirtazapine compared with placebo, and we observed a potentially higher mortality with use of mirtazapine. The data from this study do not support using mirtazapine as a treatment for agitation in dementia. FUNDING: UK National Institute for Health Research Health Technology Assessment Programme.

Clinical and cost-effectiveness of social recovery therapy for the prevention and treatment of long-term social disability among young people with emerging severe mental illness (PRODIGY): randomised controlled trial.

BACKGROUND: Young people with social disability and severe and complex mental health problems have poor outcomes, frequently struggling with treatment access and engagement. Outcomes may be improved by enhancing care and providing targeted psychological or psychosocial intervention. AIMS: We aimed to test the hypothesis that adding social recovery therapy (SRT) to enhanced standard care (ESC) would improve social recovery compared with ESC alone. METHOD: A pragmatic, assessor-masked, randomised controlled trial (PRODIGY: ISRCTN47998710) was conducted in three UK centres. Participants (n = 270) were aged 16-25 years, with persistent social disability, defined as under 30 hours of structured activity per week, social impairment for at least 6 months and severe and complex mental health problems. Participants were randomised to ESC alone or SRT plus ESC. SRT was an individual psychosocial therapy delivered over 9 months. The primary outcome was time spent in structured activity 15 months post-randomisation. RESULTS: We randomised 132 participants to SRT plus ESC and 138 to ESC alone. Mean weekly hours in structured activity at 15 months increased by 11.1 h for SRT plus ESC (mean 22.4, s.d. = 21.4) and 16.6 h for ESC alone (mean 27.7, s.d. = 26.5). There was no significant difference between arms; treatment effect was -4.44 (95% CI -10.19 to 1.31, P = 0.13). Missingness was consistently greater in the ESC alone arm. CONCLUSIONS: We found no evidence for the superiority of SRT as an adjunct to ESC. Participants in both arms made large, clinically significant improvements on all outcomes. When providing comprehensive evidence-based standard care, there are no additional gains by providing specialised SRT. Optimising standard care to ensure targeted delivery of existing interventions may further improve outcomes.

AiDAPT: automated insulin delivery amongst pregnant women with type 1 diabetes: a multicentre randomized controlled trial - study protocol.

BACKGROUND: Pregnant women with type 1 diabetes strive for tight glucose targets (3.5-7.8 mmol/L) to minimise the risks of obstetric and neonatal complications. Despite using diabetes technologies including continuous glucose monitoring (CGM), insulin pumps and contemporary insulin analogues, most women struggle to achieve and maintain the recommended pregnancy glucose targets. This study aims to evaluate whether the use of automated closed-loop insulin delivery improves antenatal glucose levels in pregnant women with type 1 diabetes. METHODS/DESIGN: A multicentre, open label, randomized, controlled trial of pregnant women with type 1 diabetes and a HbA1c of ≥48 mmol/mol (6.5%) at pregnancy confirmation and ≤ 86 mmol/mol (10%) at randomization. Participants who provide written informed consent before 13 weeks 6 days gestation will be entered into a run-in phase to collect 96 h (24 h overnight) of CGM glucose values. Eligible participants will be randomized on a 1:1 basis to CGM (Dexcom G6) with usual insulin delivery (control) or closed-loop (intervention). The closed-loop system includes a model predictive control algorithm (CamAPS FX application), hosted on an android smartphone that communicates wirelessly with the insulin pump (Dana Diabecare RS) and CGM transmitter. Research visits and device training will be provided virtually or face-to-face in conjunction with 4-weekly antenatal clinic visits where possible. Randomization will stratify for clinic site. One hundred twenty-four participants will be recruited. This takes into account 10% attrition and 10% who experience miscarriage or pregnancy loss. Analyses will be performed according to intention to treat. The primary analysis will evaluate the change in the time spent in the target glucose range (3.5-7.8 mmol/l) between the intervention and control group from 16 weeks gestation until delivery. Secondary outcomes include overnight time in target, time above target (> 7.8 mmol/l), standard CGM metrics, HbA1c and psychosocial functioning and health economic measures. Safety outcomes include the number and severity of ketoacidosis, severe hypoglycaemia and adverse device events. DISCUSSION: This will be the largest randomized controlled trial to evaluate the impact of closed-loop insulin delivery during type 1 diabetes pregnancy. TRIAL REGISTRATION: ISRCTN 56898625 Registration Date: 10 April, 2018.

Cost-effectiveness of mirtazapine for agitated behaviors in dementia: findings from a randomized controlled trial.

OBJECTIVES: To examine the costs and cost-effectiveness of mirtazapine compared to placebo over 12-week follow-up. DESIGN: Economic evaluation in a double-blind randomized controlled trial of mirtazapine vs. placebo. SETTING: Community settings and care homes in 26 UK centers. PARTICIPANTS: People with probable or possible Alzheimer's disease and agitation. MEASUREMENTS: Primary outcome included incremental cost of participants' health and social care per 6-point difference in CMAI score at 12 weeks. Secondary cost-utility analyses examined participants' and unpaid carers' gain in quality-adjusted life years (derived from EQ-5D-5L, DEMQOL-Proxy-U, and DEMQOL-U) from the health and social care and societal perspectives. RESULTS: One hundred and two participants were allocated to each group; 81 mirtazapine and 90 placebo participants completed a 12-week assessment (87 and 95, respectively, completed a 6-week assessment). Mirtazapine and placebo groups did not differ on mean CMAI scores or health and social care costs over the study period, before or after adjustment for center and living arrangement (independent living/care home). On the primary outcome, neither mirtazapine nor placebo could be considered a cost-effective strategy with a high level of confidence. Groups did not differ in terms of participant self- or proxy-rated or carer self-rated quality of life scores, health and social care or societal costs, before or after adjustment. CONCLUSIONS: On cost-effectiveness grounds, the use of mirtazapine cannot be recommended for agitated behaviors in people living with dementia. Effective and cost-effective medications for agitation in dementia remain to be identified in cases where non-pharmacological strategies for managing agitation have been unsuccessful.

Cross-sectional associations between 24-hour activity behaviours and mental health indicators in children and adolescents: A compositional data analysis.

We examined associations between youth 24-hour activity behaviour compositions and mental health. Data were collected from 359 participants (aged 9-13 years). Activity behaviours (sleep, sedentary time (ST), light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA)) were assessed using wrist-worn accelerometers. Questionnaires and a computerized cognitive test battery assessed mental health outcomes. Linear mixed models examined associations between activity behaviour compositions and mental health. Post-hoc analyses modelled the influence of reallocating fixed durations of time between activity behaviours on mental health. ST was associated with worse internalizing problems (all participants; p< 0.05) and poorer prosocial behaviour (primary school participants only; p< 0.05), relative to the other activity behaviours. LPA was associated with worse cognitive test scores among primary school participants; p< 0.05). For all participants, reallocating time to ST from sleep and MVPA was associated with higher internalizing problems. Among primary school participants, reallocating time to ST from any other behaviour was associated with poorer prosocial behaviour, and reallocating time to LPA from any other behaviour was associated with lower executive function. Children's mental health may be promoted by schools integrating opportunities for MVPA throughout the day. Our results provide further evidence for the influence of daily activity behaviours on youth mental health.

Clinical outcome measures in anterior cruciate ligament reconstruction: Clinician vs patient completed knee scores.

INTRODUCTION: Clinical outcome measures are important in both the conduct of clinical research and evaluation of knee surgery in every day clinical practice. A wide variety of validated outcome scores are available in the literature. The objective of this study was to investigate if there is a difference between clinician-completed and patient-completed outcome scores in detecting improvement following anterior cruciate ligament (ACL) reconstruction. METHODS: Fifty patients with ACL rupture were prospectively evaluated using nine clinical outcome measures. Five clinician-completed knee scores included Tegner Activity Score, Lysholm Knee Score, Cincinnati Knee Score, International Knee Documentation Committee (IKDC) Objective Knee Score and Tapper and Hoover Meniscal Grading Score. Four patient-completed knee scores included IKDC Subjective Knee Score, Knee Outcome Survey - Activities of Daily Living Scale (KOS-ADLS), Short Form-12 Item Health Survey (SF-12) and Knee Injury and Osteoarthritis Outcome Score (KOOS). Thirty-four of the 50 patients underwent an ACL reconstruction and were reassessed with all nine outcome scores upon their follow-up review 3 months post-operatively. RESULTS: A significant longitudinal improvement was observed of all five clinician-completed knee scores including Tegner (3.3-4.1 (p = 0.006)), Lysholm (71.7-85.3 (p < 0.001)), Cincinnati (62.6-75.9 (p < 0.001)), IKDC Objective (Abnormal to Nearly Normal (p = 0.001)) and Tapper and Hoover (Fair to Good (p < 0.001)). However, none of the four patient-completed knee scores revealed a statistically significant improvement post-operatively. CONCLUSIONS: Results of clinician-completed scores were found to be inconsistent with those of patient-completed instruments. It's important to consider the mode of administering outcome measures either for research or clinical practice as it can have a significant influence on the end results. The use of both a clinician-completed and a patient-completed instrument maybe the more prudent approach to assessing and quantifying ACL injuries and the outcome post-operatively. Ultimately, better methods of objectively evaluating surgical interventions of the knee are required.

Can cardiovascular risk management be improved by shared care with general practice to prevent cognitive decline following stroke/TIA? A feasibility randomised controlled trial (SERVED memory).

BACKGROUND: Cognitive impairment and dementia following cerebrovascular disease are increasingly common in the UK. One potential strategy to prevent post-stroke cognitive decline is multimodal vascular risk factor management. However, its efficacy remains uncertain and its application in vulnerable patients with incident cerebrovascular disease and early cognitive impairment has not been assessed. The primary aim of this study was to assess the feasibility of recruitment and retention of patients with early cognitive impairment post-stroke or transient ischaemic attack (TIA) to a trial of enhanced vascular risk factor management combining primary and secondary care. METHODS: In this single centre, open label trial adults with a recent stroke or TIA and mild cognitive impairment (MCI) were randomised 1:1 to a three-monthly multimodal vascular risk factor intervention jointly delivered by the trial team and General Practitioner (GP), or control (defined as usual care from the GP). Chosen risk factors were blood pressure (BP), total cholesterol, blood glucose (HbA1C) in those with diabetes, and heart rate and adequacy of anticoagulation in those with atrial fibrillation (AF). Similar patients with normal cognition were enrolled in an embedded observational cohort and also received usual care from the GP. Repeat cognitive screening was undertaken in all participants after 12 months. RESULTS: Seventy three participants were recruited to the randomised trial and 94 to the observational cohort (21.8% of those screened). From the randomised trial 35/73 (47.9%) dropped out before final follow-up. In all groups guideline based rates of risk factor control were mostly poor at baseline and did not significantly improve during follow-up. The observational cohort demonstrated greater decline in cognitive test scores at 12 months, with no difference between the randomised groups. CONCLUSIONS: Recruitment to such a study was feasible, but retention of participants was difficult and generally poor rates of risk factor control suggested insufficient application of the intervention. Consequently, successful scaling up of the trial would require protocol changes with less reliance on primary care services. Any future trial should include participants with normal cognition post-stroke as they may be at greatest risk of cognitive decline. TRIAL REGISTRATION: ISRCTN, ISRCTN42688361 . Registered 16 April 2015.

Screening in the community to reduce fractures in older women (SCOOP): a randomised controlled trial.

BACKGROUND: Despite effective assessment methods and medications targeting osteoporosis and related fractures, screening for fracture risk is not currently advocated in the UK. We tested whether a community-based screening intervention could reduce fractures in older women. METHODS: We did a two-arm randomised controlled trial in women aged 70-85 years to compare a screening programme using the Fracture Risk Assessment Tool (FRAX) with usual management. Women were recruited from 100 general practitioner (GP) practices in seven regions of the UK: Birmingham, Bristol, Manchester, Norwich, Sheffield, Southampton, and York. We excluded women who were currently on prescription anti-osteoporotic drugs and any individuals deemed to be unsuitable to enter a research study (eg, known dementia, terminally ill, or recently bereaved). The primary outcome was the proportion of individuals who had one or more osteoporosis-related fractures over a 5-year period. In the screening group, treatment was recommended in women identified to be at high risk of hip fracture, according to the FRAX 10-year hip fracture probability. Prespecified secondary outcomes were the proportions of participants who had at least one hip fracture, any clinical fracture, or mortality; and the effect of screening on anxiety and health-related quality of life. This trial is registered with the International Standard Randomised Controlled Trial registry, number ISRCTN 55814835. FINDINGS: 12 483 eligible women were identified and participated in the trial, and 6233 women randomly assigned to the screening group between April 15, 2008, and July 2, 2009. Treatment was recommended in 898 (14%) of 6233 women. Use of osteoporosis medication was higher at the end of year 1 in the screening group compared with controls (15% vs 4%), with uptake particularly high (78% at 6 months) in the screening high-risk subgroup. Screening did not reduce the primary outcome of incidence of all osteoporosis-related fractures (hazard ratio [HR] 0·94, 95% CI 0·85-1·03, p=0·178), nor the overall incidence of all clinical fractures (0·94, 0·86-1·03, p=0·183), but screening reduced the incidence of hip fractures (0·72, 0·59-0·89, p=0·002). There was no evidence of differences in mortality, anxiety levels, or quality of life. INTERPRETATION: Systematic, community-based screening programme of fracture risk in older women in the UK is feasible, and could be effective in reducing hip fractures. FUNDING: Arthritis Research UK and Medical Research Council.

Prognostic factors for response to treatment by corticosteroid injection or surgery in carpal tunnel syndrome (palms study): A prospective multicenter cohort study.

INTRODUCTION: Studies of prognosis for surgery and corticosteroid injection for carpal tunnel syndrome (CTS) have considered only a limited range of explanatory variables for outcome. METHODS: Data were prospectively collected on patient-reported symptoms, physical and psychological functioning, comorbidity, and quality of life at baseline and every 6 months for up to 2 years. Outcomes were patient-rated change over a 6-month period and symptom-severity score at 18 months. RESULTS: In total, 754 patients with CTS completed baseline questionnaires, and 626 (83%) completed follow-up to 18 months. Multivariable modeling identified, independent of symptom severity at outset, higher health utility, fewer comorbidities, and lower anxiety as significant predictors of better outcome from surgery. In patients treated by steroid injection, independent of symptom severity at outset, shorter duration of symptoms and having no prior injection were significant predictors of better outcome. DISCUSSION: These multivariable models of outcome may inform shared decision making about treatment for CTS. Muscle Nerve, 2019.

Study protocol: ASCRIBED: the impact of Acute SystematiC inflammation upon cerebRospinal fluId and blood BiomarkErs of brain inflammation and injury in dementia: a study in acute hip fracture patients.

BACKGROUND: Hip fracture represents a substantial acute inflammatory trauma, which may constitute a significant insult to the degenerating brain. Research suggests that an injury of this kind can affect memory and thinking in the future but it is unclear whether, and how, inflammatory trauma injures the brain. The impact of Acute SystematiC inflammation upon cerebRospinal fluId and blood BiomarkErs of brain inflammation and injury in Dementia: a study in acute hip fracture patients (ASCRIBED) explores this relationship, to understand the effect of inflammation on the progression of dementia. METHODS: This protocol describes a multi-centre sample collection observational study. The study utilises the unique opportunity provided by hip fracture operations undertaken via spinal anaesthesia to collect cerebrospinal fluid (CSF) and blood, to investigate the impact of acute brain inflammation caused by hip fracture on the exacerbation of dementia. We will recruit 200 hip fracture patients with a diagnosis or evidence of dementia; and 200 hip fracture patients without dementia. We will also recruit 'Suitable informants', individuals in regular contact with the patient, to provide further proxy evidence of a patient's potential cognitive decline. We will compare these 400 samples with existing CSF and blood samples from a cohort of dementia patients who had not experienced a systemic inflammatory response due to injury. This will provide a comparison between patients with and without dementia who are suffering a systemic inflammatory response; with stable patients living with dementia. DISCUSSION: We will test the hypothesis that hip fracture patients living with dementia show elevated markers of brain inflammation, as well as neuronal injury and Alzheimer-related plaque pathology, in comparison to (1) stable patients living with dementia and (2) hip fracture patients without dementia, as measured by biomarkers in CSF and blood. The findings will address the hypothesis that systemic inflammatory events can exacerbate underlying dementia and inform the search for new treatments targeting inflammation in dementia. TRIAL REGISTRATION: ISRCTN43803769 . Registered 11 May 2017.

Self-efficacy and risk of persistent shoulder pain: results of a Classification and Regression Tree (CART) analysis.

OBJECTIVES: To (i) identify predictors of outcome for the physiotherapy management of shoulder pain and (ii) enable clinicians to subgroup people into risk groups for persistent shoulder pain and disability. METHODS: 1030 people aged ≥18 years, referred to physiotherapy for the management of musculoskeletal shoulder pain were recruited. 810 provided data at 6 months for 4 outcomes: Shoulder Pain and Disability Index (SPADI) (total score, pain subscale, disability subscale) and Quick Disability of the Arm, Shoulder and Hand (QuickDASH). 34 potential prognostic factors were used in this analysis. RESULTS: Four classification trees (prognostic pathways or decision trees) were created, one for each outcome. The most important predictor was baseline pain and/or disability: higher or lower baseline levels were associated with higher or lower levels at follow-up for all outcomes. One additional baseline factor split participants into four subgroups. For the SPADI trees, high pain self-efficacy reduced the likelihood of continued pain and disability. Notably, participants with low baseline pain but concomitant low pain self-efficacy had similar outcomes to patients with high baseline pain and high pain self-efficacy. Cut-off points for defining high and low pain self-efficacy differed according to baseline pain and disability. In the QuickDASH tree, the association between moderate baseline pain and disability with outcome was influenced by patient expectation: participants who expected to recover because of physiotherapy did better than those who expected no benefit. CONCLUSIONS: Patient expectation and pain self-efficacy are associated with clinical outcome. These clinical elements should be included at the first assessment and a low pain self-efficacy response considered as a target for treatment intervention.

Learning to live with a hand nerve disorder: A constructed grounded theory.

STUDY DESIGN: Grounded theory. INTRODUCTION: The broader perspective of health offered by the World Health Organization's International Classification of Functioning, Disability and Health has had a significant bearing on how we view the measurement of health outcomes after surgical or therapy interventions for peripheral nerve disorders affecting the hand. The value of the patient's perspective is now recognized and outcomes which reflect this are being advocated in the clinical management and support of this population. PURPOSE OF THE STUDY: This qualitative study sought to explore the lived experience of a hand nerve disorder and in particular the impact on body structure/function, activities, and participation. METHODS: In depth, one-to-one interviews with 14 people with a range of hand nerve disorders were conducted. Constructivist grounded theory methods were used to collect and analyze the data. Patients were also given the option of taking photographs to visually represent what it is like to live with a nerve disorder, to bring with them for discussion during the interview. RESULTS: The impact of hand nerve disorders forms part of a wider narrative on adaptation. A process of "struggling" and then "overcoming" was experienced. This was followed by an interior aspect of adaptation described as "accepting." This gave rise to participants "transforming," being changed as a result of the journey that they had been on. CONCLUSIONS: This study provides an explanatory theory on the adaptive process following a hand nerve disorder which may inform future patient-therapist interactions.

An evaluation of the structural validity of the shoulder pain and disability index (SPADI) using the Rasch model.

PURPOSE: The shoulder pain and disability index (SPADI) has been extensively evaluated for its psychometric properties using classical test theory (CTT). The purpose of this study was to evaluate its structural validity using Rasch model analysis. METHODS: Responses to the SPADI from 1030 patients referred for physiotherapy with shoulder pain and enrolled in a prospective cohort study were available for Rasch model analysis. Overall fit, individual person and item fit, response format, dependence, unidimensionality, targeting, reliability and differential item functioning (DIF) were examined. RESULTS: The SPADI pain subscale initially demonstrated a misfit due to DIF by age and gender. After iterative analysis it showed good fit to the Rasch model with acceptable targeting and unidimensionality (overall fit Chi-square statistic 57.2, p = 0.1; mean item fit residual 0.19 (1.5) and mean person fit residual 0.44 (1.1); person separation index (PSI) of 0.83. The disability subscale however shows significant misfit due to uniform DIF even after iterative analyses were used to explore different solutions to the sources of misfit (overall fit (Chi-square statistic 57.2, p = 0.1); mean item fit residual 0.54 (1.26) and mean person fit residual 0.38 (1.0); PSI 0.84). CONCLUSIONS: Rasch Model analysis of the SPADI has identified some strengths and limitations not previously observed using CTT methods. The SPADI should be treated as two separate subscales. The SPADI is a widely used outcome measure in clinical practice and research; however, the scores derived from it must be interpreted with caution. The pain subscale fits the Rasch model expectations well. The disability subscale does not fit the Rasch model and its current format does not meet the criteria for true interval-level measurement required for use as a primary endpoint in clinical trials. Clinicians should therefore exercise caution when interpreting score changes on the disability subscale and attempt to compare their scores to age- and sex-stratified data.

Psychological factors are associated with the outcome of physiotherapy for people with shoulder pain: a multicentre longitudinal cohort study.

BACKGROUND/AIM: Shoulder pain is a major musculoskeletal problem. We aimed to identify which baseline patient and clinical characteristics are associated with a better outcome, 6 weeks and 6 months after starting a course of physiotherapy for shoulder pain. METHODS: 1030 patients aged ≥18 years referred to physiotherapy for the management of musculoskeletal shoulder pain were recruited and provided baseline data. 840 (82%) provided outcome data at 6 weeks and 811 (79%) at 6 months. 71 putative prognostic factors were collected at baseline. Outcomes were the Shoulder Pain and Disability Index (SPADI) and Quick Disability of the Arm, Shoulder and Hand Questionnaire. Multivariable linear regression was used to analyse prognostic factors associated with outcome. RESULTS: Parameter estimates (ß) are presented for the untransformed SPADI at 6 months, a negative value indicating less pain and disability. 4 factors were associated with better outcomes for both measures and time points: lower baseline disability (ß=-0.32, 95% CI -0.23 to -0.40), patient expectation of 'complete recovery' compared to 'slight improvement' as 'a result of physiotherapy' (ß=-12.43, 95% CI -8.20 to -16.67), higher pain self-efficacy (ß=-0.36, 95% CI -0.50 to -0.22) and lower pain severity at rest (ß=-1.89, 95% CI -1.26 to -2.51). CONCLUSIONS: Psychological factors were consistently associated with patient-rated outcome, whereas clinical examination findings associated with a specific structural diagnosis were not. When assessing people with musculoskeletal shoulder pain and considering referral to physiotherapy services, psychosocial and medical information should be considered. STUDY REGISTRATION: Protocol published at http://www.biomedcentral.com/1471-2474/14/192.

Effectiveness of edema management techniques for subacute hand edema: A systematic review.

STUDY DESIGN: Systematic review. INTRODUCTION: Prolonged hand edema can have detrimental effects on range of motion and function. There is no consensus on how best to manage traumatic subacute edema. This is the first systematic review which examines the clinical effectiveness of edema treatments on hand volume. PURPOSE OF THE STUDY: The purpose of this systematic review was to examine the evidence of effectiveness of treatments for sub-acute hand edema. METHODS: A literature search of AMED, CINAHL, Embase, and OVID MEDLINE (from inception to August 2015) was undertaken. Studies were selected if they met the following inclusion criteria: randomized controlled or controlled trials in adults who have subacute swelling after a recent upper limb musculoskeletal trauma or cerebral vascular attack or after surgery. Two independent assessors rated study quality and risk of bias using the 24-point MacDermid Structured Effectiveness Quality Evaluation Scale (SEQES). RESULTS: Ten studies met the inclusion criteria. Study quality ranged from 23 to 41 out of 48 points on the SEQES. A total of 16 edema interventions were evaluated across the studies. Due to heterogeneity of the patient characteristics, interventions, and outcomes assessed, it was not possible to pool the results from all studies. Therefore, a narrative best evidence synthesis was undertaken. There is low to moderate quality evidence with limited confidence in the effect estimate to support the use of manual edema mobilization methods in conjunction with standard therapy to reduce problematic hand edema. CONCLUSION: Manual edema mobilization techniques should be considered in conjunction with conventional therapies, in cases of excessive edema or when the edema has not responded to conventional treatment alone; however, manual edema mobilization is not advocated as a routine intervention. LEVEL OF EVIDENCE: 2b.