RESUMO
STUDY OBJECTIVE: We evaluate current evidence for the diagnostic accuracy and safety of the Emergency Department Assessment of Chest Pain Score (EDACS) for patients presenting to the emergency department (ED) with possible acute coronary syndromes. METHODS: MEDLINE, EMBASE, and Cochrane databases were searched for publications reporting data on the EDACS score. No date restrictions were used. Two independent researchers assessed studies for eligibility, bias, and quality. The primary outcome was major adverse cardiac events occurring within 30 days. Heterogeneity was assessed and data were pooled by meta-analysis using a random-effects model. RESULTS: Eight diagnostic test accuracy studies including 11,578 patients and 1 randomized controlled trial including 558 patients were eligible for inclusion. On meta-analysis, the EDACS score had a pooled sensitivity of 96.1% (95% confidence interval 89.6% to 98.6%) and specificity of 61.1% (95% confidence interval 55.5% to 66.3%). A total of 55.0% of patients (n=6,370/11,578) were identified as low risk and eligible for early discharge. Sixty-two patients (0.54%) identified as low risk had an outcome of major adverse cardiac events within 30 days. CONCLUSION: The EDACS score identified greater than 50% of patients with suspected acute coronary syndrome as suitable for discharge after serial troponin sampling during 2 hours. Sensitivity for major adverse cardiac events was relatively high overall and may be acceptable to clinicians.
Assuntos
Síndrome Coronariana Aguda/diagnóstico , Dor no Peito/diagnóstico , Serviço Hospitalar de Emergência , Medição de Risco/métodos , HumanosRESUMO
It is currently hypothesised that a combination of genetic and environmental factors underlies the development of idiopathic isolated dystonia (IID). In this study, we examined several possible environmental or other non-genetic factors that may influence the risk for IID in Queensland, Australia. We surveyed several environmental exposures, lifestyle factors, medical and family histories to investigate potential risk factors for IID. Associations between putative risk factors and IID were assessed using a total of 184 dystonia patients and 1048 neurologically-normal control subjects sampled from Queensland between 2005 and 2012. Our analyses revealed that anxiety disorders, depression, tremor, cigarette smoking and head injuries with a loss of consciousness were associated with increased risk for IID (p<0.05), all of which remained statistically significant following an adjustment for multiple hypothesis testing except for depression. We also observed that the risk for dystonia increased with higher cigarette smoking pack-year quartiles in our analyses. Our results suggest possible environmental factors that influence the development of IID and complement the findings of similar dystonia risk factor studies. Further investigation defining the environmental and other non-genetic risk factors for IID may provide insight into the development of the disorder in genetically-susceptible individuals.
Assuntos
Transtorno Distímico/epidemiologia , Transtorno Distímico/etiologia , Adulto , Sintomas Afetivos/etiologia , Idoso , Austrália/epidemiologia , Transtorno Distímico/complicações , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
Genes involved in familial dystonia syndromes (DYT genes) are ideal candidates for investigating whether common genetic variants influence the susceptibility to sporadic primary dystonia. To date, there have been few candidate gene studies for primary dystonia and only two DYT genes, TOR1A and THAP1, have been assessed. We therefore employed a haplotype-tagging strategy to comprehensively assess if common polymorphisms in eight DYT genes (TOR1A, TAF1, GCH1, THAP1, MR-1 (PNKD), SGCE, ATP1A3 and PRKRA) confer risk for sporadic primary dystonia. The 230 primary dystonia cases were matched for age and gender to 228 controls, recruited from movement disorder clinics in Brisbane, Australia and the Australian electoral roll. All subjects were genotyped for 56 tagging SNPs and genotype associations were investigated. Modest genotypic associations (P<0.05) were observed for three GCH1 SNPs (rs12147422, rs3759664 and rs10483639) when comparing all cases against controls. Associations were also seen when the cases were stratified based on presentation. Overall, our findings do not support the hypothesis that common TOR1A variants affect susceptibility for sporadic primary dystonia, and that it is unlikely that common variants around the DYT genes confer substantial risk for sporadic primary dystonia. Further work is warranted to follow up the GCH1 SNPs and the subgroup analyses.
Assuntos
Distúrbios Distônicos/genética , GTP Cicloidrolase/genética , Predisposição Genética para Doença/genética , Chaperonas Moleculares/genética , Polimorfismo de Nucleotídeo Único , Idoso , Austrália , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Metanálise como Assunto , Pessoa de Meia-IdadeRESUMO
Recent whole genome association studies provided little evidence that polymorphisms at the familial Parkinsonism loci influence the risk for Parkinson's disease (PD). However, these studies are not designed to detect the types of subtle effects that common variants may impose. Here, we use an alternative targeted candidate gene approach to examine common variation in 11 genes related to familial Parkinsonism. PD cases (n = 331) and unaffected control subjects (n = 296) were recruited from three specialist movement disorder clinics in Brisbane, Australia and the Australian Electoral Roll. Common genetic variables (76 SNPs and 1 STR) were assessed in all subjects and haplotype, genotype, and allele associations explored. Modest associations (uncorrected P < 0.05) were observed for common variants around SNCA, UCHL1, MAPT, and LRRK2 although none were of sufficient magnitude to survive strict statistical corrections for multiple comparisons. No associations were seen for PRKN, PINK1, GBA, ATP13A2, HTRA2, NR4A2, and DJ1. Our findings suggest that common genetic variables of selected PD-related loci contribute modestly to PD risk in Australians.
Assuntos
Predisposição Genética para Doença , Doença de Parkinson/genética , Transtornos Parkinsonianos/genética , Polimorfismo Genético/genética , Idoso , Austrália/epidemiologia , Feminino , Frequência do Gene , Estudo de Associação Genômica Ampla , Genótipo , Glucosilceramidase/genética , Serina Peptidase 2 de Requerimento de Alta Temperatura A , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Masculino , Proteínas Mitocondriais/genética , Proteínas Oncogênicas/genética , Proteína Desglicase DJ-1 , Proteínas Quinases/genética , Proteínas Serina-Treonina Quinases/genética , ATPases Translocadoras de Prótons/genética , Estudos Retrospectivos , Serina Endopeptidases/genética , Ubiquitina Tiolesterase/genética , Ubiquitina-Proteína Ligases/genética , alfa-Sinucleína/genética , Proteínas tau/genéticaRESUMO
Familial Parkinsonism (PARK) genes are strong candidates for conferring susceptibility to common forms of PD. However, most studies to date have provided little evidence that their common variants substantially influence disease risk. Recently, mutations were described in the gene, GIGYF2 (TNRC15), located at the PARK11 locus (2q37.1). Here, we use a haplotype tagging approach to examine common variation in the GIGYF2 gene and PD risk. PD cases (n = 568) and age and gender-matched control subjects (n = 568) were recruited from three specialist movement disorder clinics in Brisbane (Australia) and the Australian electoral roll. Twelve tagging SNPs were assessed in all subjects and haplotype and genotype associations were explored. Overall our findings suggest that common genetic variants of GIGYF2 do not significantly affect sporadic PD risk in Australian Caucasians.
Assuntos
Proteínas de Transporte/genética , Haplótipos/genética , Doença de Parkinson/genética , Ubiquitina-Proteína Ligases/genética , Idoso , Análise Mutacional de DNA , Feminino , Genótipo , Humanos , Masculino , Mutação Puntual/genéticaRESUMO
The study of family history in Parkinson's disease (PD) has resulted in considerable debate over the role of genetic factors in the development of PD. Despite this, family history is consistently identified as an independent risk factor for PD. A multifactorial disease process in which genetic, environmental and lifestyle factors culminate in overall risk seems most likely. This article reviews existing studies of familial aggregation in PD. Recent insights into rare genetic causes of PD have affirmed the importance of ongoing family history research. Future efforts should emphasise well-designed family studies with extensive, non-exclusive phenotyping and ideally long-term follow-up.