Tea Consumption and Risk of Cancer: An Umbrella Review and Meta-Analysis of Observational Studies.

Tea is one of the most widely consumed beverages, but its association with cancer risk remains controversial and unclear. We performed an umbrella review to clarify and determine the associations between tea consumption and various types of cancer by summarizing and recalculating the existing meta-analyses. Meta-analyses of observational studies reporting associations between tea consumption and cancer risk were searched on PubMed and Embase. Associations found to be statistically significant were further classified into levels of evidence (convincing, suggestive, or weak), based on P value, between-study heterogeneity, prediction intervals, and small study effects. Sixty-four observational studies (case-control or cohort) corresponding to 154 effect sizes on the incidence of 25 types of cancer were included. Forty-three (27.9%) results in 15 different types of cancer were statistically significant. When combining all studies on the same type of cancer, 19 results in 11 different types of cancer showed significant associations with lower risk of gastrointestinal tract organ cancer (oral, gastric, colorectal, biliary tract, and liver cancer), breast cancer, and gynecological cancer (endometrial and ovarian cancer) as well as leukemia, lung cancer, and thyroid cancer. Only the reduced risk of oral cancer in tea-consuming populations (OR = 0.62; 95% CI: 0.55, 0.72; P value < 10-6) was supported by convincing evidence. Suggestive evidence was found for 6 results on biliary tract, breast, endometrial, liver, and oral cancer. To summarize, tea consumption was shown to have protective effects on some types of cancer, particularly oral cancer. More well-designed prospective studies are needed with consideration of other factors that can cause biases.

Consumption of Fish and ω-3 Fatty Acids and Cancer Risk: An Umbrella Review of Meta-Analyses of Observational Studies.

Multiple studies have suggested that ω-3 fatty acid intake may have a protective effect on cancer risk; however, its true association with cancer risk remains controversial. We performed an umbrella review of meta-analyses to summarize and evaluate the evidence for the association between ω-3 fatty acid intake and cancer outcomes. We searched PubMed, Embase, and the Cochrane Database of Systematic Reviews from inception to December 1, 2018. We included meta-analyses of observational studies that examined associations between intake of fish or ω-3 fatty acid and cancer risk (gastrointestinal, liver, breast, gynecologic, prostate, brain, lung, and skin) and determined the level of evidence of associations. In addition, we appraised the quality of the evidence of significant meta-analyses by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. We initially screened 598 articles, and 15 articles, including 57 meta-analyses, were eligible. Among 57 meta-analyses, 15 reported statistically significant results. We found that 12 meta-analyses showed weak evidence of an association between ω-3 fatty acid intake and risk of the following types of cancer: liver cancer (n = 4 of 6), breast cancer (n = 3 of 14), prostate cancer (n = 3 of 11), and brain tumor (n = 2 of 2). In the other 3 meta-analyses, studies of endometrial cancer and skin cancer, there were no assessable data for determining the evidence levels. No meta-analysis showed convincing, highly suggestive, or suggestive evidence of an association. In the sensitivity analysis of meta-analyses by study design, we found weak associations between ω-3 fatty acid intake and breast cancer risk in cohort studies, but no statistically significant association in case-control studies. However, the opposite results were found in case of brain tumor risk. Although ω-3 fatty acids have been studied in several meta-analyses with regard to a wide range of cancer outcomes, only weak associations were identified in some cancer types, with several limitations. Considering the nonsignificant or weak evidence level, clinicians and researchers should cautiously interpret reported associations between ω-3 fatty acid consumption and cancer risks.

Hyperprogressive Disease during Anti-PD-1 (PDCD1) / PD-L1 (CD274) Therapy: A Systematic Review and Meta-Analysis.

Hyperprogressive disease (HPD) is a recently acknowledged pattern of rapid tumor progression after the initiation of immune checkpoint inhibitors. HPD has been observed across various types of tumors and has been associated with poor survival. We performed a meta-analysis to identify baseline (i.e., prior to programmed cell death 1 [PD-1, PDCD1] / programmed cell death 1 ligand 1 [PD-L1, CD274] inhibitor therapy) patient factors associated with risks of developing HPD during PD-1/PD-L1 inhibitor therapy. We searched eight databases until 6 June 2019. We calculated the summary odds ratio (OR) and its 95% confidence interval (CI) using the random-effects model and explored between-study heterogeneity and small-study effects. A total of nine articles was eligible (217 HPD cases, 1519 cancer patients) for meta-analysis. There was no standard definition of HPD, and the incidence of HPD ranged from 1 to 30%. We identified twenty-three baseline patient factors, of which five factors were statistically significantly associated with HPD. These were serum lactate dehydrogenase (LDH) above the upper normal limit (OR = 1.89, 95% CI = 1.02-3.49, p = 0.043), more than two metastatic sites (OR = 1.86, 1.34-2.57, p < 0.001), liver metastases (OR = 3.33, 2.07-5.34, p < 0.001), Royal Marsden Hospital prognostic score of 2 or above (OR = 3.33, 1.96-5.66, p < 0.001), and positive PD-L1 expression status that was inversely correlated with HPD (OR = 0.60, 0.36-0.99, p = 0.044). Between-study heterogeneity was low. Evidence of small-study effect was found in one association (PD-L1 expression). Subset analyses of patients with non-small cell lung cancer showed similar results. Future studies are warranted to identify underlying molecular mechanisms and to test their roles as predictive biomarkers of HPD.

Co-occurrence and clustering of the four major non-communicable disease risk factors in Brazilian adolescents: Analysis of a national school-based survey.

BACKGROUND: The major non-communicable chronic diseases (NCD) are associated with a small group of modifiable lifestyle-related risk factors, including smoking, insufficient physical activity, unhealthy eating, and alcohol abuse. In this study, we evaluated the co-occurrence and clustering of the major NCD risk factors among Brazilian adolescents. METHODS: This cross-sectional study analyzed data of 101,607 adolescents from the Brazilian National Survey of School Health (PeNSE) 2015. The risk factors included were: regular consumption of ultra-processed foods, irregular consumption of fruits and vegetables, insufficient physical activity, smoking, and alcohol consumption. Clustering was defined through the ratio between observed and expected prevalences of combination of risk factors greater than 1. Expected prevalence of the co-occurrence of risk factors was calculated from the joint probability of the behaviors. Additionally, we examined the presence of at least four risk factors according to socioeconomic characteristics. RESULTS: Of the 32 combinations of risk factors, 13 corresponded to clustering. We observed a strong correlation between alcohol consumption and smoking, which were found together in 8 of the 13 clusters identified. The most frequent combinations of risk factors involved unhealthy eating and insufficient physical activity. Only 2.9% of the adolescents did not present any risk behaviors, while 38.0%, 32.9%, 9.4% and 1.8% accumulated two, three, four and five risk factors, respectively. The accumulation of risk factors was higher in girls, older adolescents, those who did not live with both parents, children of less-educated mothers, students attending public school, and residents of cities in more developed urban areas of the country. CONCLUSIONS: The main risk factors for NCD are frequent and not randomly distributed among Brazilian adolescents. Our results provide information for policymakers to target specific groups and joint behavioral risk factors for health improvement in adolescents.

Progress and setbacks in socioeconomic inequalities in adolescent health-related behaviours in Brazil: results from three cross-sectional surveys 2009-2015.

OBJECTIVES: Despite some progress, Brazil is still one of the most unequal countries, and the extent of socioeconomic inequalities in adolescent health is unclear. We assessed trends in socioeconomic inequalities in adolescent's health-related behaviours in Brazil between 2009 and 2015. DESIGN: We used cross-sectional data from the Brazilian National Survey of School Health carried out in 2009, 2012 and 2015. SETTING: Brazilian state capitals. PARTICIPANTS: Students attending ninth grade from public and private schools in Brazilian state capitals in 2009 (60 973 students), 2012 (61 145 students) and 2015 (51 192 students). MAIN OUTCOME MEASURE: We assessed 12 health-related behaviours (irregular fruit, vegetables and bean consumption; regular soft drink consumption; irregular physical activity; alcohol, drug and tobacco use; unsafe sex; involvement in gun fights; bullying victimisation and domestic violence victimisation), under the broad domains of lifestyle risk behaviours, engagement in risky activities and exposure to violence. Socioeconomic status was assessed through an asset-based wealth index derived from principal component analysis. Absolute and relative inequalities in these health behaviours and inequalities trends were investigated. RESULTS: From 2009 to 2015, prevalence of certain harmful health-related behaviours increased, such as unsafe sex (21.5% to 33.9%), domestic violence (9.5% to 16.2%), bullying victimisation (14.2% to 21.7%) and irregular consumption of beans (37.5% to 43.7%). Other indicators decreased: alcohol use (27.1% to 23.2%), irregular physical activity (83.0% to 75.6%) and consumption of soft drinks (37.2% to 28.8%). Over the period, we found consistent evidence of decreasing health inequalities for lifestyle behaviours (fruit, bean and soft drink consumption) and alcohol use, set against increasing inequalities in violence (domestic violence, fights using guns and bullying victimisation). CONCLUSION: Socioeconomic inequality increased in the violence domain and decreased for lifestyle behaviours among Brazilian adolescents. Widening gaps in violence domain urge immediately policy measures in Brazil.

Association of type and intensity of physical activity with plasma biomarkers of inflammation and insulin response.

Several biological mechanisms linking physical activity with cancer have been proposed. However, the influence of specific components of physical activity (volume, type and intensity), and their interaction with adiposity and diet, on cancer-related biomarkers remain unclear. We used cross-sectional data on 7,219 men in the Health Professionals Follow-up Study (1992-1994) with C-reactive protein (CRP), interleukin-6 (IL6), tumor necrosis factor alpha receptor 2 (TNFαR2), adiponectin, C-peptide and triglycerides/high-density lipoprotein cholesterol ratio (TG/HDL). Details on physical activity, diet and adiposity were assessed by questionnaires. We used multivariable-adjusted linear regression analyses to estimate relative concentrations of biomarkers by physical activity. Total physical activity was favorably associated with all biomarkers in a fairly linear manner. Comparing the highest (63+ metabolic equivalent (MET)-hr/week) to the lowest (0-8.9 MET-hr/week) physical activity groups, the percent relative difference in concentration of biomarkers was -31% for CRP, -22% for IL6, -8% for TNFαR2, +9% for adiponectin, -22% for C-peptide, and -20% for TG/HDL. These differences were modestly attenuated after adjustment for adiposity. For the same total MET-hours of physical activity, the association was stronger for men engaging in both aerobic and resistance exercises compared to those engaging in aerobic only. However, no difference was found between those engaging in vigorous activities (≥20% of total MET-hours) compared to those who did smaller amount of vigorous activities. Physical activity showed similar associations for these biomarkers regardless of adiposity and dietary pattern. In conclusion, high physical activity, preferably aerobic plus resistance training, was associated with favorable cancer-related biomarkers.

Resting heart rate and risk of type 2 diabetes: A prospective cohort study and meta-analysis.

BACKGROUND: Positive association between resting heart rate (RHR) and risk of type 2 diabetes (T2D) has been documented in several studies. However, whether RHR is an independent predictor of T2D and its potential interaction with other risk factors of T2D remain unclear. METHODS: We conducted a prospective cohort study of 31 156 men from the Health Professionals Follow-up Study (1992-2012). Cox proportional hazard model was used to examine the association between RHR and T2D risk. We further examined whether this association is modified by known risk factors. Lastly, we conducted a meta-analysis of prospective cohort studies. RESULTS: During 505 380 person-years of follow-up, we identified 2338 incident T2D cases. The multivariable-adjusted hazard ratio (HR) comparing the highest vs lowest categories of RHR was 1.69 (95% confidence interval [CI], 1.43-2.01). Increase in 10 bpm of RHR was associated with 19% increased risk of T2D in the fully adjusted model (HR, 1.19; 95% CI, 1.14-1.24). The HRs of T2D associated with RHR were stronger among those with normal weight or without hypertension (P interaction < 0.001). Moreover, RHR with other known risk factors cumulatively increased T2D risk. A meta-analysis consistently showed a positive association between RHR and T2D risk (the summary relative risk [RR] for highest vs lowest RHR, 1.53; 95% CI, 1.26-1.86, n = 12, the summary RR per 10 bpm increase, 1.17; 95% CI, 1.09-1.26, n = 13). CONCLUSIONS: High RHR was independently associated with increased risk of T2D. Our findings suggest that RHR, with other known risk factors, could be a useful tool to predict T2D risk.

Be Aware of Aggregators in the Search for Potential Human ecto-5'-Nucleotidase Inhibitors.

Promiscuous inhibition due to aggregate formation has been recognized as a major concern in drug discovery campaigns. Here, we report some aggregators identified in a virtual screening (VS) protocol to search for inhibitors of human ecto-5'-nucleotidase (ecto-5'-NT/CD73), a promising target for several diseases and pathophysiological events, including cancer, inflammation and autoimmune diseases. Four compounds (A, B, C and D), selected from the ZINC-11 database, showed IC50 values in the micromolar range, being at the same time computationally predicted as potential aggregators. To confirm if they inhibit human ecto-5'-NT via promiscuous mechanism, forming aggregates, enzymatic assays were done in the presence of 0.01% (v/v) Triton X-100 and an increase in the enzyme concentration by 10-fold. Under both experimental conditions, these four compounds showed a significant decrease in their inhibitory activities. To corroborate these findings, turbidimetric assays were performed, confirming that they form aggregate species. Additionally, aggregation kinetic studies were done by dynamic light scattering (DLS) for compound C. None of the identified aggregators has been previously reported in the literature. For the first time, aggregation and promiscuous inhibition issues were systematically studied and evaluated for compounds selected by VS as potential inhibitors for human ecto-5'-NT. Together, our results reinforce the importance of accounting for potential false-positive hits acting by aggregation in drug discovery campaigns to avoid misleading assay results.

Correction to: Personal, relational and school factors associated with involvement in fights with weapons among school-age youth in Brazil: a multilevel ecological approach.

The authors would like to include the funding note here which was found missing in the original publication.

Personal, relational and school factors associated with involvement in fights with weapons among school-age youth in Brazil: a multilevel ecological approach.

OBJECTIVES: To investigate the association between personal, relational and school factors with involvement in fights with weapon among Brazilian school-age youth. METHODS: Using data from the Adolescent School-Based Health Survey 2015 (n = 102.072), we conducted multilevel logistic regression models. RESULTS: IFW was associated with female sex (OR = 0.45), and with older age (OR = 1.15), previous involvement in physical violence (OR = 2.05), history of peer verbal (OR = 1.14) and domestic victimization (OR = 2.11), alcohol use (OR = 2.42) and drug use (OR = 3.23). The relational variables (e.g., parent's supervision) were mostly negatively associated with IFW. At the school level, attending public school and attending schools in violent surroundings were both positively associated with IFW. The intraclass correlation coefficient estimated in the empty model showed that 5.77% of the variance of IFW was at school level. When all individual- and school-level variables were included in the model, the proportional changes in variance were 61.7 and 71.55%, respectively. CONCLUSIONS: IFW is associated with personal, relational and school factors. Part of the variance in IFW by school is explained by characteristics of the school context.

Reporting bias in the literature on the associations of health-related behaviors and statins with cardiovascular disease and all-cause mortality.

Reporting bias in the literature occurs when there is selective revealing or suppression of results, influenced by the direction of findings. We assessed the risk of reporting bias in the epidemiological literature on health-related behavior (tobacco, alcohol, diet, physical activity, and sedentary behavior) and cardiovascular disease mortality and all-cause mortality and provided a comparative assessment of reporting bias between health-related behavior and statin (in primary prevention) meta-analyses. We searched Medline, Embase, Cochrane Methodology Register Database, and Web of Science for systematic reviews synthesizing the associations of health-related behavior and statins with cardiovascular disease mortality and all-cause mortality published between 2010 and 2016. Risk of bias in systematic reviews was assessed using the ROBIS tool. Reporting bias in the literature was evaluated via small-study effect and excess significance tests. We included 49 systematic reviews in our study. The majority of these reviews exhibited a high overall risk of bias, with a higher extent in health-related behavior reviews, relative to statins. We reperformed 111 meta-analyses conducted across these reviews, of which 65% had statistically significant results (P < 0.05). Around 22% of health-related behavior meta-analyses showed small-study effect, as compared to none of statin meta-analyses. Physical activity and the smoking research areas had more than 40% of meta-analyses with small-study effect. We found evidence of excess significance in 26% of health-related behavior meta-analyses, as compared to none of statin meta-analyses. Half of the meta-analyses from physical activity, 26% from diet, 18% from sedentary behavior, 14% for smoking, and 12% from alcohol showed evidence of excess significance bias. These biases may be distorting the body of evidence available by providing inaccurate estimates of preventive effects on cardiovascular and all-cause mortality.

Prevalence of active transportation among adults in Latin America and the Caribbean: a systematic review of population-based studies.

OBJECTIVE: To describe the prevalence of "active" (self-propelled, human-powered) transportation in the Latin America and Caribbean (LAC) region over the past decade. METHODS: MEDLINE, Excerpta Medica (Embase), SportDiscus, Lilacs, MediCarib, Web of Science, OVID, CINAHL, Scopus, Google Scholar, National Transportation Library, and TRIS/TRID were searched for articles on active transportation published between January 2003 and December 2014 with (at least) a title and abstract in English, Portuguese, or Spanish. Research was included in the study if the two reviewing authors agreed it 1) was conducted in an adult sample (≥ 18 years old), 2) was designed to be representative of any LAC area, and 3) reported at least one measure of active transportation. Reference lists of included papers and retrieved reviews were also checked. A total of 129 key informants (87 scientific experts and 42 government authorities) were contacted to identify additional candidate publications. Two other authors extracted the data independently. RESULTS: A total of 10 459 unique records were found; the full texts of 143 were reviewed; and a total of 45 studies were included in the study, yielding estimates for 72 LAC settings, most of which were in Argentina, Brazil, and Colombia. No eligible studies were found for the years 2003-2004, resulting in a 10-year study time frame. Estimates were available for walking, cycling, or the combination of both, with a high degree of heterogeneity (heterogeneity index (I2) ≥ 99%). The median prevalence of active transportation (combining walking and cycling) was 12.0%, ranging from 5.1% (in Palmas, Brazil) to 58.9% (in Rio Claro, Brazil). Men cycled more than women in all regions for which information was available. The opposite was true for walking. CONCLUSIONS: Prevalence of active transportation in LAC varied widely, with great heterogeneity and uneven distribution of studies across countries, indicating the need for efforts to build comprehensive surveillance systems with standardized, timely, and detailed estimates of active transportation in order to support policy planning and evaluation.

Physical activity as part of daily living: Moving beyond quantitative recommendations.

The purpose of this study is to discuss a paradigm shift towards a broader understanding of physical activity (PA) as part of daily living and, therefore, a different approach for PA guidelines, research, and promotion. To this aim, we centered the discussion in two topics: 1) PA: from a restricted view to a broader phenomenon; and 2) Recommendations for PA: moving beyond minutes and dose-response. A holistic understanding of PA and its relationship with health is not possible unless it is considered values, meanings, and symbols that impregnate the human behavior linked to the modes of living of a given people. If we do believe that PA is a behavior essential to human life, we must align our actions to our speech. However, current guidelines, as well as in most policies and programs of PA is largely portrayed as a way to attain longer life expectancy and less diseases, which runs against our consolidated understanding of PA as part of our everyday life. New guidelines could focus on how, when, why, where, and with whom we include PA in our daily lives, based on a day-long approach, instead of how much we should do in order to prevent non-communicable diseases.

Food environments in schools and in the immediate vicinity are associated with unhealthy food consumption among Brazilian adolescents.

BACKGROUND: Evidence of the influence of the school food environment on adolescent diet is still little explored in low- and middle-income countries. We aimed to evaluate the association between food environment in schools and the immediate vicinity and the regular consumption of unhealthy food among adolescents. METHODS: We used cross-sectional data collected by the Brazilian National Survey of School Health (PeNSE) from a representative sample of adolescents attending 9th grade public and private schools in Brazil, in 2012. We estimated students' regular consumption (>5days/week) of unhealthy food (soft drinks, bagged salty snacks, deep fried salty snacks and sweets) and school availability, in the cafeteria or an alternative outlet, of the same food plus some healthy options (fruit and natural fruit juice). We performed multilevel logistic regression models. RESULTS: Having a cafeteria inside school selling soft drinks (private schools OR=1.23; 95% CI=1.14-1.33; public schools OR=1.13; 95% CI=1.06-1.20) and deep fried salty snacks (private schools OR=1.41 95% CI=1.26-1.57; public schools OR=1.16 95% CI=1.08-1.24) was associated with a higher consumption of these unhealthy foods of among students. In private schools, cafeteria selling fruit and natural fruit juice was associated with lower student consumption of bagged salty snacks (OR=0.86; 95% CI 0.77-0.96) and soft drinks (OR=0.85; 95% CI=0.76-0.94). In addition, eating meals from the Brazilian School Food Program in public schools was associated with a lower consumption of unhealthy foods. CONCLUSIONS: Foods available in the school food environment are associated with the consumption of unhealthy food among adolescents in Brazil.

Lifestyle among former cancer patients in Brazil in 2013.

People who have been diagnosed with cancer tend to adopt healthier lifestyles. This study analyzes the prevalence of smoking, eating fruits and vegetables, exercise and the use of alcoholic beverages among individuals who reported to have been diagnosed with cancer in the PNS (Pesquisa Nacional de Saúde or National Health Survey). The prevalence and corresponding 95% confidence intervals were calculated for consuming fruits and vegetables, sedentary lifestyle (no exercise), use of alcoholic beverages, being overweight and tobacco use. The associa-tion between having received a diagnosis of cancer and the risk and protection factors was analyzed using a Poisson regression, adjusted by sociodemographic variables and other chronic comorbidities. The analyses were stratified by time since the diagnosis and the type of cancer related to the factors analyzed. The types of cancer most often reported were breast and cervix in women, and prostate and stomach in men. Among those who had cancer diagnoses, there was a higher consumption of fruits and vegetables, higher proportion of ex-smokers, however, increased use of alcohol. There was no difference in the frequency of exercise or incidence of being overweight between the two groups. Measures to promote health and prevent chronic diseases should be implemented in the follow-up of people who have had cancer, in an effort to ensure integrated healthcare.

Is the metabolically healthy obesity phenotype an irrelevant artifact for public health?

Some obese persons do not develop (at least in the short term) the metabolic complications of obesity that are thought to be causally linked to cardiovascular events or premature mortality. This phenomenon has been termed "metabolically healthy obesity" (MHO), and it has received much attention recently, to the extent that some authors argue that "new metrics" must be developed to estimate the risk associated with obesity beyond body mass index. In this commentary, we argue that the MHO phenotype is not benign and as such has very limited relevance as a public health target. More efforts must be allocated to reducing the distal and actual causal agents that lead to weight gain, instead of the current disproportionate scientific interest in the biological processes that explain the heterogeneity of obesity.

The Role of School Environment in Physical Activity among Brazilian Adolescents.

OBJECTIVE: To analyze the association of physical activity facilities and extracurricular sports activities in schools with physical activity among adolescents. METHODOLOGY/PRINCIPAL FINDINGS: We used data collected for the National Survey of School Health in 2012. The national representative sample comprised 109,104 Brazilian students from 2,842 schools. We calculated the prevalence of participation in physical education classes, leisure-time physical activity, and total physical activity level. We also evaluated the following physical activity facilities: sports courts, running/athletics tracks, schoolyard with teacher-directed physical activities, swimming pools, locker rooms; and the offer of extracurricular sports activities. Schools with at least one physical activity facility had increased odds of participation in physical education (OR 1.59; 95% CI 1.20 to 2.10). However, in order to increase leisure-time physical activity (OR1.14; 95% CI 1.03 to 1.26) and total physical activity level (OR 1.15; 95% CI 1.06 to 1.24) at least four and two facilities, respectively, were necessary. Extracurricular sports activities in schools were positively associated with leisure-time physical activity and physical activity level. The number of sports courts and swimming pool in a school were associated with participation in physical education classes. Availability of sports courts, running/athletics tracks, and swimming pool in schools were associated with leisure-time physical activity. Total physical activity was associated with schools with sports courts, schoolyard with teacher-directed physical activities, and swimming pool. CONCLUSIONS: School-level characteristics have important potential to increase the possibility of engagement in physical activity in and out of school, and therefore have a fundamental role in promoting these practices.