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PubMed1998

Meta-analysis of antisecretory and gastrokinetic compounds in functional dyspepsia.

In view of therapeutic advances, we carried out meta-analysis of results from 18 randomized, controlled clinical studies to update a previous meta-analysis and to provide an overview of clinical trials involving treatment of functional dyspepsia. The studies were included only if they satisfied inclusion and exclusion criteria and assessed treatment of functional dyspepsia with the antisecretory compounds cimetidine and ranitidine and the gastrokinetic compounds cisapride and domperidone. Outcomes of each of these trials were classified in terms of differences in therapeutic success between active treatment and placebo. For antisecretory treatments, the 95% confidence intervals for the difference in therapeutic success between active treatment and placebo were inconsistent for cimetidine, but analysis of both ranitidine trials gave favorable results. For the gastrokinetic compounds cisapride and domperidone, the differences in success rates were generally higher and more in favor of active treatment than placebo. By combining the results from both antisecretory treatments and comparing them with the combined results for gastrokinetic compounds, we observed that gastrokinetic compounds had a greater difference in success rates than did antisecretory agents. Overall, our meta-analysis shows that antisecretory treatment with cimetidine or ranitidine offers little advantage over placebo, whereas gastrokinetic treatment with cisapride or domperidone is significantly better than placebo for treatment of functional dyspepsia.

Anti-Ulcer Agents↗
PubMed2003

Head-to-head comparison of dipyridamole echocardiography and stress perfusion scintigraphy for the detection of coronary artery disease: a meta-analysis. Comparison between stress echo and scintigraphy.

OBJECTIVES: This meta-analysis was performed to assess and compare the diagnostic accuracy of dipyridamole echocardiography test (DET) vs. stress perfusion scintigraphy (SPS) for the diagnosis of coronary artery disease (CAD). METHODS: We performed a meta-analysis of peer reviewed articles, published in English language reporting head-to-head comparison of DET vs. SPS for the diagnosis of CAD. Data of 10 studies comprising 651 patients from 10 different institutions were analyzed. DET dose was 0.56 mg/kg (low dose) in two studies, 0.75 mg/kg in 10 min or 0.84 mg/kg in 10 min (high dose) in six studies, and 0.84 mg/kg in 6 min (accelerated high dose) in one study and 0.84 mg/kg in 10 min + 1 mg atropine co-administration (augmented dose) in one study. SPS was performed with dipyridamole in six studies, with exercise in three studies and with dobutamine in one study. RESULTS: The overall diagnostic accuracy of the two tests was almost similar, 77% (95% CI = 74-81) for DET vs. 81% (95% CI = 78-84) for SPS (p = ns). SPS gave higher sensitivity, 88% (95% CI = 85-89) than DET, 70% (95% CI = 66-75) in cumulative data (p < 0.0001) while DET gave higher specificity, 90% (95% CI = 86-94) vs. 67% (95% CI = 60-73) (p < 0.0001). With state of the art protocols, i.e. accelerated dose and atropine augmented high dose, sensitivity of DET improved and overall accuracy was better than SPS (p < 0.05). CONCLUSION: DET and SPS have a similar diagnostic accuracy. DET has a markedly higher specificity regardless of the dose employed. SPS shows a superior sensitivity, however this sensitivity gap diminishes when more aggressive dipyridamole dosage is used for the stress echocardiography.

Coronary Disease↗
PubMed2002

Intravenous chemotherapy for resected gastric cancer: meta-analysis of randomized controlled trials.

AIM: To assess the safety and efficacy of different intravenous chemotherapeutic regimens in patients with gastric carcinomas who had undergone gastrectomy. METHODS: A meta-analysis of all the relevant randomized controlled trials (RCTs) was performed. Language was restricted to Chinese and English. RCTs were identified from Medline and Embase (1980-2001/4), and Chinese Bio-medicine Database (1990-2001/1). Literature references were checked at the same time. We included randomized and quasi-randomized trials comparing the efficacy of intravenous chemotherapy after gastrectomy with that of surgery alone in patients with confirmed gastric carcinomas who had undergone gastrectomy. Selection criteria were: randomized or quasi-randomized trials with following-up results; Trials could be double-blind, single-blind or not blind; Chemotherapy groups were given intravenous chemotherapy after gastrectomy without neo-adjuvant chemotherapy, intraperitoneal hyperthermic perfusion, radiotherapy or chemoimmunotherapy; Controlled group included those receiving gastrectomy alone. The following data were extracted: the number of survival and death by the end of the follow-up; the different agents and doses of the intravenous chemotherapy; the baseline of the chemotherapy group and the controlled arm; the serious adverse events; the statistical consideration; cost-effectiveness analysis. The statistical analysis was performed by RevMan4.1 software which was provided by the Cochrane Collaboration. A P value of <0.05 was considered statistically significant. Meta-analysis was done with random effects model. Heterogeneity was checked by chi-square test. Sensitivity analysis was performed by excluding the trials in which Jadad-scale was only 1 score. The result was expressed with odds ratio (OR) for the categorical variable. RESULTS: Fourteen trials involving 4543 patients were included. Meta-analysis was done with random effects model. Heterogeneity and sensitivity analysis were performed also. The effect of intravenous chemotherapy after gastrectomy was better than surgery alone (odds ratio 0.56, 95 %CI 0.40-0.79). There was a significant difference between the two groups by u-test (P=0.0008). Sensitivity analysis revealed the same difference (odds ratio 0.81, 95 % CI 0.70-0.94). Of fourteen trials, only three studies were of high quality according to the Jadad-scale (with three score). There was one meta-analysis trial and the others, about ten trials, were of low quality. There was no trial which mentioned sample-size calculation, allocation concealment, intention-to-treat analysis. Most of the trials didn't describe the blind-procedure. There were five trials which detailed the side-effects according to the toxicity grade by WHO standard. The side-effects halting treatment were haematologic and biochemical toxicity, debilitating nausea and vomiting. There were two patients died of chemotherapy toxicity. CONCLUSION: Based on the review, intravenous chemotherapy after gastrectomy may have positive treatment effect on gastric cancer. However, the evidence is not strong because of the general low methodologic quality of the RCTs. Therefore, we can't make the conclusion that intravenous chemotherapy after gastrectomy may have better treatment effect on gastric cancer than that of surgery alone. Rigorously designed, randomised, double-blind, placebo-controlled trials are required.

Antineoplastic Agents↗
PubMed2000

Concordance of endotoxemia with gram-negative bacteremia. A meta-analysis using receiver operating characteristic curves.

OBJECTIVE: To apply meta-analysis to compare the concordance between the results of 2 types of limulus amebocyte lysate (LAL) assay, gelation (GLAL) and chromogenic (CLAL), with the detection of gram-negative bacteremia in patients with suspected bacteremia. DESIGN: Meta-analysis using receiver operating characteristic-based analytical method. DATA SOURCES: MEDLINE literature search and manual reviews of article bibliographies together with direct approaches to authors of potentially eligible studies. STUDY SELECTION: The studies that were selected had all included at least 10 patients, of whom at least 2 patients were diagnosed with gram-negative bacteremia, and all had data available for extraction into a contingency table format. RESULTS: Fifty-six studies (28 GLAL and 28 CLAL studies) met the inclusion criteria. Studies were stratified by type of test (GLAL vs CLAL). Each analysis was repeated with smaller studies excluded. There was no difference between the 2 types of LAL assays. Among the CLAL studies, there was no difference between studies that did versus those that did not use the sepsis syndrome criteria as a basis for patient inclusion. Among 45 studies for which data on the proportion of non-Enterobacteriaceae were available, there was a trend toward higher concordance as this proportion increased. CONCLUSIONS: The concordance between the LAL test and the detection of gram-negative bacteremia in patients with suspected bacteremia is no higher with the CLAL assay than with the original GLAL version. However, the concordance is higher among studies with a higher proportion of non-Enterobacteriaceae among the gram-negative bacteremia isolates.

Endotoxemia↗
PubMed1994

Selections from current literature: magnesium, myocardial infarction and meta-analysis.

If the results of LIMIT-2, the two meta-analyses reviewed and the cumulative meta-analysis by Lau et al. are viewed in aggregate, there can be very little doubt regarding the beneficial effects of i.v. magnesium on mortality in suspected acute MI. The results of ISIS-4 should strengthen these odds ratios and help clarify the role of magnesium and arrhythmias in acute MI. Furthermore, the combined effect of i.v. magnesium and thrombolytics will again be focused upon. Though the cardioprotective effects of magnesium are unknown, this should only spur more studies to elucidate these mechanisms and should not be a reason to delay the inclusion of i.v. magnesium in the usual regimen for treating suspected acute MI. The regimen of i.v. magnesium needs to be standardized. Further studies are also needed to evaluate whether oral magnesium can be used as tertiary prevention for MI. Finally, meta-analyses are studies of studies that are valid and reliable if they follow certain rules. This is true of all types of research. Due to the exponential increase in the medical literature of these types of studies, and the fact that they may eventually supplant the traditional narrative review, it is incumbent upon physicians to understand the process by which a meta-analysis is conducted.

Humans↗
PubMed1996

A clinical approach for the diagnosis of diabetes mellitus: an analysis using glycosylated hemoglobin levels. Meta-analysis Research Group on the Diagnosis of Diabetes Using Glycated Hemoglobin Levels.

OBJECTIVE: To determine whether a glycosylated hemoglobin level can be used in place of an oral glucose tolerance test (OGTT) to diagnose diabetes. DATA SOURCES/STUDY SELECTION: An augmented MEDLINE search was performed to identify all reports from 1966 through June 1994 in which glycosylated hemoglobin levels were measured concurrently with performance of OGTTs in the same study. The corresponding authors were contacted and asked to provide individual data for all subjects tested. A total of 31 investigators representing 34 possible studies responded, and 18 were able to provide us with the data requested. Overall fasting plasma glucose concentrations, 2-hour postdextrose glucose concentrations, and glycosylated hemoglobin levels were available from 11 276 individuals. DATA EXTRACTION: To define normal glucose tolerance, impaired glucose tolerance (IGT), and diabetes, modified World Health Organization criteria were used. DATA SYNTHESIS: An analysis of the methods used for measurement of glycosylated hemoglobin levels revealed that the HbA1c assay showed the least variance in normal subjects. Therefore, only data from the 8984 subjects who had HbA1c levels measured were used. When we used the mean HbA1c level plus 4 SDs as a cutpoint, the sensitivity was 36% and specificity was 100% compared with the results of the OGTT. Because of the lack of agreement between OGTT results and HbA1c levels, models were created to analyze the distribution of HbA1c levels in each study. Using these models, we identified 3 subpopulations. The third subpopulation was likely to represent subjects with diabetes. When we applied an HbA1c level of 7.0% as a cutpoint, the sensitivity was 99.6% for the third subpopulation. When this cutpoint was reapplied to the OGTT results, of those subjects with an HbA1c level of at least 7.0%, 89% had diabetes, 7% had IGT, and 4% were normal. CONCLUSIONS: Although the OGTT is the "gold standard" for diagnosing diabetes, it is known to be poorly reproducible and is often not performed. Not only is use of an HbA1c level to diagnose diabetes more convenient, but therapeutic decisions are based on this value, regardless of the findings on the OGTT. An HbA1c level of 7.0% or higher often requires pharmacological intervention and is most often associated with the diagnosis of diabetes by World Health Organization standards. An HbA1c level below 7.0% would generally be treated with diet and exercise, regardless of the diagnosis of IGT or diabetes by OGTT. Thus, measurement of HbA1c levels may represent a reasonable approach to identifying treatment-requiring diabetes.

Diabetes Mellitus↗
PubMed1994

A meta-analysis of durability data on conventional fixed bridges.

A meta-analysis was performed on the dental literature since 1970, presenting clinical data of conventional bridges. 42 publications were found that contained durability data of conventional fixed bridges. These publications dealt with 33 different samples. According to the exclusion criteria 26 studies were excluded for the meta-analysis. The data of 4118 conventional bridges were analyzed. The calculated overall survival rate was 74.0 +/- 2.1% after 15 yr.

Adult↗
PubMed2004

The effect of music on decreasing arousal due to stress: a meta-analysis.

A meta-analytic review of research articles using music to decrease arousal due to stress was conducted on 22 quantitative studies. Results demonstrated that music alone and music assisted relaxation techniques significantly decreased arousal (d = +.67). Further analysis of each study revealed that the amount of stress reduction was significantly different when considering age, type of stress, music assisted relaxation technique, musical preference, previous music experience, and type of intervention. Implications and suggestions for future research are discussed.

Arousal↗
PubMedDate not supplied

[Meta-analysis].

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Meta-Analysis as Topic↗
PubMed1999

Meta-analysis of brain size in bipolar disorder.

A recent meta-analysis concluded that patients with schizophrenia have reduced cerebral volume, and this finding has been used to implicate neurodevelopmental events in the etiology of this disorder. Since bipolar-disorder patients and schizophrenia patients have some similar brain abnormalities, it was of interest to meta-analytically review the literature on brain size in bipolar disorder. Only seven studies met the inclusion/exclusion criteria for our meta-analysis, but none reported the brain size differences between the bipolar patients and the controls to be statistically significant. The composite effect size was a negligible 0.04 (95% CI: -0.17 to 0.25) and statistically not significantly different from 0.0 (no effect). Thus, it appears that bipolar disorder is not associated with the same cerebral volume reductions noted in schizophrenia. Implications for hypotheses regarding the etiology of the two disorders are discussed.

Bipolar Disorder↗
PubMed2006

Association of TNF-alpha -308 G/A polymorphism with responsiveness to TNF-alpha-blockers in rheumatoid arthritis: a meta-analysis.

Tumor necrosis factor (TNF) antagonists are among the most effective therapies for rheumatoid arthritis (RA), yet not all patients show a response. Using meta-analysis, this present study was designed to investigate whether or not the TNF-alpha promoter -308 A/G polymorphism is associated with responsiveness to anti-TNF therapy in RA patients. We performed an exhaustive search for studies that examined the association of the TNF-alpha promoter -308 A/G polymorphism and responsiveness of anti-TNF therapy in RA using MEDLINE citations and manual review. Meta-analysis was performed for A allele carrier (genotypes A/A + A/G) between responders to anti-TNF therapy and a non-responder group in a random effects model. A total of 6 studies met the inclusion criteria. The number of patients in individual studies ranged from 33 to 123. There were 311 RA patients who were included in this meta-analysis. There was no heterogeneity between studies (I (2) = 0%, P = 0.42). The overall OR for the A allele carrier status was significantly decreased in the responder group (OR = 0.33, 95% confidence interval = 0.17-0.63, P = 0.0008). The frequency of the A allele carrier was 53/240 (22.1%) in responders and 32/71 (45.1%) in non-responders. Patients not responding to anti-TNF therapy showed an increased frequency of the A allele. The meta-analysis of the available data shows a significant association between the TNF-alpha promoter -308 A/G polymorphism and responsiveness to anti-TNF therapy, suggesting that the individuals with RA who carry the A allele have a poorer response to anti-TNF therapy than those with the G allele.

Antirheumatic Agents↗
PubMed1996

The relation between treatment benefit and underlying risk in meta-analysis.

In meta-analyses of clinical trials comparing a treated group with a control group it has been common to ask whether the treatment benefit varies according to the underlying risk of the patients in the different trials, with the hope of defining which patients would benefit most and which least from medical interventions. The usual analysis used to investigate this issue, however, which uses the observed proportions of events in the control groups of the trials as a measure of the underlying risk, is flawed and produces seriously misleading results. This arises through a bias due to regression to the mean and will be particularly acute in meta-analyses which include some small trials or in which the variability in the true underlying risks across trials is small. Approaches which previously have been thought to be more appropriate are to substitute the average proportion of events in the control and treated groups as the measure of underlying risk or to plot the proportion of events in the treated group against that in the control group (L'Abbé plot). However, these are still subject to bias in most circumstances. Because of the potentially seriously flawed conclusions that can result from such analyses, they should be replaced either by statistically appropriate (but more complex) approaches or, preferably, by analyses which investigate the dependence of the treatment effect on measured baseline characteristics of the patients in each trial.

Clinical Trials as Topic↗
PubMed1992

Meta-analysis: the fashion of summing-up evidence. Part II: Interpretations and uses.

In this commentary, we use evidence produced by the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) ten-year update of a meta-analysis of trials of adjuvant therapies for early breast cancer which started prior to 1985 to illustrate aspects of interpretations and uses of meta-analysis results. The following issues are discussed: i) The meta-analysis provides an average summary for the effect of a treatment. Greater statistical power is obtained by increasing the number of events contributing to the analysis. However, summing up the results of various trials necessitates the loss of individual information concerning the magnitude of treatment effects which depend on tumor- and patient-related factors. Subgroup analyses within the meta-analysis process allow some recovery of such features; ii) The absolute benefit obtained from an effective treatment depends not only on the relative benefit of the treatment but also on the prognosis of the individual patients; iii) The results are more immediately applicable if less reliance is placed on the arithmetic construct inherent in the overview, using instead unconfounded information about the value of treatments actually administered. This avoids the need to extrapolate the effect for one component of the therapy by assuming a lack of interaction with its other components; iv) Although indirect comparisons between different meta-analyses are regularly made to pick the "winner" from among tested treatment modalities, it is unlikely that the optimal therapeutic regimen can be defined via such indirect comparisons, though such comparisons may raise interesting, testable hypotheses.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Steroids for post-tonsillectomy pain reduction: meta-analysis of randomized controlled trials.

OBJECTIVES: To determine whether meta-analysis supports the use of corticosteroids to reduce post-tonsillectomy pain for pediatric patients. METHODS: A systematic review of currently available randomized controlled trials using a single-dose, intravenous corticosteroid during pediatric tonsillectomy was performed. Visual analog pain scale (VAS) data was extracted with reviewers blinded to results. Meta-analysis was performed with weighted mean difference and random-effects model using Revman 4.2 software. RESULTS: Eight randomized trials were included in analysis of post-tonsillectomy pain. A statistically significant reduction in pain as measured by VAS on postoperative day 1 was noted (mean VAS difference = -0.97; CI 95 % = -1.74,-0.19; P = 0.01). CONCLUSIONS: A single, intraoperative dose of dexamethasone may reduce post-tonsillectomy pain on postoperative day 1, by a factor of 1 on a 10-point pain scale. As the side effects and cost of dexamethasone dose appear negligible, consideration of routine use seems reasonable.

Anti-Inflammatory Agents↗
PubMed2006

Coffee and gastric cancer: systematic review and meta-analysis.

We systematically reviewed the literature on the association between coffee consumption and gastric cancer and performed a meta-analysis of the results. Published cohort and case-control studies were identified in PubMed and reference lists. Random effects meta-analysis was used to pool effects from 23 studies, and heterogeneity was explored by stratification and meta-regression. The odds ratio (OR) for the overall association between coffee and gastric cancer (highest vs. lowest category of exposure) was 0.97 (95%CI: 0.86-1.09), similar for cohort (OR = 1.02; 95%CI: 0.76-1.37) and case-control studies (population-based: OR = 0.90; 95%CI: 0.70-1.15; hospital-based: OR = 0.97; 95%CI: 0.83-1.13). The OR was 1.26 (95%CI: 1.02-1.57) when considering five studies conducted in the USA, 0.97 (95%CI: 0.82-1.14) for the five Japanese studies, 0.98 (95%CI: 0.81-1.17) for the six studies from Europe, and 0.64 (95%CI: 0.47-0.86) for the two studies from South America. In this meta-analysis we found no adverse effect of coffee associated with gastric cancer. Knowledge on the level of exposure to different coffee constituents may provide a deeper understanding of this reassuring result and the real role of coffee on cancer risk.

Coffee↗
PubMed1993

Meta-analysis of the effectiveness of current drug therapy of ulcerative colitis.

We have conducted a meta-analysis of 16 placebo-controlled trials of single drug therapy in ulcerative colitis (UC) for both induction (11 trials) and maintenance of remission (five trials). A total of 468 and 343 patients, respectively, was studied. Various clinical criteria of success were analyzed. The Dersimonian-Laird method for meta-analysis was used to calculate the risk difference. Therapeutic advantage, defined as the difference between drug and placebo response, was also determined. Using various criteria of success, single drug therapy for the induction of remission conferred a therapeutic advantage of 37-48% over placebo. In trials for maintenance of remission, the therapeutic advantage at 6 months was 21%, whereas at 12 months the therapeutic advantage rose to 46% because of a decline in placebo responders with time. In conclusion, meta-analysis has established a standard of reference against which future drug trials can be compared. This standard of reference for drug and placebo rates, as well as the corresponding therapeutic advantages, can help determine the relative value of newer agents in the therapy of UC.

Aminosalicylic Acids↗