ABSTRACT
BACKGROUND: Human rabies can be prevented through postexposure prophylaxis (PEP). Although the case fatality rate is high, there are only one to three human cases per year in the United States. Despite the low incidence, the cost of rabies diagnostics, prevention, and control is significant. Recommendations exist regarding which patients should receive PEP, though several studies demonstrate a high frequency of unnecessary prescribing of PEP. OBJECTIVE: The purpose of this study is to determine if an animal bite protocol improves compliance with state and national recommendations regarding treatment of patients presenting to the emergency department (ED). Potential cost savings will also be evaluated. METHODS: An institutional review board-approved, single-center, retrospective chart review was conducted from January 1, 2017 to March 18, 2018 to evaluate patients presenting to the ED with an animal bite prior to and after implementation of a protocol. The primary outcome was defined as the percentage of PEP offered as indicated by the protocol. Secondary outcomes included the appropriateness of not offering PEP and estimated cost savings after protocol implementation. RESULTS: PEP was indicated four times out of 29 offers pre-protocol and three times out of five offers post-protocol (p = 0.0476). There was no difference in the appropriateness of not offering PEP (pre-protocol 105/107 times vs. 29/29 times; p = 0.9998). Cost savings was associated with protocol implementation. CONCLUSION: A pharmacist-driven protocol can beneficially influence prescribing habits after potential rabies exposure and is associated with cost savings.
Subject(s)
Bites and Stings , Rabies Vaccines , Rabies , Animals , Humans , Pharmacists , Post-Exposure Prophylaxis , Rabies/prevention & control , Retrospective StudiesABSTRACT
Impaired hematologic status (IHS) was investigated as a determinant of immune function defined as cluster of differentiation 4 (CD4) T-helper cell count, quality of life (QOL) weight and hospitalization/mortality over 18-months among 398 adult persons living with HIV/AIDS (PLWHA) on anti-retroviral therapy. IHS was defined as having anemia at baseline (Hemoglobin: <12 g/dL for women and <13 g/dL for men), time-updated anemia or having low (<30 µg/L) or high (>200 µg/L for men and >150 µg/L for women) ferritin levels at baseline. Months-to-hospitalization/death or study-end (if no event) was calculated from enrollment. Multivariable linear-mixed models quantified associations between IHS and changes in CD4 cell-count, weight gain and QOL. Cox proportional hazards models calculated hazard ratios (HR) and corresponding 95% confidence intervals (CI) for IHS-related differences in time-to-hospitalization/death. The prevalences of anemia and high and low ferritin levels at baseline were 48.7% (n = 194), 40.5% (n = 161) and 17% (n = 68), respectively. Most patients (63.4%, n = 123) remained anemic during follow-up. Weight gained (ferritin-time interaction, p < 0.01) and QOL (anemia-time interaction, p = 0.05; ferritin-time interaction, p = 0.01) were lower for PLWHA with versus without IHS. Relative to anemia-free/normal ferritin, the risk of hospitalization/death was elevated for PLWHA with anemia (HR = 2.0; 95% CI: 1.2-3.6), low or high ferritin (HR: 1.8-1.9, 95% CI: 0.9-4.1) and those that developed new/persistent/progressive anemia (HR: 2.3-6.7, 95% CI: 1.0-12.7). Among PLWHA, IHS predicted deficits in QOL, low weight gain and a high risk of hospitalization/death. Intervention to mitigate persistent IHS may be warranted among PLWHA on long-term highly active antiretroviral therapy (HAART) to improve health outcomes.
Subject(s)
Anemia/blood , Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , T-Lymphocytes, Helper-Inducer/drug effects , Adolescent , Adult , Anemia/immunology , Anemia/mortality , Anti-HIV Agents/adverse effects , Antiretroviral Therapy, Highly Active , Biomarkers/blood , Body Mass Index , CD4 Lymphocyte Count , Female , Ferritins/blood , HIV Infections/blood , HIV Infections/immunology , HIV Infections/mortality , Hemoglobins/metabolism , Humans , Iron/blood , Linear Models , Longitudinal Studies , Male , Multivariate Analysis , Nutritional Status , Patient Admission , Prevalence , Proportional Hazards Models , Prospective Studies , Quality of Life , Risk Factors , Severity of Illness Index , T-Lymphocytes, Helper-Inducer/immunology , Time Factors , Treatment Outcome , Uganda/epidemiology , Weight Gain , Young AdultABSTRACT
A-kinase anchoring proteins (AKAPs) play an important role in the spatial and temporal regulation of protein kinase A (PKA) by scaffolding critical intracellular signaling complexes. Here we report the design of conformationally constrained peptides that disrupt interactions between PKA and AKAPs in an isoform-selective manner. Peptides derived from the A Kinase Binding (AKB) domain of several AKAPs were chemically modified to contain an all-hydrocarbon staple and target the docking/dimerization domain of PKA-R, thereby occluding AKAP interactions. The peptides are cell-permeable against diverse human cell lines, are highly isoform-selective for PKA-RII, and can effectively inhibit interactions between AKAPs and PKA-RII in intact cells. These peptides can be applied as useful reagents in cell-based studies to selectively disrupt AKAP-localized PKA-RII activity and block AKAP signaling complexes. In summary, the novel hydrocarbon-stapled peptides developed in this study represent a new class of AKAP disruptors to study compartmentalized RII-regulated PKA signaling in cells.
