Systematic review and meta-analysis of the association between complement component 3 and age-related macular degeneration: A HUGE review and meta-analysis

We performed a meta-analysis to estimate the magnitude of C3 gene polymorphism effects, and their possible mode of action, on age-related macular degeneration (AMD). The meta-analysis included 16 studies for rs2230199 and 7 studies for rs1047286. Data extraction and risk of bias assessments were performed in duplicate, and heterogeneity and publication bias were explored. There was moderate evidence for association between both polymorphisms and AMD in individuals of European descent. For rs2230199, patients with CG and GG genotypes were 1.44 (95% CI: 1.33 – 1.56) and 1.88 (95% CI: 1.59 – 2.23) times more likely to have AMD than patients with CC genotype. For rs1047286, those with GA and AA genotypes had 1.27 (95% CI: 1.15 – 1.41) and 1.70 (95% CI: 1.27 – 2.11) times higher risk of AMD than those with GG genotypes. These gene effects suggested an additive model. The population attributable risks for the GG/GC and AA/GA genotypes are approximately 5-10%. Stratification of studies on the basis of ethnicity indicates that these variants are very infrequent in Asian populations and the significance of the effect observed is based largely on the high frequency of these variants within individuals of European descent. This meta-analysis supports the association between C3 and AMD and provides a robust estimate of the genetic risk.

The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration

Systematic reviews and meta-analyses are essential to summarize evidence relating to efficacy and safety of health care interventions accurately and reliably. The clarity and transparency of these reports, however, is not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers, and other users. Since the development of the QUOROM (QUality Of Reporting Of Meta-analysis) Statement-a reporting guideline published in 1999-there have been several conceptual, methodological, and practical advances regarding the conduct and reporting of systematic reviews and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realizing these issues, an international group that included experienced authors and methodologists developed PRISMA ( Preferred Reporting Items for Systematic reviews and Meta-Analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions. The PRISMA Statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential for transparent reporting of a systematic review. In this Explanation and Elaboration document, we explain the meaning and rationale for each checklist item. For each item, we include an example of good reporting and, where possible, references to relevant empirical studies and methodological literature. The PRISMA Statement, this document, and the associated Web site (http://www.prisma-statement.org/) should be helpful resources to improve reporting of systematic reviews and metaanalyses.

Adjuvant chemotherapy in oestrogen-receptor-poor breast cancer: patient-level meta-analysis of randomised trials

Background: The long-term effects of adjuvant polychemotherapy regimens in oestrogen-receptor-poor (ER-poor) breast cancer, and the extent to which these effects are modified by age or tamoxifen use, can be assessed by an updated meta-analysis of individual patient data from randomised trials. Methods: Collaborative meta-analyses of individual patient data for about 6000 women with ER-poor breast cancer in 46 trials of polychemotherapy versus not (non-taxane-based polychemotherapy, typically about six cycles; trial start dates 1975-96, median 1984) and about 14 000 women with ER-poor breast cancer in 50 trials of tamoxifen versus not (some trials in the presence and some in the absence of polychemotherapy; trial start dates 1972-93, median 1982). Findings: In women with ER-poor breast cancer, polychemotherapy significantly reduced recurrence, breast cancer mortality, and death from any cause, in those younger than 50 years and those aged 50-69 years at entry into trials of polychemotherapy versus not. In those aged younger than 50 years (1907 women, 15% node-positive), the 10-year risks were: recurrence 33% versus 45% (ratio of 10-year risks 0·73, 2p<0·00001), breast cancer mortality 24% versus 32% (ratio 0·73, 2p=0·0002), and death from any cause 25% versus 33% (ratio 0·75, 2p=0·0003). In women aged 50-69 years (3965 women, 58% node-positive), the 10-year risks were: recurrence 42% versus 52% (ratio 0·82, 2p<0·00001), breast cancer mortality 36% versus 42% (ratio 0·86, 2p=0·0004), and death from any cause 39% versus 45% (ratio 0·87, 2p=0·0009). Few were aged 70 years or older. Tamoxifen had little effect on recurrence or death in women who were classified in these trials as having ER-poor disease, and did not significantly modify the effects of polychemotherapy. Interpretation: In women who had ER-poor breast cancer, and were either younger than 50 years or between 50 and 69 years, these older adjuvant polychemotherapy regimens were safe (ie, had little effect on mortality from causes other than breast cancer) and produced substantial and definite reductions in the 10-year risks of recurrence and death. Current and future chemotherapy regimens could well yield larger proportional reductions in breast cancer mortality.

Dioxygenase-catalysed cis-dihydroxylation of meta-substituted phenols to yield cyclohexenone cis-diol and derived enantiopure cis-triol metabolites

cis-Dihydroxylation of meta-substituted phenol (m-phenol) substrates, to yield the corresponding cyclohexenone cis-diol metabolites, was catalysed by arene dioxygenases present in mutant and recombinant bacterial strains. The presence of cyclohexenone cis-diol metabolites and several of their cyclohexene and cyclohexane cis-triol derivatives was detected by LC-TOFMS analysis and confirmed by NMR spectroscopy. Structural and stereochemical analyses of chiral ketodiol bioproducts, was carried out using NMR and CD spectroscopy and stereochemical correlation methods. The formation of enantiopure cyclohexenone cis-diol metabolites is discussed in the context of postulated binding interactions of the m-phenol substrates at the active site of toluene dioxygenase (TDO).

Review and meta-analysis of the short-term effects of a vegetable oil emulsion on food intake

Several short-term studies have investigated the effects of a vegetable oil emulsion on subsequent food intake, although findings have been inconsistent. This work aimed to review all studies, and investigate differences in study outcomes based on methodology. All known studies were identified. Data were abstracted from published studies (n = 7). Details of unpublished studies were gained from investigators/sponsors (n = 5), or were unavailable for reasons of confidentiality (n = 4). Available data were combined using meta-analyses. A combined appetite suppressant effect of the emulsion compared with control was found for test meal intake at approximately 4, 12 and 36 h post-treatment: smallest combined mean difference (random effects model) = 0.53 MJ (95% confidence interval 0.20, 0.86), P < 0.01. However, considerable heterogeneity (variability) between study results was also found (smallest I2 = 94%, P < 0.01), questioning the predictive validity of the above findings. Meta-regression suggested this heterogeneity to be related to differences in the processed nature of the product, treatment dose and in particular year of study (smallest B = 0.54, 95% confidence interval 0.06, 1.03, P = 0.04), although again heterogeneity was found. The only consistent finding was a lack of effect on food intake 4 h post-preload in studies conducted after 2003. These results suggest a small but inconsistent appetite suppressant effect of the vegetable oil emulsion. However, due to the large heterogeneity, no definitive conclusions can be drawn.

Updated systematic review and meta-analysis of the effects of n-3 long-chain polyunsaturated fatty acids on depressed mood

Background: The debate over a role for n-3 long-chain polyunsaturated fatty acids (n-3 PUFAs) in depressed mood continues.

The association between complement component 2/complement factor B polymorphisms and age-related macular degeneration: A HuGE review and meta-analysis

The authors performed a systematic review of the association of complement component 2(C2)/complement factor B (CFB) gene polymorphisms with age-related macular degeneration (AMD). In total, data from 19 studies published between 2006 and 2011 were pooled for 4 polymorphisms: rs9332739 and rs547154 in the C2 gene and rs4151667 and rs641153 in the CFB gene. Data extraction and assessments for risk of bias were independently performed by 2 reviewers. Allele frequencies and allele and genotypic effects were pooled. Heterogeneity and publication bias were explored. Pooled minor allele frequencies for all 4 SNPs were between 4.7% and 9.6% for all polymorphisms, except for an Indian population in which the C allele at rs9332739 was the major allele. For the C2 polymorphisms, the minor C allele at rs9332739 and the minor T allele at rs547154 carried estimated relative risks (odds ratios) of 0.55 (95% confidence interval (CI): 0.46, 0.65) and 0.47 (95% CI: 0.39, 0.57), respectively. For the CFB polymorphisms, the minor A alleles at rs4151667 and rs614153 carried estimated risks of 0.54 (95% CI: 0.45, 0.64) and 0.41 (95% CI: 0.34, 0.51), respectively. These allele effects contributed to an absolute lowering of the risk of all AMD in Caucasian populations by 2.0%-6.0%. This meta-analysis provides a robust estimate of the protective association of C2/CFB with AMD.

Work stress in the etiology of coronary heart disease - a meta-analysis

Objectives This study focused on estimating the relative risk of coronary heart disease (CHD) in association with work stress, as indicated by the job-strain model, the effort-reward imbalance model, and the organizational injustice model.