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Background Obstructive sleep apnoea (OSA) is very common in patients with type 2 diabetes (T2D). We and others have shown that OSA was associated with diabetes-related microvascular complications in patients with T2D in cross-sectional and longitudinal studies and that compliance with continuous positive airway pressure (CPAP) reduced the progression of microvascular complications. Hence, we hypothesised that adequate CPAP reduces the development of microvascular complication in patients with T2D. Methods SLEEP T2D is a cohort study with embedded feasibility, open-label, parallel-arm, randomised control trial (RCT) over 2 years. The primary aim is the feasibility of conducting a definitive RCT assessing the impact of CPAP on chronic kidney disease and other microvascular complications in patients with T2D. The main parameters are to assess willingness of participants to be randomised, follow-up rates, CPAP adherence/compliance, to optimise the choice of outcome measures for a substantive trial, and to identify the parameters for sample size calculations. The secondary aims of the study are related to the impact of CPAP, sleep-related disorders, and sleep chronotype on a variety of diabetes-related end points. The study participants were recruited from the T2D services in multiple NHS trusts across England. The main exclusion criteria for the cohort study are as follows: T1D, eGFR 2, known OSA, active malignancy or chronic kidney disease from reasons other than diabetes, pregnancy, professional drivers, and a history of falling asleep whilst driving within last 2 years. The main exclusion criteria from the RCT were as follows: Apnoea-Hypopnoea Index TM, Resmed). Discussion The feasibility RCT will help us design the future RCT to assess the impact of CPAP on diabetes-related microvascular complications. The cohort study will generate preliminary data regarding the impact of sleep quality, duration, and chronotype on diabetes-related outcomes which could lead to further mechanistic and interventional studies. Trial registration ISRCTN, ISRCTN12361838. Registered 04 April 2018, Protocol version: v5.0 02.12.19.

Background The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. Methods The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). Findings We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9–6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40–59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity. Interpretation We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care. Funding UK Research and Innovation and National Institute for Health Research.

Background The PD COMM pilot randomised controlled trial compared Lee Silverman Voice Treatment (LSVT® LOUD) with standard NHS speech and language therapy (SLT) and a control arm in people with Parkinson’s disease (PwPD) with self-reported problems with voice or speech. This analysis compares costs and quality of life outcomes between the trial arms, and considers the validity of the alternative outcome measures for economic evaluations. Methods A comparison of costs and outcomes was undertaken alongside the PD COMM pilot trial involving three arms: LSVT® LOUD treatment (n = 30); standard NHS SLT (n = 30); and a control arm (n = 29) excluded from receiving therapy for at least 6 months after randomisation unless deemed medically necessary. For all trial arms, resource use and NHS, social care and patient costs and quality of life were collected prospectively at baseline, 3, 6, and 12 months. Total economic costs and outcomes (EQ-5D-3L, ICECAP-O) were considered over the 12-month follow-up period from an NHS payer perspective. Quality of life measures for economic evaluation of SLT for people with Parkinson’s disease were compared. Results Whilst there was no difference between arms in voice or quality of life outcomes at 12 months, there were indications of differences at 3 months in favour of SLT, which need to be confirmed in the main trial. The estimated mean cost of NHS care was £3288 per patient per year for the LSVT® LOUD arm, £2033 for NHS SLT, and £1788 for the control arm. EQ-5D-3L was more strongly correlated to voice impairment than ICECAP-O, and was sensitive to differences in voice impairment between arms. Conclusions The pilot did not identify an effect of SLT on disease-specific or economic outcomes for PwPD at 12 months; however, there appeared to be improvements at 3 months. In addition to the sample size not powered to detect difference in cost-consequence analysis, many patients in the control arm started SLT during the 12-month period used for economic analysis, in line with the study protocol. The LSVT® LOUD intervention was more intense and therefore more costly. Early indications suggest that the preferred economic outcome measure for the full trial is EQ-5D-3L; however, the ICECAP-O should still be included to capture a broader measure of wellbeing. Trial registration International Standard Randomised Controlled Trial Number Register: ISRCTN75223808. Registered 22 March 2012.

Overstating the impact of interventions through incomplete or inaccurate reporting can lead to inappropriate scale-up of interventions with low impact. Accurate reporting of the impact of interventions is of great importance in global health research to protect scarce resources. In global health, the cluster randomised trial design is commonly used to evaluate complex, multicomponent interventions, and outcomes are often binary. Complete reporting of impact for binary outcomes means reporting both relative and absolute measures. We did a systematic review to assess reporting practices and potential to overstate impact in contemporary cluster randomised trials with binary primary outcome. We included all reports registered in the Cochrane Central Register of Controlled Trials of two-arm parallel cluster randomised trials with at least one binary primary outcome that were published in 2017. Of 73 cluster randomised trials, most (60 [82%]) showed incomplete reporting. Of 64 cluster randomised trials for which it was possible to evaluate, most (40 [63%]) reported results in such a way that impact could be overstated. Care is needed to report complete evidence of impact for the many interventions evaluated using the cluster randomised trial design worldwide.

Intelligibility of speech is a key outcome in speech and language therapy (SLT) and research. SLT students frequently participate as raters of intelligibility but we lack information about whether they rate intelligibility in the same way as the general public. This paper aims to determine if there is a difference in the intelligibility ratings made by SLT students (trained in speech related topics) compared to individuals from the general public (untrained). The SLT students were in year 2 of a BSc programme or the first 6 months of a MSc programme. We recorded 10 speakers with Parkinson’s disease (PD) related speech reading aloud the words and sentences from the Assessment of Intelligibility of Dysarthric Speech. These speech recordings were rated for intelligibility by ‘trained’ raters and ‘untrained’ raters. The effort required to understand the speech was also reported. There were no significant differences in the measures of intelligibility from the trained and untrained raters for words or sentences after adjusting for speaker by including them as a covariate in the model. There was a slight increase in effort reported by the untrained raters for the sentences. This difference in reported effort was not evident with the words. SLT students can be recruited alongside individuals from the general public as naïve raters for evaluating intelligibility in people with speech disorders.

BACKGROUND The PD MED study reported small but persistent benefits in patient-rated mobility scores and quality of life from initiating therapy with levodopa compared with levodopa-sparing therapies in early Parkinson's disease (PD). OBJECTIVES The objective was to estimate the cost-effectiveness of levodopa-sparing therapy (dopamine agonists or monoamine oxidase type B inhibitors compared with levodopa alone. METHODS PD MED is a pragmatic, open-label randomized, controlled trial in which patients newly diagnosed with PD were randomly assigned between levodopa-sparing therapy (dopamine agonists or monoamine oxidase type B inhibitors ) and levodopa alone. Mean quality-adjusted life-years and costs were calculated for each participant. Differences in mean quality-adjusted life-years and costs between levodopa and levodopa-sparing therapies and between dopamine agonists and monoamine oxidase type B inhibitors were estimated using linear regression. RESULTS Over a mean observation period of 4 years, levodopa was associated with significantly higher quality-adjusted life-years (difference, 0.18; 95% CI, 0.05-0.30; P

Additional file 1. Detailed description of the outcome measures and assessments.

BACKGROUND Since the turn of the millennium, there has been a worldwide trend towards an endovascular-first strategy where possible revascularization strategy for chronic limb-threatening ischemia. There is concern that this may be inappropriate and can result in net patient harm. The aim of this study, therefore, is to compare important clinical outcomes following femoropopliteal plain balloon angioplasty (FP-PBA), with selective use of bare metal stents (BMSs), in a contemporary series (CS) of patients treated in our unit between 2009 and 2014 with those observed following FP-PBA ± BMS in the United Kingdom National Institute of Health Research Health Technology Assessment-funded Bypass vs Angioplasty in Severe Ischaemia of the Leg (BASIL-1 [B1]) trial (treated 1999-2004). METHODS Baseline and clinical outcome data (amputation-free survival [AFS], overall survival [OS], limb salvage, freedom from reintervention, and freedom from major adverse limb events) were obtained from prospectively gathered hospital data and B1 trial case record forms. RESULTS There were 237 CS and 218 B1 patients. CS patients were older (77 vs 73 years; P = .0002). B1 patients were more likely to be current smokers, less likely to be on best medical therapy, and underwent more extensive endovascular interventions. CS had more hospital admissions (4 vs 2; P < .0001) before they reached their primary endpoint (AFS). Immediate technical success was nonsignificantly higher in the CS patients (87% vs 83%; P = .2). BMS were used in 20 CS (8%) and 2 B1 (1%) patients (P = .0002). AFS (hazard ratio, 0.64; 95% confidence interval, 0.49-0.82; P = .0005) and OS (hazard ratio, 0.58; 95% confidence interval, 0.44-0.76; P = .0001) were significantly worse in the CS cohort. There was no significant difference in limb salvage, freedom from reintervention, or freedom from major adverse limb events. CONCLUSIONS Patients with chronic limb-threatening ischemia managed in our unit (2009-2014) by means of a FP-PBA ± BMS first (where possible) revascularization strategy experienced significantly worse AFS and OS than patients treated with FP-PBA ± BMS in the B1 trial 10 years earlier (1999-2004).

Background Parkinson’s disease (PD) affects approximately 145,519 people in the UK. Speech impairments are common with a reported prevalence of 68%, which increase physical and mental demands during conversation, reliance on family and/or carers, and the likelihood of social withdrawal reducing quality of life. In the UK, two approaches to Speech and Language Therapy (SLT) intervention are commonly available: National Health Service (NHS) SLT or Lee Silverman Voice Treatment (LSVT LOUD®). NHS SLT is tailored to the individuals’ needs per local practice typically consisting of six to eight weekly sessions; LSVT LOUD® comprises 16 sessions of individual treatment with home-based practice over 4 weeks. The evidence-base for their effectiveness is inconclusive. Methods/design PD COMM is a phase III, multicentre, three-arm, unblinded, randomised controlled trial. Five hundred and forty-six people with idiopathic PD, reporting speech or voice problems will be enrolled. We will exclude those with a diagnosis of dementia, laryngeal pathology or those who have received SLT for speech problems in the previous 2 years. Following informed consent and completion of baseline assessments, participants will be randomised in a 1:1:1 ratio to no-intervention control, NHS SLT or LSVT LOUD® via a central computer-generated programme, using a minimisation procedure with a random element, to ensure allocation concealment. Participants randomised to the intervention groups will start treatment within 4 (NHS SLT) or 7 (LSVT LOUD®) weeks of randomisation. Primary outcome: Voice Handicap Index (VHI) total score at 3 months. Secondary outcomes include: VHI subscales, Parkinson’s Disease Questionnaire-39; Questionnaire on Acquired Speech Disorders; EuroQol-5D-5 L; ICECAP-O; resource utilisation; adverse events and carer quality of life. Mixed-methods process and health economic evaluations will take place alongside the trial. Assessments will be completed before randomisation and at 3, 6 and 12 months after randomisation. The trial started in December 2015 and will run for 77 months. Recruitment will take place in approximately 42 sites around the UK. Discussion The trial will test the hypothesis that SLT is effective for the treatment of speech or voice problems in people with PD compared to no SLT. It will further test whether NHS SLT or LSVT LOUD® provide greater benefit and determine the cost-effectiveness of both interventions. Trial registration International Standard Randomised Controlled Trials Number (ISRCTN) Registry, ID: 12421382. Registered on 18 April 2016.

The aim was to compare outcomes in a subgroup of patients with infrapopliteal (IP) disease randomised to infrapopliteal vein bypass (VB) or plain balloon angioplasty (PBA) in the original BASIL trial.A comparison of outcomes from patients randomised to VB or PBA undergoing revascularisation for severe limb ischaemia (SLI) because of IP disease with or without femoropopliteal disease. Data were extracted from case report forms from the BASIL trial. The primary outcome was amputation free survival (AFS); secondary outcomes included overall survival (OS), 30 day mortality and morbidity, freedom from arterial re-intervention, immediate technical success, repeat and crossover interventions, length of hospital stay, and quality of revascularisation.A total of 104 patients were identified in the BASIL study with IP disease, 56 randomised to IP VB, and 48 to IP PBA. Groups were similar at baseline except for more chronic kidney disease and non-steroidal anti-inflammatory drug use in the VB group, and more previous surgical arterial intervention and antihypertensive use in the PBA group. There were no statistically significant differences in AFS or OS; however, clinically important trends were apparent in favour of a VB first strategy. Patients allocated to VB demonstrated significantly quicker relief of rest pain when compared with PBA (p = .005), but no significant differences in improved tissue healing. Median length of index hospital admission was significantly greater in the VB than in the PBA group (18 vs. 10 days, p .0001) but there was no difference between the two groups in median total hospital stay between randomisation and the primary endpoint (VB 43.5 vs. PBA 42 days).Further randomised trials, like BASIL-2 and BEST-CLI, are required to determine whether patients with severe limb ischaemia who require IP revascularisation and who are suitable for VB should have bypass or endovascular intervention as their primary revascularisation procedure.

BACKGROUND Bypass surgery (BS) remains the gold standard revascularization strategy in patients with chronic limb-threatening ischemia (CLTI) owing to infrainguinal disease. The Bypass versus Angioplasty for Severe Ischaemia of the Leg (BASIL)-1 trial showed that, in patients with CLTI who survived for 2 years or more, BS resulted in better clinical outcomes. Despite this finding, there has been an increasing trend toward an endovascular-first approach to infrainguinal CLTI. Our aim was to investigate whether changes in practice have impacted the clinical outcomes of BS in our unit 10 years after BASIL-1. METHODS Data for patients who underwent femoropopliteal (FP) BS in BASIL-1 (1999-2004) were retrieved from trial case record forms. The comparator contemporary series (CS) comprised all patients undergoing FP BS for CLTI in our unit between 2009 and 2014. Demographic and clinical outcome data on patients in the CS were collected from the prospectively collected hospital electronic notes. Anatomic patterns of disease in the BASIL-1 and CS cohorts were scored using the Bollinger and GLASS criteria. Statistical analysis was performed in SAS v9.4. RESULTS There were 128 patients from BASIL-1 and 50 patients in the CS. Baseline age, gender, affected limb, and diabetes prevalence were similar, as were days spent in hospital out to 12 months and length of follow-up. BASIL-1 patients were more likely to be current smokers (P = .000) and had a higher creatinine (P = .04). The 30-day morbidity and mortality were higher in BASIL-1 (45.3% vs 22%; P = .004). There was no significant difference between BASIL-1 and CS with regard to run-off Bollinger (37.7 vs 32.1; P = .167) and IP GLASS (0 vs 0; P = .390) scores, with both groups having a median of two runoff vessels. Amputation-free survival (62% vs 28%; hazard ratio [HR], 1.86; 95% confidence interval [CI], 1.18-2.93; P = .007), limb salvage (85% vs 69%; HR, 2.31; 95% CI, 1.14-4.68; P = .02), overall survival (69% vs 35%; HR, 1.66; 95% CI, 1.00-2.74; P = .05) and major adverse limb events (67% vs 47%; HR, 1.93; 95% CI, 1.15-3.22; P = .01) were all significantly better in BASIL-1. CONCLUSIONS Although 30-day mortality and morbidity were significantly lower, all of the examined longer term clinical outcomes after FP BS were significantly worse in the CS group a decade on from BASIL-1. Further research in the form of prospective cohort studies and randomized controlled trials is urgently required to determine if the CS data reported herein are generalizable to current vascular surgical practice and, if so, to determine the reasons for these unexpected outcomes.

To compare outcomes in patients with chronic limb threatening ischaemia (CLTI) due to femoropopliteal (FP), with or without infrapopliteal (IP), disease who underwent FP (vein or synthetic) open surgical bypass (OSB), or plain balloon angioplasty (PBA), with or without bare metal stenting (BMS), in the Bypass versus Angioplasty in Severe Ischaemia of the Limb (BASIL-1) trial.Data were extracted from BASIL-1 case record forms. Outcomes reported include immediate technical success, freedom from major adverse limb events (FF-MALE) and further re-intervention (FF-R), amputation free survival (AFS), overall survival (OS), and limb salvage (LS).Patients underwent primary OSB (n = 128; 89 vein, 39 synthetic) or primary PBA (n = 183; six had BMS). Mean follow up was 46.2 and 43.6 months respectively. Patients were well matched at baseline except that PBA ± BMS patients were significantly more likely to be current smokers. There was no difference in overall or IP (runoff) Bollinger angiogram scores between groups. Immediate technical success was significantly higher for OSB (98% vs. 81%; p .001). OSB was associated with a longer mean index hospital admission (p = .001), but there was no difference in hospital days at 12 months. FF-MALE (hazard ratio [HR] 1.51; p = .04) and FF-R (HR 1.68; p = .02) but not AFS (HR 1.18; p = .4), OS (HR 1.14; p = .5), and LS (HR 1.09; p = .8) were significantly better after OSB.Although AFS, OS, and LS were similar in the two groups, OSB was associated with significantly fewer MALE and re-interventions. So, while PBA ± BMS may be a less resource intensive (expensive) and morbid option in the short term, this appears unlikely to be the case in the longer term. Present data add further weight to the argument that, where possible, patients presenting with CLTI due to FP disease should be offered OSB as their primary revascularisation procedure.

Objective Chronic limb threatening ischaemia (CLTI) is a growing global health problem. The UK NIHR HTA funded BASIL trial is still the only randomised controlled trial to have compared a “bypass surgery first” with a “plain balloon angioplasty (PBA) first” strategy for the management of CLTI. In patients who were likely to survive for 2 years and had a suitable vein, primary bypass (PB) was associated with better clinical outcomes. Furthermore, PBA was associated with a high technical and clinical failure rate and many went on to have secondary bypass (SB). This study aimed at comparing clinical outcomes following PB and SB in the BASIL trial. Methods Demographic, procedural, and outcome data were obtained from the BASIL case report forms. Outcomes were amputation free survival (AFS), limb salvage (LS), overall survival (OS), and freedom from revascularisation (FFR). The SB cohort comprises patients whose first trial intervention was PBA and who subsequently underwent bypass during follow up. The PB cohort comprises those patients whose first trial intervention was bypass. Results The 190 PB and 49 SB patients were well matched except that the SB patients were more likely to be current smokers. At a median of 7 years, PB was associated with better AFS (PB 60% vs. SB 40%; HR 1.58, p = .04), LS (PB 85% vs. SB 73%, p = .06), and OS (PB 68% vs. 51%, p = .06). FFR was equivalent (PB 53% vs. 53%, p = .3). Conclusion In the BASIL trial, clinical outcomes following PB were significantly better than in patients undergoing SB after failed PBA. Prior to treating patients with CLTI with primary PBA, clinicians should consider that if this should fail, the outcome of attempted subsequent bypass is likely to be significantly worse than if PB were attempted.

BASIL-3 SPIRIT Checklist. (DOC 122Â kb)

Background Severe limb ischaemia (SLI) is defined as the presence of rest pain and/or tissue loss secondary to lower extremity atherosclerotic peripheral arterial disease. The superficial femoral and popliteal arteries are the most commonly diseased vessels in such patients and are being increasingly treated using endovascular revascularisation techniques. However, it is currently unknown whether drug-eluting stents and drug-coated balloons confer additional clinical benefits over more established techniques using plain balloons and bare metal stents, or whether they represent a cost-effective use of NHS resources. Methods The BASIL-3 trial is a UK National Institute for Health Research, Health Technology Assessment Programme-funded, multicentre, randomised controlled trial (RCT) comparing the clinical and cost-effectiveness of plain balloon angioplasty with or without bail-out bare metal stenting, drug-coated balloon angioplasty with or without bail-out bare metal stenting, and primary stenting with drug-eluting stents for SLI secondary to femoro-popliteal disease. Patients with ‘multilevel’ disease may receive aorto-iliac and/or infrapopliteal treatments concurrently with their randomised femoro-popliteal intervention. The primary clinical outcome is amputation-free survival defined as the time to major (above the ankle) amputation of the index limb or death from any cause. The primary outcome for the economic analysis is cost per quality-adjusted life year. Secondary outcome measures include overall survival, major adverse limb events, major adverse cardiac events, relief of ischaemic pain, healing of tissue loss, and quality of life. The required sample size has been calculated at 861 participants (287 on each arm). These patients will be recruited over 3 years and followed-up for between 2 and 5 years. Discussion BASIL-3 is a pragmatic RCT designed to reflect current UK clinical practice. The results will inform decision-making regarding the appropriateness of funding the use of drug-coated balloons and drug-eluting stents, by the NHS, for the management of SLI due to femoro-popliteal disease. Trial registration ISRCTN Registry, identifier: ISRCTN14469736. Registered on 22 October 2015. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-1968-6) contains supplementary material, which is available to authorized users.

Summary Background Surgical intervention for advanced Parkinson's disease is an option if medical therapy fails to control symptoms adequately. We aimed to assess whether surgery and best medical therapy improved self-reported quality of life more than best medical therapy alone in patients with advanced Parkinson's disease. Methods The PD SURG trial is an ongoing randomised, open-label trial. At 13 neurosurgical centres in the UK, between November, 2000, and December, 2006, patients with Parkinson's disease that was not adequately controlled by medical therapy were randomly assigned by use of a computerised minimisation procedure to immediate surgery (lesioning or deep brain stimulation at the discretion of the local clinician) and best medical therapy or to best medical therapy alone. Patients were analysed in the treatment group to which they were randomised, irrespective of whether they received their allocated treatment. The primary endpoint was patient self-reported quality of life on the 39-item Parkinson's disease questionnaire (PDQ-39). Changes between baseline and 1 year were compared by use of t tests. This trial is registered with Current Controlled Trials, number ISRCTN34111222. Findings 366 patients were randomly assigned to receive immediate surgery and best medical therapy (183) or best medical therapy alone (183). All patients who had surgery had deep brain stimulation. At 1 year, the mean improvement in PDQ-39 summary index score compared with baseline was 5·0 points in the surgery group and 0·3 points in the medical therapy group (difference −4·7, 95% CI −7·6 to −1·8; p=0·001); the difference in mean change in PDQ-39 score in the mobility domain between the surgery group and the best medical therapy group was −8·9 (95% CI −13·8 to −4·0; p=0·0004), in the activities of daily living domain was −12·4 (−17·3 to −7·5; p

IMPORTANCE It is unclear whether physiotherapy and occupational therapy are clinically effective and cost-effective in Parkinson disease (PD). OBJECTIVE To perform a large pragmatic randomized clinical trial to evaluate the clinical effectiveness of individualized physiotherapy and occupational therapy in PD. DESIGN, SETTING, AND PARTICIPANTS The PD REHAB Trial was a multicenter, open-label, parallel group, controlled efficacy trial. A total of 762 patients with mild to moderate PD were recruited from 38 sites across the United Kingdom. Recruitment took place between October 2009 and June 2012, with 15 months of follow-up. INTERVENTIONS Participants with limitations in activities of daily living (ADL) were randomized to physiotherapy and occupational therapy or no therapy. MAIN OUTCOMES AND MEASURES The primary outcome was the Nottingham Extended Activities of Daily Living (NEADL) Scale score at 3 months after randomization. Secondary outcomes were health-related quality of life (assessed by Parkinson Disease Questionnaire–39 and EuroQol-5D); adverse events; and caregiver quality of life. Outcomes were assessed before trial entry and then 3, 9, and 15 months after randomization. RESULTS Of the 762 patients included in the study (mean [SD] age, 70 [9.1] years), 381 received physiotherapy and occupational therapy and 381 received no therapy. At 3 months, there was no difference between groups in NEADL total score (difference, 0.5 points; 95%CI, −0.7 to 1.7; P = .41) or Parkinson Disease Questionnaire–39 summary index (0.007 points; 95%CI, −1.5 to 1.5; P = .99). The EuroQol-5D quotient was of borderline significance in favor of therapy (−0.03; 95%CI, −0.07 to −0.002; P = .04). The median therapist contact time was 4 visits of 58 minutes over 8 weeks. Repeated-measures analysis showed no difference in NEADL total score, but Parkinson Disease Questionnaire–39 summary index (diverging 1.6 points per annum; 95%CI, 0.47 to 2.62; P = .005) and EuroQol-5D score (0.02; 95%CI, 0.00007 to 0.03; P = .04) showed small differences in favor of therapy. There was no difference in adverse events. CONCLUSIONS AND RELEVANCE Physiotherapy and occupational therapy were not associated with immediate or medium-term clinically meaningful improvements in ADL or quality of life in mild to moderate PD. This evidence does not support the use of low-dose, patient-centered, goal-directed physiotherapy and occupational therapy in patients in the early stages of PD. Future research should explore the development and testing of more structured and intensive physical and occupational therapy programs in patients with all stages of PD.

Background: Evidence from clinical trials with monoamine oxidase type B inhibitors (TEMPO, ADAGIO and DATATOP) and levodopa (ELLDOPA) suggests that Parkinson's disease patients may benefit from treatment being commenced immediately on diagnosis rather than waiting for functional disability to develop, as is traditional clinical practice. Methods: We performed a narrative literature review and meta‐analysis of delayed‐start design trials in Parkinson's disease. Results: There was inconsistency in the results of the two rasagiline delayed‐start design trials, with early treatment with a 2 mg dose significantly superior in the TEMPO trial, but the 1 mg dose significantly better in the ADAGIO trial, making interpretation difficult. Further, the benefits of immediate treatment were small in terms of total unified Parkinson's disease rating scale scores, with a mean difference of 0.91 units (95% confidence interval 0.01, 1.80; P=0.05) in a meta‐analysis of the TEMPO and ADAGIO delayed‐start design trials. Such small differences are unlikely to be of clinical relevance. There is also little information on whether immediate treatment has a beneficial effect on patient quality of life with an acceptable adverse reaction profile, and we have no data on whether imediate treatment is cost‐effective. Discussion: Based on the evidence available, changing clinical practice to immediate therapy on diagnosis is not warranted and further trials are needed. © 2011 Movement Disorder Society

Interpretation of clinical trials comparing different drug regimens for Parkinson's disease (PD) is complicated by the different dose intensities used: higher doses of levodopa and, possibly, other drugs produce better symptomatic control but more late complications. To address this problem, conversion factors have been calculated for antiparkinsonian drugs that yield a total daily levodopa equivalent dose (LED). LED estimates vary, so we undertook a systematic review of studies reporting LEDs to provide standardized formulae. Electronic database and hand searching of references identified 56 primary reports of LED estimates. Data were extracted and the mean and modal LEDs calculated. This yielded a standardized LED for each drug, providing a useful tool to express dose intensity of different antiparkinsonian drug regimens on a single scale. Using these conversion formulae to report LEDs would improve the consistency of reporting and assist the interpretation of clinical trials comparing different PD medications.

A randomised controlled trial was conducted to assess and quantify the efficacy and acceptability of non-invasive testing (NIT) for sexually transmitted infections (STI) in asymptomatic patients within a genitourinary medicine clinic.Patients were randomly assigned to either standard of care (SOC-STI testing with genital examination) or NIT. The length of time patients spent in the clinic was recorded and patients were asked to complete a satisfaction survey.391 participants were randomly assigned. The length of time male and female patients spent in the clinic was significantly shorter with NIT (men 26 min; women 23 min) compared with SOC (men 41 min; women 45 min, p0.0001), but most of this decrease was due to reduced patient waiting time within the clinic, rather than less time spent with medical or nursing staff. Those randomly assigned to NIT were significantly more likely to state they were in clinic for less time than expected (p0.01) and report that the tests were less uncomfortable than expected (p≤0.04). For both men and women, more patients in the SOC group declined testing for syphilis (14%) and HIV (20%) compared with NIT (7% and 13%, respectively), but this was only significantly different between treatments for female patients (p≤0.02).NIT for STI in asymptomatic patients can reduce the time patients spend in the clinic when combined with appropriate patient care pathways, and is an acceptable alternative to physician-taken genital swabs.

Objective: To investigate the feasibility, acceptability and potential efficacy of group exercise for residents in care homes. Design: Exploratory cluster randomized controlled trial. Setting: Five randomly selected care homes in South Birmingham, UK. Participants: Fifty-six care home residents (mean age 84.5, 71% female), 39 (70%) with cognitive impairments. Intervention: Two homes (n = 28) were randomized to group exercise held twice weekly for five weeks. The remaining three homes (n = 28) formed the control group and received usual care, with no person specifically responsible for exercise training. Outcome measures: Assessments were conducted at zero (pre-intervention), three (post-intervention) and six months (follow-up) using the Rivermead Mobility Index and Hospital Anxiety and Depression Scale or Stroke Aphasic Depression Questionnaire (depending on cognitive impairment). Adherence to group exercise and retention to the study were also documented. Results: No statistically significant improvements in mobility or depression were found in favour of group exercise. Retention to the study was high with 46 (82%) participants completing all assessments. Adherence to group exercise was somewhat lower with participants attending a mean of 3.61 out of 8.5 prescribed sessions (42.5%). Conclusions: Group exercise can be delivered to care home residents with reduced mobility but it is not suitable for residents with severe cognitive impairment. An estimated sample size of 240 participants would be required to detect a clinically significant difference in the Rivermead Mobility Index with 90% power.

Background and Purpose— Complications after stroke have been shown to impede rehabilitation, lead to poor functional outcome, and increase cost of care. This inception cohort study sought to investigate the prevalence of immobility-related complications during the first year after severely disabling stroke in relation to functional independence and place of residence. Methods— Over a 7-month period, 600 stroke survivors were identified in the hospital through the Nottingham Stroke Register. Those who had a Barthel Index score ≤10 3 months poststroke and did not have a primary diagnosis of dementia were eligible to participate in the study. Assessments of complications were carried out at 3, 6, and 12 months poststroke. Results— Complications were recorded for 122 stroke survivors (mean age, 76 years; 57% male). Sixty-three (52%) had significant language impairment and of the remaining 59 who were able to complete an assessment of cognitive function, 10 (8%) were cognitively impaired. The numbers of reported complications over 12 months, in rank order, were falls, 89 (73%); contracture, 73 (60%); pain, 67 (55%); shoulder pain, 64 (52%); depression, 61 (50%); and pressure sores, 26 (22%). A negative correlation was found between Barthel Index score and the number of complications experienced (low scores on the Barthel Index correlate with a high number of complications). The highest relative percentages of complications were experienced by patients who were living in a nursing home at the time of their last completed assessment. Conclusions— Immobility-related complications are very common in the first year after a severely disabling stroke. Patients who are more functionally dependent in self-care are likely to experience a greater number of complications than those who are less dependent. Trials of techniques to limit and prevent complication are required.

Background Severe limb ischaemia is defined by ischaemic rest/night pain, tissue loss, or both, secondary to arterial insufficiency and is increasingly caused by infra-popliteal (below the knee) disease, mainly as a result of the increasing worldwide prevalence of diabetes. Currently, it is unknown whether vein bypass surgery or the best endovascular treatment (angioplasty or stenting) represents the optimal revascularisation strategy in terms of amputation-free survival, overall survival, relief of symptoms, quality of life and cost-effective use of health care resources. Methods/Design The Bypass vs. Angioplasty in Severe Ischaemia of the Leg - 2 Trial is a UK National Institute of Health Research, Health Technology Assessment funded, multi-centre randomised controlled trial that compares, at the point of clinical equipoise, the clinical and cost-effectiveness of a ‘vein bypass first’ and a ‘best endovascular treatment first’ revascularisation strategy for severe limb ischaemia due to infra-popliteal disease. The primary clinical outcome is amputation-free survival defined as the time to major (above the ankle) amputation of the trial limb or death from any cause. The primary outcome for the cost-effectiveness analysis is cost per quality-adjusted life year. Secondary outcomes include overall survival, quality of life, in-hospital mortality and morbidity, repeat and crossover interventions, healing of tissue loss and haemodynamic changes following revascularisation. Sample size is estimated at 600 patients. An economic evaluation will be conducted from the perspective of the National Health Service and comprise a ‘within-study’ analysis, based on prospectively collected trial data and a ‘model-based’ analysis, which will extrapolate and compare costs and effects beyond the study follow-up period. Discussion The BASIL-2 trial is designed to be pragmatic and represent current practice within the United Kingdom. Patients with severe limb ischaemia can only be randomised into the trial where clinical equipose exists. The advent of hybrid operating procedures should not be a barrier to randomisation, should a patient require inflow correction prior to tibial revascularisation. Trial registration ISRCTN:27728689 Date of registration: 12 May 2014.

Background The effect of idiopathic intracranial hypertension (IIH) on quality of life (QOL) is poorly understood. Our objectives were to compare QOL in IIH to the normal UK population; to investigate QOL changes with treatment of IIH, using a weight loss intervention, and to determine which clinical factors influence QOL. Methods This was a prospective cohort evaluation of QOL, using the 36-Item Short Form (SF-36) Health Survey questionnaire, before and after a therapeutic dietary intervention which resulted in significant reduction in body mass index (BMI), intracranial pressure (ICP), papilloedema, visual acuity, perimetric mean deviation (Humphrey 24–2) and headache (six-item headache impact test (HIT-6) and headache diary). Baseline QOL was compared to an age and gender matched population. The relationship between each clinical outcome and change in QOL was evaluated. Results At baseline, QOL was significantly lower in IIH compared to an age and gender matched population in most domains, p < 0.001. Therapeutic weight loss led to a significant improvement in 10 out of 11 QOL domains in conjunction with the previously published data demonstrating significant improvement in papilloedema, visual acuity, perimetry and headache (p < 0.001) and large effect size. Despite significant improvement in clinical measures only headache correlated significantly (p < 0.001) with improving QOL domains. Conclusions QOL in IIH patients is significantly reduced. It improved with weight loss alongside significant improvement in clinical measures and headache. However, headache was the only clinical outcome that correlated with enhanced QOL. Effective headache management is required to improve QOL in IIH. Electronic supplementary material The online version of this article (doi:10.1186/s10194-015-0521-9) contains supplementary material, which is available to authorized users.

Introduction Williams and colleagues reported that DBS surgery for patients with advanced PD improves motor function and quality of life compared to best medical therapy alone at 1 year, but with surgery-related side effects in a minority. This article reports on the economic evaluation alongside this trial. Methods Detailed resource use and quality of life over 12 months after randomization was obtained from the trial reported by Williams and colleagues. Outcomes were measured using the EQ-5D and quality-adjusted life years calculated. Results Year 1 costs for surgery were significantly higher than in best medical therapy, at £19,069 compared to £9,813, a difference of £9,256 (95% confidence interval [CI]: £7,625, £10,887). There was a small, significant gain in utility at 1 year but a statistically insignificant gain of 0.02 quality-adjusted life years (95% CI: −0.015, 0.05) in the surgical arm. The incremental cost per quality-adjusted life year of surgery at 1 year was £468,528. Extrapolation reveals that after 5 years, this ratio is likely to reduce to £45,180, but subsequently rise to £70,537 at 10 years owing to the increased probability of battery replacements (and re-replacements) beyond 5 years. Conclusion In this patient group, DBS is not cost-effective at 1 year. Extrapolation, however, reveals an increasing likelihood of cost-effectiveness up to 5 years and reducing cost-effectiveness between 5 and 10 years. These models are sensitive to assumptions about future costs and quality-adjusted life years gained. © 2016 International Parkinson and Movement Disorder Society