Global, regional, and national prevalence and mortality burden of sickle cell disease, 2000-2021: a systematic analysis from the Global Burden of Disease Study 2021

BACKGROUND: Previous global analyses, with known underdiagnosis and single cause per death attribution systems, provide only a small insight into the suspected high population health effect of sickle cell disease. Completed as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, this study delivers a comprehensive global assessment of prevalence of sickle cell disease and mortality burden by age and sex for 204 countries and territories from 2000 to 2021. METHODS: We estimated cause-specific sickle cell disease mortality using standardised GBD approaches, in which each death is assigned to a single underlying cause, to estimate mortality rates from the International Classification of Diseases (ICD)-coded vital registration, surveillance, and verbal autopsy data. In parallel, our goal was to estimate a more accurate account of sickle cell disease health burden using four types of epidemiological data on sickle cell disease: birth incidence, age-specific prevalence, with-condition mortality (total deaths), and excess mortality (excess deaths). Systematic reviews, supplemented with ICD-coded hospital discharge and insurance claims data, informed this modelling approach. We employed DisMod-MR 2.1 to triangulate between these measures-borrowing strength from predictive covariates and across age, time, and geography-and generated internally consistent estimates of incidence, prevalence, and mortality for three distinct genotypes of sickle cell disease: homozygous sickle cell disease and severe sickle cell β-thalassaemia, sickle-haemoglobin C disease, and mild sickle cell β-thalassaemia. Summing the three models yielded final estimates of incidence at birth, prevalence by age and sex, and total sickle cell disease mortality, the latter of which was compared directly against cause-specific mortality estimates to evaluate differences in mortality burden assessment and implications for the Sustainable Development Goals (SDGs). FINDINGS: Between 2000 and 2021, national incidence rates of sickle cell disease were relatively stable, but total births of babies with sickle cell disease increased globally by 13·7% (95% uncertainty interval 11·1-16·5), to 515 000 (425 000-614 000), primarily due to population growth in the Caribbean and western and central sub-Saharan Africa. The number of people living with sickle cell disease globally increased by 41·4% (38·3-44·9), from 5·46 million (4·62-6·45) in 2000 to 7·74 million (6·51-9·2) in 2021. We estimated 34 400 (25 000-45 200) cause-specific all-age deaths globally in 2021, but total sickle cell disease mortality burden was nearly 11-times higher at 376 000 (303 000-467 000). In children younger than 5 years, there were 81 100 (58 800-108 000) deaths, ranking total sickle cell disease mortality as 12th (compared to 40th for cause-specific sickle cell disease mortality) across all causes estimated by the GBD in 2021. INTERPRETATION: Our findings show a strikingly high contribution of sickle cell disease to all-cause mortality that is not apparent when each death is assigned to only a single cause. Sickle cell disease mortality burden is highest in children, especially in countries with the greatest under-5 mortality rates. Without comprehensive strategies to address morbidity and mortality associated with sickle cell disease, attainment of SDG 3.1, 3.2, and 3.4 is uncertain. Widespread data gaps and correspondingly high uncertainty in the estimates highlight the urgent need for routine and sustained surveillance efforts, further research to assess the contribution of conditions associated with sickle cell disease, and widespread deployment of evidence-based prevention and treatment for those with sickle cell disease. FUNDING: Bill & Melinda Gates Foundation

Postural orientation in subjects with anterior cruciate ligament injury: development and first evaluation of a new observational test battery.

Anterior cruciate ligament (ACL) injury is associated with mechanical instability and defective neuromuscular function, and can lead to further injury, increased joint loading and osteoarthritis. Patients with ACL injury demonstrate altered postural orientation, manifested as observable "substitution patterns" (SPs) but no one has applied a clinically useful method to systematically study postural orientation in these patients. Here, we investigated the presence of such patterns in 24 adults with ACL injury and in 49 controls, in parallel with the development and a first evaluation of a new test battery, test for SPs. The rationale behind the test for SPs was to characterize postural orientation as the ability to maintain appropriate relationships between body segments and environment during weight-bearing movements. In this first study, patients displayed SPs more frequently and/or more clearly on their injured, but also their uninjured side than did controls. Inter-rater and intra-rater reproducibility was good at a group level. Future studies of validity, responsiveness and including other subgroups of patients with ACL injury will have to prove if the test for SPs can be used in the diagnostics of defective neuromuscular function following knee injury, when planning and carrying out training and rehabilitation and when deciding appropriate time to return to activity and sports after ACL injury

Iconoclasm – religious and political motivations for destroying art

Iconoclasm has existed around the world for thousands of years. This chapter traces the etymology and genealogy of religious iconoclasm, then examines why and how ideological programmes are advanced through destruction of cultural property. It explores the use of iconoclasm as an instrument of religious instruction in Egypt; social transformation in China; political appropriation of territory, consolidation of power and resistance to power in Cyprus; destruction of community in the former Yugoslavia; religious ‘purification’ in Mali; protest against monarchist secularism in Iran and Western fetishism in Afghanistan; and conquest and genocide in Syria and Iraq. Particularly as some acts of iconoclasm are nonviolent, iconoclasm may be understood better as transforming signs than as breaking images

The epithelial cell rests of Malassez - a role in periodontal regeneration?

The definitive version is available at www.blackwell-synergy.comThis article reviews general aspects about the epithelial cell rests of Malassez (ERM). The historical and general morphological features of the ERM are briefly described. The embryological derivation of the ERM is presented as an important consideration in understanding the events associated with their origin and possible functional roles within the periodontal ligament. The ultrastructural description of the ERM is also included to complement the morphological characteristics which distinguish these cells as the unique epithelial element of the periodontal ligament. The unique ability of these cells to synthesize and secrete a number of proteins usually associated with cells of mesenchymal origin, rather than ectodermal origin, is discussed in light of their role in cementum repair and regeneration. Such considerations lead to our hypothesis that one of the functional roles of the ERM may lie not only their role in maintaining and contributing to the normal periodontal cellular elements and function but also contributing, in a significant manner, to periodontal regeneration.J. C. Rincon, W. G. Young, P. M. Bartol