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Seizure Nov 2012Retigabine (RTG) is now approved in Europe and the US for the adjunctive treatment of partial-onset seizures in adults with epilepsy. To support submissions to EU... (Comparative Study)
Comparative Study Review
INTRODUCTION
Retigabine (RTG) is now approved in Europe and the US for the adjunctive treatment of partial-onset seizures in adults with epilepsy. To support submissions to EU reimbursement authorities, we explored its efficacy and tolerability relative to selected antiepileptic drugs (AEDs).
METHODS
A systematic review was conducted to identify placebo-controlled trials of RTG and selected AEDs approved for use in a similar position in the management pathway of partial epilepsy (eslicarbazepine acetate [ESL], lacosamide [LCM], pregabalin [PGB], tiagabine [TGB] and zonisamide [ZNS]). Using conventional and network meta-analyses as appropriate, we report efficacy and tolerability outcomes for each AED versus placebo and the performance of RTG relative to other AEDs.
RESULTS
Twenty studies met the inclusion criteria: three each for RTG, ESL, LCM, TGB and ZNS; five for PGB. Comparisons comprised 1-5 studies per AED. In the network meta-analysis, RTG was not found to be different from the other AEDs for responder rate (maintenance period), seizure freedom (maintenance period and double-blind period), withdrawals due to adverse events, and incidences of ataxia, dizziness, fatigue and nausea. Differences between RTG and other AEDs were found for a few comparisons, which did not reveal any trends: RTG was associated with a lower responder rate than PGB during the double-blind period, higher withdrawal rate due to any reason than ESL and a higher incidence of somnolence than TGB.
CONCLUSIONS
Findings suggest that the risk/benefit for RTG is similar to that for comparator AEDs. However, results should be interpreted in the context of the limitations of the analyses.
Topics: Anticonvulsants; Carbamates; Disorders of Excessive Somnolence; Epilepsies, Partial; Humans; Phenylenediamines; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 22902288
DOI: 10.1016/j.seizure.2012.07.011 -
The American Journal of Clinical... Aug 2012The utility of iron fortification of food to improve iron deficiency, anemia, and biological outcomes is not proven unequivocally. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The utility of iron fortification of food to improve iron deficiency, anemia, and biological outcomes is not proven unequivocally.
OBJECTIVES
The objectives were to evaluate 1) the effect of iron fortification on hemoglobin and serum ferritin and the prevalence of iron deficiency and anemia, 2) the possible predictors of a positive hemoglobin response, 3) the effect of iron fortification on zinc and iron status, and 4) the effect of iron-fortified foods on mental and motor development, anthropometric measures, and infections.
DESIGN
Randomized and pseudorandomized controlled trials that included food fortification or biofortification with iron were included.
RESULTS
Data from 60 trials showed that iron fortification of foods resulted in a significant increase in hemoglobin (0.42 g/dL; 95% CI: 0.28, 0.56; P < 0.001) and serum ferritin (1.36 μg/L; 95% CI: 1.23, 1.52; P < 0.001), a reduced risk of anemia (RR: 0.59; 95% CI: 0.48, 0.71; P < 0.001) and iron deficiency (RR: 0.48; 95% CI: 0.38, 0.62; P < 0.001), improvement in other indicators of iron nutriture, and no effect on serum zinc concentrations, infections, physical growth, and mental and motor development. Significant heterogeneity was observed for most of the evaluated outcomes. Sensitivity analyses and meta-regression for hemoglobin suggested a higher response with lower trial quality (suboptimal allocation concealment and blinding), use of condiments, and sodium iron edetate and a lower response when adults were included.
CONCLUSION
Consumption of iron-fortified foods results in an improvement in hemoglobin, serum ferritin, and iron nutriture and a reduced risk of remaining anemic and iron deficient.
Topics: Anemia, Iron-Deficiency; Edetic Acid; Ferric Compounds; Ferritins; Food, Fortified; Hemoglobins; Humans; Iron, Dietary; Nutritional Status; Randomized Controlled Trials as Topic; Treatment Outcome; Zinc
PubMed: 22760566
DOI: 10.3945/ajcn.111.031500 -
The American Journal of Clinical... Jun 2009The assessment of dietary adequacy of copper is constrained by the absence of recognized copper status biomarkers. (Review)
Review
BACKGROUND
The assessment of dietary adequacy of copper is constrained by the absence of recognized copper status biomarkers.
OBJECTIVES
The objectives were to systematically review the usefulness of copper status biomarkers and identify those that reflected changes in status over > or =4 wk.
DESIGN
The methods included a structured search on Ovid MEDLINE, EMBASE (Ovid), and Cochrane databases to October 2007, followed by the use of formal inclusion/exclusion criteria, data extraction, validity assessment, and meta-analysis.
RESULTS
A total of 16 studies (288 participants) were included in the review, with data on 16 possible copper biomarkers. All of the included studies were small and at high risk of bias. Data for serum copper suggested its value as a biomarker, reflecting changes in status in both depleted and replete individuals, although these changes were smaller in the latter. Total ceruloplasmin protein is related to copper status but reflects changes in highly depleted individuals only. Erythrocyte superoxide dismutase and urinary deoxypyridinoline are not useful biomarkers, but there were insufficient data to draw firm conclusions about plasma, erythrocyte, and platelet copper; leukocyte superoxide dismutase; erythrocyte, platelet, and plasma glutathione peroxidase; platelet and leukocyte cytochrome-c oxidase; total glutathione; diamine oxidase; and urinary pyridinoline. The paucity of data prevented detailed subgroup analysis.
CONCLUSIONS
Despite limited data, serum copper appears to be a useful biomarker of copper status at the population level. Further large studies with low risk of bias are needed to explore the effectiveness of other biomarkers of copper status and the relation between biomarker responsiveness, dose, and period of supplementation.
Topics: Biomarkers; Copper; Dietary Supplements; Humans; Methods; Nutrition Assessment; Nutritional Status; Trace Elements
PubMed: 19420093
DOI: 10.3945/ajcn.2009.27230E -
The Cochrane Database of Systematic... Jan 2006Xanthines have been used in the treatment of asthma as a bronchodilator, though they may also have anti-inflammatory effects. The current role of xanthines in the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Xanthines have been used in the treatment of asthma as a bronchodilator, though they may also have anti-inflammatory effects. The current role of xanthines in the long-term treatment of childhood asthma needs to be reassessed.
OBJECTIVES
To determine the efficacy of xanthines (e.g. theophylline) in the maintenance treatment of paediatric asthma.
SEARCH STRATEGY
A search of the Cochrane Airways Group Specialised Register was undertaken with predefined search terms. Searches are current to May 2005.
SELECTION CRITERIA
Randomised controlled trials,lasting at least four weeks comparing a xanthine with placebo, regular short-acting beta-agonist (SABA), inhaled corticosteroids (ICS), cromoglycate (SCG), ketotifen (KET) or leukotriene antagonist, in children with diagnosed with chronic asthma between 18 months and 18 years old.
DATA COLLECTION AND ANALYSIS
Two reviewers independently selected each study for inclusion in the review and extracted data. Primary outcome was percentage of symptom-free days.
MAIN RESULTS
Thirty-four studies (2734 participants) of adequate quality were included. Xanthine versus placebo (17 studies): The proportion of symptom free days was larger with xanthine compared with placebo (7.97% [95% CI 3.41, 12.53]). Rescue medication usage was lower with xanthine, with no significant difference in symptom scores or hospitalisations. FEV1 , and PEF were better with xanthine. Xanthine was associated with non - specific side-effects. Data from behavioural scores were inconclusive. Xanthine versus ICS (four studies) : Exacerbations were less frequent with ICS, but no significant difference on lung function was observed. Individual studies reported significant improvements in symptom measures in favour of steroids, and one study reported a difference in growth rate in favour of xanthine. No difference was observed for study withdrawal or tremor. Xanthine was associated with more frequent headache and nausea. Xanthine versus regular SABA (10 studies): No significant difference in symptoms, rescue medication usage and spirometry. Individual studies reported improvement in PEF with beta-agonist. Beta-agonist treatment led to fewer hospitalisations and headaches. Xanthine was associated with less tremor. Xanthine versus SCG (six studies ): No significant difference in symptoms, exacerbations and rescue medication. Sodium cromoglycate was associated with fewer gastro-intestinal side-effects than xanthine. Xanthine versus KET (one study): No statistical tests of significance between xanthine and ketotifen were reported. Xanthine + ICS versus placebo + same dose ICS (three studies) : Results were conflicting due to clinical/methodological differences, and could not be aggregated.
AUTHORS' CONCLUSIONS
Xanthines as first-line preventer alleviate symptoms and reduce requirement for rescue medication in children with mild to moderate asthma. When compared with ICS they were less effective in preventing exacerbations. Xanthines had similar efficacy as single preventative agent compared with regular SABA and SCG. Evidence on AEs (adverse effects) was equivocal: there was evidence for increased AEs overall, but no evidence that any specific AE (including effects on behaviour and attention) occurred more frequently than with placebo. There is insufficient evidence from available studies to make firm conclusions about the effectiveness of xanthines as add-on preventative treatment to ICS, and there are no published paediatric studies comparing xanthines with alternatives in this role. Our data suggest that xanthines are only suitable as first-line preventative asthma therapy in children when ICS are not available. They may have a role as add-on therapy in more severe asthma not controlled by ICS, but further studies are needed to examine this, and to define the risk-benefit ratio compared with other agents.
Topics: Aminophylline; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Humans; Randomized Controlled Trials as Topic; Theophylline; Xanthines
PubMed: 16437447
DOI: 10.1002/14651858.CD002885.pub2 -
BMC Cardiovascular Disorders Nov 2005Numerous practitioners of both conventional and complementary and alternative medicine throughout North America and Europe claim that chelation therapy with EDTA is an... (Review)
Review
BACKGROUND
Numerous practitioners of both conventional and complementary and alternative medicine throughout North America and Europe claim that chelation therapy with EDTA is an effective means to both control and treat cardiovascular disease. These claims are controversial, and several randomized controlled trials have been completed dealing with this topic. To address this issue we conducted a systematic review to evaluate the best available evidence for the use of EDTA chelation therapy in the treatment of cardiovascular disease.
METHODS
We conducted a systematic review of 7 databases from inception to May 2005. Hand searches were conducted in review articles and in any of the trials found. Experts in the field were contacted and registries of clinical trials were searched for unpublished data. To be included in the final systematic review, the studies had to be randomized controlled clinical trials.
RESULTS
A total of seven articles were found assessing EDTA chelation for the treatment of cardiovascular disease. Two of these articles were subgroup analyses of one RCT that looked at different clinical outcomes. Of the remaining five studies, two smaller studies found a beneficial effect whereas the other three exhibited no benefit for cardiovascular disease from the use of EDTA chelation therapy. Adverse effects were rare but those of note included a few cases of hypocalcemia and a single case of increased creatinine in a patient on the EDTA intervention.
CONCLUSION
The best available evidence does not support the therapeutic use of EDTA chelation therapy in the treatment of cardiovascular disease. Although not considered to be a highly invasive or harmful therapy, it is possible that the use of EDTA chelation therapy in lieu of proven therapy may result in causing indirect harm to the patient.
Topics: Cardiovascular Diseases; Chelating Agents; Chelation Therapy; Edetic Acid; Humans; Randomized Controlled Trials as Topic
PubMed: 16262904
DOI: 10.1186/1471-2261-5-32 -
The Cochrane Database of Systematic... Apr 2005Since the advent of inhaled beta2-agonists, anticholinergic agents and glucocorticoids, the role of aminophylline in paediatric acute asthma has become less clear. There... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Since the advent of inhaled beta2-agonists, anticholinergic agents and glucocorticoids, the role of aminophylline in paediatric acute asthma has become less clear. There remains some consensus that it is beneficial in children with acute severe asthma, receiving maximised therapy (oxygen, inhaled bronchodilators, and glucocorticoids).
OBJECTIVES
To determine if the addition of intravenous aminophylline produces a beneficial effect in children with acute severe asthma receiving conventional therapy.
SEARCH STRATEGY
The Cochrane Airways Group register of trials was used to identify relevant studies. The latest search was carried out in December 2004
SELECTION CRITERIA
Randomised-controlled trials comparing intravenous aminophylline with placebo in addition to usual care in children met the inclusion criteria.
DATA COLLECTION AND ANALYSIS
Two reviewers independently assessed studies and extracted data. Disagreement in the selection of trials was resolved by consensus. Attempts were made to contact authors to verify accuracy of data.
MAIN RESULTS
Seven trials met the inclusion criteria (380 participants). Methodological quality was high. All studies recruited children with acute severe asthma and requiring hospital admission. Six studies sought participants who were unresponsive to nebulised short-acting beta-agonist and administered systemic steroids to study participants. In two studies where some children were able to perform spirometry, baseline FEV1 was between 35 and 45% predicted. The addition of aminophylline to steroids and beta2-agonist significantly improved FEV1% predicted over placebo at 6-8 hours, 12-18 hours and 24 hours. Aminophylline led to a greater improvement in PEF% predicted over placebo at 12-18 hours. There was no significant difference in length of hospital stay, symptoms, frequency of nebulsations and mechanical ventilation rates. There were insufficient data to permit aggregation for oxygenation and duration of supplemental oxygen therapy. Aminophylline led to a three-fold increase in the risk of vomiting. There was no significant difference between treatment groups with regard to hypokalaemia, headaches, tremour, seizures, arrhythmias and deaths.
AUTHORS' CONCLUSIONS
In children with a severe asthma exacerbation, the addition of intravenous aminophylline to beta2-agonists and glucocorticoids (with or without anticholinergics) improves lung function within 6 hours of treatment. However there is no apparent reduction in symptoms, number of nebulised treatment and length of hospital stay. There is insufficient evidence to assess the impact on oxygenation, PICU admission and mechanical ventilation. Aminophylline is associated with a significant increased risk of vomiting.
Topics: Acute Disease; Administration, Inhalation; Adolescent; Aminophylline; Asthma; Bronchodilator Agents; Child; Child, Preschool; Humans; Injections, Intravenous; Randomized Controlled Trials as Topic; Vomiting
PubMed: 15846615
DOI: 10.1002/14651858.CD001276.pub2 -
The Cochrane Database of Systematic... 2004Theophylline causes potent cerebral vasoconstriction which decreases blood flow in the non-ischaemic areas of the brain and increases collateral blood flow surrounding... (Review)
Review
BACKGROUND
Theophylline causes potent cerebral vasoconstriction which decreases blood flow in the non-ischaemic areas of the brain and increases collateral blood flow surrounding the ischaemic region. NOTE: This review covers an area where no active research is taking place. It will be updated if relevant information becomes available, e.g. on completion of an appropriate study.
OBJECTIVES
The objective of this review was to assess the effect of theophylline and its analogues, aminophylline and caffeine, in people with confirmed or presumed acute ischaemic stroke.
SEARCH STRATEGY
We searched the Cochrane Stroke Group Trials Register (last searched November 2003). For the first version, we also searched EMBASE (1980 to 1999), MEDLINE (1966 to 1999) and Science Citation Index (1981 to 1999). We also contacted the principal investigators of the identified trials.
SELECTION CRITERIA
Randomised trials of theophylline or an analogue compound compared with placebo or control in people with confirmed or presumed acute ischaemic stroke. Trials were included if treatment was started within one week of stroke onset.
DATA COLLECTION AND ANALYSIS
Three reviewers applied the inclusion criteria, assessed trial quality and extracted data for the first version. The review was updated by one reviewer.
MAIN RESULTS
Two trials involving just 119 patients were included; 6 studies were excluded. Trial quality was good. Both of the trials tested aminophylline. Analysis was by intention-to-treat where possible. No significant difference was shown in early case fatality (within four weeks) between aminophylline and placebo although the confidence intervals were wide (odds ratio [OR] 1.12, 95% confidence interval [CI] 0.49 to 2.56). There was no significant difference for early death and deterioration (OR 0.87, 95% CI 0.41 to 1.88). Death or disability was not significantly reduced by treatment based on 73 patients in one trial (OR 0.64, 95% CI 0.24 to 1.68). Data for late death and disability were not in a form suitable for analysis. No data on quality of life were available.
REVIEWERS' CONCLUSIONS
There is not enough evidence to assess whether theophylline or its analogues, e.g. aminophylline, are safe and improve outcome in people with acute ischaemic stroke.
Topics: Aminophylline; Brain Ischemia; Caffeine; Humans; Randomized Controlled Trials as Topic; Stroke; Theophylline; Vasodilator Agents
PubMed: 15266427
DOI: 10.1002/14651858.CD000211.pub2 -
The Cochrane Database of Systematic... 2001International guidelines currently recommend the use of methyl-xanthines for exacerbations of chronic obstructive pulmonary disease (COPD) for patients who have... (Review)
Review
BACKGROUND
International guidelines currently recommend the use of methyl-xanthines for exacerbations of chronic obstructive pulmonary disease (COPD) for patients who have incomplete responses to bronchodilators. However, available clinical trials are small and underpowered to evaluate the benefits and risks of methyl-xanthines in this acute setting.
OBJECTIVES
To determine the benefit of methyl-xanthines compared to standard care for COPD exacerbations.
SEARCH STRATEGY
Randomised controlled trials (RCTs) were identified from the Cochrane Airways Review Group COPD Register which is a compilation of systematic searches of CINAHL, EMBASE, MEDLINE and CENTRAL and hand searching of 20 respiratory journals. In addition, primary authors and content experts were contacted to identify eligible studies. Bibliographies from included studies, known reviews and texts were also searched.
SELECTION CRITERIA
Only RCTs were eligible for inclusion. Studies were included if patients presented with acute COPD exacerbations and were treated with either methyl-xanthines (oral or intravenous) or placebo (with or without standard care) early in the acute treatment. Studies also needed to report either pulmonary function or admission results. Two reviewers independently selected potentially relevant articles and selected articles for inclusion. Methodological quality was independently assessed by two reviewers.
DATA COLLECTION AND ANALYSIS
Data were extracted independently by two reviewers if the authors were unable to verify the validity of information. Missing data were obtained from authors or calculated from other data presented in the paper. The data were analysed using the Cochrane Review Manager 4.0.4 Studies were pooled to yield weighted mean differences (WMD) or odds ratios (OR) and reported using 95% confidence intervals (95%CI).
MAIN RESULTS
From 28 identified references, 4 RCTs met inclusion criteria (172 patients). Mean change in forced expiratory volume in one second (FEV1) at 2 hours was similar in methyl-xanthine and placebo groups (FEV1 WMD: -8 ml; 95% CI: -85 to 69 ml). The only study to report hospitalization rates showed a non-significant reduction with methyl-xanthines (OR: 0.3; 95% CI: 0.1 to 1.8) among 39 patients. Patients receiving methyl-xanthines had similar improvements in symptom scores, but reported more gastrointestinal side effects (OR: 5.3; 95% CI: 1.3 to 21.0) than patients receiving placebo.
REVIEWER'S CONCLUSIONS
There is no evidence to support the routine use of methyl-xanthines for COPD exacerbations. Methyl-xanthines do not appreciably improve FEV1 during COPD exacerbations and cause adverse effects; evidence of their effect on admissions is limited.
Topics: Aminophylline; Bronchodilator Agents; Humans; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Theophylline
PubMed: 11279755
DOI: 10.1002/14651858.CD002168 -
The Cochrane Database of Systematic... 2001Bronchiectasis is characterised by chronic sputum production,bronchial wall dilation,recurrent infection and airflow limitation. Methylxanthines are used in the... (Review)
Review
BACKGROUND
Bronchiectasis is characterised by chronic sputum production,bronchial wall dilation,recurrent infection and airflow limitation. Methylxanthines are used in the management of airflow limitation associated with asthma and COPD, where they are also purported to have anti-inflammatory properties. In theory they may be of use in bronchiectasis.
OBJECTIVES
To determine the efficacy of methylxanthines in the treatment of bronchiectasis.
SEARCH STRATEGY
The Cochrane Airways Group clinical trials register derived from MEDLINE,EMBASE and hand searches using the terms bronchiectasis, aminophylline, theophylline and methyl- xanthine
SELECTION CRITERIA
Only randomised controlled trials were to be considered.
DATA COLLECTION AND ANALYSIS
The results of the searches were reviewed by two authors. Searches yielded seven trials none of which met the inclusion criteria.
MAIN RESULTS
No randomised controlled trials were identified.
REVIEWER'S CONCLUSIONS
Further research is required to establish if the methylxanthines have a role in the treatment of bronchiectasis.
Topics: Administration, Oral; Aminophylline; Bronchiectasis; Bronchodilator Agents; Humans; Randomized Controlled Trials as Topic; Theophylline
PubMed: 11279764
DOI: 10.1002/14651858.CD002734