ABSTRACT
BACKGROUND: Non-invasive tests, such as Fibrosis-4 index and transient elastography (commonly FibroScan), are utilized in clinical pathways to risk stratify and diagnose non-alcoholic fatty liver disease (NAFLD). In 2018, a clinical decision support tool (CDST) was implemented to guide primary care providers (PCPs) on use of FibroScan for NAFLD. AIM: To analyze how this CDST impacted health care utilization and patient outcomes. METHODS: We performed a retrospective review of adults who had FibroScan for NAFLD indication from January 2015 to December 2017 (pre-CDST) or January 2018 to December 2020 (post-CDST). Outcomes included FibroScan result, laboratory tests, imaging studies, specialty referral, patient morbidity and mortality. RESULTS: We identified 958 patients who had FibroScan, 115 before and 843 after the CDST was implemented. The percentage of FibroScans ordered by PCPs increased from 33% to 67.1%. The percentage of patients diagnosed with early F1 fibrosis, on a scale from F0 to F4, increased from 7.8% to 14.2%. Those diagnosed with advanced F4 fibrosis decreased from 28.7% to 16.5%. There were fewer laboratory tests, imaging studies and biopsy after the CDST was implemented. Though there were more specialty referrals placed after the CDST was implemented, multivariate analysis revealed that healthcare utilization aligned with fibrosis score, whereby patients with more advanced disease had more referrals. Very few patients were hospitalized or died. CONCLUSION: This CDST empowered PCPs to diagnose and manage patients with NAFLD with appropriate allocation of care towards patients with more advanced disease.
ABSTRACT
Despite growing interest in remote patient monitoring, limited evidence exists to substantiate claims of its ability to improve outcomes. Our aim was to evaluate randomized controlled trials (RCTs) that assess the effects of using wearable biosensors (e.g. activity trackers) for remote patient monitoring on clinical outcomes. We expanded upon prior reviews by assessing effectiveness across indications and presenting quantitative summary data. We searched for articles from January 2000 to October 2016 in PubMed, reviewed 4,348 titles, selected 777 for abstract review, and 64 for full text review. A total of 27 RCTs from 13 different countries focused on a range of clinical outcomes and were retained for final analysis; of these, we identified 16 high-quality studies. We estimated a difference-in-differences random effects meta-analysis on select outcomes. We weighted the studies by sample size and used 95% confidence intervals (CI) around point estimates. Difference-in-difference point estimation revealed no statistically significant impact of remote patient monitoring on any of six reported clinical outcomes, including body mass index (-0.73; 95% CI: -1.84, 0.38), weight (-1.29; -3.06, 0.48), waist circumference (-2.41; -5.16, 0.34), body fat percentage (0.11; -1.56, 1.34), systolic blood pressure (-2.62; -5.31, 0.06), and diastolic blood pressure (-0.99; -2.73, 0.74). Studies were highly heterogeneous in their design, device type, and outcomes. Interventions based on health behavior models and personalized coaching were most successful. We found substantial gaps in the evidence base that should be considered before implementation of remote patient monitoring in the clinical setting.
ABSTRACT
[This corrects the article DOI: 10.1038/s41746-017-0002-4.].
ABSTRACT
Integrase-defective lentiviral vectors (IDLVs) have been of limited success in the delivery of zinc finger nucleases (ZFNs) to human cells, due to low expression. A reason for reduced gene expression has been proposed to involve the epigenetic silencing of vector genomes, carried out primarily by histone deacetylases (HDACs). In this study, we tested valproic acid (VPA), a known HDAC inhibitor (HDACi), for its ability to increase transgene expression from IDLVs, especially in the context of ZFN delivery. Using ZFNs targeting the human adenosine deaminase (ADA) gene in K562 cells, we demonstrated that treatment with VPA enhanced ZFN expression by up to 3-fold, resulting in improved allelic disruption at the ADA locus. Furthermore, three other U.S. Food and Drug Administration-approved HDACis (vorinostat, givinostat, and trichostatin-A) exhibited a similar effect on the activity of ZFN-IDLVs in K562 cells. In primary human CD34(+) cells, VPA- and vorinostat-treated cells showed higher levels of expression of both green fluorescent protein (GFP) as well as ZFNs from IDLVs. A major mechanism for the effects of HDAC inhibitors on improving expression was from their modulation of the cell cycle, and the influence of heterochromatinization was determined to be a lesser contributing factor.
