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Timely and comprehensive analyses of causes of death stratified by age, sex, and location are essential for shaping effective health policies aimed at reducing global mortality. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides cause-specific mortality estimates measured in counts, rates, and years of life lost (YLLs). GBD 2023 aimed to enhance our understanding of the relationship between age and cause of death by quantifying the probability of dying before age 70 years (70q0) and the mean age at death by cause and sex. This study enables comparisons of the impact of causes of death over time, offering a deeper understanding of how these causes affect global populations. GBD 2023 produced estimates for 292 causes of death disaggregated by age-sex-location-year in 204 countries and territories and 660 subnational locations for each year from 1990 until 2023. We used a modelling tool developed for GBD, the Cause of Death Ensemble model (CODEm), to estimate cause-specific death rates for most causes. We computed YLLs as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. Probability of death was calculated as the chance of dying from a given cause in a specific age period, for a specific population. Mean age at death was calculated by first assigning the midpoint age of each age group for every death, followed by computing the mean of all midpoint ages across all deaths attributed to a given cause. We used GBD death estimates to calculate the observed mean age at death and to model the expected mean age across causes, sexes, years, and locations. The expected mean age reflects the expected mean age at death for individuals within a population, based on global mortality rates and the population's age structure. Comparatively, the observed mean age represents the actual mean age at death, influenced by all factors unique to a location-specific population, including its age structure. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 250-draw distribution for each metric. Findings are reported as counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2023 include a correction for the misclassification of deaths due to COVID-19, updates to the method used to estimate COVID-19, and updates to the CODEm modelling framework. This analysis used 55 761 data sources, including vital registration and verbal autopsy data as well as data from surveys, censuses, surveillance systems, and cancer registries, among others. For GBD 2023, there were 312 new country-years of vital registration cause-of-death data, 3 country-years of surveillance data, 51 country-years of verbal autopsy data, and 144 country-years of other data types that were added to those used in previous GBD rounds. The initial years of the COVID-19 pandemic caused shifts in long-standing rankings of the leading causes of global deaths: it ranked as the number one age-standardised cause of death at Level 3 of the GBD cause classification hierarchy in 2021. By 2023, COVID-19 dropped to the 20th place among the leading global causes, returning the rankings of the leading two causes to those typical across the time series (ie, ischaemic heart disease and stroke). While ischaemic heart disease and stroke persist as leading causes of death, there has been progress in reducing their age-standardised mortality rates globally. Four other leading causes have also shown large declines in global age-standardised mortality rates across the study period: diarrhoeal diseases, tuberculosis, stomach cancer, and measles. Other causes of death showed disparate patterns between sexes, notably for deaths from conflict and terrorism in some locations. A large reduction in age-standardised rates of YLLs occurred for neonatal disorders. Despite this, neonatal disorders remained the leading cause of global YLLs over the period studied, except in 2021, when COVID-19 was temporarily the leading cause. Compared to 1990, there has been a considerable reduction in total YLLs in many vaccine-preventable diseases, most notably diphtheria, pertussis, tetanus, and measles. In addition, this study quantified the mean age at death for all-cause mortality and cause-specific mortality and found noticeable variation by sex and location. The global all-cause mean age at death increased from 46·8 years (95% UI 46·6-47·0) in 1990 to 63·4 years (63·1-63·7) in 2023. For males, mean age increased from 45·4 years (45·1-45·7) to 61·2 years (60·7-61·6), and for females it increased from 48·5 years (48·1-48·8) to 65·9 years (65·5-66·3), from 1990 to 2023. The highest all-cause mean age at death in 2023 was found in the high-income super-region, where the mean age for females reached 80·9 years (80·9-81·0) and for males 74·8 years (74·8-74·9). By comparison, the lowest all-cause mean age at death occurred in sub-Saharan Africa, where it was 38·0 years (37·5-38·4) for females and 35·6 years (35·2-35·9) for males in 2023. Lastly, our study found that all-cause 70q0 decreased across each GBD super-region and region from 2000 to 2023, although with large variability between them. For females, we found that 70q0 notably increased from drug use disorders and conflict and terrorism. Leading causes that increased 70q0 for males also included drug use disorders, as well as diabetes. In sub-Saharan Africa, there was an increase in 70q0 for many non-communicable diseases (NCDs). Additionally, the mean age at death from NCDs was lower than the expected mean age at death for this super-region. By comparison, there was an increase in 70q0 for drug use disorders in the high-income super-region, which also had an observed mean age at death lower than the expected value. We examined global mortality patterns over the past three decades, highlighting-with enhanced estimation methods-the impacts of major events such as the COVID-19 pandemic, in addition to broader trends such as increasing NCDs in low-income regions that reflect ongoing shifts in the global epidemiological transition. This study also delves into premature mortality patterns, exploring the interplay between age and causes of death and deepening our understanding of where targeted resources could be applied to further reduce preventable sources of mortality. We provide essential insights into global and regional health disparities, identifying locations in need of targeted interventions to address both communicable and non-communicable diseases. There is an ever-present need for strengthened health-care systems that are resilient to future pandemics and the shifting burden of disease, particularly among ageing populations in regions with high mortality rates. Robust estimates of causes of death are increasingly essential to inform health priorities and guide efforts toward achieving global health equity. The need for global collaboration to reduce preventable mortality is more important than ever, as shifting burdens of disease are affecting all nations, albeit at different paces and scales. Gates Foundation.

Breastfeeding is universally recognised as the nutritional gold standard for the neonate, with well-established benefits on immunological, metabolic, and relational levels. However, in light of the evidence accumulated over recent years, limiting its value to the nutritional dimension alone is reductive. Breastfeeding also represents a powerful functional modulator of craniofacial growth and, consequently, an early potential determinant of orthodontic health. Suckling at the breast activates a complex neuromuscular pattern involving the tongue, lips, mandible, and perioral musculature in a coordinated and physiological manner. This functional pattern, which is more demanding and dynamic than artificial feeding, generates mechanical stimuli that are essential for the modelling of the hard palate, transverse expansion of the maxilla, and the correct maxillo-mandibular balance. In accordance with the functional matrix principle, bone growth is not an autonomous process but responds to the functional stimuli of the soft tissues: breastfeeding constitutes, during the first months of life, one of the principal biological inputs capable of directing such development. Epidemiological evidence reinforces this biological rationale. The meta-analysis by Peres et al. [2015] documented a significant reduction in the risk of malocclusion in breastfed children compared to those fed formula. Likewise, Boronat-Catalá et al. [2017] identified a dose-response association between duration of breastfeeding and lower prevalence of occlusal anomalies in the primary and mixed dentitions. Subsequent observational studies confirmed a reduced risk of anterior open bite and posterior crossbite in subjects breastfed for longer periods. The data pertaining to duration are particularly noteworthy: the protective effect appears to be more pronounced the longer breastfeeding is maintained. This suggests that the window of the first months of life represents a critical period of craniofacial plasticity, during which functional stimuli may exert a lasting influence on morphological development. Major health institutions have progressively incorporated these findings into their recommendations. The American Academy of Pediatrics, in the 2022 policy statement [Meek and Noble], highlights the contribution of breastfeeding to oro-facial functional development. Similarly, the Ministry of Health recommends exclusive breastfeeding for the first six months and its continuation until two years of age or beyond, acknowledging its impact on harmonious child development. Within the dental and orthodontic fields, these data warrant reflection: breastfeeding can no longer be regarded as an "external" factor with respect to dentofacial prevention. On the contrary, it represents the first natural functional orthodontic intervention, capable of reducing the incidence of malocclusions and oro-facial dysfunctions through the early modulation of muscular and respiratory stimuli. Methodological limitations remain in the available literature, however: diagnostic heterogeneity, variability in the definition of breastfeeding duration, and the presence of confounding factors such as dummy/pacifier use, non-nutritive sucking habits, and genetic predisposition. Controlled longitudinal studies are required that integrate standardised clinical assessments and objective functional analyses, in order to clarify causal mechanisms and more precisely quantify the magnitude of the protective effect. Notwithstanding these limitations, the clinical message is already sufficiently robust: promoting breastfeeding means investing not only in the child's systemic health but also in early orthodontic prevention. In an era in which the interception of malocclusions is occurring at increasingly early ages, it would be paradoxical to overlook the most physiological and primary of all functional stimuli. Orthodontic prevention begins at birth. And it begins, above all, with breastfeeding.

Orofacial Myofunctional Disorders (OMDs) affect oral functions and influence craniofacial development, contributing to skeletal and dental malocclusions. The collaboration between orthodontists and speech-language pathologists (SLPs) is crucial for early diagnosis and comprehensive treatment. This study aims to evaluate the diagnostic competence of orthodontic residents in identifying OMDs, and to determine whether the application of a standardised interdisciplinary orofacial assessment protocol enhances diagnostic accuracy and interprofessional consistency. Twenty-nine postgraduate orthodontic residents (PORs) at the University of Pavia were asked to conduct the first visit of one patient each to assign a Diagnostic Score (DS) from 1 to 10, where 1 indicated no need for intervention and 10 indicated an absolute necessity for orofacial myofunctional therapy (T0). Subsequently, an adapted version of the Interdisciplinary Orofacial Examination Protocol for Children and Adolescents (aIOEPCA) was used to improve the diagnostic ability of PORs. aIOEPCA comprised 15 clinical items, including assessment of sagittal, vertical, and transverse malocclusion patterns, lip competence, tongue mobility, breathing, swallowing, and speech articulation-each scored to quantify the severity of dysfunction. A second evaluation of the DS was conducted after the use of the protocol (T1), to assess improvements in PORs diagnostic ability. An expert SLP independently evaluated the same patients using the interdisciplinary protocol and DS were compared. Statistically significant differences (p < 0.05) were observed between the PORs and the SLP evaluations across several functional parameters. Regarding DS, a significant difference was found between PORs T0 and SLP (p < 0.05), while after the use of the protocol the score improved, and PORs T1 vs SLP resulted not significant (p > 0.05). The use of the aIOEPCA improved diagnostic consistency, highlighting its potential as a standardised interdisciplinary diagnostic tool. The findings highlight a deficiency in the ability of orthodontic residents to identify functional impairments requiring orofacial myofunctional therapy. Implementing interdisciplinary assessment tools could help to mitigate this deficit and foster more cohesive diagnostic pathways. Structured interprofessional education should be considered an imperative part of orthodontic education.

The purpose of this study was to survey Italian dental practitioners on behaviour guidance techniques (BGTs). Use of tell-show-do (TSD), sedation with nitrous oxide and oxygen according to the Langa technique, audio-visual distraction (AVD) and referral to general anaesthesia (GA) were enquired, particularly focusing on nitrous oxide usage in paediatric dental patients. The research was conducted between September 2022 and December 2023. Data from 153 surveys were eligible to be processed using the STATA/BE software program, version18.0. The sample was stratified based on time in practice (&#x2264;10 and >10 years in practice), gender, practicing area (northern, central or southern Italy). Descriptive and inferential analysis were conducted comparing groups using X2 test or Fisher's exact test as appropriate. The level of statistical significance was set at P value <0.05. One hundred fifty-three complete surveys were analysed. Of the respondents, 79.8% (121) were female and 20.92% (32) were male. Regarding years in practice, 53.59% (82) were in practice for less than or equal to 10 years and 46.41% (71) were in practice for more than 10 years. As for location of the practice, 45.10% (69) worked in northern Italy, 23.53% (36) practiced in central Italy and 31.37% (48) were from southern Italy, Sicily and Sardegna included. Significant difference was found between genders, with 55.37% (67) female practitioners who assessed to have more than 50% of their patients in paediatric age, compared to 28.12% (9) male participants. Statistical significance was also found between years in practice and referral to general anaesthesia: 29.27% (24) respondents in practice for equal or less than 10 years stated to refer no patients to general anaesthesia compared to 9.86% (7) providers in practice for more than 10 years. In the sample stratified by geographical area, statistical significance was noticed among practitioners who do not refer any paediatric patient to GA: 37.50% (18) Southern Italian practitioners versus 27.78% (10) central Italian practitioners and 4.35% (3) northern Italian practitioners. Northern Italy was found to be the territory with the highest referral to GA: the answer category <10% paediatric patients indicated for GA was selected by 71.01% (49) northern practitioners versus 66.67% (24) central respondents and 45.83% (22) southern participants in the survey. Behaviour guidance technique selection and utilisation among Italian practicing paediatric dentists is influenced by multiple factors, including gender, time in practice and geographic location of practice. The results showed Tell-Show-Do as the preferred behaviour guidance technique among Italian practitioners. GA referral was assessed to be significantly higher among northern practitioners. Responders in practice for more than 10 years referred to GA a statistically higher percentage of paediatric patients, who were more prevalent in female providers' practices. Sedation with nitrous oxide and oxygen according to the Langa technique was noticed to be the least prevalent among the enquired BGTs; there is a need to implement the use and knowledge of nitrous oxide/oxygen analgesia among Italian practitioners.

The Parental-Caregivers Perceptions Questionnaire (P-CPQ) is designed to measure how parents or caregivers perceive the influence of children's oral health on their quality of life. P-CPQ can be extremely useful in measuring oral health-related quality of life for patients who are unable to provide firsthand information about their oral health, such as many autistic patients who may have impaired communication abilities or different degrees of intellectual development. Italian version of the Parental/Caregiver - Child Perception Questionnaire (P-CPQ) was used to evaluate the oral health-related quality of life of children with autism spectrum disorder (ASD) as perceived by their parents or caregivers. The questionnaire comprises 31 items categorised into four domains: oral symptoms (OS), functional limitations (FL), emotional well-being (EWB), and social well-being (SWB) of the child. Participants included parents or caregivers of neurotypical and autistic children aged 6 to 14 years, recruited from the Padua University Dental Clinic. Data collected from the questionnaires were analysed, and scores from autistic and neurotypical children were compared. Parents of children and adolescents with ASD have a worse perception of the OHRQoL of their children than parents of unaffected children. In some cases, the relevance of oral conditions may be overlooked because parents of children with ASD have a huge workload related to the child's general health problems. Dentists should be part of the multidisciplinary team of professionals who are concerned with the health of individuals with ASD to provide appropriate preventive and rehabilitative oral care.

For more than three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has provided a framework to quantify health loss due to diseases, injuries, and associated risk factors. This paper presents GBD 2023 findings on disease and injury burden and risk-attributable health loss, offering a global audit of the state of world health to inform public health priorities. This work captures the evolving landscape of health metrics across age groups, sexes, and locations, while reflecting on the remaining post-COVID-19 challenges to achieving our collective global health ambitions. The GBD 2023 combined analysis estimated years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 375 diseases and injuries, and risk-attributable burden associated with 88 modifiable risk factors. Of the more than 310&#x2008;000 total data sources used for all GBD 2023 (about 30% of which were new to this estimation round), more than 120&#x2008;000 sources were used for estimation of disease and injury burden and 59&#x2008;000 for risk factor estimation, and included vital registration systems, surveys, disease registries, and published scientific literature. Data were analysed using previously established modelling approaches, such as disease modelling meta-regression version 2.1 (DisMod-MR 2.1) and comparative risk assessment methods. Diseases and injuries were categorised into four levels on the basis of the established GBD cause hierarchy, as were risk factors using the GBD risk hierarchy. Estimates stratified by age, sex, location, and year from 1990 to 2023 were focused on disease-specific time trends over the 2010-23 period and presented as counts (to three significant figures) and age-standardised rates per 100&#x2008;000 person-years (to one decimal place). For each measure, 95% uncertainty intervals [UIs] were calculated with the 2&#xb7;5th and 97&#xb7;5th percentile ordered values from a 250-draw distribution. Total numbers of global DALYs grew 6&#xb7;1% (95% UI 4&#xb7;0-8&#xb7;1), from 2&#xb7;64 billion (2&#xb7;46-2&#xb7;86) in 2010 to 2&#xb7;80 billion (2&#xb7;57-3&#xb7;08) in 2023, but age-standardised DALY rates, which account for population growth and ageing, decreased by 12&#xb7;6% (11&#xb7;0-14&#xb7;1), revealing large long-term health improvements. Non-communicable diseases (NCDs) contributed 1&#xb7;45 billion (1&#xb7;31-1&#xb7;61) global DALYs in 2010, increasing to 1&#xb7;80 billion (1&#xb7;63-2&#xb7;03) in 2023, alongside a concurrent 4&#xb7;1% (1&#xb7;9-6&#xb7;3) reduction in age-standardised rates. Based on DALY counts, the leading level 3 NCDs in 2023 were ischaemic heart disease (193 million [176-209] DALYs), stroke (157 million [141-172]), and diabetes (90&#xb7;2 million [75&#xb7;2-107]), with the largest increases in age-standardised rates since 2010 occurring for anxiety disorders (62&#xb7;8% [34&#xb7;0-107&#xb7;5]), depressive disorders (26&#xb7;3% [11&#xb7;6-42&#xb7;9]), and diabetes (14&#xb7;9% [7&#xb7;5-25&#xb7;6]). Remarkable health gains were made for communicable, maternal, neonatal, and nutritional (CMNN) diseases, with DALYs falling from 874 million (837-917) in 2010 to 681 million (642-736) in 2023, and a 25&#xb7;8% (22&#xb7;6-28&#xb7;7) reduction in age-standardised DALY rates. During the COVID-19 pandemic, DALYs due to CMNN diseases rose but returned to pre-pandemic levels by 2023. From 2010 to 2023, decreases in age-standardised rates for CMNN diseases were led by rate decreases of 49&#xb7;1% (32&#xb7;7-61&#xb7;0) for diarrhoeal diseases, 42&#xb7;9% (38&#xb7;0-48&#xb7;0) for HIV/AIDS, and 42&#xb7;2% (23&#xb7;6-56&#xb7;6) for tuberculosis. Neonatal disorders and lower respiratory infections remained the leading level 3 CMNN causes globally in 2023, although both showed notable rate decreases from 2010, declining by 16&#xb7;5% (10&#xb7;6-22&#xb7;0) and 24&#xb7;8% (7&#xb7;4-36&#xb7;7), respectively. Injury-related age-standardised DALY rates decreased by 15&#xb7;6% (10&#xb7;7-19&#xb7;8) over the same period. Differences in burden due to NCDs, CMNN diseases, and injuries persisted across age, sex, time, and location. Based on our risk analysis, nearly 50% (1&#xb7;27 billion [1&#xb7;18-1&#xb7;38]) of the roughly 2&#xb7;80 billion total global DALYs in 2023 were attributable to the 88 risk factors analysed in GBD. Globally, the five level 3 risk factors contributing the highest proportion of risk-attributable DALYs were high systolic blood pressure (SBP), particulate matter pollution, high fasting plasma glucose (FPG), smoking, and low birthweight and short gestation-with high SBP accounting for 8&#xb7;4% (6&#xb7;9-10&#xb7;0) of total DALYs. Of the three overarching level 1 GBD risk factor categories-behavioural, metabolic, and environmental and occupational-risk-attributable DALYs rose between 2010 and 2023 only for metabolic risks, increasing by 30&#xb7;7% (24&#xb7;8-37&#xb7;3); however, age-standardised DALY rates attributable to metabolic risks decreased by 6&#xb7;7% (2&#xb7;0-11&#xb7;0) over the same period. For all but three of the 25 leading level 3 risk factors, age-standardised rates dropped between 2010 and 2023-eg, declining by 54&#xb7;4% (38&#xb7;7-65&#xb7;3) for unsafe sanitation, 50&#xb7;5% (33&#xb7;3-63&#xb7;1) for unsafe water source, and 45&#xb7;2% (25&#xb7;6-72&#xb7;0) for no access to handwashing facility, and by 44&#xb7;9% (37&#xb7;3-53&#xb7;5) for child growth failure. The three leading level 3 risk factors for which age-standardised attributable DALY rates rose were high BMI (10&#xb7;5% [0&#xb7;1 to 20&#xb7;9]), drug use (8&#xb7;4% [2&#xb7;6 to 15&#xb7;3]), and high FPG (6&#xb7;2% [-2&#xb7;7 to 15&#xb7;6]; non-significant). Our findings underscore the complex and dynamic nature of global health challenges. Since 2010, there have been large decreases in burden due to CMNN diseases and many environmental and behavioural risk factors, juxtaposed with sizeable increases in DALYs attributable to metabolic risk factors and NCDs in growing and ageing populations. This long-observed consequence of the global epidemiological transition was only temporarily interrupted by the COVID-19 pandemic. The substantially decreasing CMNN disease burden, despite the 2008 global financial crisis and pandemic-related disruptions, is one of the greatest collective public health successes known. However, these achievements are at risk of being reversed due to major cuts to development assistance for health globally, the effects of which will hit low-income countries with high burden the hardest. Without sustained investment in evidence-based interventions and policies, progress could stall or reverse, leading to widespread human costs and geopolitical instability. Moreover, the rising NCD burden necessitates intensified efforts to mitigate exposure to leading risk factors-eg, air pollution, smoking, and metabolic risks, such as high SBP, BMI, and FPG-including policies that promote food security, healthier diets, physical activity, and equitable and expanded access to potential treatments, such as GLP-1 receptor agonists. Decisive, coordinated action is needed to address long-standing yet growing health challenges, including depressive and anxiety disorders. Yet this can be only part of the solution. Our response to the NCD syndemic-the complex interaction of multiple health risks, social determinants, and systemic challenges-will define the future landscape of global health. To ensure human wellbeing, economic stability, and social equity, global action to sustain and advance health gains must prioritise reducing disparities by addressing socioeconomic and demographic determinants, ensuring equitable health-care access, tackling malnutrition, strengthening health systems, and improving vaccination coverage. We live in times of great opportunity. Gates Foundation and Bloomberg Philanthropies.

The aim of this paper is to propose a new concept of "biological parking" for the prevention of upper impacted canine in the early mixed dentition, illustrating the management of palatal expansion, followed by serial extraction of first deciduous molar and than deciduous canine. This approach, applied in the early mixed dentition, can obtain an important improving of the infrabony path of the canines, either in case of vestibular or palatal risk of impaction, because it promotes a guided acceleration of the eruption of the first premolar avoiding o reducing the risk of its mesial eruption and frees up space for the eruption of the canine, improving its inclination, better if associated with an open root apex. If pretreatment variables regarding the possible success of treatment on the eruption of canine are more severe, this approach can make easier the next surgical-orthodontic threrapy. Early maxillary expansion followed by the extraction first of the first milk molar and then of the deciduous canine, after the initial eruption of first premolars, in this exact sequence, can be effective in treating patients in early mixed dentition with risk of impacted canines.

Cardiovascular diseases (CVDs) are the leading cause of mortality and are among the foremost causes of disability globally. CVD burden has continued to increase in most countries since 1990, with trends driven by changing exposures to harmful risk factors, population growth, and population aging. We report estimates of global, national, and subnational CVD burden, including 18 subdiseases and 12 associated modifiable risk factors. We analyzed change in CVD burden from 1990 to 2023 and identified drivers of change including population growth, population aging, and risk factor exposure. The Global Burden of Disease (GBD) 2023 study, a multinational collaborative research study, quantified burden due to 375 diseases including CVD burden and identified drivers of change from 1990 to 2023 using all available data and statistical models. GBD 2023 estimated the population-level burden of diseases in 204 countries and territories from 1990 to 2023. CVDs were the leading cause of disability-adjusted life years (DALYs) and deaths estimated in the GBD. As of 2023, there were 437 million (95% UI: 401 to 465 million) CVD DALYs globally, a 1.4-fold increase from the number in 1990 of 320 million (292 to 344 million). Ischemic heart disease, intracerebral hemorrhage, ischemic stroke, and hypertensive heart disease were the leading cardiovascular causes of DALYs in 2023 globally. As of 2023, age-standardized CVD DALY rates were highest in low and low-middle Socio-demographic Index (SDI) settings and lowest in high SDI settings. The number of CVD deaths increased globally from 13.1 million (95% UI: 12.2 to 14.0 million) in 1990 to 19.2 million (95% UI: 17.4 to 20.4 million) in 2023. The number of prevalent cases of CVD more than doubled since 1990, with 311 million (95% UI: 294 to 333 million) prevalent cases of CVD in 1990 and 626 million (95% UI: 591 to 672 million) prevalent cases in 2023 globally. A total of 79.6% (95% UI: 75.7% to 82.5%) of CVD burden is attributable to modifiable risk factors 347 million [95% UI: 318 to 373 million] DALYs in 2023). Globally, high systolic blood pressure, dietary risks, high low-density lipoprotein cholesterol, and air pollution were the modifiable risks responsible for most attributable CVD burden in 2023. Since 1990, changes in exposure to modifiable risk factors have had mixed effects on CVD burden, with increases in high body mass index, high fasting plasma glucose, and low physical activity leading to higher burden, while reductions in tobacco usage have mitigated some of these increases. Population growth and population aging were the main drivers of the increasing burden since 1990, adding 128 million (95% UI: 115 to 139 million) and 139 million (95% UI: 126 to 151 million) CVD DALYs to the increase in CVD burden since 1990. CVD remains the leading cause of disease burden and death worldwide with the greatest burden in low, low-middle, and middle SDI regions. Large variation exists in CVD burden even for countries at similar levels of development, a gap explained substantially by known, modifiable risk factors that are inadequately controlled. The decades-long increase in CVD burden was the result of population growth, population aging, and increased exposure to a subset of risk factors led by metabolic risks. Countries will need to adopt effective health system and public health strategies if they are to progress in achieving global goals to reduce the burden of CVD.

Despite increasing recognition of bronchiectasis worldwide, there are no multicountry data characterising bronchiectasis in children. We aimed to describe clinical features, comparing inter-country and regional variations, and describe indices of overall quality-of-care standards assessed against international consensus statements for children and young people with bronchiectasis. Child-BEAR-Net is an international collaborative paediatric bronchiectasis network across several continents. Using our International Paediatric Bronchiectasis Registry data from secondary and tertiary hospitals across eight countries, we conducted a multicentre, cross-sectional cohort study of all patients in the registry younger than 18 years diagnosed with bronchiectasis. Data were grouped into four geographical regions: Australia, South Africa, Greece-Italy-Spain, and Albania-T&#xfc;rkiye-Ukraine. Patients with cystic fibrosis or a history of heart or lung transplantation were excluded. We assessed baseline clinical characteristics, causes, treatments, and quality-of-care indicators, and compared findings across regions. Data were analysed using descriptive statistics and non-parametric tests for between-group comparisons. Between June 1, 2020, and Feb 9, 2024, 408 patients were enrolled (median age at diagnosis 6&#xb7;0 years [IQR 3&#xb7;2-9&#xb7;0]; 229 (56%) male and 179 (44%) female patients). The most common underlying causes were post-infection (127 [31%]), primary and secondary immunodeficiencies (79 [19%]), and known genetic disorders (55 [13%]). Common comorbidities included asthma (70 [17%]), otorhinolaryngeal disorders (58 [14%]), and congenital major airway malformation (51 [13%]). In the previous 12 months, 106 (38%) had at least three exacerbations and 89 (49%) required hospitalisation at least once. 107 (27%) of 400 reported daily sputum. Lung function was normal in 133 (59%) of 227 patients but with considerable between-group differences (median forced vital capacity Z score ranged from -0&#xb7;12 [-0&#xb7;95 to 0&#xb7;65] in Australia to -1&#xb7;54 [-3&#xb7;39 to -0&#xb7;04] in South Africa). We found marked inter-group differences in lower airway bacteria (Haemophilus influenzae in 56 [70%] of 80 patients in Australia to three [16%] of 19 in Albania-T&#xfc;rkiye-Ukraine; Pseudomonas aeruginosa in eight [24%] of 34 in South Africa to one [5%] in Albania-T&#xfc;rkiye-Ukraine), treatment (long-term azithromycin for 47 [50%] of 94 in Greece-Italy-Spain to 15 [19%] of 79 in Albania-T&#xfc;rkiye-Ukraine; and inhaled corticosteroids for 48 [61%] in Albania-T&#xfc;rkiye-Ukraine to 28 [22%] of 126 in Australia), and radiographic markers (cystic bronchiectasis in 49 [45%] of 109 in South Africa to three [2%] of 126 in Australia [p<0&#xb7;0001]). In quality-of-care standard markers, the recommended panel of investigations was done in 66-95% of patients; only 78 (47%) of 167 saw a paediatric physiotherapist in the previous 12 months. Our study presents the first internationally derived paediatric registry data highlighting geographical variations in cause, lung function, bacteriology, and treatment in children and young people with bronchiectasis, as well as the need to improve quality care. None.

Comprehensive, comparable, and timely estimates of demographic metrics-including life expectancy and age-specific mortality-are essential for evaluating, understanding, and addressing trends in population health. The COVID-19 pandemic highlighted the importance of timely and all-cause mortality estimates for being able to respond to changing trends in health outcomes, showing a strong need for demographic analysis tools that can produce all-cause mortality estimates more rapidly with more readily available all-age vital registration (VR) data. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) is an ongoing research effort that quantifies human health by estimating a range of epidemiological quantities of interest across time, age, sex, location, cause, and risk. This study-part of the latest GBD release, GBD 2023-aims to provide new and updated estimates of all-cause mortality and life expectancy for 1950 to 2023 using a novel statistical model that accounts for complex correlation structures in demographic data across age and time. We used 24&#x2008;025 data sources from VR, sample registration, surveys, censuses, and other sources to estimate all-cause mortality for males, females, and all sexes combined across 25 age groups in 204 countries and territories as well as 660 subnational units in 20 countries and territories, for the years 1950-2023. For the first time, we used complete birth history data for ages 5-14 years, age-specific sibling history data for ages 15-49 years, and age-specific mortality data from Health and Demographic Surveillance Systems. We developed a single statistical model that incorporates both parametric and non-parametric methods, referred to as OneMod, to produce estimates of all-cause mortality for each age-sex-location group. OneMod includes two main steps: a detailed regression analysis with a generalised linear modelling tool that accounts for age-specific covariate effects such as the Socio-demographic Index (SDI) and a population attributable fraction (PAF) for all risk factors combined; and a non-parametric analysis of residuals using a multivariate kernel regression model that smooths across age and time to adaptably follow trends in the data without overfitting. We calibrated asymptotic uncertainty estimates using Pearson residuals to produce 95% uncertainty intervals (UIs) and corresponding 1000 draws. Life expectancy was calculated from age-specific mortality rates with standard demographic methods. For each measure, 95% UIs were calculated with the 25th and 975th ordered values from a 1000-draw posterior distribution. In 2023, 60&#xb7;1 million (95% UI 59&#xb7;0-61&#xb7;1) deaths occurred globally, of which 4&#xb7;67 million (4&#xb7;59-4&#xb7;75) were in children younger than 5 years. Due to considerable population growth and ageing since 1950, the number of annual deaths globally increased by 35&#xb7;2% (32&#xb7;2-38&#xb7;4) over the 1950-2023 study period, during which the global age-standardised all-cause mortality rate declined by 66&#xb7;6% (65&#xb7;8-67&#xb7;3). Trends in age-specific mortality rates between 2011 and 2023 varied by age group and location, with the largest decline in under-5 mortality occurring in east Asia (67&#xb7;7% decrease); the largest increases in mortality for those aged 5-14 years, 25-29 years, and 30-39 years occurring in high-income North America (11&#xb7;5%, 31&#xb7;7%, and 49&#xb7;9%, respectively); and the largest increases in mortality for those aged 15-19 years and 20-24 years occurring in Eastern Europe (53&#xb7;9% and 40&#xb7;1%, respectively). We also identified higher than previously estimated mortality rates in sub-Saharan Africa for all sexes combined aged 5-14 years (87&#xb7;3% higher in GBD 2023 than GBD 2021 on average across countries and territories over the 1950-2021 period) and for females aged 15-29 years (61&#xb7;2% higher), as well as lower than previously estimated mortality rates in sub-Saharan Africa for all sexes combined aged 50 years and older (13&#xb7;2% lower), reflecting advances in our modelling approach. Global life expectancy followed three distinct trends over the study period. First, between 1950 and 2019, there were considerable improvements, from 51&#xb7;2 (50&#xb7;6-51&#xb7;7) years for females and 47&#xb7;9 (47&#xb7;4-48&#xb7;4) years for males in 1950 to 76&#xb7;3 (76&#xb7;2-76&#xb7;4) years for females and 71&#xb7;4 (71&#xb7;3-71&#xb7;5) years for males in 2019. Second, this period was followed by a decrease in life expectancy during the COVID-19 pandemic, to 74&#xb7;7 (74&#xb7;6-74&#xb7;8) years for females and 69&#xb7;3 (69&#xb7;2-69&#xb7;4) years for males in 2021. Finally, the world experienced a period of post-pandemic recovery in 2022 and 2023, wherein life expectancy generally returned to pre-pandemic (2019) levels in 2023 (76&#xb7;3 [76&#xb7;0-76&#xb7;6] years for females and 71&#xb7;5 [71&#xb7;2-71&#xb7;8] years for males). 194 (95&#xb7;1%) of 204 countries and territories experienced at least partial post-pandemic recovery in age-standardised mortality rates by 2023, with 61&#xb7;8% (126 of 204) recovering to or falling below pre-pandemic levels. There were several mortality trajectories during and following the pandemic across countries and territories. Long-term mortality trends also varied considerably between age groups and locations, demonstrating the diverse landscape of health outcomes globally. This analysis identified several key differences in mortality trends from previous estimates, including higher rates of adolescent mortality, higher rates of young adult mortality in females, and lower rates of mortality in older age groups in much of sub-Saharan Africa. The findings also highlight stark differences across countries and territories in the timing and scale of changes in all-cause mortality trends during and following the COVID-19 pandemic (2020-23). Our estimates of evolving trends in mortality and life expectancy across locations, ages, sexes, and SDI levels in recent years as well as over the entire 1950-2023 study period provide crucial information for governments, policy makers, and the public to ensure that health-care systems, economies, and societies are prepared to address the world's health needs, particularly in populations with higher rates of mortality than previously known. The estimates from this study provide a robust framework for GBD and a valuable foundation for policy development, implementation, and evaluation around the world. Gates Foundation.

The caries risk assessment (CRA) is the set of procedures that aim to determine a personalised treatment of the caries pathology in the patient. CRA establishes the probability to develop carious lesions over a certain time period or the likelihood that there will be a change in size or activity of lesions already present [Kriegler et al., 2021]. This "assessment" occurs in two phases: the first phase is to determine specific disease indicators, risk factors, and protective factors each patient has such as the presence of bacterial biofilm, the quantity and quality of saliva, the quality and quantity of the patient's diet, the presence or absence of a correct lifestyle from a hygienic point of view; the use of fluorine and calcium phosphate substances; In the second phase a risk level is assigned to the patient (low, moderate, high, or extreme) in order to allow an individualised treatment plan, which combines restorative treatments with a preventive chemical therapy [Featherstone and Chaffee, 2018; Khallaf et al., 2021]. The aim of this preliminary study is to analyse the correlation of caries with the risk factors related in young patients from 6 to 12 years old, associated to moderate and severe risk levels of caries. This was a cross-sectional and descriptive study that included 64 children and adolescents aged from 6 to 12 years, considering the possible and possible samples not acceptable to the study, due to the exclusion criteria. Inclusion criteria were as follows: all children visiting the pediatric dental clinic who co-operated during the oral examination who have from "moderate" to" high" risk of caries according with CAMBRA [Featherstone et al., 2007]. The sample consisted of 64 subjects, of which only one with a C.R.A. score less than 11 (score 1 for the compliance factor, workable soil index, and score 3 for the fluorine factor to indicate no fluoroprophylactic measure) and was considered "low risk". This patient was excluded from the subsequent analysis, which compared subjects with a C.R.A. score of 11-15 ("high risk", n = 29) with those with a score of 16-27 ("extreme risk", n = 34). The results showed that patients at extreme risk of tooth decay compared to high-risk patients, not only had all the highest rating rates, but also had more difficulty changing their habits. We can therefore conclude that both the risk of caries is directly proportional to a worsening of the clinical conditions and the delay of the intervention by the clinician is itself a risk factor.

The Italian Society of Paediatric Dentistry (SIOI) is committed to encouraging the different health professionals taking care of children (e.g., paediatric dental practitioners, paediatricians, gynecologists, obstetricians, dental hygienists, and dieticians) to educate parents (up to the period of pregnancy) and caregivers to limit their children's consumption of cariogenic sugars. The purpose of this SIOI policy is to provide quality communication and information, based on the most updated scientific evidence, on the amount of free sugars (those classified as cariogenic) that can be consumed daily in the diet during the first two years of life, and then from childhood throughout life. This Policy communication aims to reduce the prevalence and severity of caries in both childhood and adulthood and, in addition, to prevent the occurrence of other specific non-communicable diseases (NCDs) that share the risk factor of excessive free sugar intake with caries. NCDs related to free sugar intake are obesity, type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), cardiovascular disease (CVD), hypertension, as well as some cancers and all-cause mortality. This policy is based on the most updated and methodologically valid evidence, drawing from data found in systematic reviews (with or without meta-analysis) as well as guidelines and policies (or any official statements/documents) promulgated by the most relevant international scientific societies in this field. The references collection was carried out by searching the PubMed&#xae;/MEDLINE electronic database using the following keyword terms: sugar, monosaccharide, disaccharide, sucrose, lactose, galactose, fructose, glucose, maltose, sweetened beverage, sweet food, dessert, snack, candy, cookies, chewing gum, chocolate, dairy products, fruit juice, honey, syrup, and molasses. Only studies and statements/documents written in English, available in their full text, and published within the last 10 years were included in this policy. No restrictions were adopted on the age, gender, and provenience of study participants. The interpretation of the literature findings and the subsequent formulation of policy recommendations were based on the consensus of a multidisciplinary expert panel of researchers and clinicians working in this field.

Cancer is a leading cause of death globally. Accurate cancer burden information is crucial for policy planning, but many countries do not have up-to-date cancer surveillance data. To inform global cancer-control efforts, we used the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 framework to generate and analyse estimates of cancer burden for 47 cancer types or groupings by age, sex, and 204 countries and territories from 1990 to 2023, cancer burden attributable to selected risk factors from 1990 to 2023, and forecasted cancer burden up to 2050. Cancer estimation in GBD 2023 used data from population-based cancer registration systems, vital registration systems, and verbal autopsies. Cancer mortality was estimated using ensemble models, with incidence informed by mortality estimates and mortality-to-incidence ratios (MIRs). Prevalence estimates were generated from modelled survival estimates, then multiplied by disability weights to estimate years lived with disability (YLDs). Years of life lost (YLLs) were estimated by multiplying age-specific cancer deaths by the GBD standard life expectancy at the age of death. Disability-adjusted life-years (DALYs) were calculated as the sum of YLLs and YLDs. We used the GBD 2023 comparative risk assessment framework to estimate cancer burden attributable to 44 behavioural, environmental and occupational, and metabolic risk factors. To forecast cancer burden from 2024 to 2050, we used the GBD 2023 forecasting framework, which included forecasts of relevant risk factor exposures and used Socio-demographic Index as a covariate for forecasting the proportion of each cancer not affected by these risk factors. Progress towards the UN Sustainable Development Goal (SDG) target 3.4 aim to reduce non-communicable disease mortality by a third between 2015 and 2030 was estimated for cancer. In 2023, excluding non-melanoma skin cancers, there were 18&#xb7;5 million (95% uncertainty interval 16&#xb7;4 to 20&#xb7;7) incident cases of cancer and 10&#xb7;4 million (9&#xb7;65 to 10&#xb7;9) deaths, contributing to 271 million (255 to 285) DALYs globally. Of these, 57&#xb7;9% (56&#xb7;1 to 59&#xb7;8) of incident cases and 65&#xb7;8% (64&#xb7;3 to 67&#xb7;6) of cancer deaths occurred in low-income to upper-middle-income countries based on World Bank income group classifications. Cancer was the second leading cause of deaths globally in 2023 after cardiovascular diseases. There were 4&#xb7;33 million (3&#xb7;85 to 4&#xb7;78) risk-attributable cancer deaths globally in 2023, comprising 41&#xb7;7% (37&#xb7;8 to 45&#xb7;4) of all cancer deaths. Risk-attributable cancer deaths increased by 72&#xb7;3% (57&#xb7;1 to 86&#xb7;8) from 1990 to 2023, whereas overall global cancer deaths increased by 74&#xb7;3% (62&#xb7;2 to 86&#xb7;2) over the same period. The reference forecasts (the most likely future) estimate that in 2050 there will be 30&#xb7;5 million (22&#xb7;9 to 38&#xb7;9) cases and 18&#xb7;6 million (15&#xb7;6 to 21&#xb7;5) deaths from cancer globally, 60&#xb7;7% (41&#xb7;9 to 80&#xb7;6) and 74&#xb7;5% (50&#xb7;1 to 104&#xb7;2) increases from 2024, respectively. These forecasted increases in deaths are greater in low-income and middle-income countries (90&#xb7;6% [61&#xb7;0 to 127&#xb7;0]) compared with high-income countries (42&#xb7;8% [28&#xb7;3 to 58&#xb7;6]). Most of these increases are likely due to demographic changes, as age-standardised death rates are forecast to change by -5&#xb7;6% (-12&#xb7;8 to 4&#xb7;6) between 2024 and 2050 globally. Between 2015 and 2030, the probability of dying due to cancer between the ages of 30 years and 70 years was forecasted to have a relative decrease of 6&#xb7;5% (3&#xb7;2 to 10&#xb7;3). Cancer is a major contributor to global disease burden, with increasing numbers of cases and deaths forecasted up to 2050 and a disproportionate growth in burden in countries with scarce resources. The decline in age-standardised mortality rates from cancer is encouraging but insufficient to meet the SDG target set for 2030. Effectively and sustainably addressing cancer burden globally will require comprehensive national and international efforts that consider health systems and context in the development and implementation of cancer-control strategies across the continuum of prevention, diagnosis, and treatment. Gates Foundation, St Jude Children's Research Hospital, and St Baldrick's Foundation.

Lower respiratory infections (LRIs) remain the world's leading infectious cause of death. This analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides global, regional, and national estimates of LRI incidence, mortality, and disability-adjusted life-years (DALYs), with attribution to 26 pathogens, including 11 newly modelled pathogens, across 204 countries and territories from 1990 to 2023. With new data and revised modelling techniques, these estimates serve as an update and expansion to GBD 2021. Through these estimates, we also aimed to assess progress towards the 2025 Global Action Plan for the Prevention and Control of Pneumonia and Diarrhoea (GAPPD) target for pneumonia mortality in children younger than 5 years. Mortality from LRIs, defined as physician-diagnosed pneumonia or bronchiolitis, was estimated using the Cause of Death Ensemble model with data from vital registration, verbal autopsy, surveillance, and minimally invasive tissue sampling. The Bayesian meta-regression tool DisMod-MR 2.1 was used to model overall morbidity due to LRIs. DALYs were calculated as the sum of years of life lost (YLLs) and years lived with disability (YLDs) for all locations, years, age groups, and sexes. We modelled pathogen-specific case-fatality ratios (CFRs) for each age group and location using splined binomial regression to create internally consistent estimates of incidence and mortality proportions attributable to viral, fungal, parasitic, and bacterial pathogens. Progress was assessed towards the GAPPD target of less than three deaths from pneumonia per 1000 livebirths, which is roughly equivalent to a mortality rate of less than 60 deaths per 100 000 children younger than 5 years. In 2023, LRIs were responsible for 2&#xb7;50 million (95% uncertainty interval [UI] 2&#xb7;24-2&#xb7;81) deaths and 98&#xb7;7 million (87&#xb7;7-112) DALYs, with children younger than 5 years and adults aged 70 years and older carrying the highest burden. LRI mortality in children younger than 5 years fell by 33&#xb7;4% (10&#xb7;4-47&#xb7;4) since 2010, with a global mortality rate of 94&#xb7;8 (75&#xb7;6-116&#xb7;4) per 100&#x2009;000 person-years in 2023. Among adults aged 70 years and older, the burden remained substantial with only marginal declines since 2010. A mortality rate of less than 60 deaths per 100&#x2009;000 for children younger than 5 years was met by 129 of the 204 modelled countries in 2023. At a super-regional level, sub-Saharan Africa had an aggregate mortality rate in children younger than 5 years (hereafter referred to as under-5 mortality rate) furthest from the GAPPD target. Streptococcus pneumoniae continued to account for the largest number of LRI deaths globally (634&#x2009;000 [95% UI 565&#x2009;000-721&#x2009;000] deaths or 25&#xb7;3% [24&#xb7;5-26&#xb7;1] of all LRI deaths), followed by Staphylococcus aureus (271&#x2009;000 [243&#x2009;000-298&#x2009;000] deaths or 10&#xb7;9% [10&#xb7;3-11&#xb7;3]), and Klebsiella pneumoniae (228&#x2009;000 [204&#x2009;000-261&#x2009;000] deaths or 9&#xb7;1% [8&#xb7;8-9&#xb7;5]). Among pathogens newly modelled in this study, non-tuberculous mycobacteria (responsible for 177&#x2009;000 [95% UI 155&#x2009;000-201&#x2009;000] deaths) and Aspergillus spp (responsible for 67&#x2009;800 [59&#x2009;900-75&#x2009;900] deaths) emerged as important contributors. Altogether, the 11 newly modelled pathogens accounted for approximately 22% of LRI deaths. This comprehensive analysis underscores both the gains achieved through vaccination and the challenges that remain in controlling the LRI burden globally. Furthermore, it demonstrates persistent disparities in disease burden, with the highest mortality rates concentrated in countries in sub-Saharan Africa. Globally, as well as in these high-burden locations, the under-5 LRI mortality rate remains well above the GAPPD target. Progress towards this target requires equitable access to vaccines and preventive therapies-including newer interventions such as respiratory syncytial virus monoclonal antibodies-and health systems capable of early diagnosis and treatment. Expanding surveillance of emerging pathogens, strengthening adult immunisation programmes, and combating vaccine hesitancy are also crucial. As the global population ages, the dual challenge of sustaining gains in child survival while addressing the rising vulnerability in older adults will shape future pneumonia control strategies. Gates Foundation.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, is one of the most prevalent liver diseases globally, contributing to both economic and health-related challenges. We aimed to evaluate the global, regional, and national burden of MASLD from 1990 to 2023, quantify the contribution of identified modifiable risk factors, and project future prevalence up to the year 2050. Estimates of MASLD prevalence and disability-adjusted life-years (DALYs) were produced by age, sex, region, Socio-demographic Index (SDI), and Healthcare Access and Quality (HAQ) index across 204 countries and territories from 1990 to 2023 as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023. The MASLD burden attributable to three risk factors (smoking, high BMI, and high fasting plasma glucose) was assessed as part of the GBD comparative risk assessment. As a secondary analysis, we used these estimates to forecast MASLD prevalence up to 2050 using fasting plasma glucose and mean BMI as predictors. Furthermore, to examine the relative contributions of population ageing, population growth, and changes in MASLD prevalence rate to the forecasted changes in case counts from 2023 to 2050, we conducted a decomposition analysis. In 2023, approximately 1&#xb7;3 billion (95% uncertainty interval [UI] 1&#xb7;2 to 1&#xb7;4) individuals were estimated to be living with MASLD (ie, 16&#xb7;1% of the global population), with an age-standardised prevalence rate of 14&#x2009;429&#xb7;3 (95% UI 13&#x2009;268&#xb7;3 to 15&#x2009;990&#xb7;6) per 100&#x2009;000 population, representing a percentage increase of 142&#xb7;7% (95% UI 139&#xb7;2 to 146&#xb7;7) in crude numbers from 1990 (0&#xb7;5 billion [0&#xb7;5 to 0&#xb7;6]) and of 28&#xb7;6% (27&#xb7;8 to 29&#xb7;5) in the rate (11&#x2009;217&#xb7;2 [10&#x2009;276&#xb7;8 to 12&#x2009;467&#xb7;0] per 100&#x2009;000 in 1990). An estimated 3&#xb7;6 million (2&#xb7;8 to 4&#xb7;5) total DALYs were attributable to MASLD worldwide in 2023, corresponding to an age-standardised DALY rate of 39&#xb7;6 (31&#xb7;2 to 49&#xb7;9) per 100&#x2009;000 population. Despite a 116&#xb7;3% (93&#xb7;3 to 139&#xb7;4) increase in crude DALYs (from 1&#xb7;7 million [1&#xb7;3 to 2&#xb7;1] in 1990), its age-standardised estimate remained consistent (1&#xb7;8% [-8&#xb7;6 to 12&#xb7;8]) from 1990 (38&#xb7;9 [30&#xb7;1 to 49&#xb7;8] per 100&#x2009;000) to 2023. There was substantial variation in age-standardised estimates across regions. North Africa and the Middle East had the highest prevalence rate (29&#x2009;246&#xb7;1 [26&#x2009;848&#xb7;3 to 32&#x2009;048&#xb7;7] per 100&#x2009;000) and Andean Latin America showed the highest DALY rate (152&#xb7;3 [114&#xb7;1 to 194&#xb7;7] per 100&#x2009;000). By contrast, the high-income Asia Pacific region had the lowest prevalence rate (8653&#xb7;5 [7923&#xb7;7 to 9592&#xb7;8] per 100&#x2009;000) and east Asia had the lowest DALY rate (16&#xb7;3 [13&#xb7;5 to 19&#xb7;9] per 100&#x2009;000) among all GBD regions. North Africa and the Middle East showed disproportionately higher prevalence rates relative to other regions with similar SDIs. Lower SDIs and HAQs were associated with higher age-standardised DALY rates. The age-standardised prevalence rate was consistently higher in males (15&#x2009;616&#xb7;4 [14&#x2009;349&#xb7;2 to 17&#x2009;263&#xb7;3] per 100&#x2009;000 people in 2023) than in females (13&#x2009;245&#xb7;2 [12&#x2009;132&#xb7;0 to 14&#x2009;692&#xb7;6] per 100&#x2009;000 people), and peaked at age 80-84 years in both sexes. The number of MASLD prevalent cases was the highest in younger adults, peaking at age 35-39 years for males and age 55-59 years for females. Among the risk factors for MASLD, high fasting plasma glucose presented the largest contribution to the age-standardised DALY rate of total MASLD in 2023 (2&#xb7;2 [95% UI 1&#xb7;6 to 3&#xb7;1] per 100&#x2009;000 people), followed by high BMI (1&#xb7;4 [0&#xb7;6 to 2&#xb7;4] per 100&#x2009;000 people) and smoking (1&#xb7;0 [0&#xb7;3 to 1&#xb7;8] per 100&#x2009;000 people). Our forecasting model estimates that 1&#xb7;8 billion (95% UI 1&#xb7;6 to 2&#xb7;0) individuals are likely to have MASLD by 2050, representing a 42&#xb7;0% increase from 2023. The age-standardised prevalence rate is expected to increase to 15&#x2009;774&#xb7;9 (95% UI 14&#x2009;613&#xb7;9 to 17&#x2009;336&#xb7;2) per 100&#x2009;000 people in 2050, representing an average annual percentage change of 0&#xb7;3% (95% UI 0&#xb7;3-0&#xb7;3). According to our decomposition analysis, this change will be primarily due to population growth, particularly in sub-Saharan Africa and North Africa and Middle East, and less by population ageing or epidemiological change. With a global prevalence of 16&#xb7;1% and approximately 1&#xb7;3 billion people already living with MASLD in 2023, the condition has and will continue to have substantial health and economic impacts worldwide. An inverse association between the HAQ Index and age-standardised DALY rates suggests that countries with lower health-care access and quality might be less well positioned to manage the growing MASLD burden, underscoring the need for strengthened health-system capacity in these settings. Gates Foundation.

Breast cancer is a leading cause of mortality and morbidity among females worldwide. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, we provided an updated comprehensive assessment of the epidemiological trends, disease burden, and risk factors associated with breast cancer globally, regionally, and nationally from 1990 to 2023. Breast cancer incidence, mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) were estimated by age and sex for 204 countries and territories from 1990 to 2023. Mortality estimates were generated using GBD Cause of Death Ensemble models, leveraging data from population-based cancer registration systems, vital registration systems, and verbal autopsies. Mortality-to-incidence ratios were calculated to derive both mortality and incidence estimates. Prevalence was calculated by combining incidence and modelled survival estimates. YLLs were established by multiplying age-specific deaths with the GBD standard life expectancy at the age of death. YLDs were estimated by applying disability weights to prevalence estimates. The sum of YLLs and YLDs equalled the number of DALYs. Breast cancer burden attributable to seven risk factors was examined through the comparative risk assessment framework. The GBD forecasting framework was used to forecast breast cancer incidence and mortality from 2024 to 2050. Age-standardised rates were calculated for each metric using the GBD 2023 world standard population. In 2023, there were an estimated 2&#xb7;30 million (95% uncertainty interval [UI] 2&#xb7;01 to 2&#xb7;61) breast cancer incident cases, 764&#x2008;000 deaths (672&#x2008;000 to 854&#x2008;000), and 24&#xb7;1 million (21&#xb7;3 to 27&#xb7;5) DALYs among females globally. In the World Bank low-income group, where a low age-standardised incidence rate (ASIR) was estimated (44&#xb7;2 per 100&#x2008;000 person-years [31&#xb7;2 to 58&#xb7;4]), the age-standardised mortality rate (ASMR) was the highest (24&#xb7;1 per 100&#x2008;000 [16&#xb7;8 to 31&#xb7;9]). The highest ASIR was in the high-income group (75&#xb7;7 per 100&#x2008;000 [67&#xb7;1 to 84&#xb7;0]), and the lowest ASMR was in the upper-middle-income group (11&#xb7;2 per 100&#x2008;000 [10&#xb7;2 to 12&#xb7;3]). Between 1990 and 2023, the ASIR in the low-income group increased by 147&#xb7;2% (38&#xb7;1 to 271&#xb7;7), compared with a 1&#xb7;2% (-11&#xb7;5 to 17&#xb7;2) change in the high-income group. The ASMR decreased in the high-income group, changing by -29&#xb7;9% (-33&#xb7;6 to -25&#xb7;9), but increased by 99&#xb7;3% (12&#xb7;5 to 202&#xb7;9) in the low-income group. The increase in age-standardised DALY rates followed that of ASMRs. Risk factors such as dietary risks, tobacco use, and high fasting plasma glucose contributed to 28&#xb7;3% (16&#xb7;6 to 38&#xb7;9) of breast cancer DALYs in 2023. The risk factors with a decrease in attributable DALYs between 1990 and 2023 were high alcohol use and tobacco. By 2050, the global incident cases of breast cancer among females were forecast to reach 3&#xb7;56 million (2&#xb7;29 to 4&#xb7;83), with 1&#xb7;37 million (0&#xb7;841 to 2&#xb7;02) deaths. The stable incidence and declining mortality rates of female breast cancer in high-income nations reflect success in screening, diagnosis, and treatment. In contrast, the concurrent rise in incidence and mortality in other regions signals health system deficits. Without effective interventions, many countries will fall short of the WHO Global Breast Cancer Initiative's ambitious target of achieving an annual reduction of 2&#xb7;5% in age-standardised mortality rates by 2040. The mounting breast cancer burden, disproportionately affecting some of the world's most vulnerable populations, will further exacerbate health inequalities across the globe without decisive immediate action. Gates Foundation, St Jude Children's Research Hospital.

To study root resorption of the primary dentition in children with osteogenesis imperfecta (OI) medicated with bisphosphonates (BPs) and compare the results with a control group of healthy patients. A cross-sectional study was conducted analysing 20 panoramic radiographs belonging to children with OI with a mean age of 8.18 (&#xb1;1.60), who had received BPs in a period equal to or greater than 1 year, comparing them to a control group of 367 panoramic radiographs belonging to healthy children with a mean age of 9.19 (&#xb1;1.62). Children with tooth agenesis, caries or bilateral restorative treatments in the lower arch were excluded. Root resorption of primary teeth was examined with the Haavikko method and with the PixelStick&#xae; software. To indicate the presence of dentinogenesis imperfecta (DI), the radiographic characteristic of DI such as obliteration of the pulp chambers, bulbous crowns, and very narrow root walls, were taken into account. The cumulative dose of BPs was obtained by mathematically calculating the total dosage received (mg)/weight (kg) and multiplying the relative potency of the medication. The Mann-Whitney U test was used for comparisons, and p&#x2009;<&#x2009;0.05 indicated statistical significance. Not differences in root resorption was found between children with DI or without DI. BPs therapy was associated with delay in root resorption of the primary molars and delay in the exfoliation of primary dentition in children with OI. Delayed root resorption should be considered, particularly as it may increase the number of impacted teeth in children already suffering from dental disorders.

Child growth failure (CGF), which includes underweight, wasting, and stunting, is among the factors most strongly associated with mortality and morbidity in children younger than 5 years worldwide. Poor height and bodyweight gain arise from a variety of biological and sociodemographic factors and are associated with increased vulnerability to infectious diseases. We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 to estimate CGF prevalence, the risk of infectious diseases associated with CGF, and the disease mortality, morbidity, and overall burden associated with CGF. In this analysis we estimated the all-cause and cause-specific (diarrhoea, lower respiratory tract infections, malaria, and measles) disability-adjusted life-years (DALYs) lost and mortality associated with stunting, wasting, underweight, and CGF in aggregate. We combined the burden associated with mild, moderate, and severe forms of CGF: stunting was defined as height-for-age Z scores (HAZ) less than -1, underweight was defined as weight-for-age Z scores (WAZ) less than -1, and wasting was defined as weight-for-height Z scores (WHZ) less than -1, according to WHO Child Growth Standards. Population-level continuous distributions of HAZ, WAZ, and WHZ were estimated for 2000 to 2023 using data from surveys, literature, and individual-level study data. The risk of incidence of, and mortality due to, diarrhoea, lower respiratory infections, malaria, and measles was separately estimated in a meta-regression framework from longitudinal cohort data for Z scores less than -1. Finally, fatal outcomes associated with these diseases were estimated with vital registration, verbal autopsy, and case-fatality data, while non-fatal outcomes were estimated with surveys as well as health-care utilisation and case reporting data. The exposure prevalence and relative risk estimates were from continuous distributions, allowing for direct assessment of the attributable fractions for mild, moderate, and severe stunting, underweight, wasting, and the combined impact of child growth failure within populations. All estimates were age-specific, sex-specific, geography-specific, and year-specific. We estimated that, in children younger than 5 years in 2023, CGF was associated with 79&#xb7;4 million (95% uncertainty interval [UI] 47&#xb7;0-106) DALYs lost and 880&#x2008;000 (517&#x2008;000-1&#x2008;170&#x2008;000) deaths. This represented 17&#xb7;9% (10&#xb7;6-23&#xb7;8) of 444 million (434-457) total under-5 DALYs and 18&#xb7;8% (11&#xb7;1-25&#xb7;0) of all 4&#xb7;67 million (4&#xb7;59-4&#xb7;75) under-5 deaths. Compared to stunting (33&#xb7;0 million [24&#xb7;1-42&#xb7;2] DALYs, 373&#x2008;000 [272&#x2008;000-477&#x2008;000] deaths) and wasting (39&#xb7;2 million [23&#xb7;8-53&#xb7;0] DALYs, 428&#x2008;000 [256&#x2008;000-583&#x2008;000] deaths), childhood underweight was associated with the largest share of CGF-related disease burden: 52&#xb7;2 million (21&#xb7;9-75&#xb7;1) DALYs and 573&#x2008;000 (236&#x2008;000-824&#x2008;000) deaths in children younger than 5 years in 2023. CGF remains a leading factor associated with death and disability in children younger than 5 years, despite global attention and focused interventions to reduce the prevalence of associated CGF indicators. Our findings underscore the need for policies, strategies, and interventions that focus on all indicators of CGF to reduce its associated health burden. Gates Foundation.