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OBJECTIVES: To assess the clinical effectiveness of two speech and language therapy approaches versus no speech and language therapy for dysarthria in people with Parkinson's disease. DESIGN: Pragmatic, UK based, multicentre, three arm, parallel group, unblinded, randomised controlled trial. SETTING: The speech and language therapy interventions were delivered in outpatient or home settings between 26 September 2016 and 16 March 2020. PARTICIPANTS: 388 people with Parkinson's disease and dysarthria. INTERVENTIONS: Participants were randomly assigned to one of three groups (1:1:1): 130 to Lee Silverman voice treatment (LSVT LOUD), 129 to NHS speech and language therapy, and 129 to no speech and language therapy. LSVT LOUD consisted of four, face-to-face or remote, 50 min sessions each week delivered over four weeks. Home based practice activities were set for up to 5-10 mins daily on treatment days and 15 mins twice daily on non-treatment days. Dosage for the NHS speech and language therapy was determined by the local therapist in response to the participants' needs (estimated from prior research that NHS speech and language therapy participants would receive an average of one session per week over six to eight weeks). Local practices for NHS speech and language therapy were accepted, except for those within the LSVT LOUD protocol. Analyses were based on the intention to treat principle. MAIN OUTCOME MEASURES: The primary outcome was total score at three months of self-reported voice handicap index. RESULTS: People who received LSVT LOUD reported lower voice handicap index scores at three months after randomisation than those who did not receive speech and language therapy (-8.0 points (99% confidence interval -13.3 to -2.6); P<0.001). No evidence suggests a difference in voice handicap index scores between NHS speech and language therapy and no speech and language therapy (1.7 points (-3.8 to 7.1); P=0.43). Patients in the LSVT LOUD group also reported lower voice handicap index scores than did those randomised to NHS speech and language therapy (-9.6 points (-14.9 to -4.4); P<0.001). 93 adverse events (predominately vocal strain) were reported in the LSVT LOUD group, 46 in the NHS speech and language therapy group, and none in the no speech and language therapy group. No serious adverse events were recorded. CONCLUSIONS: LSVT LOUD was more effective at reducing the participant reported impact of voice problems than was no speech and language therapy and NHS speech and language therapy. NHS speech and language therapy showed no evidence of benefit compared with no speech and language therapy. TRIAL REGISTRATION: ISRCTN registry ISRCTN12421382.
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Disartria , Terapia da Linguagem , Doença de Parkinson , Fonoterapia , Humanos , Doença de Parkinson/complicações , Disartria/etiologia , Disartria/terapia , Disartria/reabilitação , Masculino , Feminino , Fonoterapia/métodos , Idoso , Terapia da Linguagem/métodos , Reino Unido , Pessoa de Meia-Idade , Resultado do Tratamento , Treinamento da Voz , Medicina EstatalRESUMO
In the UK, guidance exists to aid clinicians and patients deciding when treatment for Parkinson's disease (PD) should be initiated and which therapies to consider. National Institute for Health and Care Excellence (NICE) guidance recommends that before starting PD treatment clinicians should discuss the following: the patient's individual clinical circumstances; lifestyle; preferences; needs and goals; as well as the potential benefits and harms of the different drug classes. Individualization of medicines and management in PD significantly improves patients' outcomes and quality of life. This article aims to provide simple and practical guidance to help clinicians address common, but often overlooked, co-morbidities. A multi-disciplinary group of PD experts discussed areas where clinical care can be improved by addressing commonly found co-morbidities in people with Parkinson's (PwP) based on clinical experience and existing literature, in a roundtable meeting organized and funded by Bial Pharma UK Ltd. The experts identified four core areas (bone health, cardiovascular risk, anticholinergic burden, and sleep quality) that, if further standardized may improve treatment outcomes for PwP patients. Focusing on anticholinergic burden, cardiac risk, sleep, and bone health could offer a significant contribution to personalizing regimes for PwP and improving overall patient outcomes. Within this opinion-based paper, the experts offer a list of guiding factors to help practitioners in the management of PwP.
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Doença de Parkinson , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/epidemiologia , Qualidade de Vida , Estilo de Vida , Antagonistas Colinérgicos/uso terapêutico , SonoRESUMO
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 < 0.01) and lower mean costs (£3390; £2671-£4109; P < 0.01) than levodopa-sparing therapies, the difference in costs driven by the higher costs of levodopa-sparing therapies. There were no significant differences in the costs of inpatient, social care, and institutional care between arms. There was no significant difference in quality-adjusted life-years between those allocated dopamine agonists and monoamine oxidase type B inhibitors (0.02; -0.17 to 0.13 in favor of dopamine agonists; P = 0.81); however costs were significantly lower for those allocated monoamine oxidase type B inhibitors (£2321; £1628-£3015; P < 0.01) because of the higher costs of dopamine agonists. There were no significant differences between arms for other costs. CONCLUSIONS: Initial treatment with levodopa is highly cost-effective compared with levodopa-sparing therapies. Monoamine oxidase type B inhibitors, as initial levodopa-sparing therapy was more cost-effective, with similar quality-adjusted life-years but lower costs than dopamine agonists. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Agonistas de Dopamina , Doença de Parkinson , Antiparkinsonianos/uso terapêutico , Análise Custo-Benefício , Agonistas de Dopamina/uso terapêutico , Humanos , Monoaminoxidase , Inibidores da Monoaminoxidase/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Qualidade de VidaRESUMO
Debate is ongoing regarding when, why, and how to initiate pharmacotherapy for Parkinson's disease. Early initiation of dopaminergic therapies does not convey disease-modifying effects but does reduce disability. Concerns about the development of motor complications arising from the early initiation of levodopa, which led to misconceived levodopa-sparing strategies, have been largely mitigated by the outcomes of the PD MED and Levodopa in Early Parkinson's Disease (LEAP) studies. The LEAP study also showed the potential for early improvement in quality of life, even when disability is negligible. Until more effective methods of providing stable dopamine concentrations are developed, current evidence supports the use of levodopa as initial symptomatic treatment in most patients with Parkinson's disease, starting with low doses and titrating to therapeutic threshold. Monoamine oxidase-B inhibitors and dopamine agonists can be reserved as potential adjunct treatments later in the disease course. Future research will need to establish effective disease-modifying treatments, address whether patients' quality of life is substantially improved with early initiation of treatment rather than a wait and watch strategy, and establish whether new levodopa formulations will delay onset of dyskinesia.
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Antiparkinsonianos/uso terapêutico , Dopaminérgicos/uso terapêutico , Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Humanos , Qualidade de Vida , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: To assess the effects of botulinum toxin for prevention of migraine in adults. DESIGN: Systematic review and meta-analysis. DATA SOURCES: CENTRAL, MEDLINE, Embase and trial registries. ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) of botulinum toxin compared with placebo, active treatment or clinically relevant different dose for adults with chronic or episodic migraine, with or without the additional diagnosis of medication overuse headache. DATA EXTRACTION AND SYNTHESIS: Cochrane methods were used to review double-blind RCTs. Twelve week post-treatment time-point data was analysed. RESULTS: Twenty-eight trials (n=4190) were included. Trial quality was mixed. Botulinum toxin treatment resulted in reduced frequency of -2.0 migraine days/month (95% CI -2.8 to -1.1, n=1384) in chronic migraineurs compared with placebo. An improvement was seen in migraine severity, measured on a numerical rating scale 0 to 10 with 10 being maximal pain, of -2.70 cm (95% CI -3.31 to -2.09, n=75) and -4.9 cm (95% CI -6.56 to -3.24, n=32) for chronic and episodic migraine respectively. Botulinum toxin had a relative risk of treatment related adverse events twice that of placebo, but a reduced risk compared with active comparators (relative risk 0.76, 95% CI 0.59 to 0.98) and a low withdrawal rate (3%). Although individual trials reported non-inferiority to oral treatments, insufficient data were available for meta-analysis of effectiveness outcomes. CONCLUSIONS: In chronic migraine, botulinum toxin reduces migraine frequency by 2 days/month and has a favourable safety profile. Inclusion of medication overuse headache does not preclude its effectiveness. Evidence to support or refute efficacy in episodic migraine was not identified.
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Toxinas Botulínicas Tipo A/uso terapêutico , Transtornos de Enxaqueca/prevenção & controle , Adulto , Doença Crônica , Humanos , Transtornos de Enxaqueca/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
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.
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Disartria/fisiopatologia , Variações Dependentes do Observador , Doença de Parkinson/complicações , Inteligibilidade da Fala/fisiologia , Patologia da Fala e Linguagem/educação , Estudantes , Percepção Auditiva/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Leitura , Percepção da Fala/fisiologiaRESUMO
BACKGROUND: Migraine occurs in around 15% of adults and is ranked as the seventh most disabling disease amongst all diseases globally. Despite the available treatments many people suffer prolonged and frequent attacks which have a major impact on their quality of life. Chronic migraine is defined as 15 or more days of headache per month, at least eight of those days being migraine. People with episodic migraine have fewer than 15 headache days per month. Botulinum toxin type A has been licensed in some countries for chronic migraine treatment, due to the results of just two trials. OBJECTIVES: To assess the effects of botulinum toxins versus placebo or active treatment for the prevention or reduction in frequency of chronic or episodic migraine in adults. SEARCH METHODS: We searched CENTRAL, MEDLINE & MEDLINE in Process, Embase, ClinicalTrials.gov and World Health Organization International Clinical Trials Registry (to December 2017). We examined reference lists and carried out citation searches on key publications. We sent correspondence to major manufacturers of botulinum toxin. SELECTION CRITERIA: Randomised, double-blind, controlled trials of botulinum toxin (any sero-type) injections into the head and neck for prophylaxis of chronic or episodic migraine in adults. Eligible comparators were placebo, alternative prophylactic agent or different dose of botulinum toxin. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials and extracted data. For continuous outcomes we used mean change data when available. For dichotomous data we calculated risk ratios (RRs). We used data from the 12-week post-treatment follow-up time point. We assessed the evidence using GRADE and created two 'Summary of findings' tables. MAIN RESULTS: Description of trialsWe found 90 articles describing 28 trials (4190 participants), which were eligible for inclusion. The longest treatment duration was three rounds of injections with three months between treatments, so we could not analyse long-term effects. For the primary analyses, we pooled data from both chronic and episodic participant populations. Where possible, we also separated data into chronic migraine, episodic migraine and 'mixed group' classification subgroups. Most trials (21 out of 28) were small (fewer than 50 participants per trial arm). The risk of bias for included trials was low or unclear across most domains, with some trials reporting a high risk of bias for incomplete outcome data and selective outcome reporting.Botulinum toxin versus placeboTwenty-three trials compared botulinum toxin with placebo. Botulinum toxin may reduce the number of migraine days per month in the chronic migraine population by 3.1 days (95% confidence interval (CI) -4.7 to -1.4, 4 trials, 1497 participants, low-quality evidence). This was reduced to -2 days (95% CI -2.8 to -1.1, 2 trials, 1384 participants; moderate-quality evidence) when we removed small trials.A single trial of people with episodic migraine (N = 418) showed no difference between groups for this outcome measure (P = 0.49).In the chronic migraine population, botulinum toxin reduces the number of headache days per month by 1.9 days (95% CI -2.7 to -1.0, 2 trials, 1384 participants, high-quality evidence). We did not find evidence of a difference in the number of migraine attacks for both chronic and episodic migraine participants (6 trials, N = 2004, P = 0.30, low-quality evidence). For the population of both chronic and episodic migraine participants a reduction in severity of migraine rated during clinical visits, on a 10 cm visual analogue scale (VAS) of 3.3 cm (95% CI -4.2 to -2.5, very low-quality evidence) in favour of botulinum toxin treatment came from four small trials (N = 209); better reporting of this outcome measure from the additional eight trials that recorded it may have improved our confidence in the pooled estimate. Global assessment and quality-of-life measures were poorly reported and it was not possible to carry out statistical analysis of these outcome measures. Analysis of adverse events showed an increase in the risk ratio with treatment with botulinum toxin over placebo 30% (RR 1.28, 95% CI 1.12 to 1.47, moderate-quality evidence). For every 100 participants 60 experienced an adverse event in the botulinum toxin group compared with 47 in the placebo group.Botulinum toxin versus other prophylactic agentThree trials studied comparisons with alternative oral prophylactic medications. Meta-analyses were not possible for number of migraine days, number of headache days or number of migraine attacks due to insufficient data, but individually trials reported no differences between groups for a variety of efficacy measures in the population of both chronic and episodic migraine participants. The global impression of disease measured using Migraine Disability Assessment (MIDAS) scores were reported from two trials that showed no difference between groups. Compared with oral treatments, botulinum toxin showed no between-group difference in the risk of adverse events (2 trials, N = 114, very low-quality evidence). The relative risk reduction (RRR) for withdrawing from botulinum toxin due to adverse events compared with the alternative prophylactic agent was 72% (P = 0.02, 2 trials, N = 119).Dosing trialsThere were insufficient data available for the comparison of different doses.Quality of the evidenceThe quality of the evidence assessed using GRADE methods was varied but mostly very low; the quality of the evidence for the placebo and active control comparisons was low and very low, respectively for the primary outcome measure. Small trial size, high risk of bias and unexplained heterogeneity were common reasons for downgrading the quality of the evidence. AUTHORS' CONCLUSIONS: In chronic migraine, botulinum toxin type A may reduce the number of migraine days per month by 2 days compared with placebo treatment. Non-serious adverse events were probably experienced by 60/100 participants in the treated group compared with 47/100 in the placebo group. For people with episodic migraine, we remain uncertain whether or not this treatment is effective because the quality of this limited evidence is very low. Better reporting of outcome measures in published trials would provide a more complete evidence base on which to draw conclusions.
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Toxinas Botulínicas Tipo A/uso terapêutico , Transtornos de Enxaqueca/prevenção & controle , Adulto , Doença Crônica , Feminino , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Speech-related problems are common in Parkinson's disease (PD), but there is little evidence for the effectiveness of standard speech and language therapy (SLT) or Lee Silverman Voice Treatment (LSVT LOUD®). METHODS: The PD COMM pilot was a three-arm, assessor-blinded, randomised controlled trial (RCT) of LSVT LOUD®, SLT and no intervention (1:1:1 ratio) to assess the feasibility and to inform the design of a full-scale RCT. Non-demented patients with idiopathic PD and speech problems and no SLT for speech problems in the past 2 years were eligible. LSVT LOUD® is a standardised regime (16 sessions over 4 weeks). SLT comprised individualised content per local practice (typically weekly sessions for 6-8 weeks). Outcomes included recruitment and retention, treatment adherence, and data completeness. Outcome data collected at baseline, 3, 6, and 12 months included patient-reported voice and quality of life measures, resource use, and assessor-rated speech recordings. RESULTS: Eighty-nine patients were randomised with 90% in the therapy groups and 100% in the control group completing the trial. The response rate for Voice Handicap Index (VHI) in each arm was ≥ 90% at all time-points. VHI was highly correlated with the other speech-related outcome measures. There was a trend to improvement in VHI with LSVT LOUD® (difference at 3 months compared with control: - 12.5 points; 95% CI - 26.2, 1.2) and SLT (difference at 3 months compared with control: - 9.8 points; 95% CI - 23.2, 3.7) which needs to be confirmed in an adequately powered trial. CONCLUSION: Randomisation to a three-arm trial of speech therapy including a no intervention control is feasible and acceptable. Compliance with both interventions was good. VHI and other patient-reported outcomes were relevant measures and provided data to inform the sample size for a substantive trial. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number Register: ISRCTN75223808. registered 22 March 2012.
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BACKGROUND: The 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/DESIGN: Drawing 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. DISCUSSION: To 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 REGISTRATION: ISRCTN Registry, ISRCTN12421382 . Registered on 18 April 2016.
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Doença de Parkinson/terapia , Patologia da Fala e Linguagem/métodos , Qualidade da Voz , Treinamento da Voz , Protocolos Clínicos , Análise Custo-Benefício , Custos de Cuidados de Saúde , Humanos , Doença de Parkinson/diagnóstico , Doença de Parkinson/economia , Doença de Parkinson/fisiopatologia , Recuperação de Função Fisiológica , Projetos de Pesquisa , Patologia da Fala e Linguagem/economia , Fatores de Tempo , Resultado do Tratamento , Reino UnidoRESUMO
[This corrects the article DOI: 10.1155/2015/839895.].
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BACKGROUND: Cochrane reviews of physiotherapy (PT) and occupational therapy (OT) for Parkinson's 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 Parkinson's 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 Parkinson's 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 [Parkinson's 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 Parkinson's 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 Parkinson's disease. Future research should include the development and testing of more structured and intensive PT and OT programmes in patients with all stages of Parkinson's 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.
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Terapia Ocupacional/economia , Terapia Ocupacional/métodos , Doença de Parkinson/reabilitação , Modalidades de Fisioterapia/economia , Atividades Cotidianas , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Análise Custo-Benefício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Índice de Gravidade de Doença , Medicina Estatal , Avaliação da Tecnologia Biomédica , Reino UnidoAssuntos
Terapia Ocupacional , Doença de Parkinson , Humanos , Medicina , Modalidades de FisioterapiaRESUMO
BACKGROUND: Parkinson's disease has been reported in a small number of patients with chromosome 22q11.2 deletion syndrome. In this study, we screened a series of large, independent Parkinson's disease case-control studies for deletions at 22q11.2. METHODS: We used data on deletions spanning the 22q11.2 locus from four independent case-control Parkinson's disease studies (UK Wellcome Trust Case Control Consortium 2, Dutch Parkinson's Disease Genetics Consortium, US National Institute on Aging, and International Parkinson's Disease Genomics Consortium studies), which were independent of the original reports of chromosome 22q11.2 deletion syndrome. We did case-control association analysis to compare the proportion of 22q11.2 deletions found, using the Fisher's exact test for the independent case-control studies and the Mantel-Haenszel test for the meta-analyses. We retrieved clinical details of patients with Parkinson's disease who had 22q11.2 deletions from the medical records of these patients. FINDINGS: We included array-based copy number variation data from 9387 patients with Parkinson's disease and 13â863 controls. Eight patients with Parkinson's disease and none of the controls had 22q11.2 deletions (p=0·00082). In the 8451 patients for whom age at onset data were available, deletions at 22q11.2 were associated with Parkinson's disease age at onset (Mann-Whitney U test p=0·001). Age at onset of Parkinson's disease was lower in patients carrying a 22q11.2 deletion (median 37 years, 95% CI 32·0-55·5; mean 42·1 years [SD 11·9]) than in those who did not carry a deletion (median 61 years, 95% CI 60·5-61·0; mean 60·3 years [SD 12·8]). A 22q11.2 deletion was present in more patients with early-onset (p<0·0001) and late-onset Parkinson's disease (p=0·016) than in controls, and in more patients with early-onset than late-onset Parkinson's disease (p=0·005). INTERPRETATION: Clinicians should be alert to the possibility of 22q11.2 deletions in patients with Parkinson's disease who have early presentation or features associated with the chromosome 22q11.2 deletion syndrome, or both. FUNDING: UK Medical Research Council, UK Wellcome Trust, Parkinson's UK, Patrick Berthoud Trust, National Institutes of Health, "Investissements d'Avenir" ANR-10-IAIHU-06, Dutch Parkinson Foundation (Parkinson Vereniging), Neuroscience Campus Amsterdam, National Institute for Health Research, National Institute on Aging, National Institutes of Health.
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Síndrome de DiGeorge/genética , Estudo de Associação Genômica Ampla , Doença de Parkinson/genética , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Variações do Número de Cópias de DNA , Síndrome de DiGeorge/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/epidemiologiaRESUMO
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.
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Atividades Cotidianas , Terapia Ocupacional/métodos , Avaliação de Resultados em Cuidados de Saúde , Doença de Parkinson/terapia , Modalidades de Fisioterapia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Falha de Tratamento , Reino UnidoAssuntos
Antiparkinsonianos/administração & dosagem , Agonistas de Dopamina/administração & dosagem , Levodopa/administração & dosagem , Inibidores da Monoaminoxidase/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Análise Custo-Benefício , Relação Dose-Resposta a Droga , Esquema de Medicação , Humanos , Doença de Parkinson/diagnóstico , Doença de Parkinson/fisiopatologia , Resultado do TratamentoRESUMO
Purpose. Parkinson's disease can produce a range of speech-language pathologies, which may require intervention. While evaluations of speech-language therapy have been undertaken, no work has been undertaken to capture patients' experiences of therapy. This was the aim of the present study. Methods. Semistructured interviews, using themes derived from the literature, were conducted with nine Parkinson's disease patients, all of whom had undergone speech-language therapy. Participants' responses were analysed in accordance with Thematic Network Analysis. Results. Four themes emerged: emotional reactions (frustration, embarrassment, lack of confidence, disappointment, and anxiety); physical impact (fatigue, breathing and swallowing, and word production); practical aspects (cost of treatment, waiting times, and the actual clinical experience); and expectations about treatment (met versus unmet). Conclusions. While many benefits of speech-language therapy were reported, several negative issues emerged which could impact adversely on rehabilitation. Parkinson's disease is associated with a range of psychological and physical sequelae, such as fatigue and depression; recognising any individual experiences which could exacerbate the existing condition and incorporating these into treatment planning may improve rehabilitation outcomes.
RESUMO
BACKGROUND: Patients with Parkinson's disease have higher hospital admission rates than the general population. We examined the reasons for admission, length of stay, costs, and in-hospital mortality in a national sample of Parkinson's disease patients. METHODS: We used hospital admission data from the English Hospital Episodes Statistics database (2009-2013). Patients with Parkinson's disease or Parkinson's disease dementia and aged over 35 years were compared to all other admissions, excluding the above, with the same age criteria. We examined reasons for admissions (ICD-10), length of stay and in-hospital mortality. We used indirect standardisation and Poisson modelling to derive proportional ratios adjusting for age group and sex. RESULTS: There were 324,055 Parkinson's disease admissions in 182,859 patients over 4 years which included 232,905 non-elective admissions (72%). This resulted in expenditure of £907 million (£777 million for non-elective admissions). The main reasons for admission were pneumonia (13.5%), motor decline (9.4%), urinary tract infection (9.2%), and hip fractures (4.3%). These conditions occurred 1.5 to 2.6 times more frequently in patients than controls. Patients with Parkinson's disease were almost twice as likely to stay in hospital for more than 3 months (ratio 1.90, 95% CI 1.83, 1.97) and even more likely die in hospital (ratio 2.46, 95% CI 2.42, 2.49). CONCLUSIONS: Parkinson's disease patients in England have higher rates of emergency admissions with longer hospital stays, higher costs and in-hospital mortality. Urgent attention should be given to developing cost-effective interventions to reduce the burden of hospitalisation for patients, carers and healthcare systems.