The neurosteroid allopregnanolone (ALLO) is a potent positive modulator of g -aminobutyric acid A (GABA A ) receptors. Earlier work indicates that sensitivity to the anticonvulsant effect of ALLO was enhanced during ethanol (EtOH) withdrawal in rats and in C57BL/6 mice, an inbred strain with mild EtOH withdrawal. In contrast, ALLO sensitivity was reduced during EtOH withdrawal in DBA/2 mice, an inbred strain with severe EtOH withdrawal. Thus, the present studies examined ALLO sensitivity during EtOH withdrawal in another animal model of EtOH withdrawal severity, the Withdrawal SeizureProne (WSP) and Withdrawal Seizure-Resistant (WSR) selected lines. Male mice were exposed to EtOH vapor or air for 72 h. During peak withdrawal, animals were injected with ALLO [0, 3.2, 5, 10 or 17 mg/kg, intraperitoneally (i.p.)] and tested for their sensitivity to the anticonvulsant effect. In separate studies, potentiation of GABA-stimulated chloride uptake by ALLO (10 nM to 10 mM) was assessed in microsacs prepared from mouse brain mice during peak withdrawal. Notably, WSP mice were cross-tolerant to the anticonvulsant effect of ALLO during EtOH withdrawal (i.e. significant decrease in the efficacy of ALLO) when compared with values in airexposed mice. In contrast, sensitivity to the anticonvulsant effect of ALLO was unchanged during EtOH withdrawal in the WSR line. Functional sensitivity of GABA A receptors to ALLO was significantly decreased during EtOH withdrawal in WSP mice in a manner consistent with the change in behavioral sensitivity to ALLO. These findings suggest that mice selectively bred for differences in EtOH withdrawal severity are differentially sensitive to ALLO during EtOH withdrawal.
BackgroundOutpatient parenteral antimicrobial therapy (OPAT), widely used for serious infections, has high failure rates in people with substances use disorders (SUD)1–2. At our institution, completing therapy in the hospital was previously the best option for high-risk patients; but long hospital stays are often unacceptable to patients and costly. To improve outcomes, our Infectious Diseases division, OPAT program, and Improving Addiction Care Team (IMPACT) developed and implemented a novel multidisciplinary conference (OPTIONS-DC) for inpatients with SUD requiring prolonged antibiotics. This study describes the conference development, tool, and initial experience.MethodsFrom June 2017 to June 2018, diverse stakeholders collaboratively created and implemented a structured conference to discuss treatment options that balance medical efficacy, patient preferences, and feasibility using harm-reduction principles. After 10 months of hospital-wide implementation, we elicited provider feedback and performed a content analysis of OPTIONS-DC notes and patient records to evaluate the impact.ResultsThe goal of conference development was prioritizing patient preferences and engaging multidisciplinary input. One RN facilitates the conference using the tool (Figure 1) to elicit input from the relevant providers. The tool systematically addresses components that may predict treatment success (i.e., working phone) while emphasizing patient preference and harm reduction. The IMPACT social work PICC safety assessment informs risks for IV access. Antibiotic recommendations are not a binary of optimal/suboptimal choices for the infection but options that best fit patient context. The average conference length was 28 minutes (IQR 21). Preliminary data shows good clinical outcomes and savings to inpatient days and cost. Initial feedback suggests the model was positively experienced by medical providers (Figure 2) and supported patient preferences.ConclusionA multidisciplinary patient-centered conference that prioritizes patient preference and uses harm-reduction principles for this high-risk population is practical, effective, and positively experienced by providers. This model may serve as a roadmap for other institutions. Disclosures All authors: No reported disclosures.
Background The use of dalbavancin (DAL) enhances the management of serious gram-positive infections in people with substance use disorder (SUD) by eliminating the need for central lines, weekly lab monitoring, and may decrease length of hospitalizations. Though administered weekly, care coordination for DAL is often complex, due to variable access to resources, insurance variation and treatment settings. Our institution uses OPTIONS-DC, a multi-disciplinary discharge planning conference facilitated by an outpatient parenteral antimicrobial therapy (OPAT) registered nurse (RN) to determine safe treatment plans while emphasizing patient preference for hospitalized patients with SUD and serious infections. When DAL is selected for treatment, patients are enrolled in the RN-led OPAT program for coordination and monitoring. DAL has been shown to result in monetary savings but these estimates have yet to incorporate the true cost of coordination. Methods We conducted a retrospective chart review of OPAT staff interventions required to coordinate DAL doses for patients with SUD (identified via ICD-10 code or chart notes). Additionally, we recorded in real time, the amount of time spent per intervention over a one month period for 7 additional patients. Results 53 courses of DAL in patients with SUD were included with a variety of dosing regimens and treatment settings (Table 1). 41 (77%) patients endorsed IV substance use. 68% of patients received DAL for osteomyelitis or endocarditis. The majority were insured by Oregon Medicaid (70%). The number of RN interventions per course averaged 3.35 with the most common being coordinating with patients and vendors (Table 2). The average time spent per patient course during a one-month sample was 39.4 minutes (range 15 – 58 minutes). The most time-consuming interventions were conducting the OPTIONS-DC conferences and attempting to reach patients after hospital discharge. Readmission for adverse effects or infection occurred for 4 (8%) patients. Conclusion The OPAT-RN time required to coordinate outpatient DAL for patients with SUD is substantial. This enhanced coordination allows for potential cost savings to health systems. Disclosures Amber C. Streifel, PharmD, BCPS, Melinta (Advisor or Review Panel member) Monica K. Sikka, MD, FG2 (Scientific Research Study Investigator)
Background Vancomycin and daptomycin are commonly used in outpatient parenteral antimicrobial therapy (OPAT) for patients requiring lengthy courses of intravenous antimicrobials who are otherwise stable for discharge. Balancing the convenience and cost-savings of OPAT with the potential for adverse effects is challenging, this study compared the rates of complications and antimicrobial interventions for patients receiving vancomycin versus daptomycin across multiple OPAT settings. Methods We performed a retrospective chart review of adult OPAT patients who received >72 hours of vancomycin or daptomycin via home infusion, infusion center, or skilled nursing facility between January 2017 and August 2019. The outcomes evaluated included the rates of adverse drug reactions (ADRs), laboratory results above a defined threshold (vancomycin levels >20 mg/mL in the vancomycin arm and creatinine phosphokinase (CPK) levels >500 units/L in the daptomycin group), line complications, emergency department (ED) visits, and hospital readmissions. Other outcomes included additional phone calls and interventions required to coordinate care (additional labs, assessment of symptoms, additional test or antimicrobial-related dose changes) by the OPAT team. Results 180 patients were included; 130 received vancomycin and 50 received daptomycin. (Table 1) Patients in the vancomycin group had more supratherapeutic vancomycin troughs than elevated CPK for patients in the daptomycin group (rate ratio [RR] 0.16, 95% CI 0.05-0.50, p=0.0018). Rates of interventions (RR 0.37, 95% CI 0.26-0.52, p< 0.0001) and additional phone calls (RR 0.56, 95% CI 0.43-0.72, p< 0.0001) were also higher for patients in the vancomycin group. There were no statistically significant differences between groups in the rates of ADRs, line complications, ED visits, or hospital readmissions. (Table 2) Table 1. Baseline Characteristics Table 2. Outcomes Conclusion Vancomycin-treated patients had significantly more laboratory abnormalities and required significantly more time in patient care coordination by the OPAT team. The difference in healthcare utilization between these groups suggests a potential for significant cost-savings for OPAT patients and the healthcare system. Disclosures All Authors: No reported disclosures
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