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Background Tumors of the metastatic colorectal cancer (mCRC) patients that are wildtype (WT) for KRAS or NRAS mutations respond more favorably to anti-epidermal growth factor receptor (EGFR) treatments. Treatment guidelines now recommend that all mCRC patients have WT KRAS and NRAS tumor status confirmed prior to initiating anti-EGFR therapy. Evidence also suggests that BRAF mutations may predict lack of response to anti-EGFR therapy. As such, there is now a need for comprehensive data on the prevalence of KRAS, NRAS, and BRAF mutations among patients with mCRC. Methods A systematic literature review was conducted among studies that described the prevalence of KRAS, NRAS, and BRAF gene mutations in mCRC patients. Observational cohort studies and standard of care arm of randomized clinical trials were included. Random effects meta-analysis models were used to create summary prevalence estimates for each of the mutation types. Subgroup analyses were also conducted to identify potential sources of heterogeneity. Exploratory analyses of overall and progression-free survival by mutation status were also conducted. Results This systematic review and meta-analysis included 275 studies comprising 77,104 mCRC patients. The summary prevalence estimate was 35.9% for KRAS mutations, 7.1% for BRAF mutations, and 4.1% for NRAS mutations. Female patients had significantly more KRAS and BRAF mutations than males, and significant variation by study location was observed for both KRAS and BRAF mutation prevalence. Overall survival was significantly decreased for patients with KRAS, BRAF, and NRAS mutations compared to those with WT tumors. Progression-free survival was also significantly decreased among patients with KRAS and BRAF mutations. Conclusions KRAS, NRAS, and BRAF mutation statuses in patients with mCRC are important predictors of treatment success and may also have prognostic value. In this paper we present the first systematic and comprehensive literature review and meta-analysis of the prevalence of KRAS, BRAF, and NRAS mutations and demonstrate the prognostic impact of mutation status on survival.

Background Systemic cancer therapies may induce infusion reactions (IRs) or hypersensitivities. Metastatic colorectal cancer (mCRC) patients treated with anti‐EGFR therapies, including cetuximab and panitumumab, may be subject to these reactions. We conducted a meta‐analysis to estimate the IR incidence in this population and identify variations in this incidence by patient or study characteristics. Methods A systematic review was conducted to identify observational studies or clinical trials of mCRC patients treated with anti‐EGFR therapies that reported occurrences of IRs, hypersensitivity, or allergy/anaphylaxis. The objective of the study was to estimate the incidence of IRs. Random effects models were used to meta‐analyze the incidence of IRs overall and stratified by therapy type, study design, geographic location, RAS or KRAS mutation status, grade of reaction severity, and terminology used to describe the reaction. Results The pooled estimate for IR incidence was 4.9% (95% confidence interval: 3.6%‐6.5%). Lower‐grade reactions were more common than higher‐grade reactions overall and the incidence of reactions among cetuximab patients was nearly four times that of panitumumab patients (6.1% vs 1.6%). Conclusions IRs occur in approximately 5% of mCRC patients treated with anti‐EGFR therapies, and the incidence varies significantly by grade of severity and therapy type. Studies evaluating these outcomes should consider investigating survival outcomes by IR status to determine its prognostic relevance., Infusion reactions and hypersensitivities have been reported among metastatic colorectal cancer patients treated with anti‐EGFR therapies, but the summary incidence has not previously been characterized. This systematic review and meta‐analysis demonstrated that the summary incidence of infusion reactions was 4.9% in this population.

Objective To conduct meta-analyses of randomized controlled trials (RCTs) to estimate the effect of eicosapentaenoic and docosahexaenoic acid (EPA+DHA) on coronary heart disease (CHD), and to conduct meta-analyses of prospective cohort studies to estimate the association between EPA+DHA intake and CHD risk. Methods A systematic literature search of Ovid/Medline, PubMed, Embase, and the Cochrane Library from January 1, 1947, to November 2, 2015, was conducted; 18 RCTs and 16 prospective cohort studies examining EPA+DHA from foods or supplements and CHD, including myocardial infarction, sudden cardiac death, coronary death, and angina, were identified. Random-effects meta-analysis models were used to generate summary relative risk estimates (SRREs) and 95% CIs. Heterogeneity was examined in subgroup and sensitivity analyses and by meta-regression. Dose-response was evaluated in stratified dose or intake analyses. Publication bias assessments were performed. Results Among RCTs, there was a nonstatistically significant reduction in CHD risk with EPA+DHA provision (SRRE=0.94; 95% CI, 0.85-1.05). Subgroup analyses of data from RCTs indicated a statistically significant CHD risk reduction with EPA+DHA provision among higher-risk populations, including participants with elevated triglyceride levels (SRRE=0.84; 95% CI, 0.72-0.98) and elevated low-density lipoprotein cholesterol (SRRE=0.86; 95% CI, 0.76-0.98). Meta-analysis of data from prospective cohort studies resulted in a statistically significant SRRE of 0.82 (95% CI, 0.74-0.92) for higher intakes of EPA+DHA and risk of any CHD event. Conclusion Results indicate that EPA+DHA may be associated with reducing CHD risk, with a greater benefit observed among higher-risk populations in RCTs.

Background Tumors of the metastatic colorectal cancer (mCRC) patients that are wildtype (WT) for KRAS or NRAS mutations respond more favorably to anti-epidermal growth factor receptor (EGFR) treatments. Treatment guidelines now recommend that all mCRC patients have WT KRAS and NRAS tumor status confirmed prior to initiating anti-EGFR therapy. Evidence also suggests that BRAF mutations may predict lack of response to anti-EGFR therapy. As such, there is now a need for comprehensive data on the prevalence of KRAS, NRAS, and BRAF mutations among patients with mCRC. Methods A systematic literature review was conducted among studies that described the prevalence of KRAS, NRAS, and BRAF gene mutations in mCRC patients. Observational cohort studies and standard of care arm of randomized clinical trials were included. Random effects meta-analysis models were used to create summary prevalence estimates for each of the mutation types. Subgroup analyses were also conducted to identify potential sources of heterogeneity. Exploratory analyses of overall and progression-free survival by mutation status were also conducted. Results This systematic review and meta-analysis included 275 studies comprising 77,104 mCRC patients. The summary prevalence estimate was 35.9% for KRAS mutations, 7.1% for BRAF mutations, and 4.1% for NRAS mutations. Female patients had significantly more KRAS and BRAF mutations than males, and significant variation by study location was observed for both KRAS and BRAF mutation prevalence. Overall survival was significantly decreased for patients with KRAS, BRAF, and NRAS mutations compared to those with WT tumors. Progression-free survival was also significantly decreased among patients with KRAS and BRAF mutations. Conclusions KRAS, NRAS, and BRAF mutation statuses in patients with mCRC are important predictors of treatment success and may also have prognostic value. In this paper we present the first systematic and comprehensive literature review and meta-analysis of the prevalence of KRAS, BRAF, and NRAS mutations and demonstrate the prognostic impact of mutation status on survival.

Purpose To conduct a systematic review and meta-analysis of lung cancer among acrylonitrile-exposed workers. Methods A literature search through April 2020 was performed to identify relevant cohort and case-control studies. Data from these studies were meta-analyzed to generate summary relative risk estimates (SRREs). Heterogeneity was examined in sub-group and sensitivity analyses, and by meta-regression. Results Twenty-two studies were reviewed systematically, and 10 cohort studies and one case-control study were meta-analyzed. Individual relative risk estimates reported across studies were heterogeneous, with most being relatively weak in statistical strength and non-statistically significant on both sides of the null value. Meta-analysis of these data resulted in an SRRE of 1.04 (95% CI: 0.89–1.21; overall model, largely consisting of all workers exposed to acrylonitrile). Sub-group analyses and meta-regression did not support patterns of positive dose-response relationships by duration of exposure/employment or cumulative exposure. Conclusions Although some positive associations have been reported in internal comparison analyses based on increasing exposure categories, few associations are statistically significant, there are no apparent or consistent patterns of dose-response, and the confounding influence of cigarette smoking was not adequately controlled. Thus, findings from this review and meta-analysis do not support an increased risk of lung cancer among acrylonitrile workers.

The possible relationship between dietary cholesterol and cardiac outcomes has been scrutinized for decades. However, recent reviews of the literature have suggested that dietary cholesterol is not a nutrient of concern. Thus, we conducted a meta-analysis of egg intake (a significant contributor to dietary cholesterol) and risk of coronary heart disease (CHD) and stroke. A comprehensive literature search was conducted through August 2015 to identify prospective cohort studies that reported risk estimates for egg consumption in association with CHD or stroke. Random-effects meta-analysis was used to generate summary relative risk estimates (SRREs) for high vs low intake and stratified intake dose-response analyses. Heterogeneity was examined in subgroups where sensitivity and meta regression analyses were conducted based on increasing egg intake. A 12% decreased risk (SRRE = 0.88, 95% confidence interval [CI], 0.81-0.97) of stroke was observed in the meta-analysis of 7 studies of egg intake (high vs low; generally 1/d vs2/wk), with little heterogeneity (p-H = 0.37, I

Inverse associations between dairy consumption and CVD have been reported in several epidemiological studies. Our objective was to conduct a meta-analysis of prospective cohort studies of dairy intake and CVD. A comprehensive literature search was conducted to identify studies that reported risk estimates for total dairy intake, individual dairy products, low/full-fat dairy intake, Ca from dairy sources and CVD, CHD and stroke. Random-effects meta-analyses were used to generate summary relative risk estimates (SRRE) for high v. low intake and stratified intake dose–response analyses. Additional dose–response analyses were performed. Heterogeneity was examined in sub-group and sensitivity analyses. In total, thirty-one unique cohort studies were identified and included in the meta-analysis. Several statistically significant SRRE below 1.0 were observed, namely for total dairy intake and stroke (SRRE=0·91; 95 % CI 0·83, 0·99), cheese intake and CHD (SRRE=0·82; 95 % CI 0·72, 0·93) and stroke (SRRE=0·87; 95 % CI 0·77, 0·99), and Ca from dairy sources and stroke (SRRE=0·69; 95 % CI 0·60, 0·81). However, there was little evidence for inverse dose–response relationships between the dairy variables and CHD and stroke after adjusting for within-study covariance. The results of this meta-analysis of prospective cohort studies have shown that dairy consumption may be associated with reduced risks of CVD, although additional data are needed to more comprehensively examine potential dose–response patterns.

Background The objective of this study was to conduct an indirect treatment comparison between cabazitaxel, abiraterone and enzalutamide to determine the clinical efficacy and safety of cabazitaxel relative to comparators in the treatment of patients with metastatic castrate-resistant prostate cancer who progress on docetaxel-based therapies. Methods A systematic literature review was conducted to inform the network meta-analysis of cabazitaxel, abiraterone and enzalutamide. Due to a lack of head-to-head trials, studies with a comparator arm of best supportive care were included in the analysis. Overall survival, progression-free survival, and adverse events were compared within both Bayesian and Frequentist frameworks. The ratios for survival outcomes were estimated using hazard ratios (HR), and the ratios for adverse events between groups were estimated using odds ratios (ORs); uncertainty was reported as 95% confidence (Frequentist) and credible (Baysesian) Intervals. Results Three of thirteen trials identified for abstraction were relevant for analyses. Median overall survival was not statistically significantly different for abiraterone (HR = 1.04; 95% CI = 0.83–1.28) or enzalutamide (HR = 0.88; 95% CI = 0.69–1.11) when compared to cabazitaxel in the Bayesian analysis. Anaemia (OR = 3.71; 95% CI = 1.01–10.44), diarrhoea (OR = 16.60; 95% CI = 1.41–75.31) and haematuria (OR = 3.88; 95% CI = 1.03–10.09) were more likely to occur in the cabazitaxel group than the abiraterone group, while pyrexia risk was higher in cabazitaxel compared to enzalutamide (OR = 36.23; 95% CI = 1.14–206.40). Frequentist analyses produced similar results. Conclusions The scarcity of clinical studies and lack of a common comparator limited analyses. The adverse event results must be interpreted with caution as many were based on small numbers. The results from this analysis indicate comparable survival outcomes and adverse event profiles. As these pivotal studies may not reflect the contemporary treatment landscape and patient profiles, additional research, including head-to-head clinical trials and real world observational studies, should be conducted to further elucidate the beneficial effects of these therapies.

The potential relationship between red meat consumption and colorectal cancer (CRC) has been the subject of scientific debate. Given the high degree of resulting uncertainty, our objective was to update the state of the science by conducting a systematic quantitative assessment of the epidemiologic literature. Specifically, we updated and expanded our previous meta-analysis by integrating data from new prospective cohort studies and conducting a broader evaluation of the relative risk estimates by specific intake categories. Data from 27 independent prospective cohort studies were meta-analyzed using random-effects models, and sources of potential heterogeneity were examined through subgroup and sensitivity analyses. In addition, a comprehensive evaluation of potential dose-response patterns was conducted. In the meta-analysis of all cohorts, a weakly elevated summary relative risk was observed (1.11, 95% CI: 1.03-1.19); however, statistically significant heterogeneity was present. In general, summary associations were attenuated (closer to the null and less heterogeneous) in models that isolated fresh red meat (from processed meat), adjusted for more relevant factors, analyzed women only, and were conducted in countries outside of the United States. Furthermore, no clear patterns of dose-response were apparent. In conclusion, the state of the epidemiologic science on red meat consumption and CRC is best described in terms of weak associations, heterogeneity, an inability to disentangle effects from other dietary and lifestyle factors, lack of a clear dose-response effect, and weakening evidence over time. KEY TEACHING POINTS: •The role of red meat consumption in colorectal cancer risk has been widely contested among the scientific community.•In the current meta-analysis of red meat intake and colorectal cancer, we comprehensively examined associations by creating numerous sub-group stratifications, conducting extensive sensitivity analyses, and evaluating dose-response using several different methods.•Overall, all summary associations were weak in magnitude with no clear dose-response patterns.•Interpretation of findings from epidemiologic studies investigating diet and health outcomes involves numerous methodological considerations, such as accurately measuring food intake, dietary pattern differences across populations, food definitions, outcome classifications, bias and confounding, multicollinearity, biological mechanisms, genetic variation in metabolizing enzymes, and differences in analytical metrics and statistical testing parameters.

Total disc replacement was clinically introduced to reduce pain and preserve segmental motion of the lumbar and cervical spine. Previous case studies have reported on the wear and adverse local tissue reactions around artificial prostheses, but it is unclear how design and biomaterials affect clinical outcomes.Which design and material factors are associated with differences in clinical wear performance (implant wear and periprosthetic tissue response) of (1) lumbar and (2) cervical total disc replacements?We performed a systematic review on the topics of implant wear and periprosthetic tissue response using an advanced search in MEDLINE and Scopus electronic databases. Of the 340 references identified, 33 were retrieved for full-text evaluation, from which 16 papers met the inclusion criteria (12 on lumbar disc replacement and five on cervical disc replacement; one of the included studies reported on both lumbar and cervical disc replacement), which involved semiquantitative analysis of wear and adverse local tissue reactions along with a description of the device used. An additional three papers were located by searching bibliographies of key articles. There were seven case reports, three case series, two case-control studies, and seven analytical studies. The Methodological Index for Non-randomized Studies (MINORS) Scale was used to score case series and case-control studies, which yielded mean scores of 10.3 of 16 and 17.5 of 24, respectively. In general, the case series (three) and case-control (two) studies were of good quality.In lumbar regions, metal-on-polymer devices with mobile-bearing designs consistently generated small and large polymeric wear debris, triggering periprosthetic tissue activation of macrophages and giant cells, respectively. In the cervical regions, metal-on-polymer devices with fixed-bearing designs had similar outcomes. All metal-on-metal constructs tended to generate small metallic wear debris, which typically triggered an adaptive immune response of predominantly activated lymphocytes. There were no retrieval studies on one-piece prostheses.This review provides evidence that design and biomaterials affect the type of wear and inflammation. However, clinical study design, followup, and analytical techniques differ among investigations, preventing us from drawing firm conclusions about the relationship between implant design and wear performance for both cervical and lumbar total disc replacement.

Interpreting epidemiologic studies of diet and health is often complex because it involves many methodological issues and sources of uncertainty. Pertinent examples are false-positive and false-negative results, that is, findings that erroneously indicate the presence or absence, respectively, of association. Our objective in this commentary is to help nutrition and other health professionals interpret epidemiological studies when faced with this task. Our aim is not to provide an exhaustive discussion of all the methodological nuances of nutritional epidemiology; rather, we focus on some of the salient factors when interpreting findings from dietary studies, and the role that uncertainty (namely, from false-positives) plays, using relevant examples from the past few decades.

background Although a large body of literature has been devoted to examining the relationship between eicosapentaenoic and docosahexaenoic acids (EPA+DHA) and blood pressure, past systematic reviews have been hampered by narrow inclusion criteria and a limited scope of analytical subgroups. In addition, no meta-analysis to date has captured the substantial volume of randomized controlled trials (RCTs) published in the past 2 years. The objective of this meta-analysis was to examine the effect of EPA+DHA, without upper dose limits and including food sources, on blood pressure in RCTs. methods Random-effects meta-analyses were used to generate weighted group mean differences and 95% confidence intervals (CIs) between the EPA+DHA group and the placebo group. Analyses were conducted for subgroups defined by key subject or study characteristics. results Seventy RCTs were included. Compared with placebo, EPA+DHA provision reduced systolic blood pressure (−1.52 mm Hg; 95% confidence interval (CI) = −2.25 to −0.79) and diastolic blood pressure (−0.99 mm Hg; 95% CI = −1.54 to −0.44) in the meta-analyses of all studies combined. The strongest effects of EPA+DHA were observed among untreated hypertensive subjects (systolic blood pressure = −4.51 mm Hg, 95% CI = −6.12 to −2.83; diastolic blood pressure = −3.05 mm Hg, 95% CI = −4.35 to −1.74), although blood pressure also was lowered among normotensive subjects (systolic blood pressure = −1.25 mm Hg, 95% CI = −2.05 to −0.46; diastolic blood pressure = −0.62 mm Hg, 95% CI = −1.22 to −0.02). conclusions Overall, available evidence from RCTs indicates that provision of EPA+DHA reduces systolic blood pressure, while provision of ≥2 grams reduces diastolic blood pressure.

The objective of the present meta-analysis was to examine the effect of whey protein (WP), with or without resistance exercise, on body weight and body composition in randomized controlled trials (RCTs) conducted in generally healthy adult study populations.A comprehensive literature search was conducted to identify RCTs that investigated WP (concentrate, isolate, or hydrolystate) and body weight, body mass index (BMI), body fat, lean body mass (LBM), fat-free mass (FFM), and waist circumference. Random effects meta-analyses were conducted to generate weighted group mean differences (WGMD) for between-group comparisons (WP vs other protein sources or carbohydrates) and within-WP group comparisons (i.e., differences from baseline to trial end). Studies were classified into 2 distinct groups-WP as a supplement without dietary modification (WPS) and WP as a replacement for other sources of calories (WPR)-and were meta-analyzed separately. Subgroup analyses included examining the effect of resistance exercise and type of WP on the relationship between WP and body composition.Fourteen RCTs were included, with a total of 626 adult study completers. Five studies examined the effects of WPR and the remaining 9 studies examined the effects of WPS. Body weight (WGMD: -4.20 kg, 95% confidence interval [CI], -7.67, -0.73) and body fat (WGMD: -3.74 kg, 95% CI, -5.98, -1.50) were significantly decreased from baseline in the WPR within-group analyses. In the between-group analyses, the effects of WP were more favorable when compared with carbohydrates than protein sources other than whey, although findings did not reach statistical significance. Results from the subgroup analyses indicated a statistically significant increase in LBM (WGMD: 2.24 kg, 95% CI, 0.66, 3.81) among studies that included a resistance exercise component along with WP provision.The current body of literature supports the use of WP, either as a supplement combined with resistance exercise or as part of a weight loss or weight maintenance diet, to improve body composition parameters.

523 Background: A systematic literature review and meta-analysis was conducted to summarize the prevalence of KRAS, NRAS, and BRAF mutations in mCRC patients. These mutations have substantial implications for treatment decisions among mCRC patients. Methods: Multiple databases were searched to identify observational studies and clinical trials (standard of care arms only) that reported mutation status among mCRC patients. Random effects meta-analysis models were used to estimate summary prevalence estimates for each of the mutations. Subgroup and sensitivity analyses were conducted to identify potential sources of heterogeneity in mutation prevalence. Results: The meta-analyses included 275 studies comprising over 77,000 mCRC patients. The summary prevalence estimate was 35.9% for KRAS mutations, 7.1% for BRAF mutations, and 4.1% for NRAS mutations. Female patients had significantly more KRAS and BRAF mutations than males ( KRAS: 42.2% vs. 37.3%, p = 0.011; BRAF: 11.0% vs. 7.9%, p = 0.018), and significant variation by study location was observed for both KRAS (p = 0.025) and BRAF (p = 0.002) mutation prevalence. Conclusions: The prevalence of KRAS, BRAF, or NRAS mutations in mCRC patients varies significantly by gender and study location. compared to patients with wild-type tumors. The results of these analyses are informative for clinicians, patients, and researchers.

526 Background: Infusion reactions have been reported in studies of metastatic colorectal cancer (mCRC) patients treated with anti-EGFR therapies, including cetuximab and panitumumab, with incidences ranging from 0-33%. A systematic literature review and meta-analysis were conducted to estimate the incidence of infusion reactions in this population and identify variations in this incidence by patient and study characteristics. Methods: Multiple scientific databases were searched to identify observational studies or clinical trials of mCRC patients treated with anti-EGFR therapies that reported rates of infusion reactions, hypersensitivity, or allergy/anaphylaxis. Random effects models were used to meta-analyze the incidence of infusion reactions overall and stratified by therapy, study design, geographic location, KRAS mutation status, and grade of reaction severity. Results: Among 48 studies included in this meta-analysis, the pooled estimate for infusion reaction incidence was 0.049 (95% CI: 0.036 – 0.065), or nearly 5%. Reactions of grades 1 or 2 were more common than reactions of grades 3-5 (0.089 vs. 0.028) No significant variations in infusion reaction incidence were observed by study design, KRAS status, or study location. Conclusions: Infusion reactions occur in approximately 5% of mCRC patients treated with anti-EGFR therapies and the incidence varies significantly by grade and severity. Future studies should consider investigating survival outcomes for only those patients with infusion reactions to determine its prognostic relevance.

Adopting a Mediterranean-style diet has garnered a great deal of scientific and public interest based, at least in part, on claims that it may help to prevent chronic disease, particularly when compared with a so-called Western dietary pattern or lifestyle. Mediterranean diets may be defined in variable ways, although they are commonly characterized by a high consumption of vegetables, fruit, grains, legumes, fish, and eggs, along with a moderate intake of meat, oil, and wine (1). It may have originated in ancient civilizations, but scientifically, the Mediterranean diet has been the focal point of much research over the past 20 y (2). Indeed, a large volume of studies have been published that have evaluated potential associations betweenMediterranean-style diets and chronic disease, and as a result, many reviews on this topic have been published. Whether these reviews are high-quality assessments of the evidence is an open question. In this issue of the Journal, Huedo-Medina et al. (3) conducted a review of the methodologic quality of meta-analyses and systematic reviews on the Mediterranean diet and cardiovascular disease outcomes. The authors evaluated quality using the AMSTAR method, which stands for A Measurement Tool to Assess Systematic Reviews (4). AMSTAR has been shown to be a valid and reliable measurement tool for the assessment of the methodologic quality of systematic reviews (5). In brief, the AMSTAR tool contains 11 items, which were modified slightly by Huedo-Medina et al.. AMSTAR can be used to assess whether the following components were reported: 1) study design including the study population characteristics, 2) the literature search protocol including the ability to replicate the identification of relevant articles, 3) the coding of studies in terms of individual study quality, and 4) the analysis and interpretation of reviews including meta-analysis methodology. Overall, the authors found that the body of review literature on Mediterranean diets and cardiovascular disease outcomes did not satisfy fully the methodologic quality standards of the modified AMSTAR instrument. The average score was only 31.2% of 11 AMSTAR elements (i.e.,;3.4 of 11 items). Reviews assessed to be of higher methodologic quality were more likely to be published in journals with higher impact factors. This may be expected, given that it is likely that higher quality journals may place more emphasis on rigorous methodology standards by requiring prospective authors to use quality tools, including others such as the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement when submitting a manuscript for publication. On the basis of a review of Huedo-Medina et al.’s evaluation, reviews of the scientific evidence pertaining to the relation between the Mediterranean diet and cardiovascular disease are not particularly informative, although the authors themselves did not review the underlying evidence. That is the bottom line here and an unfortunate one. Put another way, we need reviews of higher methodologic quality to advance the science of diet and chronic disease, and we need analytic studies with better methodologic characteristics to build the foundation for the reviews. In line with these conclusions, the purpose of this brief commentary is to highlight the challenges of both conducting systematic reviews (which include quantitative meta-analyses) and performing “reviews of reviews.” The scientific community has been discussing the need for a systematic approach to reviewing the scientific and medical literature since the mid-1980s (6). For detailed discussions of the method and examples of its application, see references 4 and 6–21. With this background in mind, we suggest that some key questions need to be remembered.

Background: We published a meta-analysis of the association between work as a motor vehicle mechanic and mesothelioma in 2004. Since then, several relevant studies on this topic have been published. Thus, to update the state-of-the-science on this issue, we conducted a new systematic review and meta-analysis. Methods: A comprehensive PubMed literature search through May 2014 was conducted to identify studies that reported relative risk estimates for mesothelioma among motor vehicle mechanics (in general), and those who were engaged in brake repair (specifically). Studies were scored and classified based on study characteristics. Random-effects meta-analyses generated summary relative risk estimates (SRREs) and corresponding 95% confidence intervals (CI). Heterogeneity of results was examined by calculating Q-test P-values (P-H) and I 2 estimates. Sub-group and sensitivity analyses were conducted for relevant study characteristics and quality measures. Results: Ten case-control studies, one cohort study, and five proportionate mortality ratio (PMR)/standardized mortality odds ratio (SMOR) studies were identified and included in the quantitative assessment. Most meta-analysis models produced SRREs below 1.0, and no statistically significant increases in mesothelioma were observed. The SRRE for all studies was 0.80 (95% CI: 0.61-1.05) with significant heterogeneity (P-H

Addition of probiotics to infant formula may positively affect immune function in nonexclusively breastfed infants. This study aimed to investigate the effect of infant starter formula containing the probiotic Bifidobacterium animalis subspecies lactis (Bb12) on intestinal immunity and inflammation.Six-week-old healthy, full-term infants (n = 172) were enrolled in a prospective, randomized, double-blind, controlled clinical trial with 2 groups studied in parallel to a breastfed comparison group. Formula-fed (FF) infants were randomized to partially hydrolyzed whey formula (CON) or the same formula containing 10(6) colony-forming units (CFU) Bb12/g (PRO) for 6 weeks. Fecal secretory IgA (sIgA), calprotectin, lactate, and stool pH were assessed at baseline, 2 weeks, and 6 weeks. Anti-poliovirus-specific IgA and anti-rotavirus-specific IgA were assessed at 2 and 6 weeks.Among vaginally delivered FF infants, PRO consumption increased (P.05) fecal sIgA compared to CON. Anti-poliovirus-specific IgA concentration increased (P.05) in all infants consuming PRO, whereas anti-rotavirus-specific IgA tended to increase (P = .056) with PRO consumption in cesarean-delivered infants. Anthropometrics and tolerance did not differ significantly between FF infants.Infants consuming formula with Bb12 produced feces with detectable presence of Bb12 and augmented sIgA concentration. Furthermore, cesarean-delivered infants consuming Bb12 had heightened immune response, as evidenced by increased anti-rotavirus- and anti-poliovirus-specific IgA following immunization. These results demonstrate that negative immune-related effects of not breastfeeding and cesarean delivery can be mitigated by including Bb12 in infant formula, thereby providing infants a safe, dietary, immune-modulating bacterial introduction.

To systematically evaluate epidemiologic studies on pesticides and colon cancer and rectal cancer in agricultural pesticide applicator populations using a transparent “weight-of-evidence” (WOE) methodological approach. Twenty-nine (29) publications from the Agricultural Health Study (AHS) and 13 additional epidemiologic studies were identified that reported data for pesticide applicators and/or specific pesticide compounds and colorectal, colon, or rectal cancer. The AHS evaluated pesticide applicators as well as dose–response associations for specific pesticide compounds, whereas the large majority of non-AHS evaluated applicators but did not analyze specific compounds or dose–response trends. This WOE assessment of 153 different pesticide–outcome pairs emphasized several key evidentiary features: existence of statistically significant relative risks, magnitude of observed associations, results from the most reliable exposure assessments, and evidence of convincing dose–response relationships (i.e., those monotonically increasing, with statistically significant trend tests). Occupation as a pesticide applicator or pesticide application as a farming-related function was not associated with increasing the risk of colon or rectal cancer. Deficits of colon or rectal cancer were observed across most studies of pesticide applicators. After applying the WOE methodology to the epidemiologic studies of specific pesticide compounds and colon or rectal cancer, a number of pesticide–outcome pairs were identified and evaluated further based on positive statistical associations. Of these, only two—aldicarb and colon cancer and imazethapyr and proximal colon cancer—appears to warrant further discussion regarding a possible causal relationship, although the epidemiologic data are limited. For the remainder, a lack of a clear dose–response trend, inconsistencies in associations between exposure metrics and comparison groups, imprecise associations, variable participation rates for analyses of specific compounds, and the reliance upon data from one study (the AHS) limit interpretation regarding risk. The available epidemiologic evidence does not support a causal relationship between occupation as a pesticide applicator or specific pesticide exposures and colon or rectal cancer.

Background Bone metastases are common in breast cancer patients and an important cause of morbidity and mortality. This review provides the first systematic and quantitative summary of the proportion of breast cancer patients with bone metastasis and their survival, presented by stage at diagnosis and length of follow-up. Materials and methods: A literature review was conducted using PubMed to identify full-text studies published in English 1999–2009. Studies were included if they had ≥100 adult patients with Stage I-IV breast cancer and were generalizable to the overall breast cancer population. The design and intent of included studies varied, including clinical trials of bone-targeted therapies and observational studies of cancer patients evaluating staging techniques, biomarkers, and other factors. To improve homogeneity, studies were grouped by stage at diagnosis, whether follow-up for bone metastases occurred, and the clinical point at which the proportion of patients with bone metastasis was estimated (e.g., at initial staging). Studies reporting survival were only included in quantitative summaries if survival was measured from the date of bone metastasis diagnosis. With regard to clinical trials of bisphosphonates, only proportion and survival data from the placebo group were utilized since the goal was to describe bone metastasis among patients untreated with bone-targeted therapy. Meta-analytic techniques were applied to (1) proportion data using random effects models to calculate weighted averages, and (2) survival data using an average of reported median survivals. Various sensitivity analyses were also conducted. Results: Nineteen studies were included in our quantitative summary of proportion data. At initial staging of breast cancer, 7% (N=2; 95% confidence interval [CI]=5-9%) of all patients had bone metastases and 69% (N=2; 95% CI=47-85%) of Stage IV patients had bone metastases. Among breast cancer patients followed from the diagnosis of Stage I-III breast cancer, 10% (N=6; 95% CI=6-15%) had bone metastases after a median follow-up Discussion: Significant heterogeneity across studies was observed, reflecting the variability in study populations, locations, and other factors. Despite this and other limitations (e.g., few studies in some categories), this represents the first analysis of the literature to quantify the prevalence and survival of bone metastasis in breast cancer. Our results indicated that bone is a site of metastasis among more than 50% of Stage IV patients at diagnosis of breast cancer. Median survival among breast cancer patients with metastases located solely in the bone is at least six months longer compared to those with metastases at multiple sites (including bone) and sites other than bone. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-16-07.

Meat consumption and cancer has been evaluated in hundreds of epidemiologic studies over the past three decades; however, the possible role of this food group on carcinogenesis is equivocal. In this comprehensive review, the currently available epidemiologic prospective studies of red meat intake and colorectal cancer are summarized to provide a greater understanding of any potential relationships. Specifically, salient demographic, methodological and analytical information is synthesized across 35 prospective studies. Collectively, associations between red meat consumption and colorectal cancer are generally weak in magnitude, with most relative risks below 1.50 and not statistically significant, and there is a lack of a clear dose-response trend. Results are variable by anatomic tumour site (colon vs. rectum) and by gender, as the epidemiologic data are not indicative of a positive association among women while most associations are weakly elevated among men. Colinearity between red meat intake and other dietary factors (e.g. Western lifestyle, high intake of refined sugars and alcohol, low intake of fruits, vegetables and fibre) and behavioural factors (e.g. low physical activity, high smoking prevalence, high body mass index) limit the ability to analytically isolate the independent effects of red meat consumption. Because of these factors, the currently available epidemiologic evidence is not sufficient to support an independent positive association between red meat consumption and colorectal cancer.

We reanalyzed the Libby vermiculite miners' cohort assembled by Sullivan to estimate potency factors for lung cancer, mesothelioma, nonmalignant respiratory disease (NMRD), and all-cause mortality associated with exposure to Libby fibers. Our principal statistical tool for analyses of lung cancer, NMRD, and total mortality in the cohort was the time-dependent proportional hazards model. For mesothelioma, we used an extension of the Peto formula. For a cumulative exposure to Libby fiber of 100 f/mL-yr, our estimates of relative risk (RR) are as follows: lung cancer, RR = 1.12, 95% confidence interval (CI) =[1.06, 1.17]; NMRD, RR = 1.14, 95% CI =[1.09, 1.18]; total mortality, RR = 1.06, 95% CI =[1.04, 1.08]. These estimates were virtually identical when analyses were restricted to the subcohort of workers who were employed for at least one year. For mesothelioma, our estimate of potency is K(M) = 0.5 x 10(-8), 95% CI =[0.3 x 10(-8), 0.8 x 10(-8)]. Finally, we estimated the mortality ratios standardized against the U.S. population for lung cancer, NMRD, and total mortality and obtained estimates that were in good agreement with those reported by Sullivan. The estimated potency factors form the basis for a quantitative risk assessment at Libby.

The incidence of atopic dermatitis (AD) is increasing worldwide. Clinical studies have observed reduced risks of AD among infants fed with 100% whey partially hydrolyzed infant formula (PHF-W) compared with intact protein cow's milk formula. To evaluate this potential relationship more comprehensively, a systematic review of the literature was conducted. Studies (n = 18, representing 12 distinct study populations) that specified the protein source of the formula, evaluated healthy-term infants, compared the use of PHF-W with intact protein cow's milk formula, and reported results for AD were included. A critical assessment of the methodological quality of studies was conducted. In all studies, a reduced incidence of AD and/or atopic manifestations that included AD was observed. The cumulative incidence of AD was significantly lower among infants over at least 3 years of follow-up in the PHF-W group compared with the intact protein cow's milk group. Exclusive breastfeeding should be encouraged as the primary means to prevent atopic risk. However, when infants are not exclusively breastfed, PHF-W may be considered an effective measure to potentially reduce the risk of developing AD.

The objective of the present review was to examine the potential association between animal fat intake and breast cancer. We conducted a meta-analysis and review of epidemiological cohort studies, including data reported in the Pooling Project publication of Prospective Studies of Diet and Cancer. Random- and fixed-effects models were utilised to generate summary relative risk estimates (SRRE), and sensitivity and influence analyses were conducted. In the meta-analysis that included data reported in the Pooling Project publication of prospective cohorts (n 8) and subsequent publications of cohort studies (n 3), no significant association was observed comparing the highest category of animal fat intake with the lowest (SRRE 1·03; 95 % CI: 0·76, 1·40). Similarly, no significant association between a 5 % increment of energy from animal fat intake and breast cancer (SRRE 1·02; 95 % CI 0·97, 1·07) was observed in the meta-analysis of these studies. In conclusion, the results of the present quantitative assessment are not supportive of a positive independent association between consumption of animal fat and breast cancer, although findings may be sensitive to the type of dietary instrument used in cohort studies.

Most discoveries of cancer biomarkers involve construction of a single model to determine predictions of survival.. 'Data-mining' techniques, such as artificial neural networks (ANNs), perform better than traditional methods, such as logistic regression. In this study, the quality of multiple predictive models built on a molecular data set for colorectal cancer (CRC) was evaluated. Predictive models (logistic regressions, ANNs, and decision trees) were compared, and the effect of techniques for variable selection on the predictive quality of these models was investigated. The Kolmogorov-Smirnoff (KS) statistic was used to compare the models. Overall, the logistic regression and ANN methods outperformed use of a decision tree. In some instances (e.g., for a model that included 'all variables without tumor stage' and use of a decision tree for variable selection), the ANN marginally outperformed logistic regression, although the difference between the accuracy of the KS statistic was minimal (0.80 versus 0.82). Regardless of the variable(s) and the methods for variable selection, all three predictive models identified survivors and non-survivors with the same level of statistical accuracy.

Background: In the recent World Cancer Research Fund/American Institute for Cancer Research report of diet and cancer, it was concluded that there is limited but suggestive evidence that animal fat intake increases the risk of colorectal cancer. Objective: To clarify this potential relation, we conducted metaanalyses across a variety of subgroups, incorporating data from additional studies. Design: Analyses of high compared with low animal fat intakes and categorical dose-response evaluations were conducted. Subgroup analyses, consisting of evaluations by study design, sex, and tumor site were also performed. Results: Six prospective cohort studies with comprehensive dietary assessments, contributing 1070 cases of colorectal cancer and ’1.5 million person-years of follow-up, were identified. The summary relative risk estimate (SRRE) for these studies was 1.04 (95% CI: 0.83, 1.31; P for heterogeneity ¼ 0.221) on the basis of high compared with low intakes. When data from case-control studies were combined with the cohort data, the resulting SRRE was 1.15 (95% CI: 0.93, 1.42) with increased variability (P for heterogeneity ¼ 0.015). In our dose-response analysis of the cohort studies, no association between a 20-g/d increment in animal fat intake and colorectal cancer was observed (SRRE: 1.02; 95% CI: 0.95, 1.09). In a separate analysis of 3 prospective cohort studies that reported data for animal protein or meat protein, no significant association with colorectal cancer was observed (SRRE: 0.90; 95% CI: 0.70, 1.15). Conclusion: On the basis of the results of this quantitative assessment, the available epidemiologic evidence does not appear to support an independent association between animal fat intake or animal protein intake and colorectal cancer. Am J Clin Nutr 2009;89:1‐8.

We compared, updated, and expanded the analyses of two previous meta-analyses of personal hair dye exposure and bladder cancer, and briefly discussed the biological plausibility of a systemic hazard to human health from exposure to para-phenylenediamine (PPD), a key chemical in hair dyes.The meta-analysis included 11 case-control studies and one cohort study. We evaluated heterogeneity across studies and conducted sensitivity and influence analyses.No association was found between any personal use of hair dye and bladder cancer among women (meta-relative risk [mRR] = 1.01, 95% CI: 0.89-1.14), men (mRR = 0.82, 95% CI: 0.60-1.14), or both sexes combined (mRR = 0.97, 95% CI: 0.87-1.08). No statistically significant mRRs were found among the studies that reported data for permanent hair dye use (mRR = 1.06, 95% CI: 0.89-1.27), duration of any hair dye use (mRR = 1.00, 95% CI: 0.85-1.19), duration of permanent hair dye use (mRR = 1.31 95% CI 0.78-2.19), lifetime applications of any hair dye use (mRR = 1.12 (95% CI: 0.72-1.72) or permanent hair dye use (mRR = 1.59, 95% CI 0.69-3.64), or dark color hair dye use (mRR = 0.94, 95% CI: 0.74-1.19).The results of this meta-analysis of epidemiologic studies do not indicate a causal association between personal hair dye use and bladder cancer.

The non-Hodgkin lymphomas (NHL) are a heterogeneous group of B-cell and T-cell neoplasms that arise primarily in the lymph nodes. NHL incidence rates in the US doubled between about 1970 and 1990, and stabilized during the 1990s. NHL accounts for approximately 3.4% of cancer deaths in the US. Although some of the observed patterns in NHL have been related to HIV/AIDS, these conditions cannot fully explain the magnitude of the changes; neither do changes in classification systems nor improved diagnostic capabilities. Studies of occupational and environmental exposures (e.g., pesticides, solvents) have produced no consistent pattern of significant positive associations. Inverse associations with ultraviolet radiation exposure and alcohol and fish intake, and positive associations with meat and saturated fat intake have been reported in several studies; additional studies are needed to confirm or refute these associations. Family history of NHL or other hematolympho-proliferative cancers and personal history of several autoimmune disorders are associated with increased risk of NHL, but are not likely to account for a large proportion of cases. HIV and other infectious agents, such as human herpesvirus 8 and Epstein-Barr, appear to be associated with differing types of NHL, such as some B-cell lymphomas. Future epidemiologic studies should evaluate associations by NHL type, enhance exposure information collected, and elucidate factors that may identify susceptible (or resistant) subpopulations because of genetic, immunologic or other characteristics. The extent to which the etiology of NHL types may differ is important to resolve in ongoing and future studies.

Multiple myeloma, a neoplasm of plasma cells, accounts for approximately approximately 15% of lymphatohematopoietic cancers (LHC) and 2% of all cancers in the US. Incidence rates increase with age, particularly after age 40, and are higher in men, particularly African American men. The etiology is unknown with no established lifestyle, occupational or environmental risk factors. Although several factors have been implicated as potentially etiologic, findings are inconsistent. We reviewed epidemiologic studies that evaluated lifestyle, dietary, occupational and environmental factors; immune function, family history and genetic factors; and the hypothesized precursor, monoclonal gammopathies of undetermined significance (MGUS). Because multiple myeloma is an uncommon disease, etiologic assessments can be difficult because of small numbers of cases in occupational cohort studies, and few subjects reporting exposure to specific agents in case-control studies. Elevated risks have been reported consistently among persons with a positive family history of LHC. A few studies have reported a relationship between obesity and multiple myeloma, and this may be a promising area of research. Factors underlying higher incidence rates of multiple myeloma in African Americans are not understood. The progression from MGUS to multiple myeloma has been reported in several studies; however, there are no established risk factors for MGUS. To improve our understanding of the causes of multiple myeloma, future research efforts should seek the causes of MGUS. More research is also needed on the genetic factors of multiple myeloma, given the strong familial clustering of the disease.

Prostate cancer remains a significant public health concern among men in the U.S. and worldwide. Epidemiologic studies have generally produced inconclusive results for dietary risk factors for prostate cancer, including consumption of red and processed meats. We aimed to update a previous meta-analysis of prospective cohorts of red and processed meats and prostate cancer with the inclusion of new and updated cohort studies, as well as evaluate meat cooking methods, heme iron, and heterocyclic amine (HCA) intake exposure data. A comprehensive literature search was performed and 26 publications from 19 different cohort studies were included. Random effects models were used to calculate summary relative risk estimates (SRREs) for high vs. low exposure categories. Additionally, meta-regression analyses and stratified intake analyses were conducted to evaluate dose-response relationships. The SRREs for total prostate cancer and total red meat consumption, fresh red meat consumption, and processed meat consumption were 1.02 (95 % CI: 0.92–1.12), 1.06 (95 % CI: 0.97–1.16), and 1.05 (95 % CI: 1.01–1.10), respectively. Analyses were also conducted for the outcomes of non-advanced, advanced, and fatal prostate cancer when sufficient data were available, but these analyses did not produce significant results. No significant SRREs were observed for any of the meat cooking methods, HCA, or heme iron analyses. Dose-response analyses did not reveal significant patterns of associations between red or processed meat and prostate cancer. In conclusion, the results from our analyses do not support an association between red meat or processed consumption and prostate cancer, although we observed a weak positive summary estimate for processed meats.

This review aimed to update the state of the epidemiologic science by conducting a systematic review and meta-analysis to estimate the potential association between red meat consumption and type 2 diabetes. A comprehensive literature search was performed to identify relevant prospective studies. Random-effects meta-analyses were conducted to generate summary relative risk estimates (SRREs) between intakes of total red meat and individual items and risk of type 2 diabetes. Heterogeneity was examined in sub-group analyses. Meta regression, sensitivity, influence, and publication bias analyses were performed. A total of 20 studies were included and meta-analyzed. Meta-analysis of 13 independent cohorts of red meat intake and type 2 diabetes resulted in an SRRE of 1.18 (95% CI: 1.10-1.26), but statistically significant heterogeneity was present (p-H < 0.001, I2 = 64.08). Most meta-analysis models produced summary associations ranging between 1.0 and 1.3, but statistically significant heterogeneity was present...

We conducted a systematic review and meta-analysis to estimate the potential association between LCω-3PUFAs and prostate cancer (PC). A comprehensive literature search was performed through 2013 to identify prospective studies that examined dietary intakes of long-chain omega-3 polyunsaturated fatty acids (LCω-3PUFA) or blood biomarkers of LCω-3PUFA status and risk of PC. Random-effects meta-analyses were conducted to generate summary relative risk estimates (SRREs) for LCω-3PUFAs and total PC, and by stage and grade. Subgroup analyses were also conducted for specific fatty acids and other study characteristics. Twelve self-reported dietary intake and 9 biomarker studies from independent study populations were included in the analysis, with 446,243 and 14,897 total participants, respectively. No association between LCω-3PUFAs and total PC was observed (SRRE = 1.00, 95% CI: 0.93-1.09) for the dietary intake studies (high vs. low LCω-3PUFAs category comparison) or for the biomarker studies (SRRE of 1.07, 95% CI: 0.94-1.20). In general, most summary associations for the dietary intake studies were in the inverse direction, whereas the majority of summary associations for the biomarker studies were in the positive direction, but all were weak in magnitude. The results from this meta-analysis do not support an association between LCω-3PUFAs and PC.

Calcium plus vitamin D supplementation has been widely recommended to prevent osteoporosis and subsequent fractures; however, considerable controversy exists regarding the association of such suppl...

Methods: Meta-analysis and review of 14 occupational cohort and four case-control studies of workers exposed to trichloroethylene (TCE) to investigate the relation between TCE exposure and the risk of non-Hodgkin’s lymphoma (NHL). Studies were selected and categorised based on a priori criteria, and results from random effects meta-analyses are presented. Results: The summary relative risk estimates (SRRE) for the group of cohort studies that had more detailed information on TCE exposure was 1.29 (95% CI 1.00 to 1.66) for the total cohort and 1.59 (95% CI 1.21 to 2.08) for the seven studies that identified a specific TCE exposed sub-cohort. SRREs for three studies with cumulative exposure information were 1.8 (95% CI 0.62 to 5.26) for the lowest exposure category and 1.41 (95% CI 0.61 to 3.23) for the highest category. Comparison of SRREs by levels of TCE exposure did not indicate exposure-response trends. The remaining cohort studies that identified TCE exposure but lacked detailed exposure information had an SRRE of 0.843 (95% CI 0.72 to 0.98). Case-control studies had an SRRE of 1.39 (95% CI 0.62 to 3.10). Statistically significant findings for the Group 1 studies were driven by the results from the subgroup of multiple industry cohort studies (conducted in Europe) (SRRE = 1.86; 95% CI 1.27 to 2.71). The SRRE for single industry cohort studies was not significantly elevated (SRRE = 1.25; 95% CI 0.87 to 1.79). Conclusions: Interpretation of overall findings is hampered by variability in results across the Group 1 studies, limited exposure assessments, lack of evidence of exposure response trends, lack of supportive information from toxicological and mechanistic data, and absence of consistent findings in epidemiologic studies of exposure and NHL. Although a modest positive association was found in the TCE sub-cohort analysis, a finding attributable to studies that included workers from multiple industries, there is insufficient evidence to suggest a causal link between TCE exposure and NHL.

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.

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Introduction Subjective memory complaints are common with aging. Docosahexaenoic acid (DHA; 22:6 n-3) is a long-chain polyunsaturated fatty acid (LCPUFA) and an integral part of neural membrane phospholipids that impacts brain structure and function. Past research demonstrates a positive association between DHA plasma status/dietary intake and cognitive function. Objectives The current meta-analysis was designed to determine the effect of DHA intake, alone or combined with eicosapentaenoic acid (EPA; 20:5 n-3), on specific memory domains: episodic, working, and semantic in healthy adults aged 18 years and older. A secondary objective was to systematically review/summarize the related observational epidemiologic literature. Methods A systematic literature search of clinical trials and observational studies that examined the relationship between n-3 LCPUFA on memory outcomes in healthy adults was conducted in Ovid MEDLINE and EMBASE databases. Studies of subjects free of neurologic disease at baseline, with or without mild memory complaints (MMC), were included. Random effects meta-analyses were conducted to generate weighted group mean differences, standardized weighted group mean differences (Hedge’s g), z-scores, and p-values for heterogeneity comparing DHA/EPA to a placebo. A priori sub-group analyses were conducted to evaluate the effect of age at enrollment, dose level, and memory type tested. Results Episodic memory outcomes of adults with MMC were significantly (P 1 g/day DHA/EPA improved episodic memory (P

The U.S. Environmental Protection Agency (EPA) is developing an integrated assessment of non-cancer and cancer risk assessment of inorganic arsenic (iAs). Cardiovascular disease (CVD) in association with iAs exposure has been examined in a number of studies and provides a basis for evaluating a reference dose (RfD) for assessing potential non-cancer health risks of arsenic exposure. In this systematic review of low-level iAs exposure (i.e.

Background Nearly five percent of Americans suffer from functional constipation, many of whom may benefit from increasing dietary fiber consumption. The annual constipation-related healthcare cost savings associated with increasing intakes may be considerable but have not been examined previously. The objective of the present study was to estimate the economic impact of increased dietary fiber consumption on direct medical costs associated with constipation. Methods Literature searches were conducted to identify nationally representative input parameters for the U.S. population, which included prevalence of functional constipation; current dietary fiber intakes; proportion of the population meeting recommended intakes; and the percentage that would be expected to respond, in terms of alleviation of constipation, to a change in dietary fiber consumption. A dose–response analysis of published data was conducted to estimate the percent reduction in constipation prevalence per 1 g/day increase in dietary fiber intake. Annual direct medical costs for constipation were derived from the literature and updated to U.S. $ 2012. Sensitivity analyses explored the impact on adult vs. pediatric populations and the robustness of the model to each input parameter. Results The base case direct medical cost-savings was $12.7 billion annually among adults. The base case assumed that 3% of men and 6% of women currently met recommended dietary fiber intakes; each 1 g/day increase in dietary fiber intake would lead to a reduction of 1.9% in constipation prevalence; and all adults would increase their dietary fiber intake to recommended levels (mean increase of 9 g/day). Sensitivity analyses, which explored numerous alternatives, found that even if only 50% of the adult population increased dietary fiber intake by 3 g/day, annual medical costs savings exceeded $2 billion. All plausible scenarios resulted in cost savings of at least $1 billion. Conclusions Increasing dietary fiber consumption is associated with considerable cost savings, potentially exceeding $12 billion, which is a conservative estimate given the exclusion of lost productivity costs in the model. The finding that $12.7 billion in direct medical costs of constipation could be averted through simple, realistic changes in dietary practices is promising and highlights the need for strategies to increase dietary fiber intakes.

The potential relationship between red meat consumption and colorectal cancer (CRC) has been the subject of scientific debate, resulting in a high degree of uncertainty among scientists, public hea...

The present study estimated the economic impact of increased dietary fiber consumption on direct medical costs associated with constipation in the U.S. using a decision-analytic model. The model wa...

Multivitamin-multimineral (MVM) supplements are the most frequently used dietary supplements in the United States, with one third or more of the population using at least one daily. However, the health-related implications of MVM use are unclear. Thus, we systematically reviewed and summarized the prospective studies of MVM supplementation and all-cause and cause-specific mortality, as well as cardiovascular disease (CVD) and cancer incidence, to critically evaluate the current evidence on this topic. We included studies of generally healthy adult populations that evaluated multivitamin (the most commonly used dietary supplement) and/or multimineral supplement use or simultaneous use of 3 or more vitamins and minerals. We did not evaluate individual supplements. A total of 12 cohort studies and 3 primary prevention randomized controlled trials met our inclusion criteria. The majority of the studies were conducted in the United States (n = 11), and the remaining were conducted in European countries (n = 3) and Japan (n = 1). Although between-study methodological variation was present, most relative risks hovered closely around or slightly below the null value. No clear patterns of associations by study country, gender, smoking status, or frequency of use were observed. Based upon the available scientific evidence to date, supplementation with MVMs does not appear to increase all-cause mortality, cancer incidence or mortality, or CVD incidence or mortality and may provide a modest protective benefit.

Inhalation of asbestos resulting from living with and handling the clothing of workers directly exposed to asbestos has been established as a possible contributor to disease. This review evaluates epidemiologic studies of asbestos-related disease or conditions (mesothelioma, lung cancer, and pleural and interstitial abnormalities) among domestically exposed individuals and exposure studies that provide either direct exposure measurements or surrogate measures of asbestos exposure. A meta-analysis of studies providing relative risk estimates (n = 12) of mesothelioma was performed, resulting in a summary relative risk estimate (SRRE) of 5.02 (95% confidence interval [CI]: 2.48–10.13). This SRRE pertains to persons domestically exposed via workers involved in occupations with a traditionally high risk of disease from exposure to asbestos (i.e., asbestos product manufacturing workers, insulators, shipyard workers, and asbestos miners). The epidemiologic studies also show an elevated risk of interstitial, but more likely pleural, abnormalities (n = 6), though only half accounted for confounding exposures. The studies are limited with regard to lung cancer (n = 2). Several exposure-related studies describe results from airborne samples collected within the home (n = 3), during laundering of contaminated clothing (n = 1) or in controlled exposure simulations (n = 5) of domestic exposures, the latter of which were generally associated with low-level chrysotile-exposed workers. Lung burden studies (n = 6) were also evaluated as a surrogate of exposure. In general, available results for domestic exposures are lower than the workers’ exposures. Recent simulations of low-level chrysotile-exposed workers indicate asbestos levels commensurate with background concentrations in those exposed domestically.

To critically review and summarize the literature on nutritional and health outcomes of semi-elemental formulations on various nutritionally vulnerable patient populations who are unable to achieve adequate nutrition from standard oral diets.We conducted a comprehensive literature search of Pubmed and Embase databases. We manually screened articles that examined nutritional and health outcomes (e.g., growth, disease activity, gastrointestinal impairment, mortality, and economic impact) among various patient groups receiving semi-elemental diets. This review focused on full-text articles of randomized controlled clinical trials and other intervention studies, but pertinent abstracts and case studies were also included. Results pertaining primarily to tolerance, digestion, and absorption were summarized for each patient population in this systematic review.Results pertaining primarily to tolerance, digestion, and absorption were summarized for each patient population. The efficacy of semi-elemental whey hydrolyzed protein (WHP) diet have been reported in various nutritionally high risk patient populations including - Crohn's disease, short bowel syndrome, acute and chronic pancreatitis, cerebral palsy, cystic fibrosis, cerebrovascular accidents, human immunodeficiency virus, critically ill, and geriatrics. Collectively, the evidence from the medical literature indicates that feeding with a semi-elemental diet performs as well or better than parenteral or amino acid based diets in terms of tolerance, digestion, and nutrient assimilation measures across various disease conditions.Based on this comprehensive review of the literature, patient populations who have difficulty digesting or absorbing standard diets may be able to achieve improved health and nutritional outcomes through the use of semi-elemental WHP diets.

Background Hepatic metastases develop in approximately 50% of colorectal cancer (CRC) cases. We performed a review and meta-analysis to evaluate survival after resection of CRC liver metastases (CLMs) and estimated the summary effect for seven prognostic factors. Methods Studies published between 1999 and 2010, indexed on Medline, that reported survival after resection of CLMs, were reviewed. Meta-relative risks for survival by prognostic factor were calculated, stratified by study size and annual clinic volume. Cumulative meta-analysis results by annual clinic volume were plotted. Results Five- and 10-year survival ranged from 16% to 74% (median 38%) and 9% to 69% (median 26%), respectively, based on 60 studies. The overall summary median survival time was 3.6 (range: 1.7–7.3) years. Meta-relative risks (95% confidence intervals) by prognostic factor were: node positive primary, 1.6 (1.5–1.7); carcinoembryonic antigen level, 1.9 (1.1–3.2); extrahepatic disease, 1.9 (1.5–2.4); poor tumor grade, 1.9 (1.3–2.7); positive margin, 2.0 (1.7–2.5); >1 liver metastases, 1.6 (1.4–1.8); and >3 cm tumor diameter, 1.5 (1.3–1.8). Cumulative meta-analyses by annual clinic volume suggested improved survival with increasing volume. Conclusion The overall median survival following CLM liver resection was 3.6 years. All seven investigated prognostic factors showed a modest but significant predictive relationship with survival, and certain prognostic factors may prove useful in determining optimal therapeutic options. Due to the increasing complexity of surgical interventions for CLM and the inclusion of patients with higher disease burdens, future studies should consider the potential for selection and referral bias on survival.

Bryan, Nathan S Alexander, Dominik D Coughlin, James R Milkowski, Andrew L Boffetta, Paolo eng Research Support, Non-U.S. Gov't Review England 2012/08/15 06:00 Food Chem Toxicol. 2012 Oct;50(10):3646-65. doi: 10.1016/j.fct.2012.07.062. Epub 2012 Aug 4.; International audience; Nitrite and nitrate are naturally occurring molecules in vegetables and also added to cured and processed meats to delay spoilage and pathogenic bacteria growth. Research over the past 15 years has led to a paradigm change in our ideas about health effects of both nitrite and nitrate. Whereas, historically nitrite and nitrate were considered harmful food additives and listed as probable human carcinogens under conditions where endogenous nitrosation could take place, they are now considered by some as indispensible nutrients essential for cardiovascular health by promoting nitric oxide (NO) production. We provide an update to the literature and knowledge base concerning their safety. Most nitrite and nitrate exposure comes from naturally occurring and endogenous sources and part of the cell signaling effects of NO involve nitrosation. Nitrosation must now be considered broadly in terms of both S- and N-nitrosated species, since S-nitrosation is kinetically favored. Protein S-nitrosation is a significant part of the role of NO in cellular signal transduction and is involved in critical aspects of cardiovascular health. A critical review of the animal toxicology literature of nitrite indicates that in the absence of co-administration of a carcinogenic nitrosamine precursor, there is no evidence for carcinogenesis. Newly published prospective epidemiological cohort studies indicate that there is no association between estimated intake of nitrite and nitrate in the diet and stomach cancer. This new and growing body of evidence calls for a reconsideration of nitrite and nitrate safety.