The use of buprenorphine to-go packs in the emergency department.

OBJECTIVE: Buprenorphine is an effective treatment for opioid use disorder (OUD). Patients in the emergency department (ED) can be initiated or continued on buprenorphine as a bridge to follow-up in the outpatient setting, but gaps in care may arise. The objective was to evaluate the impact of buprenorphine to-go packs as a continuing treatment option for patients presenting to the ED with OUD across a health system. METHODS: Adult patients discharged with a buprenorphine to-go pack from one of ten EDs within a major health system were included. The primary outcomes assessed within 30 days of ED discharge were: (1) return to a health system ED, and (2) fill history of buprenorphine in the state prescription drug monitoring program database. Data was analyzed using descriptive statistics in Microsoft Excel (Redmond, WA). RESULTS: A total of 124 patients received buprenorphine to-go packs. The sample was primarily male (79; 63.7%), white (89; 71.8%), on Medicaid (79; 63.7%), and had a mean age of 40.9 years. A total of 43 patients (34.7%) were initiated on buprenorphine for the first time, while 81 (65.3%) had received buprenorphine (prescription or to-go) previously. At 30 days post-visit, 76 (61.3%) had filled buprenorphine prescriptions, and 40 (32.3%) returned to an ED within the health system for opioid withdrawal (17; 42.5%), non-OUD-related reasons (22; 55%), or overdose (1; 2.5%). CONCLUSION: The implementation of a system-wide buprenorphine to-go supply at ED discharge is a feasible option to provide continuity of care to patients with OUD.

Comparison of clinical outcomes with cangrelor plus aspirin versus oral dual antiplatelet therapy in patients supported with venoarterial extracorporeal membrane oxygenation.

BACKGROUND: Patients with refractory cardiogenic shock from an acute myocardial infarction may receive percutaneous coronary intervention (PCI) and require the use of venoarterial extracorporeal membrane oxygenation (VA-ECMO). The purpose of this study was to compare bleeding and thrombotic events in patients treated with cangrelor plus aspirin versus oral dual antiplatelet therapy (DAPT) while supported with VA-ECMO. METHODS: We conducted a retrospective review of patients who received PCI, were supported with VA-ECMO, and were treated with either cangrelor plus aspirin or oral DAPT from February 2016 through May 2021 at Allegheny General Hospital. The primary objective was the incidence of major bleeding, defined as Bleeding Academic Research Consortium (BARC) type 3 or greater. The incidence of thrombotic events was a secondary objective. RESULTS: Thirty-seven patients were included, 19 in the cangrelor plus aspirin group, and 18 in the oral DAPT group. All the patients in the cangrelor group received a dose of 0.75 mcg/kg/min. Major bleeding occurred in 7 patients (36.8%) in the cangrelor group compared to 7 patients (38.9%) in the oral DAPT group (p = 0.90). No patient developed stent thrombosis. Two patients (10.5%) in the cangrelor group had a thrombotic event versus 3 patients (16.7%) in the oral DAPT group (p = 0.66). CONCLUSIONS: Bleeding and thrombotic events were comparable between patients receiving cangrelor plus aspirin versus oral DAPT while on VA-ECMO.

Cephalosporins for the treatment of uncomplicated pyelonephritis: A systematic review.

BACKGROUND: The 2011 Infectious Diseases Society of America and European Society of Clinical Microbiology and Infectious Diseases guidelines recommend ciprofloxacin or sulfamethoxazole-trimethoprim (SMX-TMP) as first-line agents to treat uncomplicated acute pyelonephritis (APN). OBJECTIVE: With increasing antimicrobial resistance rates and recent changes in practice patterns, the objective of this systematic review was to describe the effectiveness of cephalosporins for uncomplicated APN in more recently published literature. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used for reporting. We searched PubMed, Embase, and Scopus for publications between January 2010 and September 2022. Eligible articles detailed patients with uncomplicated APN, treated with first- to fourth-generation cephalosporins, and identified a clinical, microbiological, or health care utilization outcome. Studies with more than 30% of complicated APN patients, non-English-language studies, case reports, case series, pharmacodynamic or pharmacokinetic studies, and in vitro laboratory or animal studies were excluded. Screening, review, and extraction were performed independently by 2 researchers, plus a third for conflict resolution. Critical appraisal of studies was performed using Joanna Briggs Institute checklists. RESULTS: Eight studies met inclusion, including 5 cohort studies (62.5%), 2 randomized controlled trials (25%), and 1 nonrandomized experimental study (12.5%). Cephalosporins most used across the studies included cefazolin, cephalexin, cefuroxime, cefotaxime, cefdinir, cefditoren, and ceftriaxone. Outcomes assessed were diverse, including clinical or microbiological success and time to defervescence or symptom resolution. Cephalosporins displayed effectiveness for the treatment of acute uncomplicated APN regardless of study design or the presence of a comparison group. No trials reported inferiority of clinical treatment outcomes compared with a fluoroquinolone or SMX-TMP. CONCLUSION: Cephalosporins may be viable treatment options for the management of uncomplicated APN.

Safety and efficacy of intravenous hydralazine and labetalol for the treatment of asymptomatic hypertension in hospitalised patients: A systematic review.

BACKGROUND: Current guidelines for the management of asymptomatic hypertension (HTN) in the inpatient setting recommend the use of oral antihypertensives. However, in clinical practice, intravenous (IV) antihypertensives are commonly utilised with little supporting evidence. The objective of this study was to evaluate literature examining the safety/efficacy of IV hydralazine and labetalol in hospitalised patients with non-emergent, asymptomatic HTN. METHODS: The PRISMA guidelines were utilised to structure the systematic review. A search strategy composed of drug-, inpatient- and HTN-related terms was conducted utilising PubMed, Embase and Scopus databases through May 2020. Full-text, English-language articles describing IV labetalol and/or hydralazine use for non-emergent HTN in an inpatient setting that focused on clinical outcomes (ie vitals, adverse effects, healthcare utilisation) were included. Identified studies were screened/extracted using DistillerSR by two reviewers at each stage, and studies were evaluated qualitatively for the presence of bias. RESULTS: From 3362 records identified in the search, a final set of 10 articles were identified. Four studies focused on labetalol (40%), five studies on hydralazine and labetalol (50%), and one study on hydralazine (10%). The included studies presented a variety of outcomes, but several trends were identified, including reduction in average blood pressure in eight (80%) studies, a risk of adverse effects in six (60%) and increased length of stay in one (10%). DISCUSSION: The studies identified in this review raise concerns regarding the safety of IV hydralazine and labetalol in non-emergent HTN. Despite relatively broad clinical experience with these drugs, experimental investigations regarding their utility are recommended.

Platelet Function Testing to Guide Cangrelor Dosing in Patients with Temporary Mechanical Circulatory Support or as a Bridge to Procedure.

Cangrelor is a rapid-acting, intravenous P2Y12 inhibitor that can be used in patients after percutaneous coronary intervention who require mechanical circulatory support or as a bridge to procedure. We retrospectively reviewed adult patients who received platelet function testing (PFT) with the VerifyNow P2Y12 assay while on cangrelor from March 2021 through November 2022. All patients were initiated on 0.75 mcg/kg/min of cangrelor with P2Y12 reaction unit (PRU) values collected 12-24 h after initiation. Cangrelor doses were adjusted per protocol to maintain PRU values of 85-208. A total of 42 patients were included. Thirty-eight patients (90.5%) required temporary mechanical circulatory support while on cangrelor, and 4 patients (9.5%) received cangrelor as a bridge to procedure. The median cangrelor maintenance dose was 0.5 (interquartile range [IQR]: 0.375-0.75) mcg/kg/min, and the median time in therapeutic range with a PRU value between 85 and 208 was 66.6% (IQR: 39.6%-100%). No patients experienced stent thrombosis. A composite major adverse cardiovascular event occurred in 4 patients (9.5%), and major bleeding occurred in 16 patients (38.1%). Compared to empiric cangrelor dosing of 0.75 mcg/kg/min, PFT-guided cangrelor dose adjustment was associated with a median drug cost savings of $1605.60 (IQR: $0-4281.56). Utilizing PFT with cangrelor may allow for lower, individualized dosing while preventing stent thrombosis.

The effect of potassium supplementation and concomitant medications on potassium homeostasis for hospitalized patients.

PURPOSE: Hospitalized patients receive potassium (K+) supplementation for hypokalemia, with clinicians often estimating a rise in serum K+ levels of 0.1 mEq/L per 10 mEq delivered. However, there is limited evidence to support this expectation. Patients also concomitantly take medications that may alter K+ levels, and it is not known to what degree these may impact interventions to correct K+ levels via supplementation. The objective of this study was to identify the impact of oral and/or intravenous K+ supplementation on serum K+ levels, including the influence of selected concomitant medications, in adult hospitalized patients. METHODS: A single-center, retrospective descriptive study of adult hospitalized patients receiving K+ supplementation at a tertiary hospital between 2021 and 2022 was conducted. Patients were included if they received at least one dose of potassium chloride while admitted to the general medicine ward. The primary outcome was the daily median change in serum K+, normalized per 10 mEq of supplementation administered. The secondary outcome was the impact of selected concomitant medication use on supplement-induced changes in serum K+. RESULTS: A total of 800 patients and 1,291 daily episodes of K+ supplementation were evaluated. The sample was approximately 53% women, was 78% white, and had a median age of 68 years. The overall daily median change in serum K+ level was 0.05 mEq/L per 10 mEq of supplementation delivered. Patients received a median of 40 mEq of supplementation per day, primarily via the oral route (80.6%). Among the concomitant medications assessed, loop diuretics significantly dampened the impact of K+ supplementation. CONCLUSION: Supplementation of K+ in non-critically ill hospitalized patients is variable and dependent on concomitant medication use.

Evaluating the evidence for sacubitril/valsartan across the continuum of heart failure.

Since initial publication of the PARADIGM-HF trial in 2014, sacubitril/valsartan has been investigated in various settings to establish optimal use, further expanding its indications in patients with heart failure (HF). Although numerous studies have been published, until recently these have primarily involved post hoc analyses from the PARADIGM-HF study itself with a consistent focus on use of sacubitril/valsartan in patients with HF with reduced ejection fraction (HFrEF). This has led to a gap in the literature regarding utility of sacubitril/valsartan in other HF subpopulations. The aim of this review is to provide a summary of recent clinical trials further expanding use and guideline recommendations for sacubitril/valsartan. The findings of 15 studies, including clinical trials and post hoc analyses, are summarized and describe the use of sacubitril/valsartan in additional HF subpopulations, such as HFrEF following hospitalization for acute decompensated HF and advanced HF, HF with preserved ejection fraction (HFpEF), and HF postmyocardial infarction. In addition, three studies investigating timing of initiation, dose titration regimens, and cost-effectiveness are examined. Select ongoing trials are also reviewed to demonstrate the continued commitment to further advance care of patients with HF. This comprehensive review serves as a resource for health care providers who pursue optimal utilization of sacubitril/valsartan in their respective clinical practices.

Gabapentin initiation in the inpatient setting: A characterization of prescribing.

PURPOSE: Gabapentin is a widely prescribed analgesic with increased popularity over recent years. Previous studies have characterized use of gabapentin in the outpatient setting, but minimal data exist for its initiation in the inpatient setting. The objective of this study was to characterize the prescribing patterns of gabapentin when it was initiated in the inpatient setting. METHODS: This was a retrospective cohort study of a random sample of adult patients who received new-start gabapentin during hospital admission. Patients for whom gabapentin was prescribed as a home medication, with one-time, on-call, or as-needed orders, or who died during hospital admission were excluded. The primary outcome was characterization of the gabapentin indication; secondary outcomes included the starting and discharge doses, the number of dose titrations, the rate of concomitant opioid prescribing, and pain clinic follow-up. Patients were stratified by surgical vs nonsurgical status. RESULTS: A total of 464 patients were included, 283 (61.0%) of whom were surgical and 181 (39.0%) of whom were nonsurgical. The cohort was 60% male with a mean (SD) age of 56 (18) years; surgical patients were younger and included more women. The most common indications for surgical patients were multimodal analgesia (161; 56.9%), postoperative pain (53; 18.7%), and neuropathic pain (26; 9.2%), while those for nonsurgical patients were neuropathic pain (72; 39.8%) and multimodal analgesia (53; 29.3%). The mean starting dose was similar between the subgroups (613 mg for surgical patients vs 560 mg for nonsurgical patients; P = 0.196). A total of 51.6% vs 81.8% of patients received gabapentin at discharge (P < 0.0001), while referral/follow-up to a pain clinic was minimal and similar between the subgroups (1.1% vs 3.9%; P = 0.210). CONCLUSION: Inpatients were commonly initiated on gabapentin for generalized indications, with approximately half discharged on gabapentin. Further studies are needed to assess the impact of this prescribing on chronic utilization.

Safety and efficacy of cefiderocol for off-label treatment indications: A systematic review.

PURPOSE: Cefiderocol is a siderophore cephalosporin recently approved by the United States Food and Drug Administration for the treatment of hospital- and ventilator-acquired bacterial pneumonia and complicated urinary tract infections. However, there is potential for cefiderocol utility for a variety of other infections. The purpose of this systematic review was to identify literature examining the safety and efficacy of cefiderocol for off-label indications. METHODS: The PRISMA guidelines were utilized for reporting. Databases searched included PubMed, Scopus, and Embase, from inception to September 2021. Manuscripts describing cefiderocol off-label use in clinical settings were included. Exclusion criteria were studies focused on labeled indications, animal studies, pharmacodynamic/pharmacokinetic studies, in vitro or laboratory studies, and manuscripts in languages other than English or Arabic. Each stage of review utilized two independent investigators, with conflicts resolved and critical appraisal performed. Data regarding presentation, clinical course, and infection characteristics were extracted and descriptively analyzed. RESULTS: The search identified a total of 985 records, narrowed to a final set of 27 studies. Among studies included were 18 (66.7%) case reports, 8 (29.6%) case series, and 1 (3.7%) phase 3 clinical trial. Cefiderocol was most frequently used off-label for bacteremia/sepsis with or without an identified source in 51 (67.1%) out of a total of 76 included patients. Among case series/reports with available data, 43 of 53 patients (81.1%) received combination antibiotic therapy. The most common pathogens identified included multi/extensively drug-resistant Pseudomonas aeruginosa and/or Acinetobacter baumannii. Various clinical end points were reported, while microbiological end points were reported in 18 (66.7%) studies. Cefiderocol-related side effects were uncommon and rarely use-limiting. CONCLUSIONS: This systematic review depicts relative clinical effectiveness of off-label cefiderocol, most commonly for P. aeruginosa and A. baumannii infections as combination antibiotic therapy. Further study is needed to elucidate the safety and efficacy of cefiderocol across an expanded set of patients and indications.

Xylazine poisoning: a systematic review.

PURPOSE: Xylazine is an alpha-2-adrenergic agonist used for its sedative and analgesic properties in veterinary medicine. While not approved by the Food and Drug Administration for use in humans, anecdotal evidence suggests that exposures in humans is on the rise. We sought to systematically review and synthesize the evidence on xylazine exposure in humans focusing on the clinical presentation, management, and outcomes. METHODS: We conducted a systematic review of the literature including PubMed, Embase, and Scopus from their inception to September 9, 2021. We searched abstracts from selected emergency medicine and toxicology conferences from 2011 through 2021. We included clinical reports of xylazine exposure in humans. We excluded animal studies, in vitro studies, laboratory studies, or articles in a language other than English. From each included article, we extracted subjective and objective data that focused on clinical presentation, management, and outcomes of patients exposed to xylazine. RESULTS: We evaluated a total of 1409 records, rendering a final set of 17 articles and 2 abstracts meeting inclusion criteria. We identified a total of 98 patients amongst reports ranging from 1979 to 2020 and across nine countries. The most common types of xylazine exposures reported were unintentional exposure and intentional misuse/abuse. Common symptoms on presentation included hypotension, bradycardia, drowsiness, lethargy, while apnea with intubation and death were less frequently reported. CONCLUSION: Human exposure to xylazine appears to be a rising concern within the prehospital and emergency medicine setting. Although a standardized treatment algorithm cannot be recommended at this time, further research is needed to improve the care of patients exposed to xylazine.

Problem-based learning case studies: Delivery of an educational method and perceptions at two schools of pharmacy in Italy.

BACKGROUND AND PURPOSE: Problem-based learning (PBL) case studies are not currently offered in the pharmacy school curriculum in Italy. This study sought to assess the perceptions of a PBL case study activity delivered at two pharmacy schools in Italy. EDUCATIONAL ACTIVITY AND SETTING: A total of 64 pharmacy students and three pharmacy faculty from Italy participated in the live PBL activity. They collaborated on teams with pharmacy students from the United States to discuss a patient case and prepare drug therapy recommendations. A cross-sectional survey was performed to assess the Italian participants' perceptions before and after partaking in the PBL activity. FINDINGS: Results from the survey utilizing a five-point Likert-type scale (1 = strongly disagree to 5 = strongly agree) demonstrated that students and faculty from both pharmacy schools in Italy perceived the value in applying information learned in PBL to their current or future practices (4.48 ± 0.79) and in collaborating with a team to improve patient care (4.66 ± 0.79). In addition, the vast majority (93%) of participants agreed or strongly agreed that they would be interested in continuing to participate in PBL in the future. SUMMARY: Students and faculty at two pharmacy schools in Italy found the delivery of a PBL exercise to be beneficial for their professional development. This may suggest an opportunity for pharmacy schools in Italy to add the PBL case-based teaching method into their curriculum.

Health-system implementation of a collaborative core curriculum for advanced pharmacy experiential education during the COVID-19 pandemic.

PURPOSE: A collaborative advanced pharmacy practice experience (APPE) education model established within a healthcare institution during the coronavirus disease 2019 (COVID-19) pandemic is described. SUMMARY: The COVID-19 pandemic caused a nationwide disruption of APPE pharmacy education. Healthcare institutions faced the challenge of educating APPE students while attempting to simultaneously de-densify work areas and reduce transmission risk for employees and patients. A pharmacist coordinator and pharmacist academic partners at a large teaching hospital created a collaborative common core curriculum model for resourceful implementation of APPE education. Healthcare network pharmacists, clinical pharmacist academic partners, and pharmacy residents delivered the curriculum to 35 pharmacy students over a 9-week time period. Main components of the curriculum included patient case discussions, topic discussions, journal club presentations, live continuing education (CE) webinars, and development of pharmacy technician CE programs. A majority of students reported positive experiences working with a variety of preceptors from different specialties (81%) and collaborating with students from other universities (62%). CONCLUSION: A health system can leverage institutional, network-wide, and academic partner resources to implement a collaborative APPE curriculum during challenging times such as those experienced during the COVID-19 pandemic.

Safety and Efficacy of Rivaroxaban and Apixaban in Patients with Increased Body Mass: a Systematic Review.

BACKGROUND AND OBJECTIVE: Rivaroxaban and apixaban are direct oral anticoagulants increasing in popularity as convenient alternatives to warfarin. However, current guidelines recommend against use in patients with a BMI > 40 kg/m2 or bodyweight > 120 kg unless drug-specific levels are measured, which may not be feasible across all clinical practices. Accordingly, the objective of this study was to broadly examine literature evaluating the clinical outcomes of rivaroxaban and/or apixaban in patients with increased body mass. METHODS: A systematic literature review (guided by PRISMA) was performed through January 27, 2021 using PubMed, Embase, and Scopus. Key search term clusters included drug and weight-related concepts (overweight/obese, body mass index [BMI], waist circumference). DistillerSR was utilized to review and process search results. Studies met inclusion if they analyzed the risk of bleeding and/or thrombosis in patients with increased body mass (i.e., via BMI or other criteria) receiving rivaroxaban or apixaban. Clinical guidelines, case reports/series, pharmacokinetic/dynamic analyses, and commentaries were excluded. Bias was examined qualitatively across studies. RESULTS: After duplicates were removed, the original search rendered 1822 abstracts and 200 full-texts for screening, ultimately providing a final set of 24 studies for qualitative review. Of these studies, 13 (54.2%) enabled comparisons between patients of increased versus normal body mass, while 11 (45.8%) reported outcomes only for patients of increased body mass. The working definition of 'increased body mass' varied amongst the studies, including 11 (45.8%) studies that utilized BMI, seven (29.2%) with a combination of BMI and body measurement, two (8.3%) that relied on body weight alone, and four (16.7%) that identified obesity-related ICD codes. All 13 comparative studies found similar or reduced rates of safety and efficacy outcomes with rivaroxaban and apixaban. CONCLUSION: The literature reports similar or lower bleeding and thrombotic risk for rivaroxaban and apixaban in patients of increased body mass compared to patients of normal body mass. Future prospective controlled studies are needed to further define guidelines for use in this population.