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1.  Continuing to Confront COPD International Surveys: comparison of patient and physician perceptions about COPD risk and management 
Purpose
Using data from the Continuing to Confront COPD International Physician and Patient Surveys, this paper describes physicians’ attitudes and beliefs regarding chronic obstructive pulmonary disease (COPD) prognosis, and compares physician and patient perceptions with respect to COPD.
Methods
In 12 countries worldwide, 4,343 patients with COPD were identified through systematic screening of population samples, and 1,307 physicians who regularly saw patients with COPD were sampled from in-country professional databases. Both patients and physicians completed surveys about their COPD knowledge, beliefs, and perceptions; physicians answered further questions about diagnostic methods and treatment choices for COPD.
Results
Most physicians (79%) responded that the long-term health outlook for patients with COPD has improved over the past decade, largely attributed to the introduction of better medications. However, patient access to medication remains an issue in many countries, and some physicians (39%) and patients (46%) agreed/strongly agreed with the statement “there are no truly effective treatments for COPD”. There was strong concordance between physicians and patients regarding COPD management practices, including the use of spirometry (86% of physicians and 76% of patients reporting they used/had undergone a spirometry test) and smoking cessation counseling (76% of physicians reported they counseled their smoking patients at every clinic visit, and 71% of smoking patients stated that they had received counseling in the past year). However, the groups differed in their perception about the role of smoking in COPD, with 78% of physicians versus 38% of patients strongly agreeing with the statement “smoking is the cause of most cases of COPD”.
Conclusion
The Continuing to Confront COPD International Surveys demonstrate that while physicians and patients largely agreed about COPD management practices and the need for more effective treatments for COPD, a gap exists about the causal role of smoking in COPD.
doi:10.2147/COPD.S74315
PMCID: PMC4310342  PMID: 25653515
chronic obstructive pulmonary disease; physician survey; patient survey; beliefs; perceptions
2.  Continuing to Confront COPD International Physician Survey: physician knowledge and application of COPD management guidelines in 12 countries 
Aim
Utilizing data from the Continuing to Confront COPD (chronic obstructive pulmonary disease) International Physician Survey, this study aimed to describe physicians’ knowledge and application of the GOLD (Global initiative for chronic Obstructive Lung Disease) Global Strategy for the Diagnosis, Management and Prevention of COPD diagnosis and treatment recommendations and compare performance between primary care physicians (PCPs) and respiratory specialists.
Materials and methods
Physicians from 12 countries were sampled from in-country professional databases; 1,307 physicians (PCP to respiratory specialist ratio three to one) who regularly consult with COPD, emphysema, or chronic bronchitis patients were interviewed online, by telephone or face to face. Physicians were questioned about COPD risk factors, prognosis, diagnosis, and treatment, including knowledge and application of the GOLD global strategy using patient scenarios.
Results
Physicians reported using spirometry routinely (PCPs 82%, respiratory specialists 100%; P<0.001) to diagnose COPD and frequently included validated patient-reported outcome measures (PCPs 67%, respiratory specialists 81%; P<0.001). Respiratory specialists were more likely than PCPs to report awareness of the GOLD global strategy (93% versus 58%, P<0.001); however, when presented with patient scenarios, they did not always perform better than PCPs with regard to recommending GOLD-concordant treatment options. The proportion of PCPs and respiratory specialists providing first- or second-choice treatment options concordant with GOLD strategy for a GOLD B-type patient was 38% versus 67%, respectively. For GOLD C and D-type patients, the concordant proportions for PCPs and respiratory specialists were 40% versus 38%, and 57% versus 58%, respectively.
Conclusion
This survey of physicians in 12 countries practicing in the primary care and respiratory specialty settings showed high awareness of COPD-management guidelines. Frequent use of guideline-recommended COPD diagnostic practices was reported; however, gaps in the application of COPD-treatment recommendations were observed, warranting further evaluation to understand potential barriers to adopt guideline recommendations.
doi:10.2147/COPD.S70162
PMCID: PMC4284025  PMID: 25565799
chronic obstructive pulmonary disease; physician beliefs; adherence to guidelines
3.  Self-Medication Among Adolescents Aged 18 Years: The 1993 Pelotas (Brazil) Birth Cohort Study 
The Journal of Adolescent Health  2014;55(2):175-181.
Purpose
To estimate the point prevalence of self-medication among adolescents aged 18 years and to evaluate the type of drugs used (either over-the-counter or prescription drugs) and socioeconomic, health-related, and behavioral correlates of self-medication.
Methods
This cross-sectional study used data from the 1993 Pelotas (Brazil) Birth Cohort Study. Data were obtained through the administration of a questionnaire to adolescents aged 18 years. The outcome variables were point prevalence of medicine use and self-medication collected by self-report. The independent variables studied were gender, continuous medicine use, socioeconomic status, schooling, self-rated health, body mass index, and physical activity levels. Medicines were classified into therapeutic groups according to the Anatomical Therapeutic Chemical classification system.
Results
A total of 4,106 adolescents were interviewed. The point prevalence of medicine use was 41.1% (95% confidence interval [CI] 39.6–42.6), and the proportion of self-medication among medicine users was 65.1% (95% CI 62.8–67.4). The point prevalence of self-medication was 26.7% (95% CI 25.4–28.1), and it was higher among female adolescents, those more educated, and those who rated their health as poor. Out of the drugs used for self-medication (58% of all drugs used), 1,003 (78.7%) were nonprescription drugs and 271 (21.3%) were prescription drugs. The most frequently used drugs for self-medication were analgesics (56.1%), systemic antihistamines (7.4%), and anti-inflammatory and antirheumatic products (7.1%).
Conclusions
A high point prevalence of self-medication was found among adolescents, which is particularly concerning due to high use of prescription drugs for self-medication. Interventions are needed to promote rational use of medicines in this population.
doi:10.1016/j.jadohealth.2014.02.010
PMCID: PMC4104043  PMID: 24713443
Self-medication; Adolescent; Pharmacoepidemiology; Cohort study
4.  Continuing to Confront COPD International Patient Survey: methods, COPD prevalence, and disease burden in 2012–2013 
Purpose
The Continuing to Confront COPD International Patient Survey aimed to estimate the prevalence and burden of COPD globally and to update findings from the Confronting COPD International Survey conducted in 1999–2000.
Materials and methods
Chronic obstructive pulmonary disease (COPD) patients in 12 countries worldwide were identified through systematic screening of population samples. Telephone and face-to-face interviews were conducted between November 2012 and May 2013 using a structured survey that incorporated validated patient-reported outcome instruments. Eligible patients were adults aged 40 years and older who were taking regular respiratory medications or suffered with chronic respiratory symptoms and reported either 1) a physician diagnosis of COPD/emphysema, 2) a physician diagnosis of chronic bronchitis, or 3) a symptom-based definition of chronic bronchitis. The burden of COPD was measured with the COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) Dyspnea Scale.
Results
Of 106,876 households with at least one person aged ≥40 years, 4,343 respondents fulfilled the case definition of COPD and completed the full survey. COPD prevalence ranged from 7% to 12%, with most countries falling within the range of 7%–9%. In all countries, prevalence increased with age, and in all countries except the US was greater among men (range 6%–14%) than among women (range 5%–11%). A significant disease burden was observed when considering COPD symptoms or health status, and showed wide variations across countries. Prevalence of moderate-to-severe dyspnea (mMRC scale ≥2) ranged from 27% to 61%, and mean CAT score ranged from 16.0 to 24.8, indicating medium-to-high impairment.
Conclusion
This survey, representing 12 countries, showed similar rates of estimated COPD prevalence across countries that were higher than those reported a decade ago in the original Confronting COPD International Survey. A significant burden of COPD was demonstrated by symptoms and health care-resource use, similar to that reported in the original survey.
doi:10.2147/COPD.S61854
PMCID: PMC4057333  PMID: 24944511
chronic obstructive pulmonary disease; patient perspective; prevalence; patient-reported outcomes
5.  Active Commuting Throughout Adolescence and Central Fatness before Adulthood: Prospective Birth Cohort Study 
PLoS ONE  2014;9(5):e96634.
Background
Active commuting is a good opportunity to accumulate physical activity (PA) across the lifespan that potentially might influence central body fat. We aimed to examine the prospective associations of active commuting at 11, 15 and 18 years of age with central body fat at 18 years.
Methods
Participants were part of a large birth cohort study in Pelotas, Brazil (n = 3,649 participants). Active commuting, leisure-time PA and income were self-reported at 11, 15 and 18 years. Waist circumference and trunk fat mass were collected at 18 years with the use of a 3-dimensional photonic scanner and dual-energy X-ray absorptiometry, respectively.
Results
Active commuting at 11 years was not prospectively associated with central body fat. However, we found that active commuting at 15 and 18 years were prospectively and cross-sectionally associated with central body fat variables, respectively, in boys but not in girls. Also, boys in the highest tertile of accumulated active commuting (i.e., average of active commuting at 11, 13 and 18 years) were associated with −2.09 cm (95%CI: −3.24; −0.94) of waist circumference and −1.11 kg (95%CI: −1.74; −0.48) of trunk fat mass compared to boys in the lowest tertile. Analyses on changes in tertiles of active commuting from 11 and 15 years to 18 years with central body fat variables at 18 years showed that boys who remained consistently in the highest tertile or moved to a higher tertile had lower levels of central body fat compared to those consistently in the lowest tertile.
Conclusions
Active commuting throughout adolescence in boys, especially during middle and late adolescence, is associated with lower levels in central fatness before adulthood.
doi:10.1371/journal.pone.0096634
PMCID: PMC4008595  PMID: 24791780
6.  Physical Activity and Lung Function in Adolescents: The 1993 Pelotas (Brazil) Birth Cohort Study 
The Journal of Adolescent Health  2012;51(6):S27-S31.
Purpose
To evaluate the association between physical activity changes in those aged 11 to 15 years and lung function at age 15 years.
Methods
The original cohort comprised 5,249 hospital-born children during the calendar year of 1993 in Pelotas, Brazil. In 2004–2005 and 2008–2009, all cohort members were sought for follow-up visits. Self-reported physical activity was measured at ages 11 and 15 years. At the 2008–2009 visit, when participants were 15 years old, spirometry was performed. Linear regression was used, and all analyses were stratified by sex.
Results
Of the 5,249 original members of the cohort, 4,325 were located at 15 years of age, and spirometry was performed on 4,010 members. Forced expiratory volume in 1 second was not associated with physical activity. In girls, those who were active in leisure time in both periods have better percent-predicted forced vital capacity (β = 3.573 [95% confidence interval {CI}: 1.015, 6.130]) and forced expiratory volume in the 6 seconds (β = .095 [95% CI: .021, .168]) than those who were inactive in the two periods. Also in girls, those who became active at 15 years of age had higher peak expiratory flow than those who were inactive at 11 and 15 years of age. In boys, only those who became inactive in leisure time had worse peak expiratory flow (β = −.180 [95% CI: −.339, −.021]) than boys who were inactive at ages 11 and 15 years.
Conclusions
Self-reported leisure-time physical activity was associated with better effort-dependent lung function parameters, particularly among girls.
doi:10.1016/j.jadohealth.2012.06.023
PMCID: PMC3508410  PMID: 23283156
Physical activity; Lung function; Cohort; Adolescents
7.  DRD4 Rare Variants in Attention-Deficit/Hyperactivity Disorder (ADHD): Further Evidence from a Birth Cohort Study 
PLoS ONE  2013;8(12):e85164.
The dopamine receptor D4 (DRD4) is one of the most studied candidate genes for Attention-Deficit/Hyperactivity Disorder (ADHD). An excess of rare variants and non-synonymous mutations in the VNTR region of 7R allele in ADHD subjects was observed in previous studies with clinical samples. We hypothesize that genetic heterogeneity in the VNTR is an important factor in the pathophysiology of ADHD. The subjects included in the present study are members of the 1993 Pelotas Birth Cohort Study (N=5,249). We conducted an association study with the 4,101 subjects who had DNA samples collected. The hyperactivity-inattention scores were assessed through the parent version of the Strengths and Difficulties Questionnaire at 11 and 15 years of age. The contribution of allele’s length and rare variants to high hyperactivity/inattention scores predisposition was evaluated by multivariate logistic regression. No effect of allele length was observed on high scores of hyperactivity-inattention. By contrast, when resequencing/haplotyping was conducted in a subsample, all 7R rare variants as well as non-synonymous 7R rare variants were associated with high hyperactivity/inattention scores (OR=2.561; P=0.024 and OR=3.216; P=0.008 respectively). A trend for association was observed with 4R rare variants. New coding mutations covered 10 novel motifs and many of them are previously unreported deletions leading to different stop codons. Our findings suggest a contribution of DRD4 7R rare variants to high hyperactivity-inattention scores in a population-based sample from a large birth cohort. These findings provide further evidence for an effect of DRD4 7R rare variants and allelic heterogeneity in ADHD genetic susceptibility.
doi:10.1371/journal.pone.0085164
PMCID: PMC3877354  PMID: 24391992
8.  Nutritional status of adolescents: the 11-year follow-up of the 1993 Pelotas (Brazil) birth cohort study 
Cadernos de saude publica  2010;26(10):1895-1903.
We evaluate the influence of demographic, socioeconomic, and maternal variables on the nutritional status of adolescents aged 11 years. We conducted a prospective cohort study including 4,452 adolescents born in Pelotas, Southern Brazil, in 1993, accounting for 87.5% of the original cohort. Nutritional status was evaluated based on World Health Organization criteria. Subjects were classified according to nutritional status into thin, normal, overweight and obese. Independent variables analyzed included skin color, socioeconomic status, maternal schooling, and maternal body mass index (BMI). Analyses were stratified by sex, and multivariable regression was performed using the multinomial logistic approach. Overall, 7% of adolescents were classified as thin, 11.6% as overweight, and 11.6% as obese. Among boys, thinness was inversely associated with maternal schooling and maternal BMI. Among girls, thinness was directly associated with maternal BMI. Overweight and obesity were directly associated with socioeconomic status and maternal BMI, the former showing the strongest association with nutritional status among adolescents.
PMCID: PMC3836176  PMID: 20963286
Nutritional Status; Adolescent; Cohort Studies
9.  Energy Expenditure Compared to Physical Activity Measured by Accelerometry and Self-Report in Adolescents: A Validation Study 
PLoS ONE  2013;8(11):e77036.
Background
Physical inactivity is responsible for 5.3 million deaths annually worldwide. To measure physical activity energy expenditure, the doubly labeled water (DLW) method is the gold standard. However, questionnaires and accelerometry are more widely used. We compared physical activity measured by accelerometer and questionnaire against total (TEE) and physical activity energy expenditure (PAEE) estimated by DLW.
Methods
TEE, PAEE (TEE minus resting energy expenditure) and body composition were measured using the DLW technique in 25 adolescents (16 girls) aged 13 years living in Pelotas, Brazil. Physical activity was assessed using the Actigraph accelerometer and by self-report. Physical activity data from accelerometry and self-report were tested against energy expenditure data derived from the DLW method. Further, tests were done to assess the ability of moderate-to-vigorous intensity physical activity (MVPA) to predict variability in TEE and to what extent adjustment for fat and fat-free mass predicted the variability in TEE.
Results
TEE varied from 1,265 to 4,143 kcal/day. It was positively correlated with physical activity (counts) estimated by accelerometry (rho  = 0.57; p = 0.003) and with minutes per week of physical activity by questionnaire (rho  = 0.41; p = 0.04). An increase of 10 minutes per day in moderate-to-vigorous intensity physical activity (MVPA) relates to an increase in TEE of 141 kcal/day. PAEE was positively correlated with accelerometry (rho  = 0.64; p = 0.007), but not with minutes per week of physical activity estimated by questionnaire (rho  = 0.30; p = 0.15). Physical activity by accelerometry explained 31% of the vssariability in TEE. By incorporating fat and fat-free mass in the model, we were able to explain 58% of the variability in TEE.
Conclusion
Objectively measured physical activity significantly contributes to the explained variance in both TEE and PAEE in Brazilian youth. Independently, body composition also explains variance in TEE, and should ideally be taken into account when using accelerometry to predict energy expenditure values.
doi:10.1371/journal.pone.0077036
PMCID: PMC3817188  PMID: 24223707
10.  Hospital admissions from birth to early adolescence and early-life risk factors: the 11-year follow-up of the 1993 Pelotas (Brazil) birth cohort study 
Cadernos de saude publica  2010;26(10):1980-1989.
The aim of this prospective analysis was to describe the cumulative incidence of hospital admissions in the first year of life and between 1 and 11 years of age and to explore associated factors. Hospital admissions were collected through regular monitoring in the first year of life, and through maternal report on admissions between 1 and 11 years. Analyses were stratified by sex and adjusted for confounding factors. 18.1% of children were hospitalized in the first year of life, and 30.7% between ages 1 and 11 years. Among boys, hospital admission in the first year was associated with low family income, paternal smoking during pregnancy, preterm delivery, and low birthweight. Among girls, in addition to the variables described for boys, black/mixed skin color was also a risk factor for hospital admission. For admissions between 1 and 11 years of age, low family income and gestational age ≥ 37 weeks were found to be significant risk factors.
PMCID: PMC3795331  PMID: 20963296
Hospitalization; Adolescent; Child; Cohort Studies
11.  Oral health follow-up studies in the 1993 Pelotas (Brazil) birth cohort study: methodology and principal results 
Cadernos de saude publica  2010;26(10):1990-1999.
The aim of this study was to describe oral health follow-up studies nested in a birth cohort. A population-based birth cohort was launched in 1993 in Pelotas, Rio Grande do Sul State, Brazil. Two oral health follow-up studies were conducted at six (n = 359) and 12 (n = 339) years of age. A high response rate was observed at 12 years of age; 94.4% of the children examined at six years of age were restudied in 2005. The mean DMF-T index at age 12 was 1.2 (SD = 1.6) for the entire sample, ranging from 0.6 (SD = 1.1) for children that were caries-free at age six, 1.3 (SD = 1.5) for those with 1-3 carious teeth at six years, and 1.8 (SD = 1.8) for those with 4-19 carious teeth at six years (p < 0.01). The number of individuals with severe malocclusions at 12 years was proportional to the number of malocclusions at six years. Oral health problems in early adolescence were more prevalent in individuals with dental problems at six years of age.
PMCID: PMC3794421  PMID: 20963297
Oral Health; Cohort Studies; Child; Adolescent
12.  Intake of fat and fiber-rich foods according to socioeconomic status: the 11-year follow-up of the 1993 Pelotas (Brazil) birth cohort study 
Cadernos de saude publica  2010;26(10):1904-1911.
This study describes the food intake of adolescents participating in the 1993 birth cohort from Pelotas, Southern Brazil, according to socioeconomic position. We carried out a cross-sectional analysis of data collected in the 2004-2005 follow-up visit. Food intake in the previous year was evaluated using the Block questionnaire. Socioeconomic status was evaluated based on an assets index, divided into quintiles. Foods with the highest frequency of daily intake were white bread (83%), butter or margarine (74.6%), beans (66.4%) and milk (48.5%). Intake of butter or margarine, bread, and beans was more frequent among poorer adolescents, and the inverse was true for milk. Intake of fruits and vegetables was low in all socioeconomic strata, but particularly low among the poor. In early adolescence, all socioeconomic groups showed high consumption of foods rich in fat and low consumption of foods rich in fiber.
PMCID: PMC3794422  PMID: 20963287
Eating; Food Habits; Socioeconomic Factors; Adolescent; Cohort Studies
13.  Concurrent determinants of blood pressure among adolescents: the 11-year follow-up of the 1993 Pelotas (Brazil) birth cohort study 
Cadernos de saude publica  2010;26(10):1972-1979.
The aim of this study was to evaluate concurrent risk factors for high blood pressure in adolescents. This is a prospective cohort study including 4,452 adolescents born in Pelotas, Rio Grande do Sul State, Brazil, in 1993. Blood pressure was measured before and after the interview, and the mean value was used in the analyses. Mean systolic blood pressure was 101.9mmHg (SD = 12.3) and mean diastolic pressure was 63.4mmHg (SD = 9.9). Adolescents with black skin had higher blood pressure than those with white skin. Mean systolic pressure among subjects in the top quartile of body mass index (BMI) was 11.6mmHg higher than among those in the lowest quartile. Mean systolic pressure among postmenarcheal girls was 5.4mmHg higher than among premenarcheal girls. Similar trends were found for diastolic arterial pressure. Our findings suggest that blood pressure control must begin already in childhood and adolescence.
PMCID: PMC3794424  PMID: 20963295
Blood Pressure; Adolescent; Cohort Studies
14.  Cross-Sectional and Longitudinal Associations Between Physical Activity and Blood Pressure in Adolescence: Birth Cohort Study 
Objectives
To explore cross-sectional and longitudinal associations between self-reported and accelerometry-based physical activity (PA) and blood pressure (BP) between 11 and 14 years of age.
Methods
Prospective birth cohort study in Pelotas, Brazil. Participants were 427 cohort members who were followed up with at 11, 12, and 14 years of age, and had questionnaire data on PA and BP at 11 and 14 years, as well as accelerometry and questionnaire data on PA at 12 years. Outcome measures were continuous systolic and diastolic BP at 14 years, and change in BP from 11 to 14 years.
Results
PA was unrelated to systolic BP in any analyses. PA measured by accelerometry at 12 years, but not questionnaire-derived PA, was inversely associated with diastolic BP at 14 years of age in fully adjusted models. Those who exceeded the 300-minutes PA threshold at all 3 visits had a 2.6 mmHg lower mean increase in DBP from 11 to 14 years compared with those classified below the threshold in all visits.
Conclusions
Accelerometry-based PA was longitudinally inversely associated with diastolic BP. This finding was not evident when analyzing self-reported PA at a given age, suggesting a possible underestimation of the association when using subjective data.
PMCID: PMC3672951  PMID: 21597118
motor activity; adolescence; prospective studies
15.  Inactivation of the putative suppressor gene DOK1 by promoter hypermethylation in primary human cancers 
The DOK1 gene is a putative tumour suppressor gene located on the human chromosome 2p13 which is frequently rearranged in leukemia and other human tumours. We previously reported that the DOK1 gene can be mutated and its expression down-regulated in human malignancies. However, the mechanism underlying DOK1 silencing remains largely unknown. We show here that unscheduled silencing of DOK1 expression through aberrant hypermethylation is a frequent event in a variety of human malignancies. DOK1 was found to be silenced in nine head and neck cancer (HNC) cell lines studied and DOK1 CpG hypermethylation correlated with loss of gene expression in these cells. DOK1 expression could be restored via demethylating treatment using 5-aza-2′deoxycytidine. In addition, transduction of cancer cell lines with DOK1 impaired their proliferation, consistent with the critical role of epigenetic silencing of DOK1 in the development and maintenance of malignant cells. We further observed that DOK1 hypermethylation occurs frequently in a variety of primary human neoplasm including solid tumours (93% in HNC, 81% in lung cancer) and hematopoietic malignancy (64% in Burkitt’s lymphoma). Control blood samples and exfoliated mouth epithelial cells from healthy individuals showed a low level of DOK1 methylation, suggesting that DOK1 hypermethylation is a tumour specific event. Finally, an inverse correlation was observed between the level of DOK1 gene methylation and its expression in tumour and adjacent non tumour tissues. Thus, hypermethylation of DOK1 is a potentially critical event in human carcinogenesis, and may be a potential cancer biomarker and an attractive target for epigenetic-based therapy.
doi:10.1002/ijc.26299
PMCID: PMC3422753  PMID: 21796618
DOK1; DNA hypermethylation; gene silencing; tumour suppressor; cancer
16.  A Longitudinal Evaluation of Physical Activity in Brazilian Adolescents: Tracking, Change and Predictors 
Pediatric exercise science  2012;24(1):58-71.
This study aimed to: 1) describe the change in leisure-time physical activity (LTPA) during early-to-mid adolescence; 2) analyze the tracking of LTPA; 3) identify the predictors of LTPA change. 4,120 adolescents were from 11 to 15 years old. Outcome was self-reported LTPA (min/wk). Boys increased their LTPA level over the four years (mean: 75 min/wk; 95%CI: 49,100), whereas a decrease was observed among girls (mean: −42 min/wk; 95%CI: −57,−28). Likelihood to be active at 15 years of age was 50% higher (95%CI: 39–62) among those who were active at 11 years. The main predictor of LTPA change was the number of physical activities performed at baseline. Regular physical activity early in life can predict this behavior afterward.
PMCID: PMC3650301  PMID: 22433265
17.  Large-scale international validation of the ADO index in subjects with COPD: an individual subject data analysis of 10 cohorts 
BMJ Open  2012;2(6):e002152.
Background
Little evidence on the validity of simple and widely applicable tools to predict mortality in patients with chronic obstructive pulmonary disease (COPD) exists.
Objective
To conduct a large international study to validate the ADO index that uses age, dyspnoea and FEV1 to predict 3-year mortality and to update it in order to make prediction of mortality in COPD patients as generalisable as possible.
Design
Individual subject data analysis of 10 European and American cohorts (n=13 914).
Setting
Population-based, primary, secondary and tertiary care.
Patients
COPD GOLD stages I–IV.
Measurements
We validated the original ADO index. We then obtained an updated ADO index in half of our cohorts to improve its predictive accuracy, which in turn was validated comprehensively in the remaining cohorts using discrimination, calibration and decision curve analysis and a number of sensitivity analyses.
Results
1350 (9.7%) of all subjects with COPD (60% male, mean age 61 years, mean FEV1 66% predicted) had died at 3 years. The original ADO index showed high discrimination but poor calibration (p<0.001 for difference between predicted and observed risk). The updated ADO index (scores from 0 to 14) preserved excellent discrimination (area under curve 0.81, 95% CI 0.80 to 0.82) but showed much improved calibration with predicted 3-year risks from 0.7% (95% CI 0.6% to 0.9%, score of 0) to 64.5% (61.2% to 67.7%, score of 14). The ADO index showed higher net benefit in subjects at low-to-moderate risk of 3-year mortality than FEV1 alone.
Interpretation
The updated 15-point ADO index accurately predicts 3-year mortality across the COPD severity spectrum and can be used to inform patients about their prognosis, clinical trial study design or benefit harm assessment of medical interventions.
doi:10.1136/bmjopen-2012-002152
PMCID: PMC3533065  PMID: 23242246
Pulmonary Disease, Chronic Obstructive; Mortality; Prognosis; Validation Studies
18.  Incidence of School Failure According to Baseline Leisure-Time Physical Activity Practice: Prospective Study 
The Journal of Adolescent Health  2012;51(6):S22-S26.
Purpose
To evaluate the prospective association between leisure-time physical activity practice at 11 years of age and incidence of school failure from 11 to 15 years of age.
Methods
The sample comprised >4,300 adolescents followed up from birth to 15 years of age participating in a birth cohort study in Pelotas, Brazil. The incidence of school failure from age 11 to 15 years was calculated by first excluding from the analyses all subjects who experienced a school failure before 11 years of age, and then categorizing as “positive” all those who reported repeating a grade at school from 11 to 15 years of age. Leisure-time physical activity was measured using a validated questionnaire.
Results
The incidence of school failure was 47.9% among boys and 38.2% among girls. Adolescents in the top quartile of leisure-time physical activity practice at 11 years of age had a higher likelihood of school failure (OR: 1.36; 95% CI: 1.06, 1.75) compared with the least active adolescents. In adjusted analyses stratified by sex, boys in the top quartile of leisure-time physical activity practice at 11 years of age were also more likely to have failed at school from age 11 to 15 years (OR: 1.60; 95% CI: 1.09, 2.33).
Conclusions
Adolescents allocating >1,000 min/wk to leisure-time physical activity were more likely to experience a school failure from 11 to 15 years of age. Although this finding does not advocate against physical activity promotion, it indicates that excess time allocated to physical activity may jeopardize school performance among adolescents.
doi:10.1016/j.jadohealth.2012.06.024
PMCID: PMC3508407  PMID: 23283155
School achievement; Adolescents; Cohort; Physical activity
19.  Life Course Association of Maternal Smoking During Pregnancy and Offspring's Height: Data From the 1993 Pelotas (Brazil) Birth Cohort 
The Journal of Adolescent Health  2012;51(6):S53-S57.
Purpose
To evaluate the effect of (1) maternal smoking during pregnancy; and (2) partner smoking on offspring's height in infancy, childhood, and adolescence.
Methods
All hospital live births from 1993 (5,249) were identified, and these infants were followed up at several ages. Height for age, expressed as z-scores using the World Health Organization growth curves, was measured at all follow-up visits. Maternal smoking during pregnancy was collected retrospectively at birth and analyzed as number of cigarettes/day smoked categorized in four categories (never smoked, <10, 10–19, and ≥20 cigarettes/day). Partner smoking was analyzed as a dichotomous variable (No/Yes). Unadjusted and adjusted analyses were performed by use of linear regression.
Results
The prevalence of self-reported maternal smoking during pregnancy was 33.5%. In the crude analysis, the number of cigarettes/day smoked by the mother during pregnancy negatively affected offspring's height in infancy, childhood, and adolescence. After adjustment for confounders and mediators, this association remained statistically significant, although the magnitude of the regression coefficients was reduced. Paternal smoking was not associated with offspring's height in the adjusted analyses.
Conclusions
In addition to the well-known harmful effects of smoking, maternal smoking during pregnancy negatively affects offspring's height. Public health policies aimed at continuing to reduce the prevalence of maternal smoking during pregnancy must be encouraged.
doi:10.1016/j.jadohealth.2012.08.014
PMCID: PMC3508408  PMID: 23283162
Smoking; Height by age; Body height; Growth; Child; Adolescent; Cohort studies
20.  Tracking of Medicine Use and Self-Medication From Infancy to Adolescence: 1993 Pelotas (Brazil) Birth Cohort Study 
The Journal of Adolescent Health  2012;51(6):S11-S15.
Purpose
To track the use of medicine and self-medication from infancy to adolescence.
Methods
All newborns in the city of Pelotas, Brazil, were monitored and enrolled in the 1993 Pelotas (Brazil) Birth Cohort Study. Subsamples of the cohort were visited at 1, 3, and 6 months and at 1 and 4 years of age. At 11 and 15 years of age, all cohort members were sought. In each of these visits, information on medicine use in the 15 days before the interview was collected. Two outcomes were analyzed: prevalence of medicine use and prevalence of self-medication.
Results
Prevalence of medicine use in the first year of life ranged from 52.0% to 68.6%. From 4 to 15 years of age, the prevalence decreased, ranging from 30.9% to 37.2%. At age 15, girls presented a 33% higher prevalence of medicine use than boys. The proportion of self-medication ranged from 12.4% to 29.0% and was higher in girls aged 11 and 15 years than boys of the same age. In all follow-up periods, use of medicines was significantly higher among children who used medicines in the earlier period. Prevalence of self-medication was higher among those who were self-medicated in the previous periods.
Conclusions
Tracking studies are important to public health because they can predict future behavior by analyzing past behavior, thus helping in designing preventive actions. In this study, previous use of medicines predicts future use, thus creating an opportunity to plan actions that promote the rational use of medicines.
doi:10.1016/j.jadohealth.2012.06.027
PMCID: PMC3508411  PMID: 23283153
Drug use; Self-medication; Cohort studies; Adolescent; Child
21.  Predictors of Body Mass Index Change From 11 to 15 Years of Age: The 1993 Pelotas (Brazil) Birth Cohort Study 
The Journal of Adolescent Health  2012;51(6):S65-S69.
Purpose
We explored predictors of nutritional status change from 11 to 15 years of age by analyzing prospective data.
Methods
We collected data at 11 and 15 years of age from individuals born in 1993 in Pelotas, Brazil. We assessed nutritional status using body mass index (BMI) for age in z-score according to the World Health Organization 2007 standards. Independent variables collected at 11 years of age were socioeconomic position, adolescent's perception of own weight, body dissatisfaction, and weight loss dieting.
Results
Of the 4,032 adolescents whose nutritional status could be evaluated in the two follow-ups, 93% maintained their nutritional status classification from 11 to 15 years. A total of 102 (2.8%) became obese and 181 (4.5%) ceased to be obese in the 4-year period. The prevalence of obesity decreased from 11 to 15 years of age in both boys and girls. Low-income girls were more likely to become obese from 11 to 15 years of age compared with high-income ones. Among boys, those with high income were more likely to cease being obese compared those with low income. Those who perceived themselves to be obese, who wished to have a smaller silhouette, and who were on diets to lose weight were more likely to become obese or to achieve a normal BMI category at 15 years of age.
Conclusions
BMI tracks strongly in early adolescence. This finding suggests that interventions to more effectively change nutritional status should be implemented in childhood and should consider emotional aspects as well as social and biological ones.
doi:10.1016/j.jadohealth.2012.08.012
PMCID: PMC3508412  PMID: 23283164
Obesity; Adolescent; Cohort studies; Body mass index
22.  Associations of Intrauterine and Postnatal Weight and Length Gains With Adolescent Body Composition: Prospective Birth Cohort Study From Brazil 
The Journal of Adolescent Health  2012;51(6):S58-S64.
Purpose
Early growth patterns have been associated with subsequent obesity risk. However, findings from middle-income populations suggest that early infant growth may benefit lean mass and height rather than adiposity. We tested the hypothesis that rapid weight or length gain in different growth periods would be associated with size and body composition in adolescence, in a prospective birth cohort from southern Brazil.
Methods
Body composition was assessed in 425 adolescents (52.2% male) at 14 years. Exposures were birth weight z-score and conditional growth in weight or length for the periods 0–6, 6–12 and 12–48 months. Differences in anthropometric and body composition outcomes between tertiles of growth in each period were tested by one-way analysis of variance.
Results
Size at birth and conditional weight and length at 6 months were associated with later height. The effect of infant weight gain on lean mass was greater for males than females, and effect on fat mass greater for females than males. By early childhood, rapid weight gain generated relatively similar effects on both tissue masses in both sexes. Rapid length gain had stronger effects on outcomes in males than females at each time point, and benefited lean mass more than adiposity. All effects were substantially attenuated after adjusting for current height. Early weight gain was more important than length gain at influencing body composition outcomes in adolescence.
Conclusions
Rapid infant weight and length gains were primarily associated with larger size in adolescence rather than increased adiposity. From one year onwards, associations between rapid weight gain and fat and lean masses remained after adjustment for height.
doi:10.1016/j.jadohealth.2012.08.013
PMCID: PMC3508414  PMID: 23283163
Body composition; Growth; Obesity; Nutritional programming
23.  Adolescents' Perception of Causes of Obesity: Unhealthy Lifestyles or Heritage? 
The Journal of Adolescent Health  2012;51(6):S46-S52.
Purpose
To evaluate adolescents' perception of the causes of obesity, with emphasis on differences according to nutritional status and socioeconomic position.
Methods
We conducted qualitative research including 80 adolescents belonging to the 1993 Pelotas (Brazil) Birth Cohort Study, and their mothers. We classified adolescent boys and girls into four groups (girls–obese, girls–eutrophic, boys–obese, and boys-eutrophic) according to body mass index for age and sex, and systematically selected them according to family income at age 15 years. Research techniques included semistructured interviews and history of life. Topics covered in the interviews included early experiences with weight management, effect of weight on social relationships, family history, eating habits, and values.
Results
Low-income obese adolescents and their mothers perceive obesity as a heritage, caused by family genes, side effects of medication use, and stressful life events. However, low-income eutrophic adolescents emphasize the role of unhealthy diets on obesity development. Among the high-income adolescents, those who are obese attribute it to genetic factors and emotional problems, whereas those who are eutrophic mention unhealthy diets and lack of physical activity as the main causes of obesity.
Conclusions
Perceptions of the causes of obesity in adolescents from a middle-income setting vary by gender, socioeconomic position, and nutritional status. Whereas some blame genetics as responsible for obesity development, others blame unhealthy diets and lifestyles, and others acknowledge the roles of early life experiences and family traditions in the process of obesity development.
doi:10.1016/j.jadohealth.2012.08.015
PMCID: PMC3508415  PMID: 23283160
Adolescence; Obesity; Medicalization; Qualitative research; Fatness; Social control; Cohort studies
24.  Socioeconomic Trajectories From Birth to Adolescence and Risk Factors for Noncommunicable Disease: Prospective Analyses 
The Journal of Adolescent Health  2012;51(6):S32-S37.
Purpose
To evaluate the associations between family socioeconomic trajectories from 0 to 11 years of age and risk factors for noncommunicable disease at 15 years.
Methods
Individuals born in the city of Pelotas, Brazil, in 1993 are part of a birth cohort study. Socioeconomic position, collected at birth and at 11 years of age, was our main exposure. Risk factors for chronic disease were collected at 15 years. Body mass index was transformed into Z score using the World Health Organization standard. Transport and leisure-time physical activity, smoking, and alcohol consumption were assessed by self-report. Blood pressure was measured using a digital sphygmomanometer.
Results
Of 5,249 cohort members, 85.7% were located at the 15-year follow-up visit. Rich adolescents were more likely to be overweight, be obese, and not use active modes of transport to school. Poor adolescents were more likely to smoke. In relation to socioeconomic trajectories, the odds of obesity were 46% higher among those who were “always rich” compared with those who were “always poor”; the odds of use of an inactive mode of transportation were 326% greater among the “always rich” than the “always poor,” whereas the reverse was observed for smoking (odds of 200%). The “always rich” had one-half the odds of walking or cycling to school compared with those who became wealthy in the studied period.
Conclusions
Adolescent socioeconomic position is a stronger determinant of risk factors for noncommunicable diseases than socioeconomic trajectories. However, trajectories do matter, particularly in terms of use of active transportation to school.
doi:10.1016/j.jadohealth.2012.06.022
PMCID: PMC3508416  PMID: 23283158
Socioeconomic factors; Poverty; Adolescent; Chronic diseases
25.  Socioeconomic Changes and Adolescent Psychopathology in a Brazilian Birth Cohort Study 
The Journal of Adolescent Health  2012;51(6):S5-S10.
Purpose
To investigate the effects of socioeconomic changes from birth to 11 years of life on emotional, conduct, and attentional/hyperactivity problems in 15-year-old adolescents, from the 1993 Pelotas (Brazil) birth cohort study.
Methods
The original cohort was composed of 5,249 hospital-born children whose mothers answered a questionnaire. We conducted interviews with 87.5% and 85.7% of the original cohort in 2004–2005 and 2008, respectively. We divided family income changes into nine possible categories based on two assessment points (birth and 11 years of age) and three income levels. To assess the psychopathology of the adolescents at 15 years of age, 4,423 mothers answered the Strengths and Difficulties Questionnaire.
Results
Adolescents who were always poor or who became poor between birth and 11 years of age had greater conduct problems at 15 years of age. There was no consistent association between poverty and emotional and attentional/hyperactivity problems.
Conclusions
The effects of income change were more specific to conduct problems than to emotional and attentional/hyperactivity problems, similar to what has been previously described in developed countries.
doi:10.1016/j.jadohealth.2012.06.026
PMCID: PMC3508417  PMID: 23283161
Psychopathology; Income; Poverty; Socioeconomic status; Conduct disorders; Emotional disorders; Attention deficit/hyperactivity disorder adolescence

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