Role of pharmacist counseling in preventing adverse drug events after hospitalization

BACKGROUND: Hospitalization and subsequent discharge home often involve discontinuity of care, multiple changes in medication regimens, and inadequate patient education, which can lead to adverse drug events (ADEs) and avoidable health care utilization. Our objectives were to identify drug-related problems during and after hospitalization and to determine the effect of patient counseling and follow-up by pharmacists on preventable ADEs. METHODS: We conducted a randomized trial of 178 patients being discharged home from the general medicine service at a large teaching hospital. Patients in the intervention group received pharmacist counseling at discharge and a follow-up telephone call 3 to 5 days later. Interventions focused on clarifying medication regimens; reviewing indications, directions, and potential side effects of medications; screening for barriers to adherence and early side effects; and providing patient counseling and/or physician feedback when appropriate. The primary outcome was rate of preventable ADEs. RESULTS: Pharmacists observed the following drug-related problems in the intervention group: unexplained discrepancies between patients' preadmission medication regimens and discharge medication orders in 49% of patients, unexplained discrepancies between discharge medication lists and postdischarge regimens in 29% of patients, and medication nonadherence in 23%. Comparing trial outcomes 30 days after discharge, preventable ADEs were detected in 11% of patients in the control group and 1% of patients in the intervention group (P = .01). No differences were found between groups in total ADEs or total health care utilization. CONCLUSIONS: Pharmacist medication review, patient counseling, and telephone follow-up were associated with a lower rate of preventable ADEs 30 days after hospital discharge. Medication discrepancies before and after discharge were common targets of intervention.     

Diabetic retinopathy is associated with a switch in splicing from anti- to pro-angiogenic isoforms of vascular endothelial growth factor

Aims/hypothesis Proliferative diabetic retinopathy results from excess blood vessel growth into the vitreous fluid of the eye. Retinal angiogenesis is regulated by expression of vascular endothelial growth factor (VEGF), and many studies have shown that VEGF is critically involved in proliferative diabetic retinopathy. VEGF is alternatively spliced to form the angiogenic (VEGF_xxx) and potentially anti-angiogenic (VEGF_xxxb) family of isoforms. The VEGF_xxxb family is found in normal tissues, but down-regulated in renal and prostate cancer. Previous studies on endogenous expression of VEGF in the eye have not distinguished between the two families of isoforms.Methods We measured VEGF_xxxb isoform expression in normal human eye tissue (lens, sclera, retina and iris) and vitreous fluid using enzyme-linked immunosorbent assay and Western blotting with a VEGF_xxxb-specific antibody.Results VEGF_xxxb protein was expressed in lens, sclera, retina, iris and vitreous fluid. Multiple isoforms were seen, including VEGF₁₆₅b, VEGF₁₂₁b, VEGF₁₄₅b, VEGF₁₈₃b and VEGF₁₈₉b. In non-diabetic patients, 64±7% of the VEGF in the vitreous was VEGF_xxxb (n=18), whereas in diabetic patients only 12.5±3.6% of total VEGF was VEGF_xxxb.Conclusions/interpretation Since VEGF_xxxb inhibits VEGF_xxx-induced angiogenesis in a one-to-one stoichiometric manner, these results show that in the eye of diabetic patients VEGF splicing was switched from an anti-angiogenic to a pro-angiogenic environment. This occurred through changes to the ratio of VEGF_xxx : VEGF_xxxb. Alterations to splicing, and through that to the balance of VEGF isoforms, could therefore be a potential therapeutic strategy for diabetic retinopathy.Konopatskaya and Perrin are joint first authors.     

A potent small molecule inhibits polyglutamine aggregation in Huntington's disease neurons and suppresses neurodegeneration in vivo

Polyglutamine (polyQ) disorders, including Huntington's disease (HD), are caused by expansion of polyQ-encoding repeats within otherwise unrelated gene products. In polyQ diseases, the pathology and death of affected neurons are associated with the accumulation of mutant proteins in insoluble aggregates. Several studies implicate polyQ-dependent aggregation as a cause of neurodegeneration in HD, suggesting that inhibition of neuronal polyQ aggregation may be therapeutic in HD patients. We have used a yeast-based high-throughput screening assay to identify small-molecule inhibitors of polyQ aggregation. We validated the effects of four hit compounds in mammalian cell-based models of HD, optimized compound structures for potency, and then tested them in vitro in cultured brain slices from HD transgenic mice. These efforts identified a potent compound (IC50=10 nM) with long-term inhibitory effects on polyQ aggregation in HD neurons. Testing of this compound in a Drosophila HD model showed that it suppresses neurodegeneration in vivo, strongly suggesting an essential role for polyQ aggregation in HD pathology. The aggregation inhibitors identified in this screen represent four primary chemical scaffolds and are strong lead compounds for the development of therapeutics for human polyQ diseases.     

Fc receptor gamma-chain activation via hOSCAR induces survival and maturation of dendritic cells and modulates Toll-like receptor responses

We previously reported the characterization of human osteoclast-associated receptor (hOSCAR), a novel Fc receptor gamma-chain (FcRgamma)-associated receptor expressed by myeloid cells. Here we show that ligation of hOSCAR by specific antibodies promotes dendritic cell (DC) survival by an extracellular signal-regulated kinase (ERK)- and phosphatidylinositol 3-kinase (PI3K)-dependent pathway, linked to expression of the Bcl-2 and Bcl-x(L) antiapoptotic molecules. Crosslinking of hOSCAR leads to maturation of DCs, as demonstrated by up-regulation of maturation markers, decrease in dextran uptake capacity, and secretion of immunesystem effectors such as interleukin-8 (IL-8)/CXC chemokine ligand 8 (CXCL8), IL-12 p40, monocyte chemoattractant protein-1 (MCP-1)/chemokine receptor ligand 2 (CCL2) and macrophage-derived chemokine (MDC)/CCL22. Stimulation of hOSCAR acts in conjunction with the Toll-like receptor (TLR) ligands, lipopolysaccharide (LPS), R-848, and polyinosinic-polycytidylic acid (poly(I:C)), to increase the expression of maturation markers, and to modulate cytokine release. A PI3K-dependent up-regulation of IL-10 release is observed with all the TLR ligands used, whereas regulation of IL-12 production is variable depending on the TLR stimulated. hOSCAR engagement on DCs did not significantly increase the proliferation of naive T cells; however, when co-incubated with TLR ligands, an enhanced proliferation was observed. The percentage of interferon (IFN)-gamma-producing T cells is decreased when hOSCAR engagement is combined with LPS stimulation. Altogether, these data suggest that hOSCAR may modulate the responses of both innate resistance and adaptive immunity.     

The type 2 iodothyronine deiodinase is expressed in the rat uterus and induced during pregnancy

Thyroid hormones are of considerable importance for vertebrate reproductive function and during development. To further assess the role of these compounds in this capacity, we examined the expression pattern of the type 2 iodothyronine deiodinase (D2), which converts T(4) to the more active hormone T(3), in the rat uterus in both the nonpregnant and the pregnant state. D2 activity was identified as the predominant, if not only, 5'-deiodinase in the nonpregnant rat uterus. The expression of D2 messenger RNA was located by in situ hybridization to the endometrial stromal cells, where the signal was particularly enriched in the region adjacent to the epithelial cells of the uterine lumen. During pregnancy, D2 activity increased, peaking on day 17 of gestation (embryonic day 17). At that time, uterine D2 activity exceeded that in the placenta, as well as that in the fetal tissues. In the earlier stages of pregnancy before placental formation (e.g. embryonic days 10-11), D2 messenger RNA in the rat uterus was located outside the decidual tissue, which was observed, as in previous studies, to highly express the inactivating type 3 deiodinase. In summary, the rat uterus, particularly during pregnancy, seems to be a site of active thyroid hormone metabolism, presumably designed to maintain the optimal thyroid hormone environment for both the fetus and the maternal uterine tissue.     

Developmental trajectories of externalizing and internalizing behaviors: factors underlying resilience in physically abused children

Using a multisite community sample of 585 children, this study examined how protective and vulnerability factors alter trajectories of teacher-reported externalizing and internalizing behavior from kindergarten through Grade 8 for children who were and were not physically abused during the first 5 years of life. Early lifetime history of physical abuse (11.8% of sample) was determined through interviews with mothers during the prekindergarten period; mothers and children provided data on vulnerability and protective factors. Regardless of whether the child was abused, being African American; being male; having low early social competence, low early socioeconomic status (SES), and low adolescent SES; and experiencing adolescent harsh discipline, low monitoring, and low parental knowledge were related to higher levels of externalizing problems over time. Having low early social competence, low early SES, low adolescent SES, and low proactive parenting were related to higher levels of internalizing problems over time. Furthermore, resilience effects, defined as significant interaction effects, were found for unilateral parental decision making (lower levels are protective of externalizing outcomes for abused children), early stress (lower levels are protective of internalizing outcomes for abused children), adolescent stress (lower levels are protective of internalizing outcomes for abused children), and hostile attributions (higher levels are protective of internalizing outcomes for abused children). The findings provide a great deal of support for an additive or main effect perspective on vulnerability and protective factors and some support for an interactive perspective. It appears that some protective and vulnerability factors do not have stronger effects for physically abused children, but instead are equally beneficial or harmful to children regardless of their abuse status.     

Reduced Effectiveness of Interruptive Drug-Drug Interaction Alerts after Conversion to a Commercial Electronic Health Record

Background

Drug-drug interaction (DDI) alerts in electronic health records (EHRs) can help prevent adverse drug events, but such alerts are frequently overridden, raising concerns about their clinical usefulness and contribution to alert fatigue.

Objective

To study the effect of conversion to a commercial EHR on DDI alert and acceptance rates.

Design

Two before-and-after studies.

Participants

3277 clinicians who received a DDI alert in the outpatient setting.

Intervention

Introduction of a new, commercial EHR and subsequent adjustment of DDI alerting criteria.

Main Measures

Alert burden and proportion of alerts accepted.

Key Results

Overall interruptive DDI alert burden increased by a factor of 6 from the legacy EHR to the commercial EHR. The acceptance rate for the most severe alerts fell from 100 to 8.4%, and from 29.3 to 7.5% for medium severity alerts (P?<?0.001). After disabling the least severe alerts, total DDI alert burden fell by 50.5%, and acceptance of Tier 1 alerts rose from 9.1 to 12.7% (P?<?0.01).

Conclusions

Changing from a highly tailored DDI alerting system to a more general one as part of an EHR conversion decreased acceptance of DDI alerts and increased alert burden on users. The decrease in acceptance rates cannot be fully explained by differences in the clinical knowledge base, nor can it be fully explained by alert fatigue associated with increased alert burden. Instead, workflow factors probably predominate, including timing of alerts in the prescribing process, lack of differentiation of more and less severe alerts, and features of how users interact with alerts.

     

Leprosy trends in Zambia 1991–2009

Objective To document leprosy trends in Zambia over the past two decades to ascertain the importance of leprosy as a health problem in Zambia. Methods Retrospective study covering the period 1991–2009 of routine national leprosy surveillance data, published national programme review reports and desk reviews of in‐country TB reports. Results Data reports were available for all the years under study apart from years 2001, 2002 and 2006. The Leprosy case notification rates (CNR) declined from 2.73/10 000 population in 1991 to 0.43/10 000 population in 2009. The general leprosy burden showed a downward trend for both adults and children. Leprosy case burden dropped from approximately 18 000 cases in 1980 to only about 1000 cases in 1996, and by the year 2000, the prevalence rates had fallen to 0.67/10 000 population. There were more multibacillary cases of leprosy than pauci‐bacillary cases. Several major gaps in data recording, entry and surveillance were identified. Data on disaggregation by gender, HIV status or geographical origin were not available. Conclusion Whilst Zambia has achieved WHO targets for leprosy control, leprosy prevalence data from Zambia may not reflect real situation because of poor data recording and surveillance. Greater investment into infrastructure and training are required for more accurate surveillance of leprosy in Zambia.