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The Cochrane Database of Systematic... Apr 2016Uncomplicated urinary tract infection (UTI) is the most common bacterial infection in women, characterised by dysuria and urinary frequency. Urinary alkalisers are... (Review)
Review
BACKGROUND
Uncomplicated urinary tract infection (UTI) is the most common bacterial infection in women, characterised by dysuria and urinary frequency. Urinary alkalisers are widely used in some countries for the symptomatic treatment of uncomplicated UTI, and they are recommended in some national formularies. However, there is a lack of empirical evidence to support their use for UTI and some healthcare guidelines advise against their use.
OBJECTIVES
We aimed to look at the benefits and harms of the use of urinary alkalisers for the treatment of uncomplicated UTIs in adult women.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Specialised Register to 19 January 2016 through contact with the Trials Search Co-ordinator using search terms relevant to this review.
SELECTION CRITERIA
All randomised controlled trials (RCTs) and quasi-RCTs on the use of (any) urinary alkalisers (either exclusively or non-exclusively) for the symptomatic treatment of uncomplicated UTI amongst women aged 16 and over, were included. Studies were eligible if they included patients whose diagnosis of UTI was decided by symptoms alone, or positive urine dipstick test or urine culture; and patients with recurrent UTI, provided patients had no symptoms of UTI in the two weeks prior to the onset of symptoms that lead them to seek medical advice. Studies were ineligible if they studied patients with complicated UTIs; immune-compromising conditions; acute pyelonephritis; or chronic conditions such as interstitial cystitis.
DATA COLLECTION AND ANALYSIS
Three authors independently assessed and screened papers, and this was repeated by two separate authors (independently). An additional investigator acted as arbitrator, where necessary. There were no papers which fulfilled the inclusion criteria for this review, and therefore no data extraction was performed.
MAIN RESULTS
Our search identified 172 potential studies for inclusion. However, following assessment none fulfilled the inclusion criteria for this review.
AUTHORS' CONCLUSIONS
Until relevant evidence is generated from randomised trials, the safety and efficacy of urinary alkalisers for the symptomatic treatment of uncomplicated UTI remains unknown.
Topics: Adult; Antacids; Anti-Infective Agents, Urinary; Female; Humans; Hydrogen-Ion Concentration; Urinary Tract Infections; Urine
PubMed: 27090883
DOI: 10.1002/14651858.CD010745.pub2 -
The Cochrane Database of Systematic... Mar 2016Refractory peptic ulcers are ulcers in the stomach or duodenum that do not heal after eight to 12 weeks of medical treatment or those that are associated with... (Review)
Review
BACKGROUND
Refractory peptic ulcers are ulcers in the stomach or duodenum that do not heal after eight to 12 weeks of medical treatment or those that are associated with complications despite medical treatment. Recurrent peptic ulcers are peptic ulcers that recur after healing of the ulcer. Given the number of deaths due to peptic ulcer-related complications and the long-term complications of medical treatment (increased incidence of fracture), it is unclear whether medical or surgical intervention is the better treatment option in people with recurrent or refractory peptic ulcers.
OBJECTIVES
To assess the benefits and harms of medical versus surgical treatment for people with recurrent or refractory peptic ulcer.
SEARCH METHODS
We searched the specialised register of the Cochrane Upper GI and Pancreatic Diseases group, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and trials registers until September 2015 to identify randomised trials and non-randomised studies, using search strategies. We also searched the references of included studies to identify further studies.
SELECTION CRITERIA
We considered randomised controlled trials and non-randomised studies comparing medical treatment with surgical treatment in people with refractory or recurrent peptic ulcer, irrespective of language, blinding, or publication status for inclusion in the review.
DATA COLLECTION AND ANALYSIS
Two review authors independently identified trials and extracted data. We planned to calculate the risk ratio, mean difference, standardised mean difference, or hazard ratio with 95% confidence intervals using both fixed-effect and random-effects models with Review Manager 5 based on intention-to-treat analysis.
MAIN RESULTS
We included only one non-randomised study published 30 years ago in the review. This study included 77 participants who had gastric ulcer and in whom medical therapy (histamine H2 receptor blockers, antacids, and diet) had failed after an average duration of treatment of 29 months. The authors do not state whether these were recurrent or refractory ulcers. It appears that the participants did not have previous complications such as bleeding or perforation. Of the 77 included participants, 37 participants continued to have medical therapy while 40 participants received surgical therapy (antrectomy with or without vagotomy; subtotal gastrectomy with or without vagotomy; vagotomy; pyloroplasty and suture of the ulcer; suture or closure of ulcer without vagotomy or excision of the ulcer; proximal gastric or parietal cell vagotomy alone; suture or closure of the ulcer with proximal gastric or parietal cell vagotomy). Whether to use medical or surgical treatment was determined by participant's or treating physician's preference.The study authors reported that two participants in the medical treatment group (2 out of 37; 5.4%) had gastric cancer, which was identified by repeated biopsy. They did not report the proportion of participants who had gastric cancer in the surgical treatment group. They also did not report the implications of the delayed diagnosis of gastric cancer in the medical treatment group. They did not report any other outcomes of interest for this review (that is health-related quality of life (using any validated scale), adverse events and serious adverse events, peptic ulcer bleeding, peptic ulcer perforation, abdominal pain, and long-term mortality).
AUTHORS' CONCLUSIONS
We found no studies that provide the relative benefits and harms of medical versus surgical treatment for recurrent or refractory peptic ulcers. Studies that evaluate the natural history of recurrent and refractory peptic ulcers are urgently required to determine whether randomised controlled trials comparing medical versus surgical management in patients with recurrent or refractory peptic ulcers or both are necessary. Such studies will also provide information for the design of such randomised controlled trials. A minimum follow-up of two to three years will allow the calculation of the incidence of complications and gastric cancer (in gastric ulcers only) in recurrent and refractory peptic ulcers. In addition to complications related to treatment and disease, health-related quality of life and loss of productivity should also be measured.
Topics: Antacids; Histamine H2 Antagonists; Humans; Peptic Ulcer; Recurrence; Stomach Neoplasms; Stomach Ulcer; Treatment Failure
PubMed: 27025289
DOI: 10.1002/14651858.CD011523.pub2 -
Digestion 2016Since resistance of Helicobacter pylori is developing very fast all over the world, new treatment regimens for eradication are urgently needed. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Since resistance of Helicobacter pylori is developing very fast all over the world, new treatment regimens for eradication are urgently needed.
AIM
To compare eradication success rate of H. pylori treatment regimens with and without doxycycline.
METHODS
English medical literature searches were conducted for regimens including doxycycline for eradication of H. pylori. Searches were performed up to August 31, 2015, using MEDLINE, PubMed, EMBASE, Scopus and CENTRAL. Meta-analysis was performed by using comprehensive meta-analysis software. Pooled ORs and 95% CIs were calculated comparing treatment regimens for eradication of H. pylori infection with and without doxycycline.
RESULTS
The OR for eradication success rate in a fixed model was in favor for treatment regimens with doxycycline: 1.292, 95% CI 1.048-1.594, p = 0.016. There was no significant heterogeneity in the included studies: Q = 15.130, d.f. (Q) = 8, I2 = 47.126, p > 0.10. When treatment regimens with doxycycline were compared only with treatment regimens with tetracycline, no significant difference was found in eradication success rate: OR 0.95, 95% CI 0.68-1.32, p = 0.77. But when treatment regimens with doxycycline were compared with treatment regimens without tetracycline, the OR in favor of doxycycline was even higher: OR 1.59, 95% CI 1.21-2.09, p < 0.001.
CONCLUSION
In this meta-analysis, we confirmed doxycycline efficiency in the eradication of H. pylori. Thus, triple, quadruple or even high dose dual therapy with regimens containing doxycycline should be considered.
Topics: Amoxicillin; Antacids; Anti-Bacterial Agents; Clarithromycin; Doxycycline; Drug Therapy, Combination; Esomeprazole; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Lansoprazole; Metronidazole; Proton Pump Inhibitors; Ranitidine; Tetracycline
PubMed: 26849820
DOI: 10.1159/000443683 -
The Cochrane Database of Systematic... Nov 2015Bone 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. This is an update of a review first published in 2010.
OBJECTIVES
This review aimed to examine the benefits (improved growth rates, reduced risk of bone fractures and deformities, reduction in PTH levels) and harms (hypercalcaemia, blood vessel calcification, deterioration in kidney function) of interventions (including vitamin D preparations and phosphate binders) for the prevention and treatment of metabolic bone disease in children with CKD.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Specialised Register to 8 September 2015 through contact with the Trial's Search Co-ordinator using search terms relevant for this review.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing different interventions used to prevent or treat bone disease in children with CKD stages 2 to 5D.
DATA COLLECTION AND ANALYSIS
Data were assessed for study eligibility, risk of bias and extracted independently by two authors. Results were reported as risk ratios (RR) or risk differences (RD) with 95% confidence intervals (CI) for dichotomous outcomes. For continuous outcomes the mean difference (MD) or standardised mean difference (SMD) with 95% confidence intervals (CI) was used. Statistical analyses were performed using the random-effects model.
MAIN RESULTS
This review included 18 studies (576 children); three new studies were added for this update. Adequate sequence generation and allocation concealment were reported in 12 and 11 studies respectively. Only four studies reported blinding of children, investigators or outcome assessors. Nine studies were at low risk of attrition bias and 12 studies were at low risk of selective reporting bias.Eight different interventions were compared. Two studies compared intraperitoneal (IP) with oral calcitriol. PTH levels were significantly lower with IP compared with oral calcitriol (1 study: MD -501.00 pg/mL, 95% CI -721.54 to -280.46) but the number of children with abnormal bone histology did not differ between treatments. Three studies compared intermittent with daily oral calcitriol. The change in mean height SDS (1 study: MD 0.13, 95% CI -0.22 to 0.48) and the percentage fall in parathyroid hormone (PTH) levels at eight weeks (1 study: MD -5.50%, 95% CI -32.37 to 21.37) and 12 months (1 study: MD -6.00% 95% CI -25.27 to 13.27) did not differ between treatments.Four studies compared active vitamin D preparations (calcitriol, paricalcitol, 1α-hydroxyvitamin D) with placebo or no specific treatment. One study reported vitamin D preparations significantly reduced PTH levels (-55.00 pmol/L, 95% CI -83.03 to -26.97). There was no significant difference in hypercalcaemia risk with vitamin D preparations compared with placebo or no specific treatment (4 studies, 103 children: RD 0.08 mg/dL, 95% CI -0.08 to 0.24). However, there was heterogeneity (I(2) = 55%) with one study showing a significantly greater risk of hypercalcaemia with intravenous (IV) calcitriol administration. Two studies (97 children) compared calcitriol with other vitamin D preparations and both found no significant differences in growth between preparations.Two studies compared ergocalciferol in patients with CKD and vitamin D deficiency. Elevated PTH levels developed significantly later in ergocalciferol treated children (1 study: hazard ratio 0.30, 95% CI 0.09 to 0.93) though the number with elevated PTH levels did not differ between groups (1 study, 40 children: RR 0.33, 95% CI 0.11 to 1.05).Two studies compared calcium carbonate with aluminium hydroxide as phosphate binders. One study (17 children: MD -0.86 SDS, 95% CI -2.24 to 0.52) reported no significant difference in mean final height SDS between treatments. Three studies compared sevelamer with calcium-containing phosphate binders. There were no significant differences in the final calcium, phosphorus or PTH levels between binders. More episodes of hypercalcaemia occurred with calcium-containing binders. One study reported no significant differences between calcitriol and doxercalciferol in bone histology or biochemical parameters.
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 were demonstrated. Although fewer episodes of high calcium levels occurred with the non-calcium-containing phosphate 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 studies were small with few data available on patient-centred outcomes (growth, bone deformities) and limited data on biochemical parameters or bone histology resulting in considerable imprecision of results thus limiting the applicability to the care of children with CKD.
Topics: Aluminum Hydroxide; Bone Density Conservation Agents; Bone Diseases, Metabolic; Calcitriol; Calcium; Calcium Carbonate; Child; Chronic Disease; Ergocalciferols; Humans; Kidney Diseases; Parathyroid Hormone; Phosphorus; Polyamines; Randomized Controlled Trials as Topic; Sevelamer; Vitamin D
PubMed: 26561037
DOI: 10.1002/14651858.CD008327.pub2 -
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 -
The Cochrane Database of Systematic... May 2015This article describes the second update of a Cochrane review on the effectiveness of laxatives for the management of constipation in people receiving palliative care.... (Review)
Review
BACKGROUND
This article describes the second update of a Cochrane review on the effectiveness of laxatives for the management of constipation in people receiving palliative care. Previous versions were published in 2006 and 2010 where we also evaluated trials of methylnaltrexone; these trials have been removed as they are included in another review in press. In these earlier versions, we drew no conclusions on individual effectiveness of different laxatives because of the limited number of evaluations. This is despite constipation being common in palliative care, generating considerable suffering due to the unpleasant physical symptoms and the availability of a wide range of laxatives with known differences in effect in other populations.
OBJECTIVES
To determine the effectiveness and differential efficacy of laxatives used to manage constipation in people receiving palliative care.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library), MEDLINE, EMBASE, CINAHL and Web of Science (SCI & CPCI-S) for trials to September 2014.
SELECTION CRITERIA
Randomised controlled trials (RCTs) evaluating laxatives for constipation in people receiving palliative care.
DATA COLLECTION AND ANALYSIS
Two authors assessed trial quality and extracted data. The appropriateness of combining data from the studies depended upon clinical and outcome measure homogeneity.
MAIN RESULTS
We identified five studies involving the laxatives lactulose, senna, co-danthramer, misrakasneham, docusate and magnesium hydroxide with liquid paraffin. Overall, the study findings were at an unclear risk of bias. As all five studies compared different laxatives or combinations of laxatives, it was not possible to perform a meta-analysis. There was no evidence on whether individual laxatives were more effective than others or caused fewer adverse effects.
AUTHORS' CONCLUSIONS
This second update found that laxatives were of similar effectiveness but the evidence remains limited due to insufficient data from a few small RCTs. None of the studies evaluated polyethylene glycol or any intervention given rectally. There is a need for more trials to evaluate the effectiveness of laxatives in palliative care populations. Extrapolating findings on the effectiveness of laxatives evaluated in other populations should proceed with caution. This is because of the differences inherent in people receiving palliative care that may impact, in a likely negative way, on the effect of a laxative.
Topics: Analgesics, Opioid; Anthraquinones; Cathartics; Constipation; Humans; Lactulose; Magnesium Hydroxide; Naltrexone; Palliative Care; Paraffin; Quaternary Ammonium Compounds; Randomized Controlled Trials as Topic; Senna Extract
PubMed: 25967924
DOI: 10.1002/14651858.CD003448.pub4 -
BMJ Clinical Evidence Apr 2015It is estimated that approximately 30% to 70% of international travellers will develop diarrhoea during their travels or after returning home. (Review)
Review
INTRODUCTION
It is estimated that approximately 30% to 70% of international travellers will develop diarrhoea during their travels or after returning home.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for acute mild-to-moderate diarrhoea in adults from resource-rich countries travelling to resource-poor countries? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 24 studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics (empirical), antibiotics plus antimotility agents, antimotility agents, bismuth subsalicylate, diet, oral rehydration solutions, and racecadotril for travellers' diarrhoea.
Topics: Anti-Bacterial Agents; Antidiarrheals; Bismuth; Diarrhea; Diet; Fluid Therapy; Humans; Organometallic Compounds; Salicylates; Thiorphan; Travel-Related Illness
PubMed: 25928418
DOI: No ID Found -
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 -
Canadian Journal of Gastroenterology &... Nov 2014Constipation is an uncomfortable and common condition that affects many, irrespective of age. Since 1500 BC and before, health care practitioners have provided... (Review)
Review
BACKGROUND
Constipation is an uncomfortable and common condition that affects many, irrespective of age. Since 1500 BC and before, health care practitioners have provided treatments and prevention strategies to patients for chronic constipation despite the significant variation in both medical and personal perceptions of the condition.
OBJECTIVE
To review relevant research evidence from clinical studies investigating the efficacy and safety of commercially available pharmacological laxatives in Canada, with emphasis on studies adopting the Rome criteria for defining functional constipation.
SEARCH METHODS
PubMed, Medline, Embase and Evidence-Based Medicine Reviews databases were searched for blinded or randomized clinical trials and meta-analyses assessing the efficacy of nonstimulant and stimulant laxatives for the treatment of functional constipation.
RESULTS
A total of 19 clinical studies and four meta-analyses were retrieved and abstracted regarding study design, participants, interventions and outcomes. The majority of studies focused on polyethylene glycol compared with placebo. Both nonstimulant and stimulant laxatives provided better relief of constipation symptoms than placebo according to both objective and subjective measures. Only one study compared the efficacy of a nonstimulant versus a stimulant laxative, while only two reported changes in quality of life. All studies reported minor side effects due to laxative use, regardless of treatment duration, which ranged from one week to one year. Laxatives were well tolerated by both adults and children.
Topics: Bisacodyl; Canada; Citrates; Constipation; Dioctyl Sulfosuccinic Acid; Humans; Lactulose; Laxatives; Magnesium Oxide; Organometallic Compounds; Paraffin; Picolines; Polyethylene Glycols; Psyllium; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 25390617
DOI: 10.1155/2014/631740