Evaluation of four gamma-based methods for calculating confidence intervals for age-adjusted mortality rates when data are sparse

Background Equal-tailed confidence intervals that maintain nominal coverage (0.95 or greater probability that a 95% confidence interval covers the true value) are useful in interval-based statistical reliability standards, because they remain conservative. For age-adjusted death rates, while the Fay–Feuer gamma method remains the gold standard, modifications have been proposed to streamline implementation and/or obtain more efficient intervals (shorter intervals that retain nominal coverage). Methods This paper evaluates three such modifications for use in interval-based statistical reliability standards, the Anderson–Rosenberg, Tiwari, and Fay–Kim intervals, when data are sparse and sample size-based standards alone are overly coarse. Initial simulations were anchored around small populations (P = 2400 or 1200), the median crude all-cause US mortality rate in 2010–2019 (833.8 per 100,000), and the corresponding age-specific probabilities of death. To allow for greater variation in the age-adjustment weights and age-specific probabilities, a second set of simulations draws those at random, while holding the mean number of deaths at 20 or 10. Finally, county-level mortality data by race/ethnicity from four causes are selected to capture even greater variation: all causes, external causes, congenital malformations, and Alzheimer disease. Results The three modifications had comparable performance when the number of deaths was large relative to the denominator and the age distribution was as in the standard population. However, for sparse county-level data by race/ethnicity for rarer causes of death, and for which the age distribution differed sharply from the standard population, coverage probability in all but the Fay–Feuer method sometimes fell below 0.95. More efficient intervals than the Fay–Feuer interval were identified under specific circumstances. When the coefficient of variation of the age-adjustment weights was below 0.5, the Anderson–Rosenberg and Tiwari intervals appeared to be more efficient, whereas when it was above 0.5, the Fay–Kim interval appeared to be more efficient. Conclusions As national and international agencies reassess prevailing data presentation standards to release age-adjusted estimates for smaller areas or population subgroups than previously presented, the Fay–Feuer interval can be used to develop interval-based statistical reliability standards with appropriate thresholds that are generally applicable. For data that meet certain statistical conditions, more efficient intervals could be considered

Refining the prediction of multisite pain in 13-year-old boys and girls by using parent-reported pain experiences in the first decade of life

Background We evaluated different pain profiles as prospective predictors of multisite pain in 13-year-old adolescents (1300 girls and 1457 boys) enrolled in Generation XXI, a birth cohort study in Portugal. Methods Pain history was queried using the Luebeck Pain Questionnaire through parent proxy- (ages 7 and 10) and adolescent (age 13) self-reports. We estimated the risk of multisite pain (2 or more pain sites) at age 13, according to previous pain experiences, including accumulation and timing. We defined five profiles that combined adverse features at ages 7 and 10 (recurrence, multisite, frequency, duration, intensity, triggers, activity restrictions, passive coping, and family history) and estimated their relative risks (RR) and likelihood ratios (LR) for adolescent multisite pain. Results At age 13, 39.2% of girls and 27.2% of boys reported multisite pain in the previous three months. The risk was higher among girls with multisite and recurrent pain at ages 7 and 10 than in girls without those adverse features, especially if psychosocial triggers were also present (RR 1.87; 95% confidence interval 1.36, 2.36 and LR 3.49; 1.53, 7.96). Boys with recurrent pain of higher frequency and causing activity restrictions at ages 7 and 10 had a higher risk of multisite pain at 13 (RR 2.05; 1.03, 3.05 and LR 3.06; 1.12, 8.39). Earlier adverse experiences were more predictive of future pain in girls than in boys. Conclusions Different profiles were useful to rule in future multisite pain in boys and girls. This provides clues for early stratification of chronic pain risk. Significance We identified sex-specific pain features that can be collected by practitioners in the first decade of life to improve the stratification of children in terms of their future risk of a maladaptive pain experience in adolescence. Using a prospective population-based cohort design, we show that early multisite pain and psychosocial triggers are relevant predictors of future multisite pain in girls, whereas repeated reports of high-frequency pain leading to activity restrictions are predictive of adolescent multisite pain in boys.This study was funded by the European Regional Development Fund (ERDF), through COMPETE 2020 Operational Programme 'Competitiveness and Internationalization' together with national funding from the Foundation for Science and Technology (FCT) – Portuguese Ministry of Science, Technology and Higher Education – through the project 'STEPACHE – The pediatric roots of amplified pain: from contextual influences to risk stratification' (POCI-01-0145-FEDER-029087, info:eu-repo/grantAgreement/FCT/9471 - RIDTI/PTDC/SAU-EPI/29087/2017/PT) and by the Epidemiology Research Unit – Instituto de Saúde Pública, Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862; UID/DTP/04750/2019), Administração Regional de Saúde Norte (Regional Department of the Portuguese Ministry of Health) and Calouste Gulbenkian Foundation. This work was also supported by a research grant from FOREUM Foundation for Research in Rheumatology (Career Research Grant)

Bullying Involvement and Physical Pain Between Ages 10 and 13 Years: Reported History and Quantitative Sensory Testing in a Population-Based Cohort

We aimed to quantify the prospective association between bullying and physical pain in a population-based cohort of adolescents. We assessed 4,049 participants of the 10 and 13 years waves of the Generation XXI birth cohort study in Portugal. Pain history was collected using the Luebeck pain screening questionnaire. A subsample of 1,727 adolescents underwent computerized cuff pressure algometry to estimate pain detection/tolerance thresholds, temporal pain summation and conditioned pain modulation. Participants completed the Bully Scale Survey and were classified as “victim only”, “both victim and aggressor”, “aggressor only”, or “not involved”. Associations were quantified using Poisson or linear regression, adjusted for sex and adverse childhood experiences. When compared to adolescents “not involved”, participants classified as “victim only” or “both victim and aggressor” at age 10 had higher risk of pain with psychosocial triggers, pain that led to skipping leisure activities, multisite pain, pain of higher intensity, and pain of longer duration, with relative risks between 1.21 (95% confidence interval: .99, 1.49) and 2.17 (1.57, 3.01). “Victims only” at age 10 had lower average pain detection and tolerance thresholds at 13 years (linear regression coefficients: −1.81 [−3.29, −.33] and −2.73 [−5.17, −.29] kPa, respectively), as well as higher pain intensity ratings (.37 [.07, .68] and .39 [.06, .72] mm), when compared with adolescents not involved. No differences were seen for the remaining bullying profiles or sensory measures. Our findings suggest that bullying may have long-term influence on the risk of chronic musculoskeletal pain and may interfere with responses to painful stimuli. Perspective: We found prospective evidence that bullying victimization in youth: 1) is more likely to lead to negative reported pain experiences than the reverse, 2) may have long-term influence on adverse pain experiences, and 3) may contribute to pain phenotypes partly by interfering with somatosensory responses to painful stimuli. © 2023 The AuthorsThe authors have no conflicts of interest to disclose. This work was supported by a research grant from FOREUM Foundation for Research in Rheumatology (Career Research Grant). This study was also funded by the Foundation for Science and Technology of the Portuguese Ministry of Science, Technology and Higher Education, through the projects “H3ARTS: Moving upstream in the determinants of cardiovascular health: A lifecourse approach using population-based cohorts from three world regions (2022.05496. PTDC)” and UNFOLD: In the shadow of violence: a life-course approach to unfold the scars on the body and mind over childhood and adolescence (2022.06837. PTDC)”. The Generation XXI cohort is funded by the Epidemiology Research Unit - Instituto de Saúde Pública, Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862; UID/DTP/04750/2019) and Laboratory for Integrative and Translational Research in Population Health (ITR) (LA/P/0064/2020), Administração Regional de Saúde—Norte (Regional Department of the Portuguese Ministry of Health) and Calouste Gulbenkian Foundation. MT was funded by the ERDF, through the North Regional Operational Program in the framework of the project HEALTH-UNORTE (NORTE-01–0145-FEDER-000039)

Mother-reported pain experience between ages 7 and 10: A prospective study in a population-based birth cohort

Background Trajectory studies suggest considerable stability of persistent or recurrent pain in adolescence. This points to the first decade of life as an important aetiologic window for shaping future pain, where the potential for prevention may be optimised. Objectives We aimed to quantify changes in mother-reported pain experience in children between ages 7 and 10 and describe clusters of different pain experiences defined by complementary pain features. Methods We conducted a prospective study using data from 4036 Generation XXI birth cohort participants recruited in 2005-06. Pain history was reported by mothers at ages 7 and 10 using the Luebeck pain screening questionnaire. We tracked changes in six pain features over time using relative risks (RRs) and their 95% confidence intervals (95% CIs). Clusters were obtained using the k-medoids algorithm. Results The risk of severe pain at age 10 increased with increasing severity at age 7, with RRs ranging from 2.18 (95% CI 1.90, 2.50) for multisite to 4.43 (95% CI 3.19, 6.15) for high frequency pain at age 7. A majority of children (59.4%) had transient or no pain but two clusters included children with stable recurrent pain (n = 404, 10.2% of the sample). One of those (n = 177) was characterised by higher probabilities of multisite pain (74.6% and 66.7% at ages 7 and 10, respectively), with psychosocial triggers/contexts (59.3% and 61.0%) and daily-living restrictions (72.2% and 84.6%). Most children in that cluster (58.3%) also self-reported recent pain at age 10 and had more frequent family history of chronic pain (60.5%). Conclusions All pain features assessed tracked with a positive gradient between ages 7 and 10, arguing for the significance of the first decade of life in the escalation of the pain experience. Multisite pain and psychosocial attributions appeared to be early markers of more adverse pain experiences.This study was funded by the European Regional Development Fund (ERDF), through COMPETE 2020 Operational Programme ‘Competitiveness and Internationalisation’ together with national funding from the Foundation for Science and Technology (FCT)—Portuguese Ministry of Science, Technology and Higher Education—through the projects “STEPACHE—The paediatric roots of amplified pain: from contextual influences to risk stratification” (POCI-01-0145-FEDER-029087, info:eu-repo/grantAgreement/FCT/9471 - RIDTI/PTDC/SAU-EPI/29087/2017/PT), and “HIneC: When do health inequalities start? Understanding the impact of childhood social adversity on health trajectories from birth to early adolescence” (POCI-01-0145-FEDER-029567, info:eu-repo/grantAgreement/FCT/9471 - RIDTI/info:eu-repo/grantAgreement/FCT/9471 - RIDTI/PTDC/SAU-PUB/29567/2017/PT017/PT). This work was also supported by the Epidemiology Research Unit—Instituto de Saúde Pública, Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862; UID/DTP/04750/2019), by Administração Regional de Saúde Norte (Regional Department of the Portuguese Ministry of Health) and Calouste Gulbenkian Foundation

Adverse childhood experiences and bodily pain at 10 years of age: Findings from the Generation XXI cohort

Background: Youth and young adults with pain conditions report having a history of adverse childhood experiences (ACEs) more frequently than their healthy peers. The relationship between ACEs and pain before adolescence in population-based settings is not extensively researched. Objective: To examine the association between the history of ACEs and bodily pain at 10 years of age. Participants and setting: Cross-sectional analysis of 4738 participants of Generation XXI population-based birth cohort, recruited in 2005–06 in Porto, Portugal. Methods: Study includes self-reported data on ACEs exposures and bodily pain (pain presence, sites, and intensity a week prior to the interview). Adjusted odds ratios (AOR) and 95% confidence intervals (CI) were obtained from binary and multinomial logistic regression analyses to estimate the likelihood of various pain features according to the extent of exposure to ACEs (i.e., 0 ACEs, 1–3 ACEs, 4–5 ACEs, and ≥ 6 ACEs). Results: Prevalence of pain, multisite, and high-intensity pain a week prior to the interview increased with increasing exposure to ACEs. After controlling for sociodemographic characteristics, children who had experienced ≥6 ACEs were more likely to report pain [AOR 3.18 (95% CI 2.19, 4.74)], multisite pain [AOR 2.45 (95% CI 1.37, 4.40)], and high-intensity pain [AOR 4.27 (95% CI 2.56, 7.12)] compared with children with no ACEs. Conclusions: A dose-response association was observed between the cumulative number of ACEs and reports of pain in 10-year-old children, suggesting that embodiment of ACEs starts as early as childhood and that pain related to ACEs begins earlier than previously reported. © 2022 Elsevier LtdFunding text 1: This work was supported by the European Regional Development Fund (ERDF) through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology (FCT), Portuguese Ministry of Science, Technology and Higher Education under the projects “HIneC: When do health inequalities start? Understanding the impact of childhood social adversity on health trajectories from birth to early adolescence” ( POCI-01-0145-FEDER-029567 ; PTDC/SAU-PUB/29567/2017 ) and “STEPACHE: The pediatric roots of amplified pain: from contextual influences to risk stratification” ( POCI-01-0145-FEDER-029087 ; PTDC/SAU-EPI/29087/2017 ). It is also supported by Unidade de Investigação em Epidemiologia - Instituto de Saúde Pública da Universidade do Porto (EPIUnit) ( UIDB/04750/2020 ), Laboratório para a Investigação Integrativa e Translacional (ITR), Porto, Portugal ( LA/P/0064/2020 ), PhD Grant SFRH/BD/144503/2019 (to AA) funded by FCT through Fundo Social Europeu (FSE) and FCT Investigator contract CEECIND/01516/2017 (to SF). ; Funding text 2: This work was supported by the European Regional Development Fund (ERDF) through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology (FCT), Portuguese Ministry of Science, Technology and Higher Education under the projects “HIneC: When do health inequalities start? Understanding the impact of childhood social adversity on health trajectories from birth to early adolescence” (POCI-01-0145-FEDER-029567; PTDC/SAU-PUB/29567/2017) and “STEPACHE: The pediatric roots of amplified pain: from contextual influences to risk stratification” (POCI-01-0145-FEDER-029087; PTDC/SAU-EPI/29087/2017). It is also supported by Unidade de Investigação em Epidemiologia - Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (UIDB/04750/2020), Laboratório para a Investigação Integrativa e Translacional (ITR), Porto, Portugal (LA/P/0064/2020), PhD Grant SFRH/BD/144503/2019 (to AA) funded by FCT through Fundo Social Europeu (FSE) and FCT Investigator contract CEECIND/01516/2017 (to SF)