Prostatitis,Sexually Transmitted Diseases,and Prostate Cancer: The California Men's Health Study

Background

Prostatitis and sexually transmitted diseases (STDs) have been positively associated with prostate cancer in previous case-control studies. However, results from recent prospective studies have been inconclusive.

Methodogy/Principal Findings

We investigated the association between prostatitis, STDs, and prostate cancer among African American, Asian American, Latino, and White participants of the California Men''s Health Study. Our analysis included 68,675 men, who completed a detailed baseline questionnaire in 2002–2003. We identified 1,658 incident prostate cancer cases during the follow-up period to June 30, 2006. Cox proportional hazards models were used to estimate relative risks and 95% confidence intervals. Overall, men having a history of prostatitis had an increased risk of prostate cancer than men with no history (RR = 1.30; 95% CI: 1.10–1.54). Longer duration of prostatitis symptoms was also associated with an increased risk of prostate cancer (P trend = 0.003). In addition, among men screened for prostate cancer (1 or 2 PSA tests), a non-significant positive association was observed between prostatitis and prostate cancer (RR = 1.10; 95% CI: 0.75–1.63). STDs were not associated with overall prostate cancer risk. In racial/ethnic stratified analysis, Latinos reporting any STDs had an increased risk of disease than those with no STDs (RR = 1.43; 95% CI: 1.07–1.91). Interestingly, foreign-born Latinos displayed a larger risk associated with STDs (RR = 1.87; 95% CI: 1.16–3.02) than U.S. born Latinos (RR = 1.15; 95% CI: 0.76–3.02).

Conclusion

In summary, results from this prospective study suggest that prostatitis and STDs may be involved in prostate cancer susceptibility. While we cannot rule out the possible influence of incidental detection, future studies are warranted to further investigate the role of infectious agents related to prostatitis and STDs in prostate cancer development.     

Developmental Model of Depression Applied to Prenatal Depression: Role of Present and Past Life Events,Past Emotional Disorders and Pregnancy Stress

Background

Several risk factors for depression during pregnancy have already been established. However, very few studies have conducted a multivariate analysis incorporating both the major predictors of depression in women, in accordance with comprehensive developmental models of depression, and specific stressors associated with the biological and psychosocial state of the mother-to-be.

Methodology/Principal Findings

We used a cross-sectional cohort design to analyze the associations between prenatal depression and potential risk factors. 693 French-speaking women with singleton pregnancies at 20–28 weeks'' gestation were consecutively recruited at Caen University Hospital. Fifty women with missing values were subsequently excluded from the analysis. Depressive symptoms were assessed on the Edinburgh Postnatal Depression Scale. Risk factors were either extracted from the computerized obstetric records or assessed by means of self-administered questionnaires. The associations between prenatal depression and the potential risk factors were assessed using log-binomial regression models to obtain a direct estimate of relative risk (RR). The following factors were found to be significant in the multivariate analysis: level of education (p<0.001), past psychiatric history (adjusted RR = 1.8, 95% confidence interval (CI): 1.1;2.8, p = 0.014), stress related to the health and viability of the fetus (adjusted RR = 2.6, 95% CI: 1.6;4.1, p<0.001), and stress related to severe marital conflicts (adjusted RR = 2.4, 95% CI: 1.5;3.9, p<0.001) or to serious difficulties at work (adjusted RR = 1.6, 95% CI :1.04;2.4, p = 0.031). An association was also found with the previous delivery of a child with a major or minor birth defect (adjusted RR = 2.0, 95% CI: 1.04;4.0, p = 0.038). Univariate analyses revealed a strong association with childhood adversity (parental rejection: RR = 1.8, 95% CI: 1.2;2.8, p = 0.0055 and family secrets: RR = 2.0, 95% CI: 1.2;3.1, p = 0.0046) and with lack of partner support (RR = 0.50, 95% CI: 0.30;0.84, p = 0.0086).

Conclusions/Significance

Our study identifies several risk factors that could easily be assessed in clinical practice. It draws attention to the impact of previously delivering a child with a birth defect. The association with childhood adversity warrants further study.     

Sedentary Behavior and Incident Cancer: A Meta-Analysis of Prospective Studies

Background

Sedentary behavior is ubiquitous in modern adults'' daily lives and it has been suggested to be associated with incident cancer. However, the results have been inconsistent. In this study, we performed a systematic review and meta-analysis of prospective cohort studies to clarify the association between sedentary behavior and incident cancer.

Method

PubMed and Embase databases were searched up to March 2014. All prospective cohort studies on the association between sedentary behavior and incident cancer were included. The summary relative risks (RRs) with 95% confidence intervals (CIs) were estimated using random effect model.

Results

A total of 17 prospective studies from 14 articles, including a total of 857,581 participants and 18,553 cases, were included in the analysis for sedentary behavior and risk of incident cancer. The overall meta-analysis suggested that sedentary behavior increased risk of cancer (RR = 1.20, 95%CI = 1.12–1.28), with no evidence of heterogeneity between studies (I ² = 7.3%, P = 0.368). Subgroup analyses demonstrated that there were statistical associations between sedentary behavior and some cancer types (endometrial cancer: RR = 1.28, 95% CI = 1.08–1.53; colorectal cancer: RR = 1.30, 95%CI = 1.12–1.49; breast cancer: RR = 1.17, 95%CI = 1.03–1.33; lung cancer: RR = 1.27, 95%CI = 1.06–1.52). However, there was no association of sedentary behavior with ovarian cancer (RR = 1.26, 95%CI = 0.87–1.82), renal cell carcinoma (RR = 1.11, 95%CI = 0.87–1.41) or non-Hodgkin lymphoid neoplasms (RR = 1.09, 95%CI = 0.82–1.43).

Conclusion

The present meta-analysis suggested that prolonged sedentary behavior was independently associated with an increased risk of incident endometrial, colorectal, breast, and lung cancers, but not with ovarian cancer, renal cell carcinoma or non-Hodgkin lymphoid neoplasms.     

Maternal Socioeconomic Status and the Risk of Congenital Heart Defects in Offspring: A Meta-Analysis of 33 Studies

Background

We conducted this meta-analysis to address the open question of a possible association between maternal socioeconomic status and congenital heart defects (CHDs).

Methods

We searched MEDLINE and EMBASE from their inception to January 1, 2014 for case-control and cohort studies that assessed the association between maternal socioeconomic status and the risk of CHDs. Study-specific relative risk estimates were polled according to random-effect or fixed-effect models.

Results

From 3343 references, a total of 31 case-control studies and 2 cohort studies were enrolled in this meta-analysis, including more than 50,000 cases. We observed that maternal educational attainment, family income and maternal occupation were negatively associated with an 11% (pooled RR = 1.11, 95% CI: 1.03, 1.21), 5% (pooled RR = 1.05, 95% CI: 1.01, 1.09) and 51% (pooled RR = 1.51, 95% CI: 1.02, 2.24) increased risk of CHDs, respectively. In a subgroup analysis by geographic region, the results were inconsistent for the European region (RR = 1.29, 95% CI: 0.99–1.69) and USA/Canada region (RR = 1.06, 95% CI: 0.97, 1.16) in maternal educational attainment.

Conclusion

In summary, this meta-analysis suggests that a lower degree of maternal socioeconomic status is modestly associated with an increased risk of CHDs. However, further investigations are needed to confirm the association.     

Meat Consumption and Risk of Oral Cavity and Oropharynx Cancer: A Meta-Analysis of Observational Studies

Purpose

High meat consumption, especially red and processed meat consumption is associated with an increased risk of several cancers, however, evidence for oral cavity and oropharynx cancer is limited. Thus, we performed this meta-analysis to determine the association between intakes of total meat, processed meat, red meat, and white meat, and the risk of oral cavity and oropharynx cancer.

Methods

Electronic search of Pubmed, Embase, and Cochrane Library Central database was conducted to select relevant studies. Fixed-effect and random-effect models were used to estimate summary relative risks (RR) and the corresponding 95% confidence intervals (CIs). Potential sources of heterogeneity were detected by meta-regression. Subgroup analyses and sensitivity analysis were also performed.

Results

12 case–control studies and one cohort study were included in the analyses, including 501,730 subjects and 4,104 oral cavity and oropharynx cancer cases. Pooled results indicated that high consumption of total meat, red meat, and white meat were not significantly associated with increased risk of oral cavity and oropharynx cancer (RR = 1.14, 95% CI[0.78–1.68]; RR = 1.05, 95% CI[0.66, 1.66] and RR = 0.81, 95% CI[0.54, 1.22], respectively), while the high consumption of processed meat was significantly associated with a 91% increased risk of oral cavity and oropharynx cancer (RR = 1.91, 95% CI [1.19–3.06]). Sensitivity analysis indicated that no significant variation in combined RR by excluding any of the study, confirming the stability of present results.

Conclusions

The present meta-analysis suggested that high consumption of processed meat was significantly associated with an increased risk of oral cavity and oropharynx cancer, while there was no significantly association between total meat, red meat or white meat and the risk of oral cavity and oropharynx cancer. More prospective cohort studies are warranted to confirm these associations.     

Risk of a Second Primary Cancer after Non-melanoma Skin Cancer in White Men and Women: A Prospective Cohort Study

Background

Previous studies suggest a positive association between history of non-melanoma skin cancer (NMSC) and risk of subsequent cancer at other sites. The purpose of this study is to prospectively examine the risk of primary cancer according to personal history of NMSC.

Methods and Findings

In two large US cohorts, the Health Professionals Follow-up Study (HPFS) and the Nurses'' Health Study (NHS), we prospectively investigated this association in self-identified white men and women. In the HPFS, we followed 46,237 men from June 1986 to June 2008 (833,496 person-years). In the NHS, we followed 107,339 women from June 1984 to June 2008 (2,116,178 person-years). We documented 29,447 incident cancer cases other than NMSC. Cox proportional hazard models were used to calculate relative risks (RRs) and 95% confidence intervals (CIs). A personal history of NMSC was significantly associated with a higher risk of other primary cancers excluding melanoma in men (RR = 1.11; 95% CI 1.05–1.18), and in women (RR = 1.20; 95% CI 1.15–1.25). Age-standardized absolute risk (AR) was 176 in men and 182 in women per 100,000 person-years. For individual cancer sites, after the Bonferroni correction for multiple comparisons (n = 28), in men, a personal history of NMSC was significantly associated with an increased risk of melanoma (RR = 1.99, AR = 116 per 100,000 person-years). In women, a personal history of NMSC was significantly associated with an increased risk of breast (RR = 1.19, AR = 87 per 100,000 person-years), lung (RR = 1.32, AR = 22 per 100,000 person-years), and melanoma (RR = 2.58, AR = 79 per 100,000 person-years).

Conclusion

This prospective study found a modestly increased risk of subsequent malignancies among individuals with a history of NMSC, specifically breast and lung cancer in women and melanoma in both men and women. Please see later in the article for the Editors'' Summary     

Coffee Consumption and Risk of Breast Cancer: An Up-To-Date Meta-Analysis

Objectives

This updated meta-analysis was conducted to assess the association between coffee consumption and breast cancer risk.

Methods

We conducted a systematic search updated July 2012 to identify observational studies providing quantitative estimates for breast cancer risk in relation to coffee consumption. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model, and generalized least square trend estimation was used to assess dose–response relationships.

Results

A total of 26 studies (16 cohort and 10 case–control studies) on coffee intake with 49497 breast cancer cases were included in the meta-analysis. The pooled RR showed a borderline significant influence of highest coffee consumption (RR = 0.96; 95% CI 0.93–1.00), low-to moderate coffee consumption (RR = 0.99; 95% CI 0.95–1.04), or an increment of 2 cups/day of coffee consumption (RR = 0.98; 95% CI 0.97–1.00) on the risk of breast cancer. In stratified analysis, a significant inverse association was observed in ER-negative subgroup. However, no significant association was noted in the others.

Conclusions

Our findings suggest that increased coffee intake is not associated with a significantly reduced risk of breast cancer, but we observe an inverse association in ER-negative subgroup analysis. More large studies are needed to determine subgroups to obtain more valuable data on coffee drinking and breast cancer risk.     

Cruciferous Vegetables Intake Is Associated with Lower Risk of Renal Cell Carcinoma: Evidence from a Meta-Analysis of Observational Studies

Background

Epidemiologic studies have evaluated the association between cruciferous vegetables(CV) intake and the risk of renal cell carcinoma(RCC); however, the existing results are controversial. The aim of this meta-analysis was to investigate the association between CV intake and RCC risk.

Methods

A literature search was carried out using PUBMED and EMBASE database between January 1966 and March 2013. Fixed-effect and random-effect models were used to estimate summary relative risks (RR) and the corresponding 95% confidence intervals (CIs). Potential sources of heterogeneity were detected by meta-regression. Subgroup analyses, sensitivity analysis and cumulative meta-analysis were also performed.

Results

A total of 12 studies (six cohorts, six case–control) contributed to the analysis, involving 1,228,518 participants and 5,773 RCC cases. When all studies were pooled, we observed a significantly inverse association between CV intake and RCC risk (RR = 0.81, 95% CI [0.72, 0.91]). This association was also significant when analyses were restricted to six high-quality studies (RR = 0.89, 95% CI [0.82, 0.98]). In subgroup analyses, CV intake was significantly associated with reduced RCC risk among studies conducted in America (RR = 0.77, 95%CI [0.70, 0.86]); however, CV intake had no significant association with RCC risk among studies conducted in Europe (RR = 0.87, 95%CI [0.71, 1.07]). Furthermore, sensitivity analysis confirmed the stability of results.

Conclusions

The findings of this meta-analysis suggested that high intake of CV was inversely associated with RCC risk among Americans. More studies, especially high quality cohort studies with larger sample size, well controlled confounding factors are warranted to confirm this association.     

Cancer Incidence and Mortality in Patients with Type 2 Diabetes Treated with Human Insulin: A Cohort Study in Shanghai

Aim

The aim was to investigate the association between human insulin and cancer incidence and mortality in Chinese patients with type 2 diabetes.

Methods

We recruited 8,774 insulin-naïve diabetes patients from the Shanghai Diabetes Registry (SDR). The follow-up rate was 85.4%. All subjects were divided into the insulin use cohort (n = 3,639) and the non-insulin use cohort (n = 5,135). The primary outcome was the first diagnosis of any cancer. The secondary outcome was all-cause mortality. Cox proportional hazards model was used to estimate the relative risk (RR) of cancer and mortality.

Results

We observed 98 cancer events in the insulin use cohort and 170 in the non-insulin use cohort. Cancer incidence rates were 78.6 and 74.3 per 10,000 patients per year in the insulin users and the non-insulin users, respectively. No significant difference in cancer risk was observed between the two cohorts (adjusted RR = 1.20, 95% CI 0.89–1.62, P = 0.228). Regarding site-specific cancers, only the risk of liver cancer was significantly higher in the insulin users compared to that in the non-insulin users (adjusted RR = 2.84, 95% CI 1.12–7.17, P = 0.028). The risks of overall mortality (adjusted RR = 1.89, 95% CI 1.47–2.43, P<0.0001) and death from cancer (adjusted RR = 2.16, 95% CI 1.39–3.35, P = 0.001) were all significantly higher in the insulin users than in the non-insulin users.

Conclusion

There was no excess risk of overall cancer in patients with type 2 diabetes who were treated with human insulin. However, a significantly higher risk of liver cancer was found in these patients. Moreover, insulin users showed higher risks of overall and cancer mortality. Considering that individuals treated with insulin were more likely to be advanced diabetic patients, caution should be used in interpreting these results.     

Dose–Risk and Duration–Risk Relationships between Aspirin and Colorectal Cancer: A Meta-Analysis of Published Cohort Studies

Background

In previous meta-analyses, aspirin use has been associated with reduced risk of colorectal cancer. However, uncertainty remains on the exact dose–risk and duration–risk relationships.

Methods

We identified studies by searching several English and Chinese electronic databases and reviewing relevant articles. The dose-response meta-analysis was performed by linear trend regression and restricted cubic spline regression. Subgroup analyses were conducted to explore possible heterogeneity among studies. Potential heterogeneity was calculated as Q statistic and I ² value. Publication bias was evaluated using funnel plots and quantified by the Begg’s and Egger’s test.

Results

Twelve studies were included in this meta-analysis. An inverse association between aspirin use and colorectal cancer was observed in both the overall group (RR = 0.74, 95% CI 0.64–0.83 for aspirin dose; RR = 0.80, 95% CI 0.75–0.85 for frequency of aspirin use; RR = 0.75, 95% CI 0.68–0.81 for years of aspirin use) and subgroups stratified by sex and cancer site. The dose-response meta-analysis showed that there was a 20% statistically significant decreased risk of colorectal cancer for 325 mg aspirin per day increment, 18% decreased risk for 7 times aspirin per week increment and 18% decreased risk for 10 years aspirin increment.

Conclusion

Long-term (>5 years), low-dose (75–325 mg per day) and regular aspirin use (2–7 times per week) can effectively reduce the risk of colorectal cancer.     

Maternal Parity and the Risk of Congenital Heart Defects in Offspring: A Dose-Response Meta-Analysis of Epidemiological Observational Studies

Background

Epidemiological studies have reported conflicting results regarding maternal parity and the risk of congenital heart defects (CHDs). However, a meta-analysis of the association between maternal parity and CHDs in offspring has not been conducted.

Methods

We searched MEDLINE and EMBASE for articles catalogued between their inception and March 8, 2014; we identified relevant published studies that assessed the association between maternal parity and CHD risk. Two authors independently assessed the eligibility of the retrieved articles and extracted data from them. Study-specific relative risk estimates were pooled by random-effects or fixed-effects models. From the 11272 references, a total of 16 case-control studies and 3 cohort studies were enrolled in this meta-analysis.

Results

The overall relative risk of CHD in parous versus nulliparous women was 1.01 (95% CI, 0.97–1.06; Q = 32.34; P = 0.006; I² = 53.6%). Furthermore, we observed a significant association between the highest versus lowest parity number, with an overall RR = 1.20 (95% CI, 1.10–1.31; (Q = 74.61, P<0.001, I² = 82.6%). A dose–response analysis also indicated a positive effect of maternal parity on CHD risk, and the overall increase in relative risk per one live birth was 1.06 (95% CI, 1.02–1.09); Q = 68.09; P<0.001; I² = 80.9%). We conducted stratified and meta-regression analyses to identify the origin of the heterogeneity among studies. A Galbraith plot was created to graphically assess the sources of heterogeneity.

Conclusion

In summary, this meta-analysis provided a robust estimate of the positive association between maternal parity and risk of CHD.     

Statin Use Is Associated with Reduced Risk of Haematological Malignancies: Evidence from a Meta-Analysis

Background

Several observational studies have shown that statin use may modify the risk of haematological malignancies. To quantify the association between statin use and risk for haematological malignancies, we performed a detailed meta-analysis of published studies regarding this subject.

Methods

We conducted a systematic search of multiple databases including PubMed, Embase, and Cochrane Library Central database up to July 2013. Fixed-effect and random-effect models were used to estimate summary relative risks (RR) and the corresponding 95% confidence intervals (CIs). Potential sources of heterogeneity were detected by meta-regression. Subgroup analyses and sensitivity analysis were also performed.

Results

A total of 20 eligible studies (ten case-control studies, four cohort studies, and six RCTs) reporting 1,139,584 subjects and 15,297 haematological malignancies cases were included. Meta-analysis showed that statin use was associated with a statistically significant 19% reduction in haematological malignancies incidence (RR = 0.81, 95% CI [0.70, 0.92]). During subgroup analyses, statin use was associated with a significantly reduced risk of haematological malignancies among observational studies (RR = 0.79, 95% CI [0.67, 0.93]), but not among RCTs (RR = 0.92, 95% CI [0.77, 1.09]).

Conclusions

Based on this comprehensive meta-analysis, statin use may have chemopreventive effects against haematological malignancies. More studies, especially definitive, randomized chemoprevention trials are needed to confirm this association.     

Prognostic Significance of Tumor-Associated Macrophages in Solid Tumor: A Meta-Analysis of the Literature

Purpose

Tumor associated macrophages (TAMs) are considered with the capacity to have both negative and positive effects on tumor growth. The prognostic value of TAM for survival in patients with solid tumor remains controversial.

Experimental Design

We conducted a meta-analysis of 55 studies (n = 8,692 patients) that evaluated the correlation between TAM (detected by immunohistochemistry) and clinical staging, overall survival (OS) and disease free survival (DFS). The impact of M1 and M2 type TAM (n = 5) on survival was also examined.

Results

High density of TAM was significantly associated with late clinical staging in patients with breast cancer [risk ratio (RR)  = 1.20 (95% confidence interval (CI), 1.14–1.28)] and bladder cancer [RR = 3.30 (95%CI, 1.56–6.96)] and with early clinical staging in patients with ovarian cancer [RR = 0.52 (95%CI, 0.35–0.77)]. Negative effects of TAM on OS was shown in patients with gastric cancer [RR = 1.64 (95%CI, 1.24–2.16)], breast cancer [RR = 8.62 (95%CI, 3.10–23.95)], bladder cancer [RR = 5.00 (95%CI, 1.98–12.63)], ovarian cancer [RR = 2.55 (95%CI, 1.60–4.06)], oral cancer [RR = 2.03 (95%CI, 1.47–2.80)] and thyroid cancer [RR = 2.72 (95%CI, 1.26–5.86)],and positive effects was displayed in patients with colorectal cancer [RR = 0.64 (95%CI, 0.43–0.96)]. No significant effect was showed between TAM and DFS. There was also no significant effect of two phenotypes of TAM on survival.

Conclusions

Although some modest bias cannot be excluded, high density of TAM seems to be associated with worse OS in patients with gastric cancer, urogenital cancer and head and neck cancer, with better OS in patients with colorectal cancer.     

Hyperuricemia and Risk of Incident Hypertension: A Systematic Review and Meta-Analysis of Observational Studies

Background

Observational studies of the relationship between hyperuricemia and the incidence of hypertension are controversial. We conducted a systematic review and meta-analysis to assess the association and consistency between uric acid levels and the risk of hypertension development.

Methods

We searched MEDLINE, EMBASE, CBM (Chinese Biomedicine Database) through September 2013 and reference lists of retrieved studies to identify cohort studies and nested case-control studies with uric acid levels as exposure and incident hypertension as outcome variables. Two reviewers independently extracted data and assessed study quality using Newcastle-Ottawa Scale. Extracted information included study design, population, definition of hyperuricemia and hypertension, number of incident hypertension, effect sizes, and adjusted confounders. Pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs) for the association between hyperuricemia and risk of hypertension were calculated using a random-effects model.

Results

We included 25 studies with 97,824 participants assessing the association between uric acid and incident hypertension in our meta-analysis. The quality of included studies is moderate to high. Random-effects meta-analysis showed that hyperuricemia was associated with a higher risk of incident hypertension, regardless of whether the effect size was adjusted or not, whether the data were categorical or continuous as 1 SD/1 mg/dl increase in uric acid level (unadjusted: RR = 1.73, 95% CI 1.46∼2.06 for categorical data, RR = 1.22, 95% CI 1.03∼1.45 for a 1 SD increase; adjusted: RR = 1.48, 95% CI 1.33∼1.65 for categorical data, RR = 1.15, 95% CI 1.06∼1.26 for a 1 mg/dl increase), and the risk is consistent in subgroup analyses and have a dose-response relationship.

Conclusions

Hyperuricemia may modestly increase the risk of hypertension incidence, consistent with a dose-response relationship.     

Impact of the Method of G6PD Deficiency Assessment on Genetic Association Studies of Malaria Susceptibility

Background

Clinical association studies have yielded varied results regarding the impact of glucose-6-phosphate dehydrogenase (G6PD) deficiency upon susceptibility to malaria. Analyses have been complicated by varied methods used to diagnose G6PD deficiency.

Methodology/Prinicipal Findings

We compared the association between uncomplicated malaria incidence and G6PD deficiency in a cohort of 601 Ugandan children using two different diagnostic methods, enzyme activity and G6PD genotype (G202A, the predominant East African allele). Although roughly the same percentage of males were identified as deficient using enzyme activity (12%) and genotype (14%), nearly 30% of males who were enzymatically deficient were wild-type at G202A. The number of deficient females was three-fold higher with assessment by genotype (21%) compared to enzyme activity (7%). Heterozygous females accounted for the majority (46/54) of children with a mutant genotype but normal enzyme activity. G6PD deficiency, as determined by G6PD enzyme activity, conferred a 52% (relative risk [RR] 0.48, 95% CI 0.31–0.75) reduced risk of uncomplicated malaria in females. In contrast, when G6PD deficiency was defined based on genotype, the protective association for females was no longer seen (RR = 0.99, 95% CI 0.70–1.39). Notably, restricting the analysis to those females who were both genotypically and enzymatically deficient, the association of deficiency and protection from uncomplicated malaria was again demonstrated in females, but not in males (RR = 0.57, 95% CI 0.37–0.88 for females).

Conclusions/Significance

This study underscores the impact that the method of identifying G6PD deficient individuals has upon association studies of G6PD deficiency and uncomplicated malaria. We found that G6PD-deficient females were significantly protected against uncomplicated malaria, but this protection was only seen when G6PD deficiency is described using enzyme activity. These observations may help to explain the discrepancy in some published association studies involving G6PD deficiency and uncomplicated malaria.     

Double Trouble: Does Co-Morbid Chronic Somatic Illness Increase Risk for Recurrence in Depression? A Systematic Review

Objective

To perform a systematic review, and if possible a meta-analysis, to establish whether depressed patients with co-morbid chronic somatic illnesses are a high risk “double trouble” group for depressive recurrence.

Method

The databases PubMed, EMbase and PsycINFO were systematically searched until the 4^th of December 2012 by using MeSH and free text terms. Additionally, reference lists of retrieved publications and treatment guidelines were reviewed, and experts were consulted. Inclusion criteria were: depression had to be measured at least twice during the study with qualified instruments and the chronic somatic illness had to be assessed by self-report or by a medical professional. Information on depressive recurrence was extracted and additionally risk ratios of recurrence were calculated.

Results

The search generated four articles that fulfilled our inclusion criteria. These studies showed no differences in recurrence over one- two- three- and 6.5 years of follow-up for a total of 2010 depressed patients of which 694 patients with a co-morbid chronic somatic illness versus 1316 patients without (Study 1: RR = 0.49, 95% CI, 0.17–1.41 at one year follow-up and RR = 1.37, 95% CI, 0.78–2.41 at two year follow-up; Study 2: RR = 0.94, 95% CI, 0.65–1.36 at two year follow-up; Study 3: RR = 1.15, 95% CI, 0.40–3.27 at one year follow-up; RR = 1.07, 95% CI, 0.48–2.42 at two year follow-up and RR = 0.99, 95% CI,0.55–1.77 at 6.5 years follow-up; Study 4: RR = 1.16, 95% CI, 0.86–1.57 at three year follow-up).

Conclusion

We found no association between a heightened risk for depressive recurrence and co-morbid chronic somatic illnesses. There is a need for more longitudinal studies to justify the current specific treatment advice such as long-term pharmacological maintenance treatment for this presumed “double trouble” group.     

Maternal Obesity in Early Pregnancy and Risk of Adverse Outcomes

Objectives

To assess the role of the health consequences of maternal overweight and obesity at the start of pregnancy on gestational pathologies, delivery and newborn characteristics.

Methods

A cohort of pregnant women (n = 6.558) having delivered at the Maternal & Child University Hospital of Gran Canaria (HUMIGC) in 2008 has been studied. Outcomes were compared using multivariate analyses controlling for confounding variables.

Results

Compared to normoweight, overweight and obese women have greater risks of gestational diabetes mellitus (RR = 2.13 (95% CI: 1.52–2.98) and (RR = 2.85 (95% CI: 2.01–4.04), gestational hypertension (RR = 2.01 (95% CI: 1.27–3.19) and (RR = 4.79 (95% CI: 3.13–7.32) and preeclampsia (RR = 3.16 (95% CI: 1.12–8.91) and (RR = 8.80 (95% CI: 3.46–22.40). Obese women have also more frequently oligodramnios (RR = 2.02 (95% CI: 1.25–3.27), polyhydramnios. (RR = 1.76 (95% CI: 1.03–2.99), tearing (RR = 1.24 (95% CI: 1.05–1.46) and a lower risk of induced deliveries (RR = 0.83 (95% CI: 0.72–0.95). Both groups have more frequently caesarean section (RR = 1.36 (95% CI: 1.14–1.63) and (RR = 1.84 (95% CI: 1.53–2.22) and manual placenta extraction (RR = 1.65 (95% CI: 1.28–2.11) and (RR = 1.77 (95% CI: 1.35–2.33). Newborns from overweight and obese women have higher weight (p<0.001) and a greater risk of being macrosomic (RR = 2.00 (95% CI: 1.56–2.56) and (RR = 2.74 (95% CI: 2.12–3.54). Finally, neonates from obese mother have a higher risk of being admitted to special care units (RR = 1.34 (95% CI: 1.01–1.77). Apgar 1 min was significantly higher in newborns from normoweight mothers: 8.65 (95% CI: 8.62–8.69) than from overweight: 8.56 (95% CI: 8.50–8.61) or obese mothers: 8.48 (95% CI: 8.41–8.54).

Conclusion

Obesity and overweight status at the beginning of pregnancy increase the adverse outcomes of the pregnancy. It is important to promote the normalization of bodyweight in those women who intend to get pregnant and to provide appropriate advice to the obese women of the risks of obesity at the start of the pregnancy.     

Reappraisal of Metformin Efficacy in the Treatment of Type 2 Diabetes: A Meta-Analysis of Randomised Controlled Trials

Background

The UK Prospective Diabetes Study showed that metformin decreases mortality compared to diet alone in overweight patients with type 2 diabetes mellitus. Since then, it has been the first-line treatment in overweight patients with type 2 diabetes. However, metformin-sulphonylurea bitherapy may increase mortality.

Methods and Findings

This meta-analysis of randomised controlled trials evaluated metformin efficacy (in studies of metformin versus diet alone, versus placebo, and versus no treatment; metformin as an add-on therapy; and metformin withdrawal) against cardiovascular morbidity or mortality in patients with type 2 diabetes. We searched Medline, Embase, and the Cochrane database. Primary end points were all-cause mortality and cardiovascular death. Secondary end points included all myocardial infarctions, all strokes, congestive heart failure, peripheral vascular disease, leg amputations, and microvascular complications. Thirteen randomised controlled trials (13,110 patients) were retrieved; 9,560 patients were given metformin, and 3,550 patients were given conventional treatment or placebo. Metformin did not significantly affect the primary outcomes all-cause mortality, risk ratio (RR) = 0.99 (95% CI: 0.75 to 1.31), and cardiovascular mortality, RR = 1.05 (95% CI: 0.67 to 1.64). The secondary outcomes were also unaffected by metformin treatment: all myocardial infarctions, RR = 0.90 (95% CI: 0.74 to 1.09); all strokes, RR = 0.76 (95% CI: 0.51 to 1.14); heart failure, RR = 1.03 (95% CI: 0.67 to 1.59); peripheral vascular disease, RR = 0.90 (95% CI: 0.46 to 1.78); leg amputations, RR = 1.04 (95% CI: 0.44 to 2.44); and microvascular complications, RR = 0.83 (95% CI: 0.59 to 1.17). For all-cause mortality and cardiovascular mortality, there was significant heterogeneity when including the UK Prospective Diabetes Study subgroups (I ² = 41% and 59%). There was significant interaction with sulphonylurea as a concomitant treatment for myocardial infarction (p = 0.10 and 0.02, respectively).

Conclusions

Although metformin is considered the gold standard, its benefit/risk ratio remains uncertain. We cannot exclude a 25% reduction or a 31% increase in all-cause mortality. We cannot exclude a 33% reduction or a 64% increase in cardiovascular mortality. Further studies are needed to clarify this situation. Please see later in the article for the Editors'' Summary     

Association of Adiponectin Gene (ADIPOQ) rs2241766 Polymorphism with Obesity in Adults: A Meta-Analysis

Background

Adiponectin plays an important role in regulating glucose levels and fatty acid oxidation. Multiple studies have assessed the association between rs2241766 polymorphism in the adiponectin (ADIPOQ) gene and obesity susceptibility. However, the results are inconsistent and inconclusive. The aim of this meta-analysis was to investigate this association in adults.

Method

Several electronic databases were searched for relevant literature published up to November 2013. Statistical analyses were performed using software Review Manager (Version 5.02) and STATA (Version 10.0). The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with a random-effects model or a fixed-effect model depending on heterogeneity among studies. Q tests and Egger’s tests were performed to assess heterogeneity and publication bias. Sensitivity analysis was conducted to confirm the reliability and stability of the meta-analysis.

Results

A total of 2,819 obese and 3,024 controls in 18 case-control studies were included in the meta-analysis. The results indicated that compared with TT genotype, the ADIPOQ-rs2241766 GG genotype was associated with an increased risk for obesity (OR = 1.39, 95% CI: 1.11–1.73, P for heterogeneity = 0.520, I² = 0%) in overall studies. Whereas, GT genotype was associated with a borderland increased risk for obesity (OR = 1.13, 95% CI: 0.94–1.36, P for heterogeneity = 0.006, I² = 51%). The susceptibility of obesity was increased based on genotypes of TT<GT<GG (P for trend = 0.011). Subgroup analysis of different regions revealed that the ADIPOQ-rs2241766 GG genotype increased obesity risk in the Chinese studies (OR = 1.54, 95% CI: 1.19–2.00) but not in the non-Chinese studies (OR = 1.02, 95% CI: 0.66–1.58). Similar results were observed in allelic, recessive, and dominant genetic models. There was no significant evidence of publication bias in the overall, Chinese, and non-Chinese studies (P = 0.426, P = 0.935, and P = 0.390, respectively).

Conclusion

The results of this meta-analysis suggest that the ADIPOQ-rs2241766 G/T polymorphism might be associated with obesity in Chinese studies but not in non-Chinese studies in adults. Better-designed studies that consider confounding factors and assess larger sample sizes with a focus on ADIPOQ-rs2241766G/T polymorphisms and obesity are required in the future.