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BACKGROUND: As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016. METHODS: We estimated prevalence and incidence for 328 diseases and injuries and 2982 sequelae, their non-fatal consequences. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between incidence, prevalence, remission, and cause of death rates for each condition. For some causes, we used alternative modelling strategies if incidence or prevalence needed to be derived from other data. YLDs were estimated as the product of prevalence and a disability weight for all mutually exclusive sequelae, corrected for comorbidity and aggregated to cause level. We updated the Socio-demographic Index (SDI), a summary indicator of income per capita, years of schooling, and total fertility rate. GBD 2016 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). FINDINGS: Globally, low back pain, migraine, age-related and other hearing loss, iron-deficiency anaemia, and major depressive disorder were the five leading causes of YLDs in 2016, contributing 57·6 million (95% uncertainty interval [UI] 40·8-75·9 million [7·2%, 6·0-8·3]), 45·1 million (29·0-62·8 million [5·6%, 4·0-7·2]), 36·3 million (25·3-50·9 million [4·5%, 3·8-5·3]), 34·7 million (23·0-49·6 million [4·3%, 3·5-5·2]), and 34·1 million (23·5-46·0 million [4·2%, 3·2-5·3]) of total YLDs, respectively. Age-standardised rates of YLDs for all causes combined decreased between 1990 and 2016 by 2·7% (95% UI 2·3-3·1). Despite mostly stagnant age-standardised rates, the absolute number of YLDs from non-communicable diseases has been growing rapidly across all SDI quintiles, partly because of population growth, but also the ageing of populations. The largest absolute increases in total numbers of YLDs globally were between the ages of 40 and 69 years. Age-standardised YLD rates for all conditions combined were 10·4% (95% UI 9·0-11·8) higher in women than in men. Iron-deficiency anaemia, migraine, Alzheimer's disease and other dementias, major depressive disorder, anxiety, and all musculoskeletal disorders apart from gout were the main conditions contributing to higher YLD rates in women. Men had higher age-standardised rates of substance use disorders, diabetes, cardiovascular diseases, cancers, and all injuries apart from sexual violence. Globally, we noted much less geographical variation in disability than has been documented for premature mortality. In 2016, there was a less than two times difference in age-standardised YLD rates for all causes between the location with the lowest rate (China, 9201 YLDs per 100 000, 95% UI 6862-11943) and highest rate (Yemen, 14 774 YLDs per 100 000, 11 018-19 228). INTERPRETATION: The decrease in death rates since 1990 for most causes has not been matched by a similar decline in age-standardised YLD rates. For many large causes, YLD rates have either been stagnant or have increased for some causes, such as diabetes. As populations are ageing, and the prevalence of disabling disease generally increases steeply with age, health systems will face increasing demand for services that are generally costlier than the interventions that have led to declines in mortality in childhood or for the major causes of mortality in adults. Up-to-date information about the trends of disease and how this varies between countries is essential to plan for an adequate health-system response. FUNDING: Bill & Melinda Gates Foundation, and the National Institute on Aging and the National Institute of Mental Health of the National Institutes of Health.

Abstract This study expanded the Benevolent Childhood Experiences scale (termed the “BCEs-Original” scale) with 10 new multisystem items and identified a subset of items (termed the “BCEs-Revised” scale) that are systematically less commonly reported across samples. Total BCEs-Revised scores were tested against total BCEs-Original scores and three dimensions of childhood adversity (maltreatment, threat, and deprivation) as predictors of young adulthood mental health problems (depression, anxiety, and PTSD symptoms). Hypotheses expected stronger inverse associations of BCEs-Revised scores than BCEs-Original scores with all mental health problems. Participants were 1,746 U.S. young adults ( M = 26.6 years, SD = 4.7, range = 19–35 years; 55.3% female, 42.4% male, 2.3% gender non-conforming; 67.0% White, 10.3% Asian, 8.6% Black, 8.4% Latine, 5.7% other) who completed a 20-item BCEs scale and well-validated instruments on childhood adversities and mental health problems. Compared to BCEs-Original scores, BCEs-Revised scores were significantly more strongly inversely associated with all mental health outcomes. Compared to childhood threat and deprivation, maltreatment was significantly more strongly associated with PTSD symptoms. After controlling for current depression symptoms, BCEs-Revised scores interacted with maltreatment to predict PTSD symptoms. Maltreatment and BCEs-Revised scores also influenced PTSD symptoms in person-oriented analyses. The BCEs-Revised scale has strong psychometric properties and unique strengths in research and practice. Implications for multisystem resilience are discussed.

Importance: Many studies have demonstrated an association between early-life adversity (ELA) and executive functioning in children and adolescents. However, the aggregate magnitude of this association is unknown in the context of threat and deprivation types of adversity and various executive functioning domains. Objective: To test the hypothesis that experiences of deprivation are more strongly associated with reduced executive functioning compared with experiences of threat during childhood and adolescence. Data Sources: Embase, ERIC, MEDLINE, and PsycInfo databases were searched from inception to December 31, 2020. Both forward and reverse snowball citation searches were performed to identify additional articles. Study Selection: Articles were selected for inclusion if they (1) had a child and/or adolescent sample, (2) included measures of ELA, (3) measured executive functioning, (4) evaluated the association between adversity and executive functioning, (5) were published in a peer-reviewed journal, and (6) were published in the English language. No temporal or geographic limits were set. A 2-reviewer, blinded screening process was conducted. Data Extraction and Synthesis: PRISMA guidelines were used to guide data extraction and article diagnostics (for heterogeneity, small study bias, and p-hacking). Article quality was assessed, and data extraction was performed by multiple independent observers. A 3-level meta-analytic model with a restricted maximum likelihood method was used. Moderator analyses were conducted to explore heterogeneity. Main Outcomes and Measures: Primary outcomes included measures of the 3 domains of executive functioning: cognitive flexibility, inhibitory control, and working memory. Results: A total of 91 articles were included, representing 82 unique cohorts and 31 188 unique individuals. Deprivation, compared with threat, was associated with significantly lower inhibitory control (F1,90 = 5.69; P = .02) and working memory (F1,54 = 5.78; P = .02). No significant difference was observed for cognitive flexibility (F1,36 = 2.38; P = .12). The pooled effect size of the association of inhibitory control with deprivation was stronger (Hedges g = -0.43; 95% CI, -0.57 to -0.29) compared with threat (Hedges g = -0.27; 95% CI, -0.46 to -0.08). The pooled effect size of the association of working memory with deprivation was stronger (Hedges g = -0.54; 95% CI, -0.75 to -0.33) compared with threat (Hedges g = -0.28; 95% CI, -0.51 to -0.05). Conclusions and Relevance: Experiences of both threat and deprivation in childhood and adolescence were associated with reduced executive functioning, but the association was stronger for exposure to deprivation. Efforts to address the consequences of ELA for development should consider the associations between specific dimensions of adversity and specific developmental outcomes.

BACKGROUND: Exposure to adverse childhood experiences (ACEs) and being female are distinct risk factors for having a major depressive episode (MDE) or an anxiety disorder (AD) in adulthood, but it is unclear whether these two risk factors are synergistic. The purpose of this study was to determine whether exposure to ACEs and being female are more than additive (synergistic) in their association with MDE and AD in US adults. METHODS: We pooled cross-sectional survey data in the Midlife in the United States study from two nationally-representative cohorts of English-speaking US adults. Data from the first cohort were collected in 2004-2006 and from the second in 2011-2014. Data from both cohorts included the 12-month prevalence of MDE and AD (generalized anxiety disorder or panic disorder) assessed with the Composite International Diagnostic Interview Short Form, gender (here termed female and male), and the count of five categories of exposure to ACEs: physical, sexual, or emotional abuse; household alcohol or substance abuse; and parental separation or divorce. RESULTS: Of the 5834 survey respondents, 4344 (74.5%) with complete data on ACEs were included in the analysis. Mean (SD) age was 54.1 (13.8) years and 53.9% were female. The prevalences of MDE, AD, and exposure to 3-5 categories of ACEs were 13.7, 10.0, and 12.5%, respectively. After adjusting for covariates (age, race, and current and childhood socioeconomic disadvantage), for those with both risk factors (female and 3-5 ACEs) the prevalence of MDE was 26.9%. This was 10.2% (95% CI: 1.8, 18.5%) higher than the expected prevalence based on the additive associations of the two risk factors. The adjusted prevalence of AD among females with 3-5 ACEs was 21.9%, which was 11.4% (95% CI: 4.0, 18.9%) higher than the expected prevalence. CONCLUSIONS: For both MDE and AD, there was synergy between the two risk factors of exposure to ACEs and being female. Identification and treatment of MDE and AD may benefit from understanding the mechanisms involved in the synergistic interaction of gender with ACEs.

BACKGROUND: This is an update of the original Cochrane review, last published in 2009 (Huertas-Ceballos 2009). Recurrent abdominal pain (RAP), including children with irritable bowel syndrome, is a common problem affecting between 4% and 25% of school-aged children. For the majority of such children, no organic cause for their pain can be found on physical examination or investigation. Many dietary inventions have been suggested to improve the symptoms of RAP. These may involve either excluding ingredients from the diet or adding supplements such as fibre or probiotics. OBJECTIVES: To examine the effectiveness of dietary interventions in improving pain in children of school age with RAP. SEARCH METHODS: We searched CENTRAL, Ovid MEDLINE, Embase, eight other databases, and two trials registers, together with reference checking, citation searching and contact with study authors, in June 2016. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing dietary interventions with placebo or no treatment in children aged five to 18 years with RAP or an abdominal pain-related, functional gastrointestinal disorder, as defined by the Rome III criteria (Rasquin 2006). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We grouped dietary interventions together by category for analysis. We contacted study authors to ask for missing information and clarification, when needed. We assessed the quality of the evidence for each outcome using the GRADE approach. MAIN RESULTS: We included 19 RCTs, reported in 27 papers with a total of 1453 participants. Fifteen of these studies were not included in the previous review. All 19 RCTs had follow-up ranging from one to five months. Participants were aged between four and 18 years from eight different countries and were recruited largely from paediatric gastroenterology clinics. The mean age at recruitment ranged from 6.3 years to 13.1 years. Girls outnumbered boys in most trials. Fourteen trials recruited children with a diagnosis under the broad umbrella of RAP or functional gastrointestinal disorders; five trials specifically recruited only children with irritable bowel syndrome. The studies fell into four categories: trials of probiotic-based interventions (13 studies), trials of fibre-based interventions (four studies), trials of low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diets (one study), and trials of fructose-restricted diets (one study).We found that children treated with probiotics reported a greater reduction in pain frequency at zero to three months postintervention than those given placebo (standardised mean difference (SMD) -0.55, 95% confidence interval (CI) -0.98 to -0.12; 6 trials; 523 children). There was also a decrease in pain intensity in the intervention group at the same time point (SMD -0.50, 95% CI -0.85 to -0.15; 7 studies; 575 children). However, we judged the evidence for these outcomes to be of low quality using GRADE due to an unclear risk of bias from incomplete outcome data and significant heterogeneity.We found that children treated with probiotics were more likely to experience improvement in pain at zero to three months postintervention than those given placebo (odds ratio (OR) 1.63, 95% CI 1.07 to 2.47; 7 studies; 722 children). The estimated number needed to treat for an additional beneficial outcome (NNTB) was eight, meaning that eight children would need to receive probiotics for one to experience improvement in pain in this timescale. We judged the evidence for this outcome to be of moderate quality due to significant heterogeneity.Children with a symptom profile defined as irritable bowel syndrome treated with probiotics were more likely to experience improvement in pain at zero to three months postintervention than those given placebo (OR 3.01, 95% CI 1.77 to 5.13; 4 studies; 344 children). Children treated with probiotics were more likely to experience improvement in pain at three to six months postintervention compared to those receiving placebo (OR 1.94, 95% CI 1.10 to 3.43; 2 studies; 224 children). We judged the evidence for these two outcomes to be of moderate quality due to small numbers of participants included in the studies.We found that children treated with fibre-based interventions were not more likely to experience an improvement in pain at zero to three months postintervention than children given placebo (OR 1.83, 95% CI 0.92 to 3.65; 2 studies; 136 children). There was also no reduction in pain intensity compared to placebo at the same time point (SMD -1.24, 95% CI -3.41 to 0.94; 2 studies; 135 children). We judged the evidence for these outcomes to be of low quality due to an unclear risk of bias, imprecision, and significant heterogeneity.We found only one study of low FODMAP diets and only one trial of fructose-restricted diets, meaning no pooled analyses were possible.We were unable to perform any meta-analyses for the secondary outcomes of school performance, social or psychological functioning, or quality of daily life, as not enough studies included these outcomes or used comparable measures to assess them.With the exception of one study, all studies reported monitoring children for adverse events; no major adverse events were reported. AUTHORS' CONCLUSIONS: Overall, we found moderate- to low-quality evidence suggesting that probiotics may be effective in improving pain in children with RAP. Clinicians may therefore consider probiotic interventions as part of a holistic management strategy. However, further trials are needed to examine longer-term outcomes and to improve confidence in estimating the size of the effect, as well as to determine the optimal strain and dosage. Future research should also explore the effectiveness of probiotics in children with different symptom profiles, such as those with irritable bowel syndrome.We found only a small number of trials of fibre-based interventions, with overall low-quality evidence for the outcomes. There was therefore no convincing evidence that fibre-based interventions improve pain in children with RAP. Further high-quality RCTs of fibre supplements involving larger numbers of participants are required. Future trials of low FODMAP diets and other dietary interventions are also required to facilitate evidence-based recommendations.

BACKGROUND: Research suggests that ACEs have a long-term impact on the behavioral, emotional, and cognitive development of children. These disruptions can lead to adoption of unhealthy coping behaviors throughout the lifespan. The present study sought to examine psychological distress as a potential mediator of sex-specific associations between adverse childhood experiences (ACEs) and adult smoking. METHOD: Data from 7,210 Kaiser-Permanente members in San Diego California collected between April and October 1997 were used. RESULTS: Among women, psychological distress mediated a significant portion of the association between ACEs and smoking (21% for emotional abuse, 16% for physical abuse, 15% for physical neglect, 10% for parental separation or divorce). Among men, the associations between ACEs and smoking were not significant. CONCLUSIONS: These findings suggest that for women, current smoking cessation strategies may benefit from understanding the potential role of childhood trauma.

BACKGROUND: The relationship between childhood adversity and bipolar affective disorder remains unclear. AIMS: To understand the size and significance of this effect through a statistical synthesis of reported research. METHOD: Search terms relating to childhood adversity and bipolar disorder were entered into Medline, EMBASE, PsycINFO and Web of Science. Eligible studies included a sample diagnosed with bipolar disorder, a comparison sample and a quantitative measure of childhood adversity. RESULTS: In 19 eligible studies childhood adversity was 2.63 times (95% CI 2.00-3.47) more likely to have occurred in bipolar disorder compared with non-clinical controls. The effect of emotional abuse was particularly robust (OR = 4.04, 95% CI 3.12-5.22), but rates of adversity were similar to those in psychiatric controls. CONCLUSIONS: Childhood adversity is associated with bipolar disorder, which has implications for the treatment of this clinical group. Further prospective research could clarify temporal causality and explanatory mechanisms.

PURPOSE: To determine rates, patterns, and predictors of neurocognitive impairment in adults decades after treatment for childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Survivors of childhood ALL treated at St Jude Children's Research Hospital who were still alive at 10 or more years after diagnosis and were age ≥ 18 years were recruited for neurocognitive testing. In all, 1,014 survivors were eligible, 738 (72.8%) agreed to participate, and 567 (76.8%) of these were evaluated. Mean age was 33 years; mean time since diagnosis was 26 years. Medical record abstraction was performed for data on doses of cranial radiation therapy (CRT) and cumulative chemotherapy. Multivariable modeling was conducted and glmulti package was used to select the best model with minimum Akaike information criterion. RESULTS: Impairment rates across neurocognitive domains ranged from 28.6% to 58.9%, and those treated with chemotherapy only demonstrated increased impairment in all domains (all P values < .006). In survivors who received no CRT, dexamethasone was associated with impaired attention (relative risk [RR], 2.12; 95% CI, 1.11 to 4.03) and executive function (RR, 2.42; 95% CI, 1.20 to 4.91). The impact of CRT was dependent on young age at diagnosis for intelligence, academic, and memory functions. Risk for executive function problems increased with survival time in a CRT dose-dependent fashion. In all survivors, self-reported behavior problems increased by 5% (RR, 1.05; 95% CI, 1.01 to 1.09) with each year from diagnosis. Impairment was associated with reduced educational attainment and unemployment. CONCLUSION: This study demonstrates persistent and significant neurocognitive impairment in adult survivors of childhood ALL and warrants ongoing monitoring of brain health to facilitate successful adult development and to detect early onset of decline as survivors mature.