Validation of a risk stratification tool for a Hospital Outreach Medication Review (HOMR) program.

BACKGROUND: Early hospital readmissions are a challenging and costly experience for both patients and the healthcare service. Reducing hospital readmission rates is a priority for health services globally and this is evident with the establishment of multiple outpatient services to promote early follow-up and to initiate secondary preventative care measures. One such intervention has been the introduction of a pharmacist-led, Hospital Outreach Medication Review (HOMR) service. However, the demand for the service has meant reaching this target has become an increasingly ambitious goal within allocated resources. OBJECTIVE: To validate a risk-stratification tool to identify low-risk patients in whom a telephone medication review would be a safe and effective alternative to a home-based review. METHOD: A risk tool was derived and applied to a retrospective sample to act as the parent cohort. A prospective cohort was stratified into low and high-risk based on this tool, and received either a telephone or a traditional home medication review respectively. RESULTS: 235 patients were included in final analysis (n = 113 prospective, n = 122 baseline controls). High-risk patients were more likely to be readmitted at 60 and 90 days in the baseline cohort (9/38 vs 7/84, p = 0.04 and 11/38 vs 9/84, p = 0.02 respectively), with a trend towards increased readmissions at 30 days (5/38 vs 3/84, p = 0.11). Logistic regression identified the risk tool as an independent predictor of hospital readmission (IRR 1.18, p = 0.04), whereas age and Charlson comorbidity were not (p = 0.80 and 0.31 respectively). There was no significant difference between the new model (incorporating phone reviews) and the parent cohort (p = 0.25). CONCLUSION: Our risk score was able to identify those at highest risk of hospital readmission at 60 and 90 days. Utilising this risk score, a telephone HOMR for low-risk patients was a safe and efficient alternative to a traditional home review.

Biomarkers for genome instability in some genetic disorders: a pilot study.

CONTEXT: The study of genome integrity in some genetic disorders has diagnostic and prognostic importance because of the evident relationship between genome instability and both DNA repair deficiencies and cancer predisposition. OBJECTIVE: The objective was to compare the chromosomal and DNA damage responses in lymphocytes from patients with Nijmegen breakage syndrome (NBS), Fanconi anemia (FA) and Williams-Beuren syndrome (WBS) to find additional biomarkers of genome instability. METHODS: The cytogenetic approaches were combined with the alkaline Comet assay to estimate genome integrity in cultured or freshly isolated and H(2)O(2)-treated lymphocytes. RESULTS: Basal frequencies of chromosome aberrations were significantly increased in NBS/FA probands and NBS heterozygous carriers. The NBS diagnosis was confirmed by detecting site-specific rearrangements, while the mitomycin C (MMC)-stress test was highly positive in a FA patient. Among patients with suspected WBS, 12 individuals had a 7q11.23 microdeletion. In the Comet assay, genome instability was revealed in all three disorders, impaired capacity to repair oxidative damage being observed in NBS and WBS in contrast to FA and controls. CONCLUSION: The results indicate that the estimates of DNA damage response may be proposed as efficient biomarkers for detecting and characterizing genome instability in the genetic disorders under study.

Chromosomal instability at the 7q11.23 region impacts on DNA-damage response in lymphocytes from Williams-Beuren syndrome patients.

Williams-Beuren syndrome (WBS) is the chromosomal disorder arising from a hemizygous microdeletion at 7q11.23. The present study was focused on a comparative investigation of genomic integrity in WBS patients by use of cytogenetic methods and the alkaline comet assay. Lymphocytes of whole peripheral blood were cultured and metaphases were examined for frequency and spectrum of chromosome aberrations. A WBS-related microdeletion was detected by means of the FISH (fluorescence in situ hybridization) technique. The blood samples from patients who were carriers of this microdeletion, were tested in the comet assay. For this purpose, freshly collected lymphocytes were exposed to hydrogen peroxide (100µM, 1min, 4°C). The frequencies of endogenous and exogenous DNA damage, and the kinetics and efficiency of DNA repair were measured during three subsequent hours of incubation. Comparison of the two data sets in this group of patients demonstrated a slightly elevated average frequency of chromosome aberrations, significantly increased levels of endogenous and H(2)O(2)-induced DNA damage, and somewhat impaired DNA repair. The relationship between an abnormal DNA-damage response and the 7q11.23 hemizygous microdeletion was confirmed experimentally when comparing the comet assay data in FISH-positive and FISH-negative lymphocytes from WBS-suspected patients. Briefly, our results indicate the impact of chromosomal instability within this region on susceptibility towards DNA damage, which may contribute to pathogenesis of this disease. It was shown also that the comet assay, as well as an experimental design proposed here, seem to be useful tools for estimating genome integrity in WBS patients.