Progress in adolescent health and wellbeing: tracking 12 headline indicators for 195 countries and territories, 1990–2016

Background: Rapid demographic, epidemiological, and nutritional transitons have brought a pressing need to track progress in adolescent health. Here, we present country-level estimates of 12 headline indicators from the Lancet Commission on adolescent health and wellbeing, from 1990 to 2016. Methods: Indicators included those of health outcomes (disability-adjusted life-years [DALYs] due to communicable, maternal, and nutritional diseases; injuries; and non-communicable diseases); health risks (tobacco smoking, binge drinking, overweight, and anaemia); and social determinants of health (adolescent fertility; completion of secondary education; not in education, employment, or training [NEET]; child marriage; and demand for contraception satisfied with modern methods). We drew data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016, International Labour Organisation, household surveys, and the Barro-Lee education dataset. Findings: From 1990 to 2016, remarkable shifts in adolescent health occurred. A decrease in disease burden in many countries has been offset by population growth in countries with the poorest adolescent health profiles. Compared with 1990, an additional 250 million adolescents were living in multi-burden countries in 2016, where they face a heavy and complex burden of disease. The rapidity of nutritional transition is evident from the 324·1 million (18%) of 1·8 billion adolescents globally who were overweight or obese in 2016, an increase of 176·9 million compared with 1990, and the 430·7 million (24%) who had anaemia in 2016, an increase of 74·2 million compared with 1990. Child marriage remains common, with an estimated 66 million women aged 20–24 years married before age 18 years. Although gender-parity in secondary school completion exists globally, prevalence of NEET remains high for young women in multi-burden countries, suggesting few opportunities to enter the workforce in these settings. Interpretation: Although disease burden has fallen in many settings, demographic shifts have heightened global inequalities. Global disease burden has changed little since 1990 and the prevalence of many adolescent health risks have increased. Health, education, and legal systems have not kept pace with shifting adolescent needs and demographic changes. Gender inequity remains a powerful driver of poor adolescent health in many countries. Funding: Australian National Health and Medical Research Council, and the Bill & Melinda Gates Foundatio

Differential Links Between Expressive Suppression and Well-Being Among Chinese and Mexican American College Students

Previous research on culture and emotion regulation has focused primarily on comparing participants from individualistic and collectivistic backgrounds (e.g., European Americans vs. Asians/Asian Americans). However, ethnic groups that are equally individualistic or collectivistic can still vary notably in cultural norms and practices regarding emotion regulation. The present study examined the association between expressive suppression and well-being in two collectivistic ethnic groups (i.e., Chinese Americans and Mexican Americans). Results indicated that suppression of positive emotions was related to lower hedonic and eudaimonic well-being among Mexican Americans but not among Chinese Americans. Moreover, post hoc analysis revealed that Mexican Americans with a stronger collective identity reported lower eudaimonic well-being when suppressing positive emotions than Mexican Americans with a weaker collective identity. Suppression of negative emotions, by contrast, was unrelated to hedonic and eudaimonic well-being for both ethnic groups. Overall, our findings underscore the importance of taking into account the role that culture and the characteristics of emotion (e.g., valence) may play in the link between emotion regulation and well-being

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Genome-wide imputation study identifies novel HLA locus for pulmonary fibrosis and potential role for auto-immunity in fibrotic idiopathic interstitial pneumonia.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Fibrotic idiopathic interstitial pneumonias (fIIP) are a group of fatal lung diseases with largely unknown etiology and without definitive treatment other than lung transplant to prolong life. There is strong evidence for the importance of both rare and common genetic risk alleles in familial and sporadic disease. We have previously used genome-wide single nucleotide polymorphism data to identify 10 risk loci for fIIP. Here we extend that work to imputed genome-wide genotypes and conduct new RNA sequencing studies of lung tissue to identify and characterize new fIIP risk loci.We performed genome-wide genotype imputation association analyses in 1616 non-Hispanic white (NHW) cases and 4683 NHW controls followed by validation and replication (878 cases, 2017 controls) genotyping and targeted gene expression in lung tissue. Following meta-analysis of the discovery and replication populations, we identified a novel fIIP locus in the HLA region of chromosome 6 (rs7887 P meta  = 3.7 × 10(-09)). Imputation of classic HLA alleles identified two in high linkage disequilibrium that are associated with fIIP (DRB1*15:01 P = 1.3 × 10(-7) and DQB1*06:02 P = 6.1 × 10(-8)). Targeted RNA-sequencing of the HLA locus identified 21 genes differentially expressed between fibrotic and control lung tissue (Q < 0.001), many of which are involved in immune and inflammatory response regulation. In addition, the putative risk alleles, DRB1*15:01 and DQB1*06:02, are associated with expression of the DQB1 gene among fIIP cases (Q < 1 × 10(-16)).We have identified a genome-wide significant association between the HLA region and fIIP. Two HLA alleles are associated with fIIP and affect expression of HLA genes in lung tissue, indicating that the potential genetic risk due to HLA alleles may involve gene regulation in addition to altered protein structure. These studies reveal the importance of the HLA region for risk of fIIP and a basis for the potential etiologic role of auto-immunity in fIIP.National Heart, Lung and Blood Institute R01-HL095393 R01-HL097163 P01-HL092870 RC2-HL101715 U01-HL089897 U01-HL089856 U01-HL108642 P50-HL089493

Human and mouse essentiality screens as a resource for disease gene discovery

The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development. After screening developmental disorder cases from three independent disease sequencing consortia, we identify potentially pathogenic variants in genes not previously associated with rare diseases. We therefore propose FUSIL as an efficient approach for disease gene discovery. Discovery of causal variants for monogenic disorders has been facilitated by whole exome and genome sequencing, but does not provide a diagnosis for all patients. Here, the authors propose a Full Spectrum of Intolerance to Loss-of-Function (FUSIL) categorization that integrates gene essentiality information to aid disease gene discovery

Leukocyte Telomere Length in Major Depression: Correlations with Chronicity, Inflammation and Oxidative Stress - Preliminary Findings

Depression is associated with an unusually high rate of aging-related illnesses and early mortality. One aspect of “accelerated aging” in depression may be shortened leukocyte telomeres. When telomeres critically shorten, as often occurs with repeated mitoses or in response to oxidation and inflammation, cells may die. Indeed, leukocyte telomere shortening predicts early mortality and medical illnesses in non-depressed populations. We sought to determine if leukocyte telomeres are shortened in Major Depressive Disorder (MDD), whether this is a function of lifetime depression exposure and whether this is related to putative mediators, oxidation and inflammation.Leukocyte telomere length was compared between 18 unmedicated MDD subjects and 17 controls and was correlated with lifetime depression chronicity and peripheral markers of oxidation (F2-isoprostane/Vitamin C ratio) and inflammation (IL-6). Analyses were controlled for age and sex.The depressed group, as a whole, did not differ from the controls in telomere length. However, telomere length was significantly inversely correlated with lifetime depression exposure, even after controlling for age (p<0.05). Average telomere length in the depressed subjects who were above the median of lifetime depression exposure (≥9.2 years' cumulative duration) was 281 base pairs shorter than that in controls (p<0.05), corresponding to approximately seven years of “accelerated cell aging.” Telomere length was inversely correlated with oxidative stress in the depressed subjects (p<0.01) and in the controls (p<0.05) and with inflammation in the depressed subjects (p<0.05).These preliminary data indicate that accelerated aging at the level of leukocyte telomeres is proportional to lifetime exposure to MDD. This might be related to cumulative exposure to oxidative stress and inflammation in MDD. This suggest that telomere shortening does not antedate depression and is not an intrinsic feature. Rather, telomere shortening may progress in proportion to lifetime depression exposure

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine

The unfinished agenda of communicable diseases among children and adolescents before the COVID-19 pandemic, 1990-2019: a systematic analysis of the Global Burden of Disease Study 2019

BACKGROUND: Communicable disease control has long been a focus of global health policy. There have been substantial reductions in the burden and mortality of communicable diseases among children younger than 5 years, but we know less about this burden in older children and adolescents, and it is unclear whether current programmes and policies remain aligned with targets for intervention. This knowledge is especially important for policy and programmes in the context of the COVID-19 pandemic. We aimed to use the Global Burden of Disease (GBD) Study 2019 to systematically characterise the burden of communicable diseases across childhood and adolescence. METHODS: In this systematic analysis of the GBD study from 1990 to 2019, all communicable diseases and their manifestations as modelled within GBD 2019 were included, categorised as 16 subgroups of common diseases or presentations. Data were reported for absolute count, prevalence, and incidence across measures of cause-specific mortality (deaths and years of life lost), disability (years lived with disability [YLDs]), and disease burden (disability-adjusted life-years [DALYs]) for children and adolescents aged 0-24 years. Data were reported across the Socio-demographic Index (SDI) and across time (1990-2019), and for 204 countries and territories. For HIV, we reported the mortality-to-incidence ratio (MIR) as a measure of health system performance. FINDINGS: In 2019, there were 3·0 million deaths and 30·0 million years of healthy life lost to disability (as measured by YLDs), corresponding to 288·4 million DALYs from communicable diseases among children and adolescents globally (57·3% of total communicable disease burden across all ages). Over time, there has been a shift in communicable disease burden from young children to older children and adolescents (largely driven by the considerable reductions in children younger than 5 years and slower progress elsewhere), although children younger than 5 years still accounted for most of the communicable disease burden in 2019. Disease burden and mortality were predominantly in low-SDI settings, with high and high-middle SDI settings also having an appreciable burden of communicable disease morbidity (4·0 million YLDs in 2019 alone). Three cause groups (enteric infections, lower-respiratory-tract infections, and malaria) accounted for 59·8% of the global communicable disease burden in children and adolescents, with tuberculosis and HIV both emerging as important causes during adolescence. HIV was the only cause for which disease burden increased over time, particularly in children and adolescents older than 5 years, and especially in females. Excess MIRs for HIV were observed for males aged 15-19 years in low-SDI settings. INTERPRETATION: Our analysis supports continued policy focus on enteric infections and lower-respiratory-tract infections, with orientation to children younger than 5 years in settings of low socioeconomic development. However, efforts should also be targeted to other conditions, particularly HIV, given its increased burden in older children and adolescents. Older children and adolescents also experience a large burden of communicable disease, further highlighting the need for efforts to extend beyond the first 5 years of life. Our analysis also identified substantial morbidity caused by communicable diseases affecting child and adolescent health across the world. FUNDING: The Australian National Health and Medical Research Council Centre for Research Excellence for Driving Investment in Global Adolescent Health and the Bill & Melinda Gates Foundation

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication