Positive predictive value of computerized records for major congenital malformations.

PURPOSE: To assess the positive predictive value of computerized records in a linked database of vital records and infant claims, with medical record confirmation to detect congenital malformations in a Medicaid population. METHODS: Study subjects were selected from cases identified for three studies of congenital malformations in the Tennessee Medicaid (TennCare) population including 173 827 (studies 1 and 2) and 519 465 (study 3) mother/infant pairs. Possible malformations were identified from computerized databases of birth certificates linked with maternal and infant claims. Medical records were reviewed for all possible congenital malformations and positive predictive values were calculated for each data source and for each malformation. RESULTS: Among 1430 potential congenital malformations identified from either birth certificates or inpatient claims, 67.7% were confirmed by medical record review. The positive predictive value varied considerably depending on the data source and the organ system. For example, cardiac defects had a very low positive predictive value when identified from birth certificates, and somewhat higher positive predictive value when identified from inpatient claims. Orofacial defects had 90.9% positive predictive value from birth certificates and inpatient claims. Requiring evidence of a diagnostic or therapeutic procedure increased the positive predictive value to >90% for specific defects, but substantially reduced the number of included cases. CONCLUSIONS: Depending on the defect, computerized claims data linked to vital records offer opportunities for identifying birth defects in populations of vulnerable persons. However, for many defects, medical record confirmation is likely to be required to provide valid identification of malformation occurrence.

Development of a Center for Personalized Cancer Care at a Regional Cancer Center: Feasibility Trial of an Institutional Tumor Sequencing Advisory Board.

Next-generation sequencing (NGS) capabilities can affect therapeutic decisions in patients with complex, advanced, or refractory cancer. We report the feasibility of a tumor sequencing advisory board at a regional cancer center. Specimens were analyzed for approximately 2800 mutations in 50 genes. Outcomes of interest included tumor sequencing advisory board function and processes, timely discussion of results, and proportion of reports having potentially actionable mutations. NGS results were successfully generated for 15 patients, with median time from tissue processing to reporting of 11.6 days (range, 5 to 21 days), and presented at a biweekly multidisciplinary tumor sequencing advisory board. Attendance averaged 19 participants (range, 12 to 24) at 20 days after patient enrollment (range, 10 to 30 days). Twenty-seven (range, 1 to 4 per patient) potentially actionable mutations were detected in 11 of 15 patients: TP53 (n = 6), KRAS (n = 4), MET (n = 3), APC (n = 3), CDKN2A (n = 2), PTEN (n = 2), PIK3CA, FLT3, NRAS, VHL, BRAF, SMAD4, and ATM. The Hotspot Panel is now offered as a clinically available test at our institution. NGS results can be obtained by in-house high-throughput sequencing and reviewed in a multidisciplinary tumor sequencing advisory board in a clinically relevant manner. The essential components of a center for personalized cancer care can support clinical decisions outside the university.

PSF and p54nrb bind a conserved stem in U5 snRNA.

PTB-associated splicing factor (PSF) has been implicated in both early and late steps of pre-mRNA splicing, but its exact role in this process remains unclear. Here we show that PSF interacts with p54nrb, a highly related protein first identified based on cross-reactivity to antibodies against the yeast second-step splicing factor Prpl8. We performed RNA-binding experiments to determine the preferred RNA-binding sequences for PSF and p54nrb, both individually and in combination. In all cases, iterative selection assays identified a purine-rich sequence located on the 3' side of U5 snRNA stem 1b. Filter-binding assays and RNA affinity selection experiments demonstrated that PSF and p54nrb bind U5 snRNA with both the sequence and structure of stem 1b contributing to binding specificity. Sedimentation analyses show that both proteins associate with spliceosomes and with U4/U6.U5 tri-snPNP.