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J Costa

Publications and source records attributed to J Costa.

At least 19 recordsLinked to original sources
PubMed2006

Upper limb tremor induced by peripheral nerve injury.

We report a patient with proximal right upper limb tremor, secondary to direct peripheral nerve lesion caused by prior thoracic surgery. Electromyography demonstrated neurogenic abnormalities and tremor in muscles innervated by the thoracodorsal and long thoracic nerves. Somatosensory evoked potentials, transcranial magnetic stimulation, and MRI of the cervical and thoracic spine were normal. Tremor persisted in REM and non-REM sleep. These findings suggest a peripheral generator.

Arm↗
PubMed2006

Antitumor necrosis factor-induced neutropenia: a case report with double positive rechallenges.

A 50-year-old man with ankylosing spondylitis who developed neutropenia after treatment of etanercept, with two positive rechallenges, and after the first infliximab infusion, is described. Although leukopenia and neutropenia related to etanercept and infliximab have been described as rare adverse events from clinical trials data, their mechanism of action are unknown. This patient developed recurrent mild neutropenia after exposition of two different antitumor necrosis factors; therefore, it seems to be an adverse reaction related to the therapeutic group. Doctors should be aware of this potentially severe adverse effect in patients treated with antitumor necrosis factor.

Antibodies, Monoclonal↗
PubMed2006

Ganglioglioma of conus medullaris.

Gangliogliomas are glioneuronal tumours of the young, and occur more frequently supratentorially. Among those uncommon cases in the spinal cord, the conus medullaris is an extremely rare site. We reviewed the literature of such cases and report another case of a ganglioglioma of the conus in a 13-year-old boy with an insidious sensory sensitive and motor deficit of the right lower limb. Subtotal resection was accomplished with no recurrence after two years of follow-up. As for the supratentorial locations, the extent of surgical resection is the main prognostic factor for gangliogliomas of the spinal cord, and they should be considered in the differential diagnosis of intramedullar neoplasm.

Adolescent↗
PubMed2006

Antibiotic prophylaxis for surgical introduction of intracranial ventricular shunts.

BACKGROUND: Systemic antibiotics and antibiotic-impregnated shunt systems are often used to prevent shunt infection. OBJECTIVES: To evaluate the effectiveness of either prophylactic systemic antibiotics or antibiotic-impregnated shunt systems for preventing infection in patients who underwent surgical introduction of intracranial ventricular shunts. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS and the meeting proceedings from the American Association of Neurological Surgeons and from the European Association of Neurosurgical Societies, until June 2005. SELECTION CRITERIA: We included randomized or quasi-randomized controlled trials comparing the use of prophylactic antibiotics (either systemic or antibiotic-impregnated shunt systems) in intracranial ventricular shunt procedures with placebo or no antibiotics. DATA COLLECTION AND ANALYSIS: Two authors appraised quality and extracted data independently. MAIN RESULTS: We included seventeen trials with overall 2134 participants. We performed two separate meta-analyses: one that evaluated the use of systemic prophylactic antibiotics and another that evaluated the use of antibiotic-impregnated systems. All studies included shunt infection in their primary outcome. We could not analyse all-cause mortality regarding systemic antibiotics due to lack of data. No significant differences were found (odds ratio (OR): 1.47, 95% confidence intervals (CI) 0.83 to 2.62) for this outcome regarding the use of antibiotic-impregnated catheters compared with standard ones. The use of systemic antibiotic prophylaxis and the use of antibiotic-impregnated catheters were associated with a decrease in shunt infection (OR: 0.52, 95% CI 0.36 to 0.74 and OR: 0.21, 95% CI 0.08 to 0.55 respectively). We found no significant benefit for shunt revision in both meta-analyses that evaluated systemic antibiotics and impregnated-shunt systems. We found no significant differences between the subgroups evaluated: type of shunt (internal/external, ventriculoperitoneal/ventriculoatrial), age and duration of the administration of antibiotics. AUTHORS' CONCLUSIONS: We could demonstrate a benefit of systemic prophylactic antibiotics for the first 24 hours postoperatively to prevent shunt infection, regardless of the patient's age and the type of internal shunt used. The benefit of its use after this period remains uncertain. However this data derives from the rate of shunt infection, which is an intermediary outcome. Future trials should evaluate the effectiveness of different regimens of systemic antibiotics rather than placebo, and should include all-cause mortality, shunt revision and adverse events as additional outcomes. Evidence suggests that antibiotic-impregnated catheters reduce the incidence of shunt infection although more well-designed clinical trials testing the effect of antibiotic-impregnated shunts are required to confirm their net benefit.

Anti-Bacterial Agents↗
PubMed2006

Antibiotic prophylaxis for preventing meningitis in patients with basilar skull fractures.

BACKGROUND: Basilar skull fractures (BSF) predispose patients to meningitis because of the possible direct contact of bacteria in the paranasal sinuses, nasopharynx or middle ear with the central nervous system (CNS). Cerebrospinal fluid (CSF) leakage has been associated with a greater risk of contracting meningitis. Antibiotics are often given prophylactically, although their role for preventing bacterial meningitis is not established. OBJECTIVES: To evaluate the effectiveness of prophylactic antibiotics for preventing meningitis in patients with BSF. SEARCH STRATEGY: We searched the Cochrane Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2005), MEDLINE (1966 to September 2005), EMBASE (1974 to June 2005), and LILACS (1982 to September 2005). We also performed an electronic search of meeting proceedings from the American Association of Neurological Surgeons (1997 to September 2005) and handsearched the abstracts of meeting proceedings of the European Association of Neurosurgical Societies (1995, 1999 and 2003). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing any antibiotic versus placebo or no intervention. We also identified non-RCTs to perform a separate meta-analysis to compare results. DATA COLLECTION AND ANALYSIS: At least two authors independently appraised the quality and extracted the data of each trial. MAIN RESULTS: Five RCTs and 17 non-RCTs comparing different types of antibiotic prophylaxis with placebo or no intervention in patients with BSF were identified. Most trials presented insufficient methodological detail. All studies included meningitis in their primary outcome. Overall, we evaluated 208 participants from the four RCTs that were considered suitable for inclusion in the meta-analysis. There were no significant differences between antibiotic prophylaxis groups and control groups in terms of reduction of the frequency of meningitis, all-cause mortality, meningitis-related mortality, and need for surgical correction in patients with CSF leakage. We performed a subgroup analysis to evaluate the primary outcome in patients with and without CSF leakage. We also completed a meta-analysis of all the identified controlled non-RCTs (enrolling a total of 2168 patients), producing results consistent with the randomised data. AUTHORS' CONCLUSIONS: Currently available evidence from RCTs does not support prophylactic antibiotic use in patients with BSF, whether there is evidence of CSF leakage or not. Until more research is completed, the effectiveness of antibiotics in patients with BSF cannot be determined because studies published to date are flawed by biases. Large, appropriately designed RCTs are needed.

Antibiotic Prophylaxis↗
PubMed2006

Seroprevalence of measles, rubella, and mumps antibodies in Catalonia, Spain: results of a cross-sectional study.

Determination of antibody levels against vaccine-preventable diseases is of great value to assess immunization programmes. The objective of this study was to determine the prevalence of measles, rubella, and mumps antibodies in representative samples of the child and adult population of Catalonia and compare the findings to those obtained in 1996. A representative sample of the child and adult (>or=15 years) population of Catalonia was studied. Enzyme-linked immunosorbent assay techniques were used to determine the presence of antibodies. Equivocal results for antibodies against measles and rubella were tested using an immunofluorescence technique. To compare proportions, the chi-square test and the Fisher's exact test were used. Statistical significance was set at 0.05. Adjusted odds ratios were calculated using multiple logistic regression analysis. Samples from 2,619 people were analyzed. The global prevalence of antibodies was 98.3% for measles, 91.1% for mumps, and 98.1% for rubella. The prevalence of rubella antibodies was higher in women than in men (98.8 vs. 97.2%, respectively). Compared with the results obtained in the 1996 seroprevalence study, only the prevalence of rubella antibodies showed a statistically significant increase in men (97.2 vs. 94.6%; p=0.002) and, in particular, in women (98.8 vs. 95.3%; p<0.001). The low prevalence of susceptible subjects has already led to the elimination of indigenous measles in Catalonia and should allow the elimination of indigenous rubella by 2005. The level of antibodies necessary to interrupt the transmission of mumps has still not been reached in all age groups.

Adolescent↗
PubMed2006

Sensitivity to antiviral therapy may change after liver transplantation in patients with chronic hepatitis C virus infection.

In hepatitis C virus (HCV)-infected patients, it is generally assumed that the pattern of response to antiviral therapy remains unaltered after liver transplantation (LT). However, changes in the circulating HCV quasispecies and in the gene expression profiles of the graft might influence response to treatment after LT. We evaluated 22 HCV-infected patients who received antiviral treatment while awaiting LT and in whom HCV infection recurred. Eleven of these patients underwent a new antiviral treatment course. Our study analyses the early virological response to both treatment courses to assess the influence of the changes in HCV on the response to therapy. Patients were considered early virological responders (EVR) if viral load declined > or = 2 log10 during the first 12 weeks of therapy. The remaining individuals were considered nonresponders (NR). HCV sequences from hypervariable region 1 and nonstructural 5A (NS5A) region before both treatment regimens were compared. Of 11 patients, 8 (73%) showed identical early response to both courses of therapy (group A: five EVR-EVR, three NR-NR). Interestingly, the response changed in three patients (27%) (group B): two NR became EVR after transplantation, whereas one EVR became NR. Fixation of mutations within the NS5A occurred preferentially in group B (100%) compared with group A (37%)(P = 0.12). However, the number of fixed mutations was not significantly different between groups, suggesting that the changes in sensitivity to therapy after LT are not exclusively dependent on variations in HCV strains. In conclusion, in HCV-infected patients undergoing LT, the pattern of response to antiviral treatment may change after transplantation, and this possibility needs to be incorporated in clinical practice.

Adult↗
PubMed2006

Effect of food intake on the bioavailability of almotriptan, an antimigraine compound, in healthy volunteers: an open, randomized, crossover, single-dose clinical trial.

This open, randomized, crossover, single-dose clinical trial evaluated the possible pharmacokinetic interaction between a single oral dose of almotriptan 25 mg, a 5-HT1B/1D receptor agonist for the acute treatment of migraine, and food intake in healthy volunteers. The influence of food intake in the rate and extent of almotriptan absorption was evaluated by bioequivalence criteria. Tolerability and safety of treatment were also assessed. 16 healthy volunteers (8 men and 8 women, aged 19-27 years) received a crossed single oral dose of almotriptan 25 mg under fasting and fed conditions, separated by a 7-day washout period. The treatment given under fasting condition was considered as reference. Plasma levels of almotriptan were analyzed using high-performance liquid chromatography (HPLC) and UV detection at 227 nm. The 90% confidence intervals (CI) for the logarithmically transformed Cmax and AUC0-infinity, values of almotriptan under fasting and fed conditions (97.8 - 124% and 102.9 - 108.2%, respectively) fell into the predetermined accepted range of 80 - 125%. No statistically significant differences in Cmax, tmax, AUC0-infinity, MRT and t1/2 were observed under fasting and fed conditions between men and women. Tolerability of treatments was good throughout the whole study period. In conclusion, administration of almotriptan 25 mg is bioequivalent under fasting and fed conditions in healthy men and women. Therefore, it is unlikely that concomitant food intake would produce clinially relevant differences in therapeutic effect with almotriptan at the dose studied here.

Administration, Oral↗
PubMed2006

Ethanol does not significantly affect the bioavailability of almotriptan: an open, randomized, crossover, single-dose, phase I clinical trial in healthy volunteers.

OBJECTIVE: A number of clinical reports have revealed a link between the use of alcohol and the onset or exacerbation of migraine headaches. This open, randomized, crossover, single-dose, phase I clinical trial evaluated the possible pharmacokinetic interactions between a single oral dose of almotriptan 12.5 mg, a 5-HT(1B/1D receptor agonist for the acute treatment of migraine, and ethanol in 16 healthy male volunteers. Tolerability and safety of this combined treatment were also assessed. METHODS: Subjects received a crossed oral dose of almotriptan (12.5 mg) with and without concomitant alcohol intake (target plasma concentration 0.8 g/kg) in two different treatment periods. Almotriptan was administered alone, while ethanol was diluted with orange juice, which was also given to the control group. There was a washout period of 7 days between treatments. Plasma levels of almotriptan were analyzed using a sensitive and specific liquid chromatographic-tandem mass spectrometry method. RESULTS: The 90% non-parametric confidence interval for the median t(max) of almotriptan plus ethanol compared to almotriptan alone (0.61/2.72) was outside the acceptable range (0.70 - 1.30), demonstrating that concomitant ethanol administration slightly increases the variability of absorption of almotriptan 12.5 mg. In contrast, the main bioavailability criteria parameters, C(max) and AUC, which show the rate and extent of systemic absorption, were not affected by alcohol ingestion. Therefore, it is unlikely that concomitant ethanol intake would produce clinically relevant differences in the therapeutic effect of almotriptan at the dose studied here. Tolerability of treatments was good throughout the entire study period. CONCLUSIONS: Almotriptan 12.5 mg, with or without concomitant alcohol ingestion, showed similar plasma concentrations after a single dose in healthy volunteers with no clinically relevant drug-to-drug interactions.

Adult↗
PubMed2006

Different expression levels of alpha3/4 fucosyltransferases and Lewis determinants in ovarian carcinoma tissues and cell lines.

Ovarian carcinoma is the leading cause of death from gynecological cancers in many countries. Fucosylated glycoconjugates have been associated with various carcinomas. In the present study, we have characterized the expression of alpha3/4 fucosyltransferases transcripts and their products, the Lewis carbohydrate determinants, and their in vitro specificity towards synthetic acceptors using ovarian carcinoma cell lines OVM, m130, GG and SKOV3. We found different expression patterns: GG cells expressed mostly Lewisx (Lex), Lewisy (Ley), sLea and Leb, and m130 cells expressed mostly Lex and Ley. The detection was on the plasma membrane and in intracellular vesicles. OVM and SKOV3 cells had very low amounts of staining. From RT-PCR studies, enzyme specificity of cellular extracts towards a panel of synthetic carbohydrate acceptors and Western blot analysis we concluded that Lea, sLea and Leb were synthesised by FUT3, whereas Lex and Ley were synthesized by FUT4 and FUT9 in both cell lines. The GG and m130 cell lines are adequate models to investigate the role of Lex, Ley, sLea and Leb in ovarian carcinoma development.

Adenocarcinoma, Mucinous↗
PubMed2006

[Impact of a new parasitologic laboratory for malaria diagnosis on diagnosis and cost of malaria in a company setting: experience from Angola].

In malaria endemic areas treating every fever episode as a malaria onset would result in overdiagnosis with a margin of the error varying in function of epidemiological factors. When further compounded by overestimation related to errors in parasitologic diagnosis, clinical misdiagnosis leads to unwarranted hospitalization and inappropriate treatment. In a company setting this would mean unnecessary loss of employee work time. False positive diagnosis causes overestimation of chemoresistance, overconsumption of antimalarial drugs and underestimation of other infectious diseases. Judging from these high costs, it can be assumed that improving the reliability of parasitologic diagnosis would have a positive impact on the quality of clinical management, efficiency of antimalarial use and accuracy of epidemiological surveys. This assumption was confirmed by analysis of data following start-up of a parasitologic laboratory for malaria diagnosis in the health care clinic at Sonamet's fabrication yard in Lobito, Angola. Laboratory personnel receives expert training and audit findings demonstrate consistently reliable diagnosis. This experience underscores the need for reliable parasitologic diagnosis as a prerequisite for any large-scale malaria control program.

Absenteeism↗
PubMed2005

Triflusal for preventing serious vascular events in people at high risk.

BACKGROUND: Aspirin is the standard treatment for secondary prevention of stroke and other vascular events. Several studies suggest that triflusal may have a better safety profile. OBJECTIVES: To determine in people at high risk of vascular events whether triflusal is an effective and safe treatment for primary and secondary prevention of serious vascular events. SEARCH STRATEGY: We searched the trials registers of the following Cochrane Review Groups: Stroke Group (last searched October 2004), Heart Group, Peripheral Vascular Diseases Group and Metabolic and Endocrine Disorders Group (last searched May 2003). In addition, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2003), MEDLINE (1977 to 2003) and EMBASE (1980 to 2003). We searched reference lists and contacted researchers in the field, authors of relevant trials and the drug manufacturer. SELECTION CRITERIA: Randomised and quasi-randomised studies comparing triflusal with placebo or aspirin in people at high risk of vascular events. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. The primary outcome was a serious vascular event (non-fatal acute myocardial infarction (AMI), non-fatal ischemic or hemorrhagic stroke, or vascular death). Other efficacy and safety measures collected were frequency of different vascular events, adverse events, minor and major hemorrhages. MAIN RESULTS: (1) Aspirin versus triflusal: five studies enrolled patients with stroke or transient ischemic attack (TIA) (4 trials; 2944 patients; followed for 6 to 47 months) or AMI (one trial; 2275 patients; followed for 35 days). Entry criteria were similar within each subgroup of patients. Patient groups were appropriately selected and well matched. The primary outcome in all trials was a composite outcome of vascular events. Trials had no important bias except in one study (217 patients). For the primary outcome of a serious vascular event there was no significant difference between triflusal and aspirin; the odds ratio (OR) was 1.04 (95% confidence interval (CI) 0.87 to 1.23). Significant differences were found for frequency of hemorrhages, both minor (OR 1.60, 95% CI 1.31 to 1.95) and major (OR 2.34, 95% CI 1.58 to 3.46) and for non-hemorrhagic gastrointestinal adverse events (OR 0.84, 95% CI 0.75 to 0.95). Sensitivity analysis of well versus poorly allocated trials showed no significant differences. (2) Triflusal versus placebo: two trials enrolled patients with unstable angina (281 patients) or peripheral arteriopathy (122 patients), who were followed for 6 months. Triflusal was associated with a reduction in serious vascular events (OR 2.29, 95% CI 1.01 to 5.19; OR greater than 1 favours triflusal) and with a higher frequency of adverse events (OR 1.68, 95% CI 1.00 to 2.80). AUTHORS' CONCLUSIONS: No significant differences were found between triflusal and aspirin for secondary prevention of serious vascular events in patients with stroke or TIA and AMI. However, our review cannot exclude moderate differences in efficacy. Triflusal was associated with a lower risk of hemorrhagic complications.

Aspirin↗
PubMed2005

Anticonvulsants for preventing seizures in patients with chronic subdural haematoma.

BACKGROUND: Anticonvulsant therapy is sometimes used prophylactically in patients with chronic subdural haematoma, although the benefit is unclear. OBJECTIVES: To establish the effectiveness of prophylactic anticonvulsants in patients with chronic subdural haematoma, for both pre- and post-operative periods. SEARCH STRATEGY: We searched the Cochrane Injuries Group Specialised Register, Cochrane Controlled Trials Register, MEDLINE, EMBASE, LILACS, the American Association of Neurological Surgeons Database and abstract books of conference proceedings of the European Association of Neurosurgical Societies. We also searched the references of all identified studies. SELECTION CRITERIA: Randomised controlled trials comparing any anticonvulsant versus placebo or no intervention. DATA COLLECTION AND ANALYSIS: No trials met the inclusion criteria for the review. MAIN RESULTS: No randomised, controlled trials were identified. AUTHORS' CONCLUSIONS: No formal recommendations can be made about the use of prophylactic anticonvulsants in patients with chronic subdural haematoma based on the literature currently available. Non-controlled studies came up with conflicting results. There is an urgent need for well-designed randomised controlled trials.

Anticonvulsants↗
PubMed2005

Botulinum toxin type A therapy for cervical dystonia.

BACKGROUND: Cervical dystonia is characterized by involuntary posturing of the head and frequently is associated with neck pain. Disability and social withdrawal are common. In recent years, Botulinum toxin Type A (BtA) has become the first line therapy. However its true efficacy, in particular the potential effect size, is still unclear. OBJECTIVES: To determine whether botulinum toxin (BtA) is an effective and safe treatment for cervical dystonia. SEARCH STRATEGY: We searched the Cochrane Movement Disorders Group trials register (June 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2003, MEDLINE (1977 to June 2003), EMBASE (1977 to June 2003) and reference lists of articles. We also contacted drug manufacturers and researchers in the field. SELECTION CRITERIA: Randomised studies comparing BtA with placebo in adults with cervical dystonia. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. MAIN RESULTS: We found thirteen high quality eligible studies. They were short term (6 to 16 weeks). Eight trials, enrolling 361 patients, used the BtA formulation Botox(r) and five, enrolling 319 patients, used the BtA formulation Dysport. The dose and technique of administration varied significantly between studies.Meta-analysis showed statistically and clinically significant improvements on objective rating scales: (Peto OR 4.31; 95% confidence interval (CI) 2.68 to 6.94) and subjective rating scales (Peto OR 6.58; 95% CI 4.55 to 9.54); and for pain relief in subjective scales (Peto OR 11.92; 95% CI 6.32 to 22.5). However, for many of the outcomes, we could use data from only a few studies. Only adverse events clearly associated with the mechanism of action of BtA were more frequent in the treatment group. These included neck weakness, dysphagia, dry mouth/sore throat and voice changes/hoarseness. Sub-group and sensitivity analyses showed a clear dose-response relationship for subjective and objective benefit and for frequency and severity of adverse events. Indirect comparisons between trials that used Dysport against placebo and trials that used Botox against placebo showed no significant differences between Dysport and Botox in terms of benefits or adverse events. AUTHORS' CONCLUSIONS: A single injection cycle of BtA is effective and safe for treating cervical dystonia. Enriched trials (using patients previously treated with BtA), suggest that further injection cycles continue to work for most patients.

Botulinum Toxins, Type A↗
PubMed2005

Botulinum toxin type A versus anticholinergics for cervical dystonia.

BACKGROUND: Cervical dystonia is the most common form of focal dystonia. It is characterized by involuntary posturing of the head and frequently is associated with neck pain. Disability and social withdrawal are common. Most cases are idiopathic and generally cervical dystonia is a life-long disorder. Botulinum toxin Type A (BtA) is now the first line therapy. Before BtA, anticholinergics were the most widely accepted treatment, so it is important to understand how these two treatments compare. OBJECTIVES: To compare the clinical efficacy and safety of BtA versus anticholinergic drugs in the treatment of cervical dystonia. SEARCH STRATEGY: We searched the Cochrane Movement Disorders Group trials register (June 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 2, 2003), MEDLINE 1977 to June 2003), EMBASE (1977 to June 2003) and reference lists of articles. We also contacted manufacturers and researchers in the field. SELECTION CRITERIA: Randomised studies comparing BtA versus any anticholinergic drug for the treatment of cervical dystonia. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. MAIN RESULTS: We found only one trial suitable for inclusion and accordingly no meta-analysis was performed. It compared BtA versus trihexyphenidyl in 66 patients with cervical dystonia. Although this was a relatively small trial with short duration, the results can probably be generalized for the population, since the trial appears to be unbiased and produced clear clinically significant results. The results favoured BtA, and the difference was similar in size to that obtained in a systematic review comparing BtA with placebo. BtA was better tolerated. AUTHORS' CONCLUSIONS: The available evidence suggests that BtA injections provide more objective and subjective benefit than trihexyphenidyl to patients with cervical dystonia. We could not draw any conclusions about other anticholinergic drugs. Future trials should explore the role of anticholinergic drugs in patients that do not get benefit with BtA.

Botulinum Toxins, Type A↗
PubMed2005

Botulinum toxin type A versus botulinum toxin type B for cervical dystonia.

BACKGROUND: Cervical dystonia is the most common form of focal dystonia. It is characterized by involuntary posturing of the head and frequently is associated with neck pain. Disability and social withdrawal are common. Most cases are idiopathic, and generally it is a life-long disorder. In recent years, botulinum toxin type A (BtA) has become first line therapy for cervical dystonia. However, not all patients respond well to BtA, and 5 to 10% become resistant to it. Botulinum toxin B (BtB) is an alternative to BtA and offers the potential to help patients who do not respond to BtA. At present there is no compelling theoretical reason why it should not be as effective as, or even more effective than, BtA. OBJECTIVES: To compare the clinical efficacy and safety of BtA versus BtB in cervical dystonia. SEARCH STRATEGY: Studies for inclusion in the review were identified using the Cochrane Movement Disorders Group trials register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, by handsearching the Movement Disorders Journal and abstracts of international congresses on movement disorders and botulinum toxin, by communication with other researchers in the field, by searching reference lists of papers found using the above search strategies, and by contact with authors and drug manufacturer. SELECTION CRITERIA: Studies were considered eligible for inclusion in the review if they evaluated the efficacy of BtA versus BtB for the treatment of cervical dystonia. Trials must have been randomised and placebo-controlled. DATA COLLECTION AND ANALYSIS: A paper pro-forma was used to collect data from the included studies using double extraction by two independent reviewers. Each trial was assessed for internal validity by each of the two reviewers. Differences were settled by discussion. The outcome measures used included improvement in symptomatic rating scales, subjective evaluation by patients and clinicians, changes in pain scores, changes in quality of life assessments, and frequency and severity of adverse events. MAIN RESULTS: We cannot give any results since we have only identified two ongoing trials and there are no preliminary results or interim analyses available for them. The full results of these trials are expected in late 2004 or 2005. AUTHORS' CONCLUSIONS: It is currently not possible to make definitive comparisons between BtA and BtB for the treatment of cervical dystonia; uncontrolled comparisons should be regarded with suspicion.

Botulinum Toxins↗
PubMed2005

Botulinum toxin type B for cervical dystonia.

BACKGROUND: Cervical dystonia is the most common form of focal dystonia. It is characterized by involuntary posturing of the head and frequently is associated with neck pain. Disability and social withdrawal are common. Most cases of cervical dystonia are idiopathic and generally it is a life-long disorder. In recent years, Botulinum toxin type A (BtA) has become the first line therapy. However, some patients become resistant to it. This problem led to the study of another Botulinum toxin (Bt) serotype, Bt type B (BtB) to address the issues of clinical efficacy, effect size, and safety of BtB in the treatment of cervical dystonia. OBJECTIVES: To determine whether botulinum toxin (BtB) is an effective and safe treatment for cervical dystonia. SEARCH STRATEGY: We identified studies for inclusion in the review using the Cochrane Movement Disorders Group trials register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE; and by handsearching the Movement Disorders Journal and abstracts of international congresses on movement disorders and botulinum toxin, by communication with other researchers in the field, by searching reference lists of papers found using the above search strategies, and by contacting authors and drug manufacturers. SELECTION CRITERIA: We considered studies eligible for inclusion in the review if they evaluated the efficacy of BtB for the treatment of cervical dystonia in randomized, placebo-controlled trials. DATA COLLECTION AND ANALYSIS: We used a paper pro forma to collect data from the included studies with double extraction by two independent reviewers. Both reviewers assessed each trial for internal validity and settled differences by discussion. The outcome measures used included adverse events, improvement in symptomatic rating scales, subjective evaluation by patients and clinicians, changes in pain scores, changes in quality of life assessments. MAIN RESULTS: Studies were short term (16 weeks) employing a single BtB injection session. All were multicentre and conducted in the US. All patients included had previously received BtA. The trials differed with respect to whether or not the patients were still responding to BtA but other entry criteria were similar. All studies used a dose of 10,000 Units of BtB in one group and the technique of administration was the same. Meta-analysis of three trials enrolling 308 participants showed statistically and clinically significant improvements in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score at week four with a Peto odds ratio (OR) for the number of patients who had at least a 20% improvement of 4.69 (95% CI 2.06 to 10.69) and a weighted mean difference of -5.92 (95% CI -9.61 to -2.23). Subjective rating scales (Patient Global Assessment of Change, Investigator Global Assessment of Change, and Patient Analog Pain Assessment) also improved. Adverse events clearly associated with the mechanism of action of BtB included dysphagia and dry mouth and the number of patients with any adverse event were more frequent in BtB treatment groups. Subgroup analyses showed a clear dose-response relationship for subjective and objective benefit, for frequency and severity of adverse events, and a greater benefit for BtA resistant patients than BtA responders in the primary outcome. The duration of effect was about 16 weeks. We found three eligible studies enrolling 308 participants. Studies were short term (16 weeks) employing a single BtB injection session. All were multicentre and conducted in the US. All patients included had previously received BtA. The trials differed with respect to whether or not the patients were still responding to BtA but other entry criteria were similar. Patient groups were appropriately selected and well matched. From the methodological point of view these trials were probably not subjected to important selection, performance or attrition bias and all studies used an intention-to-treat analysis.The dose varied significantly between studies although all used 10,000 Units of BtB in one group and the technique of administration was the same. The primary outcome in all trials was change in TWSTRS total score at week four and other efficacy outcomes were similar between studies. The number of dropouts was small and balanced in all trials. Reasons for withdrawals were given. One randomized double-blind placebo-controlled study was excluded because data couldn't be extracted for the outcomes. Meta-analysis showed statistically and clinically significant improvements with a Peto odds ratio (OR) of 20% in TWSTRS total score at week four (OR 4.69; 95% CI 2.06 to 10.69) and a weighted mean difference of -5.92 (95% CI -9.61 to -2.23). Subjective rating scales (Patient Global Assessment of Change, Investigator Global Assessment of Change, and Patient Analog Pain Assessment) also improved. The weighted mean difference for changes in these subjective scales varied between -13% to -21%. However, for many of the outcomes, we could not combine data from all studies. Only adverse events clearly associated with the mechanism of action of BtB were more frequent in the treatment group. These included dysphagia and dry mouth. The number of patients with any adverse event was more frequent with BtB. Subgroup analyses showed a clear dose-response relationship for subjective and objective benefit and for frequency and severity of adverse events. Subgroup analyses showed a greater benefit for the BtA resistant patients than BtA responders in the primary outcome. The duration of effect was about 16 weeks. These trials did not measure quality of life nor did they establish the long term duration of effect or immunogenicity AUTHORS' CONCLUSIONS: A single injection of BtB was effective and safe for treating cervical dystonia. Long-term uncontrolled studies suggested that further injection cycles continue to work for most patients. Future research should explore technical factors such as the optimum treatment intervals and use of image or electromyographic guidance for administration. Other issues include service delivery, quality of life, long-term efficacy and safety, and the relative indications for BtA, BtB and other treatments such as deep brain stimulation.

Botulinum Toxins↗