RESUMO
In addition to commonly associated environmental factors, genomic factors may cause cerebral palsy. We performed whole-exome sequencing of 250 parent-offspring trios, and observed enrichment of damaging de novo mutations in cerebral palsy cases. Eight genes had multiple damaging de novo mutations; of these, two (TUBA1A and CTNNB1) met genome-wide significance. We identified two novel monogenic etiologies, FBXO31 and RHOB, and showed that the RHOB mutation enhances active-state Rho effector binding while the FBXO31 mutation diminishes cyclin D levels. Candidate cerebral palsy risk genes overlapped with neurodevelopmental disorder genes. Network analyses identified enrichment of Rho GTPase, extracellular matrix, focal adhesion and cytoskeleton pathways. Cerebral palsy risk genes in enriched pathways were shown to regulate neuromotor function in a Drosophila reverse genetics screen. We estimate that 14% of cases could be attributed to an excess of damaging de novo or recessive variants. These findings provide evidence for genetically mediated dysregulation of early neuronal connectivity in cerebral palsy.
Assuntos
Paralisia Cerebral/genética , Proteínas F-Box/genética , Tubulina (Proteína)/genética , Proteínas Supressoras de Tumor/genética , beta Catenina/genética , Animais , Paralisia Cerebral/patologia , Ciclina D/genética , Citoesqueleto/genética , Drosophila/genética , Exoma/genética , Matriz Extracelular/genética , Feminino , Adesões Focais/genética , Predisposição Genética para Doença , Genoma Humano/genética , Humanos , Masculino , Mutação/genética , Neuritos/metabolismo , Neuritos/patologia , Fatores de Risco , Análise de Sequência de DNA , Transdução de Sinais/genética , Sequenciamento do Exoma , Proteína rhoB de Ligação ao GTP/genéticaRESUMO
BACKGROUND: Studies investigating adverse events have traditionally been principally undertaken from a medical perspective. The impact that experience of an adverse event has on consumer confidence in health care is largely unknown. The objectives of the study were to seek public opinion on 1) the rate and severity of adverse events experienced in hospitals; and 2) the perception of safety in hospitals, so that predictors of lack of safety could be identified. METHODS: A multistage, clustered survey of persons residing in South Australia (2001), using household interviews (weighted n = 2,884). RESULTS: A total of 67% of respondents aged over forty years reported having at least one member of their household hospitalised in the past five years; with the average being two hospital admissions in five years. Respondents stated that 7.0% (95%CI: 6.2% to 7.9%) of those hospital admissions were associated with an adverse event; 59.7% of respondents (95% CI: 51.4% to 67.5%) rated the adverse event as really serious and 48.5% (95% CI: 40.4% to 56.8%) stated prolonged hospitalisation was required as a consequence of the adverse event. Perception of safety in hospitals was largely affected by the experience of an adverse event; really serious events were the most significant predictor of lack of safety in those aged 40 years and over (RR 2.38; p<0.001). CONCLUSION: The experience of adverse events negatively impacted on public confidence in hospitals. The consumer-reported adverse event rate in hospitals (7.0%) is similar to that identified using medical record review. Based on estimates from other studies, self-reported claims of adverse events in hospital by consumers appear credible, and should be considered when developing appropriate treatment regimes.
Assuntos
Atitude Frente a Saúde , Hospitais/normas , Doença Iatrogênica/epidemiologia , Erros Médicos/estatística & dados numéricos , Opinião Pública , Medição de Risco , Segurança/estatística & dados numéricos , Adolescente , Adulto , Características da Família , Pesquisas sobre Atenção à Saúde , Humanos , Entrevistas como Assunto , Erros Médicos/classificação , Pessoa de Meia-Idade , Satisfação do Paciente/estatística & dados numéricos , Qualidade da Assistência à Saúde , Índice de Gravidade de Doença , Percepção Social , Austrália do SulRESUMO
OBJECTIVES: To seek public opinion on the reporting of medical errors and the anonymity of healthcare workers who report medical errors. DESIGN AND PARTICIPANTS: A random, representative survey of 2005 South Australians in April 2002, using telephone interviews based on a vignette provided. MAIN OUTCOME MEASURES: When a medical error occurs (i) whether the incident should be reported, and (ii) whether the report should disclose the healthcare worker's identity. RESULTS: (i) Most respondents (94.2%; 95% CI, 93.0%-95.2%) believed healthcare workers should report medical errors. (ii) 68.0% (95% CI, 65.5%-70.5%) of those in favour of reporting believed the healthcare worker should be identified on the report, while 29.2% (95% CI, 26.7%-31.7%) favoured anonymous reporting. CONCLUSIONS: Most respondents believed that, when a healthcare worker makes an error, an incident report should be written and the individual should be identified on the report. Respondents were reluctant to accept healthcare worker anonymity, even though this may encourage reporting.