Speech and language therapy versus placebo or no intervention for speech problems in Parkinson's disease

Parkinson's disease patients commonly suffer from speech and vocal problems including dysarthric speech, reduced loudness and loss of articulation. These symptoms increase in frequency and intensity with progression of the disease). Speech and language therapy (SLT) aims to improve the intelligibility of speech with behavioural treatment techniques or instrumental aids

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

Botulinum toxins for the prevention of migraine in adults

BackgroundMigraine 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.ObjectivesTo 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 methodsWe 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 criteriaRandomised, 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 analysisTwo 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 resultsDescription 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' conclusionsIn 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

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

What are the research priorities for idiopathic intracranial hypertension? A priority setting partnership between patients and healthcare professionals.

OBJECTIVE Idiopathic intracranial hypertension (IIH) is under-researched and the aim was to determine the top 10 research priorities for this disease. DESIGN A modified nominal group technique was used to engage participants who had experience of IIH. SETTING This James Lind Alliance Priority Setting Partnership was commissioned by IIH UK, a charity. PARTICIPANTS People with IIH, carers, family and friends, and healthcare professionals participated in two rounds of surveys to identify unique research questions unanswered by current evidence. The most popular 26 uncertainties were presented to stakeholders who then agreed the top 10 topics. RESULTS The top 10 research priorities for IIH included aetiology of IIH, the pathological mechanisms of headache in IIH, new treatments in IIH, the difference between acute and gradual visual loss, the best ways to monitor visual function, biomarkers of the disease, hormonal causes of IIH, drug therapies for the treatment of headache, weight loss and its role in IIH and finally, the best intervention to treat IIH and when should surgery be performed. CONCLUSIONS This priority setting encouraged people with direct experience of IIH to collectively identify critical gaps in the existing evidence. The overarching research aspiration was to understand the aetiology and management of IIH