The Somatic Genomic Landscape of Glioblastoma

We describe the landscape of somatic genomic alterations based on multi-dimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer

Retrieving Medical Records Within FDA’s Sentinel Distributed Network: Lessons Learned During a Protocol-Based Assessment Involving 13 Data Partners

Background: The U.S. Food and Drug Administration’s Sentinel system has developed the capability to conduct active safety surveillance of marketed medical products in a large distributed network. Medical record retrieval in such an environment is logistically challenging and resource-intensive. We describe lessons learned during a protocol-based assessment of thromboembolic events (TEE) following intravenous immunoglobulin (IGIV) administration, a project that necessitated chart retrieval requests for a large number of patients from 13 Sentinel data partners. Methods: The Sentinel IGIV-TEE workgroup requested medical records pertaining to 442 potential post-IGIV-TEE cases identified from the Sentinel Distributed Database. Charts were requested from 13 different data partners (including 4 Health Care Systems Research Network members). Six partners were claims-based health plans (CBHPs), and 7 were integrated care delivery systems (ICDSs). Dates of medical records spanned March 2006 to February 2013. Records were received and tracked by the Sentinel Operations Center at Harvard Pilgrim Health Care Institute. We report on the retrieval process, chart retrieval rates and reasons identified by data partners for nonretrieval by data partner type. Results: The vast majority of cases identified for record retrieval were from CBHPs (88%). Retrieval processes varied by data partner type: 4 of the 7 CBHPs contracted with vendors to conduct record retrieval across their facilities, whereas the ICDSs relied on internal personnel to either electronically pull charts or seek paper records. These differing processes had implications for troubleshooting missing records and information, resulting in diverse strategies for data partner-facility consultation. Rates of retrieval varied by data partner type (64% in CBHPs vs 94% in ICDSs) as did speed of retrieval and resources. Reasons records were unobtainable fell into three major categories: inability to map Sentinel Distributed Database records to patient and provider identifiers needed for retrieval; provider refusal to participate due to legal/compliance/HIPAA concerns; and missing information (eg, no record of patient at facility, charts for the requested service dates were unavailable). Conclusion: We will describe key lessons learned, broadly applicable to any chart retrieval project in a distributed environment, and include a discussion focused on the pros and cons of working with multiple collaborators with different data environments

Chart validation of inpatient International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) administrative diagnosis codes for venous thromboembolism (VTE) among intravenous immune globulin (IGIV) users in the Sentinel Distributed Database

Abstract The Sentinel Distributed Database (SDD) is a database of patient administrative healthcare records, derived from insurance claims and electronic health records, sponsored by the US Food and Drug Administration for evaluation of medical product outcomes. There is limited information on the validity of diagnosis codes for acute venous thromboembolism (VTE) in the SDD and administrative healthcare data more generally. In this chart validation study, we report on the positive predictive value (PPV) of inpatient administrative diagnosis codes for acute VTE—pulmonary embolism (PE) or lower-extremity or site-unspecified deep vein thrombosis (DVT)—within the SDD. As part of an assessment of thromboembolic adverse event risk following treatment with intravenous immune globulin (IGIV), charts were obtained for 75 potential VTE cases, abstracted, and physician-adjudicated. VTE status was determined for 62 potential cases. PPVs for lower-extremity DVT and/or PE were 90% (95% CI: 73–98%) for principal-position diagnoses, 80% (95% CI: 28–99%) for secondary diagnoses, and 26% (95% CI: 11–46%) for position-unspecified diagnoses (originating from physician claims associated with an inpatient stay). Average symptom onset was 1.5 days prior to hospital admission (range: 19 days prior to 4 days after admission). PPVs for principal and secondary VTE discharge diagnoses were similar to prior study estimates. Position-unspecified diagnoses were less likely to represent true acute VTE cases

Sapovirus Outbreaks in Long-Term Care Facilities, Oregon and Minnesota, USA, 2002–2009

Sapovirus gives new meaning to the phrase “cradle to grave.” Historically, sapovirus has been associated with gastrointestinal illness in children living in group settings such as hospitals, shelters, or refugee camps. But now, sapovirus outbreaks are occurring among elderly residents of long-term care and similar facilities. These elderly residents are especially vulnerable to rapidly transmitted gastrointestinal viruses and serious complications. This virus has been making the rounds in long-term care facilities since 2002, and outbreaks started increasing in 2007. Sapovirus testing should be added to routine diagnostic workups for gastrointestinal infections, regardless of patient age group. Results can be used to develop prevention, control, and treatment guidelines, especially for vulnerable elderly populations