Veterans Health Administration

About: Veterans Health Administration is a government organization based out in Washington D.C., District of Columbia, United States. It is known for research contribution in the topics: Population & Veterans Affairs. The organization has 63820 authors who have published 98417 publications receiving 4835425 citations. The organization is also known as: VHA.

Efficacy of screening mammography. A meta-analysis.

Abstract: Objective. —To determine the efficacy of screening mammography by age, number of mammographic views per screen, screening interval, and duration of follow-up. Design. —Literature review and meta-analysis. Data Identification and Analysis. —Literature search of English-language studies reported from January 1966 to October 31, 1993, using MEDLINE, manual literature review, and consultation with experts. A total of 13 studies were selected, and their results were combined using meta-analytic techniques based on the assumption of fixed effects. Main Results. —The overall summary relative risk (RR) estimate for breast cancer mortality for women aged 50 to 74 years undergoing screening mammography compared with those who did not was 0.74 (95% confidence interval [CI], 0.66 to 0.83). The magnitude of the benefit in this age group was similar regardless of number of mammographic views per screen, screening interval, or duration of follow-up. In contrast, none of the summary RR estimates for women aged 40 to 49 years was significantly less than 1.0, irrespective of screening intervention or duration of follow-up. The overall summary RR estimate in women aged 40 to 49 years was 0.93 (95% CI, 0.76 to 1.13); the summary RR estimate for those studies that used two-view mammography was 0.87 (95% CI, 0.68 to 1.12) compared with 1.02 (95% CI, 0.73 to 1.44) for those studies that used one-view mammography, and for those studies with 7 to 9 years of follow-up, the summary RR estimate was 1.02 (95% CI, 0.82 to 1.27) compared with 0.83 (95% CI, 0.65 to 1.06) for those studies with 10 to 12 years of follow-up. Conclusion. —Screening mammography significantly reduces breast cancer mortality in women aged 50 to 74 years after 7 to 9 years of follow-up, regardless of screening interval or number of mammographic views per screen. There is no reduction in breast cancer mortality in women aged 40 to 49 years after 7 to 9 years of follow-up. Screening mammography may be effective in reducing breast cancer mortality in women aged 40 to 49 years after 10 to 12 years of follow-up, but the same benefit could probably be achieved by beginning screening at menopause or 50 years of age. (JAMA. 1995;273:149-154)

Interventions for the prevention of falls in older adults: systematic review and meta-analysis of randomised clinical trials

Abstract: Objective To assess the relative effectiveness of interventions to prevent falls in older adults to either a usual care group or control group. Design Systematic review and meta-analyses. Data sources Medline, HealthSTAR, Embase, the Cochrane Library, other health related databases, and the reference lists from review articles and systematic reviews. Data extraction Components of falls intervention: multifactorial falls risk assessment with management programme, exercise, environmental modifications, or education. Results 40 trials were identified. A random effects analysis combining trials with risk ratio data showed a reduction in the risk of falling (risk ratio 0.88, 95% confidence interval 0.82 to 0.95), whereas combining trials with incidence rate data showed a reduction in the monthly rate of falling (incidence rate ratio 0.80, 0.72 to 0.88). The effect of individual components was assessed by meta-regression. A multifactorial falls risk assessment and management programme was the most effective component on risk of falling (0.82, 0.72 to 0.94, number needed to treat 11) and monthly fall rate (0.63, 0.49 to 0.83; 11.8 fewer falls in treatment group per 100 patients per month). Exercise interventions also had a beneficial effect on the risk of falling (0.86, 0.75 to 0.99, number needed to treat 16) and monthly fall rate (0.86, 0.73 to 1.01; 2.7). Conclusions Interventions to prevent falls in older adults are effective in reducing both the risk of falling and the monthly rate of falling. The most effective intervention was a multifactorial falls risk assessment and management programme. Exercise programmes were also effective in reducing the risk of falling.

Risperidone in the treatment of schizophrenia.

Abstract: Objective: The purpose ofthis study was to investigate the safety and efficacy of risperidone in the treatment ofschizophrenic patients and determine its optimal dose Method: This double-blind study included 388 schizophrenic patients drawn from 20 sites in the United States Patients were randomly assigned to 8 weeks’ treatment with placebo, one of four doses of risperidone (2, 6, 1 0, or 1 6 mg), or 20 mg ofhaloperidol daily Results: Clinical improvement (20% reduction in totalscores on the Positive and Negative Syndrome Scale for Schizophrenia) at the study end point was shown by 35% ofthe patients receiving 2 mg ofrisperidone, 57% receiving 6 mg, 40% receiving 1 0 mg, and 51 % receiving 1 6 mg; and by 30% receiving haloperidoland 22% receiving placebo Statistically significant differences in clinical improvement were found between 6 and 1 6 mg of risperidone versus placebo and versus haloperidol Positive symptom scores were significantly lower after 6, 10, and 1 6 mg of risperidone and 20 mg ofhaloperidol than placebo; negative symptom scores, however, were reduced significantly, compared with placebo, only after 6 and 1 6 mg ofrisperidone The incidence of extrapyramidal side effects (measured by the Extrapyramidal Symptom Rating Scale) was significantly higher in patients treated with 1 6 mg of risperidone or 20 mg of haloperidol than placebo The results indicate that the optimal daily dose ofrisperidone for most schizophrenic patients in this study was 6 mg; this dose was as effective as 1 6 mg, and the incidence of extrapyramidal symptoms in patients receiving 6 mg of risperidone was no higher than that in patients receiving placebo Conclusions: Risperidone is a safe antipsychotic that is effective against both the positive and negative symptoms of schizophrenia (AmJ Psychiatry 1994; 151:825-835)

Somatic SF3B1 Mutation in Myelodysplasia with Ring Sideroblasts

Abstract: BACKGROUND Myelodysplastic syndromes are a diverse and common group of chronic hematologic cancers. The identification of new genetic lesions could facilitate new diagnostic and therapeutic strategies. METHODS We used massively parallel sequencing technology to identify somatically acquired point mutations across all protein-coding exons in the genome in 9 patients with low-grade myelodysplasia. Targeted resequencing of the gene encoding RNA splicing factor 3B, subunit 1 (SF3B1), was also performed in a cohort of 2087 patients with myeloid or other cancers. RESULTS We identified 64 point mutations in the 9 patients. Recurrent somatically acquired mutations were identified in SF3B1. Follow-up revealed SF3B1 mutations in 72 of 354 patients (20%) with myelodysplastic syndromes, with particularly high frequency among patients whose disease was characterized by ring sideroblasts (53 of 82 [65%]). The gene was also mutated in 1 to 5% of patients with a variety of other tumor types. The observed mutations were less deleterious than was expected on the basis of chance, suggesting that the mutated protein retains structural integrity with altered function. SF3B1 mutations were associated with down-regulation of key gene networks, including core mitochondrial pathways. Clinically, patients with SF3B1 mutations had fewer cytopenias and longer event-free survival than patients without SF3B1 mutations. CONCLUSIONS Mutations in SF3B1 implicate abnormalities of messenger RNA splicing in the pathogenesis of myelodysplastic syndromes. (Funded by the Wellcome Trust and others.).

Genome-wide association study identifies 30 loci associated with bipolar disorder

Abstract: Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10-8) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder.