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A systematic review and meta-analysis of the sex ratio for Barrett's esophagus, erosive reflux disease, and nonerosive reflux disease.

Barrett's esophagus is associated with reflux disease and substantially increases the risk of esophageal adenocarcinoma. The authors undertook a systematic review and meta-analysis of the sex ratio for Barrett's esophagus, erosive reflux disease (ERD), and nonerosive reflux disease (non-ERD) to compare these results with the sex ratio for esophageal adenocarcinoma. MEDLINE (US National Library of Medicine, Bethesda, Maryland) (1966-2004) and EMBASE (Reed Elsevier PLC, Amsterdam, Netherlands) (1980-2004) were searched for relevant citations with a highly sensitive search strategy. Studies to be included required a sample size of 50 or more patients and consecutive recruitment at an institute accessible by all. Stata, version 8.2, software (StataCorp LP, College Station, Texas) was used to conduct random effects meta-analyses. Excess heterogeneity was investigated by meta-regression. The Barrett's esophagus meta-analysis gave an overall pooled male/female sex ratio of 1.96/1 (95% confidence interval (CI): 1.77, 2.17/1). For ERD, the pooled male/female sex ratio was 1.57/1 (95% CI: 1.40, 1.76/1) and, for non-ERD, 0.72/1 (95% CI: 0.62, 0.84/1). All of these estimates were associated with substantial heterogeneity (I2 = 81.1%, 92.7%, and 88.8%, respectively). The meta-analysis estimates for ERD and Barrett's esophagus, while showing an excess of males, are substantially lower than similar estimates for esophageal adenocarcinoma. It is important to establish why male Barrett's esophagus and ERD patients are at increased risk of malignancy compared with females.

Adenocarcinoma↗

Early neonatal dexamethasone treatment for prevention of bronchopulmonary dysplasia. Randomised trial and meta-analysis evaluating the duration of dexamethasone therapy.

UNLABELLED: The aim of the aborted trial was to determine whether the short early dexamethasone (DX) given after the birth improves the early outcome. We also reviewed the evidence (meta-analysis) to determine whether the duration of early DX treatment influences the early outcome, particularly in terms of bronchopulmonary dysplasia (BPD). The participants of the randomised multicentre, double-blinded placebo-controlled trial had a birth weight 500-999 g, gestation < or = 31.0 weeks, and respiratory failure by the age of 4 h. The infants received either four doses of DX (0.25 mg/kg at 12 h intervals) or placebo. The meta-analysis was performed to determine the beneficial and adverse effects of early short (<96 h duration) versus early prolonged (>96 h) DX treatment. The trial was discontinued after 109 infants had been enrolled. There was a non-significant improvement in the outcome (survival without BPD, severe intracranial haemorrhage or periventricular leukomalacia; RR 1.27; 95% CI 0.87-1.85). The risks for gastrointestinal perforation and hyperglycaemia tended to increase. A total of 15 trials were included in the meta-analysis: 10 involved prolonged (i.e. >96 h; 1594 infants) and five short interventions (1069 infants). Early prolonged DX decreased the RR for BPD to 0.72 (95% CI 0.61-0.87), whereas early short DX course did not significantly decrease the risk (RR 0.82; 95% CI 0.64-1.05). Gastrointestinal haemorrhages and perforations were significantly increased only in the early prolonged DX group. CONCLUSION: The dosage and duration of early corticosteroid given to small premature infants influences the risk of the side-effects and the early outcome.

Anti-Inflammatory Agents↗

Use of topical sunscreen and the risk of malignant melanoma. Results of a meta-analysis of 9,067 patients.

PURPOSE: Prior epidemiological studies suggest that the use of sunscreen preparations is associated with increased risk of cutaneous malignant melanoma (CMM) although the data are conflicting. A meta-analysis was performed to evaluate this suspected association.METHODS: A protocol was developed for a meta-analysis examining the association between frequent sunscreen use versus non-use and the development of CMM. Data from observational studies were pooled using a general variance based meta-analytic method employing confidence intervals. The outcome of interest was a summary relative risk (RRs) reflecting the risk of melanoma associated with sunscreen use versus non-use. Sensitivity analyses were performed when necessary to explain any observed statistical heterogeneity.RESULTS: Eleven case-control studies enrolling 9,067 patients were combined in a meta-analysis. This yielded a RRs of 1.11 (CI = 0.37-3.32), a non-statistically significant result, (i.e. no association between sunscreen use and melanoma risk). Since the data were found to be heterogeneous, i.e. Q = 42.0 (p < 0.001), a series of sensitivity analyses were performed to explore possible sources of heterogeneity. Stratifying studies based on study design, i.e. hospital based versus population based, showed that hospital derived data were highly heterogeneous (Q = 36.9, p < 0.001) while the population registry data were not (Q = 4.9, p = 0.18). Combining those studies using population based data gave a RRs of 1.01 (95% CI = 0.46-2.28) indicating no association between sunscreen use and the development of CMM.CONCLUSIONS: The available epidemiological data do not support the existence of a relationship between topical sunscreen use and an increased risk of CMM.

Journal Article↗

Effectiveness of specific immunotherapy in the treatment of asthma: a meta-analysis of prospective, randomized, double-blind, placebo-controlled studies.

BACKGROUND: Despite decades of positive experience with specific immunotherapy (SIT) in the treatment of asthma, outcomes associated with SIT have not been evaluated. OBJECTIVE: This meta-analysis was conducted to compare the effects of SIT plus medical treatment with those of SIT without medical treatment in patients with asthma. METHODS: All studies of SIT in patients with asthma published in English between the years 1966 and 1998 were identified through a MEDLINE search. All prospective, randomized, double-blind, placebo-controlled studies of SIT identified by the search were included in the meta-analysis. One author (R.N.R.) extracted data from these studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model. RESULTS: Data were extracted from 24 identified studies of the clinical effectiveness of SIT in the treatment of asthma, involving 962 asthmatic patients with documented allergy. Immunotherapy was judged effective in 17 (71%) of the 24 studies, ineffective in 4 (17%), and equivocal in 3 (12%) (chi2 = 15.25, df = 2, P = 0.0005). Symptoms of asthma were more likely to improve in patients who received SIT than in patients who received placebo (OR 2.76, 95% CI 2.22 to 3.42). Results also favored the immunotherapy group for improvement in pulmonary function (OR 2.87, 95% CI 1.82 to 4.52), protection against bronchial challenge (OR 1.81, 95% CI 1.32 to 2.49), and reduced need for medications (OR 2.00, 95% CI 1.46 to 2.72). CONCLUSION: The findings of this meta-analysis support the conclusion that SIT is effective in a population of patients with allergen-triggered asthma.

Adolescent↗

Meta-analysis of local tetracycline in treating chronic periodontitis.

BACKGROUND: Meta-analysis was used to assess the clinical efficacy of local delivery of tetracycline alone or as an adjunct to conventional mechanical therapy in patients with chronic periodontitis. METHODS: Studies were identified in MEDLINE and others sources. Meta-analyses were performed on the basis of probing depth (PD) at baseline, type of antimicrobial used, and experimental and control regimens (i.e., tetracycline plus scaling and root planing [SRP] versus SRP, tetracycline versus SRP, and tetracycline versus placebo, or no treatment). The effect of local tetracycline was evaluated for follow-up times of 4, 8, 12, 16, 24, and 36 weeks. Sensitivity analysis was performed according to antimicrobial delivery mode (irrigation, fibers, strips). A random effects model was used. RESULTS: The literature search identified 29 studies that met our inclusion criteria and were entered Into the meta-analysis. A significant mean reduction in PD for the combined tetracycline and SRP was observed regardless of initial probing depth and independently to the duration of follow-up. Tetracycline alone did not perform better than SRP, whereas they performed significantly better than placebo. Differences in improvement of attachment level (AL) were substantially similar to those encountered for PD. CONCLUSIONS: Our results documented that local. delivery of tetracycline improves the clinical outcomes of traditional treatment and should be considered particularly as an adjunct to SRP. Considerations regarding the adverse effects of widespread use of tetracycline should be taken into account when choosing a therapeutic strategy of chronic periodontitis.

Administration, Topical↗

A meta-analysis of non-Hodgkin's lymphoma among farmers in the central United States.

A meta-analysis of studies examining the association between non-Hodgkin's lymphoma (NHL) and employment as a farmer in the central United States was performed to verify the observation by Blair et al. [1993] that this group is at excess risk of NHL. Six studies were selected for the meta-analysis, and the estimator of relative risk calculated was 1.34 (95% confidence interval (CI) = 1.17, 1.55). Exposures associated with NHL and associated with agricultural commodities frequently produced in the central United States are infectious microorganisms and pesticides. Examination of the production patterns of the farms in this region did not reveal a single specific risk factor consistently found on all farms; however, past production patterns suggest that exposure to either infectious microorganisms or pesticides might be a risk factor for NHL in this group of farmers.

Agricultural Workers' Diseases↗

Comparative effectiveness of full-length and B-domain deleted factor VIII for prophylaxis--a meta-analysis.

Recently reported data suggest the possibility of differences in clinical efficacy between full-length factor VIII (FL-FVIII) and B-domain deleted recombinant factor VIII (BDD-rFVIII). To address this question, we conducted a meta-analysis of studies reporting the incidence of bleeding under prophylaxis, as well as studies of FL-FVIII and BDD-rFVIII half-life. The pooled cumulative weekly prophylactic dose of BDD-rFVIII (81.3 +/- 13.8 IU kg(-1) week(-1)) was greater by 36% (P = 0.11) than that of FL-FVIII (60.0 +/- 5.9 IU kg(-1) week(-1)). The pooled incidence of bleeding in BDD-rFVIII recipients [16.8 bleeds per patient year; confidence interval (CI), 9.5-24.2 bleeds per patient year] was more than 2.5-fold larger (P < 0.0005) than that in patients receiving FL-FVIII (6.6 bleeds per patient year; CI, 4.7-8.5 bleeds per patient year). In a multivariate analysis, the incidence rate ratio was 2.10 (CI, 1.98-2.24), indicating that breakthrough bleeding under prophylaxis was more than twice as likely with BDD-rFVIII than FL-FVIII at equivalent doses and ages. The pooled half-life for plasma-derived FL-FVIII (13.7 h; CI, 12.8-14.6 h) was closely similar to that for recombinant FL-FVIII (14.3 h; CI, 13.3-15.4 h). By contrast, the pooled half-life for BDD-rFVIII (11.3 h; CI, 9.9-12.7 h) was shorter by approximately 3 h compared with FL-FVIII. Although the results of the meta-analysis need to be interpreted with caution, the pooled data suggest that breakthrough bleeding under prophylaxis may occur more frequently in patients receiving BDD-rFVIII than FL-FVIII and may at least partly reflect a more abbreviated half-life of BDD-rFVIII. Several biochemical differences between BDD-rFVIII and FL-FVIII may underlie the observed disparities in bleeding incidence and half-life. This meta-analysis should be confirmed by further studies.

Adolescent↗

The efficacy of hospitalization of nonorganic failure-to-thrive children: a meta-analysis.

This study ascertained the efficacy of hospitalization of children with nonorganic failure to thrive (NOFTT). A meta-analysis was performed on previously published research findings which met certain criteria for inclusion in the analysis. Two categories of outcome measures, physical growth pattern and psychosocial development, were quantitatively synthesized separately using standard meta-analytic techniques. Hospitalization was found to significantly enhance the probability of sustained catch-up physical growth among NOFTT children, but only a comparatively small effect size for hospitalization on their psychosocial development was documented. There remains need for prospective longitudinal study of effectiveness in treating NOFTT children. But meta-analysis is a powerful technique which introduces scientific rigor to the review of study results, none of which is singularly conclusive.

Child Development↗

Association of Pro12Ala polymorphism in peroxisome proliferator-activated receptor gamma with Pre-diabetic phenotypes: meta-analysis of 57 studies on nondiabetic individuals.

OBJECTIVE: The provariant of the Pro12Ala polymorphism in peroxisome proliferator-activated receptor (PPAR)gamma has been identified as a risk allele for type 2 diabetes. The purpose of the present study was to reveal a significant association with pre-diabetic phenotypes in nondiabetic individuals based on a systematic meta-analysis of all available published evidence. RESEARCH DESIGN AND METHODS: We performed a classical meta-analysis of data from approximately 32,000 nondiabetic subjects in 57 studies to assess the effect of the Pro12Ala polymorphism on pre-diabetic traits. RESULTS: In the global comparison, there were no differences in BMI, glucose, insulin, or homeostasis model assessment of insulin resistance between the Pro/Pro and X/Ala genotype. However, in the Caucasian subgroup, the X/Ala genotype was associated with significantly increased BMI. In the obese subgroup (BMI >30 kg/m(2)), fasting glucose (P = 0.041) and insulin resistance (by homeostasis model analysis) (P = 0.020) were significantly greater in the Pro/Pro group. In subjects with the homozygous Ala/Ala genotype, fasting insulin was significantly lower compared with the Pro/Pro genotype (P = 0.040, N(Ala/Ala) = 154). CONCLUSIONS: Across all studies, the Pro12Ala polymorphism had no significant effect on diabetes-related traits. Only in selected subgroups, such as Caucasians and obese subjects, did we see an association of the Ala allele with greater BMI and greater insulin sensitivity. This demonstrates the importance for appropriate stratification of analyses by environmental or other genetic factors. Meta-analysis of Ala/Ala homozygotes more clearly demonstrated the association with greater insulin sensitivity of carriers of the Ala allele.

Genetic Predisposition to Disease↗

Breast-feeding and cancer: the Boyd Orr cohort and a systematic review with meta-analysis.

BACKGROUND: Having been breast-fed has been suggested to influence cancer risk in adulthood. We investigated associations between breast-feeding during infancy and adult cancer incidence and mortality in a cohort study and meta-analyses of published studies. METHODS: The Boyd Orr cohort consisted of 4999 subjects who were originally surveyed in 1937-39, when they were 0-19 years of age. Cancer outcomes from 1948 through 2003 were available for 4379 (88%) subjects, and 3844 had complete data on all covariates. Associations of breast-feeding with cancer were investigated using proportional hazards models. We also identified 14 studies on infant feeding and cancer published from 1966 through July 2005, of which 10 could be combined with the Boyd Orr cohort results in a meta-analysis of breast cancer using random-effect models. RESULTS: In the Boyd Orr cohort, ever having been breast-fed, compared with never having been breast-fed, was not associated with the incidence of all cancers (hazard ratio [HR] = 1.07, 95% confidence interval [CI] = 0.89 to 1.28) or of any individual cancer type examined (prostate HR = 1.43, 95% CI = 0.58 to 3.52; breast HR = 1.62, 95% CI = 0.89 to 2.94; colorectal HR = 0.86, 95% CI = 0.45 to 1.63; gastric HR = 1.22, 95% CI = 0.47 to 3.15). In the meta-analysis, there was also no association between breast-feeding and breast cancer (regardless of menopausal status) (relative risk [RR] = 0.94, 95% CI = 0.85 to 1.04). However, breast-fed women had a reduced risk of premenopausal breast cancer (RR = 0.88, 95% CI = 0.79 to 0.98) but not of postmenopausal breast cancer (RR = 1.00, 95% CI = 0.86 to 1.16). CONCLUSION: Ever having been breast-fed was not associated with overall breast cancer risk, although the meta-analysis revealed a reduced risk of premenopausal breast cancer in women who had been breast-fed.

Adult↗

High-dose chemotherapy followed by autologous stem cell transplantation as first-line therapy in aggressive non-Hodgkin's lymphoma: a meta-analysis.

BACKGROUND AND OBJECTIVES: High-dose chemotherapy followed by autologous stem cell transplantation (HDT/ASCT) has proven to be superior to conventional chemotherapy in patients with chemosensitive relapse of aggressive non-Hodgkin's lymphoma (NHL). Therefore, HDT/ASCT was evaluated as part of first-line therapy. Several trials generated conflicting results. This meta-analysis summarizes the available evidence from all suitable studies. DESIGN AND METHODS: Prospective, randomized trials with HDT/ASCT as first-line therapy of aggressive lymphoma were included in this meta-analysis. The primary outcome was overall mortality. Statistical analysis applied the odds ratio (OR) and a fixed effects model. RESULTS: Eleven trials with 2228 patients were eligible for meta-analysis. Overall mortality was comparable in the HDT/ASCT and in control arms (OR=0.97, 95% CI: 0.69;1.36, p=0.9), with statistically significant heterogeneity between the trials. To resolve this, we tried to identify variables that could explain this heterogeneity. Among a range of methodological, patient- or treatment-related factors, subgroups formed by the proportion of bulky disease in treated patients, the type of therapy prior to HDT/ASCT, the drop-out rate from the HDT/ASCT arm, and the presence of high or high-intermediate risk IPI showed significant benefit for any of the treatment modalities. However, such post-hoc subgroup analysis may be considerably influenced by random or systemic biases. INTERPRETATION AND CONCLUSIONS: Overall, the analysis of published evidence reveals very heterogeneous results and no overall survival benefit. Therefore, HDT/ASCT cannot be recommended as standard first line treatment for patients with aggressive NHL. However, the exploratory analyses presented here may help to design new trials for this treatment modality.

Adolescent↗

Multiple-outcome meta-analysis of clinical trials.

When several clinical trials report multiple outcomes, meta-analyses ordinarily analyse each outcome separately. Instead, by applying generalized-least-squares (GLS) regression, Raudenbush et al. showed how to analyse the multiple outcomes jointly in a single model. A variant of their GLS approach, discussed here, can incorporate correlations among the outcomes within treatment groups and thus provide more accurate estimates. Also, it facilitates adjustment for covariates. In our approach, each study need not report all outcomes nor evaluate all treatments. For example, a meta-analysis may evaluate two or more treatments (one 'treatment' may be a control) and include all randomized controlled trials that report on any subset (of one or more) of the treatments of interest. The analysis omits other treatments that these trials evaluated but that are not of interest to the meta-analyst. In the proposed fixed-effects GLS regression model, study-level and treatment-arm-level covariates may be predictors of one or more of the outcomes. An analysis of rheumatoid arthritis data from trials of second-line drug treatments (used after initial standard therapies prove unsatisfactory for a patient) motivates and applies the method. Data from 44 randomized controlled trials were used to evaluate the effectiveness of injectable gold and auranofin on the three outcomes tender joint count, grip strength, and erythrocyte sedimentation rate. The covariates in the regression model were quality and duration of trial and baseline measures of the patients' disease severity and disease activity in each trial. The meta-analysis found that gold was significantly more effective than auranofin on all three treatment outcomes. For all estimated coefficients, the multiple-outcomes model produced moderate changes in their values and slightly smaller standard errors, to the three separate outcome models.

Antirheumatic Agents↗

Sildenafil (Viagra) for male erectile dysfunction: a meta-analysis of clinical trial reports.

BACKGROUND: Evaluation of company clinical trial reports could provide information for meta-analysis at the commercial introduction of a new technology. METHODS: Clinical trial reports of sildenafil for erectile dysfunction from September 1997 were used for meta-analysis of randomised trials (at least four weeks duration) and using fixed or dose optimisation regimens. The main outcome sought was an erection, sufficiently rigid for penetration, followed by successful intercourse, and conducted at home. RESULTS: Ten randomised controlled trials fulfilled the inclusion criteria (2123 men given sildenafil and 1131 placebo). NNT or NNH were calculated for important efficacy, adverse event and discontinuation outcomes. Dose optimisation led to at least 60% of attempts at sexual intercourse being successful in 49% of men, compared with 11% with placebo; the NNT was 2.7 (95% confidence interval 2.3 to 3.3). For global improvement in erections the NNT was 1.7 (1.6 to 1.9). Treatment-related adverse events occurred in 30% of men on dose optimised sildenafil compared with 11% on placebo; the NNH was 5.4 (4.3 to 7.3). All cause discontinuations were less frequent with sildenafil (10%) than with placebo (20%). Sildenafil dose optimisation gave efficacy equivalent to the highest fixed doses, and adverse events equivalent to the lowest fixed doses. CONCLUSION: This review of clinical trial reports available at the time of licensing agreed with later reviews that had many more trials and patients. Making reports submitted for marketing approval available publicly would provide better information when it was most needed, and would improve evidence-based introduction of new technologies.

Erectile Dysfunction↗

Cumulative meta-analysis of systemic antifungal agents for the treatment of onychomycosis.

BACKGROUND: Onychomycosis is a common nail disease that is often chronic, difficult to eradicate, and has a tendency to recur. The most common oral therapies for dermatophyte toenail onychomycosis include terbinafine, itraconazole and fluconazole. OBJECTIVES: A cumulative meta-analysis of the randomized controlled trials (RCTs) for antimycotic agents was performed to determine whether the pooled estimate of the cure rates has remained consistent over the years. Furthermore, for each agent we compared the overall meta-analytical average of both mycological and clinical response rates of RCTs vs. open studies. METHODS: We searched MEDLINE (1966 to November 2002) for relevant studies evaluating the efficacy of the oral antifungal agents terbinafine, itraconazole (pulse or continuous), fluconazole and griseofulvin for treating dermatophyte toenail onychomycosis. Studies included in this meta-analysis required a standard accepted dosage regimen, treatment duration and follow-up period. To determine the cumulative meta-analytical average, studies were sequentially pooled by adding one study at a time according to the date of publication (i.e. earliest to the most recent). RESULTS: There were 36 studies included in the analyses. For RCTs the change in efficacy of mycological cure rates from the first trial to the overall cumulative meta-average for each drug comparator is as follows (with 95% confidence interval): terbinafine, 78 +/- 6% (n = 2 studies, 79 patients) to 76 +/- 3% (n = 18 studies, 993 patients) (P = 0.68); itraconazole pulse, 75 +/- 10% (n = 1 study, 20 patients) to 63 +/- 7% (n = 6 studies, 318 patients) (P = 0.25); itraconazole continuous, 63 +/- 5% (n = 1 study, 84 patients) to 59 +/- 5% (n = 7 studies, 1131 patients) (P = 0.47); fluconazole, 53 +/- 6% (n = 1 study, 72 patients) to 48 +/- 5% (n = 3 studies, 131 patients) (P = 0.50); and griseofulvin, 55 +/- 8% (n = 2 studies, 109 patients) to 60 +/- 6% (n = 3 studies, 167 patients) (P = 0.41). The cumulative meta-analytical average of mycological cure rates when comparing RCTs vs. open studies was: terbinafine, 76 +/- 3% (n = 18 studies, 993 patients) vs. 83 +/- 12% (n = 2 studies, 391 patients) (P = 0.0028); itraconazole pulse, 63 +/- 7% (n = 6 studies, 318 patients) vs. 84 +/- 9% (n = 3 studies, 194 patients) (P = 0.0001); and fluconazole, 48 +/- 5% (n = 3 studies, 131 patients) vs. 79 +/- 3% (n = 3 studies, 208 patients) (P = 0.0001). CONCLUSIONS: The cumulative meta-analysis of cure rates for RCTs suggests that over time, as new RCTs have been conducted, the efficacy rates have remained consistent. The efficacy rates of open studies are substantially higher compared with RCTs and may therefore overestimate cure rates.

Antifungal Agents↗

Genetic architecture of flowering time in maize as inferred from quantitative trait loci meta-analysis and synteny conservation with the rice genome.

Genetic architecture of flowering time in maize was addressed by synthesizing a total of 313 quantitative trait loci (QTL) available for this trait. These were analyzed first with an overview statistic that highlighted regions of key importance and then with a meta-analysis method that yielded a synthetic genetic model with 62 consensus QTL. Six of these displayed a major effect. Meta-analysis led in this case to a twofold increase in the precision in QTL position estimation, when compared to the most precise initial QTL position within the corresponding region. The 62 consensus QTL were compared first to the positions of the few flowering-time candidate genes that have been mapped in maize. We then projected rice candidate genes onto the maize genome using a synteny conservation approach based on comparative mapping between the maize genetic map and japonica rice physical map. This yielded 19 associations between maize QTL and genes involved in flowering time in rice and in Arabidopsis. Results suggest that the combination of meta-analysis within a species of interest and synteny-based projections from a related model plant can be an efficient strategy for identifying new candidate genes for trait variation.

Chromosome Mapping↗

Angiotensin-I converting enzyme insertion/deletion polymorphism and its association with diabetic nephropathy: a meta-analysis of studies reported between 1994 and 2004 and comprising 14,727 subjects.

AIMS/HYPOTHESIS: The ACE insertion/deletion polymorphism has been examined for association with diabetic nephropathy over the past decade with conflicting results. To clarify this situation, we conducted a comprehensive meta-analysis encompassing all relevant studies that were published between 1994 and 2004 and investigated this potential genetic association. METHODS: A total of 14,727 subjects from 47 studies was included in this meta-analysis. Cases (n=8,663) were type 1 or 2 diabetic subjects with incipient (microalbuminuria) or advanced diabetic nephropathy (proteinuria, chronic renal failure, end-stage renal disease). Control subjects (n=6,064) were predominantly normoalbuminuric. RESULTS: No obvious publication bias was detected. Using a minimal-case definition based on incipient diabetic nephropathy, subjects with the II genotype had a 22% lower risk of diabetic nephropathy than carriers of the D allele (pooled odds ratio [OR]=0.78, 95% CI=0.69-0.88). While there was a reduced risk of diabetic nephropathy associated with the II genotype among Caucasians with either type 1 or type 2 diabetes, the association was most marked among type 2 diabetic Asians (Chinese, Japanese, Koreans) (OR=0.65, 95% CI=0. 51-0.83). This OR is significantly different from the OR of 0.90 (95% CI= 0.78-1.04) that was obtained for type 2 diabetic Caucasians (p=0.019). Using a stricter case definition based on advanced diabetic nephropathy, a comparable risk reduction of 24-32% was observed among the three subgroups, although statistical significance was reached only among Asians. CONCLUSIONS/INTERPRETATION: The results of our meta-analysis support a genetic association of the ACE Ins/Del polymorphism with diabetic nephropathy. These findings may have implications for the management of diabetic nephropathy using ACE inhibitors especially among type 2 diabetic Asians.

Case-Control Studies↗

Aging and the negative priming effect: a meta-analysis.

This article reports results from a meta-analysis on adult age differences in the negative priming effect (21 studies on identity negative priming and 8 on location negative priming). Both younger and older adults were found to be susceptible to the negative priming effect in identity and location tasks. Effect sizes were homogeneous for both tasks, indicating that the data are adequately described without reference to moderator variables. State trace analysis on identity tasks, in which mean latencies in negative priming conditions were regressed onto mean latencies in baseline conditions, showed (a) that in both age groups the negative priming effect is proportional rather than additive and (b) that the negative priming effect is smaller in older adults as compared with younger adults.

Adult↗

Association of paraoxonase 1 gene polymorphisms with risk of Parkinson's disease: a meta-analysis.

Paraoxonase1 (PON1) gene polymorphisms were implicated as risk factors for Parkinson's disease (PD), but the results of case-control studies that investigated these associations were controversial. In order to provide an answer to these contradictory results, a meta-analysis of all available studies relating the PON1-55M/L and PON1-192Q/R polymorphisms to the risk of developing PD was conducted. The racial descent of the populations in these studies was Caucasian and Asian. The meta-analysis revealed that there was an association of the PON1-55M allele and the risk of developing PD relative to the L allele: fixed effects pooled odds ratio (OR)=1.32 [95%CI (1.10-1.59)]. In addition, there was evidence of association for the genotypic contrast PON1-55MM+LM relative to PON1-55LL: fixed effects OR=1.50 [95%CI (1.16-1.95)]. There was no significant association between PON1-192Q/R alleles and risk of developing PD: OR=1.09 [95%CI (0.93-1.26)]. There was no evidence for an association between the genotypic contrasts of PON1-192 and development of PD. The heterogeneity between studies and the publication bias were not significant ( P> or =0.10) in either polymorphism. Therefore, the pooled results of the meta-analysis supported that there was an association between PON1-55M/L polymorphism and PD and that PON1-192Q/R polymorphism was unlikely to be a major risk factor for susceptibility to PD.

Alleles↗