The effectiveness of glucocorticoids in treating croup: meta-analysis.
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OBJECTIVE: To determine the effectiveness of glucocorticoid treatment in children with croup. DESIGN: Meta-analysis of randomised controlled trials that examine the effectiveness of glucocorticoid treatment in children with croup. MAIN OUTCOME MEASURES: Score on scale measuring severity of croup, use of cointerventions (adrenaline (epinephrine), antibiotics, or supplemental glucocorticoids), length of stay in accident and emergency or in hospital, and rate of hospitalisation. RESULTS: Twenty four studies met the inclusion criteria. Glucocorticoid treatment was associated with an improvement in the croup severity score at 6 hours with an effect size of -1.0 (95% confidence interval -1.5 to -0.6) and at 12 hours -1.0 (-1.6 to -0.4); at 24 hours this improvement was no longer significant (-1.0, -2.0 to 0.1). There was a decrease in the number of adrenaline treatments needed in children treated with glucocorticoids: a decrease of 9% (95% confidence interval 2% to 16%) among those treated with budesonide and of 12% (4% to 20%) among those treated with dexamethasone. There was also a decrease in the length of time spent in accident and emergency (-11 hours, 95% confidence interval -18 to 4 hours), and for inpatients hospital stay was reduced by 16 hours (-31 to 1 hour). Publication bias seems to play a part in these results. CONCLUSIONS: Dexamethasone and budesonide are effective in relieving the symptoms of croup as early as 6 hours after treatment. Fewer cointerventions are used and the length of time spent in hospital is decreased in patients treated with glucocorticoids. (+info)
Reanalysis of epidemiological evidence on lung cancer and passive smoking.
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OBJECTIVE: To assess the epidemiological evidence for an increase in the risk of lung cancer resulting from exposure to environmental tobacco smoke. DESIGN: Reanalysis of 37 published epidemiological studies previously included in a meta-analysis allowing for the possibility of publication bias. MAIN OUTCOME MEASURE: Relative risk of lung cancer among female lifelong non-smokers, according to whether her partner was a current smoker or a lifelong non-smoker. RESULTS: If it is assumed that all studies that have ever been carried out are included, or that those selected for review are truly representative of all such studies, then the estimated excess risk of lung cancer is 24%, as previously reported (95% confidence interval 13% to 36%, P<0.001). However, a significant correlation between study outcome and study size suggests the presence of publication bias. Adjustment for such bias implies that the risk has been overestimated. For example, if only 60% of studies have been included, the estimate of excess risk falls from 24% to 15%. CONCLUSION: A modest degree of publication bias leads to a substantial reduction in the relative risk and to a weaker level of significance, suggesting that the published estimate of the increased risk of lung cancer associated with environmental tobacco smoke needs to be interpreted with caution. (+info)
Manipulation of host behaviour by parasites: a weakening paradigm?
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New scientific paradigms often generate an early wave of enthusiasm among researchers and a barrage of studies seeking to validate or refute the newly proposed idea. All else being equal, the strength and direction of the empirical evidence being published should not change over time, allowing one to assess the generality of the paradigm based on the gradual accumulation of evidence. Here, I examine the relationship between the magnitude of published quantitative estimates of parasite-induced changes in host behaviour and year of publication from the time the adaptive host manipulation hypothesis was first proposed. Two independent data sets were used, both originally gathered for other purposes. First, across 137 comparisons between the behaviour of infected and uninfected hosts, the estimated relative influence of parasites correlated negatively with year of publication. This effect was contingent upon the transmission mode of the parasites studied. The negative relationship was very strong among studies of parasites which benefit from host manipulation (transmission to the next host occurs by predation on an infected intermediate host), i.e. among studies which were explicit tests of the adaptive manipulation hypothesis. There was no correlation with year of publication among studies on other types of parasites which do not seem to receive benefits from host manipulation. Second, among 14 estimates of the relative, parasite-mediated increase in transmission rate (i.e. increases in predation rates by definitive hosts on intermediate hosts), the estimated influence of parasites again correlated negatively with year of publication. These results have several possible explanations, but tend to suggest biases with regard to what results are published through time as accepted paradigms changed. (+info)
Empirical assessment of effect of publication bias on meta-analyses.
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OBJECTIVE: To assess the effect of publication bias on the results and conclusions of systematic reviews and meta-analyses. DESIGN: Analysis of published meta-analyses by trim and fill method. STUDIES: 48 reviews in Cochrane Database of Systematic Reviews that considered a binary endpoint and contained 10 or more individual studies. MAIN OUTCOME MEASURES: Number of reviews with missing studies and effect on conclusions of meta-analyses. RESULTS: The trim and fill fixed effects analysis method estimated that 26 (54%) of reviews had missing studies and in 10 the number missing was significant. The corresponding figures with a random effects model were 23 (48%) and eight. In four cases, statistical inferences regarding the effect of the intervention were changed after the overall estimate for publication bias was adjusted for. CONCLUSIONS: Publication or related biases were common within the sample of meta-analyses assessed. In most cases these biases did not affect the conclusions. Nevertheless, researchers should check routinely whether conclusions of systematic reviews are robust to possible non-random selection mechanisms. (+info)
Publication bias in reproductive research.
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Publication bias is defined as any tendency on the part of investigators or editors to fail to publish study results on the basis of the direction or strength of the findings. This may lead to overestimation of treatment effects in published work. Inappropriate decisions about patient management may result. We investigated what proportion of abstracts at the European Society of Human Reproduction and Embryology (ESHRE) annual meeting eventually reached full publication, what was the time to publication, and which factors might have affected publication. Among the 2691 abstracts of six ESHRE annual meetings, 151 (5.6%) reporting randomized controlled trials (RCT) were identified. Comprehensive searches of electronic databases and handsearching of the two major journals in the field yielded 79 full publications pertaining to these abstracts. Kaplan-Meier analysis estimated 56% of RCT abstracts to be eventually published in full, the median time to publication being 32.5 months. Positive outcome (i.e. significant results) did not affect the publication rate, and neither did sample size, the subject category, or the native language (English/non-English) of the country of origin. Oral presentations resulted in eventual full publication significantly more frequently (69%) than posters (42%). It is concluded that a considerable publication deficit, but not a publication bias, exists for RCT in reproductive research. (+info)
Garlic consumption and cancer prevention: meta-analyses of colorectal and stomach cancers.
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BACKGROUND: Animal and in vitro studies have provided evidence of an anticarcinogenic effect of active ingredients in garlic. OBJECTIVE: The objective was to conduct meta-analyses of the epidemiologic literature on the association between garlic consumption and risk of stomach, colon, head and neck, lung, breast, and prostate cancers. DESIGN: Meta-analyses were conducted for all cancers mutually and separately for colorectal and stomach cancers in relation to consumption of exclusively raw garlic, cooked garlic, or both (RC garlic). Eighteen studies reported a relative risk estimate for RC garlic consumption and cancer risk. RESULTS: In the meta-analyses of colorectal and stomach cancer, the reference categories ranged from no consumption to consumption of 3.5 g/wk, whereas the highest categories ranged from any consumption to >28.8 g/wk. The average difference between the highest and lowest categories was 16 g/wk. The random-effects relative risk (RR) estimate of colorectal cancer and RC garlic consumption, excluding garlic supplements, was 0.69 (95% CI: 0.55, 0.89). For stomach cancer, the random-effects RR estimate was 0.53 (95% CI: 0.31, 0.92). The heterogeneity among studies for the latter outcome (P: = 0.0002) indicates the questionableness of the generalizability of this summary estimate. An indication of publication bias for all cancers combined is evident from a funnel plot of RC garlic consumption and cancer risk and from the results of the Begg and Mazumdar test (P: = 0.049). CONCLUSIONS: High intake of RC garlic may be associated with a protective effect against stomach and colorectal cancers. Heterogeneity of effect estimates, differences in dose estimation, publication bias, and possible alternative hypotheses (eg, confounding by total vegetable consumption) preclude sole reliance on summary effect estimates. (+info)
Participation of epidemiologists and/or biostatisticians and methodological quality of published controlled clinical trials.
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STUDY OBJECTIVE: This study assessed several methodological aspects related to the quality of published controlled clinical trials (CCTs) in relation to the participation of an epidemiologist/biostatistician (E/B). DESIGN: Handsearch of CCTs published in four medical leading journals for 1993-1995. METHODS: Quality variables, abstracted from a review, were related to authors' specialties. Five hundred and ninety four CCTs were identified via a hand search. The department/unit membership was used to attribute authors' specialties. Of 594 CCTs identified, in 127 the authors' specialties could not be known, leaving 467 trials for analysis. RESULTS: E/B participation occurred in 178 trials (38.1%). This participation was more frequent in multicentric, bigger, and in those trials describing any funding agency. These factors were controlled for in the analysis. E/B participation was positively associated with pre-study sample size estimation (OR = 1.5, 95% confidence intervals (CI) 1.0, 2.3), with reporting the dates for starting/ending the study (OR = 2.1, 95% CI 1.4, 3.3), with using an objectively assessed outcome (OR = 2.4, 95% CI 1.2, 4.6) and with the intention to treat principle (OR = 2.0, 95% CI 1.3, 3.0). The overall quality score was higher in trials where E/B participated. CONCLUSIONS: The results suggest that E/B improve the quality (at least of reports) of clinical trials. Given that quality of research is frequently used to evaluate potential sources of heterogeneity between trials, these results are relevant for meta-analysis. (+info)
Preconception care and the risk of congenital anomalies in the offspring of women with diabetes mellitus: a meta-analysis.
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Offspring of women with pregestational diabetes mellitus are at increased risk for congenital malformations, largely attributable to poor periconceptional glycaemic control. We assessed the effect of preconception care in reducing congenital malformations, in a meta-analysis of published studies of preconception care in women with diabetes mellitus. Articles were retrieved from Medline (1970 to June 2000) and Embase (1980 to June 2000), and data abstracted by two independent reviewers. The rates and relative risks (RR) for major and minor congenital malformations were pooled from all eligible studies using a random effects model, as were early first-trimester glycosylated haemoglobin values. In 14 cohort studies, major congenital malformations were assessed among 1192 offspring of mothers who had received preconception care, and 1459 offspring of women who had not. The pooled rate of major anomalies was lower among preconception care recipients (2.1%) than non-recipients (6.5%) (RR 0.36, 95%CI 0.22-0.59). In nine studies, the risk for major and minor anomalies was also lower among women who received preconception care (RR 0.32, 95%CI 0.17-0.59), as were the early first-trimester mean glycosylated haemoglobin values (pooled mean difference: 2.3%, 95%CI 2.1-2.4). Women who received preconception care were, on average, 1.8 years older than non-recipients, and fewer smoked (19.6% vs. 30.2%). Only one study described the routine use of periconception folic acid. Out-patient preconception care probably reduces the risk of major congenital anomalies among the offspring of women with pregestational diabetes mellitus. Because many women with diabetes neither plan their pregnancy nor achieve adequate glycaemic control before conception, strategies are needed to improve access to these programs, and to maximize those interventions associated with improved pregnancy outcome, such as smoking cessation and folic acid use. (+info)