Adherence therapy improves medication adherence and quality of life in people with Parkinson's disease: a randomised controlled trial.

BACKGROUND: Many factors are associated with medication non-adherence in Parkinson's disease (PD), including complex treatment regimens, mood disorders and impaired cognition. However, interventions to improve adherence which acknowledge such factors are lacking. A phase II randomised controlled trial was conducted investigating whether Adherence Therapy (AT) improves medication adherence and quality of life (QoL) compared with routine care (RC) in PD. METHODS: Eligible PD patients and their spouse/carers were randomised to intervention (RC plus AT) or control (RC alone). Primary outcomes were change in adherence (Morisky Medication Adherence Scale) and QoL (Parkinson's Disease Questionnaire-39) from baseline to week-12 follow up. Secondary outcomes were MDS-UPDRS (part I, II, IV), Beliefs about Medication Questionnaire (BMQ), EuroQol (EQ-5D) and the Caregiving Distress Scale. Blinded data were analysed using logistic and linear regression models based on the intention-to-treat principle. RESULTS: Seventy-six patients and 46 spouse/carers completed the study (intervention: n = 38 patients, n = 24 spouse/carers). At week-12 AT significantly improved adherence compared with RC (OR 8.2; 95% CI: 2.8, 24.3). Numbers needed to treat (NNT) were 2.2 (CI: 1.6, 3.9). Compared with RC, AT significantly improved PDQ-39 (-9.0 CI: -12.2, -5.8), BMQ general harm (-1.0 CI: -1.9, -0.2) and MDS-UPDRS part II (-4.8 CI: -8.1, -1.4). No significant interaction was observed between the presence of a spouse/carer and the effect of AT. CONCLUSION: Adherence Therapy improved self-reported adherence and QoL in a PD sample. The small NNT suggests AT may be cost-effective. A larger pragmatic trial to test the efficacy and cost-effectiveness of AT by multiple therapists is required.

Investigating alternatives to traditional insecticides: effectiveness of entomopathogenic fungi and Bacillus thuringiensis against citrus thrips and avocado thrips (Thysanoptera: Thripidae).

Citrus thrips, Scirtothrips citri (Moulton) (Thysanoptera: Thripidae), is a plant-feeding pest most widely recognized for causing damage to citrus (Citrus spp. L. [Rutaceae]) and mango (Mangifera indica L. [Anacardiaceae]) fruits. This insect has recently broadened its known host range to become a significant pest of California grown blueberries. Avocado thrips, Scirtothrips. perseae Nakahara (Thysanoptera: Thripidae), is a recent, invasive pest of California avocados, Persea americana Mill. (Laurales: Lauraceae). Effective alternatives to traditional pesticides are desirable for both pests to reduce impacts on natural enemies and broaden control options in an effort to minimize pesticide resistance via rotation of control materials. We evaluated Bacillus thuringiensis (Bt) subsp. israelensis proteins (Cyt 1A and Cry 11A, activated and inactivated) and multiple strains (GHA, 1741ss, SFBb1, S44ss, NI1ss, and 3769ss) of Beauveria bassiana (Balsamo) Vuillemin against both species. Avocado thrips and citrus thrips were not susceptible to either Bt protein tested, regardless of activation status. All strains of B. bassiana were able to infect both avocado thrips and citrus thrips. However, the commercially available GHA strain was the most effective strain against both species and had a faster rate of infection then the other strains tested. Citrus thrips were more susceptible than avocado thrips to all B. bassiana strains (LC50 and LC95 of 8.6 x 10(4) and 4.8 x 10(6) conidia per ml for citrus thrips, respectively). Investigation of citrus thrips field control using the GHA strain of B. bassiana is therefore justified.

Evaluation of Beauveria bassiana for management of citrus thrips (Thysanoptera: Thripidae) in California blueberries.

Citrus thrips, Scirtothrips citri (Moulton), is a plant-feeding pest most widely recognized for causing damage to citrus and mango fruits. This insect has broadened its host range to become a significant pest of commercial blueberries grown in the San Joaquin Valley of California. We evaluated Beauveria bassiana (Balsamo) for control of citrus thrips in blueberries grown under two watering regimes (drip irrigation with and without overhead sprinklers) and using two fungal formulations (commercially available spores in suspension vs. colonized seed) over two sampling periods, that is, for two 3-d periods after treatment. We found significant differences in thrips densities as a function of water regime treatment and fungal formulation. Thrips levels were reduced significantly with both fungal treatments at 3 d after treatment, but at 6 d, only results with colonized seed differed from the control treatment. These data suggest entomopathogenic fungi might be useful for control of citrus thrips on blueberries in particular situations (in organic production or as a resistance management tool) but that traditional pesticides will likely remain the preferred management option.

Is the use of symphysis-fundal height measurement and ultrasound examination effective in detecting small or large fetuses?

We investigated the accuracy of using symphysis pubis-fundal height measurement and ultrasonically derived estimation of fetal weight for identifying small-for-gestational-age (SGA) and large-for-gestational-age (LGA) fetuses. A retrospective cohort study was performed using computerised records of all non-diabetic women referred for an ultrasound growth scan (US) with clinically suspected SGA or LGA singleton fetuses from 35 weeks' gestation between October 2008 and March 2009 (n = 185). Birth weight data were also collected for all births over the study period (n = 3200). One-third (34%) of ultrasound estimated fetal weights were inaccurate by >10%. However, an inaccurate ultrasound estimation did not significantly increase the likelihood of spontaneous or induced onset of labour or delivery by caesarean section. Most (79%) growth scans were performed on well-grown fetuses. The majority (80%) of SGA and LGA babies in our cohort were not identified by clinicians during routine antenatal care. From 3,200 live births, there were a total of 59 infants weighing <2,500 g or >5,000 g. Of these, only 12 had been referred for an ultrasound growth scan, indicating that abdominal palpation and fundal height measurement has a 20% sensitivity in detecting SGA or LGA fetuses. Of the 12, four were detected using ultrasound, indicating a 33% detection rate. Although ultrasound has a slightly higher sensitivity, neither clinical examination using fundal height measurements nor 3rd trimester ultrasound examinations are effective at detecting SGA or LGA fetuses.

Duration of preclinical rheumatoid arthritis-related autoantibody positivity increases in subjects with older age at time of disease diagnosis.

OBJECTIVES: To investigate factors that may influence the prevalence and timing of appearance of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies during the preclinical phase of rheumatoid arthritis (RA) development. METHODS: 243 serial prediagnosis serum samples from 83 subjects with RA were examined for the presence of RF and anti-CCP antibodies. RESULTS: Of the 83 cases, 47 (57%) and 51 (61%) subjects had at least one prediagnosis sample positive for RF or anti-CCP, respectively. Gender and race were not significantly associated with the prevalence or timing of preclinical antibody appearance. Preclinical anti-CCP positivity was strongly associated with the development of erosive RA (odds ratio = 4.64; 95% confidence interval 1.71 to 12.63; p<0.01), but RF was not (p = 0.60). Additionally, as age at the time of diagnosis of RA increased the duration of prediagnosis antibody positivity for RF and anti-CCP increased, with the longest duration of preclinical antibody positivity seen in patients diagnosed with RA over the age of 40. In no subjects did symptom onset precede the appearance of RF or anti-CCP antibodies. CONCLUSIONS: The period of time that RF and anti-CCP are present before diagnosis lengthens as the age at the time of diagnosis of RA increases. This finding suggests that factors such as genetic risk or environmental exposure influencing the temporal relationship between the development of RA-related autoantibodies and clinically apparent disease onset may differ with age.

Interventions for reducing anxiety in women undergoing colposcopy.

BACKGROUND: Before cervical cancer develops the cells of the cervix become abnormal. Following an abnormal cervical smear colposcopy is performed. Colposcopy is the visualisation of the cervix using a binocular microscope. Women experience high levels of anxiety and negative emotional responses at all stages of cervical screening. High levels of anxiety before and during colposcopy can have adverse consequences, including pain and discomfort during the procedure and high loss to follow-up rates. This review evaluates interventions designed to reduce anxiety levels during colposcopic examination. OBJECTIVES: To compare the efficacy of various interventions aimed at reducing anxiety during colposcopic examination in women. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL), (Cochrane Library, Issue 1, 2006) MEDLINE (1951-2006), EMBASE (1980-2006), CINAHL (1982-2006), Psych Lit and CancerLit, NHMRC Clinical Trials Register, UKCCCR Register of Cancer Trials, Meta-Register and Physician Data Query Protocols. SELECTION CRITERIA: Randomised and quasi randomised controlled trials of interventions to reduce anxiety during colposcopic examination. DATA COLLECTION AND ANALYSIS: One author searched the citations and reference lists. Studies that appeared to meet inclusion criteria were retrieved and assessed independently by the remaining three authors. The methodological quality of included studies was assessed using the Cochrane Collaboration Back Review Group's methodological quality criteria (van Tulder 2003). MAIN RESULTS: Eleven trials were included, these trials used various interventions to reduce anxiety. These examined 1441 women's anxiety levels after different types of intervention. These included: Information leaflets - (proved not to be associated with anxiety reduction). Counselling: pre-colposcopic counselling was not associated with anxiety reduction. Information leaflets and information video and pre-colposcopy counselling was not associated with a reduction in anxiety levels. Listening to music during colposcopy: this intervention was associated with reduction in anxiety levels (p < 0.002). Video colposcopy was associated with reduction in anxiety levels, and the reduction in anxiety was significant (p < 0.0002). Information using graphs and verbal information and information video versus information only when sought: There was no significant reduction in the level of anxiety in the intervention group. Information leaflets and information video versus information leaflets only: There was a reduction in anxiety levels in the intervention group compared to the control group (p < 0.00001). AUTHORS' CONCLUSIONS: Anxiety appears to be reduced by playing music during colposcopy, showing information videos prior to colposcopy and viewing video colposcopy during the procedure. Although information leaflets did not reduce anxiety levels, they did increase knowledge levels and so are useful in obtaining clinical consent to the colposcopic procedure.

Occupational therapy for patients with Parkinson's disease.

BACKGROUND: Despite drug and surgical therapies for Parkinson's disease, patients develop progressive disability. It has both motor and non-motor symptomatology, and their interaction with their environment can be very complex. 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 (1966-April 2007), EMBASE (1974-2000), CINAHL (1982-April 2007), Psycinfo (1806-April 2007), Ovid OLDMEDLINE (1950-1965), ISI Web of Knowledge (1981-April 2007), National Library for Health (NLH) (April 2007), Nursing, Midwifery and Allied Health (NMAP) (April 2007), Intute: Medicine (December 2005), Proquest Nursing Journals (PNJ, 1986 - April 2007); rehabilitation databases: AMED (1985-April 2007), MANTIS (1880-2000), REHABDATA (1956-2000), REHADAT (2000), GEROLIT (1979-2000); English language databases of foreign language research and third world publications: Pascal (1984-2000), LILACS (1982- April 2007), MedCarib (17th Century-April 2007), JICST-EPlus (1985-2000), AIM (1993-April 2007), IMEMR (1984-April 2007), grey literature databases: SIGLE (1980-2000), ISI-ISTP (1982-April 2007), DISSABS (1999-2000), Conference Papers Index (CPI, 1982-2000) and Aslib Index to Theses (AIT, 1716- April 2006), The Cochrane Controlled Trials Register (Issue 2, 2007), the CenterWatch Clinical Trials listing service (April 2007), the metaRegister of Controlled Trials (mRCT, April 2007), Current controlled trials (CCT) (April 2007), ClinicalTrials.gov (April 2007), CRISP (1972-April 2007), PEDro (April 2007), NIDRR (April 2007) and NRR (April 2007) 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. AUTHORS' 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 is now a consensus as to UK current and best practice in occupational therapy when treating people with Parkinson's disease. We now require large well designed placebo-controlled RCTs 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.

What is it like to take antipsychotic medication? A qualitative study of patients with first-episode psychosis.

ACCESSIBLE SUMMARY: What is known on the subject? Antipsychotic drugs are an important part of treatment for most patients with first episode psychosis. We do not know much about what it is like to take these drugs from the patient's point of view. What this paper adds to existing knowledge? We talked to 20 young people with psychosis about their experiences of taking antipsychotic drugs. Patients relationship with medication was complex, young people found medication often to be both good and bad at the same time. We were interested in how seemingly trivial issues--colour, taste, size, name--could be very important to young people and could result in them stopping. What are the implications for practice? We think our study highlights the complicated internal struggles that people with first episode psychosis have with medication. Our study highlights how Nurses and Doctors need to try and better understand what it is like to take these drugs and work collaboratively with patients to support them to make informed choices about treatment. BACKGROUND: Low-dose antipsychotic medication is an important part of treatment for people experiencing a first episode of psychosis. Little is known about this group of patients' experiences of taking medication. METHOD: A qualitative study of purposively sampled young people experiencing a first episode of psychosis was carried out. A mental health nurse working in the early psychosis team interviewed participants using a structured topic guide. Interviews were subjected to thematic analysis. RESULTS: Interviews were completed with 20 young people. Thematic analysis generated six themes: (1) the drugs do work, (2) the drugs don't work (as well as I'd like), (3) side effects, (4) the indirect effects of medication, (5) rage against the machine and (6) the not trivial issues about medication. CONCLUSION: Our overarching meta-theme was that young people's experience of taking antipsychotics was complex; medication was often considered good and bad at the same time. Our observations underpin the importance of helping patients think through the use of antipsychotic medication in supporting their personal recovery.

Systematic review of antidepressant therapies in Parkinson's disease.

Depression is the most common psychiatric disturbance in Parkinson's disease. We conducted a Cochrane systematic review to assess the efficacy and safety of antidepressant therapies in idiopathic Parkinson's 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 Parkinson's 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 Parkinson's disease are available on which to make recommendations for their use. Large scale randomised controlled trials are urgently required.

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.

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.

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 (mean administered doses 3.3 and 3.5 mg/d) in a twice daily regime. In view of this clinical heterogeneity and some statistical heterogeneity, the results of these trials have not been included in a meta-analysis. The conclusions of this review are based on the evidence from a single phase III study which was medium term (26 weeks) and used ropinirole doses in line with the current UK licensed maximum in a thrice daily regime. In view of difficulties in assessing changes in off time in ~~ Leiberman 98~~, caused by the initial imbalance between the arms of the trial, it is unsafe to draw any firm conclusion about the effect of ropinirole on off time. However, as an adverse event, dyskinesia was significantly increased in those who received ropinirole (~~ Leiberman 98~~; odds ratio 2.90; 1.36, 6.19 95% CI; Table 8). Measurements of motor impairments and disability were poor in this study with incomplete information available. Levodopa dose could be reduced in ~~ Leiberman 98~~ with a significantly larger reduction on ropinirole than on placebo (weighted mean difference 180 mg/d; 106, 253 95% CI; Table 2). 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 in ~~ Leiberman 98~~ 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 clear effect on off time reduction was found but this may have been due to the under-powering of the single evaluable trial. 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.

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: In the 3 trials identified, 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.

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.

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.

Amantadine in Parkinson's disease.

BACKGROUND: Although levodopa is the most common drug prescribed to relieve the symptoms of Parkinson's disease it is associated with motor and psychiatric side-effects. Consequently, interest has turned to alternative drugs with improved side-effect profiles to replace or augment levodopa. Amantadine, originally used as an antiviral drug, has been shown to improve the symptoms of Parkinson's disease. OBJECTIVES: To compare the efficacy and safety of amantadine therapy (monotherapy or adjuvant therapy) versus placebo in treating people with Parkinson's disease. SEARCH STRATEGY: Electronic searches of The Cochrane Controlled Trials Register (The Cochrane Library Issue 3, 2001), MEDLINE (1966-2001), EMBASE (1974-2001), SCISEARCH (1974-2001), BIOSIS (1993-2001), GEROLIT (1979-2001), OLDMEDLINE (1957-1965), LILACS (1982-2001), MedCarib (17th Century - 2001), PASCAL (1973-2001), JICST-EPLUS (1985-2001), RUSSMED (1973-2001), DISSERTATION ABSTRACTS (2000-2001), SIGLE (1980-2001), ISI-ISTP (1990-2001), Aslib Index to Theses (2001), Clinicaltrials.gov (2001), metaRegister of Controlled Trials (2001), NIDRR (2001) and NRR (2001) were conducted. Grey literature was hand searched and the reference lists of identified studies and reviews examined. The manufacturers of amantadine were contacted. SELECTION CRITERIA: Randomised controlled trials comparing amantadine with placebo in the treatment of patients with a clinical diagnosis of idiopathic Parkinson's disease. DATA COLLECTION AND ANALYSIS: Data was abstracted independently by NC and KD onto standardised forms and disagreements were resolved by discussion. MAIN RESULTS: Six randomised controlled trials were found comparing amantadine monotherapy or adjuvant therapy with placebo in the treatment of idiopathic Parkinson's disease. Five examined amantadine as adjuvant therapy with optimal levels of levodopa or anticholinergics and one examined amantadine as an adjuvant therapy with minimum tolerated levels of anticholinergics or as a monotherapy. Five were double-blind cross-over studies and one was a double-blind parallel group study. In total they examined 215 patients. The parallel group study allowed the randomisation codes to be broken and allowed patients in the placebo group to then receive amantadine. This could have led to bias. One study did not present the results of the placebo arm of the trial, hence we could not determine the difference between the two treatment groups. Two cross-over studies presented the results of the combined data from both treatment and placebo arms. The risk of carry-over effect into the second arm meant that these results could not be analysed. The final two studies presented at least some of their data from the end of the first arm of the trials. However only means were given, without standard deviations, so we could not determine the statistical significance of any difference between the amantadine and placebo groups. Although the authors did report on the side-effects from amantadine (such as livido recticularis, dry mouth and blurred vision), they state that none of them were severe. REVIEWER'S CONCLUSIONS: A considerable amount of evidence on the effectiveness of amantadine has accrued from non-controlled trials, often in patients with Parkinsonian conditions other than idiopathic Parkinson's disease. However, rigorous analysis of the six randomised controlled trials of amantadine reveals insufficient evidence of its efficacy and safety in the treatment of idiopathic Parkinson's disease.

Catechol-O-methyltransferase inhibitors versus active comparators for levodopa-induced complications in Parkinson's disease.

BACKGROUND: As Parkinson's disease progresses the control of the symptoms often requires the addition of other drugs to levodopa. The principle aim of COMT inhibitor therapy is to increase the duration of effect of the levodopa dose and thus reduce the time patients spend in the relatively immobile 'off' phase. OBJECTIVES: To compare the efficacy and safety of adjuvant COMT inhibitor therapy versus active comparators in patients with Parkinson's disease, already established on levodopa and suffering from motor complications. SEARCH STRATEGY: Electronic searches of the Cochrane Controlled Trials Register (The Cochrane Library Issue 1, 2003), MEDLINE (1966-2003), EMBASE (1974-2003), were conducted. Grey literature was hand searched and the reference lists of identified studies and reviews examined. The manufacturers of COMT inhibitors were contacted. SELECTION CRITERIA: Randomised controlled trials of adjuvant COMT inhibitor therapy versus an active comparator 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: Two trials were found that examined the efficacy of a COMT inhibitor against an active comparator (n = 349). Koller 1998 compared the efficacy of tolcapone versus pergolide (n = 203) over 12 weeks and TSG 1999 compared the efficacy of tolcapone versus bromocriptine (n = 146) over 8 weeks. No trials were found that compared entacapone with active comparators. Tolcapone produced similar benefits to bromocriptine in 'off' time reduction, motor impairment and disability ratings over three months of therapy. Tolcapone produced a greater reduction in levodopa dosage than bromocriptine. Tolcapone produced similar benefits to pergolide in levodopa dose reduction, motor impairment and disability ratings, and in generic health-related quality of life scales over the first two months of therapy. Tolcapone produced a greater improvement in the disease-specific quality of life scale PDQ-39 than pergolide. Nausea, constipation and orthostatic complaints were greater with agonist therapy, but otherwise the frequency of adverse events and withdrawals from treatment were similar with the two classes of adjuvant medication. One patient had significantly elevated liver enzymes whilst on tolcapone, but otherwise the frequency of adverse events and withdrawals from treatment were similar. REVIEWERS' CONCLUSIONS: The two trials comparing tolcapone with the dopamine agonists bromocriptine and pergolide were underpowered to detect clinically relevant differences between them. This is based on medium-term evidence. No evidence was found comparing entacapone with active comparators. Further larger and longer-term trials are required to compare tolcapone with entacapone and COMT inhibitor therapy with alternative adjuvant classes of drug in later Parkinson's disease such as dopamine agonists and monoamine oxidase inhibitors.

Catechol-O-methyltransferase inhibitors for levodopa-induced complications in Parkinson's disease.

BACKGROUND: As Parkinson's disease progresses the control of motor symptoms often requires the addition of other drugs to levodopa. The principle aim of COMT inhibitor therapy is to increase the duration of effect of each levodopa dose and thus reduce the time patients spend in the relatively immobile 'off' phase. OBJECTIVES: To compare the efficacy and safety of adjuvant COMT inhibitor therapy versus placebo in patients with Parkinson's disease, already established on levodopa and suffering from motor complications. SEARCH STRATEGY: Electronic searches of the Cochrane Controlled Trials Register, (The Cochrane Library Issue 1, 2003), MEDLINE (1966-2003), EMBASE (1974-2003), were conducted. Grey literature was hand searched and the reference lists of identified studies and reviews examined. The manufacturers of COMT inhibitors were contacted. SELECTION CRITERIA: Randomised controlled trials of adjuvant COMT inhibitor therapy versus a placebo 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: Fourteen trials fulfilled the inclusion criteria. 2566 patients with Parkinson's disease and motor fluctuations were included in this review. Eight trials examined entacapone versus placebo in a total of 1560 patients. These trials were between two and twelve months in duration. Six trials examined tolcapone versus placebo in a total of 1006 patients. These trials were between six weeks and twelve months in duration. Both tolcapone and entacapone reduced 'off' time, reduced levodopa dose and modestly improved motor impairments and disability. This was at the expense of increased risk of dyskinesias, nausea, vomiting, and diarrhoea. A few participants taking tolcapone were found to have raised liver enzyme levels. REVIEWERS' CONCLUSIONS: In the management of the motor complications seen in Parkinson's disease, tolcapone and entacapone can be used to reduce off time, reduce levodopa dose, and modestly improve motor impairment and disability. This is based on, at best, medium term evidence. However some participants on tolcapone had raised liver enzymes. This combined with three cases of fatal hepatic toxicity found during post-marketing surveillance has raised concerns over the safety of tolcapone.

Beta-blocker therapy for tremor in Parkinson's disease.

BACKGROUND: The tremor of Parkinson's disease can cause considerable disability for the individual concerned. Traditional antiparkinsonian therapies such as levodopa have only a minor effect on tremor. Beta-blockers are used to attenuate other forms of tremor such as Essential Tremor or the tremor associated with anxiety. It is thought that beta-blockers may be of use in controlling the tremor of Parkinson's disease. OBJECTIVES: To compare the efficacy and safety of adjuvant beta-blocker therapy against placebo for the treatment of tremor in patients with Parkinson's disease. SEARCH STRATEGY: Electronic searches of MEDLINE, EMBASE, SCISEARCH, BIOSIS, GEROLIT, OLDMEDLINE, LILACS, MedCarib, PASCAL, JICST-EPLUS, RUSSMED, DISSERTATION ABSTRACTS, SIGLE, ISI-ISTP, Aslib Index to Theses, The Cochrane Controlled Trials Register, Clinicaltrials.gov, metaRegister of Controlled Trials, NIDRR, NRR and CENTRAL were conducted. Grey literature was hand searched and the reference lists of identified studies and reviews examined. The manufacturers of beta-blockers were contacted. SELECTION CRITERIA: Randomised controlled trials of adjuvant beta-blocker therapy versus placebo in patients with a clinical diagnosis of idiopathic Parkinson's disease. DATA COLLECTION AND ANALYSIS: Data was abstracted independently by two of the authors onto standardised forms and disagreements were resolved by discussion. MAIN RESULTS: Four randomised controlled trials were found comparing beta-blocker therapy with placebo in patients with idiopathic Parkinson's disease. These were double-blind cross-over studies involving a total of 72 patients. Three studies did not present data from the first arm, instead presenting results as combined data from both treatment arms and both placebo arms. The risk of a carry-over effect into the second arm meant that these results were not analysed. The fourth study presented data from each arm. This was in the form of a mean total score for tremor for each group. Details of the baseline scores, the numbers of patients in each group and standard deviations were not provided, meaning that the magnitude and significance of any changes due to therapy could not be calculated. One study reported a substantial fall in heart rate in 14 of the 22 patients, with one patient withdrawing after his heart rate dropped to 56 beats per minute (baseline heart rate was not reported). REVIEWER'S CONCLUSIONS: In view of this lack of evidence, it is impossible to determine whether beta-blocker therapy is effective and safe for the treatment of tremor in Parkinson's disease. The high frequency of bradycardia in one trial raises some concerns about the prescription of beta-blockers to normotensive elderly patients but the study was too small for the true degree of risk to be calculated.

Amantadine for dyskinesia in Parkinson's disease.

BACKGROUND: Abnormal involuntary movements known as dyskinesias are amongst the most disabling side-effects of levodopa therapy. It is thought that amantadine, an NMDA-receptor antagonist, may reduce dyskinesias in patients with Parkinson's disease without worsening Parkinsonian symptoms. OBJECTIVES: To compare the efficacy and safety of adjuvant amantadine therapy versus placebo in treating dyskinesia in patients with Parkinson's disease, already established on levodopa, and suffering from motor complications. SEARCH STRATEGY: Electronic searches of The Cochrane Controlled Trials Register (The Cochrane Library Issue 3, 2001), MEDLINE (1966-2001), EMBASE (1974-2001), SCISEARCH (1974-2001), BIOSIS (1993-2001), GEROLIT (1979-2001), OLDMEDLINE (1957-1965), LILACS (1982-2001), MedCarib (17th Century - 2001), PASCAL (1973-2001), JICST-EPLUS (1985-2001), RUSSMED (1973-2001), DISSERTATION ABSTRACTS (2000-2001), SIGLE (1980-2001), ISI-ISTP (1990-2001), Aslib Index to Theses (2001), Clinicaltrials.gov (2001), metaRegister of Controlled Trials (2001), NIDRR (2001) and NRR (2001) were conducted. Grey literature was hand searched and the reference lists of identified studies and reviews examined. The manufacturers of amantadine were contacted. SELECTION CRITERIA: Randomised controlled trials comparing amantadine with placebo in the treatment of dyskinesia in patients with a clinical diagnosis of idiopathic Parkinson's disease. DATA COLLECTION AND ANALYSIS: Data was abstracted independently by NC and KD onto standardised forms and disagreements were resolved by discussion. MAIN RESULTS: Three randomised controlled trials were found comparing amantadine with placebo in the treatment of dyskinesia in patients with idiopathic Parkinson's disease. Three trials were excluded on the basis that they had no control group and a further three did not state whether they randomised the treatment that participants received. The included trials were double-blind cross-over studies involving a total of 53 patients. All three studies failed to present data from the first arm, instead presenting results as combined data from both treatment arms and both placebo arms. Two trials had no wash-out interval between the treatment periods. In view of the risk of a carry-over effect into the second arm, the results of these trials were not analysed. The final trial had a one week wash-out interval but only examined 11 participants. One study reported side-effects of amantadine in 8 of the 18 participants, including confusion and worsening of hallucinations. Another reported reversible edema of both feet in one of eleven participants. REVIEWER'S CONCLUSIONS: Due to lack of evidence it is impossible to determine whether amantadine is a safe and effective form of treatment for levodopa-induced dyskinesias in patients with Parkinson's disease.