Handgrip strength as a diagnostic tool for frailty risk in elderly patients with moderate to severe asthma / Força de preensão manual como ferramenta diagnóstica de risco de fragilidade em pacientes idosos com asma moderada a grave

ABSTRACT Objective: To evaluate handgrip strength (HGS) as a diagnostic tool for frailty risk in elderly patients with asthma, as well as to investigate the prevalence of frailty in this population. Methods: This was a cross-sectional study including 96 patients ≥ 60 years of age diagnosed with moderate to severe asthma and treated at a tertiary referral center in Brazil. We measured HGS using a calibrated hydraulic hand dynamometer. We used a frailty scale and the AUC to assess the diagnostic accuracy of the HGS test. Results: The median age of participants was 67 years. Most (78%) were women and non-White (91%) of low socioeconomic status. HGS identified those at risk for frailty, with an AUC of 71.6% (61.5-80.4%; p < 0.002), as well as a sensitivity of 73.58% and a specificity of 67.53%, on the basis of a cutoff of ≤ 19 kgf. Conclusions: HGS appears to be a simple, reliable tool for clinicians to determine frailty risk in older asthma patients in a point-of-care setting.

RESUMO Objetivo: Avaliar a força de preensão manual (FPM) como ferramenta diagnóstica de risco de fragilidade em pacientes idosos com asma e investigar a prevalência de fragilidade nessa população. Métodos: Estudo transversal com 96 pacientes com idade ≥ 60 anos e diagnóstico de asma moderada a grave, atendidos em um centro terciário de referência no Brasil. Medimos a FPM com um dinamômetro hidráulico manual calibrado. Usamos uma escala de fragilidade e a ASC para avaliar a precisão diagnóstica do teste de FPM. Resultados: A mediana da idade dos participantes foi de 67 anos. A maioria eram mulheres (78%) não brancas (91%) cujo nível socioeconômico era baixo. O ponto de corte de FPM ≤ 19 kgf identificou os participantes que apresentavam risco de fragilidade, com ASC = 71,6% (61,5-80,4%; p < 0,002), sensibilidade = 73,58% e especificidade = 67,53%. Conclusões: A FPM parece ser uma ferramenta simples e confiável para determinar, no próprio local de atendimento médico, o risco de fragilidade em pacientes idosos com asma.

Genetic interaction between NAT2, GSTM1, GSTT1, CYP2E1, and environmental factors is associated with adverse reactions to anti-tuberculosis drugs.

BACKGROUND: Adverse drug reactions (ADRs) associated with anti-tuberculosis (anti-TB) drug regimens have considerable impact on anti-TB treatment, potentially leading to unsuccessful outcomes. Nevertheless, the risk factors that play a role in anti-TB drug-induced ADRs are not well established. It is well documented that genetic polymorphisms in drug-metabolizing enzymes (DMEs) result in considerably complex variability in anti-TB drug disposition. In addition, the impact of pharmacogenetic variation on the metabolism of anti-TB drugs may be modifiable by environmental exposure. Thus, an assessment of pharmacogenetic variability combined with biomarkers of environmental exposure may be helpful for demonstrating the effect of the gene-environment interaction on susceptibility to ADRs induced by anti-TB drug therapy. OBJECTIVE: The aim of the study was to investigate the impact of the interaction between environmental risk factors and pharmacogenetic polymorphisms in four common DMEs--N-acetyltransferase 2 (arylamine N-acetyltransferase) [NAT2], glutathione S-transferase theta 1 [GSTT1], glutathione S-transferase mu 1 [GSTM1], and cytochrome P450 2E1 [CYP2E1]--on commonly reported ADRs to first-line anti-TB drugs in 129 patients receiving homogeneous TB treatment. METHODS: TB patients monitored during drug treatment were divided into subgroups according to the presence or absence of ADRs. Additionally, the patients' clinical and demographic characteristics were collected in order to identify the environmental factors that are potential triggers for ADRs induced by anti-TB drug treatment. Pharmacogenetic variability was determined by gene sequencing, TaqMan® assays, or polymerase chain reaction. RESULTS: The findings of this study suggest that the NAT2 slow acetylator haplotype, female sex, and smoking are important determinants of susceptibility to ADRs induced by anti-TB drugs. Patients carrying multiple, but not single, polymorphisms in the NAT2, GSTM1, GSTT1, and CYP2E1 genes were found to have an increased risk of ADRs, as revealed by gene-gene interaction analysis. Moreover, we also identified meaningful gene-environment interaction models that resulted in the highest levels of ADR risk. CONCLUSION: The study findings provide evidence of the clinical impact of the interaction between pharmacogenetic variability and environmental factors on ADRs induced by anti-TB drug therapy. Predictive pharmacogenetic testing and a comprehensive clinical history would therefore be helpful for identification and careful monitoring of patients at high risk of this complication.

Genetic variations in FOXO3A are associated with Bipolar Disorder without confering vulnerability for suicidal behavior.

BACKGROUND: Genetic variation plays an important role in Bipolar Disorder (BD) and suicide susceptibility. However, little is known about the genetic influence on the risk of suicide, particularly in BD patients. Since FOXO3A plays a role in distinct mood-relevant behavioral processes, this gene could be a novel gene candidate for BD. Thus, we investigated whether FOXO3A polymorphisms are associated with BD and suicidal behavior in BD patients. METHODS: TaqMan genotyping was used to detect FOXO3A SNPs in 273 BD patients and 264 control subjects. RESULTS: Three SNPs (rs1536057, rs2802292 and rs1935952) were associated with BD, but none was positively linked with suicidal behavior. LIMITATION: A systematic evaluation within the whole FOXO3A gene and drug treatment in patients was not performed. CONCLUSIONS: These data suggest that FOXO3A is a novel susceptibility locus for BD, but not for suicidal behavior in BD patients. These results may contribute to a better understanding of the BD genetics.