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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... May 2018In children, dental caries (tooth decay) is among the most prevalent chronic diseases worldwide. Pulp interventions are indicated for extensive tooth decay. Depending on... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In children, dental caries (tooth decay) 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. Materials commonly used include mineral trioxide aggregate (MTA), calcium hydroxide, formocresol or ferric sulphate.This is an update of a Cochrane Review published in 2014 when insufficient evidence was found to clearly identify one superior pulpotomy medicament and technique.
OBJECTIVES
To assess the effects of different pulp treatment techniques and associated medicaments for the treatment of extensive decay in primary teeth.
SEARCH METHODS
Cochrane Oral Health's Information Specialist searched the Cochrane Oral Health Group's Trials Register (to 10 August 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2017, Issue 7), MEDLINE Ovid (1946 to 10 August 2017), Embase Ovid (1980 to 10 August 2017) and the Web of Science (1945 to 10 August 2017). OpenGrey was searched for grey literature. The US National Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing interventions that combined a pulp treatment technique with a medicament or device in children with extensive decay in the dental pulp of their primary teeth.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed 'Risk of bias'. We contacted authors of RCTs for additional information when 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 pair-wise meta-analyses using fixed-effect models. We assessed statistical heterogeneity by using I² coefficients.
MAIN RESULTS
We included 40 new trials bringing the total to 87 included trials (7140 randomised teeth) for this update. All were small, single-centre trials (median number of randomised teeth = 68). All trials were assessed at unclear or high risk of bias.The 87 trials examined 125 different comparisons: 75 comparisons of different medicaments or techniques for pulpotomy; 25 comparisons of different medicaments for pulpectomy; four comparisons of pulpotomy and pulpectomy; and 21 comparisons of different medicaments for direct pulp capping.The proportion of clinical failures and radiological failures was low in all trials. In many trials, there were either no clinical failures or no radiographic failures in either study arm.For pulpotomy, we assessed three comparisons as providing moderate-quality evidence. Compared with formocresol, MTA reduced both clinical and radiological failures, with a statistically significant difference at 12 months for clinical failure and at six, 12 and 24 months for radiological failure (12 trials, 740 participants). Compared with calcium hydroxide, MTA reduced both clinical and radiological failures, with statistically significant differences for clinical failure at 12 and 24 months. MTA also appeared to reduce radiological failure at six, 12 and 24 months (four trials, 150 participants) (low-quality evidence). When comparing calcium hydroxide with formocresol, there was a statistically significant difference in favour of formocresol for clinical failure at six and 12 months and radiological failure at six, 12 and 24 months (six trials (one with no failures), 332 participants).Regarding pulpectomy, we found moderate-quality evidence for two comparisons. The comparison between Metapex and zinc oxide and eugenol (ZOE) paste was inconclusive, with no clear evidence of a difference between the interventions for failure at 6 or 12 months (two trials, 62 participants). Similarly inconclusive, there was no clear evidence of a difference in failure between Endoflas and ZOE (outcomes measured at 6 months; two trials, 80 participants). There was low-quality evidence of a difference in failure at 12 months that suggested ZOE paste may be better than Vitapex (calcium hydroxide/iodoform) paste (two trials, 161 participants).Regarding direct pulp capping, the small number of studies undertaking the same comparison limits any interpretation. We assessed the quality of the evidence as low or very low for all comparisons. One trial appeared to favour formocresol over calcium hydroxide; however, there are safety concerns about formocresol.
AUTHORS' CONCLUSIONS
Pulp treatment for extensive decay in primary teeth is generally successful. Many included trials had no clinical or radiological failures in either trial arm, and the overall proportion of failures was low. Any future trials in this area would require a very large sample size and follow up of a minimum of one year.The evidence suggests MTA may be the most efficacious medicament to heal the root pulp after pulpotomy of a deciduous tooth. As MTA is relatively expensive, future research could be undertaken to confirm if Biodentine, enamel matrix derivative, laser treatment or Ankaferd Blood Stopper are acceptable second choices, and whether, where none of these treatments can be used, application of sodium hypochlorite is the safest option. Formocresol, though effective, has known concerns about toxicity.Regarding pulpectomy, there is no conclusive evidence that one medicament or technique is superior to another, and so the choice of medicament remains at the clinician's discretion. Research could be undertaken to confirm if ZOE paste is more effective than Vitapex and to evaluate other alternatives.Regarding direct pulp capping, the small number of studies and low quality of the evidence limited interpretation. Formocresol may be more successful than calcium hydroxide; however, given its toxicity, any future research should focus on alternatives.
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; Treatment Failure; Zinc Oxide-Eugenol Cement
PubMed: 29852056
DOI: 10.1002/14651858.CD003220.pub3 -
The Cochrane Database of Systematic... Aug 2018Phosphate binders are used to reduce positive phosphate balance and to lower serum phosphate levels for people with chronic kidney disease (CKD) with the aim to prevent... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Phosphate binders are used to reduce positive phosphate balance and to lower serum phosphate levels for people with chronic kidney disease (CKD) with the aim to prevent progression of chronic kidney disease-mineral and bone disorder (CKD-MBD). This is an update of a review first published in 2011.
OBJECTIVES
The aim of this review was to assess the benefits and harms of phosphate binders for people with CKD with particular reference to relevant biochemical end-points, musculoskeletal and cardiovascular morbidity, hospitalisation, and death.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 12 July 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) or quasi-RCTs of adults with CKD of any GFR category comparing a phosphate binder to another phosphate binder, placebo or usual care to lower serum phosphate. Outcomes included all-cause and cardiovascular death, myocardial infarction, stroke, adverse events, vascular calcification and bone fracture, and surrogates for such outcomes including serum phosphate, parathyroid hormone (PTH), and FGF23.
DATA COLLECTION AND ANALYSIS
Two authors independently selected studies for inclusion and extracted study data. We applied the Cochrane 'Risk of Bias' tool and used the GRADE process to assess evidence certainty. We estimated treatment effects using random-effects meta-analysis. Results were expressed as risk ratios (RR) for dichotomous outcomes together with 95% confidence intervals (CI) or mean differences (MD) or standardised MD (SMD) for continuous outcomes.
MAIN RESULTS
We included 104 studies involving 13,744 adults. Sixty-nine new studies were added to this 2018 update.Most placebo or usual care controlled studies were among participants with CKD G2 to G5 not requiring dialysis (15/25 studies involving 1467 participants) while most head to head studies involved participants with CKD G5D treated with dialysis (74/81 studies involving 10,364 participants). Overall, seven studies compared sevelamer with placebo or usual care (667 participants), seven compared lanthanum to placebo or usual care (515 participants), three compared iron to placebo or usual care (422 participants), and four compared calcium to placebo or usual care (278 participants). Thirty studies compared sevelamer to calcium (5424 participants), and fourteen studies compared lanthanum to calcium (1690 participants). No study compared iron-based binders to calcium. The remaining studies evaluated comparisons between sevelamer (hydrochloride or carbonate), sevelamer plus calcium, lanthanum, iron (ferric citrate, sucroferric oxyhydroxide, stabilised polynuclear iron(III)-oxyhydroxide), calcium (acetate, ketoglutarate, carbonate), bixalomer, colestilan, magnesium (carbonate), magnesium plus calcium, aluminium hydroxide, sucralfate, the inhibitor of phosphate absorption nicotinamide, placebo, or usual care without binder. In 82 studies, treatment was evaluated among adults with CKD G5D treated with haemodialysis or peritoneal dialysis, while in 22 studies, treatment was evaluated among participants with CKD G2 to G5. The duration of study follow-up ranged from 8 weeks to 36 months (median 3.7 months). The sample size ranged from 8 to 2103 participants (median 69). The mean age ranged between 42.6 and 68.9 years.Random sequence generation and allocation concealment were low risk in 25 and 15 studies, respectively. Twenty-seven studies reported low risk methods for blinding of participants, investigators, and outcome assessors. Thirty-one studies were at low risk of attrition bias and 69 studies were at low risk of selective reporting bias.In CKD G2 to G5, compared with placebo or usual care, sevelamer, lanthanum, iron and calcium-based phosphate binders had uncertain or inestimable effects on death (all causes), cardiovascular death, myocardial infarction, stroke, fracture, or coronary artery calcification. Sevelamer may lead to constipation (RR 6.92, CI 2.24 to 21.4; low certainty) and lanthanum (RR 2.98, CI 1.21 to 7.30, moderate certainty) and iron-based binders (RR 2.66, CI 1.15 to 6.12, moderate certainty) probably increased constipation compared with placebo or usual care. Lanthanum may result in vomiting (RR 3.72, CI 1.36 to 10.18, low certainty). Iron-based binders probably result in diarrhoea (RR 2.81, CI 1.18 to 6.68, high certainty), while the risks of other adverse events for all binders were uncertain.In CKD G5D sevelamer may lead to lower death (all causes) (RR 0.53, CI 0.30 to 0.91, low certainty) and induce less hypercalcaemia (RR 0.30, CI 0.20 to 0.43, low certainty) when compared with calcium-based binders, and has uncertain or inestimable effects on cardiovascular death, myocardial infarction, stroke, fracture, or coronary artery calcification. The finding of lower death with sevelamer compared with calcium was present when the analysis was restricted to studies at low risk of bias (RR 0.50, CI 0.32 to 0.77). In absolute terms, sevelamer may lower risk of death (all causes) from 210 per 1000 to 105 per 1000 over a follow-up of up to 36 months, compared to calcium-based binders. Compared with calcium-based binders, lanthanum had uncertain effects with respect to all-cause or cardiovascular death, myocardial infarction, stroke, fracture, or coronary artery calcification and probably had reduced risks of treatment-related hypercalcaemia (RR 0.16, CI 0.06 to 0.43, low certainty). There were no head-to-head studies of iron-based binders compared with calcium. The paucity of placebo-controlled studies in CKD G5D has led to uncertainty about the effects of phosphate binders on patient-important outcomes compared with placebo.It is uncertain whether the effects of binders on clinically-relevant outcomes were different for patients who were and were not treated with dialysis in subgroup analyses.
AUTHORS' CONCLUSIONS
In studies of adults with CKD G5D treated with dialysis, sevelamer may lower death (all causes) compared to calcium-based binders and incur less treatment-related hypercalcaemia, while we found no clinically important benefits of any phosphate binder on cardiovascular death, myocardial infarction, stroke, fracture or coronary artery calcification. The effects of binders on patient-important outcomes compared to placebo are uncertain. In patients with CKD G2 to G5, the effects of sevelamer, lanthanum, and iron-based phosphate binders on cardiovascular, vascular calcification, and bone outcomes compared to placebo or usual care, are also uncertain and they may incur constipation, while iron-based binders may lead to diarrhoea.
Topics: Adult; Aged; Calcium; Calcium Compounds; Cause of Death; Chelating Agents; Chronic Disease; Chronic Kidney Disease-Mineral and Bone Disorder; Disease Progression; Fibroblast Growth Factor-23; Humans; Hypercalcemia; Iron Compounds; Lanthanum; Middle Aged; Parathyroid Hormone; Phosphorus; Polyamines; Randomized Controlled Trials as Topic; Renal Dialysis; Sevelamer
PubMed: 30132304
DOI: 10.1002/14651858.CD006023.pub3 -
Frontiers in Immunology 2022We systematically reviewed and summarized studies focusing on Bharat Biotech's Whole Virion Inactivated Corona Virus Antigen BBV152 (Covaxin), which is India's...
We systematically reviewed and summarized studies focusing on Bharat Biotech's Whole Virion Inactivated Corona Virus Antigen BBV152 (Covaxin), which is India's indigenous response to fighting the SARS-CoV-2 pandemic. Studies were searched for data on the efficacy, immunogenicity, and safety profile of BBV152. All relevant studies published up to March 22, 2022, were screened from major databases, and 25 studies were eventually inducted into the systematic review. The studies focused on the virus antigen (6 μg) adjuvanted with aluminium hydroxide gel and/or Imidazo quinolin gallamide (IMDG), aTLR7/8 agonist. Pre-clinical, phase I, and II clinical trials showed appreciable immunogenicity. Both neutralizing and binding antibody titers were significant and T cell responses were Th1-biased. Phase III trials on the 6 μg +Algel-IMDG formulation showed a 93.4% efficacy against severe COVID-19. Data from the trials revealed an acceptable safety profile with mostly mild-moderate local and systemic adverse events. No serious adverse events or fatalities were seen, and most studies reported milder and lesser adverse events with Covaxin when compared with other vaccines, especially Oxford-Astra Zeneca's AZD1222 (Covishield). The immunogenicity performance of Covaxin, which provided significant protection only after the second dose, was mediocre and it was consistently surpassed by Covishield. One study reported adjusted effectiveness against symptomatic infection to be just 50% at 2 weeks after the second dose. Nonetheless, appreciable results were seen in previously infected individuals administered both doses. There was some evidence of coverage against the Alpha, Beta, and Delta variants. However, neither Covaxin nor Covishield showed sufficient protection against the Omicron variant. Two studies reported super-additive results on mixing Covaxin with Covishield. Further exploration of heterologous prime-boost vaccination with a combination of an inactivated vaccine and an adenoviral vector-based vaccine for tackling future variants may be beneficial.
Topics: COVID-19; COVID-19 Vaccines; ChAdOx1 nCoV-19; Humans; SARS-CoV-2; Vaccines, Inactivated; Viral Vaccines
PubMed: 36016940
DOI: 10.3389/fimmu.2022.863162 -
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 -
Clinical and Experimental Dental... Dec 2023Different materials have been used for capping the pulp after exposure during caries removal in permanent teeth. The purpose of this study was to collate and analyze all... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Different materials have been used for capping the pulp after exposure during caries removal in permanent teeth. The purpose of this study was to collate and analyze all pertinent evidence from randomized controlled trials (RCTs) on different materials used in patients undergoing pulpotomy or direct pulp capping in carious teeth.
MATERIALS AND METHODS
Trials comparing two or more capping agents used for direct pulp capping (DPC) or pulpotomy were considered eligible. An electronic search of four databases and two clinical trial registries was carried out up to February 28, 2021 using a search strategy properly adapted to the PICO framework. Screening, data extraction, and risk of bias (RoB) assessment of primary studies were performed in duplicate and independently. The primary outcome was clinical and radiological success; secondary outcomes included continued root formation, tooth discoloration, and dentin bridge formation.
RESULTS
21 RCTs were included in the study. The RoB assessment indicated a moderate risk among the studies. Due to significant clinical and statistical heterogeneity among the studies, performing network meta-analysis (NMA) was not possible. An ad hoc subgroup analysis revealed strong evidence of a higher success of DPC with Mineral Trioxide Aggregate (MTA) compared to calcium hydroxide (CH) (odds ratio [OR] = 3.10, 95% confidence interval [CI]: 1.66-5.79). MTA performed better than CH in pulp capping (both DPC and pulpotomy) of mature compared to immature teeth (OR = 3.34, 95% CI: 1.81-6.17). The GRADE assessment revealed moderate strength of evidence for DPC and mature teeth, and low to very low strength of evidence for the remaining subgroups.
CONCLUSIONS
Considerable clinical and statistical heterogeneity among the trials did not allow NMA. The ad hoc subgroup analysis indicated that the clinical and radiographic success of MTA was higher than that of CH but only in mature teeth and DPC cases where the strength of evidence was moderate. PROSPERO Registration: number CRD42020127239.
Topics: Humans; Dental Pulp Capping; Pulpotomy; Calcium Compounds; Aluminum Compounds; Oxides; Silicates; Drug Combinations; Calcium Hydroxide; Dental Caries; Randomized Controlled Trials as Topic
PubMed: 37710421
DOI: 10.1002/cre2.767 -
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 -
The Cochrane Database of Systematic... Sep 2015Heartburn is one of the most common gastrointestinal symptoms in pregnant women. It can occur in all trimesters of pregnancy. The symptoms of heartburn in pregnancy may... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Heartburn is one of the most common gastrointestinal symptoms in pregnant women. It can occur in all trimesters of pregnancy. The symptoms of heartburn in pregnancy may be frequent, severe and distressing, but serious complications are rare. Many interventions have been used for the treatment of heartburn in pregnancy. These interventions include advice on diet, lifestyle modification and medications. However, there has been no evidence-based recommendation for the treatment of heartburn in pregnancy.
OBJECTIVES
To assess the effects of interventions for relieving heartburn in pregnancy.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2015), ClinicalTrials.gov (2 March 2015), Asian & Oceanic Congress of Obstetrics & Gynaecology (AOCOG) conference proceedings (20-23 October 2013, Centara Grand & Bangkok Convention Centre, Bangkok, Thailand), and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and quasi-RCTS of interventions for heartburn in pregnancy compared with another intervention, or placebo, or no intervention. Cluster-RCTs would have been eligible for inclusion but none were identified. We excluded studies available as abstracts only and those using a cross-over design.Interventions could include advice on diet, lifestyle modification and medications (such as antacids, sucralfate, histamine 2-receptor antagonists, promotility drugs and proton pump inhibitors (PPIs)).
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy.
MAIN RESULTS
We included nine RCTs involving 725 women. However, five trials did not contribute data. Four trials involving 358 women contributed data. Trials were generally at mixed risk of bias.We only identified data for three comparisons: pharmaceutical treatment versus placebo or no treatment; acupuncture versus no treatment and pharmacological intervention versus advice on dietary and lifestyle changes. Pharmaceutical treatment compared with placebo or no treatmentTwo trials evaluated any pharmaceutical treatment compared with placebo or no treatment. One trial examined a treatment rarely used nowadays (intramuscular prostigmine 0.5 mg versus placebo). One trial evaluated the effect of magnesium and aluminium hydroxide plus simethicone liquid and tablet compared with placebo. For the primary outcome of this review (relief of heartburn), women who received pharmaceutical treatment reported complete heartburn relief more often than women receiving no treatment or placebo (risk ratio (RR) 1.85, 95% confidence interval (CI) 1.36 to 2.50 in two RCTs of 256 women, I(2) = 0%, moderate-quality evidence). Data on partial relief of heartburn were heterogenous and showed no clear difference (average RR 1.35, 95% CI 0.38 to 4.76 in two RCTs of 256 women, very low-quality evidence). In terms of secondary outcomes, there was no clear difference in the rate of side effects between the pharmaceutical treatment group and the placebo/no treatment group (RR 0.63, 95% CI 0.21 to 1.89 in two RCTs of 256 women, very low-quality evidence). Pharmacological intervention versus advice on dietary and lifestyle choicesOne study compared 1 g of sucralfate with advice on dietary and lifestyle choices in treating heartburn. More women in the sucralfate group experienced complete relief of heartburn compared to women who received advice on diet and lifestyle choices (RR 2.41, 95% CI 1.42 to 4.07; participants = 65; studies = one). The only secondary outcome of interest addressed by this trial was side effects. The evidence was not clear on intervention side effects rate between the two groups (RR 1.74, 95% CI 0.07 to 41.21; participants = 66; studies = one). There was only one instance of side effects in the pharmacological group. Acupuncture compared with no treatmentOne trial evaluated acupuncture compared with no treatment but did not report data relating to this review's primary outcome (relief of heartburn). In terms of secondary outcomes, there was no difference in the rate of side effects between women who had acupuncture and women who had no treatment (RR 2.43, 95% CI 0.11 to 55.89 in one RCT of 36 women). With regard to quality of life, women who had acupuncture reported improved ability to sleep (RR 2.80, 95% CI 1.14 to 6.86) and eat (RR 2.40, 95% CI 1.11 to 5.18 in one RCT of 36 women).The following secondary outcomes were not reported upon in any of the trials included in the review: miscarriage, preterm labour, maternal satisfaction, fetal anomalies, intrauterine growth restriction, low birthweight.
AUTHORS' CONCLUSIONS
There are no large-scale RCTs to assess heartburn relief in pregnancy. This review of nine small studies (which involved data from only four small studies) indicates that there are limited data suggesting that heartburn in pregnancy could be completely relieved by pharmaceutical treatment. Three outcomes were assessed and assigned a quality rating using the GRADE methods. Evidence from two trials for the outcome of complete relief of heartburn was assessed as of moderate quality. Evidence for the outcomes of partial heartburn relief and side effects was graded to be of very low quality. Downgrading decisions were based in part on the small size of the trials and on heterogenous and imprecise results.There are insufficient data to assess acupuncture versus no treatment and no data to assess other comparisons (miscarriage, preterm labour, maternal satisfaction, fetal anomalies, intrauterine growth restriction, low birthweight).Further RCTs are needed to fully evaluate the effectiveness of interventions for heartburn in pregnancy. Future research should also address other medications such as histamine 2-receptor antagonists, promotility drugs, proton pump inhibitors, and a raft-forming alginate reflux suppressant in treatment of heartburn in pregnancy. More research is needed on acupuncture and other complimentary therapies as treatments for heartburn in pregnancy. Future research should also evaluate any adverse outcomes, maternal satisfaction with treatment and measure pregnant women's quality of life in relation to the intervention.
Topics: Acupuncture Therapy; Adult; Aluminum Hydroxide; Antacids; Female; Heartburn; Humans; Magnesium Hydroxide; Neostigmine; Pregnancy; Pregnancy Complications; Randomized Controlled Trials as Topic; Sucralfate
PubMed: 26384956
DOI: 10.1002/14651858.CD011379.pub2 -
Alimentary Pharmacology & Therapeutics Nov 2003Ursodeoxycholic acid is increasingly being used for the treatment of chronic cholestatic liver diseases. It appears to be generally well tolerated, but a systematic... (Review)
Review
BACKGROUND
Ursodeoxycholic acid is increasingly being used for the treatment of chronic cholestatic liver diseases. It appears to be generally well tolerated, but a systematic review on drug safety is lacking.
AIM
As experimental data suggest a role of bile acids in the regulation of hepatic drug metabolism at both the transcriptional and post-transcriptional level, the literature was screened for adverse drug reactions and drug interactions related to ursodeoxycholic acid.
METHODS
A systematic review of the literature was performed using a refined search strategy to evaluate the adverse effects of ursodeoxycholic acid and its interactions with other drugs.
RESULTS
Ursodeoxycholic acid caused diarrhoea in a small proportion of patients. Rare skin reactions were due to drug adjuvants rather than the active substance. Decompensation of liver cirrhosis was reported after the administration of ursodeoxycholic acid in single cases of end-stage primary biliary cirrhosis. Recurrent right upper quadrant abdominal pain was incidentally observed. The absorption of ursodeoxycholic acid was impaired by colestyramine, colestimide, colestipol, aluminium hydroxide and smectite. Metabolic drug interactions were reported for the cytochrome P4503A substrates, ciclosporin, nitrendipine and dapsone.
CONCLUSIONS
Ursodeoxycholic acid is generally well tolerated. Drug absorption interactions with anion exchange resins deserve consideration. Metabolic interactions with compounds metabolized by cytochrome P4503A are to be expected.
Topics: Cholagogues and Choleretics; Chronic Disease; Drug Interactions; Female; Humans; Liver Diseases; Pregnancy; Pregnancy Complications; Ursodeoxycholic Acid
PubMed: 14616161
DOI: 10.1046/j.1365-2036.2003.01792.x -
Frontiers in Medicine 2022Inactivated vaccine is one of the primary technology types of Coronavirus Disease 2019 (COVID-19) vaccines, which has wide application in many countries, including...
BACKGROUND
Inactivated vaccine is one of the primary technology types of Coronavirus Disease 2019 (COVID-19) vaccines, which has wide application in many countries, including mainland China. However, systematic evaluation of the efficacy and safety of COVID-19 inactivated vaccines remains limited. And trust in the vaccine is the key to solving vaccine hesitancy.
METHODS
Various academic databases were searched comprehensively for randomized controlled trials (RCTs) related to COVID-19 inactivated vaccines. The deadline for retrieval was December 2021. Study screening and data extraction were according to inclusive and exclusive criteria. Statistical analyses were performed using RevMan software 5.3 version and STATA software 16.0 version.
RESULTS
Eight studies with 79,334 subjects were included of which 48,123 had received two doses of COVID-19 inactivated vaccines, and 31,211 had received two doses of placebo. The results of the meta-analysis showed that: in terms of effectiveness evaluation, two doses of COVID-19 inactivated vaccines decreased the symptomatic infection [relative risk (RR) = 0.23, 95% confidence interval (CI) (0.18,0.30), < 0.00001], asymptomatic infection [RR = 0.48, 95%CI (0.32, 0.74), = 0.0008], total infection [RR = 0.32, 95%CI (0.24, 0.41), < 0.00001] and hospitalization [RR = 0.06, 95%CI (0.01, 0.27), = 0.0002] for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) significantly. In terms of safety assessment, two doses of COVID-19 inactivated vaccines also caused more adverse events. After two inoculations, total adverse events and systemic adverse events increased significantly [total adverse events RR = 1.14, 95%CI (1.08, 1.21), < 0.00001; systemic adverse events RR = 1.22, 95%CI (1.09, 1.35), = 0.0002]. The most common adverse event was pain at the injection site. Almost all local adverse reactions consisted of these events. The incidence of pain at the injection site was related to adjuvants. Using aluminum hydroxide as an adjuvant increased local pain significantly [RR = 1.97, 95%CI (1.52, 2.55), < 0.00001]. Two doses COVID-19 inactivated vaccines did not increase serious adverse events [RR = 0.71, 95%CI (0.57, 0.90), = 0.004].
CONCLUSION
Two doses of inactivated COVID-19 vaccines in people over 18 years of age effectively prevented SARS-CoV-2 infection and its associated hospitalizations. Short-term, mild to moderate adverse reactions had occurred, but serious adverse events were rare. No placebo or vaccine-related deaths had been reported.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier: 42021291250.
PubMed: 36419789
DOI: 10.3389/fmed.2022.1015184