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Journal of the Formosan Medical... Jul 2016Calcium hydroxide and mineral trioxide aggregate (MTA) are used for inducing a calcific barrier at an open tooth root (apexification). The purpose of this study was to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND/PURPOSE
Calcium hydroxide and mineral trioxide aggregate (MTA) are used for inducing a calcific barrier at an open tooth root (apexification). The purpose of this study was to compare the efficacy of calcium hydroxide and MTA for apexification of immature permanent teeth.
METHODS
Medline, Cochrane, EMBASE, and Google Scholar were searched until November 24, 2015, using the keywords apexification, permanent teeth, MTA, and calcium hydroxide.
RESULTS
Of 216 studies identified, four studies were included. There were no differences in the clinical success rate [pooled odds ratio (OR) = 3.03, 95% confidence interval (CI): 0.42-21.72, p = 0.271], radiographic success rate (pooled OR = 4.30, 95% CI: 0.45-41.36, p = 0.206), or apical barrier formation rate (pooled OR = 1.71, 95% CI: 0.59-4.96, p = 0.322) between calcium hydroxide and MTA groups. The time required for apical barrier formation was significantly less in the MTA group (pooled difference in means = -3.58, 95% CI: from -4.91 to -2.25, p < 0.001).
CONCLUSION
While both materials provide similar success rates, the shorter treatment time with MTA may translate into higher overall success rates because of better patient compliance.
Topics: Aluminum Compounds; Apexification; Calcium Compounds; Calcium Hydroxide; Dental Pulp Necrosis; Drug Combinations; Humans; Oxides; Patient Compliance; Root Canal Filling Materials; Silicates; Tooth Apex; Tooth Loss
PubMed: 26911724
DOI: 10.1016/j.jfma.2016.01.010 -
Clinical Oral Investigations Jul 2016We systematically assessed randomized controlled trials comparing direct pulp capping materials. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
We systematically assessed randomized controlled trials comparing direct pulp capping materials.
METHODS
Trials comparing materials for direct capping and evaluating clinically and/or radiographically determined success after minimum 3 months were included. Two reviewers independently screened electronic databases (Medline, Central, Embase) and performed hand searches. Risk of bias was assessed and meta-analyses were performed, separated for dentition. Trial sequential analysis was used to assess risk of random errors. Strength of evidence was graded using the GRADE approach.
RESULTS
From a total of 453 identified studies, 11 (all with high risk of bias) investigating 1094 teeth (922 patients) were included. Six studies were on primary teeth (all with carious exposures) and five on permanent teeth (carious and artificial exposures). Mean follow-up was 14 months (range 3-24). Most studies used calcium hydroxide as control, comparing it to mineral trioxide aggregate (MTA) (three studies), bonding without prior etching/conditioning (two), or bonding with prior etching/conditioning, enamel matrix proteins, resin-modified glass ionomer cement, calcium sulfate, zinc oxide eugenol, corticosteroids, antibiotics, or formocresol (each in only one study). One study compared MTA and calcium-enriched cement. In permanent teeth, risk of failure was significantly decreased if MTA instead of calcium hydroxide was used (risk ratio (RR) [95 % confidence intervals (CI)] 0.59 [0.39/0.90]); no difference was found for primary teeth. Other comparisons did not find significant differences or were supported by only one study. No firm evidence was reached according to trial sequential analysis.
CONCLUSION
There is insufficient data to recommend or refute the use of a specific material. More long-term practice-based studies with real-life exposures are required.
CLINICAL RELEVANCE
To reduce risk of failure, dentists might consider using MTA instead of calcium hydroxide (CH) for direct capping. Current evidence is insufficient for definitive recommendations.
Topics: Aluminum Compounds; Calcium Compounds; Calcium Hydroxide; Dental Materials; Dental Pulp Capping; Drug Combinations; Humans; Oxides; Silicates
PubMed: 27037567
DOI: 10.1007/s00784-016-1802-7 -
Clinical Toxicology (Philadelphia, Pa.) Apr 2022Aluminium exposure is associated with bone disease (an elevated bone content of aluminium and reduced bone formation on bone biopsy) and neurotoxicity (features of...
INTRODUCTION
Aluminium exposure is associated with bone disease (an elevated bone content of aluminium and reduced bone formation on bone biopsy) and neurotoxicity (features of altered brain functions and/or typical spike and slow wave waveforms on electroencephalogram) in patients with elevated blood aluminium concentrations.
OBJECTIVES
To critically analyse the literature to determine the dose-toxicity relationships between aluminium exposure and related bone disease and aluminium neurotoxicity.
METHODS
A systematic review of the literature with collation and analysis of individual data of human cases of aluminium exposure was conducted between 1 January 1966 and 30 December 2020. Embase, MEDLINE (OVID MEDLINE), PubMed and TOXNET were searched with the following strategies: "" limited to "(human)". Inclusion criteria required individual data relating to aluminium exposure in humans. Papers in which features of aluminium toxicity and analytical confirmation of aluminium exposure could not be determined in individual patients were excluded.
RESULTS
Thirty-seven papers were identified, which included data on 179 individuals exposed to aluminium. The sources of aluminium exposure (median duration of exposure) were: dialysis fluid (48 months) in 110 cases; oral aluminium hydroxide (20 months) in 20 cases; plasma exchange (2 months) in 16 cases; infant formula feed (minimal duration of 2 weeks) in 14 cases; intravesical exposures (2 days) in 13 oncology patients and potable water exposure in six cases.
EXPOSURE TO DIALYSIS FLUID
Of the 110 patients exposed to dialysis fluid, 99 were adults and 11 children, who were analysed separated. Of the adults, 50 with aluminium neurotoxicity had a median aluminium concentration of 467 µg/L (IQR 230 - 752), 28 with aluminium bone disease had a median aluminium concentration of 142 µg/L (IQR 46-309) and 21 with asymptomatic aluminium overload had a median aluminium concentration of 35 µg/L (IQR 26-51). Median aluminium concentrations were significantly greater in patients with aluminium neurotoxicity compared to those with aluminium bone disease ( < 0.0001) or asymptomatic aluminium overload ( < 0.0001).
ORAL ALUMINIUM HYDROXIDE
Of the 20 cases, 11 were adults and nine were children. Of the 11 adults, eight with aluminium neurotoxicity had a median aluminium concentration of 682 µg/L (IQR 438-770) and three with aluminium bone disease had a median aluminium concentration of 100 µg/L (IQR 62-138) ( = 0.007). Of the nine children, five had aluminium neurotoxicity with a median aluminium concentration of 335 µg/L (IQR 229-601), one had aluminium bone disease and an aluminium concentration of 1030 µg/L and three had asymptomatic aluminium overload with a median aluminium concentration 98 µg/L (IQR 65-365).
PLASMA EXCHANGE
Three patients with stage 5 chronic kidney disease developed aluminium bone disease during plasma exchange; their median blood or serum aluminium concentration was 73 µg/L (IQR 59-81). Asymptomatic aluminium overload was reported in six patients receiving outpatient plasma exchange who had a median creatinine clearance of 71 mL/min (IQR 40-106) and a median aluminium concentration of 49 µg/L (IQR 34-116), and in seven intensive care patients with acute kidney injury whose median aluminium concentration was 30 µg/L (IQR 17-35); ( = 0.02).
INTRAVESICAL EXPOSURES
All 13 intravesical exposures developed aluminium neurotoxicity and had a median aluminium concentration of 157 µg/L (IQR 45-276).
POTABLE WATER
All six patients developed aluminium bone disease and their median blood aluminium concentration was 17 µg/L (IQR 13-100).
CONCLUSIONS
Toxic aluminium exposure can result in neurotoxicity and bone disease, especially in patients with chronic kidney disease. Adults with stage 5 chronic kidney disease chronically exposed to aluminium developed aluminium neurotoxicity at higher concentrations than those with aluminium bone disease or with asymptomatic aluminium overload. Aluminium neurotoxicity was reported at lower concentrations following acute exposure to intravesical aluminium. Extrapolating the relevance of these concentrations to the general population is problematic in that the data were derived from oncology patients, however, the possibility that aluminium neurotoxicity may occur at concentrations lower that those reported historically in patients with stage 5 chronic kidney disease cannot be excluded.
Topics: Adult; Aluminum; Bone Diseases; Bone and Bones; Child; Humans; Kidney Failure, Chronic; Renal Dialysis
PubMed: 35179097
DOI: 10.1080/15563650.2022.2029879 -
Vaccines Nov 2023Aluminium adjuvants are commonly used in vaccines to boost the effects of vaccination. Here, we assessed the benefits and harms of different aluminium adjuvants vs.... (Review)
Review
Concentrations, Number of Doses, and Formulations of Aluminium Adjuvants in Vaccines: A Systematic Review with Meta-Analysis and Trial Sequential Analysis of Randomized Clinical Trials.
Aluminium adjuvants are commonly used in vaccines to boost the effects of vaccination. Here, we assessed the benefits and harms of different aluminium adjuvants vs. other aluminium adjuvants or vs. the same aluminium adjuvant at other concentrations, administered a different number of doses, or at different particle sizes used in vaccines or vaccine excipients. We conducted a systematic review with meta-analysis and Trial Sequential Analysis to assess the certainty of evidence with Grading of Recommendations Assessment, Development and Evaluation (GRADE). We obtained data from major medical databases until 20 January 2023 and included 10 randomized clinical trials of healthy volunteers. The comparisons assessed higher vs. lower aluminium adjuvant concentrations; higher vs. lower number of doses of aluminium adjuvant; and aluminium phosphate adjuvant vs. aluminium hydroxide adjuvant. For all three comparisons, meta-analyses showed no evidence of a difference on all-cause mortality, serious adverse events, and adverse events considered non-serious. The certainty of evidence was low to very low. None of the included trials reported on quality of life or proportion of participants who developed the disease being vaccinated against. The benefits and harms of different types of aluminium adjuvants, different aluminium concentrations, different number of doses, or different particle sizes, therefore, remain uncertain.
PubMed: 38140168
DOI: 10.3390/vaccines11121763 -
International Endodontic Journal Jun 2016The aim was to update a systematic review of pulp capping and partial pulpotomy by Olsson et al. (2006), by evaluating new evidence on formation of a hard tissue... (Review)
Review
The aim was to update a systematic review of pulp capping and partial pulpotomy by Olsson et al. (2006), by evaluating new evidence on formation of a hard tissue barrier after pulp capping and partial pulpotomy of experimental exposures in humans. PubMed (01-01-2005 to 01-03-2014) and CENTRAL were searched using specific keywords. Hand searches were made and the level of evidence for each included article was evaluated by the authors. The evidence of the conclusions was graded as strong, moderately strong, limited or insufficient. The initial search in PubMed yielded 215 abstracts. Hand searches of reference lists yielded no additional original scientific articles. After a selection process and interpretation, 22 articles were included and rated for level of evidence: no article was rated as high and seven as moderate. Overall the methodological quality of studies has improved since the previous systematic review was published in 2006. The conclusions are that there is limited scientific evidence that application of calcium hydroxide or mineral trioxide aggregate to an exposed pulp frequently results in formation of a hard tissue barrier, whereas adhesives or enamel matrix derivatives do not. There is insufficient scientific evidence that mineral trioxide aggregate promotes hard tissue formation more frequently than calcium hydroxide.
Topics: Aluminum Compounds; Calcium Compounds; Calcium Hydroxide; Dental Pulp Capping; Drug Combinations; Humans; Oxides; Pulpotomy; Silicates; Treatment Outcome
PubMed: 26059916
DOI: 10.1111/iej.12480 -
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 -
European Archives of Paediatric... Aug 2015The aim of this study was to evaluate the scientific evidence of pulpotomy in primary teeth comparing mineral troxide aggregate (MTA), calcium hydroxide, ferric... (Comparative Study)
Comparative Study Meta-Analysis Review
AIM
The aim of this study was to evaluate the scientific evidence of pulpotomy in primary teeth comparing mineral troxide aggregate (MTA), calcium hydroxide, ferric sulphate, and electrosurgery with formocresol.
METHODS
A systematic search using key words was conducted using seven databases up to December 10, 2013. Clinical articles in English, Portuguese and Spanish were selected, which were in accordance with the inclusion and exclusion criteria and the research objective of comparing whether pulpotomy performed with formocresol in primary teeth is more effective than other medicaments or techniques.
RESULTS
Out of the 12,515 publication initially identified, 30 clinical articles were included in the systematic review and analysed by four meta-analyses. The success rate of MTA (94.6 %) was higher than that of formocresol (87.4 %), with a statistically significant difference (OR = 0.39; 95 % CI = 0.25-0.62). Formocresol pulpotomy success was not statistically different from ferric sulphate or electrosurgery.
CONCLUSION
MTA was clinically and radiographically superior to formocresol for pulpotomy of primary teeth. The other alternatives to formocresol such as electrosurgery and ferric sulphate can be used instead of formocresol since they showed success similar to formocresol. In addition, there is no evidence to support calcium hydroxide for pulpotomies in primary teeth.
Topics: Aluminum Compounds; Calcium Compounds; Calcium Hydroxide; Drug Combinations; Electrosurgery; Ferric Compounds; Formocresols; Humans; Oxides; Pulpotomy; Root Canal Irrigants; Silicates; Tooth, Deciduous; Treatment Outcome
PubMed: 25833280
DOI: 10.1007/s40368-015-0174-z -
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 -
BMC Oral Health Oct 2019Pulpotomy is one of the most widely used methods in preserving vital pulp in teeth, which is of great significance in achieving continue root formation in immature... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pulpotomy is one of the most widely used methods in preserving vital pulp in teeth, which is of great significance in achieving continue root formation in immature permanent teeth suffering from dental caries or trauma. The aim of this meta-analysis and systemic review is to synthesize the available evidences to compare different pulpotomy dressing agents for pulpotomy treatment in immature permanent teeth.
METHODS
Electronic databases including MEDLINE (via Pubmed), EMBASE, the Cochrane library (CENTRAL) and the clinicaltrials.gov database were searched. The references of all included articles or relevant reviews were cross-checked. Only randomized controlled trials (RCTs) comparing two or more pulp dressing agent in permanent teeth with open apex would be included. Also, the studies should have at least 6 months of follow-up, report clinical and radiographic success in detail and publish in English.
RESULTS
Five RCTs were included for a systematic review, and all of them had a high risk of bias. There is little difference in success rate between mineral trioxide aggregate (MTA) and calcium hydroxide (CH) at 6-month follow-up (risk ratio (RR) 1; 95% confidence interval (CI) 0.94 to 1.06) and 12-month follow-up (RR 1.04; 95% CI 0.96 to 1.13). There is no difference between MTA versus platelet-rich fibrin and MTA versus calcium-enriched mixture (CEM). There is only weak evidence of increased success rate in using MTA and triple antibiotic paste (TAP) rather than abscess remedy.
CONCLUSIONS
Based on the present evidence, similar success rates with MTA were found between the dressing agents CH, CEM, RPF and TAP as pulpotomy-dressing agents in the treatment of immature permanent teeth. More high-quality RCTs are needed in this field in future studies.
Topics: Aluminum Compounds; Calcium Compounds; Calcium Hydroxide; Dental Caries; Dental Pulp Capping; Dental Pulp Exposure; Dentition, Permanent; Drug Combinations; Humans; Oxides; Pulpotomy; Randomized Controlled Trials as Topic; Silicates; Treatment Outcome
PubMed: 31647004
DOI: 10.1186/s12903-019-0917-z -
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