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The Cochrane Database of Systematic... Nov 2014Gastro-oesophageal reflux (GOR) is a common disorder, characterised by regurgitation of gastric contents into the oesophagus. GOR is a very common presentation in... (Review)
Review
BACKGROUND
Gastro-oesophageal reflux (GOR) is a common disorder, characterised by regurgitation of gastric contents into the oesophagus. GOR is a very common presentation in infancy in both primary and secondary care settings. GOR can affect approximately 50% of infants younger than three months old (Nelson 1997). The natural history of GOR in infancy is generally that of a functional, self-limiting condition that improves with age; < 5% of children with vomiting or regurgitation continue to have symptoms after infancy (Martin 2002). Older children and children with co-existing medical conditions can have a more protracted course. The definition of gastro-oesophageal reflux disease (GORD) and its precise distinction from GOR are debated, but consensus guidelines from the North American Society of Gastroenterology, Hepatology and Nutrition (NASPGHAN-ESPGHAN guidelines 2009) define GORD as 'troublesome symptoms or complications of GOR.'
OBJECTIVES
This Cochrane review aims to provide a robust analysis of currently available pharmacological interventions used to treat children with GOR by assessing all outcomes indicating benefit or harm.
SEARCH METHODS
We sought to identify relevant published trials by searching the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 5), MEDLINE and EMBASE (1966 to 2014), the Centralised Information Service for Complementary Medicine (CISCOM), the Institute for Scientific Information (ISI) Science Citation Index (on BIDS-UK General Science Index) and the ISI Web of Science. We also searched for ongoing trials in the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com).Reference lists from trials selected by electronic searching were handsearched for relevant paediatric studies on medical treatment of children with gastro-oesophageal reflux, as were published abstracts from conference proceedings (published in Gut and Gastroenterology) and reviews published over the past five years.No language restrictions were applied.
SELECTION CRITERIA
Abstracts were reviewed by two review authors, and relevant RCTs on study participants (birth to 16 years) with GOR receiving a pharmacological treatment were selected. Subgroup analysis was considered for children up to 12 months of age, and for children 12 months to 16 years of age, and for those with neurological impairment.
DATA COLLECTION AND ANALYSIS
Trials were critically appraised and data collected by two review authors. Risk of bias was assessed. Meta-analysis data were independently extracted by two review authors, and suitable outcome data were analysed using RevMan.
MAIN RESULTS
A total of 24 studies (1201 participants) contributed data to the review. The review authors had several concerns regarding the studies. Pharmaceutical company support for manuscript preparation was a common feature; also, because common endpoints were lacking, study populations were heterogenous and variations in study design were noted, individual drug meta-analysis was not possible.Moderate-quality evidence from individual studies suggests that proton pump inhibitors (PPIs) can reduce GOR symptoms in children with confirmed erosive oesophagitis. It was not possible to demonstrate statistical superiority of one PPI agent over another.Some evidence indicates that H₂antagonists are effective in treating children with GORD. Methodological differences precluded performance of meta-analysis on individual agents or on these agents as a class, in comparison with placebo or head-to-head versus PPIs, and additional studies are required.RCT evidence is insufficient to permit assessment of the efficacy of prokinetics. Given the diversity of study designs and the heterogeneity of outcomes, it was not possible to perform a meta-analysis of the efficacy of domperidone.In younger children, the largest RCT of 80 children (one to 18 months of age) with GOR showed no evidence of improvement in symptoms and 24-hour pH probe, but improvement in symptoms and reflux index was noted in a subgroup treated with domperidone and co-magaldrox(Maalox(®) ). In another RCT of 17 children, after eight weeks of therapy. 33% of participants treated with domperidone noted an improvement in symptoms (P value was not significant). In neonates, the evidence is even weaker; one RCT of 26 neonates treated with domperidone over 24 hours showed that although reflux frequency was significantly increased, reflux duration was significantly improved.Diversity of RCT evidence was found regarding efficacy of compound alginate preparations(Gaviscon Infant(®) ) in infants, although as a result of these studies, Gaviscon Infant(®) was changed to become aluminium-free and has been assessed in its current form in only two studies since 1999. Given the diversity of study designs and the heterogeneity of outcomes, as well as the evolution in formulation, it was not possible to perform a meta-analysis on the efficacy of Gaviscon Infant(®) . Moderate evidence indicates that Gaviscon Infant(®) improves symptoms in infants, including those with functional reflux; the largest study of the current formulation showed improvement in symptom control but was limited by length of follow-up.No serious side effects were reported.No RCTs on pharmacological treatments for children with neurodisability were identified.
AUTHORS' CONCLUSIONS
Moderate evidence was found to support the use of PPIs, along with some evidence to support the use of H₂ antagonists in older children with GORD, based on improvement in symptom scores, pH indices and endoscopic/histological appearances. However, lack of independent placebo-controlled and head-to-head trials makes conclusions as to relative efficacy difficult to determine. Further RCTs are recommended. No robust RCT evidence is available to support the use of domperidone, and further studies on prokinetics are recommended, including assessments of erythromycin.Pharmacological treatment of infants with reflux symptoms is problematic, as many infants have GOR, and little correlation has been noted between reported symptoms and endoscopic and pH findings. Better evidence has been found to support the use of PPIs in infants with GORD, but heterogeneity in outcomes and in study design impairs interpretation of placebo-controlled data regarding efficacy. Some evidence is available to support the use of Gaviscon Infant(®) , but further studies with longer follow-up times are recommended. Studies of omeprazole and lansoprazole in infants with functional GOR have demonstrated variable benefit, probably because of differences in inclusion criteria.No robust RCT evidence has been found regarding treatment of preterm babies with GOR/GORD or children with neurodisabilities. Initiation of RCTs with common endpoints is recommended, given the frequency of treatment and the use of multiple antireflux agents in these children.
Topics: Alginates; Aluminum Hydroxide; Child; Child, Preschool; Domperidone; Drug Combinations; Gastroesophageal Reflux; Gastrointestinal Agents; Histamine H2 Antagonists; Humans; Infant; Infant, Newborn; Magnesium Hydroxide; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Silicic Acid; Sodium Bicarbonate
PubMed: 25419906
DOI: 10.1002/14651858.CD008550.pub2 -
The Cochrane Database of Systematic... Nov 2014Background Tranexamic acid reduces haemorrhage through its antifibrinolytic effects. In a previous version of the present review, we found that tranexamic acid may... (Meta-Analysis)
Meta-Analysis Review
Background Tranexamic acid reduces haemorrhage through its antifibrinolytic effects. In a previous version of the present review, we found that tranexamic acid may reduce mortality. This review includes updated searches and new trials.Objectives To assess the effects of tranexamic acid versus no intervention, placebo or other antiulcer drugs for upper gastrointestinal bleeding.Search methods We updated the review by performing electronic database searches (Cochrane Central Register of Controlled Trials (CENTRAL),MEDLINE, EMBASE, Science Citation Index) and manual searches in July 2014.Selection criteriaRandomised controlled trials, irrespective of language or publication status.Data collection and analysis We used the standard methodological procedures of the The Cochrane Collaboration. All-cause mortality, bleeding and adverse events were the primary outcome measures. We performed fixed-effect and random-effects model meta-analyses and presented results as risk ratios (RRs) with 95% confidence intervals (CIs) and used I² as a measure of between-trial heterogeneity. We analysed tranexamic acid versus placebo or no intervention and tranexamic acid versus antiulcer drugs separately. To analyse sources of heterogeneity and robustness of the overall results, we performed subgroup, sensitivity and sequential analyses.Main results We included eight randomised controlled trials on tranexamic acid for upper gastrointestinal bleeding. Additionally, we identified one large ongoing pragmatic randomised controlled trial from which data are not yet available. Control groups were randomly assigned to placebo (seven trials) or no intervention (one trial). Two trials also included a control group randomly assigned to antiulcer drugs(lansoprazole or cimetidine). The included studies were published from 1973 to 2011. The number of participants randomly assigned ranged from 47 to 216 (median 204). All trials reported mortality. In total, 42 of 851 participants randomly assigned to tranexamic acid and 71 of 850 in the control group died (RR 0.60, 95% CI 0.42 to 0.87; P value 0.007; I² = 0%). The analysis was not confirmed when all participants in the intervention group with missing outcome data were included as treatment failures, or when the analysis was limited to trials with low risk of attrition bias. Rebleeding was diagnosed for 117 of 826 participants in the tranexamic acid group and for 146 of 825 participants in the control group (RR 0.80, 95% CI 0.64 to 1.00; P value 0.07; I² = 49%).We were able to evaluate the risk of serious adverse events on the basis of only four trials. Our analyses showed 'no evidence of a difference between tranexamic acid and control interventions regarding the risk of thromboembolic events.’ Tranexamic acid appeared to reduce the risk of surgery ina fixed-effect meta-analysis (RR 0.73, 95% CI 0.56 to 0.95), but this result was no longer statistically significant in a random-effects meta-analysis (RR 0.61, 95% CI 0.35 to 1.04; P value 0.07). No difference was apparent between tranexamic acid and placebo in the assessment of transfusion (RR 1.02, 95% CI 0.94 to 1.11; I² = 0%), and meta-analyses that compared tranexamic acid versus antiulcer drugs did not identify beneficial or detrimental effects of tranexamic acid for any of the outcomes assessed.Authors' conclusions This review found that tranexamic acid appears to have a beneficial effect on mortality, but a high dropout rate in some trials means that we cannot be sure of this until the findings of additional research are published. At the time of this update in 2014, one large study(8000 participants) is in progress, so this review will be much more informative in a few years. Further examination of tranexamic acid would require inclusion of high-quality randomised controlled trials. Timing of randomisation is essential to avoid attrition bias and to limit the number of withdrawals. Future trials may use a pragmatic design and should include all participants with suspected bleeding or with endoscopically verified bleeding, as well as a tranexamic placebo arm and co-administration of pump inhibitors and endoscopic therapy. Assessment of outcome measures in such studies should be clearly defined. Endoscopic examination with appropriate control of severe bleeding should be performed, as should endoscopic verification of clinically significant rebleeding. In addition, clinical measures of rebleeding should be included. Other important outcome measures include mortality (30-day or in-hospital), need for emergency surgery or blood transfusion and adverse events (major or minor).
Topics: Administration, Oral; Aluminum Hydroxide; Anti-Ulcer Agents; Antifibrinolytic Agents; Cimetidine; Drug Combinations; Endoscopy, Gastrointestinal; Gastrointestinal Hemorrhage; Humans; Injections, Intravenous; Lansoprazole; Magnesium; Magnesium Hydroxide; Randomized Controlled Trials as Topic; Tranexamic Acid
PubMed: 25414987
DOI: 10.1002/14651858.CD006640.pub3 -
Critical Reviews in Toxicology Oct 2014Abstract Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods,... (Review)
Review
Systematic review of potential health risks posed by pharmaceutical, occupational and consumer exposures to metallic and nanoscale aluminum, aluminum oxides, aluminum hydroxide and its soluble salts.
Abstract Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007) . Challenges encountered in carrying out the present review reflected the experimental use of different physical and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of "total Al"assumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold. The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al(+3) to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres [Al(O2)(H2O4)(+2) and Al(H2O)6 (+3)] that after complexation with O2(•-), generate Al superoxides [Al(O2(•))](H2O5)](+2). Semireduced AlO2(•) radicals deplete mitochondrial Fe and promote generation of H2O2, O2 (•-) and OH(•). Thus, it is the Al(+3)-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates. Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer's disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants. The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances.
Topics: Aluminum; Aluminum Hydroxide; Aluminum Oxide; Animals; Carcinogenesis; Cardiovascular System; Central Nervous System; Disease Models, Animal; Dose-Response Relationship, Drug; Endocrine System; Europe; Gastrointestinal Tract; Guidelines as Topic; Humans; Kidney; Liver; Nanoparticles; Occupational Exposure; Randomized Controlled Trials as Topic; Respiratory System; Risk Assessment; Risk Factors
PubMed: 25233067
DOI: 10.3109/10408444.2014.934439 -
The Cochrane Database of Systematic... Aug 2014In children, dental caries is among the most prevalent chronic diseases worldwide. Pulp interventions are indicated for extensive tooth decay. Depending on the severity... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In children, dental caries is among the most prevalent chronic diseases worldwide. Pulp interventions are indicated for extensive tooth decay. Depending on the severity of the disease, three pulp treatment techniques are available: direct pulp capping, pulpotomy and pulpectomy. After treatment, the cavity is filled with a medicament.This is an update of a Cochrane review first published in 2003. The previous review found insufficient evidence regarding the relative efficacy of these interventions, combining one pulp treatment technique and one medicament.
OBJECTIVES
To assess the effects of different pulp treatment techniques and associated medicaments for the treatment of extensive decay in primary teeth.
SEARCH METHODS
We searched the Cochrane Oral Health Group's Trials Register (to 25 October 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 9), MEDLINE via OVID (1946 to 25 October 2013), EMBASE via OVID (1980 to 25 October 2013) and the Web of Science (1945 to 25 October 2013). We searched OpenGrey for grey literature and the US National Institutes of Health Trials Register and the World Health Organization (WHO) Clinical Trials Registry Platform for ongoing trials. We placed no restrictions on the language or date of publication when searching the electronic databases.
SELECTION CRITERIA
Eligible studies were randomised controlled trials comparing different pulp interventions combining a pulp treatment technique and a medicament in children with extensive decay involving dental pulp in primary teeth.
DATA COLLECTION AND ANALYSIS
Two review authors independently carried out data extraction and risk of bias assessment in duplicate. We contacted authors of randomised controlled trials for additional information if necessary. The primary outcomes were clinical failure and radiological failure, as defined in trials, at six, 12 and 24 months. We performed data synthesis with pairwise meta-analyses using fixed-effect models. We assessed statistical heterogeneity using by I(2) coefficients.
MAIN RESULTS
We included 47 trials (3910 randomised teeth) compared to three trials in the previous version of the review published in 2003. All trials were single centre and small sized (median number of randomised teeth 68). Overall, the risk of bias was low in only one trial with all other trials being at unclear or high risk of bias. The overall quality of the evidence was low. The 47 trials examined 53 different comparisons: 25 comparisons between different medicaments/techniques for pulpotomy, 13 comparisons between different medicaments for pulpectomy, 13 comparisons between different medicaments for direct pulp capping and two comparisons between pulpotomy and pulpectomy. Regarding pulpotomy, 14 trials compared mineral trioxide aggregate (MTA) with formocresol (FC). MTA reduced both clinical and radiological failures at six, 12 and 24 months, although the difference was not statistically significant. MTA also showed favourable results for all secondary outcomes measured, although again, differences between MTA and FC were not statistically significant (with the exception of pathological root resorption at 24 months and dentine bridge formation at six months). MTA showed favourable results compared with calcium hydroxide (CH) (two trials) for all outcomes measured, but the differences were not statistically significant (with the exception of radiological failure at 12 months). When comparing MTA with ferric sulphate (FS) (three trials), MTA had statistically significantly fewer clinical, radiological and overall failures at 24 months. This difference was not shown at six or 12 months.FC was compared with CH in seven trials and with FS in seven trials. There was a statistically significant difference in favour of FC for clinical failure at six and 12 months, and radiological failure at six, 12 and 24 months. FC also showed favourable results for all secondary outcomes measured, although differences between FC and CH were not consistently statistically significant across time points. The comparisons between FC and FS showed no statistically significantly difference between the two medicaments for any outcome at any time point.For all other comparisons of medicaments used during pulpotomies, pulpectomies or direct pulp capping, the small numbers of studies and the inconsistency in results limits any interpretation.
AUTHORS' CONCLUSIONS
We found no evidence to identify one superior pulpotomy medicament and technique clearly. Two medicaments may be preferable: MTA or FS. The cost of MTA may preclude its clinical use and therefore FS could be used in such situations. Regarding other comparisons for pulpectomies or direct pulp capping, the small numbers of studies undertaking the same comparison limits any interpretation.
Topics: Aluminum Compounds; Calcium Compounds; Calcium Hydroxide; Child; Child, Preschool; Controlled Clinical Trials as Topic; Dental Caries; Dental Cements; Dental Materials; Drug Combinations; Electric Stimulation Therapy; Ferric Compounds; Formocresols; Humans; Molar; Oxides; Pulpectomy; Pulpotomy; Randomized Controlled Trials as Topic; Silicates; Tooth, Deciduous; Zinc Oxide-Eugenol Cement
PubMed: 25099759
DOI: 10.1002/14651858.CD003220.pub2 -
Alimentary Pharmacology & Therapeutics May 2014Bile acid malabsorption (BAM) is a common, yet under-recognised, cause of chronic diarrhoea, with limited guidance available on the appropriate management of patients... (Review)
Review
BACKGROUND
Bile acid malabsorption (BAM) is a common, yet under-recognised, cause of chronic diarrhoea, with limited guidance available on the appropriate management of patients with BAM.
AIM
To summarise the evidence supporting different treatments available for patients with bile acid malabsorption, noting their impact on clinical outcomes, tolerability and associated side effects.
METHODS
A literature search was conducted through PubMed, the Cochrane Database of Systematic Reviews and Scopus. Relevant articles studied patients who had been diagnosed with BAM and were clinically assessed before and after therapy.
RESULTS
A total of 30 relevant publications (1241 adult patients) were identified, which investigated the clinical response to drugs, including colestyramine, colestipol, colesevelam, aluminium hydroxide and obeticholic acid. The most commonly used diagnostic test of bile acid malabsorption was the SeHCAT test (24 studies). Colestyramine treatment was by far the most studied of these agents, and was successful in 70% of 801 patients (range: 63-100%).
CONCLUSIONS
Colestyramine and colestipol are generally effective treatments of gastrointestinal symptoms from BAM, but may be poorly tolerated and reduce the bioavailability of co-administered agents. Alternative therapies (including colesevelam and aluminium hydroxide) as well as dietary intervention may also have a role, and the promising results of the first proof-of-concept study of obeticholic acid suggest that its novel approach may have an exciting future in the treatment of this condition. Future trials should employ accurate diagnostic testing and be conducted over longer periods so that the long-term benefits and tolerability of these different approaches can be evaluated.
Topics: Adult; Anion Exchange Resins; Bile Acids and Salts; Chronic Disease; Diarrhea; Gastrointestinal Diseases; Humans; Steatorrhea; Taurocholic Acid
PubMed: 24602022
DOI: 10.1111/apt.12684 -
Journal of Dentistry Sep 2014Pulpotomy is a common procedure to treat asymptomatic reversible pulpitis in primary molars. The aim of this study is to undertake a systematic review and a network... (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
Pulpotomy is a common procedure to treat asymptomatic reversible pulpitis in primary molars. The aim of this study is to undertake a systematic review and a network meta-analysis to compare the clinical and radiographic outcomes of different pulpotomy procedures in primary molars.
DATA
Three authors performed data extraction independently and in duplicate using data collection forms. Disagreements were resolved by discussion.
SOURCES
An electronic literature search was performed within MEDLINE (via PubMed), ScienceDirect, Web of Science, Cochrane, and ClinicalKey databases until December 2012. Medications for pulpotomy including formocresol, ferric sulfate, calcium hydroxide, and mineral trioxide aggregate (MTA), and laser pulpotomy are compared using Bayesian network meta-analyses. The outcome is the odds ratio for clinical and radiographic failure including premature tooth loss at 12 and 24 months after treatments amongst different treatment procedures. 37 studies were included in the systematic review, and 22 of them in the final network meta-analyses. After 18-24 months, in terms of treatment failure, the odds ratio for calcium hydroxide vs. formocresol was 1.94 [95% credible interval (CI): 1.11, 3.25]; 3.38 (95% CI: 1.37, 8.61) for lasers vs. formocresol; 2.16 (95% CI: 1.12, 4.31) for calcium hydroxide vs. ferric sulfate; 3.73 (95% CI: 1.27, 11.67) for lasers vs. ferric sulfate; 0.47 (95% CI: 0.26, 0.83) for MTA vs. calcium hydroxide; 3.76 (95% CI: 1.39, 10.08) for lasers vs.
MTA CONCLUSIONS
After 18-24 months, formocresol, ferric sulfate, and MTA showed significantly better clinical and radiographic outcomes than calcium hydroxide and laser therapies in primary molar pulpotomies.
CLINICAL SIGNIFICANCE
The network meta-analyses showed that MTA is the first choice for primary molar pulpotomies. However, if treatment cost is an issue, especially when the treated primary molars are going to be replaced by permanent teeth, ferric sulfate may be the choice.
Topics: Aluminum Compounds; Calcium Compounds; Calcium Hydroxide; Drug Combinations; Ferric Compounds; Formocresols; Humans; Laser Therapy; Molar; Oxides; Pulpitis; Pulpotomy; Root Canal Irrigants; Silicates; Tooth, Deciduous; Treatment Outcome
PubMed: 24513112
DOI: 10.1016/j.jdent.2014.02.001 -
The Cochrane Database of Systematic... Jan 2012Tranexamic acid reduces haemorrhage through its antifibrinolytic effects. In a previous version of the present review, we found that tranexamic acid may reduce... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tranexamic acid reduces haemorrhage through its antifibrinolytic effects. In a previous version of the present review, we found that tranexamic acid may reduce mortality. The present review includes updated searches of randomised trials on tranexamic acid versus placebo, cimetidine or lansoprazole.
OBJECTIVES
To assess the effects of tranexamic acid for upper gastrointestinal bleeding.
SEARCH METHODS
Electronic searches (The Cochrane Library, MEDLINE, EMBASE, Science Citation Index) and manual searches were combined. The last search update was in October 2011.
SELECTION CRITERIA
Trials in which patients with upper gastrointestinal bleeding were randomised to receive either tranexamic acid or placebo, or any anti-ulcer drug, were included.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data. All-cause mortality was the primary outcome measure. Random-effects model meta-analyses were performed and results presented as relative risks (RR) with 95% confidence intervals (CI). Subgroup, sensitivity, regression and sequential analyses were performed to analyse sources of intertrial heterogeneity and the robustness of the overall result.
MAIN RESULTS
Seven double blind randomised trials on tranexamic acid versus placebo, cimetidine, or lanzoprazole were included. One trial offered endoscopic treatment to all patients that were randomised. Random-effects model meta-analysis found that tranexmic acid reduced mortality compared with placebo (41 of 829 versus 68 of 825 patients; RR: 0.61, 95% CI 0.42 to 0.89). The beneficial effect was not confirmed in subgroup analysis stratified for the quality of bias control, in worst case scenario analyses (in which 21% of the randomised patients were excluded), or in sequential analyses. No significant differences were found between tranexamic acid and placebo on bleeding, surgery, or transfusion requirements. No clear effects of tranexamic acid were identified in trials using endoscopic therapy or in the trials comparing tranexamic acid with cimetidine or lansoprazole. In the tranexamic acid group, five cases of serious thromboembolic events occurred (myocardial infarction, pulmonary embolism, and cerebral infarction). Overall, the number of patients with any thrombotic event was not significantly increased in the tranexamic acid group (RR 1.87, 95% CI 0.60 to 5.85).
AUTHORS' CONCLUSIONS
Considering the internal and external validity of the evidence, tranexamic acid cannot be recommended for routine use. Additional trials in which tranexamic acid is used in combination with the currently recommended interventions are required.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Administration, Oral; Aluminum Hydroxide; Anti-Ulcer Agents; Antifibrinolytic Agents; Cimetidine; Drug Combinations; Endoscopy, Gastrointestinal; Gastrointestinal Hemorrhage; Humans; Injections, Intravenous; Lansoprazole; Magnesium; Magnesium Hydroxide; Randomized Controlled Trials as Topic; Tranexamic Acid
PubMed: 22258969
DOI: 10.1002/14651858.CD006640.pub2 -
The Cochrane Database of Systematic... Sep 2011Latent autoimmune diabetes in adults (LADA) is a slowly developing type 1 diabetes. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Latent autoimmune diabetes in adults (LADA) is a slowly developing type 1 diabetes.
OBJECTIVES
To compare interventions used for LADA.
SEARCH STRATEGY
Studies were obtained from searches of electronic databases, supplemented by handsearches, conference proceedings and consultation with experts. Date of last search was December 2010.
SELECTION CRITERIA
Randomised controlled trials (RCT) and controlled clinical trials (CCT) evaluating interventions for LADA or type 2 diabetes with antibodies were included.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and assessed risk of bias. Studies were summarised using meta-analysis or descriptive methods.
MAIN RESULTS
Searches identified 13,306 citations. Fifteen publications (ten studies) were included, involving 1019 participants who were followed between three months to 10 years (1060 randomised). All studies had a high risk of bias. Sulphonylurea (SU) with insulin did not improve metabolic control significantly more than insulin alone at three months (one study, n = 15) and at 12 months (one study, n = 14) of treatment and follow-up. SU (with or without metformin) gave poorer metabolic control compared to insulin alone (mean difference in glycosylated haemoglobin A1c (HbA1c) from baseline to end of study, for insulin compared to oral therapy: -1.3% (95% confidence interval (CI) -2.4 to -0.1; P = 0.03, 160 participants, four studies, follow-up/duration of therapy: 12, 30, 36 and 60 months; however, heterogeneity was considerable). In addition, there was evidence that SU caused earlier insulin dependence (proportion requiring insulin at two years was 30% in the SU group compared to 5% in conventional care group (P < 0.001); patients classified as insulin dependent was 64% (SU group) and 12.5% (insulin group, P = 0.007). No intervention influenced fasting C-peptide, but insulin maintained stimulated C-peptide better than SU (one study, mean difference 7.7 ng/ml (95% CI 2.9 to 12.5)). In a five year follow-up of GAD65 (glutamic acid decarboxylase formulated with aluminium hydroxide), improvements in fasting and stimulated C-peptide levels (20 μg group) were maintained after five years. Short term (three months) follow-up in one study (n = 74) using Chinese remedies did not demonstrate a significant difference in improving fasting C-peptide levels compared to insulin alone (0.07 µg/L (95% CI -0.05 to 0.19). One study using vitamin D with insulin showed steady fasting C-peptide levels in the vitamin D group but declining fasting C-peptide levels (368 to 179 pmol/L, P = 0.006) in the insulin alone group at 12 months follow-up. Comparing studies was difficult as there was a great deal of heterogeneity in the studies and in their selection criteria. There was no information regarding health-related quality of life, complications of diabetes, cost or health service utilisation, mortality and limited evidence on adverse events (studies on oral agents or insulin reported no adverse events in terms of severe hypoglycaemic episodes).
AUTHORS' CONCLUSIONS
Two studies show SU leading to earlier insulin dependence and a meta-analysis of four studies with considerable heterogeneity showed poorer metabolic control if SU is prescribed for patients with LADA compared to insulin. One study showed that vitamin D with insulin may protect pancreatic beta cells in LADA. Novel treatments such as GAD65 in certain doses (20 μg) have been suggested to maintain fasting and stimulated C-peptide levels. However, there is no significant evidence for or against other lines of treatment of LADA.
Topics: Adult; Autoimmune Diseases; Diabetes Mellitus, Type 2; Drugs, Chinese Herbal; Glutamate Decarboxylase; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Metformin; Randomized Controlled Trials as Topic; Sulfonylurea Compounds; Thiazolidinediones
PubMed: 21901702
DOI: 10.1002/14651858.CD006165.pub3 -
Seminars in Dialysis 2011Phosphate binders include calcium acetate or carbonate, sevelamer hydrochloride or carbonate, magnesium and lanthanum carbonate, and aluminum carbonate or hydroxide.... (Review)
Review
Phosphate binders include calcium acetate or carbonate, sevelamer hydrochloride or carbonate, magnesium and lanthanum carbonate, and aluminum carbonate or hydroxide. Their relative phosphate-binding capacity has been assessed in human, in vivo studies that have measured phosphate recovery from stool and/or changes in urinary phosphate excretion or that have compared pairs of different binders where dose of binder in each group was titrated to a target level of serum phosphate. The relative phosphate-binding coefficient (RPBC) based on weight of each binder can be estimated relative to calcium carbonate, the latter being set to 1.0. A systematic review of these studies gave the following estimated RPBC: for elemental lanthanum, 2.0, for sevelamer hydrochloride or carbonate 0.75, for calcium acetate 1.0, for anhydrous magnesium carbonate 1.7, and for "heavy" or hydrated, magnesium carbonate 1.3. Estimated RPBC for aluminum-containing binders were 1.5 for aluminum hydroxide and 1.9 for aluminum carbonate. The phosphate-binding equivalent dose was then defined as the dose of each binder in g × its RPBC, which would be the binding ability of an equivalent weight of calcium carbonate. The phosphate-binding equivalent dose may be useful in comparing changes in phosphate binder prescription over time when multiple binders are being prescribed, when estimating an initial binder prescription, and also in phosphate kinetic modeling.
Topics: Chelating Agents; Humans; Kidney Failure, Chronic; Phosphates; Phosphorus Metabolism Disorders; Renal Dialysis
PubMed: 21338393
DOI: 10.1111/j.1525-139X.2011.00849.x -
The Cochrane Database of Systematic... Jan 2010Bone disease is common in children with chronic kidney disease (CKD) and when untreated may result in bone deformities, bone pain, fractures and reduced growth rates. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Bone disease is common in children with chronic kidney disease (CKD) and when untreated may result in bone deformities, bone pain, fractures and reduced growth rates.
OBJECTIVES
To investigate the benefits and harms of interventions for preventing and treating bone disease in children with CKD.
SEARCH STRATEGY
The Cochrane Renal Group's specialised register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, reference lists and abstracts were searched without language restriction.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing different interventions used to prevent or treat bone disease in children with CKD stages 2-5D compared with placebo, no treatment or other agents were included. Studies examining different routes or frequency of treatment were also included.
DATA COLLECTION AND ANALYSIS
Data were extracted by two authors. The random-effects model was used and results were reported as risk ratios or risk differences for dichotomous outcomes and mean differences for continuous outcomes with 95% confidence intervals.
MAIN RESULTS
Fifteen RCTs (369 children) were identified. Compared with oral calcitriol, intraperitoneal calcitriol significantly reduced the level of serum parathyroid hormone (PTH) but there were no significant differences in bone histology or other biochemical measures (2 RCTs). There were no significant differences detected in growth, PTH, serum calcium or phosphorus between daily versus intermittent calcitriol (3 RCTs). Vitamin D therapy significantly reduced PTH levels compared with placebo or no treatment. The number of children with hypercalcaemia did not differ significantly between groups (4 RCTs). No significant differences were detected in growth rates, bone histology or biochemical parameters between calcitriol and either dihydrotachysterol or ergocalciferol (2 RCTs). Though fewer episodes of hypercalcaemia were reported with sevelamer, no significant differences were detected in serum calcium, phosphorus and PTH levels between calcium-containing phosphate binders and either aluminium hydroxide or sevelamer (4 RCTs).
AUTHORS' CONCLUSIONS
Bone disease, assessed by changes in PTH levels, is improved by all vitamin D preparations. However no consistent differences between routes of administration, frequencies of dosing or vitamin D preparations have been demonstrated. Though fewer episodes of high calcium levels occurred with the non calcium-containing binder, sevelamer, compared with calcium-containing binders, there were no differences in serum phosphorus and calcium overall and phosphorus values were reduced to similar extents. All RCTs were small with few data available on patient-centred outcomes (growth, bone deformities) and limited data on biochemical parameters resulting in considerable imprecision of results thus limiting the applicability to care of children with CKD.
Topics: Aluminum Hydroxide; Bone Density Conservation Agents; Bone Diseases; Calcitriol; Calcium; Calcium Carbonate; Child; Chronic Disease; Humans; Kidney Diseases; Parathyroid Hormone; Phosphorus; Polyamines; Sevelamer; Vitamin D
PubMed: 20091666
DOI: 10.1002/14651858.CD008327