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Introduction: Pharmacists deploy a variety of population‐health strategies to identify needs related to pharmacotherapy. One area that deserves closer attention is medication management in atrial fibrillation (AF) since managing stroke prevention in older adults with AF requires delicately balancing the risk of thrombosis with the risk of bleeding. Objective(s): Evaluate direct‐acting oral anticoagulant (DOAC) prescribing trends and explore strategies for mitigating gastrointestinal bleeding (GIB) risk in older adults prescribed a DOAC for stroke prevention in AF. Methods: A quality improvement project was conducted and included Managed‐Medicare patients from a single primary care organization prescribed a DOAC for AF. Pharmacists estimated risk of benefit and harm from the prescribed DOAC using established algorithms and patient characteristics documented in the medical record. They then forecasted the change in net clinical benefit if the prescribed DOAC was switched to a different DOAC. Results: Overall, 200 patients met the inclusion criteria. Based on distribution of DOACs in the original study population, 52% of patients were in the definitive benefit group (benefit in reducing stroke risk outweigh risk of bleeding by 2‐fold or greater), with 37% and 10.5% in the leaning benefit (reduction in stroke risk was up to 2‐fold greater than bleeding risk) and leaning risk (bleeding risk was up to 2‐fold greater than stroke risk reduction) groups, respectively. Calculation of risk should the prescribed DOAC be changed from rivaroxaban to apixaban was estimated to improve the net clinical benefit and reduce the risk of a patient falling in a negative clinical benefit group when compared to rivaroxaban and the original study population, respectively; 92% (relative risk [RR] 0.08 [0.026‐0.277; P < 0.0001]) and 81% (RR 0.19 [0.067‐0.545; P = 0.0002]). Conclusion: Population health‐based strategies centered on DOAC use in older adults can help identify prescribing trends and allow organizations to explore ways to mitigate risk of GIB. Preferential use of apixaban could reduce bleeding risk among older adults requiring anticoagulation for AF. [ABSTRACT FROM AUTHOR]

Summary: This study evaluated the long‐term efficacy and safety of an 18‐month lamivudine prophylaxis in 68 HBsAg‐negative/anti–HBc‐positive patients with oncohaematological disease. All 68 consecutive HBsAg‐negative/anti–HBc‐positive patients with an oncohaematological disease and naïve for chemotherapy observed from April 2008 to December 2012 at 2 Hematology Units in Naples were treated with lamivudine for 18 months after stopping chemotherapy and monitored for HBsAg at months 1 and 3 during chemotherapy and then every 3 months after its discontinuation. During follow‐up, 13 (19.1%) of the 68 patients died of complications related to their oncohaematological disease, and 3 (4%) showed a virological HBV reactivation (retroconversion to HBsAg positivity) 1‐7 months after the discontinuation of lamivudine prophylaxis (2 treated for chronic lymphocytic leukaemia and one for Waldenstrom's disease); of these, 2 showed a biochemical reactivation. Comparing the demographic and clinical characteristics of the 3 patients with a virological HBV reactivation to the 65 without, the former were older (median age and range: 67 years [75‐78] vs. 61 [24‐88]; P = .05) and were less frequently treated for B‐cell non‐Hodgkin lymphoma (B‐NHL) (0 vs. 70.7%, P = .03). In conclusion, a 18 months of lamivudine prophylaxis was effective in preventing HBV reactivation in HBsAg‐negative/anti–HBc‐positive patients treated for B‐NHL. However, in patients with chronic and severe immunodepression, such as those with chronic lymphocytic leukaemia and Waldenstrom's disease, prophylaxis should be continued for an indefinite period. [ABSTRACT FROM AUTHOR]

Background & Aims A common non-synonymous polymorphism, E167K, in transmembrane six superfamily member 2 ( TM6 SF2) gene has been recently associated with an increased hepatic triglyceride content, dyslipidemia and liver fibrosis in NAFLD patients. We investigated possible associations between the TM6 SF2 variants and liver lesions in chronic hepatitis C. Patients and Methods 148 consecutive patients with biopsy proven anti- HCV/ HCV- RNA-positive chronic hepatitis, naive for antiviral therapy, were genotyped for TM6 SF2 E167K and PNPLA3 I148M variants. Results The score of liver steatosis was higher in the 18 patients with TM6 SF2 E167K variant (mean 1.9 ± 1.3) than in the 130 homozygotes for TM6 SF2 167E allele (1.1 ± 1.1, P = 0.02), and the prevalence of a steatosis score ≥ 3 was 33.3% vs. 12.3% respectively ( P = 0.02). No difference in necroinflammatory or fibrosis scores was found between the two groups. A general linear model identified as independent predictors of steatosis TM6 SF2 E167K and PNPLA3 M148M variants and waist circumference ( P = 0.0376, P = 0.0069 and P = 0.0273 respectively). Conclusions This is the first demonstration that TM6 SF2 E167K variant is an independent predictor of liver steatosis in chronic hepatitis C. [ABSTRACT FROM AUTHOR]

The patatin-like phospholipase domain-containing 3 gene ( PNPLA3) and the apolipoprotein C3 gene ( APOC3) have been studied in relation to liver steatosis and liver disease outcome. The aim of this study was to evaluate the influence of PNPLA3 p.I148M and APOC3 rs2854116 and rs2854117 polymorphisms on the clinical and histological presentation of chronic hepatitis C in an Italian population and their relationship with viral and anthropometric parameters. Patients with hepatitis C ( n = 166) entered the study receiving a clinical, histological, virological and biochemical evaluation. APOC3 (rs2854116 and rs2854117) and PNPLA3 (p.I148M) variants were genotyped. PNPLA3 polymorphisms were associated with liver steatosis, which was significantly higher in patients with p.148I/M ( P = 0.034) and p.148M/M ( P = 0.004) variants than those homozygous for the PNPLA3 wild type. Excluding patients with HCV genotype 3, the association with liver steatosis and PNPLA3 variants was more marked (p.148I/I genotype vs p.148I/M, P = 0.02, and vs p.148M/M, P = 0.005). The APOC3 polymorphism was not associated with any of the evaluated parameters. Among the interacting factors, BMI and waist circumference correlated with liver steatosis ( P = 0.008 and 0.004, respectively). Relationship between waist circumference and liver steatosis was analysed for the different PNPLA3 genotypes. Homozygous 148M patients showed a stronger correlation between waist circumference and steatosis than those carrying the other genotypes ( P = 0.0047). In our hepatitis C-infected population, the PNPLA3 polymorphism influenced the development of liver steatosis, but not fibrosis progression. APOC3 polymorphisms had no effect on the development of steatosis and no influence on the PNPLA3 polymorphism. The amount of abdominal fat can increase the association of PNPLA3 p.I148M with liver steatosis. [ABSTRACT FROM AUTHOR]

Haploinsufficiency of a region located distal to 10p14 designated HDR1, is responsible for hypoparathyroidism, sensorineural deafness, and renal anomalies (HDR syndrome). Haploinsufficiency of a more proximal region, located on 10p13-10p14, designated as DGCR2 is associated with congenital heart defects and thymus hypoplasia/aplasia or T cell defect. We describe a patient showing facial dysmorphisms, delayed psychomotor development and bilateral sensorineural hearing loss and carrying a 10p14 deletion, the smallest deletion found in the literature so far. Our patient, carrying a partial deletion of the DGCR2 region and of the HDR1 region, including the GATA3 gene, showed, unexpectedly, only few of the clinical features of DiGeorge 2 syndrome (psychomotor retardation, palpebral ptosis, epicanthic folds, anteverted nares, cryptorchidism, hand/foot abnormalities) and did not show other typical signs, such as cardiac defect, cleft palate, and abnormal T cell levels. Of the three characteristic features of the HDR syndrome, our patient had only sensorineural deafness. On the basis of the revision of the other cases reported in the literature with a deletion including the 10p14 region, we suggest that GATA3 haploinsufficiency, although not recorded for each patient, is responsible for deafness. The present case shows that even this small 10p deletion is responsible for a specific phenotype. We also underline the importance of CGH-array, in order to obtain a more precise physical mapping of the 10p deletions and an accurate genotype-phenotype correlation. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]