Herges, Joseph R.

Background: Itraconazole is the preferred antifungal agent for mild to moderate histoplasmosis and step-down therapy following amphotericin B treatment. Although hydroxy-itraconazole, a major metabolite of itraconazole, displays antifungal activity comparable with that of the parent compound, its role in therapeutic drug monitoring targets for histoplasmosis remains uncertain. Methods: The objective was to compare clinical outcomes and adverse events using itraconazole parent-compound concentrations alone versus combined itraconazole and hydroxy-itraconazole concentrations in patients treated for histoplasmosis. This retrospective cohort study included adults with probable or proven histoplasmosis who received itraconazole and had at least 1 documented serum concentration. The primary outcome was clinical response across 3 groups: (1) parent (itraconazole parent-compound concentration >1.0 mcg/mL), (2) combined (parent-compound concentration <1.0 mcg/mL with combined itraconazole plus hydroxy-itraconazole >1.0 mcg/mL), and (3) subtherapeutic (failure to reach either threshold). Treatment response and adverse events were analyzed using the Fisher exact test. Results: Among 108 patients (parent, n = 40; combined, n = 40; subtherapeutic, n = 28), response rates differed across groups (parent (95%); combined (90%); subtherapeutic (67.9%); P = 0.006). There was no difference between the parent and combined groups. Adverse events did not differ, although drug discontinuation occurred more frequently in the subtherapeutic group (parent (5%); combined (20%); subtherapeutic (25%); P = 0.04). Conclusions: Patients who failed to achieve either an itraconazole concentration >1 mcg/mL or a combined itraconazole plus hydroxy-itraconazole concentration >1 mcg/mL had lower response rates. Similar outcomes among patients achieving the itraconazole target alone and those achieving the combined target suggest that hydroxy-itraconazole concentrations may contribute to therapeutic drug monitoring targets in histoplasmosis.

AbstractProfessional standards for academic health care system pharmacy departments and clinical pharmacists advocate for research and scholarly activities. Developing and sustaining a research program in a clinical pharmacy department is challenging. Over the span of a decade, a robust pharmacy research program was developed in an academic medical center not affiliated with a college of pharmacy. The aim of this manuscript is to provide a framework suitable for scaling research in pharmacy departments within an academic medical center. Objectives to accomplish the aim includes describing the structure and evolution of the clinical pharmacy department research program, listing measurable outputs and achievements of the pharmacists and the program and describing the barriers encountered and solutions that were enacted to overcome them. Elements critical to building and sustaining a research program in the pharmacy department included long‐term commitment from within the department, a departmental research infrastructure, support from institutional leadership, research funding from the institution, and a growth mindset in accordance with company initiatives to support evolving research needs. A research curriculum was developed for pharmacy residents and pharmacists, created electronic tools for research proposal scientific reviews and allocation of funds, and established departmental research career development awards that allowed for protected time to pursue research and professional development. Over the first 10 years of the program, publication rates grew more than three‐fold, faculty appointments and promotions increased approximately five‐fold, and pharmacist investigators obtained extramural federal funding. Further offsetting clinical workload relative to dedicated research time remains a challenge. The experience and success at this academic medical center suggest it is feasible to develop a robust, sustainable clinical pharmacy department research program.

OBJECTIVETo characterize contemporary trends in glucagon fill rates and expenditures in a nationwide cohort of adults with diabetes overall and by key demographic and clinical characteristics.RESEARCH DESIGN AND METHODSIn this retrospective cohort study, we examined 1) glucagon fill rates per 1,000 person-years and 2) patient out-of-pocket and health plan costs per filled glucagon dose among adults with diabetes included in OptumLabs Data Warehouse between 1 January 2011 and 31 March 2021.RESULTSThe study population comprised 2,814,464 adults with diabetes with a mean age of 62.8 (SD 13.2) years. The overall glucagon fill rate decreased from 2.91 to 2.28 per 1,000 person-years (−22%) over the study period. In groups at high risk for severe hypoglycemia, glucagon fill rates increased from 22.46 to 36.76 per 1,000 person-years (64%) among patients with type 1 diabetes, 11.64 to 16.63 per 1,000 person-years (43%) among those treated with short-acting insulin, and 16.08 to 20.12 per 1,000 person-years (25%) among those with a history of severe hypoglycemia. White patients, women, individuals with high income, and commercially insured patients had higher glucagon fill rates compared with minority patients, males, individuals with low income, and Medicare Advantage patients, respectively. Total cost per dosing unit increased from $157.97 to $275.32 (74%) among commercial insurance beneficiaries and from $150.37 to $293.57 (95%) among Medicare Advantage beneficiaries.CONCLUSIONSGlucagon fill rates are concerningly low and declined between 2011 and 2021 but increased in appropriate subgroups with type 1 diabetes, using short-acting insulin, or with a history of severe hypoglycemia. Fill rates were disproportionately low among minority patients and individuals with low income.

Background: Acute kidney injury (AKI) survivors are at heightened risk for poor short- and long-term health outcomes. Even among those who recover after an AKI episode, the risk for chronic kidney disease is 4- to 6-fold higher than in patients without AKI, underscoring the importance of identifying methods to improve AKI survivorship. Objective: The purpose of this report was to describe the development and feasibility of a novel multidisciplinary approach to caring for AKI survivors at care transitions (ACT). Design: Observational process improvement initiative. Setting: Single academic medical center in the United States. Patients: The studied population was adults with stage 3 AKI not discharging on dialysis who were established with a primary care provider (PCP) at our institution. Methods: An electronic health record tool was developed prior to implementation to identify AKI survivors. The ACT program encompassed engaging patients in the hospital, delivering education by nephrology-trained nurses before discharge, completing recommended laboratory testing after discharge, and conducting structured kidney-focused follow-up with a pharmacist and a PCP within 7 to 14 days after discharge. Patients could be referred for nephrology evaluation at the discretion of the PCP. Results: Preliminary data demonstrated that most AKI survivors of interest could be identified, educated, and followed up with this model. This strategy appeared feasible, scalable, and maximized the unique expertise of each member of the multidisciplinary team. Limitations: Small sample size, future assessment of process, clinical, and patient-reported outcomes needed. Conclusions: The multidisciplinary ACT workflow supported by clinical decision support was feasible and addressed gaps in existing care transition models. Team-based care delivery in primary care appears to be a mechanism to extend the capacity for kidney health monitoring for AKI survivors.

Introduction Bumetanide can induce generalized musculoskeletal pain when administered as a continuous infusion, an effect that may be underrecognized. The purpose of this case series is to educate health care providers about the incidence and presentation of pain associated with bumetanide infusions, adding to the existing literature describing this adverse event. Clinical Findings Of 40 critically ill patients, 15 (38%) had increased pain scores after initiation of a continuous infusion of bumetanide, with symptoms commonly occurring 12 to 24 hours after initiation of the infusion. Reported descriptions of the pain included generalized aching, soreness, burning, allodynia, headaches, and exacerbation of underlying pain in localized areas. Increases in patient-reported pain correlated directly with initiation of the continuous infusion of bumetanide. Diagnosis Four of the 15 bumetanide-associated pain events (27%) were recognized as such by the health care team. Interventions Bumetanide was promptly discontinued in the 4 identified cases. The 11 patients (73%) whose pain was not recognized as related to bumetanide remained on a continuous infusion of bumetanide and received pain medications including opioids. Infusions were stopped when patients transitioned to dialysis (n = 8 [53%]), began receiving comfort care (n = 5 [33%]), or completed diuresis therapy (n = 2 [13%]). Outcomes For all patients, pain symptoms resolved within 24 to 48 hours after discontinuation of bumetanide infusion with no significant electrolyte abnormalities. Conclusion Bumetanide-induced pain is more common than previously described. Early recognition of this adverse event can prevent patient discomfort and escalation of treatment.

Abstract Purpose To evaluate the impact of a collaborative intervention by pharmacists and primary care clinicians on total cost of care, including costs of inpatient readmissions, emergency department visits, and outpatient care, at 30, 60, and 180 days after hospital discharge in a population of patients at high risk for readmission due to polypharmacy. Methods A retrospective study of cost outcomes in a cohort of adult patients discharged from a single institution from July 1, 2013 to March 25, 2016, was conducted. All patients had at least 10 medications listed on their discharge list, including at least 1 drug frequently associated with adverse events leading to hospital readmission. About half of the cohort (n = 496) attended a postdischarge visit involving both a pharmacist and a primary care clinician (a physician, physician assistant, or licensed nurse practitioner); this was designated the pharmacist/clinician collaborative (PCC) group. The remainder of the cohort (n = 500) attended a visit without pharmacist involvement; this was designated as the usual care (UC) group. Costs were compared using a quantile regression to assess the potential heterogeneous impacts of the PCC intervention across different parts of the cost distribution. All outcomes were adjusted for differences in baseline characteristics. Results At 30 days post index discharge, there was a significant decrease in total costs in the 10th and 90th cost quantiles in the PCC cohort vs the UC cohort, without a statistically significant decrease in the 25th, 50th or 75th quantiles. The difference was significant in the 75th and 90th quantiles at 60 days and in the 25th, 50th, and 75th quantiles at 180 days. There was a nonsignificant cost reduction in all other quantiles. Conclusion Medically complex patients had a significantly lower total cost of care in approximately half of the adjusted cost quantiles at 30, 60, and 180 days after hospital discharge when they had a PCC visit. PCC visits can improve patient clinical outcomes while improving cost metrics.