Katherine Deane

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.

Systematic review of paramedical therapies for Parkinson's disease

We evaluated the efficacy of physiotherapy, occupational therapy, and speech and language therapy in Parkinsons disease by synthesizing six Cochrane systematic reviews. All randomised, controlled trials examining the efficacy of a paramedical therapy versus control intervention and all those comparing the efficacy of two forms of active therapy in Parkinsons disease were included. Trials were identified by searching biomedical databases, reference lists, hand searching, and contacting investigators. The main outcome measures were quality of life, speech intelligibility, activities of daily living, and individual measures of motor and speech impairment. We identified 16 physiotherapy randomised controlled trials (399 patients), two occupational therapy trials (84 patients), and five speech and language therapy for dysarthria trials (154 patients). None of these studies examined nonpharmacological swallowing therapy for dysphagia. We were unable to perform meta‐analysis of the results because the trials used heterogeneous therapy methods and outcome measures. The trials also had marked methodological flaws that could have introduced bias. In summary, we failed to find conclusive evidence of benefit for any form of paramedical therapy sufficient to recommend them in routine clinical practice. However, this lack of evidence is not proof of a lack of effect. Further large pragmatic randomised controlled trials are required to determine the effectiveness of paramedical therapies in Parkinsons disease.

Systematic review of antidepressant therapies in Parkinson's disease☆

Depression is the most common psychiatric disturbance in Parkinsons disease. We conducted a Cochrane systematic review to assess the efficacy and safety of antidepressant therapies in idiopathic Parkinsons disease. Relevant trials were identified from electronic databases, reference lists and queries to antidepressant manufacturers. Three randomised controlled trials examined oral antidepressants in 106 patients with Parkinsons disease. No eligible trials of electroconvulsive or behavioural therapy were found. In the first arm of the crossover trial by Andersen et al. (n=22), nortriptyline treated patients showed a larger improvement than placebo in a unique depression rating scale after 16 weeks although significance levels were not provided. A parallel group trial by Wermuth et al. (n=37) did not show any significant difference between citalopram and placebo in Hamilton score after 52 weeks. Rabey et al. (n=47) performed an open-label trial comparing fluvoxamine with amitriptyline. Similar numbers in each group had a 50% reduction in Hamilton score after 16 months. Major side effects including visual hallucinations and confusion were reported with fluvoxamine and amitriptyline. Insufficient data on the effectiveness and safety of antidepressant therapies in Parkinsons disease are available on which to make recommendations for their use. Large scale randomised controlled trials are urgently required.

Adherence therapy for medication non-compliant patients with hypertension: a randomised controlled trial

The objective of this study is to establish the efficacy of adherence therapy (AT) compared with treatment as usual (TAU) in reducing blood pressure (BP) in non-compliant hypertensive patients. This study was designed as a parallel-group single-blind randomised controlled trial. The study was carried out at three general hospital outpatient clinics in Jordan. A total of 136 non-compliant hypertensive patients with a mean baseline BP of 164.5 mm Hg (s.d. 10.0) over 102.2 mm Hg (s.d. 7.0) participated in the study. 7 weekly 20-min sessions of AT in addition to TAU. The main outcome of this study is systolic blood pressure (SBP) at 11-weeks follow-up. In all, 68 patients received TAU and 68 AT. Intention-to-treat analysis included all participants randomised. AT lowered SBP by −23.11 mm Hg (95% CI: −25.85, −20.36) and diastolic BP (DBP) by −15.18 mm Hg (95% CI: −17.55, −12.80) at 11 weeks compared with TAU. Adherence (measured by pill counting) was also improved in the AT group by 37% at 11 weeks compared with TAU. No significant adverse events were reported. AT increases adherence to medication for hypertension which then leads to a clinically important reduction in BP.

A Delphi survey of best practice occupational therapy for Parkinson's disease in the United Kingdom

This study was designed to determine the character of best occupational therapy practice for Parkinsons disease in the United Kingdom. Two hundred and forty-two occupational therapists treating people with Parkinsons disease were sent a Delphi survey containing statements about best practice and asked to indicate their level of agreement with each statement. The second survey contained the same list of statements, with group levels of agreement from the first round for each statement. The respondents re-rated their answers and gave their opinion on the efficacy of various interventions. One hundred and fifty occupational therapists (62%) completed both rounds. Ninety-nine per cent of the respondents agreed that Parkinsons disease required lifelong provision of occupational therapy, within multidisciplinary teams, and that the social and psychological aspects of the disease were as important as the physical ones. The occupational therapists had confidence in many techniques for achieving physical, social and psychological goals. However, 40% of the respondents could not rate the efficacy of social and psychological techniques owing to a lack of knowledge. There was a high level of consensus nationally on the character of best practice occupational therapy for Parkinsons disease. The survey highlighted a need for more postgraduate training, especially in psychological techniques.

Meta-analysis of the comparative efficacy and safety of adjuvant treatment to levodopa in later Parkinson's disease.

Levodopa initially provides good symptomatic control of the symptoms of Parkinsons disease, but motor complications often develop after long‐term use. Other classes of antiparkinsonian drugs including dopamine agonists, catechol‐O‐methyl transferase inhibitors, or monoamine oxidase type B inhibitors are then added as adjuvant therapy. It is unclear whether one class of drug is more effective than another. This meta‐analysis evaluates the comparative benefits and risks of these agents as adjuvant treatment in Parkinsons disease patients with motor complications.

Identification and characterization of a DR4-restricted T cell epitope within chlamydia heat shock protein 60

An epitope within the 60 kD Chlamydia trachomatis heat shock protein (hsp) 60, recognized by a HLA‐DRB1*0401‐restricted T cell clone from a reactive arthritis patient, has been characterized. Stimulatory peptides contained a nine amino acid sequence (residues 38–46) predicted by algorithm to confer strong binding to DRB1*0401, with valine in the P1 position. The overall length of the peptide was critical for efficient recognition; peptides with at least one residue N‐terminal to the putative P1 position were markedly more stimulatory than a peptide whose N‐terminal is the P1 valine. Optimal responses were seen with 14mer peptides having two to three amino acids N‐ and C‐terminal to the core 9mer. The sequence of the defined epitope is identical in hsp60 from both C. trachomatis and C. pneumoniae. Since the latter is a common respiratory pathogen, patients infected with C. trachomatis may already be primed for responses to hsp60 by prior infection with C. pneumoniae. Such secondary responses are important in the pathogenesis of chlamydia‐induced inflammatory diseases such as trachoma. Priming by infection with enteric organisms was considered because of the similarity of the epitope sequence in Escherichia coli hsp60. However, although an E. coli‐related peptide was recognized, intact E. coli hsp60 was not, suggesting that the epitope is cryptic in E. coli hsp60. Human hsp60 has six amino acid differences from chlamydial hsp60 in the epitope sequence and was not recognized. Thus cross‐reactive recognition of self hsp60 could not be implicated in the pathogenesis of chlamydia‐induced reactive arthritis in this patient.

National survey of speech and language therapy provision for people with Parkinson's disease in the United Kingdom: therapists’ practices

BACKGROUND Communication and swallowing changes feature prominently in Parkinsons disease. People with Parkinsons disease appear under-represented in speech-language therapy clinics in the United Kingdom. The nature of the speech-language therapy services in the UK to people with Parkinsons disease has not been examined. AIMS To ascertain the number of speech-language therapists in the UK who work with people with Parkinsons disease; to establish the nature of contacts in terms of caseloads, referral stages and routes, management practices, assessments and treatments employed; and to reflect on service provision in relation to published guidelines. METHODS & PROCEDURES A questionnaire survey of speech-language therapists. OUTCOMES & RESULTS A total of 185 speech-language therapists responded. They were treating a median of three (inter-quartile range (IQR) = 1-6) people with Parkinsons disease with a further median of five (IQR = 1-10) on review. The majority of contacts were for assessment and advice given, especially in later and earlier stages of Parkinsons disease. Typically, respondents offered a median of six sessions (IQR = 6-8) of treatment, each session lasting a median of 45 min (IQR = 45-60), delivered over a median period of 42 days (IQR = 28-56). Speech-language therapists worked in a variety of settings, predominantly hospital. They received referrals principally from medical specialities, from whom the majority had support. Referrals were perceived in general to be later in Parkinsons disease progression than desired. Assessment focused primarily on impairment measures, in contrast to a belief that therapy focus on activity and participation issues. Speech-language therapists were relatively confident in treating people with Parkinsons disease, but 75% wanted more training. CONCLUSIONS & IMPLICATIONS Speech-language therapist services for people with Parkinsons disease in the UK are restricted on most dimensions. Management practices often do not match guideline suggestions. Consideration needs to be given to the training for, content of and delivery of speech-language therapy services for people with Parkinsons disease.

Priority setting partnership to identify the top 10 research priorities for the management of Parkinson's disease

Objectives This priority setting partnership was commissioned by Parkinsons UK to encourage people with direct and personal experience of the condition to work together to identify and prioritise the top 10 evidential uncertainties that impact on everyday clinical practice for the management of Parkinsons disease (PD). Setting The UK. Participants Anyone with experience of PD including: people with Parkinsons (PwP), carers, family and friends, healthcare and social care professionals. Non-clinical researchers and employees of pharmaceutical or medical devices companies were excluded. 1000 participants (60% PwP) provided ideas on research uncertainties, 475 (72% PwP) initially prioritised them and 27 (37% PwP) stakeholders agreed a final top 10. Methods Using a modified nominal group technique, participants were surveyed to identify what issues for the management of PD needed research. Unique research questions unanswered by current evidence were identified and participants were asked to identify their top 10 research priorities from this list. The top 26 uncertainties were presented to a consensus meeting with key stakeholders to agree the top 10 research priorities. Results 1000 participants provided 4100 responses, which contained 94 unique unanswered research questions that were initially prioritised by 475 participants. A consensus meeting with 27 stakeholders agreed the top 10 research priorities. The overarching research aspiration was an effective cure for PD. The top 10 research priorities for PD management included the need to address motor symptoms (balance and falls, and fine motor control), non-motor symptoms (sleep and urinary dysfunction), mental health issues (stress and anxiety, dementia and mild cognitive impairments), side effects of medications (dyskinesia) and the need to develop interventions specific to the phenotypes of PD and better monitoring methods. Conclusions These research priorities identify crucial gaps in the existing evidence to address everyday practicalities in the management of the complexities of PD.

Recognition of the 60 kilodalton cysteine-rich outer membrane protein OMP2 by CD4(+) T cells from humans infected with Chlamydia trachomatis.

T cell‐mediated immunity is important in the control of chlamydia infection but chlamydia‐specific T cells are also implicated in the inflammation and tissue damage which characterize chlamydia associated diseases. To investigate target antigens of the T cell‐mediated immune response to chlamydia infection, Chlamydia trachomatis‐specific CD4+ T cell clones were isolated from a patient with chlamydia‐induced reactive arthritis. T cell immunoblotting indicated that an antigen of ∼60 kilodaltons molecular mass was recognized, and recombinant 60 kilodalton cysteine‐rich outer membrane 2 (OMP2) proved to be stimulatory. By using deletion constructs and synthetic peptides an epitope presented by HLA‐DRB1*0401 was defined and proved to contain the nonamer peptide within the OMP2 sequence predicted to have the greatest binding affinity for DRB1*0401 The sequence of the epitope is conserved in all C. trachomatis strains but not in C. pneumoniae. Investigation of patients with acute urethritis and additional patients with sexually acquired reactive arthritis showed that OMP2‐reactive T cells were readily detectable in peripheral blood and synovial fluid. Thus OMP2 is a target antigen of the T cell‐mediated immune response to CT infection.