Universidade Federal de Pelotas

BACKGROUND: Cross-sectional studies with binary outcomes analyzed by logistic regression are frequent in the epidemiological literature. However, the odds ratio can importantly overestimate the prevalence ratio, the measure of choice in these studies. Also, controlling for confounding is not equivalent for the two measures. In this paper we explore alternatives for modeling data of such studies with techniques that directly estimate the prevalence ratio. METHODS: We compared Cox regression with constant time at risk, Poisson regression and log-binomial regression against the standard Mantel-Haenszel estimators. Models with robust variance estimators in Cox and Poisson regressions and variance corrected by the scale parameter in Poisson regression were also evaluated. RESULTS: Three outcomes, from a cross-sectional study carried out in Pelotas, Brazil, with different levels of prevalence were explored: weight-for-age deficit (4%), asthma (31%) and mother in a paid job (52%). Unadjusted Cox/Poisson regression and Poisson regression with scale parameter adjusted by deviance performed worst in terms of interval estimates. Poisson regression with scale parameter adjusted by chi2 showed variable performance depending on the outcome prevalence. Cox/Poisson regression with robust variance, and log-binomial regression performed equally well when the model was correctly specified. CONCLUSIONS: Cox or Poisson regression with robust variance and log-binomial regression provide correct estimates and are a better alternative for the analysis of cross-sectional studies with binary outcomes than logistic regression, since the prevalence ratio is more interpretable and easier to communicate to non-specialists than the odds ratio. However, precautions are needed to avoid estimation problems in specific situations.

Background: Mendelian randomization (MR) is being increasingly used to strengthen causal inference in observational studies. Availability of summary data of genetic associations for a variety of phenotypes from large genome-wide association studies (GWAS) allows straightforward application of MR using summary data methods, typically in a two-sample design. In addition to the conventional inverse variance weighting (IVW) method, recently developed summary data MR methods, such as the MR-Egger and weighted median approaches, allow a relaxation of the instrumental variable assumptions. Methods: Here, a new method - the mode-based estimate (MBE) - is proposed to obtain a single causal effect estimate from multiple genetic instruments. The MBE is consistent when the largest number of similar (identical in infinite samples) individual-instrument causal effect estimates comes from valid instruments, even if the majority of instruments are invalid. We evaluate the performance of the method in simulations designed to mimic the two-sample summary data setting, and demonstrate its use by investigating the causal effect of plasma lipid fractions and urate levels on coronary heart disease risk. Results: The MBE presented less bias and lower type-I error rates than other methods under the null in many situations. Its power to detect a causal effect was smaller compared with the IVW and weighted median methods, but was larger than that of MR-Egger regression, with sample size requirements typically smaller than those available from GWAS consortia. Conclusions: The MBE relaxes the instrumental variable assumptions, and should be used in combination with other approaches in sensitivity analyses.

BACKGROUND: This paper discusses appropriate strategies for multivariate data analysis in epidemiological studies. METHODS: In studies where determinants of disease are sought, it is suggested that the complex hierarchical inter-relationships between these determinants are best managed through the use of conceptual frameworks. Failure to take these aspects into consideration is common in the epidemiological literature and leads to underestimation of the effects of distal determinants. RESULTS: An example of this analytical approach, which is not based purely on statistical associations, is given for assessing determinants of mortality due to diarrhoea in children. CONCLUSIONS: Conceptual frameworks provide guidance for the use of multivariate techniques and aid the interpretation of their results in the light of social and biological knowledge.

<ns4:p>This paper provides guidelines for performing Mendelian randomization investigations. It is aimed at practitioners seeking to undertake analyses and write up their findings, and at journal editors and reviewers seeking to assess Mendelian randomization manuscripts. The guidelines are divided into nine sections: motivation and scope, data sources, choice of genetic variants, variant harmonization, primary analysis, supplementary and sensitivity analyses (one section on robust methods and one on other approaches), data presentation, and interpretation. These guidelines will be updated based on feedback from the community and advances in the field. Updates will be made periodically as needed, and at least every 18 months.</ns4:p>

OBJECTIVE: Our goal was to describe worldwide growth-faltering patterns by using the new World Health Organization (WHO) standards. METHODS: We analyzed information available from the WHO Global Database on Child Growth and Malnutrition, comprising data from national anthropometric surveys from 54 countries. Anthropometric data comprise weight-for-age, length/height-for-age, and weight-for-length/height z scores. The WHO regions were used to aggregate countries: Europe and Central Asia; Latin America and the Caribbean; North Africa and Middle East; South Asia; and sub-Saharan Africa. RESULTS: Sample sizes ranged from 1000 to 47 000 children. Weight for length/height starts slightly above the standard in children aged 1 to 2 months and falters slightly until 9 months of age, picking up after that age and remaining close to the standard thereafter. Weight for age starts close to the standard and falters moderately until reaching approximately -1 z at 24 months and remaining reasonably stable after that. Length/height for age also starts close to the standard and falters dramatically until 24 months, showing noticeable bumps just after 24, 36, and 48 months but otherwise increasing slightly after 24 months. CONCLUSIONS: Comparison of child growth patterns in 54 countries with WHO standards shows that growth faltering in early childhood is even more pronounced than suggested by previous analyses based on the National Center for Health Statistics reference. These findings confirm the need to scale up interventions during the window of opportunity defined by pregnancy and the first 2 years of life, including prevention of low birth weight and appropriate infant feeding practices.

This paper provides guidelines for performing Mendelian randomization investigations. It is aimed at practitioners seeking to undertake analyses and write up their findings, and at journal editors and reviewers seeking to assess Mendelian randomization manuscripts. The guidelines are divided into ten sections: motivation and scope, data sources, choice of genetic variants, variant harmonization, primary analysis, supplementary and sensitivity analyses (one section on robust statistical methods and one on other approaches), extensions and additional analyses, data presentation, and interpretation. These guidelines will be updated based on feedback from the community and advances in the field. Updates will be made periodically as needed, and at least every 24 months.

BACKGROUND: It is presumed that physical activity (PA) level declines during the lifespan, particularly in adolescence. However, currently, there is no study that quantifies these changes and pools results for a common interpretation. Therefore, the purpose was to systematically review the international literature regarding PA change during adolescence, and to quantify that change according to a series of study variables, exploring gender-and-age differences. METHODS: An electronic search was conducted in the Medline/PubMed and Web of Science databases. Longitudinal studies with, at least, two PA measures throughout adolescence (10-19 years old) or the first PA measure during childhood and the second one during adolescence were selected. From each article, study project name, country, year of the first data collection, sample size, baseline age, follow-up duration, characteristics of the instrument (type, recall time, PA intensity and PA domain), unit of PA measure and report of statistical significance were collected. RESULTS: Overall, 26 studies matched the inclusion criteria. Most were carried out in the USA, assessed PA by questionnaire, and found a decline in PA levels during the adolescence. On average, the mean percentage PA change per year, across all studies, was -7.0 (95% confidence interval: -8.8 to -5.2), ranging from -18.8 to 7.8. The decline was significant according to most sub-groups of variables analysed. Although earlier studies revealed a higher PA decline in boys, the decline has been greater in girls in more recent studies (commenced after 1997). Moreover, although the decline among girls was higher in younger ages at baseline (9-12 years), it was higher in older ages (13-16 years) among boys. CONCLUSIONS: The decline of PA during adolescence is a consistent finding in the literature. Differences between boys and girls were observed and should be explored in future studies. Interventions that attempt to attenuate the PA decline, even without an increase in PA levels, could be considered as effective.

BACKGROUND: The magnitude of risk conferred by the interaction between tobacco and alcohol use on the risk of head and neck cancers is not clear because studies have used various methods to quantify the excess head and neck cancer burden. METHODS: We analyzed individual-level pooled data from 17 European and American case-control studies (11,221 cases and 16,168 controls) participating in the International Head and Neck Cancer Epidemiology consortium. We estimated the multiplicative interaction parameter (psi) and population attributable risks (PAR). RESULTS: A greater than multiplicative joint effect between ever tobacco and alcohol use was observed for head and neck cancer risk (psi = 2.15; 95% confidence interval, 1.53-3.04). The PAR for tobacco or alcohol was 72% (95% confidence interval, 61-79%) for head and neck cancer, of which 4% was due to alcohol alone, 33% was due to tobacco alone, and 35% was due to tobacco and alcohol combined. The total PAR differed by subsite (64% for oral cavity cancer, 72% for pharyngeal cancer, 89% for laryngeal cancer), by sex (74% for men, 57% for women), by age (33% for cases <45 years, 73% for cases >60 years), and by region (84% in Europe, 51% in North America, 83% in Latin America). CONCLUSIONS: Our results confirm that the joint effect between tobacco and alcohol use is greater than multiplicative on head and neck cancer risk. However, a substantial proportion of head and neck cancers cannot be attributed to tobacco or alcohol use, particularly for oral cavity cancer and for head and neck cancer among women and among young-onset cases.

AIM: To systematically review the evidence on the associations between breastfeeding and overweight/obesity, blood pressure, total cholesterol and type 2 diabetes. METHODS: Two independent literature searches were carried out using the MEDLINE, LILACS, SCIELO and Web of Science databases. Studies restricted to infants and those without an internal comparison group were excluded. Fixed- and random-effects models were used to pool the estimates. RESULTS: Breastfed subjects were less likely to be considered obese/overweight [pooled odds ratio: 0.74 (95% confidence interval (CI): 0.70; 0.78)] (n = 113). Among the 11 high-quality studies, the association was smaller [pooled odds ratio: 0.87 (95%CI: 0.76; 0.99)]. Total cholesterol (n = 46) was independent of breastfeeding [pooled mean difference: -0.01 mmol/L (95%CI: -0.05; 0.02)]. Systolic blood pressure (n = 43) was lower among breastfed subjects [mean difference: -0.80 (95%CI: -1.17; -0.43)], but no association was observed among larger studies, and for diastolic blood pressure (n = 38) [mean difference: -0.24 (95%CI: -0.50; 0.02)]. For type 2 diabetes (n = 11), the odds ratio was lower among those subjects who had been breastfed [pooled odds ratio: 0.65 (95%CI: 0.49; 0.86)]. CONCLUSION: Breastfeeding decreased the odds of type 2 diabetes and based on high-quality studies, decreased by 13% the odds of overweight/obesity. No associations were found for total cholesterol or blood pressure.

Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.

Summary Understanding the drivers and dynamics of global ultra‐processed food (UPF) consumption is essential, given the evidence linking these foods with adverse health outcomes. In this synthesis review, we take two steps. First, we quantify per capita volumes and trends in UPF sales, and ingredients (sweeteners, fats, sodium and cosmetic additives) supplied by these foods, in countries classified by income and region. Second, we review the literature on food systems and political economy factors that likely explain the observed changes. We find evidence for a substantial expansion in the types and quantities of UPFs sold worldwide, representing a transition towards a more processed global diet but with wide variations between regions and countries. As countries grow richer, higher volumes and a wider variety of UPFs are sold. Sales are highest in Australasia, North America, Europe and Latin America but growing rapidly in Asia, the Middle East and Africa. These developments are closely linked with the industrialization of food systems, technological change and globalization, including growth in the market and political activities of transnational food corporations and inadequate policies to protect nutrition in these new contexts. The scale of dietary change underway, especially in highly populated middle‐income countries, raises serious concern for global health.

BACKGROUND: At least 75% of head and neck cancers are attributable to a combination of cigarette smoking and alcohol drinking. A precise understanding of the independent association of each of these factors in the absence of the other with the risk of head and neck cancer is needed to elucidate mechanisms of head and neck carcinogenesis and to assess the efficacy of interventions aimed at controlling either risk factor. METHODS: We examined the extent to which head and neck cancer is associated with cigarette smoking among never drinkers and with alcohol drinking among never users of tobacco. We pooled individual-level data from 15 case-control studies that included 10,244 head and neck cancer case subjects and 15,227 control subjects, of whom 1072 case subjects and 5775 control subjects were never users of tobacco and 1598 case subjects and 4051 control subjects were never drinkers of alcohol. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models. All statistical tests were two-sided. RESULTS: Among never drinkers, cigarette smoking was associated with an increased risk of head and neck cancer (OR for ever versus never smoking = 2.13, 95% CI = 1.52 to 2.98), and there were clear dose-response relationships for the frequency, duration, and number of pack-years of cigarette smoking. Approximately 24% (95% CI = 16% to 31%) of head and neck cancer cases among nondrinkers in this study would have been prevented if these individuals had not smoked cigarettes. Among never users of tobacco, alcohol consumption was associated with an increased risk of head and neck cancer only when alcohol was consumed at high frequency (OR for three or more drinks per day versus never drinking = 2.04, 95% CI = 1.29 to 3.21). The association with high-frequency alcohol intake was limited to cancers of the oropharynx/hypopharynx and larynx. CONCLUSIONS: Our results represent the most precise estimates available of the independent association of each of the two main risk factors of head and neck cancer, and they exemplify the strengths of large-scale consortia in cancer epidemiology.

Randomized controlled trials (RCTs) are essential for evaluating the efficacy of clinical interventions, where the causal chain between the agent and the outcome is relatively short and simple and where results may be safely extrapolated to other settings. However, causal chains in public health interventions are complex, making RCT results subject to effect modification in different populations. Both the internal and external validity of RCT findings can be greatly enhanced by observational studies using adequacy or plausibility designs. For evaluating large-scale interventions, studies with plausibility designs are often the only feasible option and may provide valid evidence of impact. There is an urgent need to develop evaluation standards and protocols for use in circumstances where RCTs are not appropriate.

OBJECTIVE: To estimate worldwide prevalence of chronic low back pain according to age and sex. METHODS: We consulted Medline (PubMed), LILACS and EMBASE electronic databases. The search strategy used the following descriptors and combinations: back pain, prevalence, musculoskeletal diseases, chronic musculoskeletal pain, rheumatic, low back pain, musculoskeletal disorders and chronic low back pain. We selected cross-sectional population-based or cohort studies that assessed chronic low back pain as an outcome. We also assessed the quality of the selected studies as well as the chronic low back pain prevalence according to age and sex. RESULTS: The review included 28 studies. Based on our qualitative evaluation, around one third of the studies had low scores, mainly due to high non-response rates. Chronic low back pain prevalence was 4.2% in individuals aged between 24 and 39 years old and 19.6% in those aged between 20 and 59. Of nine studies with individuals aged 18 and above, six reported chronic low back pain between 3.9% and 10.2% and three, prevalence between 13.1% and 20.3%. In the Brazilian older population, chronic low back pain prevalence was 25.4%. CONCLUSIONS: Chronic low back pain prevalence increases linearly from the third decade of life on, until the 60 years of age, being more prevalent in women. Methodological approaches aiming to reduce high heterogeneity in case definitions of chronic low back pain are essential to consistency and comparative analysis between studies. A standard chronic low back pain definition should include the precise description of the anatomical area, pain duration and limitation level.

The World Health Organization (WHO) Multicentre Growth Reference Study (MGRS) is a community-based, multicountry project to develop new growth references for infants and young children. The design combines a longitudinal study from birth to 24 months with a cross-sectional study of children aged 18 to 71 months. The pooled sample from the six participating countries (Brazil, Ghana, India, Norway, Oman, and the United States) consists of about 8,500 children. The study subpopulations had socioeconomic conditions favorable to growth, and low mobility, with at least 20% of mothers following feeding recommendations and having access to breastfeeding support. The individual inclusion criteria were absence of health or environmental constraints on growth, adherence to MGRS feeding recommendations, absence of maternal smoking, single term birth, and absence of significant morbidity. In the longitudinal study, mothers and newborns were screened and enrolled at birth and visited at home 21 times: at weeks 1, 2, 4, and 6; monthly from 2 to 12 months; and every 2 months in their second year. In addition to the data collected on anthropometry and motor development, information was gathered on socioeconomic, demographic, and environmental characteristics, perinatal factors, morbidity, and feeding practices. The prescriptive approach taken is expected to provide a single international reference that represents the best description of physiological growth for all children under five years of age and to establish the breastfed infant as the normative model for growth and development.

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The association between obesity and morbidity resulting from chronic diseases is well known. This systematic review addresses studies of the role of rapid growth in infancy and childhood as possible determinants of overweight and obesity later in the life course. We reviewed MEDLINE for studies reporting on growth in infancy and childhood, as well as measures of weight or adiposity in later childhood, adolescence or adulthood. The methodological quality of the papers was assessed using the criteria suggested by Downs and Black. Sixteen articles that fulfilled review criteria were located. There was wide variability in the indicators used for defining rapid growth as well as overweight or obesity. The age range in which weight or adiposity was measured ranged from 3 to 70 years. In spite of differences in definitions used, 13 articles that reported on early rapid growth found significant associations with later overweight or adiposity. Efforts should be made to standardize the definition of rapid growth, as well as that of overweight and obesity in children and adolescents. The most frequent definition for rapid growth in this review was a Z-score change greater than 0.67 in weight for age between two different ages in childhood. Regarding obesity, the definition proposed by the International Obesity Task Force also appears to be most appropriate. The present results indicate that early growth is indeed associated with the prevalence of obesity later in the life course.

In response to the 2013 Update of the European Strategy for Particle Physics, the Future Circular Collider (FCC) study was launched, as an international collaboration hosted by CERN. This study covers a highest-luminosity high-energy lepton collider (FCC-ee) and an energy-frontier hadron collider (FCC-hh), which could, successively, be installed in the same 100 km tunnel. The scientific capabilities of the integrated FCC programme would serve the worldwide community throughout the 21st century. The FCC study also investigates an LHC energy upgrade, using FCC-hh technology. This document constitutes the second volume of the FCC Conceptual Design Report, devoted to the electron-positron collider FCC-ee. After summarizing the physics discovery opportunities, it presents the accelerator design, performance reach, a staged operation scenario, the underlying technologies, civil engineering, technical infrastructure, and an implementation plan. FCC-ee can be built with today's technology. Most of the FCC-ee infrastructure could be reused for FCC-hh. Combining concepts from past and present lepton colliders and adding a few novel elements, the FCC-ee design promises outstandingly high luminosity. This will make the FCC-ee a unique precision instrument to study the heaviest known particles (Z, W and H bosons and the top quark), offering great direct and indirect sensitivity to new physics.

BACKGROUND: Physical activity and sedentary behaviour in youth have been reported to vary by sex, age, weight status and country. However, supporting data are often self-reported and/or do not encompass a wide range of ages or geographical locations. This study aimed to describe objectively-measured physical activity and sedentary time patterns in youth. METHODS: The International Children's Accelerometry Database (ICAD) consists of ActiGraph accelerometer data from 20 studies in ten countries, processed using common data reduction procedures. Analyses were conducted on 27,637 participants (2.8-18.4 years) who provided at least three days of valid accelerometer data. Linear regression was used to examine associations between age, sex, weight status, country and physical activity outcomes. RESULTS: Boys were less sedentary and more active than girls at all ages. After 5 years of age there was an average cross-sectional decrease of 4.2% in total physical activity with each additional year of age, due mainly to lower levels of light-intensity physical activity and greater time spent sedentary. Physical activity did not differ by weight status in the youngest children, but from age seven onwards, overweight/obese participants were less active than their normal weight counterparts. Physical activity varied between samples from different countries, with a 15-20% difference between the highest and lowest countries at age 9-10 and a 26-28% difference at age 12-13. CONCLUSIONS: Physical activity differed between samples from different countries, but the associations between demographic characteristics and physical activity were consistently observed. Further research is needed to explore environmental and sociocultural explanations for these differences.

BACKGROUND: Systematic reviews (SRs) can help decision makers interpret the deluge of published biomedical literature. However, a SR may be of limited use if the methods used to conduct the SR are flawed, and reporting of the SR is incomplete. To our knowledge, since 2004 there has been no cross-sectional study of the prevalence, focus, and completeness of reporting of SRs across different specialties. Therefore, the aim of our study was to investigate the epidemiological and reporting characteristics of a more recent cross-section of SRs. METHODS AND FINDINGS: We searched MEDLINE to identify potentially eligible SRs indexed during the month of February 2014. Citations were screened using prespecified eligibility criteria. Epidemiological and reporting characteristics of a random sample of 300 SRs were extracted by one reviewer, with a 10% sample extracted in duplicate. We compared characteristics of Cochrane versus non-Cochrane reviews, and the 2014 sample of SRs versus a 2004 sample of SRs. We identified 682 SRs, suggesting that more than 8,000 SRs are being indexed in MEDLINE annually, corresponding to a 3-fold increase over the last decade. The majority of SRs addressed a therapeutic question and were conducted by authors based in China, the UK, or the US; they included a median of 15 studies involving 2,072 participants. Meta-analysis was performed in 63% of SRs, mostly using standard pairwise methods. Study risk of bias/quality assessment was performed in 70% of SRs but was rarely incorporated into the analysis (16%). Few SRs (7%) searched sources of unpublished data, and the risk of publication bias was considered in less than half of SRs. Reporting quality was highly variable; at least a third of SRs did not report use of a SR protocol, eligibility criteria relating to publication status, years of coverage of the search, a full Boolean search logic for at least one database, methods for data extraction, methods for study risk of bias assessment, a primary outcome, an abstract conclusion that incorporated study limitations, or the funding source of the SR. Cochrane SRs, which accounted for 15% of the sample, had more complete reporting than all other types of SRs. Reporting has generally improved since 2004, but remains suboptimal for many characteristics. CONCLUSIONS: An increasing number of SRs are being published, and many are poorly conducted and reported. Strategies are needed to help reduce this avoidable waste in research.