RESUMEN

BACKGROUND: Drugs that mimic dopamine as bromocriptine were introduced as monotherapy or in combination with LD in the hope that this approach would prevent or delay the onset of motor complications in patients with Parkinson's disease (PD). However, hitherto, the role of bromocriptine (BR) in this issue has remained controversial. OBJECTIVES: To assess the efficacy and safety of bromocriptine (BR) monotherapy for delaying the onset of motor complications associated with levodopa (LD) therapy in patients with PD. SEARCH STRATEGY: We searched the Movement Disorders Group trials register which includes MEDLINE and EMBASE; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); handsearched appropriate neurology journals and reference lists of reviews found by the search-strategy. We also contacted Sandoz -now Novartis- (manufacturer of BR) and contacted colleagues who had co-ordinated trials on BR. SELECTION CRITERIA: Randomised trials evaluating the efficacy of BR monotherapy for delaying the onset of motor complications compared to LD therapy alone in PD patients. DATA COLLECTION AND ANALYSIS: Two review authors independently evaluated the methodological quality of identified trials and extracted the data from the trials. MAIN RESULTS: Six trials with 850 participants were included. The trials were of low methodological quality and were heterogeneous so we were unable to perform a meta-analysis. The occurrence of dyskinesias in three short trials was too low to draw any conclusion. The results of the longer trials indicate a lower occurrence of dyskinesias in the BR tier. In five trials that evaluated dystonia, this motor complication occurred less frequently in the BR tier. However, for both dyskinesias and dystonia a statistically significant difference in favour of BR emerged only in the largest trial. There was a trend for wearing-off and on-off fluctuations to occur less frequently in the BR group. Although all trials evaluated participants at the impairment level, only the largest trial reported a significantly larger improvement for the LD tier during the first year of therapy. Concerning disability, which was evaluated by five trials no statistically significant differences were found. Overall, a statistically larger number of dropouts occurred in the BR group because of an inadequate therapeutic response or intolerable side effects. AUTHORS' CONCLUSIONS: Based on a qualitative review of the available data we conclude that in the treatment of early Parkinson's disease, bromocriptine may be beneficial in delaying motor complications and dyskinesias with comparable effects on impairment and disability in those patients that tolerate the drug.

Asunto(s)

RESUMEN

BACKGROUND: Drugs that mimic dopamine, such as bromocriptine (BR), were introduced as monotherapy or in combination with levodopa (LD) in the hope that this approach would prevent or delay the onset of motor complications in patients with Parkinson's disease (PD). However, hitherto, the role of BR has remained controversial. We present a systematic review of all randomised controlled trials (RCTs) of BR/LD combination therapy compared with LD monotherapy in PD. OBJECTIVES: To assess the efficacy and safety of BR/LD combination therapy in delaying the onset of motor complications associated with LD monotherapy in patients with PD. SEARCH STRATEGY: We searched the Movement Disorders Group trials register which includes MEDLINE and EMBASE; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); handsearched appropriate neurology journals, symposia reports, PD handbooks and reference lists of reviews found by the search-strategy. We also contacted Sandoz -now Novartis- (manufacturer of BR) and PPD Pharmaco and contacted colleagues who had co-ordinated trials on BR. SELECTION CRITERIA: RCTs were eligible for inclusion if they evaluated the efficacy of BR/LD combination therapy for delaying the onset of motor complications compared with LD monotherapy in patients with PD. Outcome measures evaluated included the occurrence and severity of motor complications, impairment and disability scores, side effects and dropouts. DATA COLLECTION AND ANALYSIS: To determine the feasibility of a quantitative systematic review two independent reviewers evaluated the methodological quality of identified trials and extracted data from the trials. MAIN RESULTS: The methodological quality of seven trials showed important shortcomings. All studies failed adequately to describe randomisation procedures. Only three were carried out according to a double-blind design. Differences were found between studies concerning the mean age of the participants, the BR titration phase, the maximum achieved daily dose of LD (62.5 to 1000 mg) and BR (5 to 50 mg), and the applied outcomes. Our results show no evidence of consistent differences between treatment groups concerning the occurrence and severity of motor complications, scores of impairment and disability, or the occurrence of side effects. AUTHORS' CONCLUSIONS: This systematic review revealed no evidence to support the use of early BR/LD combination therapy as a strategy to prevent or delay the onset of motor complications in the treatment of PD.

Asunto(s)

RESUMEN

Three girls of Moroccan descent, aged 9, 10 and 7 years, presented with fever, joint pain and other symptoms. After Streptococcus infection and carditis were confirmed and the Jones criteria for acute rheumatic fever were met, the patients were treated with penicillin and acetylsalicylic acid. All 3 patients recovered. However, the second girl presented 2 months later with cardiac decompensation caused by valve disorders, after which aortic and mitral valvuloplasty was performed. The third girl developed joint pain again after 3 weeks and was diagnosed with juvenile idiopathic arthritis; treatment was adjusted accordingly. The prevalence of rheumatic heart diseases is 10-20 times higher in developing countries than in industrialised nations. The diagnosis 'acute rheumatic fever' should be considered in children of school age with unexplained fever, also when the Jones criteria have not yet been met. This may apply to migrant children in particular.

Asunto(s)

RESUMEN

Four children (two boys aged 1.5 and 10 years and two girls aged 2 and 9 years) vomited for one-half to four weeks. In one child, ataxia was later also noted and another tilted his head constantly to the left, but this was initially not alarming. In all four cases CT revealed a brain tumour, for which they were operated. Postoperatively, one child had residual tumour tissue that caused no further problems, in two children the tumour was completely excised with no further symptoms and no recurrence in the following 2 years, and in one child complete excision was not possible so that chemotherapy and radiotherapy were given, but metastases nevertheless developed 10 months later and the child died. Vomiting is common in children and in most cases the result of infectious or gastrointestinal causes. Intracranial pathology also can cause vomiting, both by increased intracranial pressure and by direct stimulation of the vomiting centre in the brainstem. Brain tumours in children often lack specific neurological signs in their clinical presentation. Intractable or chronic vomiting without nausea or deregulation of the water and electrolyte balance could therefore indicate the presence of an intracranial process, even when other neurological signs are absent.

Asunto(s)

RESUMEN

BACKGROUND: Drugs that mimic dopamine such as bromocriptine were introduced as monotherapy or in a combination with LD in the hope that this approach would prevent or delay the onset of motor complications in patients with Parkinson's disease (PD). However, hitherto, the role of bromocriptine (BR) in this issue has remained controversial. The present study is a systematic review of all randomised controlled trials of bromocriptine/levodopa (BR/LD) combination therapy compared with levodopa (LD) monotherapy in PD. OBJECTIVES: To assess the efficacy and safety of BR/LD combination therapy in delaying the onset of motor complications associated with LD monotherapy in patients with PD. SEARCH STRATEGY: Sources including the Cochrane Library, the search strategy of the Movement Disorders Group (includes computerised searches of MEDLINE and EMBASE and hand searching of appropriate neurology journals), reference lists of the reviews found by the MEDLINE and EMBASE search-strategy, Sandoz -now Novartis- (manufacturer of BR), PPD Pharmaco, symposia reports, PD handbooks, contacts with colleagues who had co-ordinated trials on BR and reference lists of all included studies were used to identify randomised controlled trials (RCTs) of interest. SELECTION CRITERIA: Randomised trials were eligible for inclusion if they evaluated the efficacy of BR/LD combination therapy for delaying the onset of motor complications compared to LD monotherapy in PD patients. Outcome measures that were evaluated included occurrence and severity of motor complications, scores on impairment and disability, and the occurrence of side effects and dropouts. DATA COLLECTION AND ANALYSIS: To determine the feasibility of a quantitative systematic review two independent reviewers evaluated the methodological quality of identified trials. MAIN RESULTS: The methodological quality of five trials showed important shortcomings. All studies failed to adequately describe randomisation procedures. Only two were carried out according to a double-blind design. Differences between studies concerning the mean age of the patients, the BR titration phase, the maximum achieved daily dose of LD (62.5-1000 mg) and BR (5-50 mg), and the applied outcomes were found. Our results show no evidence of consistent differences concerning the occurrence and severity of motor complications, scores of impairment and disability and the occurrence of side effects between both treatment groups. REVIEWER'S CONCLUSIONS: This systematic review found no evidence in support of early bromocriptine/levodopa combination therapy as a strategy to prevent or delay the onset of motor complications in the treatment of PD.

Asunto(s)

RESUMEN

OBJECTIVE: To compare and contrast disease-specific quality of life instruments in Parkinson's disease and assess their clinimetric properties. METHODS: Two reviewers independently evaluated both thoroughness and results of studies regarding clinimetric characteristics of identified scales. RESULTS: Twenty studies were found reporting on the clinimetric properties of four scales. The content validity of the Parkinson's disease questionnaire-39 item version (PDQ-39), the Parkinson's disease quality of life questionnaire (PDQL), and the "Fragebogen Parkinson LebensQualität" (Parkinson Quality of Life questionnaire; PLQ) was adequate to good, but for the Parkinson's impact scale (PIMS) it was insufficient. Construct validity of both the PDQ-39 and the PDQL was good, but for the PLQ and the PIMS this was insufficiently evaluated. Internal consistency of all scale totals and of subscale totals of the PDQL were good, whereas for the social support subscale of the PDQ-39 and four subscales of the PLQ this was inadequate. Test-retest reliability was not evaluated for the PDQL and was adequate in the other scales. Responsiveness was partially established for the PDQ-39, and not assessed for the other scales. The number of available translations, as well as the number of studies in which these instruments were used, differed considerably. CONCLUSIONS: The selection of an instrument partially depends on the goal of the study. In many situations however, the PDQ-39 will probably be the most appropriate HRQoL instrument. The PDQL may be considered as an alternative, whereas the PLQ may be considered in studies involving German speaking patients with Parkinson's disease. Use of the PIMS should be considered only as a means of identifying areas of potential problems.

Asunto(s)

RESUMEN

Two boys of 1 and 16 year had painful buccal lesions and were admitted for dehydration. The younger had finger and toe blisters; the older, severely ill, had conjunctivitis, urethritis and skin lesions. Only symptomatic treatment with lidocaine gel and paracetamol gave good recovery. A 5-year-old Turkish girl had recurrent painful buccal ulcers which each time cleared up spontaneously. Stomatitis is common in childhood. Viral infections are the most common causes of stomatitis, in particular infections with herpes simplex virus (herpes gingivostomatitis), Coxsackie virus (herpangina, hand-foot-mouth-disease), chickenpox and infectious mononucleosis. Bacterial infections are rare and mostly secondary to the viral infections. In infants oral candidiasis (thrush) is a common cause of stomatitis. Most infections are self-limiting and reassurance of parents is important. Dehydration is a common complication and admission to hospital can be prevented by analgesics. The most important non-infectious conditions that cause stomatitis in children are recurrent aphthous stomatitis, erythema multiforme major (Stevens-Johnson syndrome), Behçet's disease, malignancy (leukaemia), immune-mediated disorders (agranulocytosis, cyclic neutropenia), traumata, blistering disorders of the skin and lichen planus. A complete history and a thorough physical examination usually give the correct diagnosis and further investigations are seldom necessary.

Asunto(s)

RESUMEN

BACKGROUND: Drugs that mimic dopamine as bromocriptine were introduced as monotherapy or in a combination with LD in the hope that this approach would prevent or delay the onset of motor complications in patients with Parkinson's disease (PD). However, hitherto, the role of bromocriptine (BR) in this issue has remained controversial. The present study is a systematic review of all randomized controlled trials of bromocriptine monotherapy compared with levodopa (LD) monotherapy in PD. OBJECTIVES: To assess the efficacy and safety of bromocriptine (BR) monotherapy for delaying the onset of motor complications associated with levodopa (LD) therapy in patients with Parkinson's disease (PD). SEARCH STRATEGY: Sources including the Cochrane Library, the search strategy of the Movement Disorders Group (includes computerised searches of MEDLINE and EMBASE and hand searching of appropriate neurology journals), reference lists of the reviews found by the MEDLINE and EMBASE search-strategy, Sandoz -now Novartis- (manufacturer of BR), symposia reports, PD handbooks, contacts with colleagues who had co-ordinated trials on BR and reference lists of all included studies were used to identify randomized controlled trials (RCTs) of interest. SELECTION CRITERIA: Randomized trials were eligible for inclusion if they evaluated the efficacy of BR monotherapy for delaying the onset of motor complications compared to LD therapy in PD patients. Outcome measures that were evaluated included occurrence and severity of motor complications, changes in impairment and disability, and the occurrence of side effects. DATA COLLECTION AND ANALYSIS: To determine the feasibility of a quantitative systematic review two independent reviewers evaluated the methodological quality of identified trials. MAIN RESULTS: Over the period of 1974 to January 1999 we identified six studies randomizing more than 850 patients to a BR or a LD regimen. The majority of the studies lacked sample size calculations and randomization procedure remained unclear in three trials. Only two trials were performed according to a double-blind design. Important differences between studies concerning the duration of trials, the BR titration phase, the achieved mean dose of LD or BR, and the applied outcomes were found. Because of these differences, we could not pool the data from the different trials in an attempt to perform a meta-analysis. Therefore, the available data of the individual trials was re-analysed. Subsequently, the results were interpreted against the background of the sources of heterogeneity between the studies. The occurrence of dyskinesias in three short trials was too low to allow any conclusion. The results of the longer trials indicate a lower occurrence of dyskinesias in the BR tier. In five trials that evaluated dystonia, this motor complication occurred less frequent in the BR tier. However, for both dyskinesias and dystonia a statistically significant difference in favour of BR emerged only in the largest trial. There was a trend for wearing-off and on-off fluctuations to occur less frequently in the BR group. Although all trials evaluated patients at the impairment level, only the largest trial reported a significantly larger improvement for the LD tier during the first year of therapy. Concerning disability, which was evaluated by five trials no statistically significant differences were found. Overall, a statistically larger number of dropouts occurred in the BR group because of an inadequate therapeutic response or intolerable side effects. REVIEWER'S CONCLUSIONS: This systematic review identified important sources of heterogeneity between trials. Inadequate powering of the studies and clinically relevant differences in trial duration, applied outcomes, and trial design may explain the different results and why many findings failed to reach a statistically significant level. Nevertheless, based on qualitative review of available data we conclude that in the treatment of early Parkinson's disease, bromocriptine may be beneficial in delaying motor complications and dyskinesias with comparable effects on impairment and disability in those patients that tolerate the drug.

Asunto(s)

RESUMEN

OBJECTIVES: To assess the efficacy and safety of adjunct bromocriptine (BR) therapy compared to placebo in the treatment of Parkinson's disease (PD) patients with motor complications. SEARCH STRATEGY: Sources including the Cochrane Library, a MEDLINE search-strategy, reference lists of the reviews found by the MEDLINE search-strategy, Sandoz (producer of BR), symposia reports, PD handbooks, SCISEARCH, contacts with colleagues who had co-ordinated trials on BR and reference lists of all included studies were used to identify randomized controlled trials (RCTs) of interest. SELECTION CRITERIA: Randomized trials were eligible for inclusion if they evaluated the efficacy of BR as adjunctive to LD-therapy compared to placebo in PD patients with motor complications. Outcome measures that were evaluated, included occurrence and severity of motor complications, scores on impairment and disability, and the occurrence of side effects. DATA COLLECTION AND ANALYSIS: Three reviewers independently reviewed the quality of identified trials. To determine the feasibility of a quantitative systematic review each eligible study was evaluated concerning the methodological quality. MAIN RESULTS: This review identified important shortcomings regarding the methodological quality of eight trials. All studies failed to describe adequately their randomization procedure. Consultation with the trialists revealed that three trials adequately randomized their patients. Contrary to the information of the published report, one placebo-controlled trial appeared to be carried out as an open study and was therefore excluded. The remaining seven trials were reported to be carried out according to a double-blind design, although one was unblinded after five weeks. There was a conspicuous variability in the duration of trials: four to forty weeks (mean 14 weeks). None of the included trials was performed according to the intention-to-treat principle. With regard to the inclusion criteria, it frequently remained unclear if PD patients actually suffered from motor complications. Prominent differences between studies regarding the baseline characteristics and the rate by which BR was introduced during the titration phase were found. Major differences between studies emerged concerning the applied outcomes. The various methods used to evaluate the occurrence and/or severity of motor complications lacked a sound clinimetric basis. A great diversity of scales to evaluate impairment and disability was applied. None of the included trials reported whether scores on impairment and disability level referred to the "on"- or "off"-phase. REVIEWER'S CONCLUSIONS: This review highlights major methodological problems and sources of heterogeneity that not only hamper the comparability of trials but also preclude a conclusion on the efficacy of BR in the adjunct treatment of PD patients with motor complications.

Asunto(s)

RESUMEN

OBJECTIVES: To assess the efficacy and safety of adjunct bromocriptine (BR) compared with placebo in the treatment of patients with Parkinson's disease (PD) who have motor complications. DESIGN: A systematic review of the literature from 1966-1999 on randomized, controlled trials. Outcome measures were occurrence and severity of motor complications, scores on impairment and disability, and the occurrence of side effects. RESULTS: We included eight trials of which the methodologic quality of seven showed important shortcomings. All studies failed to adequately describe randomization procedures and seven studies failed to report sample size calculations. Only one trial was analyzed according to the intention-to-treat principle. It frequently remained unclear if patients with PD actually had motor complications. Differences between studies concerning the baseline characteristics, the BR titration phase, and the applied outcomes were found. The various methods used to evaluate the occurrence and/or severity of motor complications lacked a sound clinimetric basis. A great diversity of impairment and disability scales were applied. For those studies that reported the incidence of side effects, no clear pattern of BR-related side effects emerged. A trend was found for orthostatic hypotension, which more frequently resulted in withdrawal of patients in the BR group. CONCLUSIONS: Major methodologic problems and sources of heterogeneity not only hamper the comparability of trials, but also preclude a conclusion on the efficacy and safety of BR in the adjunct treatment of patients with PD who have motor complications.

Asunto(s)

Asunto(s)