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This data descriptor presents the Subnational Corruption Database (SCD), which provides data on corruption in 1,473 subnational areas of 178 countries. The SCD includes a comprehensive overall corruption index, the Subnational Corruption Index (SCI), and its two components: the Subnational Grand Corruption Index (SGCI) and Subnational Petty Corruption Index (SPCI). The SCD is constructed by combining data of 807 surveys held in the period 1995-2022 and includes the corruption experiences and perceptions of 1,326,656 respondents along 19 separate dimensions. The data are available for multiple years, allowing longitudinal analyses. At the national level, the SCI correlates strongly with established corruption indices, like the Transparency International Corruption Perceptions Index (CPI) and the World Bank Control of Corruption Index (CCI). We create subnational estimates of the CPI and CCI by superimposing the subnational variation of the SCI around the national averages of these indices. The presentation of subnational data in the SCD and the separation between grand and petty corruption significantly broaden the global knowledge base in the field of corruption.
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De novo variants are a leading cause of neurodevelopmental disorders (NDDs), but because every monogenic NDD is different and usually extremely rare, it remains a major challenge to understand the complete phenotype and genotype spectrum of any morbid gene. According to OMIM, heterozygous variants in KDM6B cause "neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities." Here, by examining the molecular and clinical spectrum of 85 reported individuals with mostly de novo (likely) pathogenic KDM6B variants, we demonstrate that this description is inaccurate and potentially misleading. Cognitive deficits are seen consistently in all individuals, but the overall phenotype is highly variable. Notably, coarse facies and distal skeletal anomalies, as defined by OMIM, are rare in this expanded cohort while other features are unexpectedly common (e.g., hypotonia, psychosis, etc.). Using 3D protein structure analysis and an innovative dual Drosophila gain-of-function assay, we demonstrated a disruptive effect of 11 missense/in-frame indels located in or near the enzymatic JmJC or Zn-containing domain of KDM6B. Consistent with the role of KDM6B in human cognition, we demonstrated a role for the Drosophila KDM6B ortholog in memory and behavior. Taken together, we accurately define the broad clinical spectrum of the KDM6B-related NDD, introduce an innovative functional testing paradigm for the assessment of KDM6B variants, and demonstrate a conserved role for KDM6B in cognition and behavior. Our study demonstrates the critical importance of international collaboration, sharing of clinical data, and rigorous functional analysis of genetic variants to ensure correct disease diagnosis for rare disorders.
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Deficiência Intelectual , Transtornos do Neurodesenvolvimento , Humanos , Animais , Fácies , Transtornos do Neurodesenvolvimento/genética , Transtornos do Neurodesenvolvimento/patologia , Fenótipo , Drosophila , Deficiência Intelectual/patologia , Histona Desmetilases com o Domínio Jumonji/genéticaRESUMO
AIMS: Hyperkalaemia is observed frequently in heart failure (HF) patients and is associated with an impaired prognosis and underuse of mineralocorticoid receptor antagonists (MRAs). However, the effects of serum potassium on prescription of the full guideline recommended daily dose of 50 mg in real-world daily practice are unknown. Therefore, we investigated serum potassium and its association with the prescribed MRA dose in a large cohort of chronic HF patients. METHODS AND RESULTS: A total of 5346 patients with chronic HF with a left ventricular ejection fraction ≤40% from 34 Dutch outpatient HF clinics between 2013 and 2016 were analysed on serum potassium and MRA (spironolactone and eplenerone) dose. Data were stratified by potassium as a serum potassium level <4.0, 4.0 to 5.0 or >5.0 mmol/L. Multivariable logistic regression models were used to assess the association between serum potassium and MRA dose and to adjust for potential confounders. Mean serum potassium was 4.4 ± 0.5 mmol/L and hyperkalaemia (serum potassium >5.0 mmol/L) was present in 399 patients (7.5%). MRA was used in 3091 patients (58.1%). Patients with hyperkalaemia significantly less often received ≥100% of the target dose (50 mg) compared with patients with a serum potassium between 4.0-5.0 mmol/L and <4.0 mmol/L (7.7% vs. 9.5% vs. 13.6% respectively, P = 0.0078). In the multivariable regression analyses, patients with hyperkalaemia were significantly less likely to receive ≥100% of the target dose compared with patients with serum potassium 4.0-5.0 mmol/L (OR 0.38, 95% CI 0.15-0.97, P = 0.044). Additionally, a one unit increase in serum potassium was significantly associated with a lower odds of receiving ≥100% of the target dose (OR 0.69, 95% CI 0.49-0.98, P = 0.036). CONCLUSIONS: In this large registry of real-world chronic HF patients, both an increase in serum potassium and hyperkalaemia were associated with a lower odds of receiving the guideline-recommended MRA dose.
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Insuficiência Cardíaca , Hiperpotassemia , Humanos , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/epidemiologia , Volume Sistólico , Função Ventricular Esquerda , Insuficiência Cardíaca/complicações , Potássio , Doença CrônicaRESUMO
A significant number of individuals with a rare disorder such as Usher syndrome (USH) and (non-)syndromic autosomal recessive retinitis pigmentosa (arRP) remain genetically unexplained. Therefore, we assessed subjects suspected of USH2A-associated disease and no or mono-allelic USH2A variants using whole genome sequencing (WGS) followed by an improved pipeline for variant interpretation to provide a conclusive diagnosis. One hundred subjects were screened using WGS to identify causative variants in USH2A or other USH/arRP-associated genes. In addition to the existing variant interpretation pipeline, a particular focus was put on assessing splice-affecting properties of variants, both in silico and in vitro. Also structural variants were extensively addressed. For variants resulting in pseudoexon inclusion, we designed and evaluated antisense oligonucleotides (AONs) using minigene splice assays and patient-derived photoreceptor precursor cells. Biallelic variants were identified in 49 of 100 subjects, including novel splice-affecting variants and structural variants, in USH2A or arRP/USH-associated genes. Thirteen variants were shown to affect USH2A pre-mRNA splicing, including four deep-intronic USH2A variants resulting in pseudoexon inclusion, which could be corrected upon AON treatment. We have shown that WGS, combined with a thorough variant interpretation pipeline focused on assessing pre-mRNA splicing defects and structural variants, is a powerful method to provide subjects with a rare genetic condition, a (likely) conclusive genetic diagnosis. This is essential for the development of future personalized treatments and for patients to be eligible for such treatments.
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Retinose Pigmentar , Síndromes de Usher , Humanos , Síndromes de Usher/diagnóstico , Precursores de RNA , Mutação , Linhagem , Retinose Pigmentar/diagnóstico , Sequenciamento Completo do Genoma , Proteínas da Matriz Extracelular/genéticaRESUMO
While according to the United Nations birth registration is a human right, in sub-Saharan Africa (SSA) only half of new-born children currently have their birth registered. To gain insight into the reasons behind this low registration rate, we study the role of determinants at the household, sub-national regional and country level, using self-reported birth registration data on 358,842 children in 40 SSA countries. While most of the variation in reported birth registration is due to factors at the household level, context factors are found to play an important role as well. At the household level, poverty, low education, restricted autonomy of women, and belonging to a traditional religion are associated with lower odds of being registered. Lack of professional care during pregnancy, delivery, and early life also decrease the odds of being registered. Important factors at the context level are the average number of prenatal care visits in the local area, living in an urban area, the kind of birth registration legislation, decentralization of the registration system, fertility rates, and the number of conflicts. To improve registration, the complex dynamics of these factors at the household and context level have to be taken into account.
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Características da Família , Parto , África Subsaariana/epidemiologia , Criança , Feminino , Humanos , Pobreza , Gravidez , Cuidado Pré-NatalRESUMO
Some pathogenic variants in mtDNA and nuclear DNA, affecting mitochondrial function, are associated with hearing loss. Behavioral and electrophysiological auditory performance are obtained from 62 patients, clinically diagnosed with different mitochondrial diseases (MD) using tone/speech audiometry and Auditory Brainstem Responses (ABR). Audiological variables (hearing loss type, pure tone average (PTA), interaural asymmetry, speech perception and brainstem neural conductivity) were analyzed and related to Newcastle Mitochondrial Disease Scale for Adults (NMDAS). In 35% of MDs, a mild to severe symmetrical sensorineural hearing loss (SNHL) was found. Patients with Maternally Inherited Diabetes and Deafness (MIDD) show significantly higher PTAs compared to other MDs. For all MDs, speech recognition scores were in accordance with their individual age- and gender-corrected tone audiometry, but ABR peak latencies were prolonged in patients with MIDD, Mitochondrial Encephalopathy Lactate acidosis and Stroke-like episodes (MELAS), Chronic Progressive External Ophthalmoplegia (CPEO) and Subacute necrotizing encephalopathy (Leigh). Correlations between NMDAS and audiological variables were low.
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Diabetes Mellitus Tipo 2 , Perda Auditiva Neurossensorial , Perda Auditiva , Doenças Mitocondriais , Adulto , Surdez , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/genética , Humanos , Doenças Mitocondriais/complicações , Estudos RetrospectivosRESUMO
Pathogenic missense variants in COCH are associated with DFNA9, an autosomal dominantly inherited type of progressive sensorineural hearing loss with or without vestibular dysfunction. This study is a comprehensive overview of genotype-phenotype correlations using the PRISMA and HuGENet guidelines. Study characteristics, risk of bias, genotyping and data on the self-reported age of onset, symptoms of vestibular dysfunction, normative test results for vestibular function, and results of audiovestibular examinations were extracted for each underlying pathogenic COCH variant. The literature search yielded 48 studies describing the audiovestibular phenotypes of 27 DFNA9-associated variants in COCH. Subsequently, meta-analysis of audiometric data was performed by constructing age-related typical audiograms and by performing non-linear regression analyses on the age of onset and progression of hearing loss. Significant differences were found between the calculated ages of onset and progression of the audiovestibular phenotypes of subjects with pathogenic variants affecting either the LCCL domain of cochlin or the vWFA2 and Ivd1 domains. We conclude that the audiovestibular phenotypes associated with DFNA9 are highly variable. Variants affecting the LCCL domain of cochlin generally lead to more progression of hearing loss when compared to variants affecting the other domains. This review serves as a reference for prospective natural history studies in anticipation of mutation-specific therapeutic interventions.
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Proteínas da Matriz Extracelular , Perda Auditiva Neurossensorial , Doenças Vestibulares , Proteínas da Matriz Extracelular/genética , Estudos de Associação Genética , Perda Auditiva Neurossensorial/genética , Humanos , Mutação , Estudos Prospectivos , Doenças Vestibulares/genética , Doenças Vestibulares/patologiaRESUMO
We recently described a novel missense variant [c.2090T>G:p.(Leu697Trp)] in the MYO3A gene, found in two Brazilian families with late-onset autosomal dominant nonsyndromic hearing loss (ADNSHL). Since then, with the objective of evaluating its contribution to ADNSHL in Brazil, the variant was screened in additional 101 pedigrees with probable ADNSHL without conclusive molecular diagnosis. The variant was found in three additional families, explaining 3/101 (~3%) of cases with ADNSHL in our Brazilian pedigree collection. In order to identify the origin of the variant, 21 individuals from the five families were genotyped with a high-density SNP array (~600 K SNPs- Axiom Human Origins; ThermoFisher). The identity by descent (IBD) approach revealed that many pairs of individuals from the different families have a kinship coefficient equivalent to that of second cousins, and all share a minimum haplotype of ~607 kb which includes the c.2090T>G variant suggesting it probably arose in a common ancestor. We inferred that the mutation occurred in a chromosomal segment of European ancestry and the time since the most common ancestor was estimated in 1100 years (CI = 775-1425). This variant was also reported in a Dutch family, which shares a 87,121 bp haplotype with the Brazilian samples, suggesting that Dutch colonists may have brought it to Northeastern Brazil in the 17th century. Therefore, the present study opens new avenues to investigate this variant not only in Brazilians but also in European families with ADNSHL.
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Frequência do Gene , Perda Auditiva Neurossensorial/genética , Cadeias Pesadas de Miosina/genética , Miosina Tipo III/genética , Brasil , Efeito Fundador , Genes Dominantes , Haplótipos , Migração Humana , Humanos , Mutação de Sentido Incorreto , Linhagem , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Pathogenic variants in SLC26A4 have been associated with autosomal recessive hearing loss (arHL) and a unilateral or bilateral enlarged vestibular aqueduct (EVA). SLC26A4 is the second most frequently mutated gene in arHL. Despite the strong genotype-phenotype correlation, a significant part of cases remains genetically unresolved. In this study, we investigated a cohort of 28 Dutch index cases diagnosed with HL in combination with an EVA but without (M0) or with a single (M1) pathogenic variant in SLC26A4. To explore the missing heritability, we first determined the presence of the previously described EVA-associated haplotype (Caucasian EVA (CEVA)), characterized by 12 single nucleotide variants located upstream of SLC26A4. We found this haplotype and a delimited V1-CEVA haplotype to be significantly enriched in our M1 patient cohort (10/16 cases). The CEVA haplotype was also present in two M0 cases (2/12). Short- and long-read whole genome sequencing and optical genome mapping could not prioritize any of the variants present within the CEVA haplotype as the likely pathogenic defect. Short-read whole-genome sequencing of the six M1 cases without this haplotype and the two M0/CEVA cases only revealed previously overlooked or misinterpreted splice-altering SLC26A4 variants in two cases, who are now genetically explained. No deep-intronic or structural variants were identified in any of the M1 subjects. With this study, we have provided important insights that will pave the way for elucidating the missing heritability in M0 and M1 SLC26A4 cases. For pinpointing the pathogenic effect of the CEVA haplotype, additional analyses are required addressing defect(s) at the RNA, protein, or epigenetic level.
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Surdez , Perda Auditiva Neurossensorial , Perda Auditiva , Perda Auditiva/genética , Perda Auditiva Neurossensorial/genética , Humanos , Proteínas de Membrana Transportadoras/genética , Mutação , Fenótipo , Transportadores de Sulfato/genética , Aqueduto Vestibular/anormalidadesRESUMO
Non-Syndromic Hereditary Hearing Loss (NSHHL) is a genetically heterogeneous sensory disorder with about 120 genes already associated. Through exome sequencing (ES) and data aggregation, we identified a family with six affected individuals and one unrelated NSHHL patient with predicted-to-be deleterious missense variants in USP48. We also uncovered an eighth patient presenting unilateral cochlear nerve aplasia and a de novo splice variant in the same gene. USP48 encodes a ubiquitin carboxyl-terminal hydrolase under evolutionary constraint. Pathogenicity of the variants is supported by in vitro assays that showed that the mutated proteins are unable to hydrolyze tetra-ubiquitin. Correspondingly, three-dimensional representation of the protein containing the familial missense variant is situated in a loop that might influence the binding to ubiquitin. Consistent with a contribution of USP48 to auditory function, immunohistology showed that the encoded protein is expressed in the developing human inner ear, specifically in the spiral ganglion neurons, outer sulcus, interdental cells of the spiral limbus, stria vascularis, Reissner's membrane and in the transient Kolliker's organ that is essential for auditory development. Engineered zebrafish knocked-down for usp48, the USP48 ortholog, presented with a delayed development of primary motor neurons, less developed statoacoustic neurons innervating the ears, decreased swimming velocity and circling swimming behavior indicative of vestibular dysfunction and hearing impairment. Corroboratingly, acoustic startle response assays revealed a significant decrease of auditory response of zebrafish lacking usp48 at 600 and 800 Hz wavelengths. In conclusion, we describe a novel autosomal dominant NSHHL gene through a multipronged approach combining ES, animal modeling, immunohistology and molecular assays.
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Perda Auditiva , Peixe-Zebra , Animais , Perda Auditiva/genética , Humanos , Hidrolases , Reflexo de Sobressalto , Ubiquitina , Proteases Específicas de Ubiquitina , Peixe-Zebra/genéticaRESUMO
In mammals, sound is detected by mechanosensory hair cells that are activated in response to vibrations at frequency-dependent positions along the cochlear duct. We demonstrate that inner ear supporting cells provide a structural framework for transmitting sound energy through the cochlear partition. Humans and mice with mutations in GAS2, encoding a cytoskeletal regulatory protein, exhibit hearing loss due to disorganization and destabilization of microtubule bundles in pillar and Deiters' cells, two types of inner ear supporting cells with unique cytoskeletal specializations. Failure to maintain microtubule bundle integrity reduced supporting cell stiffness, which in turn altered cochlear micromechanics in Gas2 mutants. Vibratory responses to sound were measured in cochleae from live mice, revealing defects in the propagation and amplification of the traveling wave in Gas2 mutants. We propose that the microtubule bundling activity of GAS2 imparts supporting cells with mechanical properties for transmitting sound energy through the cochlea.
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Cóclea/citologia , Citoesqueleto/metabolismo , Audição/fisiologia , Proteínas dos Microfilamentos/metabolismo , Sequência de Aminoácidos , Animais , Animais Recém-Nascidos , Sequência de Bases , Citoesqueleto/ultraestrutura , Células Ciliadas Auditivas/metabolismo , Células Ciliadas Auditivas/ultraestrutura , Perda Auditiva/metabolismo , Perda Auditiva/patologia , Perda Auditiva/fisiopatologia , Humanos , Camundongos Endogâmicos C57BL , Proteínas dos Microfilamentos/química , Proteínas dos Microfilamentos/genética , Microtúbulos/metabolismo , Mutação/genética , Transporte Proteico , Som , Vibração , Sequenciamento do ExomaRESUMO
STUDY QUESTION: How many twins are born in human populations and how has this changed over recent decades? SUMMARY ANSWER: Since the 1980s, the global twinning rate has increased by a third, from 9.1 to 12.0 twin deliveries per 1000 deliveries, to about 1.6 million twin pairs each year. WHAT IS KNOWN ALREADY: It was already known that in the 1980s natural twinning rates were low in (East) Asia and South America, at an intermediate level in Europe and North America, and high in many African countries. It was also known that in recent decades, twinning rates have been increasing in the wealthier parts of our world as a result of the rise in medically assisted reproduction (MAR) and delayed childbearing. STUDY DESIGN, SIZE, DURATION: We have brought together all information on national twinning rates available from statistical offices, demographic research institutes, individual survey data and the medical literature for the 1980-1985 and the 2010-2015 periods. PARTICIPANTS/MATERIALS, SETTING, METHODS: For 165 countries, covering over 99% of the global population, we were able to collect or estimate twinning rates for the 2010-2015 period. For 112 countries, we were also able to obtain twinning rates for 1980-1985. MAIN RESULTS AND THE ROLE OF CHANCE: Substantial increases in twinning rates were observed in many countries in Europe, North America and Asia. For 74 out of 112 countries the increase was more than 10%. Africa is still the continent with highest twinning rates, but Europe, North America and Oceania are catching up rapidly. Asia and Africa are currently home to 80% of all twin deliveries in the world. LIMITATIONS, REASONS FOR CAUTION: For some countries, data were derived from reports and papers based on hospital registrations which are less representative for the country as a whole than data based on public administrations and national surveys. WIDER IMPLICATIONS OF THE FINDINGS: The absolute and relative number of twins for the world as a whole is peaking at an unprecedented level. An important reason for this is the tremendous increase in medically assisted reproduction in recent decades. This is highly relevant, as twin deliveries are associated with higher infant and child mortality rates and increased complications for mother and child during pregnancy and during and after delivery. STUDY FUNDING/COMPETING INTEREST(S): The contribution of CM was partially supported by the European Research Council (ERC) under the European Union's Horizon 2020 Research and Innovation Programme (grant No 681546, FAMSIZEMATTERS), Nuffield College, and the Leverhulme Trust. The contribution of GP was partially supported by the French Agence Nationale de la Recherche (grant No ANR-18-CE36-0007-07). The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.
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Técnicas de Reprodução Assistida , África , Criança , Europa (Continente) , Feminino , Humanos , Gravidez , Taxa de Gravidez , Sistema de RegistrosRESUMO
OBJECTIVE: To study the genotype and phenotype of a Dutch family with autosomal dominantly inherited hearing loss. STUDY DESIGN: Genotype-phenotype correlation study. Genetic analysis consisted of linkage analysis, variable number of tandem repeats analysis, and Sanger sequencing. Audiovestibular function was examined. Regression analysis was performed on pure tone audiometry and speech recognition scores and correlated with the age and/or level of hearing loss. SETTING: Tertiary referral center. PATIENTS: A large Dutch family presenting with sensorineural hearing loss. MAIN OUTCOME MEASURES: Identification of the underlying genetic defect of the hearing loss in this family. Results of pure tone and speech audiometry, onset age, progression of hearing loss and vestibular (dys)function. RESULTS: A novel mutation in COCH, c.1312Câ>âT p.(Arg438Cys), cosegregates with hearing loss and a variable degree of vestibular (dys)function in this family. The reported mean age of onset of hearing loss is 33 years (range, 18-49 yr). Hearing loss primarily affects higher frequencies and its progression is relatively mild (0.8âdB/yr). Speech perception is remarkably well preserved in affected family members when compared with other DFNA9 families with different COCH mutations. CONCLUSION: These findings expand the genotypic and phenotypic spectrum of DFNA9. The c.1312Câ>âT mutation, which affects the vWFA2 domain, causes a relatively mild audiovestibular phenotype when compared with other COCH mutations.
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Proteínas da Matriz Extracelular , Perda Auditiva Neurossensorial , Adolescente , Adulto , Análise Mutacional de DNA , Proteínas da Matriz Extracelular/genética , Perda Auditiva Neurossensorial/genética , Humanos , Pessoa de Meia-Idade , Mutação , Linhagem , Fenótipo , Adulto JovemRESUMO
BACKGROUND: Hearing loss is one of the most prevalent disabilities worldwide, and has a significant impact on quality of life. The adult-onset type of the condition is highly heritable but the genetic causes are largely unknown, which is in contrast to childhood-onset hearing loss. METHODS: Family and cohort studies included exome sequencing and characterisation of the hearing phenotype. Ex vivo protein expression addressed the functional effect of a DNA variant. RESULTS: An in-frame deletion of 12 nucleotides in RIPOR2 was identified as a highly penetrant cause of adult-onset progressive hearing loss that segregated as an autosomal dominant trait in 12 families from the Netherlands. Hearing loss associated with the deletion in 63 subjects displayed variable audiometric characteristics and an average (SD) age of onset of 30.6 (14.9) years (range 0-70 years). A functional effect of the RIPOR2 variant was demonstrated by aberrant localisation of the mutant RIPOR2 in the stereocilia of cochlear hair cells and failure to rescue morphological defects in RIPOR2-deficient hair cells, in contrast to the wild-type protein. Strikingly, the RIPOR2 variant is present in 18 of 22 952 individuals not selected for hearing loss in the Southeast Netherlands. CONCLUSION: Collectively, the presented data demonstrate that an inherited form of adult-onset hearing loss is relatively common, with potentially thousands of individuals at risk in the Netherlands and beyond, which makes it an attractive target for developing a (genetic) therapy.
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AIMS: Despite previous surveys regarding device implantation rates in heart failure (HF), insight into the real-world management with devices is scarce. Therefore, we investigated device implantation rates in HF with reduced left ventricular ejection fraction (LVEF) in 34 Dutch centres. METHODS AND RESULTS: A cross-sectional outpatient registry was conducted in 6666 patients with LVEF < 50% and with information about device implantation available [74 (66-81) years of age; 64% male]. Patients were classified into conventional pacemakers (PM, n = 562), implantable cardioverter defibrillators (ICD, n = 1165), and cardiac resynchronization therapy with defibrillator function (CRT-D, n = 885) or pacemaker function only (CRT-P, n = 248), or no device (n = 3806). Centres were divided into ICD-implanting and CRT-implanting and referral centres. Overall, 17.5% had an ICD, 13.3% CRT-D, 3.7% CRT-P, and 8.4% PM. Of those with LVEF ≤ 30%, 42.5% had ICD or CRT-D therapy. A large variation in implantation rates existed between centres: 3-51% for ICD therapy, 0.3-44% for CRT-D therapy, 0-11% for CRT-P therapy, and 0-25% PM therapy. Implantation centres showed higher implantation rates of ICD, CRT-D, and CRT-P compared with referral centres [36% vs. 25% for defibrillators (ICD or CRT-D) and 17% vs. 9% for CRT devices (CRT-D or CRT-P), respectively, P < 0.001], independently of other factors. A large number of clinical factors were predictive for device usage. Among other, LVEF < 40% and male sex were independent positive predictors for ICD/CRT-D use [odds ratio (OR) = 3.33, P < 0.001; OR = 1.87, P = 0.019, respectively]. Older age was independently associated with less ICD/CRT-D (OR = 0.96 per year, P < 0.001) and more CRT-P/PM use (OR = 1.03 per year, P = 0.006). CONCLUSIONS: In this large Dutch HF registry, less than half of the patients with reduced LVEF received an ICD or CRT, even if LVEF was ≤30%, and a large variation between centres existed. Patients from implantation centres had more often ICD or CRT. More uniformity regarding guideline-based use of device therapy in clinical practice is needed.
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Insuficiência Cardíaca , Função Ventricular Esquerda , Idoso , Estudos Transversais , Feminino , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Volume SistólicoRESUMO
INTRODUCTION: Malaria continues to be a major cause of morbidity and mortality in sub-Saharan Africa (SSA) without effective interventions. Bacillus Calmette-Guérin (BCG) vaccine possesses protective non-specific effects, which extend beyond protection against tuberculosis. This study explores whether BCG is associated with protection against malaria in children under the age of 5 years in SSA. METHODS: We used data from the Demographic Health Survey programme, including 34 206 children from 13 SSA countries. BCG status was taken from vaccination cards when present; if not, mother's recall was used. Presence of malaria was defined as a positive rapid diagnostic test. Maternally reported presence or absence of fever in the previous 2 weeks defined symptomatic status. Multilevel logistic regression was used to account for the two-stage cluster sampling method. RESULTS: Of the 34 206 children, 12 325 (36.0%) children were malaria positive and 29 766 (87.0%) were BCG vaccinated. After correction for relevant child, maternal and household factors, BCG vaccination was associated with a lower malaria prevalence (adjusted OR (aOR)=0.94, 95% CI 0.90 to 0.98), especially among children of whom BCG information was retrieved from a vaccination card (aORcard=0.88, 95% CI 0.82 to 0.94). Restricting the analysis to children from regions with suboptimal BCG coverage increased the association (aORcard=0.81, 95% CI 0.73 to 0.89). We observed an increasingly beneficial association with each month of age of the child (aORcard=0.996, 95% CI 0.993 to 0.999). BCG associations were similar for asymptomatic (aORcard=0.86, 95% CI 0.81 to 0.92) and symptomatic (aORcard=0.89, 95% CI 0.78 to 1.01) malaria. CONCLUSIONS: BCG vaccination is associated with protection against malaria. This protection is highest in regions with suboptimal BCG coverage. These results indicate a possible role for timely BCG vaccination in the protection of malaria and its elimination by reducing the transmission reservoir. If confirmed in further research, our findings have substantial implications for global efforts to reduce malaria burden.
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Clean water provision remains a serious problem in low- and middle-income countries. In 2017, about 30% of the world population relied on unimproved water sources located outside of the dwellings. Often women and children are occupied in fetching water. This situation increases the prevalence of water-related diseases such as diarrhoea and reduces children's study time. School attendance may decrease due to the combined effects of diarrhoea and time spent on fetching water. We investigate the effects on school absenteeism and primary school enrolment in Indonesia, using a panel data set for 295 districts over the period 1994-2014. Districts with higher diarrhoea prevalence are found to have lower school enrolment (B: -0.202, sig p < 0.01) and higher school absenteeism (B: 2.334, sig p < 0.001). Districts where more households have access to private water facilities have higher school enrolment (B: 0.025, sig p < 0.01) and lower school absenteeism (B: -0.027, sig p < 0.01). More use of piped and bottled water in a district is associated with a lower diarrhoea prevalence (B: -0.004, sig p < 0.05). Policy-makers should take the benefits of improved water supply into account when making cost-benefit analyses regarding investments in water infrastructure.
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Absenteísmo , Água Potável/microbiologia , Criança , Feminino , Humanos , Indonésia , Instituições Acadêmicas , Abastecimento de ÁguaRESUMO
In this paper we describe the Subnational Human Development Database. This database contains for the period 1990-2017 for 1625 regions within 161 countries the national and subnational values of the Subnational Human Development Index (SHDI), for the three dimension indices on the basis of which the SHDI is constructed - education, health and standard of living --, and for the four indicators needed to create the dimension indices -- expected years of schooling, mean years of schooling, life expectancy and gross national income per capita. The subnational values of the four indicators were computed using data from statistical offices and from the Area Database of the Global Data Lab, which contains indicators aggregated from household surveys and census datasets. Values for missing years were estimated by interpolation and extrapolation from real data. By normalizing the population-weighted averages of the indicators to their national levels in the UNDP-HDI database, values of the SHDI and its dimension indices were obtained that at national level equal their official versions of the UNDP.