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Primary vesicoureteric reflux as a predictor of renal damage in children hospitalized with urinary tract infection: a systematic review and meta-analysis.

Renal parenchymal disease after urinary tract infection (UTI) has been associated with the development of hypertension and renal functional impairment. A systematic literature review and meta-analysis was performed to determine how effectively the finding of primary vesicoureteric reflux (VUR) on micturating cystography (MCU) in children hospitalized with UTI predicted renal parenchymal disease on (99m)Technetium-dimercaptosuccinic acid ((99m)Tc-DMSA) scintigraphy. Medline, Embase, and PubMed were use to find reports with original data for children hospitalized with bacteriologically-proven UTI who had undergone both MCU and (99m)Tc-DMSA scintigraphy, and which also reported both positive and negative results of these tests. A meta-analysis of likelihood ratios positive and negative for MCU was then performed, including tests for heterogeneity. Twelve valid studies were found, seven with data for 537 children, with a positive (99m)Tc-DMSA scan prevalence of 59% overall, and seven studies with data for 1062 kidneys, with a positive (99m)Tc-DMSA scan prevalence of 36%. The likelihood ratio positive for MCU was 1.96 (95% CI, 1.51 to 2.54) for children, and 2.34 (1.53 to 3.57) for kidneys. The likelihood ratio negative was 0.71 (0.58 to 0.85) for children and 0.72 (0.61 to 0.86) for kidneys. There was evidence of heterogeneity. The meta-analysis showed that a positive MCU increases the risk of renal damage in hospitalized UTI patients by about 20%, whereas a negative MCU increases the chance of no renal involvement by just 8%. VUR is hence a weak predictor of renal damage in pediatric patients hospitalized with UTI. Physicians should be aware of the limitations of using MCU-detected primary VUR as an effective screening test for renal damage in this population. Furthermore, the pathogenesis of renal damage in such patients is probably complex because it is often detected without demonstrable VUR.

Child, Hospitalized↗

A functional M196R polymorphism of tumour necrosis factor receptor type 2 is associated with systemic lupus erythematosus: a case-control study and a meta-analysis.

OBJECTIVES: To perform a case-control study of a functional M196R polymorphism of tumour necrosis factor receptor type 2 (TNF-RII) in a Japanese population and a meta-analysis of all published reports on the polymorphism to investigate the association of the M196R polymorphism of TNF-RII with systemic lupus erythematosus (SLE). METHODS: The functional M196R polymorphism of TNF-RII was genotyped by using polymerase chain reaction combined with the subsequent single-strand conformation polymorphism (PCR-SSCP) analysis for screening, followed by nucleotide sequencing for confirmation. A total of 331 patients and 359 controls were subjected to a case-control study. A meta-analysis of the available case-control studies including all published data as well as our own data was performed to investigate the association of the functional M196R polymorphism of TNF-RII with SLE. RESULTS: Our case-control study did not show any significant association of a functional M196R polymorphism of TNF-RII with SLE, although there was a trend towards association. A meta-analysis of seven case-control studies in eight different ethnic populations including our own showed that 196M/R and 196R/R genotypes combined was significantly associated with an increased risk of SLE (odds ratio (OR) 1.29, 95% confidence interval (CI) 1.04 to 1.60; p = 0.02). Stratification by ethnicity showed a more significant association in Asians, including Japanese, Korean and Vietnamese (OR 1.40, 95% CI 1.10 to 1.78; p = 0.006). The effect of the 196R allele on SLE was not clear in Caucasians. CONCLUSIONS: The 196R allele of the functional M196R polymorphism of TNF-RII is a risk factor for SLE, especially in the Asian population.

Asian People↗

Risperidone versus haloperidol: I. Meta-analysis of efficacy and safety.

Haloperidol is widely considered a reference standard in antipsychotic therapy and is commonly used in comparative studies of the efficacy and safety of antipsychotic medication. Comparative clinical trials have shown that the novel antipsychotic agent risperidone tends to have greater efficacy (i.e., clinical response defined as a > or = 20% reduction in total scores on the Positive and Negative Syndrome Scale) than haloperidol in patients with chronic schizophrenia and poses less risk of extrapyramidal symptoms (EPS). We used DerSimonian and Laird's random-effects model to analyze pooled patient data from available randomized, double-masked, comparative trials of risperidone and haloperidol in patients with schizophrenia treated for at least 4 weeks at recommended doses. The purpose of the analysis was to determine whether there are significant overall differences in the rates of patient clinical response, prescription of anticholinergic agents, and treatment dropout. Six of the nine trials revealed in a literature search met all criteria for inclusion in the meta-analysis. The meta-analysis showed that in patients with chronic schizophrenia, risperidone therapy is associated with significantly higher response rates, significantly less prescribing of anticholinergic medication, and significantly lower treatment dropout rates than haloperidol. These results demonstrate the greater treatment efficacy associated with risperidone compared with haloperidol and suggest both a lower incidence of EPS and improved treatment compliance.

Antipsychotic Agents↗

Intraocular pressure-lowering effect of adding dorzolamide or latanoprost to timolol: a meta-analysis of randomized clinical trials.

OBJECTIVE: To estimate the intraocular pressure (IOP)-lowering effect of 2% dorzolamide or 0.005% latanoprost when added to 0.5% timolol. DESIGN: Meta-analysis of randomized clinical trials. PARTICIPANTS: Seventeen articles reporting on 19 study arms with 5 possible treatment combinations and 4 study arms serving as controls. METHODS: Articles written in English, German, French, or Dutch and published up to December 2004 were identified in Medline, Embase, the Cochrane Controlled Trials Register, and references from relevant articles. For the article to be considered, over 85% of the patients had to have primary open-angle glaucoma or ocular hypertension. The pooled 1- to 3-month additional IOP-lowering effect after a run-in phase on timolol was calculated by performing meta-analysis using the random effects model. MAIN OUTCOME MEASURES: Absolute and relative changes in IOP after run-in on timolol for peak moment, trough moment, or mean diurnal curve. RESULTS: The pooled change from baseline [mean (95% confidence interval)] for 0.5% timolol varied from -0.7 mmHg (-1.2 to -0.2, for the mean diurnal curve) to -2.0 mmHg (-1.3 to -2.7, at peak). Pooled changes for 2% dorzolamide in concomitant use with 0.5% timolol were -4.1 mmHg (-4.4 to -3.8) at trough and -4.9 mmHg (-5.3 to -4.5) at peak. The fixed 2% dorzolamide and 0.5% timolol combination resulted in a pooled change of -3.8 mmHg (-4.2 to -3.4) at trough and -4.9 mmHg (-5.3 to -4.5) at peak. The concomitant use of 0.005% latanoprost and 0.5% timolol gave a pooled change from baseline of -6.0 mmHg (-6.8 to -5.2) at the mean diurnal curve. The fixed combination of 0.005% latanoprost and 0.5% timolol resulted in a mean change of -3.0 mmHg (-3.8 to -2.2) at the mean diurnal curve. CONCLUSION: In this meta-analysis of clinical trials, the addition of dorzolamide or latanoprost further lowers IOP in eyes on timolol. This result may not be generalizable because these trials may have included nonresponders to timolol.

Antihypertensive Agents↗

Meta-analysis of operative techniques for fissure-in-ano.

PURPOSE: Operative techniques commonly used for fissure-in-ano include anal stretch, open lateral sphincterotomy, closed lateral sphincterotomy, posterior midline sphincterotomy, and to a lesser extent dermal flap coverage of the fissure. Reports of direct comparisons among these techniques are variable in their results and for the most part underpowered. A rigorous analysis of the combined reports was therefore undertaken to determine whether a preferred technique for fissure surgery can be elucidated. METHODS: MEDLINE was searched for all published reports using the key words "surgery" and "anal fissure." All reports in which there was a direct comparison between at least two operative techniques were reviewed, and when more than one report existed for any given pair, that report was included in the meta-analysis. If crude data were not presented in the report, the authors were contacted, and crude data were obtained. The two most commonly used end points in these reports were persistence of the fissure and postoperative incontinence of flatus. These are the only two end points included in the meta-analysis. The meta-analysis was performed using Epi-Info software obtained from the Centers for Disease Control and Prevention (www.cdc.gov). RESULTS: Seventeen publications fulfilled the criteria of the study, encompassing 2,727 patients. Significant differences were found for both persistence and incontinence to flatus when comparing anal stretch to all forms of sphincterotomy. No significant difference was found comparing open to closed lateral internal sphincterotomy for persistence or incontinence. Posterior midline sphincterotomy was not significantly different from lateral sphincterotomy related to persistence or incontinence. CONCLUSION: Internal anal sphincterotomy is superior to anal stretch and should probably be performed in the lateral location, although both the open and closed techniques seem equally efficacious.

Databases, Factual↗

The relative effects of maternal and child problems on the quality of attachment: a meta-analysis of attachment in clinical samples.

In this meta-analysis of 34 clinical studies on attachment the hypothesis is tested that maternal problems such as mental illness lead to more deviating attachment classification distributions than child problems such as deafness. A correspondence analysis on 21 North American studies with normal subjects produced a baseline against which the clinical samples could be evaluated. Separate analyses were carried out on studies containing the traditional A, B, C classifications and on studies that also included the recently discovered D or A/C category. Results show that groups with a primary identification of maternal problems show attachment classification distributions highly divergent from the normal distributions, whereas groups with a primary identification of child problems show distributions that are similar to the distributions of normal samples. The introduction of the D or A/C classifications (about 15% in normal samples) reveals an overrepresentation of D or A/C in the child problem groups, but the resulting distribution still is much closer to the normal distributions compared to the samples with maternal problems. In clinical samples, the mother appears to play a more important role than the child in shaping the quality of the infant-mother attachment relationship.

Child Behavior Disorders↗

A meta-analysis of bladder cancer and diesel exhaust exposure.

The aim of this study is to review and summarize the available epidemiologic studies of bladder cancer and occupational exposure to diesel exhaust. We retrieved relevant studies and abstracted their characteristics and results. We assessed the heterogeneity of the results to decide whether to perform a fixed-effects model meta-analysis. We identified 35 relevant studies. No overall meta-analysis was performed because of heterogeneity in results. Results of railroad workers (N = 14) suggested an increased occurrence of bladder cancer, but we did not conduct a meta-analysis. The summary relative risk (RR) among truck drivers was 1.17 (95% confidence interval [CI] = 1.06-1.29, 15 studies) and that among bus drivers was 1.33 (95% CI = 1.22-1.45, 10 studies). Ten studies considered diesel exhaust exposure based on a job exposure matrix or a similar approach; the summary RR for these studies was 1.13 (95% CI = 1.00-1.27). A positive dose-response relation was suggested by 10 of the 12 studies that provided relevant information. The summary RR for high diesel exposure was 1.44 (95% CI = 1.18-1.76). There was some evidence of publication bias, however, with a lack of small studies with null or negative results. Our review suggests that exposure to diesel exhaust may increase the occurrence of bladder cancer, but the effects of misclassification, publication bias, and confounding cannot be fully taken into account.

Europe↗

Major bleeding rates after prophylaxis against venous thromboembolism: systematic review, meta-analysis, and cost implications.

OBJECTIVES: The frequency and consequences of major bleeding associated with anticoagulant prophylaxis for prevention of venous thromboembolism is examined. METHODS: We conducted a systematic review and meta-analysis of controlled trials that reported rates of major bleeding after pharmaceutical thromboprophylaxis in patients undergoing major orthopedic surgery. Thromboprophylactic agents were divided into four groups: warfarin/other coumarin derivatives (WARF), unfractionated heparin (UFH), low molecular weight heparin (LMWH), and pentasaccharide (PS). Meta-analysis was conducted comparing LMWH with each of WARF, UFH, and PS. The frequency of re-operation due to major bleeding was reviewed and combined with published costs to estimate the mean cost of managing major bleeding events in these patients. RESULTS: Twenty-one studies including 20,523 patients met inclusion criteria for the meta-analysis. No evidence of significant between-trial heterogeneity in risk ratios was found. Combined (fixed effects) relative risks (RR) of major bleeding compared with LMWH were WARF--RR 0.59 (95 percent confidence interval [CI], 0.44-0.80); UFH--RR 1.52 (95 percent CI, 1.04-2.23); PS--RR 1.52 (95 percent CI, 1.11-2.09). Seventy-one studies including 32,433 patients were included in the review of consequences of major bleeding. We estimated that the average cost of major bleeding is 113 dollars per patient receiving thromboprophylaxis. CONCLUSIONS: LMWH results in fewer major bleeding episodes than UFH and PS but more than WARF. These events are costly and clinically important.

Anticoagulants↗

Meta-analysis of surgical versus non-surgical methods of treatment for periodontal disease.

A meta-analysis was performed on 5 randomized controlled trials comparing surgical with non-surgical treatment for periodontal disease. The specific procedures considered were the modified Widman flap compared with scaling and root planning or curettage with anesthesia. We chose the most consistently reported outcomes, pocket depth and attachment level, for analysis. At 1 year of follow-up, surgical treatment reduced pocket depth more than non-surgical for all initial levels of disease, but by 5 years, only the deepest initial pockets (> 7 mm) showed significant improvement over non-surgically treated teeth (0.51 mm reduction, p < 0.01). Attachment level showed significantly better early results for non-surgical treatment for less diseased teeth, but by 5 years, all significant differences had disappeared. We computed quality scores following a method described by Chalmers. The mean quality score for study data analysis and presentation was 0.37 +/- 0.009 and for the study protocol, the mean quality score was 0.19 +/- 0.002. We find that this meta-analysis supports findings relating response to therapy with initial level of disease severity. We also find that the choice of outcome measure influences the choice of therapy, with surgical therapy providing greater benefit for probing depth and non-surgical therapy providing greater benefit for attachment level. These results must be viewed, however, in light of the low quality scores of the evaluated studies and the potential for bias due to lack of binding, the small mean treatment differences, and the observer measurement variability.

Analysis of Variance↗

Prevalence of unruptured intracranial aneurysms according to comorbidities, risk factors, country, and time period: a systematic review and meta-analysis.

BACKGROUND: The incidence of aneurysmal subarachnoid haemorrhage declined between 1980 and 2010, which coincided with a decline in smoking and prevalence of hypertension. We aimed to investigate whether the decrease in subarachnoid haemorrhage incidence is paralleled by declines in unruptured intracranial aneurysm (UIA) prevalence. METHODS: For this systematic review and meta-analysis, we searched Embase, PubMed, and Web of Science for articles published in any language from Jan 1, 2011 to Dec 31, 2025, and reassessed 68 articles published before March 1, 2011 from a 2011 systematic review and meta-analysis. Articles were eligible for inclusion if they used a cross-sectional or case-control design and provided the crude number of participants and those with UIA. We only included studies reporting numbers of UIA separately from ruptured aneurysms and with ten or more patients. Summary data were independently extracted by JD with AZ or CB and conflicts were resolved by GJER. The primary outcome was proportion of participants with UIA. Relative to a hypothetical reference population (mean age 50 years, 50% women, and no comorbidities), age and/or sex-adjusted prevalence ratios (PRs) for regions, comorbidities, and risk ratios (RRs) for female sex, smoking, and hypertension were estimated using generalised linear mixed models. A time trend analysis was done by binomial meta regression using the mid-year of data acquisition. We assessed the certainty of evidence using GRADE. The study was registered with PROSPERO, number CRD420261296728. FINDINGS: Our search screened 4708 studies. 67 reassessed and 95 newly identified articles, reporting on 316&#x2008;131 participants and 11&#x2008;822 people with UIAs, were included in our meta-analysis. In the reference population, the estimated prevalence of UIAs was 3&#xb7;9% (95% CI 3&#xb7;0-5&#xb7;1). The prevalence of UIAs in individuals with atherosclerosis was 5&#xb7;5% (4&#xb7;7-6&#xb7;4; 2229 of 40970 participants) and the adjusted PR was 1&#xb7;3 (95% CI 0&#xb7;8-2&#xb7;0) compared with the reference population. For positive family history of aneurysmal subarachnoid haemorrhage (aSAH) or UIA, the UIA prevalence was 7&#xb7;9% (5&#xb7;6-11&#xb7;1; 412 of 4252 participants) and the adjusted PR was 2&#xb7;4 (0&#xb7;5-11&#xb7;2). For connective-tissue disorder, the UIA prevalence was 10&#xb7;3% (6&#xb7;5-16&#xb7;0; 94 of 879 participants) and the adjusted PR was 3&#xb7;9 (2&#xb7;0-7&#xb7;6). For autosomal dominant polycystic kidney disease (ADPKD), the UIA prevalence was 12&#xb7;8% (9&#xb7;2-17&#xb7;6; 293 of 1990 participants) and the adjusted PR was 4&#xb7;4 (1&#xb7;5-12&#xb7;6). RRs were for current smoking 1&#xb7;4 (1&#xb7;2-1&#xb7;6; 798 of 27911 participants), for having hypertension 1&#xb7;6 (1&#xb7;5-1&#xb7;7, 4043 of 83053 participants), and for female sex 1&#xb7;9 (1&#xb7;8-2&#xb7;0; 3415 of 65020 women and 2122 of 76130 men). In studies on healthy individuals with MR angiography or CT angiography as imaging modality, the prevalence in 2016-2022 was 6&#xb7;6% (6&#xb7;3-6&#xb7;8; 2904 of 41191 participants). The adjusted PR was 1&#xb7;8 (1&#xb7;1-2&#xb7;8) for 2016-2022 versus 2002-2015. Prevalence of UIAs of 5 mm or larger was 0&#xb7;7% (0&#xb7;6-0&#xb7;8) in 2002-2015 and 1&#xb7;4% (1&#xb7;0-1&#xb7;9) in 2016-2022. The UIA prevalence did not differ between countries. &#x3c4;2 showed significant heterogeneity between studies. The certainty of the evidence ranged from very low to moderate. INTERPRETATION: Prevalence of UIA is increasing, particularly over the past two decades. This increase is only in part explained by improved detection of small UIAs and an ageing population, and other factors-such as environmental-are likely involved. Alongside patients with ADPKD and a positive family history of aSAH, patients with connective-tissue disorders had a higher prevalence of UIA than the reference population. Our findings warrant further investigation into the potential benefit of personalised screening and management strategies in groups at high risk for having UIAs. FUNDING: None.

Humans↗

Exercise and bone mineral density at the femoral neck in postmenopausal women: a meta-analysis of controlled clinical trials with individual patient data.

OBJECTIVE: We conducted a meta-analysis using individual patient data to examine the efficacy of exercise for improving bone mineral density at the femoral neck in postmenopausal women. STUDY DESIGN: Ten controlled clinical trials that included 595 subjects (aged 42-92 years) met our criteria for inclusion. Changes in femoral neck bone mineral density were examined by 2-way analysis of variance tests with repeated measures on 1 factor. RESULTS: Across all designs and categories, there was an increase in bone mineral density of 0.73% +/- 5.52% and 0.45% +/- 6.78%, respectively, in the exercise and control subjects. However, comparison of initial and final bone mineral density values between exercise and control subjects revealed no statistically significant effect of exercise on femoral neck bone mineral density (P > .05). CONCLUSION: Collectively, the exercise protocols that were used in this individual patient data meta-analysis do not improve femoral neck bone mineral density in postmenopausal women.

Aged↗

Effect of physician reminders on preventive care: meta-analysis of randomized clinical trials.

The objective of this study was to assess the clinical value of the physician reminder, an information intervention, in increasing compliance for selected preventive health care measures. Meta-analysis was used to combine the quantitative evidence from randomized controlled clinical trials meeting the eligibility criteria. The trials included in this meta-analysis were conducted in a family or internal medicine clinic. Physician reminders were used in the trials to influence utilization and compliance of preventive health care activities. The use of physician reminders for preventive health care activities resulted in a homogeneous effect for the subcategories of cervical cancer screening (test for heterogeneity X2(2) = 4.122, non-significant) and tetanus immunization (test for heterogeneity X2(2) = 3.139, non-significant). Similarly, the odds ratio from the combination of evidence from the three cervical cancer screening trials was significant (1.180, 95 percent CI: 1.020 to 1.339). The resulting odds ratio from the combination of evidence from the three tetanus immunization trials was significant (2.819, 95 percent CI: 2.664 to 2.975). The results of the meta-analyses for cervical cancer screening and tetanus immunizations indicate that physician reminders are an effective information intervention and can improve compliance for these two preventive health care procedures. Based on the results of this meta-analysis, further trials testing the effect of physician reminders on tetanus immunization would be unnecessary and probably unethical.

Female↗

A meta-analysis of the published research on the effects of child sexual abuse.

A meta-analysis of the published research on the effects of child sexual abuse (CSA) was undertaken for 6 outcomes: posttraumatic stress disorder (PTSD), depression, suicide, sexual promiscuity, victim-perpetrator cycle, and poor academic performance. Thirty-seven studies published between 1981 and 1995 involving 25,367 people were included. Many of the studies were published in 1994 (24; 65%), and most were done in the United States (22; 59%). All six dependent variables were coded, and effect sizes (d) were computed for each outcome. Average unweighted and weighted ds for each of the respective outcome variables were .50 and .40 for PTSD, .63 and .44 for depression, .64 and .44 for suicide, .59 and .29 for sexual promiscuity, .41 and .16 for victim-perpetrator cycle, and .24 and .19 for academic performance. A file drawer analysis indicated that 277 studies with null ds would be required to negate the present findings. The analyses provide clear evidence confirming the link between CSA and subsequent negative short- and long-term effects on development. There were no statistically significant differences on ds when various potentially mediating variables such as gender, socioeconomic status, type of abuse, age when abused, relationship to perpetrator, and number of abuse incidents were assessed. The results of the present meta-analysis support the multifaceted model of traumatization rather than a specific sexual abuse syndrome of CSA.

Child↗

Atrial flutter and the risk of thromboembolism: a systematic review and meta-analysis.

PURPOSE: We conducted a systematic review and meta-analysis of observational studies to assess the risk of thromboembolism associated with atrial flutter. METHODS: MEDLINE, EMBASE, bibliographies, and consultation with clinical experts were used to identify studies that report the risk of thromboembolism associated with attempted cardioversion and longer-term risk in chronic atrial flutter. The review process and data extraction were performed by two reviewers. Study event rates were assessed graphically, and a chi-squared test was used to assess heterogeneity across studies. Meta-regression with weighted logistic regression was used to assess the association between study-level clinical factors and reported thromboembolic event rates. RESULTS: We found 13 studies that reported the risk of thromboembolism associated with cardioversion of atrial flutter. Short-term event rates ranged from 0% to 7.3%. A chi-squared test for heterogeneity was significant (P < 0.001), so results were not pooled. Instead, a meta-regression analysis was performed, which partly explained the heterogeneity across studies. Studies were more likely to report high event rates when they included patients with a prior history of thromboembolism, and to report lower event rates when at least some patients were anticoagulated or if patients underwent echocardiography before cardioversion. Four studies reported the longer-term risk of thromboembolism, and these suggest a yearly event rate of approximately 3% with sustained atrial flutter. CONCLUSION: These findings suggest that atrial flutter is indeed associated with an increased risk of thromboembolism, and that clinical factors account for the low event rates reported in some studies.

Atrial Flutter↗

Relapse prevention in schizophrenia with new-generation antipsychotics: a systematic review and exploratory meta-analysis of randomized, controlled trials.

OBJECTIVE: The authors performed a systematic review and meta-analysis of studies of the potential of new-generation antipsychotic drugs to improve adherence and decrease relapse rates in patients with schizophrenia. METHOD: Randomized, controlled trials comparing new-generation antipsychotic drugs with placebo and/or conventional antipsychotics were identified. Data on relapse, general treatment failure, and dropout due to adverse events were extracted and combined in a meta-analysis. RESULTS: Because few trials were available for each individual drug, the effects of new-generation antipsychotic drugs as a group were analyzed. The analysis of six placebo comparisons, involving a total of 983 patients, clearly demonstrated that new-generation antipsychotic drugs are effective for relapse prevention. Eleven studies with a total of 2,032 patients provided comparative data on relapse/treatment failure for new-generation and conventional antipsychotics. The analysis revealed that rates of relapse and overall treatment failure were modestly but significantly lower with the newer drugs. Whether this advantage was partly mediated by improved adherence to treatment remains unclear. No significant superiority in terms of fewer dropouts due to adverse events was found for the newer drugs. Furthermore, a number of methodological problems were identified. CONCLUSIONS: Overall, the currently available data suggest that new-generation antipsychotics have the potential to reduce relapse rates. Methodological issues to be addressed in future trials include the choice of comparator, use of appropriate doses, application of clinically relevant relapse criteria, monitoring of adherence, and minimization of dropouts.

Antipsychotic Agents↗

[VEGF and survival of patients with lung cancer: a systematic literature review and meta-analysis].

The process of angiogenesis is an important factor in tumour development. One of the principal factors implicated in this process is vascular endothelial growth factor (VEGF) which induces, among other things, an increase in vascular permeability. We have undertaken a systematic review of the English and French literature in order to clarify its effect on the survival of patients with small cell (SCLC) and non-small cell (NSCLC) lung cancer. To be eligible studies had to deal with the the evaluation of VEGF or its receptors in lung cancer and describe the relationship of their expression to survival. The survival figures were subject to meta-analysis after a methodological evaluation by means of a specific numerical scale evaluating the design of the study, the methodology (including laboratory techniques), and the analysis of results. Among the 20 studies selected 15 identified VEGF expression, using univariate analysis, as a statistically significant indicator of poor prognosis. 17 reported sufficient data to allow aggregation of the survival figures, of which 15 were devoted to NSCLC (1,549 patients). The median overall methodological score was 48.3% (range 21.8-72.4%), without significant difference (p=0.63) between studies eligible or non-eligible for meta-analysis. The meta-analysis, using the authors' threshold of positivity for VEGF, showed that VEGF is an unfavourable prognostic factor in NSCLC (HR=1.48; 95% confidence interval 1.27-1.72). The data were insufficient to determine the prognostic value of VEGF in SCLC and that of its two receptors Flt-1 and KDR, with 1, 2 and 1 published studies respectively. In conclusion the expression of VEGF in MSCLC is a factor indicating a poor prognosis.

Carcinoma, Non-Small-Cell Lung↗

Otitis media and speech and language: a meta-analysis of prospective studies.

OBJECTIVE: Considerable controversy surrounds whether a history of otitis media with effusion (OME) in early childhood causes later speech and language problems. We conducted a meta-analysis of prospective studies to determine: 1) whether a history of OME in early childhood is related to receptive language, expressive language, vocabulary, syntax, or speech development in children 1 to 5 years old and 2) whether hearing loss caused by otitis media in early childhood is related to children's receptive language or expressive language through 2 years of age. METHODS: We searched online databases and bibliographies of OME studies and reviews for prospective or randomized clinical trials published between January 1966 and October 2002 that examined the relationship of OME or OME-associated hearing loss in early childhood to children's later speech and language development. The original search identified 38 studies, of which 14 had data suitable for calculating a pooled correlation coefficient (correlational studies) or standard difference between parallel groups (group studies). Random-effects meta-analysis was used to pool data when at least 3 studies had usable data for a particular outcome. RESULTS: We performed 11 meta-analyses. There were no significant findings for the analyses of OME during early childhood versus receptive or expressive language during the preschool years in the correlation studies. Similarly, there were no significant findings for OME versus vocabulary, syntax, or speech during the preschool years. Conversely, there was a significant negative association between OME and preschoolers' receptive and expressive language (lower language) (0.24 and 0.25 standard difference, respectively) in the group studies. Additionally, hearing was also related to receptive and expressive language in infancy (3%-9% of variance). CONCLUSIONS: Our results indicate no to very small negative associations of OME and associated hearing loss to children's later speech and language development. These findings may overestimate the impact of OME on outcomes, because most studies did not adjust for known confounding variables (such as socioeconomic status) and excluded data not suitable for statistical pooling, especially from methodologically sound studies. Although some OME language differences were detectable by meta-analysis due to increased statistical power, the clinical relevance for otherwise healthy children is uncertain.

Child, Preschool↗

A meta-analysis of occupational trichloroethylene exposure and multiple myeloma or leukaemia.

BACKGROUND: Trichloroethylene (TCE) has been widely used as an industrial solvent and degreasing agent. AIMS: We conducted a meta-analysis of epidemiologic studies of occupational TCE exposure and multiple myeloma (MM) or leukaemia. METHODS: We identified a total of eight cohort or case-control studies that enumerated a TCE-exposed study population and presented relative risk (RR) estimates for MM (n = 7) and/or leukaemia (n = 7). The individual studies included aerospace or aircraft workers (n = 3 studies), workers from a transformer manufacturing plant (n = 1 study) and workers from numerous occupations who, based on biomonitoring or extensive industrial hygiene exposure measurements, were likely exposed to TCE (n = 4). We used random effects models to calculate summary relative risk estimates (SRRE). In addition, we examined heterogeneity across studies and the relative influence of each individual study on the overall meta-analysis. RESULTS: No association was observed for MM (SRRE = 1.05, 95% CI: 0.80-1.38; P value for heterogeneity = 0.94) or leukaemia (SRRE = 1.11, 95% CI: 0.93-1.32; P value for heterogeneity = 0.50), based on TCE-exposed subgroup meta-analyses. Study-specific RR estimates for MM ranged between 0.57 and 1.62. RRs for leukaemia ranged between 1.05 and 1.15 in five studies, while one study reported a 2-fold increased RR and another study reported an inverse association of 0.60. All confidence intervals (CIs) for study-specific estimates included 1.0. CONCLUSIONS: The results of this meta-analysis do not support an etiologic association between occupational TCE exposure and risk of MM or leukaemia.

Aerospace Medicine↗