Biomedical subjects

C E Clarke

Publications and source records attributed to C E Clarke.

At least 37 records · Page 2Linked to original sources

PubMed2001

Cabergoline for levodopa-induced complications in Parkinson's disease.

BACKGROUND: Long term levodopa therapy in Parkinson's disease is associated with the development of motor complications including abnormal involuntary movements and a shortening response to each dose (wearing off phenomenon). It is thought that dopamine agonists can reduce the duration of immobile off periods and the need for levodopa therapy whilst maintaining or improving motor impairments and only minimally increasing dopaminergic adverse events. OBJECTIVES: To compare the efficacy and safety of adjuvant cabergoline therapy versus placebo in patients with Parkinson's disease, already established on levodopa and suffering from motor complications. SEARCH STRATEGY: Electronic searches of MEDLINE, EMBASE and the Cochrane Controlled Trials Register. Handsearching of the neurology literature as part of the Cochrane Movement Disorders Group's strategy. Examination of the reference lists of identified studies and other reviews. Contact with Pharmacia Upjohn Limited. SELECTION CRITERIA: Randomised controlled trials of cabergoline versus placebo in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy. DATA COLLECTION AND ANALYSIS: Data was abstracted independently by the authors and differences settled by discussion. The outcome measures used included Parkinson's disease rating scales, levodopa dosage, off time measurements and the frequency of withdrawals and adverse events. MAIN RESULTS: Cabergoline has been compared with placebo in two phase II (6 - 12 weeks) and one phase III randomised controlled trials (24 weeks). These were double-blind, parallel group, multicentre studies including 268 patients with Parkinson's disease and motor complications. The reduction of 1.14 hours (WMD; 95% CI -0.06, 2.33; p = 0.06) in off time in favour of cabergoline was not statistically significant. Inadequate data on dyskinesia was collected either on rating scales or as adverse event reporting to allow a conclusion to be drawn. A small but statistically significant advantage of cabergoline over placebo was seen in one study for UPDRS ADL (part II) score and UPDRS motor score. No such advantage was seen in one other study due to small numbers of patients and the comparatively low doses of cabergoline used. No significant differences in Schwab and England scale were seen in two studies. Levodopa dose reduction was significantly greater with cabergoline (WMD 149.6 mg/d; 95% CI 94.1, 205.1; p < 0.00001). There was a trend towards more dopaminergic adverse events with cabergoline but this did not reach statistical significance at the p < 0.01 level. However, there was a trend towards fewer withdrawals from cabergoline. REVIEWER'S CONCLUSIONS: In the management of the motor complications seen in Parkinson's disease, cabergoline can be used to reduce levodopa dose and modestly improve motor impairment and disability with an acceptable adverse event profile. These conclusions are based on, at best, medium term evidence.

Antiparkinson Agents↗

PubMed2001

Cabergoline versus bromocriptine for levodopa-induced complications in Parkinson's disease.

BACKGROUND: Long term levodopa therapy in Parkinson's disease is associated with the development of motor complications including abnormal involuntary movements and a shortening response to each dose (wearing off phenomenon). It is thought that dopamine agonists can reduce the duration of immobile off periods and the need for levodopa therapy whilst maintaining or improving motor impairments and only minimally increasing dopaminergic adverse events. OBJECTIVES: To compare the efficacy and safety of adjuvant cabergoline therapy versus bromocriptine in patients with Parkinson's disease, already established on levodopa and suffering from motor complications. SEARCH STRATEGY: Electronic searches of MEDLINE, EMBASE and the Cochrane Controlled Trials Register. Handsearching of the neurology literature as part of the Cochrane Movement Disorders Group's strategy. Examination of the reference lists of identified studies and other reviews. Contact with Pharmacia Upjohn Limited. SELECTION CRITERIA: Randomised controlled trials of cabergoline versus bromocriptine in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by the authors and differences settled by discussion. The outcome measures used included Parkinson's disease rating scales, levodopa dosage, off time measurements and the frequency of withdrawals and adverse events. MAIN RESULTS: Cabergoline has been compared with bromocriptine in five randomised, double-blind, parallel group studies including 1071 patients. Only one of the phase II studies was medium term (36 weeks), the others all being short term (12 -15 weeks). The non-significant difference in off time reduction produced by cabergoline compared with bromocriptine was 0.29 hours/day in favour of the former (weighted mean difference; 95% CI -0.10, 0.68; p = 0.15). Dyskinesia reported as an adverse event was significantly increased with cabergoline compared with bromocriptine (Peto odds ratio 1.57; 95% CI 1.05, 2.35; p = 0.03). Motor impairment and disability were measured in four of the studies using the UPDRS rating scale but the small differences in UPDRS ADL (part II) and motor (part III) scores were not statistically significant in any study. Similarly, no significant difference in Schwab and England score was seen. The number of patients rated as much or very much improved on a clinician's global impression scale was similar with both agonists. Levodopa dose reduction was no different between cabergoline and bromocriptine. There was more confusion with cabergoline (Peto odds ratio 2.02; 95% CI 1.09, 3.76; p = 0.03). Otherwise, dopaminergic adverse events were comparable with these agonists and no significant difference in all cause withdrawal rate was found. REVIEWER'S CONCLUSIONS: Cabergoline produces similar benefits to bromocriptine in off time reduction, motor impairment and disability ratings, and levodopa dose reduction over the first three months of therapy. Dyskinesia and confusion were increased with cabergoline but otherwise the frequency of adverse events and withdrawals from treatment were similar with the two agonists.

Antiparkinson Agents↗

PubMed2001

Speech and language therapy for dysarthria in Parkinson's disease.

BACKGROUND: Dysarthria is a common manifestation of Parkinson's disease which increases in frequency and intensity with the progress of the disease (Streifler 1984). Up to 20% of Parkinsonian patients are referred for speech and language therapy (S & L T), its aim being to improve the intelligibility of the patient's speech. OBJECTIVES: To compare the efficacy of speech and language therapy versus placebo or no interventions in patients with Parkinson's disease. SEARCH STRATEGY: Relevant trials were identified by electronic searches of MEDLINE, EMBASE, CINAHL, ISI-SCI, AMED, MANTIS, REHABDATA, REHADAT, GEROLIT, Pascal, LILACS, MedCarib, JICST-EPlus, AIM, IMEMR, SIGLE, ISI-ISTP, DISSABS, Conference Papers Index, Aslib Index to Theses, the Cochrane Controlled Trials Register, the CentreWatch Clinical Trials listing service, the metaRegister of Controlled Trials, ClinicalTrials.gov, CRISP, PEDro, NIDRR and NRR; and examination of the reference lists of identified studies and other reviews. SELECTION CRITERIA: Only randomised controlled trials (RCT) were included. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by KD and RW and differences settled by discussion. MAIN RESULTS: Three randomised controlled trials were found comparing speech and language therapy with placebo for speech disorders in Parkinson's disease. A total of 63 patients were examined. The loudness of the patients' voices were increased by between 7-18%, depending on the speaking task being performed. It is likely that this is a clinically significant improvement. After six months the degree of improvement was reduced but was still statistically significant. Overall measures of dysarthria were measured in two trials and also improved. The clinical significance of these improvements was less clear cut as intelligibility of speech was not measured in any of these studies. REVIEWER'S CONCLUSIONS: Considering the small number of patients examined, the methodological flaws in many of the studies, and the possibility of publication bias, there is insufficient evidence to support or refute the efficacy of speech and language therapy for dysarthria in Parkinson's disease. A Delphi-style survey is needed to develop a consensus as to what is 'standard' S< for dysarthria in Parkinson's disease. Then a large well designed placebo-controlled RCT is needed to demonstrate speech and language therapy's effectiveness for dysarthria in Parkinson's disease. The trial should conform to CONSORT guidelines. Outcome measures with particular relevance to patients should be chosen and the patients followed for at least 6 months to determine the duration of any improvement.

Dysarthria↗

PubMed2001

Occupational therapy for patients with Parkinson's disease.

BACKGROUND: Despite drug and surgical therapies for Parkinson's disease, patients develop progressive disability. The role of the occupational therapist is to support the patient and help them maintain their usual level of self-care, work and leisure activities for as long as possible. When it is no longer possible to maintain their usual activities, occupational therapists support individuals in changing and adapting their relationship with their physical and social environment to develop new valued activities and roles. OBJECTIVES: To compare the efficacy and effectiveness of occupational therapy with placebo or no interventions (control group) in patients with Parkinson's disease. SEARCH STRATEGY: Relevant trials were identified by electronic searches of MEDLINE, EMBASE, CINAHL, ISI-SCI, AMED, MANTIS, REHABDATA, REHADAT, GEROLIT, Pascal, LILACS, MedCarib, JICST-EPlus, AIM, IMEMR, SIGLE, ISI-ISTP, DISSABS, Conference Papers Index, Aslib Index to Theses, the Cochrane Controlled Trials Register, the CentreWatch Clinical Trials listing service, the metaRegister of Controlled Trials, ClinicalTrials.gov, CRISP, PEDro, NIDRR and NRR; and the reference lists of identified studies and other reviews were examined. SELECTION CRITERIA: Only randomised controlled trials (RCT) were included, however those trials that allowed quasi-random methods of allocation were allowed. DATA COLLECTION AND ANALYSIS: Data was abstracted independently by two authors and differences were settled by discussion. MAIN RESULTS: Two trials were identified with 84 patients in total. Although both trials reported a positive effect from occupational therapy, all of the improvements were small. The trials did not have adequate placebo treatments, used small numbers of patients and the method of randomisation and concealment of allocation was not specified in one trial. These methodological problems could potentially lead to bias from a number of sources reducing the strength of the studies further. REVIEWER'S CONCLUSIONS: Considering the significant methodological flaws in the studies, the small number of patients examined, and the possibility of publication bias, there is insufficient evidence to support or refute the efficacy of occupational therapy in Parkinson's disease. There does not appear to be a consensus as to the best practice in occupational therapy when treating people with Parkinson's disease. A survey of therapists is needed to determine what methods of occupational therapy are currently being used by therapists to treat Parkinson's disease, and whether there is a consensus as to 'best-practice'. Large well designed placebo-controlled RCTs are needed to demonstrate occupational therapy's effectiveness in Parkinson's disease. Outcome measures with particular relevance to patients, carers, occupational therapists and physicians should be chosen and the patients monitored for at least six months to determine the duration of benefit. The trials should be reported using CONSORT guidelines.

Humans↗

PubMed2001

A comparison of speech and language therapy techniques for dysarthria in Parkinson's disease.

BACKGROUND: Dysarthria is a common manifestation of Parkinson's disease that increases in frequency and intensity with the progress of the disease (Streifler 1984). Up to 20% of Parkinsonian patients are referred for speech and language therapy (S & LT), its aim being to improve the intelligibility of the patient's speech. OBJECTIVES: To compare the efficacy and effectiveness of novel S & LT techniques versus standard S & LT to treat dysarthria in patients with Parkinson's disease. To compare the efficacy and effectiveness of one S & LT technique versus a second form of S & LT to treat Parkinsonian dysarthria. SEARCH STRATEGY: Relevant trials were identified by electronic searches of MEDLINE, EMBASE, CINAHL, ISI-SCI, AMED, MANTIS, REHABDATA, REHADAT, GEROLIT, Pascal, LILACS, MedCarib, JICST-EPlus, AIM, IMEMR, SIGLE, ISI-ISTP, DISSABS, Conference Papers Index, Aslib Index to Theses, the Cochrane Controlled Trials Register, the CentreWatch Clinical Trials listing service, the metaRegister of Controlled Trials, ClinicalTrials.gov, CRISP, PEDro, NIDRR and NRR; and examination of the reference lists of identified studies and other reviews. SELECTION CRITERIA: Only randomised controlled trials (RCT) were included. DATA COLLECTION AND ANALYSIS: Data was abstracted independently by KD and RW and differences settled by discussion. MAIN RESULTS: Only two trials were identified with only 71 patients. The method of randomisation was good in only one trial and the concealment of allocation was inadequate in both trials. These methodological problems could potentially lead to bias from a number of sources. The methods used in the two studies varied so much that meta-analysis of the results was not possible. Scott 83 compared prosodic exercises with visual cues with prosodic exercises alone (See Glossary: Table 01). The authors examined prosody and intelligibility as outcome measures immediately after therapy. Ramig 95 compared the Lee Silverman Voice Therapy (LSVT) which emphasises increased vocal effort, with respiratory therapy which aimed to increase respiratory muscle activity. Ramig 95 examined a wide range of vocal characteristics, activities of daily living affected by speech, depression and the carer's impressions of the patient's speech quality. Some of these outcomes were measured up to 24 months after the end of the therapy. However, in neither study were changes in outcomes due to 'Therapy A' compared with the changes due to 'Therapy B' statistically. Therefore no comment on the comparative efficacy of these types of speech and language therapy can be made. REVIEWER'S CONCLUSIONS: Considering the methodological flaws in both of these studies, the small number of patients examined, and the possibility of publication bias, there is insufficient evidence to support or refute the efficacy of any given form of S & LT over another to treat dysarthria in Parkinson's disease. Given the lack of evidence from RCTs to support or refute the efficacy of S & LT in Parkinson's disease (see Cochrane review 'Speech and Language therapy for Dysarthria in Patients with Parkinson's Disease'), the consensus as to what is considered 'best-practice' S & LT must be proved first through a large well-designed placebo-controlled randomised trial before examining variations in S & LT methodology. The design of these trials should minimise bias and be reported fully using CONSORT guidelines (CONSORT 1996). Outcome measures with particular relevance to patients, their carers, physicians and speech and language therapists should be chosen and the patients followed for at least 6 months to determine the duration of any improvement.

Bias↗

PubMed2001

A comparison of physiotherapy techniques for patients with Parkinson's disease.

BACKGROUND: Despite optimal medical and surgical therapies for Parkinson's disease, patients develop progressive disability. The role of the physiotherapist is to maximise functional ability and minimise secondary complications through movement rehabilitation within a context of education and support for the whole person. What form of physiotherapy is most effective in the treatment of Parkinson's disease remains unclear. OBJECTIVES: 1. To compare the efficacy and effectiveness of novel physiotherapy techniques versus 'standard' physiotherapy in patients with Parkinson's disease. Standard physiotherapy is defined as the type of therapy that the physiotherapist would usually use to treat Parkinson's disease. 2. To compare the efficacy and effectiveness of one physiotherapy technique versus a second form of physiotherapy. SEARCH STRATEGY: Relevant trials were identified by electronic searches of MEDLINE, EMBASE, CINAHL, ISI-SCI, AMED, MANTIS, REHABDATA, REHADAT, GEROLIT, Pascal, LILACS, MedCarib, JICST-EPlus, AIM, IMEMR, SIGLE, ISI-ISTP, DISSABS, Conference Papers Index, Aslib Index to Theses, the Cochrane Controlled Trials Register, the CentreWatch Clinical Trials listing service, the metaRegister of Controlled Trials, ClinicalTrials.gov, CRISP, PEDro, NIDRR and NRR; and examination of the reference lists of identified studies and other reviews. SELECTION CRITERIA: Only randomised controlled trials (RCT) were included. DATA COLLECTION AND ANALYSIS: Data was abstracted independently by KD and CEH and differences settled by discussion. MAIN RESULTS: Seven trials were identified with 142 patients. All used small numbers of patients and the method of randomisation and concealment of allocation was poor or not statedin all of the trials. These methodological problems could potentially lead to bias from a number of sources. The methods of physiotherapy varied so widely that the data could not be combined. REVIEWER'S CONCLUSIONS: Considering the small number of patients examined, the methodological flaws in many of the studies and the possibility of publication bias, there is insufficient evidence to support or refute the efficacy of any given form of physiotherapy over another in Parkinson's disease. Another Cochrane review, Physiotherapy for patients with Parkinson's Disease, found that there was insufficient evidence to support or refute the efficacy of physiotherapy compared to no physiotherapy in Parkinson's disease. A wide range of physiotherapy approaches were used in these studies and a survey of UK physiotherapists confirmed that they also use an eclectic combination of techniques in the treatment of Parkinson's disease (Plant 1999). Therefore a consensus must be found as to 'best practice' physiotherapy for Parkinson's disease. The efficacy of 'standard' physiotherapy should be proved first before examining variations in physiotherapy methods. Therefore large well designed randomised controlled trials are needed to judge the effect of physiotherapy in Parkinson's disease. After this large RCTs are needed to demonstrate the most effective form of physiotherapy in Parkinson's disease. Outcome measures with particular relevance to patients, carers, physiotherapists and physicians should be chosen and the patients monitored for at least 6 months to determine the duration of any effect. The trials should be reported according to CONSORT guidelines (CONSORT 1996).

Humans↗

PubMed2001

Non-pharmacological therapies for dysphagia in Parkinson's disease.

BACKGROUND: Dysphagia occurs frequently in Parkinson's disease although patients themselves may be unaware of swallowing difficulties. Speech and language therapists in conjunction with nurses and dietitians use techniques that aim to improve swallowing and reduce the risk of choking, aspiration and chest infections. OBJECTIVES: ~Bullet~To compare the efficacy and effectiveness of non-pharmacological swallowing therapy for dysphagia versus placebo or no intervention in patients with Parkinson's disease. ~Bullet~To compare one form of non-pharmacological swallowing therapy for dysphagia with another in patients with Parkinson's disease. SEARCH STRATEGY: Relevant trials were identified by electronic searches of MEDLINE, EMBASE, CINAHL, ISI-SCI, AMED, MANTIS, REHABDATA, REHADAT, GEROLIT, Pascal, LILACS, MedCarib, JICST-EPlus, AIM, IMEMR, SIGLE, ISI-ISTP, DISSABS, Conference Papers Index, Aslib Index to Theses, the Cochrane Controlled Trials Register, the CentreWatch Clinical Trials listing service, the metaRegister of Controlled Trials, ClinicalTrials.gov, CRISP, PEDro, NIDRR and NRR; and examination of the reference lists of identified studies and other reviews. SELECTION CRITERIA: Only randomised controlled trials (RCT) were included. We did not examine any trials using drugs or surgery to treat the dysphagia. We did not examine any trials where part of the therapist's advice was to insert a nasogastric or percutaneous gastrostomy tube. DATA COLLECTION AND ANALYSIS: Not applicable. MAIN RESULTS: No randomised controlled trials or controlled trials were found that examined the efficacy of non-pharmacological swallowing therapy for the treatment of dysphagia in Parkinson's disease. However there is one large RCT currently recruiting patients that will compare 'chin down' posture with thickened liquids in the treatment of dysphagia. The main outcomes will be the rates of aspiration and pneumonia. REVIEWER'S CONCLUSIONS: There is currently no evidence to support or refute the efficacy of non-pharmacological swallowing therapy for dysphagia in Parkinson's disease. Large well designed placebo-controlled RCTs are required to assess the effectiveness of swallowing therapy for dysphagia in Parkinson's disease and reported according to CONSORT guidelines. Suitable outcome measures should be chosen so that the efficacy and effectiveness of non-pharmacological swallowing therapy can be assessed and an economic analysis performed. Outcomes which have meaning to patients and carers should be used wherever possible since they need to know the value of this therapy in practical terms. The patients should be followed for at least 6 months to determine the duration of any improvement.

Deglutition↗

PubMed2001

Physiotherapy for patients with Parkinson's Disease: a comparison of techniques.

BACKGROUND: Despite optimal medical and surgical therapies for Parkinson's disease, patients develop progressive disability. The role of the physiotherapist is to maximise functional ability and minimise secondary complications through movement rehabilitation within a context of education and support for the whole person. OBJECTIVES: To compare the efficacy and effectiveness of physiotherapy with placebo or no interventions in patients with Parkinson's disease. SEARCH STRATEGY: Relevant trials were identified by electronic searches of MEDLINE, EMBASE, CINAHL, ISI-SCI, AMED, MANTIS, REHABDATA, REHADAT, GEROLIT, Pascal, LILACS, MedCarib, JICST-EPlus, AIM, IMEMR, SIGLE, ISI-ISTP, DISSABS, Conference Papers Index, Aslib Index to Theses, the Cochrane Controlled Trials Register, the CentreWatch Clinical Trials listing service, the metaRegister of Controlled Trials, ClinicalTrials.gov, CRISP, PEDro, NIDRR and NRR; and examination of the reference lists of identified studies and other reviews. SELECTION CRITERIA: Only randomised controlled trials (RCT) were included, however those trials that allowed quasi-random methods of allocation were allowed. DATA COLLECTION AND ANALYSIS: Data was abstracted independently by KD and DJ and differences settled by discussion. MAIN RESULTS: Eleven trials were identified with 280 patients. Eight trials did not have adequate placebo treatments, all used small numbers of patients and the method of randomisation and concealment of allocation was good in only four trials. These methodological problems could potentially lead to bias from a number of sources. Although ten of the trials claimed a positive effect from physiotherapy, few outcomes measured were statistically significant. Walking velocity was measured in four trials and increased significantly in two of them. Stride length was the only other outcome measured in more than one trial, it was significantly improved in two trials. Five other outcomes improved significantly in individual studies, but eight other outcomes did not improve significantly. REVIEWER'S CONCLUSIONS: Considering the methodological flaws in many of the studies, the small number of patients examined, and the possibility of publication bias, there is insufficient evidence to support or refute the efficacy of physiotherapy in Parkinson's disease. The studies illustrate that a wide range of approaches are being employed by physiotherapists to treat Parkinson's disease. This was confirmed by the UK survey of physiotherapists. There is a need to develop a consensus as to 'best-practice'. Large well designed placebo-controlled RCTs are then needed to demonstrate the efficacy and effectiveness of 'best practice' physiotherapy in Parkinson's disease. The stage of the disease at which the physiotherapy is given should be specified at the outset. Outcome measures with particular relevance to patients, carers, physiotherapists and physicians should be chosen and the patients monitored for at least six months to determine the duration of any beneficial effects. The trials should be reported according to CONSORT guidelines.

Humans↗

PubMed2001

Systematic review of proton magnetic resonance spectroscopy of the striatum in parkinsonian syndromes.

It has been suggested that proton magnetic resonance spectroscopy (MRS) of the striatum can differentiate between parkinsonian syndromes. The present study aims to examine this claim by performing a systematic review of the existing literature. A MEDLINE search was performed between 1966 and October 1999, along with searches of conference abstracts and reference lists of papers identified. Eleven groups have used MRS to examine metabolite ratios in the striatum in Parkinsonian syndromes. A number of these have shown reduced N-acetylaspartate/choline (NAA/Cho) and/or N-acetylaspartate/creatine (NAA/Cr) ratios in either idiopathic Parkinson's disease (IPD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP) or corticobasal degeneration. However, the heterogeneity in the results precludes the use of any of these findings in differential diagnosis at the present time. The only group to use absolute metabolite concentrations rather than ratios showed that the decreased NAA/Cho ratio in IPD was because of an increase in choline which is of uncertain biological significance. Further large multicentre trials are required using absolute quantitation of tissue metabolite concentrations and a standardized technique. The patients entering such studies must be rigorously assessed to establish the diagnosis of the type of parkinsonism as accurately as possible. Any discriminatory abnormality must be tested in a large prospective study of newly presenting parkinsonian patients with long-term clinical follow up and ultimate pathological confirmation of the diagnosis as far as possible.

Diagnosis, Differential↗

PubMed2001

Updated guidelines for the management of Parkinson's disease.

New data on diagnosis, drug therapy, surgery and psychosocial concerns have emerged since the publication of the 1998 Guidelines for the Management of Parkinson's Disease. This article reviews new data and addresses issues left unanswered in the previous guidelines.

Aged↗

PubMed2000

A five-year study of the incidence of dyskinesia in patients with early Parkinson's disease who were treated with ropinirole or levodopa.

BACKGROUND: There is debate about whether the initial treatment for patients with Parkinson's disease should be levodopa or a dopamine agonist. METHODS: In this prospective, randomized, double-blind study, we compared the safety and efficacy of the dopamine D2-receptor agonist ropinirole with that of levodopa over a period of five years in 268 patients with early Parkinson's disease. If symptoms were not adequately controlled by the assigned study medication, patients could receive supplementary levodopa, administered in an open-label fashion. The primary outcome measure was the occurrence of dyskinesia. RESULTS: Eighty-five of the 179 patients in the ropinirole group (47 percent) and 45 of the 89 patients in the levodopa group (51 percent) completed all five years of the study. In the ropinirole group 29 of the 85 patients (34 percent) received no levodopa supplementation. The analysis of the time to dyskinesia showed a significant difference in favor of ropinirole (hazard ratio for remaining free of dyskinesia, 2.82; 95 percent confidence interval, 1.78 to 4.44; P<0.001). At five years, the cumulative incidence of dyskinesia (excluding the three patients who had dyskinesia at base line), regardless of levodopa supplementation, was 20 percent (36 of 177 patients) in the ropinirole group and 45 percent (40 of 88 patients) in the levodopa group. There was no significant difference between the two groups in the mean change in scores for activities of daily living among those who completed the study. Adverse events led to the early withdrawal from the study of 48 of 179 patients in the ropinirole group (27 percent) and 29 of 89 patients in the levodopa group (33 percent). The mean (+/-SD) daily doses given by the end of the study were 16.5+/-6.6 mg of ropinirole (plus 427+/-221 mg of levodopa in patients who received supplementation) and 753+/-398 mg of levodopa (including supplements). CONCLUSIONS: Early Parkinson's disease can be managed successfully for up to five years with a reduced risk of dyskinesia by initiating treatment with ropinirole alone and supplementing it with levodopa if necessary.

Aged↗

PubMed2000

Mutation of histidine 286 of the human P2X4 purinoceptor removes extracellular pH sensitivity.

1. Effects of external pH on the human P2X4 purinoceptor, an ATP-activated ion channel, were studied using the Xenopus oocyte expression system. 2. Changing the external pH from 7.4 to 6.5 significantly reduced, whilst an increase to pH 8 enhanced, maximum ATP-activated current amplitude, without changing the current- voltage relationship of the ATP-activated current. 3. Diethyl pyrocarbonate (DEPC; 10 mM) treatment of P2X4-injected oocytes had no effect on the pH sensitivity of the ATP-activated current. 4. Site-directed mutagenesis of histidine 286 (H286) to alanine completely abolished the pH sensitivity of the P2X4 receptor at all agonist concentrations. ATP potency showed a small (fourfold) leftward shift. Mutagenesis of the other three histidines present in the P2X4 sequence had no effect on pH sensitivity. 5. The results show that pH modulation of P2X4 in the pathophysiological range is mediated by protonation of H286. This provides direct confirmation that pH sensitivity resides in the P2X4 channel protein rather than the agonist species.

Adenosine Triphosphate↗

PubMed2000

Lisuride versus bromocriptine for levodopa-induced complications in Parkinson's disease.

OBJECTIVES: To compare the efficacy and safety of adjunct lisuride therapy versus bromocriptine in patients with Parkinson's disease, already established on levodopa and suffering the long-term complications of therapy. SEARCH STRATEGY: Electronic searches of MEDLINE, EMBASE and the Cochrane Controlled Trials Register. Handsearching of the neurology literature as part of the Cochrane Movement Disorders Group's strategy. Examination of the reference lists of identified studies and other reviews. Contact with Cambridge Laboratories, Roche Products Limited and Sandoz Limited. SELECTION CRITERIA: Randomised controlled trials of lisuride versus bromocriptine in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy. DATA COLLECTION AND ANALYSIS: Data was abstracted independently by each author and differences settled by discussion. MAIN RESULTS: Only one randomised cross-over trial including 20 patients has compared lisuride with bromocriptine as adjunct therapy in Parkinson's disease. Both lisuride and bromocriptine improved motor fluctuations with no significant differences between the agonists. However, this conclusion is based on an unvalidated 4 point rating scale which could only record positive outcomes. This, combined with the small size of the trial, suggests that firm conclusions on motor fluctuations should not be drawn. Lisuride and bromocriptine produced similar benefits in parkinsonian impairments according to the Columbia Rating Scale. Adverse events were similar with the two agonists and no withdrawals were reported from either drug. REVIEWER'S CONCLUSIONS: The small size of this study and other methodological problems do not allow any firm conclusions to be drawn regarding the efficacy and safety of lisuride compared with bromocriptine in advanced Parkinson's disease with motor complications.

Antiparkinson Agents↗

PubMed2000

Lisuride for levodopa-induced complications in Parkinson's disease.

OBJECTIVES: To compare the efficacy and safety of adjuvant lisuride therapy versus placebo in patients with Parkinson's disease, already established on levodopa and suffering from motor complications. SEARCH STRATEGY: Electronic searches of MEDLINE, EMBASE and the Cochrane Controlled Trials Register. Handsearching of the neurology literature as part of the Cochrane Movement Disorders Group's strategy. Examination of the reference lists of identified studies and other reviews. Contact with Cambridge Laboratories and Roche Products Limited. SELECTION CRITERIA: Randomised controlled trials of lisuride versus placebo in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy. DATA COLLECTION AND ANALYSIS: Data was to be abstracted independently by each author and differences settled by discussion. MAIN RESULTS: No randomised controlled trials comparing lisuride with placebo in advanced Parkinson's disease with motor complications were found. REVIEWER'S CONCLUSIONS: Well designed randomised controlled trials demonstrating efficacy and safety are required before the use of lisuride in later Parkinson's disease can be supported.

Antiparkinson Agents↗

PubMed2000

Ropinirole for levodopa-induced complications in Parkinson's disease.

BACKGROUND: Long-term levodopa therapy for Parkinson's disease is complicated by the development of motor fluctuations and abnormal involuntary movements. One approach is to add a dopamine agonist at this stage of the disease to reduce the time the patient spends immobile or off and to reduce the dose of levodopa in the hope of reducing such problems in the future. OBJECTIVES: To compare the efficacy and safety of adjuvant ropinirole therapy versus placebo in patients with Parkinson's disease already established on levodopa therapy and suffering from motor complications. SEARCH STRATEGY: Electronic searches of MEDLINE, EMBASE and the Cochrane Controlled Trials Register. Handsearching of the neurology literature as part of the Cochrane Movement Disorders Group's strategy. Examination of the reference lists of identified studies and other reviews. Contact with SmithKline Beecham. SELECTION CRITERIA: Randomised controlled trials of ropinirole versus placebo in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy. DATA COLLECTION AND ANALYSIS: Data was abstracted independently by the authors and differences settled by discussion. The outcome measures used included Parkinson's disease rating scales, levodopa dosage, 'off' time measurements and the frequency of withdrawals and adverse events. MAIN RESULTS: Three double-blind, parallel group, randomised, controlled trials have been conducted on 263 patients. The two phase II studies were relatively small, were conducted over the short term (12 weeks), and used relatively low doses of ropinirole. The other phase III study was medium term (26 weeks) and used ropinirole doses in line with the current UK licensed maximum. Additional data from the manufacturer showed that the difference in the reduction in off time was non-significantly greater with ropinirole than placebo (weighted mean difference [WMD] 0.19 hours; -0.63, 1.00 95% CI). As an adverse event, dyskinesia was significantly increased in those who received ropinirole (odds ratio [OR] 2.59; 1.35, 4.96 95% CI; p < 0.004). Measurements of motor impairments and disability were poor in these studies with incomplete information available. Levodopa dose could be reduced in two studies with a significantly larger reduction on ropinirole than on placebo (WMD 136.5mg/d; 74.5, 198.6 95% CI; p =0.00002). No significant differences in the frequency of adverse event reports were noted between ropinirole and placebo apart from the increase in dyskinesia with ropinirole. There was a trend towards fewer withdrawals from ropinirole but this did not reach statistical significance. REVIEWER'S CONCLUSIONS: Ropinirole therapy can reduce levodopa dose but at the expense of increased dyskinetic adverse events. No significant effect on off time reduction was found but this may have been due to under-powered trials and the low doses of ropinirole used in the phase II studies. Inadequate data on motor impairments and disability was collected to assess these outcomes. These conclusions apply to short and medium term treatment, up to 26 weeks. Further longer term trials are required, with measurements of effectiveness, and also studies to compare the newer with the older dopamine agonists.

Antiparkinson Agents↗

PubMed2000

Ropinirole versus bromocriptine for levodopa-induced complications in Parkinson's disease.

BACKGROUND: Long-term levodopa therapy for Parkinson's disease is complicated by the development of motor fluctuations and abnormal involuntary movements. One approach is to add a dopamine agonist at this stage of the disease to reduce the time the patient spends immobile or off and to reduce the dose of levodopa in the hope of reducing such problems in the future. OBJECTIVES: To compare the efficacy and safety of adjuvant ropinirole therapy with bromocriptine in patients with Parkinson's disease already established on levodopa therapy and suffering from motor complications. SEARCH STRATEGY: Electronic searches of MEDLINE, EMBASE and the Cochrane Controlled Trials Register. Handsearching of the neurology literature as part of the Cochrane Movement Disorders Group's strategy. Examination of the reference lists of identified studies and other reviews. Contact with SmithKline Beecham. SELECTION CRITERIA: Randomised controlled trials of ropinirole versus bromocriptine in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy. DATA COLLECTION AND ANALYSIS: Data was abstracted independently by the authors and differences settled by discussion. The outcome measures used included Parkinson's disease rating scales, levodopa dosage, 'off' time measurements and the frequency of withdrawals and adverse events. MAIN RESULTS: No significant differences between ropinirole and bromocriptine were found in off time reduction, dyskinesia as an adverse event, motor impairment and disability, or levodopa dose reduction. Withdrawal rates and adverse event frequency were similar with the two agents apart from significantly less nausea with ropinirole (odds ratio 0.50; 0.29, 0. 84 95% CI; p =0.01). REVIEWER'S CONCLUSIONS: Ropinirole is at least as good as bromocriptine in patients with Parkinson's disease with motor complications in terms of improving off time and reducing levodopa dose, without increasing adverse events including dyskinesia. However, these comparitor studies may have been underpowered to detect clinically meaningful differences between the agonists. Further, much larger, phase IV studies are required to examine the efficacy, effectiveness, and safety of all of the dopamine agonists as adjuvant therapy in Parkinson's disease.

Antiparkinson Agents↗

PubMed2000

Basal ganglia metabolite concentrations in idiopathic Parkinson's disease and multiple system atrophy measured by proton magnetic resonance spectroscopy.

Six patients with idiopathic Parkinson's disease (IPD), six with clinically probable multiple system atrophy and six control subjects underwent quantitative proton magnetic resonance spectroscopy (MRS). The concentrations of the three major metabolites, N-acetylaspartate (NAA), creatine and choline, were quantified in the lentiform nucleus using tissue water content as an internal concentration reference. Glutamate was assessed as the (glutamate + glutamine)/creatine peak area ratio (Glx/Cre). In the control subjects the mean (+/- SD) concentrations of the three metabolites were 15.2 +/- 2.9 micromol/g wet weight for NAA, 12.0 +/- 1.4 for creatine and 2.4 +/- 0.3 for choline. The Glx/Cre ratio was 1.28 +/- 0.32. The only significant difference in any metabolite concentration was in the lentiform nucleus of patients with IPD compared with controls, with an increase in choline which lead to a significant reduction in the NAA/choline ratio. The relevance of this finding is uncertain. The results of the present pilot study, combined with the conflicting findings from previous work, suggest that further, much larger, studies are required to evaluate the diagnostic capability of proton MRS.

Adult↗

PubMed2000

Systematic review of acute levodopa and apomorphine challenge tests in the diagnosis of idiopathic Parkinson's disease.

OBJECTIVES: To perform a systematic review of studies examining the diagnostic accuracy of acute challenge tests with levodopa and/or apomorphine in parkinsonian syndromes to assess their value in the diagnosis of idiopathic Parkinson's disease. METHODS: A literature search including Medline and the Cochrane Library was performed for studies published in any language comparing acute levodopa and/or apomorphine response with chronic levodopa therapy in parkinsonian syndromes. Abstracted sensitivity and specificity data were summarised using variance weighting and conditional logistic regression for studies comparing two challenge tests. RESULTS: Thirteen studies were located: four examining de novo patients and nine examining patients with well established idiopathic Parkinson's disease and non-parkinsonian conditions. Despite the significant heterogeneity in the methodologies employed, the comparable results suggest that this had little effect on the accuracy of the tests. The sensitivity for the diagnosis of established idiopathic Parkinson's disease was: apomorphine 0.86 (95% confidence interval (95% CI) 0.78-0.94), acute levodopa 0.75 (95% CI 0.64-0.85), and chronic levodopa therapy 0.91 (95% CI 0.85-0.99). The specificity for the diagnosis of established idiopathic Parkinson's disease was: apomorphine 0.85 (95% CI 0.74-0.96), acute levodopa 0.87 (95% CI 0. 77-0.97), and chronic levodopa therapy 0.77 (95% CI 0.61-0.93). The number of patients positive for each test divided by the number with clinically diagnosed de novo disease was: apomorphine 0.63 (95% CI 0. 56-0.70), acute levodopa 0.69 (95% CI 0.59-0.80), and chronic levodopa therapy 0.76 (95% CI 0.70-0.82). CONCLUSIONS: The accuracy of the acute levodopa and apomorphine challenge tests is similar to, but not superior than, that of chronic levodopa therapy in the diagnosis of idiopathic Parkinson's disease. As most patients will be given chronic dopamimetic therapy, these tests add nothing while causing significant adverse events and additional cost.

Apomorphine↗