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PubMed2000

Elective high frequency oscillatory ventilation versus conventional ventilation for acute pulmonary dysfunction in preterm infants.

BACKGROUND: Respiratory failure due to lung immaturity is a major cause of mortality in preterm infants. Although intermittent positive pressure ventilation (IPPV) saves lives, lung distortion during its use is associated with lung injury and chronic lung disease (CLD). Conventional IPPV is provided at 30-80 breaths per minute while a newer form of ventilation called high frequency oscillatory ventilation (HFOV) provides 'breaths' at 10-15 seconds. This has been shown to result in less lung injury in experimental studies. OBJECTIVES: The objective of this review is to determine whether the elective use of high frequency oscillatory ventilation (HFOV) as compared to conventional ventilation in preterm infants who are mechanically ventilated for the respiratory distress syndrome decreases the incidence of chronic lung disease (CLD) without adverse effects. SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal Trials, MEDLINE, EMBASE, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, journal handsearching by the Cochrane Collaboration, mainly in the English language. Expert informant's search in the Japanese language was made by Prof. Y. Ogawa. SELECTION CRITERIA: Randomized controlled trials comparing HFOV and CV in preterm or low birth weight infants with pulmonary dysfunction, mainly due to RDS, who are to be given IPPV. Randomization and commencement of treatment should have been as soon as possible after the start of IPPV and usually in the first 12 hours of life. DATA COLLECTION AND ANALYSIS: The methodological quality of each trial was independently reviewed by the various authors. Each author extracted data separately; they were compared and differences were resolved. The standard method of the Cochrane Neonatal Review Group was used to synthesize the data using relative risk (RR) and risk difference (RD). From 1/RD the number needed to treat (NNT) for benefits, and number needed to harm (NNH) for adverse effects, were calculated. MAIN RESULTS: Meta-analysis of the six eligible studies comparing HFOV with CV revealed that there is no difference in mortality. There are trends toward decreases in CLD in survivors at 28-30 days, 'death or CLD at 28-30 days' and CLD in survivors at 36-37 weeks postmenstrual age or discharge in the HFOV group. However, there are trends towards increases in severe (grades 3 & 4) intraventricular hemorrhage (IVH) and in periventricular leukomalacia (PVL) in the HFOV group. HFOV results in a small increase in any air leak syndrome (ALS), [summary RR 1.20 (1.03, 1.39)]. Only 2 trials have included neurodevelopmental follow up and more survivors in the HFOV group are abnormal [summary RR 1.26 (1.01, 1.58)]. In the subgroup of four trials where a high volume strategy (HVS) was used, HFOV results in more favourable pulmonary outcomes. There are significantly lower rates of CLD in survivors at 28-30 days [summary RR 0.53 (0.36, 0.76)] and of 'death or CLD at 28-30 days' [summary RR 0.56 (0.40, 0.77) with a non-significant trend towards a reduction in oxygen use at 36-37 weeks postmenstrual age or discharge [summary RR 0.74 (0.55, 1.01)]. There were no differences in the rates of IVH or PVL. Of the four trials in the subgroup using surfactant routinely, three also used the HVS. The trends in results were similar with surfactant to those for the HVS subgroup analysis. One trial suggests that HFOV may reduce the cost of in-hospital care. In the subgroup of two trials (HIFI 1989, Rettwitz-Volk 1998) not using a HVS there is no effect of HFOV on the rate of CLD; however, there is an increase in the rate of PVL [summary RR 1.64 (1.02, 2.64). REVIEWER'S CONCLUSIONS: The overall meta-analyses is dominated by the large HIFI study which did not use the HVS recommended on the basis of animal studies, and in which surfactant was not available. Studies which used HVS have shown some benefits in short term measures of CLD without an in

High-Frequency Ventilation↗
PubMed1992

The impact of stopping rules on heterogeneity of results in overviews of clinical trials.

This paper explores the extent to which application of statistical stopping rules in clinical trials can create an artificial heterogeneity of treatment effects in overviews (meta-analyses) of related trials. For illustration, we concentrate on overviews of identically designed group sequential trials, using either fixed nominal or O'Brien and Fleming two-sided boundaries. Some analytic results are obtained for two-group designs and simulation studies are otherwise used, with the following overall findings. The use of stopping rules leads to biased estimates of treatment effect so that the assessment of heterogeneity of results in an overview of trials, some of which have used stopping rules, is confounded by this bias. If the true treatment effect being studied is small, as is often the case, then artificial heterogeneity is introduced, thus increasing the Type I error rate in the test of homogeneity. This could lead to erroneous use of a random effects model, producing exaggerated estimates and confidence intervals. However, if the true mean effect is large, then between-trial heterogeneity may be underestimated. When undertaking or interpreting overviews, one should ascertain whether stopping rules have been used (either formally or informally) and should consider whether their use might account for any heterogeneity found.

Analysis of Variance↗
PubMed2004

The effect of the heterogeneity variance estimator on some tests of treatment efficacy.

The effect of two noniterative heterogeneity variance estimators on two test procedures for the overall treatment effect using the log odds ratio as the outcome measure is investigated. Using simulated significance levels, it is shown that in addition to being sensitive to changes in the magnitude of the heterogeneity variance, the standard test procedure in meta-analysis (or multicenter clinical trials) is also sensitive to the heterogeneity variance estimator used and attains significance levels that are far from the prescribed level. A second test procedure by Hartung [Hartung, J. (1999). An alternative method for meta-analysis. Biometrical J. 41:901-916], is shown to exhibit good control of type I error probability regardless of changes in the magnitude of the heterogeneity variance and the heterogeneity variance estimator used.

Meta-Analysis as Topic↗
PubMed1991

Using empirical Bayes methods in biopharmaceutical research.

A compound sampling model, where a unit-specific parameter is sampled from a prior distribution and then observed are generated by a sampling distribution depending on the parameter, underlies a wide variety of biopharmaceutical data. For example, in a multi-centre clinical trial the true treatment effect varies from centre to centre. Observed treatment effects deviate from these true effects through sampling variation. Knowledge of the prior distribution allows use of Bayesian analysis to compute the posterior distribution of clinic-specific treatment effects (frequently summarized by the posterior mean and variance). More commonly, with the prior not completely specified, observed data can be used to estimate the prior and use it to produce the posterior distribution: an empirical Bayes (or variance component) analysis. In the empirical Bayes model the estimated prior mean gives the typical treatment effect and the estimated prior standard deviation indicates the heterogeneity of treatment effects. In both the Bayes and empirical Bayes approaches, estimated clinic effects are shrunken towards a common value from estimates based on single clinics. This shrinkage produces more efficient estimates. In addition, the compound model helps structure approaches to ranking and selection, provides adjustments for multiplicity, allows estimation of the histogram of clinic-specific effects, and structures incorporation of external information. This paper outlines the empirical Bayes approach. Coverage will include development and comparison of approaches based on parametric priors (for example, a Gaussian prior with unknown mean and variance) and non-parametric priors, discussion of the importance of accounting for uncertainty in the estimated prior, comparison of the output and interpretation of fixed and random effects approaches to estimating population values, estimating histograms, and identification of key considerations in the use and interpretation of empirical Bayes methods.

Bayes Theorem↗
PubMed2002

Noninvasive ventilation in acute respiratory failure--a meta-analysis update.

OBJECTIVE: To present a meta-analytic update on the effects of noninvasive ventilation (NIV) in the management of acute respiratory failure. DESIGN: Meta-analysis of randomized controlled clinical trials in acute respiratory failure comparing NIV with standard medical therapy. PATIENTS: Randomized controlled trials of NIV in acute respiratory failure were identified by search of i) MEDLINE (1966-2000), ii) published abstracts from scientific meetings, and iii) bibliographies of relevant articles. MEASUREMENTS AND MAIN RESULTS: Of the 15 randomized controlled trials that were identified (13 published and 2 in abstract form), 8 studies were on exacerbations of chronic obstructive pulmonary disease (COPD) and 7 on diverse disease processes in both COPD and non-COPD groups ("mixed-group"). Because of underlying heterogeneity of treatment effects, only the DerSimonian-Laird random effects estimator was used and reported. The effects of NIV vs. standard therapy on mortality and subsequent invasive mechanical ventilation (MV) was assessed as risk difference, and hospital length of stay as mean weighted difference (days). NIV was associated with reduction in mortality (8%, p = .03), reduced need for MV (19%, p = .001) and shortened hospital length of stay (2.74 days, p = .004). In the COPD cohort, significant reductions in mortality (13%, p = .001), need for MV (18%, p = .02), and hospital length of stay (5.66 days, p = .01) were observed in the group treated with NIV. In contrast, in the mixed-group, there was no demonstrable reduction in mortality (0%, p = .98). However, there was significant reduction in the need for MV (22%, p = .001). Publication bias was not evident on analysis. Treatment effect i) as mortality or need for mechanical ventilation was not modified by enrollment pH, PaCO2, nor age and ii) was not related (as log odds ratio) to underlying risk (control arm log odds). Cumulative meta-analysis did not demonstrate any substantial variation in the point estimates with the addition of the recently published studies. However a contraction in the confidence intervals was observed in the COPD subgroup. Complication rates were not significantly different in the standard medical therapy group and the NIV treated patients. CONCLUSION: Substantial reductions in mortality and the need for subsequent MV were associated with NIV in acute respiratory failure, especially in the COPD subgroup. Hospital length of stay was variably affected. Heterogeneity of treatment effects was observed.

Acute Disease↗
PubMed2006

Oxime therapy and outcomes in human organophosphate poisoning: an evaluation using meta-analytic techniques.

OBJECTIVE: The status of oximes in human organophosphate poisoning is controversial. This analysis compares the outcomes of therapy with or without oximes. DESIGN: Quantitative analysis using meta-analytic techniques. METHODS: Controlled trials of oximes in human organophosphate poisoning were identified by search of MEDLINE and TOXLINE (1966 to May 2005) and review of published articles. MEASUREMENTS AND MAIN RESULTS: Of the 3,122 articles on organophosphate poisoning identified by electronic search, 116 related to oxime use in human organophosphate poisoning. Seven trials, including two randomized controlled trials, compared oximes with standard medical care. Varying dosage schedules of pralidoxime or obidoxime were used. The effects of oxime therapy on mortality rate, mechanical ventilation, incidence of intermediate syndrome, and need for intensive care therapy were analyzed and expressed as risk difference (positive values indicating oxime harm). The random effects estimator was reported because of underlying heterogeneity of treatment effects between study types. No statistically significant association of oxime therapy was demonstrated for either mortality (risk difference 0.09, 95% confidence interval -0.08 to 0.27), ventilatory requirements (risk difference 0.16, 95% confidence interval -0.07 to 0.38), or the incidence of intermediate syndrome (risk difference 0.16, 95% confidence interval -0.12 to 0.45), although point estimates of effect suggested harm. An increased need for intensive care therapy (risk difference 0.19, 95% confidence interval 0.01 to 0.36) was apparent with oxime therapy. CONCLUSIONS: Based on the current available data on human organophosphate poisoning, oxime was associated with either a null effect or possible harm. The lack of current prospective randomized controlled trials, with appropriate patient stratification, mandates ongoing assessment of the role of oximes in organophosphate poisoning.

Adult↗
PubMed2000

Heterogeneity and statistical significance in meta-analysis: an empirical study of 125 meta-analyses.

For meta-analysis, substantial uncertainty remains about the most appropriate statistical methods for combining the results of separate trials. An important issue for meta-analysis is how to incorporate heterogeneity, defined as variation among the results of individual trials beyond that expected from chance, into summary estimates of treatment effect. Another consideration is which 'metric' to use to measure treatment effect; for trials with binary outcomes, there are several possible metrics, including the odds ratio (a relative measure) and risk difference (an absolute measure). To examine empirically how assessment of treatment effect and heterogeneity may differ when different methods are utilized, we studied 125 meta-analyses representative of those performed by clinical investigators. There was no meta-analysis in which the summary risk difference and odds ratio were discrepant to the extent that one indicated significant benefit while the other indicated significant harm. Further, for most meta-analyses, summary odds ratios and risk differences agreed in statistical significance, leading to similar conclusions about whether treatments affected outcome. Heterogeneity was common regardless of whether treatment effects were measured by odds ratios or risk differences. However, risk differences usually displayed more heterogeneity than odds ratios. Random effects estimates, which incorporate heterogeneity, tended to be less precisely estimated than fixed effects estimates. We present two exceptions to these observations, which derive from the weights assigned to individual trial estimates. We discuss the implications of these findings for selection of a metric for meta-analysis and incorporation of heterogeneity into summary estimates. Published in 2000 by John Wiley & Sons, Ltd.

Bias↗
PubMed1994

Estimation and hypothesis testing of treatment effects in animal reproductive toxicology studies.

Healy (1) and Dempster et al. (8) proposed statistical methods to evaluate the treatment effects in animal reproductive toxicology research. Both methods assume homogeneous variance for the dams and the pups, respectively, in all the treatment groups. In this paper, via mixed effect modeling, we propose a method to estimate the treatment effects allowing heterogeneous variances for the dams and the pups, respectively, in different treatment groups. Covariates will also be included in the model. A procedure to test the fixed effects is also discussed. An example from an animal reproductive toxicological study is used to illustrate the procedures.

Animals↗
PubMed2003

Ibuprofen for the treatment of a patent ductus arteriosus in preterm and/or low birth weight infants.

BACKGROUND: A patent ductus arteriosus (PDA) complicates the clinical course of preterm infants, increasing their risks of developing chronic lung disease (CLD), necrotizing enterocolitis (NEC), and intraventricular hemorrhage (IVH). Indomethacin is used as standard therapy to close a PDA, but is associated with reduced blood flow to the brain, kidneys and gut. Ibuprofen, another cyclo-oxygenase inhibitor, may be as effective with fewer side effects. OBJECTIVES: To determine the effectiveness and safety of ibuprofen compared to placebo or no intervention for closing a PDA in preterm and/or low birth weight infants. To determine the effectiveness and safety of ibuprofen compared to other cyclo-oxygenase inhibitors (including indomethacin, mefenamic acid) for closing a PDA in preterm and/or low birth weight infants. SEARCH STRATEGY: Randomized (or quasi-randomized) controlled trials (RCTs) comparing ibuprofen to placebo or indomethacin or mefenamic acid for therapy of PDA were identified by searching the Cochrane Controlled Trials Register (Issue 4, 2002), MEDLINE (1996 - January 2003), CINAHL (1982 - November 2002), EMBASE (1980 - January 2002), reference lists of published RCTs and abstracts from the Pediatric Academic Societies and the European Society for Pediatric Research meetings published in Pediatric Research (1991 - 2002). No language restrictions were applied. SELECTION CRITERIA: 1) DESIGN: Randomized or quasi-randomized controlled trials 2) POPULATION: Preterm (< 37 weeks gestational age) or low birth weight infants (< 2500 grams) with a clinically or echocardiographically diagnosed PDA 3) INTERVENTION: Administration of ibuprofen for the closure of PDA 4) OUTCOMES: At least one of the following outcomes were reported: failure to close a PDA, mortality, surgical ligation, intraventricular haemorrhage (IVH), periventricular leukomalacia (PVL), NEC, decreased urine output, retinopathy of prematurity (ROP), CLD, sepsis, days on supplementary oxygen. DATA COLLECTION AND ANALYSIS: At least two reviewers worked independently at each step of the review, then compared results and resolved differences. Methodological quality of eligible studies was assessed according to blinding of randomization, of intervention and of outcome assessment, and completeness of followup. Weighted treatment effects, calculated using Revman 4.1, included typical relative risk (RR), typical risk difference (RD), number needed to treat (NNT) or harm (NNH), and weighted mean difference (WMD), all with 95% confidence intervals (CI). A fixed effect model was used for meta-analyses. Heterogeneity tests were performed to assess the appropriateness of pooling the data. MAIN RESULTS: Eight studies including 509 patients were included. All studies compared the effectiveness of ibuprofen to indomethacin for the closure of a PDA. There was no statistically significant heterogeneity of treatment effect for any of the outcomes. For the primary outcome (failure of ductal closure), there was no statistically significant difference between ibuprofen and indomethacin groups [RR 0.92 (95% CI 0.69, 1.22)]. There were no statistically significant differences in mortality, surgical duct ligation, duration of ventilator support, IVH, PVL, NEC, time to full enteral feeds, ROP, sepsis, duration of hospital stay or gastrointestinal bleed. For many of these outcomes the sample size was small and the estimates imprecise. The incidence of decreased urine output (< 1cc/kg/hr) was lower in the ibuprofen group as compared to the indomethacin group [NNT 9 (95% CI 5-14)]. This was the only statistically significant clinical finding favouring ibuprofen. Chronic lung disease defined as oxygen requirement at 28 days post-natally was statistically significantly more likely to occur in the ibuprofen group [RR 1.37 (95% CI 1.01, 1.86); NNH 7 (95% CI 3 - 100)]. No studies comparing ibuprofen versus placebo for the closure of PDA were identified. REVIEWER'S CONCLUSIONS: We found no statistically significant difference in the effectiveness of ibuprofen compared to indomethacin in closing the PDA. Ibuprofen reduces the risk of oliguria. However, ibuprofen may increase the risk for chronic lung disease, and pulmonary hypertension has been observed in three infants after prophylactic use of ibuprofen. Based on currently available information ibuprofen does not appear to confer a net benefit over indomethacin for the treatment of a PDA. We conclude that indomethacin should remain the drug of choice for the treatment of a PDA. Future research may include a four arm trial where infants are randomized at birth, either to a prophylaxis arm starting at birth or to an arm in which treatment starts after a PDA is diagnosed by echocardiography within the first seven days of life. Within the prophylaxis and treatment arms, the infants would be randomized to either ibuprofen or indomethacin. The primary outcome should be intact survival (survival without handicap) at 18 months corrected age.

Cyclooxygenase Inhibitors↗
PubMed2005

Ibuprofen for the treatment of patent ductus arteriosus in preterm and/or low birth weight infants.

BACKGROUND: A patent ductus arteriosus (PDA) complicates the clinical course of preterm infants, increasing their risks of developing chronic lung disease (CLD), necrotizing enterocolitis (NEC), and intraventricular hemorrhage (IVH). Indomethacin is used as standard therapy to close a PDA, but is associated with reduced blood flow to the brain, kidneys and gut. Ibuprofen, another cyclo-oxygenase inhibitor, may be as effective with fewer side effects. OBJECTIVES: To determine the effectiveness and safety of ibuprofen compared to placebo or no intervention for closing a PDA in preterm and/or low birth weight infants. To determine the effectiveness and safety of ibuprofen compared to other cyclo-oxygenase inhibitors (including indomethacin, mefenamic acid) for closing a PDA in preterm and/or low birth weight infants. SEARCH STRATEGY: Randomized or quasi-randomized controlled trials (RCTs) comparing ibuprofen to placebo or indomethacin or mefenamic acid for therapy of PDA were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2005), MEDLINE (1996 - July 2005), CINAHL (1982 - July 2005), EMBASE (1980 - July 2005), reference lists of published RCTs and abstracts from the Pediatric Academic Societies and the European Society for Pediatric Research meetings published in Pediatric Research (1991 - April 2005). No language restrictions were applied. SELECTION CRITERIA: 1) DESIGN: Randomized or quasi-randomized controlled trials 2) POPULATION: Preterm (< 37 weeks gestational age) or low birth weight infants (< 2500 grams) with a clinically or echocardiographically diagnosed PDA 3) INTERVENTION: Administration of ibuprofen for the closure of PDA 4) OUTCOMES: At least one of the following outcomes were reported: failure to close a PDA, mortality, surgical ligation, intraventricular haemorrhage (IVH), periventricular leukomalacia (PVL), NEC, decreased urine output, retinopathy of prematurity (ROP), chronic lung disease (CLD), sepsis, days on supplementary oxygen. DATA COLLECTION AND ANALYSIS: At least two authors worked independently at each step of the original review, then compared results and resolved differences. The current update was conducted by one author (AO). Methodological quality of eligible studies was assessed according to blinding of randomization, of intervention and of outcome assessment, and completeness of follow up. Weighted treatment effects, calculated using RevMan 4.2, included typical relative risk (RR), typical risk difference (RD), number needed to treat (NNT) or harm (NNH), and weighted mean difference (WMD), all with 95% confidence intervals (CI). A fixed effect model was used for meta-analyses. Heterogeneity tests including I(2 )were performed to assess the appropriateness of pooling the data. MAIN RESULTS: No study using mefenamic acid was identified. One study compared ibuprofen to placebo but results were not reported unblinded to group. Eleven studies including 620 patients compared the effectiveness of ibuprofen to indomethacin for the closure of a PDA. There was no statistically significant heterogeneity of treatment effect for any of the outcomes. For the primary outcome (failure of ductal closure), there was no statistically significant difference between ibuprofen and indomethacin groups [typical RR 0.96 (95% CI 0.74, 1.25)]. There were no statistically significant differences in mortality, surgical duct ligation, duration of ventilator support, IVH, PVL, NEC, time to full enteral feeds, ROP, sepsis, duration of hospital stay or gastrointestinal bleed. For many of these outcomes the sample size was small and the estimates imprecise. The incidence of decreased urine output (< 1cc/kg/hr) was lower in the ibuprofen group as compared to the indomethacin group [NNT 9 (95% CI 5-14)]. This was the only statistically significant clinical finding favouring ibuprofen. CLD defined as oxygen requirement at 28 days post-natally was statistically significantly more likely to occur in the ibuprofen group [typical RR 1.37 (95% CI 1.01, 1.86); NNH 7 (95% CI 3 - 100)]. There was a similar trend for CLD at 36 weeks corrected gestational age. AUTHORS' CONCLUSIONS: We found no statistically significant difference in the effectiveness of ibuprofen compared to indomethacin in closing the PDA. Ibuprofen reduces the risk of oliguria. However, ibuprofen may increase the risk for CLD, and pulmonary hypertension has been observed in three infants after prophylactic use of ibuprofen. Based on currently available information ibuprofen does not appear to confer a net benefit over indomethacin for the treatment of a PDA. We conclude that indomethacin should remain the drug of choice for the treatment of a PDA. The most urgent research question to be answered is weather ibuprofen compared to indomethacin confers an improved rate of intact survival (survival without impairment) at 18 months corrected age.

Cyclooxygenase Inhibitors↗
PubMed2006

Soy formula for prevention of allergy and food intolerance in infants.

BACKGROUND: Allergies and food reactions in infants and children are common and may be associated with a variety of foods including adapted cow's milk formula. Soy based formulas have been used to treat infants with allergy or food intolerance. However, it is unclear whether they can help prevent allergy and food intolerance in infants without clinical evidence of allergy or food intolerance. OBJECTIVES: To determine the effect of feeding adapted soy formula compared to human milk, cow's milk formula or a hydrolysed protein formula on preventing allergy or food intolerance in infants without clinical evidence of allergy or food intolerance. SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal Review Group was used. Updated searches were performed of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006), MEDLINE (1966-March 2006), EMBASE (1980-March 2006), CINAHL (1982-March 2006) and previous reviews including cross references. SELECTION CRITERIA: Randomised and quasi-randomised trials that compare the use of an adapted soy formula to human milk, an adapted cow's milk or a hydrolysed protein formula for feeding infants without clinical allergy or food intolerance in the first six months of life. Only trials with > 80% follow up of participants and reported in group of assignment were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Eligibility of studies for inclusion, methodological quality and data extraction were assessed independently by each review author. Primary outcomes included clinical allergy, specific allergies and food intolerance. Where no heterogeneity of treatment effect was found, the fixed effect model was used for meta-analysis. Where significant or apparent heterogeneity was found, results were reported using the random effects model and potential causes of the heterogeneity were sought. MAIN RESULTS: Three eligible studies enrolling high risk infants with a history of allergy in a first degree relative were included. No eligible study enrolled infants fed human milk. No study examined the effect of early, short term soy formula feeding. All compared prolonged soy formula to cow's milk formula feeding. One study was of adequate methodology and without unbalanced allergy preventing co-interventions in treatment groups. One study with unclear allocation concealment and 19.5% losses reported a significant reduction in infant allergy, asthma and allergic rhinitis. However, no other study reported any significant benefits from the use of a soy formula. Meta-analysis found no significant difference in childhood allergy incidence (2 studies; typical RR 0.73, 95% CI 0.37, 1.44). No significant difference was reported in one study in infant asthma (RR 1.10, 95% CI 0.86, 1.40), infant eczema (RR 1.20, 95% CI 0.95, 1.52), childhood eczema prevalence (RR 1.10, 95% CI 0.73, 1.68), infant rhinitis (RR 0.94, 95% CI 0.76, 1.16) or childhood rhinitis prevalence (RR 1.20, 95% CI 0.73, 2.00). Meta-analysis found no significant difference in childhood asthma incidence (3 studies, 728 infants; typical RR 0.71, 95% CI 0.26, 1.92), childhood eczema incidence (2 studies, 283 infants; typical RR 1.57, 95% CI 0.90, 2.75) or childhood rhinitis incidence (2 studies, 283 infants; typical RR 0.69, 95% CI 0.06, 8.00). One study reported no significant difference in infant CMPI (RR 1.09, 95% CI 0.45, 2.62), infant CMA (RR 1.09, 95% CI 0.24, 4.86), childhood soy protein allergy incidence (RR 3.26, 95% CI 0.36, 29.17) and urticaria. No study compared soy formula to hydrolysed protein formula. AUTHORS' CONCLUSIONS: Feeding with a soy formula cannot be recommended for prevention of allergy or food intolerance in infants at high risk of allergy or food intolerance. Further research may be warranted to determine the role of soy formulas for prevention of allergy or food intolerance in infants unable to be breast fed with a strong family history of allergy or cow's milk protein intolerance.

Food Hypersensitivity↗
PubMed2005

Meta-analysis of individual patient data from randomized trials: a review of methods used in practice.

BACKGROUND: Meta-analyses based on individual patient data (IPD) are regarded as the gold standard for systematic reviews. However, the methods used for analysing and presenting results from IPD meta-analyses have received little discussion. METHODS: We review 44 IPD meta-analyses published during the years 1999-2001. We summarize whether they obtained all the data they sought, what types of approaches were used in the analysis, including assumptions of common or random effects, and how they examined the effects of covariates. RESULTS: Twenty-four out of 44 analyses focused on time-to-event outcomes, and most analyses (28) estimated treatment effects within each trial and then combined the results assuming a common treatment effect across trials. Three analyses failed to stratify by trial, analysing the data is if they came from a single mega-trial. Only nine analyses used random effects methods. Covariate-treatment interactions were generally investigated by subgrouping patients. Seven of the meta-analyses included data from less than 80% of the randomized patients sought, but did not address the resulting potential biases. CONCLUSIONS: Although IPD meta-analyses have many advantages in assessing the effects of health care, there are several aspects that could be further developed to make fuller use of the potential of these time-consuming projects. In particular, IPD could be used to more fully investigate the influence of covariates on heterogeneity of treatment effects, both within and between trials. The impact of heterogeneity, or use of random effects, are seldom discussed. There is thus considerable scope for enhancing the methods of analysis and presentation of IPD meta-analysis.

Data Interpretation, Statistical↗
PubMed2005

Heparin for prolonging peripheral intravenous catheter use in neonates.

BACKGROUND: Peripheral intravenous (PIV) catheters are widely used in modern medical practice. However, mechanical or infectious complications often necessitate their removal and/or replacement. Heparin has been shown to be effective in prolonging the patency of peripheral arterial catheters and central venous catheters, but may result in life threatening complications, especially in preterm neonates. OBJECTIVES: The primary objective was to determine the effectiveness of heparin versus placebo or no treatment on duration of PIV catheter patency, defined as number of hours of catheter use. The secondary objectives were to assess the effects of heparin on catheter blockage, phlebitis or thrombophlebitis, catheter related sepsis, and complications including abnormality of coagulation profile, allergic reactions to heparin, heparin induced thrombocytopenia, intraventricular/intracranial hemorrhage and mortality. SEARCH STRATEGY: A literature search was performed using the following databases: MEDLINE (1966-February 2005), EMBASE (1980-February 2005), CINAHL (1982-February 2005), Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2005), and abstracts from the annual meetings of the Society for Pediatric Research, American Pediatric Society and Pediatric Academic Societies published in Pediatric Research (1991-2004). No language restrictions were applied. SELECTION CRITERIA: Randomized or quasi-randomized trials of heparin administered as flush or infusion versus placebo or no treatment were included. Studies which included a neonatal population and reported on at least one of the outcomes were included. DATA COLLECTION AND ANALYSIS: The methodological quality of the studies was assessed using criteria for blinding of randomization, blinding of intervention, completeness of follow-up and blinding of outcome assessment. Data on relevant outcomes were extracted and the effect size was estimated by calculating WMD (weighted mean difference, 95%CI), RR (relative risk, 95% CI) and RD (risk difference, 95% CI). MAIN RESULTS: Ten eligible studies were identified. Heparin was administered either as a flush solution, or as an additive to the total parenteral nutrition solution. Five studies reported data on the duration of use of the first catheter. Two of these studies found no statistically significant effect of heparin; two studies showed a statistically significant increase and one study showed a statistically significant decrease in the duration of PIV catheter use in the heparin group. The results were not combined for meta-analysis due to significant heterogeneity of the treatment effect (p < 0.01). In addition, there were marked differences between the studies in terms of the methodological quality, the dose, the timing, the route of administration of heparin and the outcomes reported. From a limited number of studies, there were no significant differences between the heparin and the placebo/no treatment groups in the risks of infiltration, phlebitis and intracranial hemorrhage. AUTHORS' CONCLUSIONS IMPLICATIONS FOR PRACTICE: The effect of heparin on the duration of peripheral intravenous catheter use varied across the studies. Because of clinical heterogeneity and heterogeneity in treatment effect, recommendations for heparin use in neonates with PIV catheters cannot be made. IMPLICATIONS FOR RESEARCH: There are insufficient data concerning the effect of heparin for prolonging PIV catheter use in neonates. Further research on the effectiveness, the optimal dose, and the safety of heparin is required.

Anticoagulants↗
PubMed1989

Prophylaxis of upper gastrointestinal bleeding in intensive care units: a meta-analysis.

A meta-analysis was performed of 15 randomized studies on the prophylaxis with cimetidine and/or ant-acids of upper GI bleeding acquired in the ICU. There were eight comparisons of a group receiving cimetidine with a control group, nine comparisons of a group receiving antacids with a control group, and ten comparisons of a group receiving cimetidine with a group receiving antacids. The incidence of upper GI bleeding ranged from 3.4% to 52.7% among 866 control patients who received either a placebo or no prophylaxis. In five of eight comparisons, cimetidine was significantly more effective than no treatment or a placebo to prevent occult and overt upper GI bleeding; the typical odds ratio was 0.32 (95% confidence interval 0.21 to 0.49). In six of nine comparisons, antacids were significantly more effective than no treatment or a placebo; the typical odds ratio was 0.12 (0.08 to 0.19). Finally, antacids were significantly more effective than cimetidine in two of ten comparisons; the typical odds ratio was 1.61 (0.97 to 2.65). However, weaknesses in the study designs, heterogeneity of treatment effects, the lack of strength of the accumulated evidence, and the fact that no utility has been shown in terms of reducing morbidity (shock, need for transfusion) or mortality, prevent any definitive conclusion in regard to compulsory use of upper GI bleeding prophylaxis for ICU patients.

Antacids↗
PubMed2002

Heparin for prolonging peripheral intravenous catheter use in neonates.

BACKGROUND: Peripheral intravenous (PIV) catheters are widely used in modern medical practice. However, mechanical or infectious complications often necessitate their removal and/or replacement. Heparin has been shown to be effective in prolonging the patency of peripheral arterial catheters and central venous catheters, but may result in life threatening complications, especially in preterm neonates. OBJECTIVES: The primary objective was to determine the effectiveness of heparin versus placebo or no treatment on duration of PIV catheter patency, defined as number of hours of catheter use. The secondary objectives were to assess the effects of heparin on catheter blockage, phlebitis or thrombophlebitis, catheter related sepsis, and complications including abnormality of coagulation profile, allergic reactions to heparin, heparin induced thrombocytopenia, intraventricular/intracranial hemorrhage and mortality. SEARCH STRATEGY: A literature search was performed using the following databases: MEDLINE (1966-December 2001), EMBASE (1980-December 2001), CINAHL (1982-December 2001), Cochrane Controlled Trials Register (The Cochrane Library, Issue 4, 2001), and abstracts from the annual meetings of the Society for Pediatric Research, American Pediatric Society and Pediatric Academic Societies published in Pediatric Research (1991-2001). No language restrictions were applied. SELECTION CRITERIA: Randomized or quasi-randomized trials of heparin administered as flush or infusion versus placebo or no treatment were included. Studies which included a neonatal population and reported on at least one of the outcomes were included. DATA COLLECTION AND ANALYSIS: The methodological quality of the studies was assessed using criteria for blinding of randomization, blinding of intervention, completeness of follow-up and blinding of outcome assessment. Data on relevant outcomes were extracted and the effect size was estimated by calculating WMD (weighted mean difference, 95%CI), RR (relative risk, 95% CI) and RD (risk difference, 95% CI). MAIN RESULTS: Eight eligible studies were identified. Heparin was administered either as a flush solution or as an additive to the total parenteral nutrition solution. Five studies reported data on the duration of use of the first catheter. Two of these studies found no statistically significant effect of heparin; two studies showed a statistically significant increase and one study showed a statistically significant decrease in the duration of PIV catheter use in the heparin group. The results were not combined for meta-analysis due to significant heterogeneity of the treatment effect (p<0.01). In addition, there were marked differences between the studies in terms of the methodological quality, the dose, the timing, the route of administration of heparin and the outcomes reported. From a limited number of studies, there were no significant differences between the heparin and the placebo/no treatment groups in the risks of infiltration, phlebitis and intracranial hemorrhage. REVIEWER'S CONCLUSIONS IMPLICATIONS FOR PRACTICE: The effect of heparin on the duration of peripheral intravenous catheter use varied across the studies. Because of clinical heterogeneity and heterogeneity in treatment effect, recommendations for heparin use in neonates with PIV catheters cannot be made. IMPLICATIONS FOR RESEARCH: There are insufficient data concerning the effect of heparin for prolonging PIV catheter use in neonates. Further research on the effectiveness, the optimal dose, and the safety of heparin is required.

Anticoagulants↗
PubMed2003

Platelet-rich-plasmapheresis for minimising peri-operative allogeneic blood transfusion.

BACKGROUND: Concerns regarding the safety of transfused blood have generated considerable enthusiasm for the use of technologies intended to reduce the use of allogeneic blood (blood from an unrelated donor). Platelet-rich plasmapheresis (PRP) offers an alternative approach to blood conservation. OBJECTIVES: To examine the evidence for the efficacy of PRP in reducing peri-operative allogeneic red blood cell (RBC) transfusion, and the evidence for any effect on clinical outcomes such as mortality and re-operation rates. SEARCH STRATEGY: Studies were identified by: computer searches of MEDLINE, EMBASE, Current Contents, and the Cochrane Library (to June 2001). These searches were supplemented by checking the reference lists of published articles, reports, and reviews. SELECTION CRITERIA: Controlled parallel group trials in which adult patients, scheduled for non-urgent surgery, were randomised to PRP, or to a control group who did not receive the intervention. DATA COLLECTION AND ANALYSIS: Main outcomes measured were: the number of patients receiving an allogeneic RBC transfusion, and the amount of RBC transfused. Trial quality was assessed using criteria proposed by Schulz et al. (Schulz 1995) and Jadad et al. (Jadad 1996). MAIN RESULTS: Nineteen trials of PRP were identified that reported data for the number of patients exposed to allogeneic RBC transfusion. These trials evaluated a total of 1452 patients. The pooled relative risk (RR) of exposure to allogeneic blood transfusion in those patients randomised to PRP was 0.71 (95%CI: 0.56, 0.90), equating to a relative risk reduction (RRR) of 29%; the average absolute risk reduction (ARR) was 19% (RD = -0.19: 95%CI: -0.29, -0.09). On average, PRP did not significantly reduce the total volume of RBC transfused (weighted mean difference [WMD] = -0.69: 95%CI: -1.93, 0.56 units). Substantial statistical heterogeneity was observed (p < 0.001). Trials provided inadequate data regarding the impact of PRP on morbidity, mortality, and hospital length of stay. The majority of trials were small and of poor methodological quality. REVIEWER'S CONCLUSIONS: Although the results suggest that PRP is effective in reducing allogeneic RBC transfusion in adult patients undergoing elective surgery, there was considerable heterogeneity in treatment effects and the trials were of poor methodological quality. As the majority of trials were unblinded, transfusion practices may have been influenced by knowledge of the patient's allocation status, potentially exaggerating the true magnitude of the beneficial effect of PRP. The available studies provided inadequate data for firm conclusions to be drawn regarding the impact of PRP on clinically important endpoints.

Adult↗
PubMedDate not supplied

Novel photoreactors for heterogeneous photocatalytic wastewater treatment.

Heterogeneous photocatalysis is an effective treatment method for removal of toxic pollutants from industrial wastewaters. A novel, thin film slurry photoreactor was evaluated in this work for its effectiveness in removing phenol. The efficiency of parameters, initial phenol and catalyst concentrations and the light intensity on phenol removal was studied. The reactor performed well giving near complete removal of phenol even at a higher concentration of 500 mg/l.

Disinfectants↗