Incidence, survival, and diagnostic trends in GCA across seven decades in a North American population-based cohort.

OBJECTIVES: To analyze trends in the incidence and use of diagnostic modalities for GCA in a population-based cohort over the past seven decades. To explore survival trends in patients with GCA compared with the general population. METHODS: A population-based cohort of patients diagnosed with GCA was extended with new incident cases from 2010 to 2019. Three time periods were compared: Period One (1950-1979), Period Two (1980-1999), and Period Three (2000-2019). Cases were classified as: Diagnostic Group One, temporal artery biopsy (TAB) positive; Diagnostic Group Two, TAB-negative or not done with positive large-vessel imaging; or Diagnostic Group Three, clinical diagnosis of GCA. Survival was evaluated by comparing Kaplan-Meier estimated mortality rates for cases of GCA against expected mortality rates from Minnesota life tables RESULTS: Age- and sex-adjusted incident rates per 100,000 ≥ 50 years of age (95% CI) were 13.5 (10.1, 16.9) in Period One, 21.0 (17.1, 25.0) in Period Two, and 15.0 (12.4, 17.5) in Period Three. The percent of patients in Diagnostic Group One decreased over the three time periods (89%, 86%, and 72%) while the patients in Diagnostic Group Three increased (11%, 14%, and 17%). Standardized mortality ratios (95% CI) were 1.03 (0.79, 1.32), 1.11 (0.91, 1.34), and 0.82 (0.64, 1.04) across Periods 1-3, respectively. CONCLUSIONS: Incidence of GCA in females in the population declined, resulting in a decreasing overall incidence. More patients have been identified by large-vessel imaging and fewer by positive TABs. No significant difference in survival between patients with GCA and the general population was observed.

My Treatment Approach to Giant Cell Arteritis.

Giant cell arteritis (GCA) is the most common primary systemic vasculitis in adults 50 years or older. Expanded use of advanced arterial imaging has assisted both in the diagnosis of GCA and recognition of disease subsets. Although glucocorticoids have been the mainstay of treatment for almost 7 decades, new therapeutic options have emerged. This review aims to provide the clinician with a pragmatic approach to evaluating and managing patients with GCA while also addressing recent diagnostic and therapeutic developments.

Increased patient communication using a process supplementing an electronic medical record.

BACKGROUND: Importance: Patients with cervical cytology abnormalities may require surveillance for many years, which increases the risk of management error, especially in clinics with multiple managing clinicians. National Committee for Quality Assurance (NCQA) Patient-Centered Medical Home (PCMH) certification requires tracking of abnormal results and communicating effectively with patients. OBJECTIVES: The purpose of this study was to determine whether a computer-based tracking system that is not embedded in the electronic medical record improves (1) accurate and timely communication of results and (2) patient adherence to follow-up recommendations. METHODS: Design: Pre/post study using data from 2005-2012. Intervention implemented in 2008. Data collected via chart review for at least 18 months after index result. Participants: Pre-intervention: all women (N = 72) with first abnormal cytology result from 2005-2007. Post-intervention: all women (N = 128) with first abnormal cytology result from 2008-2010. Patients were seen at a suburban, university-affiliated, family medicine residency clinic. Intervention: Tracking spreadsheet reviewed monthly with reminders generated for patients not in compliance with recommendations. Main Outcome and Measures: (1) rates of accurate and timely communication of results and (2) rates of patient adherence to follow-up recommendations. RESULTS: Intervention decreased absent or erroneous communication from clinician to patient (6.4% pre- vs 1.6% post-intervention [P = 0.04]), but did not increase patient adherence to follow-up recommendations (76.1% pre- vs 78.0% post-intervention [ P= 0.78]). CONCLUSIONS: Use of a spreadsheet tracking system improved communication of abnormal results to patients, but did not significantly improve patient adherence to recommended care. Although the tracking system complies with NCQA PCMH requirements, it was insufficient to make meaningful improvements in patient-oriented outcomes.

SULF1 inhibits tumor growth and potentiates the effects of histone deacetylase inhibitors in hepatocellular carcinoma.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is the third most common cause of cancer death worldwide. Improved treatments for advanced HCC are urgently needed. The recently identified human sulfatase 1 enzyme (SULF1) desulfates cell surface heparan sulfate glycosaminoglycans and down-regulates cell growth signaling in HCC cells in vitro. While investigating the epigenetic regulation of SULF1, we discovered that histone H4 acetylation is up-regulated by SULF1 in HCC cells. Histone deacetylase (HDAC) inhibitors reprogram cellular gene expression through the acetylation of nucleosomal histones and promote cell growth arrest and apoptosis. Hence, they are a promising modality for cancer treatment. METHODS: To explore the interaction between SULF1 expression and HDAC inhibitor action, we examined the effects of SULF1 expression on HCC cells and xenografts treated with HDAC inhibitors. RESULTS: (1) Forced expression of SULF1 significantly delayed the growth of Huh7 and Hep3B xenografts in nude mice in vivo. (2) SULF1 increased histone H4 acetylation by modulation of cellular HDAC and histone acetyltransferase activities. (3) SULF1 enhanced the induction of apoptosis by the HDAC inhibitors apicidin and scriptaid. (4) SULF1 enhanced the inhibition of tumor growth, migration, and angiogenesis by HDAC inhibitors. We also demonstrate that knockdown of SULF1 with shRNA constructs up-regulates phosphorylation of AKT and Erk and attenuates apicidin-induced apoptosis. The interaction between SULF1 and apicidin was confirmed in vivo in Huh7 and Hep3B xenografts. CONCLUSIONS: These results show that SULF1 promotes histone H4 acetylation, potentiates the effects of HDAC inhibitors, and inhibits HCC tumorigenesis.

BioSPICE: access to the most current computational tools for biologists.

The goal of the BioSPICE program is to create a framework that provides biologists access to the most current computational tools. At the program midpoint, the BioSPICE member community has produced a software system that comprises contributions from approximately 20 participating laboratories integrated under the BioSPICE Dashboard and a methodology for continued software integration. These contributed software modules are the BioSPICE Dashboard, a graphical environment that combines Open Agent Architecture and NetBeans software technologies in a coherent, biologist-friendly user interface. The current Dashboard permits data sources, models, simulation engines, and output displays provided by different investigators and running on different machines to work together across a distributed, heterogeneous network. Among several other features, the Dashboard enables users to create graphical workflows by configuring and connecting available BioSPICE components. Anticipated future enhancements to BioSPICE include a notebook capability that will permit researchers to browse and compile data to support model building, a biological model repository, and tools to support the development, control, and data reduction of wet-lab experiments. In addition to the BioSPICE software products, a project website supports information exchange and community building.