Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Detailed, comprehensive, and timely reporting on population health by underlying causes of disability and premature death is crucial to understanding and responding to complex patterns of disease and injury burden over time and across age groups, sexes, and locations. The availability of disease burden estimates can promote evidence-based interventions that enable public health researchers, policy makers, and other professionals to implement strategies that can mitigate diseases. It can also facilitate more rigorous monitoring of progress towards national and international health targets, such as the Sustainable Development Goals. For three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has filled that need. A global network of collaborators contributed to the production of GBD 2021 by providing, reviewing, and analysing all available data. GBD estimates are updated routinely with additional data and refined analytical methods. GBD 2021 presents, for the first time, estimates of health loss due to the COVID-19 pandemic. Methods: The GBD 2021 disease and injury burden analysis estimated years lived with disability (YLDs), years of life lost (YLLs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries using 100 983 data sources. Data were extracted from vital registration systems, verbal autopsies, censuses, household surveys, disease-specific registries, health service contact data, and other sources. YLDs were calculated by multiplying cause-age-sex-location-year-specific prevalence of sequelae by their respective disability weights, for each disease and injury. YLLs were calculated by multiplying cause-age-sex-location-year-specific deaths by the standard life expectancy at the age that death occurred. DALYs were calculated by summing YLDs and YLLs. HALE estimates were produced using YLDs per capita and age-specific mortality rates by location, age, sex, year, and cause. 95% uncertainty intervals (UIs) were generated for all final estimates as the 2·5th and 97·5th percentiles values of 500 draws. Uncertainty was propagated at each step of the estimation process. Counts and age-standardised rates were calculated globally, for seven super-regions, 21 regions, 204 countries and territories (including 21 countries with subnational locations), and 811 subnational locations, from 1990 to 2021. Here we report data for 2010 to 2021 to highlight trends in disease burden over the past decade and through the first 2 years of the COVID-19 pandemic. Findings: Global DALYs increased from 2·63 billion (95% UI 2·44–2·85) in 2010 to 2·88 billion (2·64–3·15) in 2021 for all causes combined. Much of this increase in the number of DALYs was due to population growth and ageing, as indicated by a decrease in global age-standardised all-cause DALY rates of 14·2% (95% UI 10·7–17·3) between 2010 and 2019. Notably, however, this decrease in rates reversed during the first 2 years of the COVID-19 pandemic, with increases in global age-standardised all-cause DALY rates since 2019 of 4·1% (1·8–6·3) in 2020 and 7·2% (4·7–10·0) in 2021. In 2021, COVID-19 was the leading cause of DALYs globally (212·0 million [198·0–234·5] DALYs), followed by ischaemic heart disease (188·3 million [176·7–198·3]), neonatal disorders (186·3 million [162·3–214·9]), and stroke (160·4 million [148·0–171·7]). However, notable health gains were seen among other leading communicable, maternal, neonatal, and nutritional (CMNN) diseases. Globally between 2010 and 2021, the age-standardised DALY rates for HIV/AIDS decreased by 47·8% (43·3–51·7) and for diarrhoeal diseases decreased by 47·0% (39·9–52·9). Non-communicable diseases contributed 1·73 billion (95% UI 1·54–1·94) DALYs in 2021, with a decrease in age-standardised DALY rates since 2010 of 6·4% (95% UI 3·5–9·5). Between 2010 and 2021, among the 25 leading Level 3 causes, age-standardised DALY rates increased most substantially for anxiety disorders (16·7% [14·0–19·8]), depressive disorders (16·4% [11·9–21·3]), and diabetes (14·0% [10·0–17·4]). Age-standardised DALY rates due to injuries decreased globally by 24·0% (20·7–27·2) between 2010 and 2021, although improvements were not uniform across locations, ages, and sexes. Globally, HALE at birth improved slightly, from 61·3 years (58·6–63·6) in 2010 to 62·2 years (59·4–64·7) in 2021. However, despite this overall increase, HALE decreased by 2·2% (1·6–2·9) between 2019 and 2021. Interpretation: Putting the COVID-19 pandemic in the context of a mutually exclusive and collectively exhaustive list of causes of health loss is crucial to understanding its impact and ensuring that health funding and policy address needs at both local and global levels through cost-effective and evidence-based interventions. A global epidemiological transition remains underway. Our findings suggest that prioritising non-communicable disease prevention and treatment policies, as well as strengthening health systems, continues to be crucially important. The progress on reducing the burden of CMNN diseases must not stall; although global trends are improving, the burden of CMNN diseases remains unacceptably high. Evidence-based interventions will help save the lives of young children and mothers and improve the overall health and economic conditions of societies across the world. Governments and multilateral organisations should prioritise pandemic preparedness planning alongside efforts to reduce the burden of diseases and injuries that will strain resources in the coming decades. Funding: Bill & Melinda Gates Foundation

Training-associated changes and stability of attention bias in youth: Implications for Attention Bias Modification Treatment for pediatric anxiety

Attention Bias Modification Treatment (ABMT), an emerging treatment for anxiety disorders, is thought to modify underlying, stable patterns of attention. Therefore, ABMT research should take into account the impact of attention bias stability on attention training response, especially in pediatric populations. ABMT research typically relies on the dot-probe task, where individuals detect a probe following an emotional-neutral stimulus pair. The current research presents two dot-probe experiments relevant to ABMT and attention-bias stability. In Experiment 1, anxious youth receiving 8-weeks of cognitive-behavioral therapy (CBT) were randomly assigned to ABMT that trains attention towards happy faces (n=18) or placebo (n=18). Two additional comparison groups, anxious youth receiving only CBT (n=17) and healthy comparison youth (n=16), were studied. Active attention training towards happy faces did not augment clinician-rated response to CBT; however, individuals receiving training exhibited reductions on self-report measures of anxiety earlier than individuals receiving CBT only. In Experiment 2, healthy youth (n=12) completed a dot-probe task twice while undergoing functional magnetic resonance imaging. Intra class-correlation demonstrated stability of neural activation in response to attention bias in the ventrolateral prefrontal cortex and amygdala. Together, these two studies investigate the ways in which attention-bias stability may impact future work on ABMT

Distinct Contributions of the Dorsolateral Prefrontal and Orbitofrontal Cortex during Emotion Regulation

<div><p>The lateral prefrontal and orbitofrontal cortices have both been implicated in emotion regulation, but their distinct roles in regulation of negative emotion remain poorly understood. To address this issue we enrolled 58 participants in an fMRI study in which participants were instructed to reappraise both negative and neutral stimuli. This design allowed us to separately study activations reflecting cognitive processes associated with reappraisal in general and activations specifically related to reappraisal of negative emotion. Our results confirmed that both the dorsolateral prefrontal cortex (DLPFC) and the lateral orbitofrontal cortex (OFC) contribute to emotion regulation through reappraisal. However, activity in the DLPFC was related to reappraisal independently of whether negative or neutral stimuli were reappraised, whereas the lateral OFC was uniquely related to reappraisal of negative stimuli. We suggest that relative to the lateral OFC, the DLPFC serves a more general role in emotion regulation, perhaps by reflecting the cognitive demand that is inherent to the regulation task.</p> </div

Group activations during Reappraise > Attend collapsed across Stimulus valence (negative/neutral) and during interaction between Instruction (Reappraise vs. Attend) and Stimulus Valence (negative vs. neutral).

<p>All reported activations are based on anatomical ROI analysis and significant at <i>p</i><.05 (FWE).</p><p>Note: BA = Brodmann area; R = Right; L = Left. Coordinates: MNI system.</p

Statistical parametric maps showing activations during the main effect of instruction and the Instruction× Valence interaction (A).

<p>Activation in the right dorsolateral prefrontal cortex (DLPFC) during the main effect of instruction across stimulus valence in Reappraise (negative + neutral) > Attend (negative + neutral). Significant activations are displayed overlaid on the DLPFC region-of-interest (ROI) image (shown in blue) in sagittal (upper left), coronal (upper right) and axial (lower left) view, respectively and the (<b>B</b>) corresponding contrast estimates for the right and left DLPFC and lateral OFC at peak activation coordinates [right doroslateral PFC: x = 39, y = 24, z = 36; left DLPFC: right OFC; x = 26, y = 46, z = −13; left OFC: x = −36, y = 46, z = −12]. Note that the activations were not significant in the lateral OFC. (<b>C</b>) Activation in the right orbitofrontal cortex (OFC) and the right DLPFC during the Instruction × Valence interaction contrast Reappraise (negative - neutral) > Attend (negative - neutral). Significant activations are displayed overlaid on the DLPFC ROI (shown in blue) and the lateral OFC ROI (shown in green) in sagittal (upper left panel), coronal (upper right panel) and axial (lower left panel) view, and the (<b>D</b>) corresponding contrast estimates during the main effect of instruction and the Instruction × Valence interaction contrasts for the right and left DLPFC and lateral OFC at peak activation coordinates [right DLPFC: x = 46, y = 21, z = 44; left DLPFC; x = −39, y = 24, z = 32; right OFC; x = 42, y = 50, z = −10; left OFC: x = −38, y = 60, z = −4]. All activations were thresholded at <i>p</i><.05 (FWE) and were based on the DLPFC and lateral OFC ROIs. * = <i>p</i><.05 (FWE). Error bars represent standard error of the mean.</p

Behavioral results.

<p>Discomfort ratings were significantly lower during <b>A</b>. Reappraise negative vs. Attend negative trials and during Reappraise neutral vs. Attend neutral trials. <b>B</b>. Successful emotion regulation as revealed by significantly lower subjective ratings of discomfort during Reappraise negative trials compared to Attend negative trials expressed as difference scores from neutral trials. Errors bars represent SEM. *** = <i>p</i><.001.</p

Mean valence and arousal ratings for the negative and neutral stimuli.

<p>Standard deviations (SD) are shown in parenthesis.</p

Group activations for “Reappraise” vs. “Attend” during negative and neutral trials.

<p>All reported activations are based on anatomical ROI analysis and significant at <i>p</i><.05 (FWE).</p><p>Note: BA = Brodmann area; R = Right; L = Left. Coordinates: MNI system.</p

Experimental procedure.

<p>Each trial began with an initial 2 sec instruction to either “Attend” or “Reappraise” which was followed by a 5 sec presentation of a negative or a neutral picture. During attend trials, participants were instructed to attend to the picture without trying to alter any ongoing feelings and on reappraise trials they were instructed to neutralize their feelings to the picture. After each picture viewing phase, participants indicated their current level of discomfort on a scale from 1 to 7 (1 = minimal or no discomfort, 7 = maximum discomfort). Each trial ended with a fixation cross jittered between trials with a duration of 3–5 seconds.</p