Caroline Rick

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.

Deep brain stimulation plus best medical therapy versus best medical therapy alone for advanced Parkinson's disease (PD SURG trial): a randomised, open-label trial

Summary Background Surgical intervention for advanced Parkinsons 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 Parkinsons 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 Parkinsons 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 Parkinsons 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<0·0001), and in the bodily discomfort domain was −7·5 (−12·6 to −2·4; p=0·004). Differences between groups in all other domains of the PDQ-39 were not significant. 36 (19%) patients had serious surgery-related adverse events; there were no suicides but there was one procedure-related death. 20 patients in the surgery group and 13 in the best medical therapy group had serious adverse events related to Parkinsons disease and drug treatment. Interpretation At 1 year, surgery and best medical therapy improved patient self-reported quality of life more than best medical therapy alone in patients with advanced Parkinsons disease. These differences are clinically meaningful, but surgery is not without risk and targeting of patients most likely to benefit might be warranted. Funding UK Medical Research Council, Parkinsons UK, and UK Department of Health.

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.

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.

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.

Randomised controlled trial of bariatric surgery versus a community weight loss programme for the sustained treatment of idiopathic intracranial hypertension: the Idiopathic Intracranial Hypertension Weight Trial (IIH:WT) protocol

Introduction Effective treatments are lacking for idiopathic intracranial hypertension (IIH), a condition characterised by raised intracranial pressure (ICP) and papilloedema, and found primarily in obese women. Weight loss and lowering body mass index (BMI) have been shown to lower ICP and improve symptoms in IIH; however, weight loss is typically not maintained, meaning IIH symptoms return. The Idiopathic Intracranial Hypertension Weight Trial (IIH:WT) will assess whether bariatric surgery is an effective long-term treatment for patients with IIH with a BMI over 35 kg/m2. The National Institute for Health and Care Excellence recommends bariatric surgery in people with a BMI over 35 kg/m2 and a qualifying comorbidity; currently IIH does not qualify as a comorbidity. Methods and analysis IIH:WT is a multicentre, open-label, randomised controlled clinical trial of 64 participants with active IIH and a BMI over 35 kg/m2. Participants will be randomised in a 1:1 ratio to bariatric surgery or a dietary weight loss programme and followed up for 5 years. The primary outcome measure is ICP at 12 months. Secondary outcome measures include ICP at 24 and 60 months, and IIH symptoms, visual function, papilloedema, headache, quality of life and cost-effectiveness at 12, 24 and 60 months. Trial registration number IIH:WT is registered as ISRCTN40152829 and on ClinicalTrials.gov as NCT02124486 and is in the pre-results stage.

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.

The PD COMM trial: A protocol for the process evaluation of a randomised trial assessing the effectiveness of two types of SLT for people with Parkinson's disease

BackgroundThe PD COMM trial is a phase III multi-centre randomised controlled trial whose aim is to evaluate the effectiveness and cost-effectiveness of two approaches to speech and language therapy (SLT) compared with no SLT intervention (control) for people with Parkinson’s disease who have self-reported or carer-reported problems with their speech or voice. Our protocol describes the process evaluation embedded within the outcome evaluation whose aim is to evaluate what happened at the time of the PD COMM intervention implementation and to provide findings that will assist in the interpretation of the PD COMM trial results. Furthermore, the aim of the PD COMM process evaluation is to investigate intervention complexity within a theoretical model of how the trialled interventions might work best and why.Methods/designDrawing from the Normalization Process Theory and frameworks for implementation fidelity, a mixed method design will be used to address process evaluation research questions. Therapists’ and participants’ perceptions and experiences will be investigated via in-depth interviews. Critical incident reports, baseline survey data from therapists, treatment record forms and home practice diaries also will be collected at relevant time points throughout the running of the PD COMM trial. Process evaluation data will be analysed independently of the outcome evaluation before the two sets of data are then combined.DiscussionTo date, there are a limited number of published process evaluation protocols, and few are linked to trials investigating rehabilitation therapies. Providing a strong theoretical framework underpinning design choices and being tailored to meet the complex characteristics of the trialled interventions, our process evaluation has the potential to provide valuable insight into which components of the interventions being delivered in PD COMM worked best (and what did not), how they worked well and why.Trial registrationISRCTN Registry, ISRCTN12421382. Registered on 18 April 2016.

A systematic review of interventions to reduce hospitalisation in Parkinson's disease

UNLABELLED The neurodegenerative process in Parkinsons disease (PD) results in a relentless progression of motor and non-motor symptoms. Affected individuals are frequently hospitalised for complications of the disease including falls, fractures, infections, and neuropsychiatric symptoms. When admitted to hospital, inpatient care is often suboptimal as it focusses on the primary cause of admission, and is associated with poor patient outcomes and significant healthcare costs. AIM To review existing literature for evidence-based interventions aimed at reducing hospital admissions in PD. METHODS Electronic literature search in EMBASE, MEDLINE and CINAHL databases for studies evaluating interventions to reduce hospital admissions in PD. We included publications with full abstracts, published in the English language and addressing interventions to reduce hospital admissions in PD. RESULTS To date there are no randomised controlled trials addressing the topic. We identified nine relevant retrospective studies. Results from these studies suggest an association between frequent neurologist consultations, open access clinics, and medication compliance with a reduction in PD hospital admissions and emergency room visits. CONCLUSION This systematic review highlights the lack of robust evidence for measures aimed at reducing hospital admissions in people with PD. Future prospective studies are required to evaluate the effectiveness of proposed interventions.

Patients’ experiences of deep brain stimulation for Parkinson's disease: a qualitative systematic review and synthesis

Objective To review and synthesise qualitative research studies that have explored patients’ experience of deep brain stimulation (DBS) in advanced Parkinsons disease (PD). Design Systematic review and meta-synthesis of 7 original papers, using metaethnography. Setting Studies conducted in Denmark, France and Sweden. Participants 116 patients who had undergone DBS and 9 spouses of patients. Results Prior to surgery, the experience of advancing PD is one of considerable loss and a feeling of loss of control. There are significant hopes for what DBS can bring. Following surgery, a sense of euphoria is described by many, although this does not persist and there is a need for significant transitions following this. We suggest that normality as a concept is core to the experience of DBS and that a sense of control may be a key condition for normality. Experience of DBS for patients and spouses, and of the transitions that they must undertake, is influenced by their hopes of what surgery will enable them to achieve, or regain (ie, a new normality). Conclusions There is a need for further qualitative research to understand the nature of these transitions to inform how best patients and their spouses can be supported by healthcare professionals before, during and after DBS. In assessing the outcomes of DBS and other treatments in advanced PD, we should consider how to capture holistic concepts such as normality and control. Studies that examine the outcomes of DBS require longer term follow-up.