Ο ρόλος της πρασουγρέλης στην αντιμετώπιση καρδιαγγειακών συμβαμάτων - Νεότερα δεδομένα

Η διπλή αντιαιμοπεταλιακή αγωγή παραμένει ο ακρογωνιαίος λίθος της φαρμακευτικής αντιμετώπισης των ασθενών με οξύ στεφανιαίο σύνδρομο. Ο συνδυασμός της ασπιρίνης και του P2Y12 αναστολέα μειώνει τα ποσοστά θρόμβωσης του stent και των μείζονων καρδιαγγειακών συμβαμάτων στους ασθενείς με οξύ στεφανιαίο σύνδρομο που αντιμετωπίζονται με αγγειοπλαστική. Παρ᾽ όλα αυτά οι ασθενείς παραμένουν σε αυξημένο κίνδυνο υποτροπής καρδιαγγειακών συμβαμάτων παρά την υπάρχουσα φαρμακευτική θεραπεία. Για αυτούς τους λόγους και λόγω της ποικίλης και καθυστερημένης αντιαιμοπεταλιακής δράσης της κλοπιδογρέλης, έχουν αναπτυχθεί νέοι αναστολείς P2Y12. Η πρασουγρέλη είναι ένα προφάρμακο που χρειάζεται βιολογική μετατροπή στους ενεργούς μεταβολίτες της. Είναι εκλεκτικός αναστολέας των υποδοχέων ADP με θεραπευτική ένδειξη τα οξέα στεφανιαία σύνδρομα. Η πρασουγρέλη έχει ταχύτερη έναρξη δράσης και παρέχει μεγαλύτερη αναστολή των αιμοπεταλίων σε σχέση με την κλοπιδογρέλη. Η μεγάλη, πολυκεντρική, τυχαιοποιημένη, διπλή τυφλή μελέτη TRITON TIMI 38 απέδειξε ότι η πρασουγρέλη είναι πιο αποτελεσματική από την κλοπιδογρέλη στη μείωση των πρωτογενών καταληκτικών σημείων (μη θανατηφόρο έμφραγμα του μυοκαρδίου, αγγειακό εγκεφαλικό επεισόδιο και καρδιαγγειακός θάνατος) στους ασθενείς με οξέα στεφανιαία επεισόδια. Η πρασουγρέλη μείωσε ακόμα και τη θνητότητα (ανεξαρτήτως αιτιολογίας) στη μελέτη αυτή. Το κλινικό όφελος της πρασουγρέλης φάνηκε στους ασθενείς που αντιμετωπίζονταν επεμβατικά. Ο κίνδυνος όμως μείζονων αιμορραγιών με την πρασουγρέλη (σχετιζόμενων και μη με CABG) είναι πολύ μεγαλύτερος σε σχέση με την κλοπιδογρέλη. Η μελέτη κατέληξε στο συμπέρασμα ότι παρά το μεγαλύτερο ποσοστό αιμορραγιών, το κλινικό όφελος από τη χρησιμοποίηση της πρασουγρέλης είναι μεγαλύτερο σε σχέση με την κλοπιδογρέλη. Οι μόνες κατηγορίες που δεν έχουν κλινικό όφελος είναι οι ασθενείς με ιστορικό αγγειακού εγκεφαλικού επεισοδίου, παροδικού εγκεφαλικού επεισοδίου, ασθενείς >75 ετών και ασθενείς με βάρος <60 kg. H μελέτη TRILOGY ACS συνέκρινε την πρασουγρέλη και την κλοπιδογρέλη σε ασθενείς που αντιμετωπίστηκαν συντηρητικά χωρίς να αναδείξει κάποια σαφή υπεροχή του ενός ή του άλλου φαρμάκου. Οι οδηγίες της Ευρωπαϊκής Καρδιολογικής Εταιρείας παρουσιἀζουν αυτή τη στιγμή την πρασουγρέλη και την τικαγρελόρη ως τα αντιαιμοπεταλιακά φάρμακα πρώτης γραμμής στην αντιμετώπιση των οξέων στεφανιαίων επεισοδίων (NSTE-ACS και STEMI). Οι οδηγίες αυτές βασίζονται σε μεγάλες τυχαιοποιημένες μελέτες που απέδειξαν το κλινικό όφελος των φαρμάκων αυτών σε σχέση με την κλοπιδογρέλη. Το 2009 η Ευρωπαϊκή Επιτροπή και ο FDA ενέκριναν τη χρήση της πρασουγρέλης σε συνδυασμό με την ασπιρίνη για τη μείωση καρδιαγγειακών συμβαμάτων σε ασθενείς με οξύ στεφανιαίο επεισόδιο που πρόκειται να αντιμετωπιστούν επεμβατικά (συμπεριλαμβανομένων και αυτών της θρόμβωσης του stent). H πρασουγρέλη αμφισβητείται πλέον από την τικαγρελόρη, ένα αναστολέα του υποδοχέα P2Y12 με διαφορετικές φαρμακοκινητικές και φαρμακοδυναμικές ιδιότητες. Η ανωτερότητα του ενός σε σχέση με το άλλο φάρμακο δεν έχει πλήρως αποσαφηνιστεί από τις έως τώρα δημοσιευμένες μελέτες. Περαιτέρω μακροπρόθεσμα δεδομένα για την ασφάλεια και την αποτελεσματικότητα της πρασουγρέλης είναι αναγκαία για να ξεκαθαρίσουν τον ακριβή ρόλο της πρασουγρέλης σε σχέση με τα άλλα αντιαιμοπεταλιακά φάρμακα. Υπάρχουν ήδη τρέχουσες μελέτες προς αυτή την κατεύθυνση. Από την υπάρχουσα βιβλιογραφία συνάγεται το συμπέρασμα ότι η πρασουγρέλη αποτελεί ένα χρήσιμο εργαλείο για την πρόληψη καρδιαγγειακών συμβαμάτων, τα οποία πρόκειται να αντιμετωπιστούν επεμβατικά.Dual antiplatelet therapy remains the cornerstone of the medical management of patients with acute coronary syndrome (ACS). In ACS patients receiving a coronary stent, the combination of aspirin and a P2Y12 inhibitor reduces rates of stent thrombosis and major adverse cardiovascular events. However, patients with acute coronary syndrome still remain at risk of recurrent cardiovascular events despite the advance of medical therapy. Given the well‐known limitations of clopidogrel with variable antiplatelet effects and delayed onset of action, newer P2Y12 inhibitors have been developed. Prasugrel is a prodrug that requires biologic conversion to active metabolites. Prasugrel is a selective adenosine diphosphate (ADP) receptor antagonist indicated for use in patients with acute coronary syndromes (ACS). Prasugrel has a faster onset of action and provides greater inhibition of platelet aggregation than clopidogrel. in the large, randomized, double-blind, multicentre, TRITON TIMI 38 trial in adult patients with ACS, treatment with prasugrel was more effective than clopidogrel in reducing the incidence of the primary composite endpoint of non-fatal myocardial infarction, stroke, or cardiovascular (CV) death. Prasugrel also reduced all-cause mortality relative to clopidogrel. Benefit with prasugrel was seen in invasively managed patients. Prasugrel was generally well tolerated and was associated with an increased risk of major bleeding relative to clopidogrel. The risk of major bleeding with prasugrel (including bleeds related to CABG and non-CABG) was higher than with clopidogrel. After taking into account the higher bleeding rates, the net clinical benefit still favored prasugrel use compared with clopidogrel. However, patients with prior stroke or TIA, patients older than 75 years, and patients weighing <60 kg did not demonstrate a net clinical benefit with prasugrel use. The TRILOGY ACS trial found no benefit with prasugrel compared to clopidogrel in patients with medically treated ACS. Prasugrel and ticagrelor are now the recommended first-line agents in patients presenting with non-ST-segment elevation ACS and ST-segment elevation ACS, due to large-scale randomized trials that demonstrated net clinical benefit of these agents over clopidogrel, as stated in the European guidelines. In 2009, the European Commission and US Food and Drug Administration (FDA) approved the use of prasugrel in combination with aspirin for the reduction of thrombotic cardiovascular events (including stent thrombosis) in patients with acute coronary syndrome who are to be managed with PCI. Prasugrel is currently challenged by ticagrelor, a P2Y12 receptor antagonist with different pharmacokinetic/pharmacodynamic properties. The superiority of one drug to the other cannot be reliably estimated from the current trials. Further long-term and comparative efficacy and tolerability data are required to definitively position prasugrel with respect to other antiplatelet agents, including ticagrelor. Ongoing randomized and observational studies may help to provide valuable information on the safety and efficacy of these two drugs and their respective places with ACS patients. Current evidence indicates that prasugrel is a useful option for the prevention of thrombotic CV events in ACS patients managed invasively

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity > 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Global, Regional, and National Burden of Nontraumatic Subarachnoid Hemorrhage

Importance: Nontraumatic subarachnoid hemorrhage (SAH) represents the third most common stroke type with unique etiologies, risk factors, diagnostics, and treatments. Nevertheless, epidemiological studies often cluster SAH with other stroke types leaving its distinct burden estimates obscure. Objective: To estimate the worldwide burden of SAH. Design, setting, and participants: Based on the repeated cross-sectional Global Burden of Disease (GBD) 2021 study, the global burden of SAH in 1990 to 2021 was estimated. Moreover, the SAH burden was compared with other diseases, and its associations with 14 individual risk factors were investigated with available data in the GBD 2021 study. The GBD study included the burden estimates of nontraumatic SAH among all ages in 204 countries and territories between 1990 and 2021. Exposures: SAH and 14 modifiable risk factors. Main outcomes and measures: Absolute numbers and age-standardized rates with 95% uncertainty intervals (UIs) of SAH incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) as well as risk factor-specific population attributable fractions (PAFs). Results: In 2021, the global age-standardized SAH incidence was 8.3 (95% UI, 7.3-9.5), prevalence was 92.2 (95% UI, 84.1-100.6), mortality was 4.2 (95% UI, 3.7-4.8), and DALY rate was 125.2 (95% UI, 110.5-142.6) per 100 000 people. The highest burden estimates were found in Latin America, the Caribbean, Oceania, and high-income Asia Pacific. Although the absolute number of SAH cases increased, especially in regions with a low sociodemographic index, all age-standardized burden rates decreased between 1990 and 2021: the incidence by 28.8% (95% UI, 25.7%-31.6%), prevalence by 16.1% (95% UI, 14.8%-17.7%), mortality by 56.1% (95% UI, 40.7%-64.3%), and DALY rate by 54.6% (95% UI, 42.8%-61.9%). Of 300 diseases, SAH ranked as the 36th most common cause of death and 59th most common cause of DALY in the world. Of all worldwide SAH-related DALYs, 71.6% (95% UI, 63.8%-78.6%) were associated with the 14 modeled risk factors of which high systolic blood pressure (population attributable fraction [PAF] = 51.6%; 95% UI, 38.0%-62.6%) and smoking (PAF = 14.4%; 95% UI, 12.4%-16.5%) had the highest attribution. Conclusions and relevance: Although the global age-standardized burden rates of SAH more than halved over the last 3 decades, SAH remained one of the most common cardiovascular and neurological causes of death and disabilities in the world, with increasing absolute case numbers. These findings suggest evidence for the potential health benefits of proactive public health planning and resource allocation toward the prevention of SAH

Global wealth disparities drive adherence to COVID-safe pathways in head and neck cancer surgery

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Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

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Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions

Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021

Background: Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050. Methods: Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. Findings: In the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8–63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0–45·0] in 2050) and south Asia (31·7% [29·2–34·1] to 15·5% [13·7–17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4–40·3) to 41·1% (33·9–48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6–25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5–43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5–17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7–11·3) in the high-income super-region to 23·9% (20·7–27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5–6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2–26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [–0·6 to 3·6]). Interpretation: Globally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND: Disorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021. METHODS: We estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined. FINDINGS: Globally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer. INTERPRETATION: As the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed