Smitaa Patel

Systematic review of levodopa dose equivalency reporting in Parkinson's disease.

Interpretation of clinical trials comparing different drug regimens for Parkinsons 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.

Physiotherapy intervention in Parkinson’s disease: systematic review and meta-analysis

Objective To assess the effectiveness of physiotherapy compared with no intervention in patients with Parkinson’s disease. Design Systematic review and meta-analysis of randomised controlled trials. Data sources Literature databases, trial registries, journals, abstract books, and conference proceedings, and reference lists, searched up to the end of January 2012. Review methods Randomised controlled trials comparing physiotherapy with no intervention in patients with Parkinson’s disease were eligible. Two authors independently abstracted data from each trial. Standard meta-analysis methods were used to assess the effectiveness of physiotherapy compared with no intervention. Tests for heterogeneity were used to assess for differences in treatment effect across different physiotherapy interventions used. Outcome measures were gait, functional mobility and balance, falls, clinician rated impairment and disability measures, patient rated quality of life, adverse events, compliance, and economic analysis outcomes. Results 39 trials of 1827 participants met the inclusion criteria, of which 29 trials provided data for the meta-analyses. Significant benefit from physiotherapy was reported for nine of 18 outcomes assessed. Outcomes which may be clinically significant were speed (0.04 m/s, 95% confidence interval 0.02 to 0.06, P<0.001), Berg balance scale (3.71 points, 2.30 to 5.11, P<0.001), and scores on the unified Parkinson’s disease rating scale (total score −6.15 points, −8.57 to −3.73, P<0.001; activities of daily living subscore −1.36, −2.41 to −0.30, P=0.01; motor subscore −5.01, −6.30 to −3.72, P<0.001). Indirect comparisons of the different physiotherapy interventions found no evidence that the treatment effect differed across the interventions for any outcomes assessed, apart from motor subscores on the unified Parkinson’s disease rating scale (in which one trial was found to be the cause of the heterogeneity). Conclusions Physiotherapy has short term benefits in Parkinson’s disease. A wide range of physiotherapy techniques are currently used to treat Parkinson’s disease, with little difference in treatment effects. Large, well designed, randomised controlled trials with improved methodology and reporting are needed to assess the efficacy and cost effectiveness of physiotherapy for treating Parkinson’s disease in the longer term.

Physiotherapy and Occupational Therapy vs No Therapy in Mild to Moderate Parkinson Disease: A Randomized Clinical Trial.

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. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN17452402.

Bypass versus angio plasty in severe ischaemia of the leg - 2 (BASIL-2) trial: study protocol for a randomised controlled trial.

BackgroundSevere 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/DesignThe 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.DiscussionThe 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 registrationISRCTN:27728689 Date of registration: 12 May 2014.

Should treatment for Parkinson's disease start immediately on diagnosis or delayed until functional disability develops?

Evidence from clinical trials with monoamine oxidase type B inhibitors (TEMPO, ADAGIO and DATATOP) and levodopa (ELLDOPA) suggests that Parkinsons disease patients may benefit from treatment being commenced immediately on diagnosis rather than waiting for functional disability to develop, as is traditional clinical practice.

An exploratory cluster randomized controlled trial of group exercise on mobility and depression in care home residents

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.

Supported community exercise in people with long-term neurological conditions: a phase II randomized controlled trial

Objective: Adults with long-term neurological conditions have low levels of participation in physical activities and report many barriers to participation in exercise. This study examines the feasibility and safety of supporting community exercise for people with long-term neurological conditions using a physical activity support system. Design: A phase II randomized controlled trial using computer-generated block randomization, allocation concealment and single blind outcome assessment. Setting: Oxfordshire and Birmingham community Inclusive Fitness Initiative gyms. Subjects: Patients with a long-term neurological condition. Interventions: The intervention group (n = 51) received a 12-week, supported exercise programme. The control group (n = 48) participants received standard care for 12 weeks and were then offered the intervention. Main measures: Physical activity, adherence to exercise, measures of mobility, health and well-being. Results: Forty-eight patients (n = 51) completed the intervention, achieving 14 gym attendances (range 0–39) over the 12 weeks. Overall activity did not increase as measured by the Physical Activity Scale for the Elderly (change score mean 14.31; 95% confidence interval (CI) −8.27 to 36.89) and there were no statistically significant changes in body function and health and well-being measures. Conclusions: People with long-term neurological conditions can safely exercise in community gyms when supported and achieve similar attendance to standard exercise referral schemes, but may reduce other life activities in order to participate at a gym.

Cost-utility analysis of deep brain stimulation surgery plus best medical therapy versus best medical therapy in patients with Parkinson's: Economic evaluation alongside the PD SURG trial.

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.

Headache determines quality of life in idiopathic intracranial hypertension.

BackgroundThe 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.MethodsThis 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.ResultsAt 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.ConclusionsQOL 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.

Clinical effectiveness and cost-effectiveness of physiotherapy and occupational therapy versus no therapy in mild to moderate Parkinson's disease: a large pragmatic randomised controlled trial (PD REHAB).

BACKGROUND Cochrane reviews of physiotherapy (PT) and occupational therapy (OT) for Parkinsons disease found insufficient evidence of effectiveness, but previous trials were methodologically flawed with small sample size and short-term follow-up. OBJECTIVES To evaluate the clinical effectiveness and cost-effectiveness of individualised PT and OT in Parkinsons disease. DESIGN Large pragmatic randomised controlled trial. SETTING Thirty-eight neurology and geriatric medicine outpatient clinics in the UK. PARTICIPANTS Seven hundred and sixty-two patients with mild to moderate Parkinsons disease reporting limitations in activities of daily living (ADL). INTERVENTION Patients were randomised online to either both PT and OT NHS services (n = 381) or no therapy (n = 381). Therapy incorporated a patient-centred approach with individual assessment and goal setting. MAIN OUTCOME MEASURES The primary outcome was instrumental ADL measured by the patient-completed Nottingham Extended Activities of Daily Living (NEADL) scale at 3 months after randomisation. Secondary outcomes were health-related quality of life [Parkinsons Disease Questionnaire-39 (PDQ-39); European Quality of Life-5 Dimensions (EQ-5D)], adverse events, resource use and carer quality of life (Short Form questionnaire-12 items). Outcomes were assessed before randomisation and at 3, 9 and 15 months after randomisation. RESULTS Data from 92% of the participants in each group were available at the primary time point of 3 months, but there was no difference in NEADL total score [difference 0.5 points, 95% confidence interval (CI) -0.7 to 1.7; p = 0.4] or PDQ-39 summary index (0.007 points, 95% CI -1.5 to 1.5; p = 1.0) between groups. The EQ-5D quotient was of borderline significance in favour of therapy (-0.03, 95% CI -0.07 to -0.002; p = 0.04). Contact time with therapists was for a median of four visits of 58 minutes each over 8 weeks (mean dose 232 minutes). Repeated measures analysis including all time points showed no difference in NEADL total score, but PDQ-39 summary index (curves diverging at 1.6 points per annum, 95% CI 0.47 to 2.62; p = 0.005) and EQ-5D quotient (0.02, 95% CI 0.00007 to 0.03; p = 0.04) showed significant but small differences in favour of the therapy arm. Cost-effective analysis showed that therapy was associated with a slight but not significant gain in quality-adjusted life-years (0.027, 95% CI -0.010 to 0.065) at a small incremental cost (£164, 95% CI -£141 to £468), resulting in an incremental cost-effectiveness ratio of under £4000 (£3493, 95% -£169,371 to £176,358). There was no difference in adverse events or serious adverse events. CONCLUSIONS NHS PT and OT did not produce immediate or long-term clinically meaningful improvements in ADL or quality of life in patients with mild to moderate Parkinsons disease. This evidence does not support the use of low-dose, patient-centred, goal-directed PT and OT in patients in the early stages of Parkinsons disease. Future research should include the development and testing of more structured and intensive PT and OT programmes in patients with all stages of Parkinsons disease. TRIAL REGISTRATION Current Controlled Trials ISRCTN17452402. FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 63. See the NIHR Journals Library website for further project information. The Birmingham Clinical Trials Unit, University of Birmingham, received support from the UK Department of Health up to March 2012. Catherine Sackley was supported by a NIHR senior investigator award, Collaboration for Leadership in Applied Health Research and Care East of England and West Midlands Strategic Health Authority Clinical Academic Training award.