Device Therapies Among Patients Receiving Primary Prevention Implantable Cardioverterâ Defibrillators in the Cardiovascular Research Network

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143721/1/jah33061_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143721/2/jah33061.pd

Variation in Pathology Examination of Extended Core Prostate Biopsies: A CRN Pilot Project

Background/Aims: Extended core prostate biopsy (ECPB) removing 10–12 tissue cores is the standard of care in men investigated for prostate cancer; however, the manner of pathologic examination varies. Urologists may process cores by laterality into two specimen jars, or separate each core into 12 specimens for pathologic review. Considering the high volume of ECPBs performed annually, varying strategies of submitting specimens for review could lead to variations of over $1 billion in health care expenditures. We will examine the association between number of jars submitted for pathologic review and rates of prostate cancer detection and equivocal diagnoses. Methods: We are conducting a pilot project at two Cancer Research Network (CRN) sites –– Meyers Primary Care Institute (MPCI) in Worcester, MA, and Marshfield Clinic (MCRF) in Marshfield, WI –– to determine patterns of processing ECPB tissue cores for pathologic review in men aged 30–95 years who underwent ECPB between 2008–2011. ECPBs and subsequent pathology services were identified in the CRN virtual data warehouse (VDW). Prostate cancer diagnoses were identified in VDW tumor files and equivocal diagnoses as repeat ECPBs within 7–180 days of the initial biopsy. Site-specific methods for identifying and validating jar number have been developed. Results: To establish this pilot study, we constructed datasets using the CRN VDW, discovered new variables in raw claims data, and performed medical record abstraction to validate new variables. At MPCI, 731 ECPBs were conducted 2008–2011, with a median of 2 jars per ECPB (range: 1–36). Jar number was extracted from raw claims data and validated through selected medical chart review. At MCRF, 902 ECPBs were conducted 2008–2011, with a median of 3 jars per ECPB (range: 1–12). A jar number algorithm that partly includes manual abstraction for some patients was developed and validated through a systematic review of all identified biopsy patients. Additional analyses linking jar number to patient outcomes are ongoing. Discussion: A two-site CRN pilot project was successfully developed to investigate the association between jar number for ECPB pathologic review and patient prostate cancer outcomes. Combining VDW and raw claims data, we have established a strong foundation for future research in this area

Evaluation and Adaptation of a Laboratory-Based cDNA Library Preparation Protocol for Retrospective Sequencing of Archived MicroRNAs from up to 35-Year-Old Clinical FFPE Specimens

Formalin-fixed paraffin-embedded (FFPE) specimens, when used in conjunction with patient clinical data history, represent an invaluable resource for molecular studies of cancer. Even though nucleic acids extracted from archived FFPE tissues are degraded, their molecular analysis has become possible. In this study, we optimized a laboratory-based next-generation sequencing barcoded cDNA library preparation protocol for analysis of small RNAs recovered from archived FFPE tissues. Using matched fresh and FFPE specimens, we evaluated the robustness and reproducibility of our optimized approach, as well as its applicability to archived clinical specimens stored for up to 35 years. We then evaluated this cDNA library preparation protocol by performing a miRNA expression analysis of archived breast ductal carcinoma in situ (DCIS) specimens, selected for their relation to the risk of subsequent breast cancer development and obtained from six different institutions. Our analyses identified six miRNAs (miR-29a, miR-221, miR-375, miR-184, miR-363, miR-455-5p) differentially expressed between DCIS lesions from women who subsequently developed an invasive breast cancer (cases) and women who did not develop invasive breast cancer within the same time interval (control). Our thorough evaluation and application of this laboratory-based miRNA sequencing analysis indicates that the preparation of small RNA cDNA libraries can reliably be performed on older, archived, clinically-classified specimens

Evaluation and Adaptation of a Laboratory-Based cDNA Library Preparation Protocol for Retrospective Sequencing of Archived MicroRNAs from up to 35-Year-Old Clinical FFPE Specimens

Formalin-fixed paraffin-embedded (FFPE) specimens, when used in conjunction with patient clinical data history, represent an invaluable resource for molecular studies of cancer. Even though nucleic acids extracted from archived FFPE tissues are degraded, their molecular analysis has become possible. In this study, we optimized a laboratory-based next-generation sequencing barcoded cDNA library preparation protocol for analysis of small RNAs recovered from archived FFPE tissues. Using matched fresh and FFPE specimens, we evaluated the robustness and reproducibility of our optimized approach, as well as its applicability to archived clinical specimens stored for up to 35 years. We then evaluated this cDNA library preparation protocol by performing a miRNA expression analysis of archived breast ductal carcinoma in situ (DCIS) specimens, selected for their relation to the risk of subsequent breast cancer development and obtained from six different institutions. Our analyses identified six miRNAs (miR-29a, miR-221, miR-375, miR-184, miR-363, miR-455-5p) differentially expressed between DCIS lesions from women who subsequently developed an invasive breast cancer (cases) and women who did not develop invasive breast cancer within the same time interval (control). Our thorough evaluation and application of this laboratory-based miRNA sequencing analysis indicates that the preparation of small RNA cDNA libraries can reliably be performed on older, archived, clinically-classified specimens

The Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial Pathology Tissue Resource

BACKGROUND: Pathology tissue specimens with associated epidemiological and clinical data are valuable for cancer research. The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial undertook a large-scale effort to create a public resource of pathology tissues from PLCO participants who developed a cancer during the trial. METHODS: Formalin-Fixed Paraffin-Embedded (FFPE) tissue blocks were obtained from pathology laboratories on a loan basis for central processing of tissue microarrays, with additional free-standing tissue cores collected for nucleic acid extraction. RESULTS: Pathology tissue specimens have been obtained for prostate cancer (n=1,052), lung cancer (n=434), colorectal cancer (n=675) and adenoma (n=658), ovarian cancer and borderline tumors (n=212), breast cancer (n=870) and bladder cancer (n=204). The process of creating this resource was complex, involving multi-disciplinary teams with expertise in pathology, epidemiology, information technology, project management and specialized laboratories. CONCLUSIONS: Creating the PLCO tissue resource required a multi-step process including obtaining medical records and contacting pathology departments where pathology materials were stored after obtaining necessary patient consent and authorization. The potential to link tissue biomarkers to prospectively collected epidemiological information, screening and clinical data, and matched blood or buccal samples offers valuable opportunities to study etiologic heterogeneity, mechanisms of carcinogenesis and biomarkers for early detection and prognosis. IMPACT: The methods and protocols developed for this effort, and the detailed description of this resource provided here will be useful for those seeking to use PLCO pathology tissue specimens for their research and may also inform future tissue collection efforts in other settings

Device Therapies Among Patients Receiving Primary Prevention Implantable Cardioverter-Defibrillators in the Cardiovascular Research Network

BACKGROUND: Primary prevention implantable cardioverter-defibrillators (ICDs) reduce mortality in selected patients with left ventricular systolic dysfunction by delivering therapies (antitachycardia pacing or shocks) to terminate potentially lethal arrhythmias; inappropriate therapies also occur. We assessed device therapies among adults receiving primary prevention ICDs in 7 healthcare systems. METHODS AND RESULTS: We linked medical record data, adjudicated device therapies, and the National Cardiovascular Data Registry ICD Registry. Survival analysis evaluated therapy probability and predictors after ICD implant from 2006 to 2009, with attention to Centers for Medicare and Medicaid Services Coverage With Evidence Development subgroups: left ventricular ejection fraction, 31% to 35%; nonischemic cardiomyopathymonths\u27 duration; and New York Heart Association class IV heart failure with cardiac resynchronization therapy defibrillator. Among 2540 patients, 35% wereold, 26% were women, and 59% were white. During 27 (median) months, 738 (29%) received ≥1 therapy. Three-year therapy risk was 36% (appropriate, 24%; inappropriate, 12%). Appropriate therapy was more common in men (adjusted hazard ratio [HR], 1.84; 95% confidence interval [CI], 1.43-2.35). Inappropriate therapy was more common in patients with atrial fibrillation (adjusted HR, 2.20; 95% CI, 1.68-2.87), but less common among patients ≥65 years old versus younger (adjusted HR, 0.72; 95% CI, 0.54-0.95) and in recent implants (eg, in 2009 versus 2006; adjusted HR, 0.66; 95% CI, 0.46-0.95). In Centers for Medicare and Medicaid Services Coverage With Evidence Development analysis, inappropriate therapy was less common with cardiac resynchronization therapy defibrillator versus single chamber (adjusted HR, 0.55; 95% CI, 0.36-0.84); therapy risk did not otherwise differ for Centers for Medicare and Medicaid Services Coverage With Evidence Development subgroups. CONCLUSIONS: In this community cohort of primary prevention patients receiving ICD, therapy delivery varied across demographic and clinical characteristics, but did not differ meaningfully for Centers for Medicare and Medicaid Services Coverage With Evidence Development subgroups