The Impact of Direct-Acting Antiviral Therapy on End-Stage Liver Disease Among Individuals with Chronic Hepatitis C and Substance Use Disorders.

BACKGROUND AND AIMS: Our aim was to evaluate the impact of direct-acting antivirals (DAAs) on decompensated cirrhosis (DCC) and HCC in patients with chronic HCV and substance use disorder (SUD) compared with those without an SUD. APPROACH AND RESULTS: This retrospective cohort study used the MarketScan database (2013-2018) to identify 29,228 patients with chronic HCV, where 22% (n = 6,385) had ≥1 SUD diagnosis. The inverse probability of treatment weighted multivariable Cox proportional hazard models were used to compare the risk of developing DCC and HCC. Among the those who were noncirrhotic, treatment reduced the DCC risk among SUD (adjusted hazard ratio [aHR] 0.13; 95% CI, 0.06-0.30) and non-SUD (aHR 0.11; 95% CI, 0.07-0.18), whereas the risk for HCC was not reduced for the SUD group (aHR 0.91; 95% CI, 0.33-2.48). For those with cirrhosis, compared with patients who were untreated, treatment reduced the HCC risk among SUD (aHR, 0.33; 95% CI, 0.13-0.88) and non-SUD (aHR, 0.40; 95% CI, 0.25-0.65), whereas the risk for DCC was not reduced for the SUD group (aHR, 0.64; 95% CI, 0.37-1.13). Among patients with cirrhosis who were untreated, the SUD group had a higher risk of DCC (aHR, 1.52; 95% CI, 1.03-2.24) and HCC (aHR, 1.69; 95% CI, 1.05-2.72) compared with non-SUD group. CONCLUSIONS: Among the HCV SUD group, DAA treatment reduced the risk of DCC but not HCC for those who were noncirrhotic, whereas DAA treatment reduced the risk of HCC but not DCC for those with cirrhosis. Among the nontreated, patients with an SUD had a significantly higher risk of DCC and HCC compared with those without an SUD. Thus, DAA treatment should be considered for all patients with HCV and an SUD while also addressing the SUD.

Brighter horizons: The necessity of concentrated sponsorship targeted toward minoritized student pharmacists.

Due to the effects of structural racism, disproportionately lower numbers of Black, Hispanic or LatinX, American Indian, and Alaska Native students pursue a career in pharmacy and successfully matriculate into the profession. Despite these disparities being present for many years, little progress has been achieved in diversifying the pharmacy profession, resulting in a persistent lack of diversity within pharmacy leadership across employers and pharmacy organizations. Consistent with recent recommendations for improving diversity in pharmacy, the PharmGradWishlist (PGWL) initiative was created as a way for practicing pharmacists and organizations to provide direct financial sponsorship to racially and ethnically minoritized trainees to offset costs incurred during training and during the transition from student to practicing pharmacist. Many of these costs, such as residency and fellowship application fees, job interview travel costs, board exam and licensing fees, and moving expenses, are not typically subsidized by federal student funding. Offsetting these costs is an important way to reduce barriers to entering the profession and postgraduate training, the latter of which may be particularly important in trainees' pursuit of academic and leadership positions in pharmacy. The initial development and advertisement of the initiative occurred through social media and the grassroots efforts of the PGWL team, a group of 10 volunteer pharmacists from across the country, and resulted in generous donations from a small proportion of practicing pharmacists nationwide. It is now time for the profession as a whole to embrace the role of direct sponsorship in improving diversity in the profession. We call upon pharmacists and pharmacy organizations to advocate for and participate in financial sponsorship of racially and ethnically minoritized trainees and pharmacists as a way to increase diversity and promote health equity.

The alteration of the gut microbiome by immunosuppressive agents used in solid organ transplantation.

INTRODUCTION: Studies have suggested that in addition to antimicrobials, some non-antibiotics may alter the gut microbiome. This systematic review sought to determine if there is an association between immunosuppressive agents used in recipients of solid organ transplants (SOT) and alterations in the gut microbiome. METHODS: English language PubMed and Scopus searches were conducted to identify relevant articles. Inclusion criteria were defined as pertaining to solid organ transplantation, immunosuppression, and the gut microbiome. Articles were excluded if they contained only genetic microbiota descriptions, narrative reviews of bacteria, or described bacteria as a pathogen for infections. PRISMA reporting was used to guide this literature review. RESULTS: A preliminary search identified 665 articles, of which 75 articles met the inclusion criteria, and 10 articles remained after application of exclusion criteria. Seventy-one percent of articles discussed calcineurin inhibitors, such as tacrolimus, 38% included mycophenolate mofetil, and 52% included steroids, such as prednisone. Some studies utilized a combination of immunosuppressants or had multiple study arms. Seventy percent of the articles indicated changes in quantities of anaerobic bacteria including Ruminococcaceae, Lachnospiraceae, Firmicutes, Bacteroides, and Clostridiales. Combinations of immunosuppressant agents were associated with an increase in colonization of Escherichia coli and Enterococcus sp. CONCLUSION: Some immunosuppressants are associated with changes in gut flora, but the impact on clinical outcomes is unknown. Robust clinical trials delineating the direct effect of immunosuppressants on the gut microbiome as well as the impact on clinical outcomes are warranted.

Doing More With Less: Review of Dolutegravir-Lamivudine, a Novel Single-Tablet Regimen for Antiretroviral-Naïve Adults With HIV-1 Infection.

OBJECTIVE: To review data on efficacy and safety of dolutegravir (DTG) and lamivudine (3TC) in treatment-naïve adults with HIV-1 infection. DATA SOURCES: Phase III clinical trials and review articles were identified through PubMed (1996 to March 2020) and ClinicalTrials.gov (2000 to May 2020) using the keywords dolutegravir, lamivudine, and HIV. STUDY SELECTION AND DATA EXTRACTION: Relevant clinical trials and review articles available in English evaluating efficacy and safety of DTG and 3TC were included. DATA SYNTHESIS: The once-daily, single-tablet regimen of DTG/3TC is the first dual antiretroviral therapy (ART) recommended for initial therapy in treatment-naïve adults with HIV-1 infection. DTG and 3TC were compared with a regimen of DTG and tenofovir disoproxil fumarate/emtricitabine in the GEMINI studies and demonstrated noninferiority for the primary end point of virological suppression at up to 96 weeks. No treatment-emergent resistance mutations were identified in a small group of participants who did not reach virological suppression. The regimen is well tolerated, and the most common adverse events reported in trials include headache, diarrhea, nausea, insomnia, and fatigue. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This dual-ART regimen is a favorable treatment option for ART-naïve patients with HIV-1 RNA <500 000 copies/mL, absence of hepatitis B virus, and no resistance to DTG or 3TC. Benefits of dual ART include reduction in treatment-related adverse events and toxicities, drug interactions, and cost. In addition, the once-daily, single-tablet formulation promotes adherence. CONCLUSIONS: DTG/3TC has demonstrated efficacy in maintaining virological suppression in ART-naïve patients at up to 96 weeks while minimizing treatment-related adverse events and toxicities.

Sofosbuvir/Velpatasvir/Voxilaprevir: A Pan-Genotypic Direct-Acting Antiviral Combination for Hepatitis C.

OBJECTIVES: To review the efficacy and safety of sofosbuvir/velpatasvir/voxilaprevir in the treatment of hepatitis C virus (HCV) infection. DATA SOURCES: A literature search through PubMed was conducted (August 2010 to August 2017) using the terms GS-9857, voxilaprevir, and NS3/4A protease inhibitor. STUDY SELECTION/DATA EXTRACTION: Studies of sofosbuvir/velpatasvir/voxilaprevir were identified. DATA SYNTHESIS: Sofosbuvir/velpatasvir/voxilaprevir is indicated for adult patients with chronic HCV without cirrhosis or with compensated cirrhosis who have (1) genotype 1 through 6 and have previously been treated with an NS5A inhibitor or (2) genotype 1a or 3 and have previously been treated with sofosbuvir without an NS5A inhibitor. POLARIS-1 demonstrated that sofosbuvir/velpatasvir/voxilaprevir for 12 weeks was highly effective in patients with HCV genotype 1 through 6 who had prior exposure to an NS5A inhibitor. POLARIS-2 failed to demonstrate that sofosbuvir/velpatasvir/voxilaprevir for 8 weeks was noninferior to sofosbuvir/velpatasvir for 12 weeks in patients with HCV genotype 1 through 6 who had no prior exposure to direct-acting antivirals (DAAs). POLARIS-3 demonstrated that sofosbuvir/velpatasvir/voxilaprevir for 8 weeks was as effective as sofosbuvir/velpatasvir for 12 weeks in patients with HCV genotype 3 and compensated cirrhosis who had no prior exposure to DAAs. POLARIS-4 demonstrated that sofosbuvir/velpatasvir/voxilaprevir was as effective as sofosbuvir/velpatasvir for 12 weeks in patients with HCV genotype 1 through 3 who had prior exposure to DAAs but not an NS5A inhibitor. The most common adverse reactions were headache, fatigue, diarrhea, and nausea. CONCLUSIONS: Sofosbuvir/velpatasvir/voxilaprevir is safe and effective to treat HCV in patients who have previously been treated with DAAs.

Learning Through Experience: Analyzing the Impact of Short Study Abroad Programs from the Students' Own Words.

OBJECTIVE: The purpose of this study was to determine what students participating in short study abroad program (SSAP) elective courses learned during their experiences and if they satisfied the course learning objectives. METHODS: University of Florida College of Pharmacy students who participated in an SSAP to Scandinavia in the years 2014, 2016, 2017, and 2018 wrote digital journals describing their experiences. This study used inductive and deductive thematic analysis to analyze the journals and identify codes and themes. RESULTS: Four cohorts with a total of 39 student journals were analyzed leading to 11 themes being identified. Example themes included Differences in Pharmacy Practice, Differences in Pharmacy Law/Processes, Differences in Pharmacy Education/Training, and History/Culture. These themes were then mapped to the course objectives, and all course objectives were deemed to be fulfilled. CONCLUSION: Students participating in one College's SSAPs over 4 years through their own words demonstrated a better understanding of health care, pharmacy, and culture as it exists in one or more foreign countries and were able to meet the course objectives.

A review of evidence, antimicrobial stability, and feasibility considerations for OPAT continuous infusion.

Outpatient parenteral antimicrobial therapy (OPAT) has been widely used in clinical practice for many decades because of its associated cost savings, reductions in inpatient hospital days, and decreases in hospital-associated infections. Despite this long history, evolving practice patterns and new drug delivery devices continue to present challenges as well as opportunities for clinicians when designing appropriate outpatient antimicrobial regimens. One such change is the increasing use of extended and continuous infusion (CI) of antimicrobials to optimize the achievement of pharmacokinetic and pharmacodynamic targets. Elastomeric devices are also becoming increasingly popular in OPAT, including for the delivery of CI. In this article, we review the clinical evidence for CI in OPAT, as well as practical considerations of patient preferences, cost, and antimicrobial stability.

Contemporary Pharmacotherapies for Nontuberculosis Mycobacterial Infections: A Narrative Review.

Nontuberculous mycobacteria (NTM) are a group of atypical bacteria that may cause a spectrum of clinical manifestations, including pulmonary, musculoskeletal, skin and soft tissue, and cardiac infections. Antimycobacterial medication regimens for NTM infections require multiple agents with prolonged treatment courses and are often associated with poor tolerance in patients and suboptimal clinical outcomes. This review summarizes NTM pharmacotherapy, including treatment concepts, preferred medication regimens according to NTM species and site of infection, and emerging treatment methods for difficult-to-treat species.

Guidance for Qualitative Research Manuscripts in Pharmacy Education.

The goal of this Best Practice Review is to support researchers in successfully preparing and publishing qualitative research in pharmacy education. Standard practice from the literature and journals' guidance from related fields were reviewed, and recommendations and resources applicable to qualitative research in pharmacy education were compiled for researchers planning to conduct and publish qualitative research. This review provides recommendations, not requirements, for publication in the Journal and is intended to be a guide, especially for authors and reviewers relatively new to the field of qualitative research. Additionally, researchers planning to publish their qualitative research are advised to review available best practices and standards, such as the Consolidated Criteria for Reporting Qualitative Research checklist and the Standards for Reporting Qualitative Research. Given the diverse methodology of qualitative research, it is important for authors to provide sufficient details and justifications of selected methods for transparency and to report collected results in a manner that allows reviewers and readers to adequately assess the validity of their study and the applicability of the findings.

A Bundle of the Top 10 OPAT Publications in 2022.

Outpatient parenteral antimicrobial therapy (OPAT) has become more common in clinical settings. Correspondingly, OPAT-related publications have also increased; the objective of this article was to summarize clinically meaningful OPAT-related publications in 2022. Seventy-five articles were initially identified, with 54 being scored. The top 20 OPAT articles published in 2022 were reviewed by a group of multidisciplinary OPAT clinicians. This article provides a summary of the "top 10" OPAT publications of 2022.

Academic Activism: An Avenue to Action.

Until now, the term "advocacy" in pharmacy education and practice has focused on advocating for the advancement of the pharmacy profession or patient advocacy. With the 2022 Curricular Outcomes and Entrustable Professional Activities publication, the focus of advocacy has broadened to include advocacy for other causes that impact the health of patients. This commentary will highlight 3 pharmacy-focused organizations advocating for social issues impacting the health of patients as well as encourage members of the Academy to continue to expand personal social advocacy efforts.

Does the Academy Have Trust Issues?

The increasing levels of workplace stress caused by the COVID-19 pandemic has caused some members of the Academy to leave their jobs, in part due to levels of distrust between employees and their supervisors. In order to rebuild trust in the Academy, we must first know what the elements of trust are: boundaries, reliability, accountability, vault, integrity, nonjudgement, and generosity. Focusing on generosity, believing that everyone is doing the best that they can, is a first step toward rebuilding trust with students, staff members, faculty members, and members of administration.

A Bundle of the Top 10 OPAT Publications in 2021.

As outpatient parenteral antimicrobial therapy (OPAT) becomes more common, it may be difficult to stay current with recent related publications. A group of multidisciplinary OPAT clinicians reviewed and ranked all OPAT publications published in 2021. This article provides a high-level summary of the OPAT manuscripts that were voted the "top 10" publications of 2021.

Pharmacy student self-assessment of strength of residency candidacy compared to clinical faculty.

INTRODUCTION: The purpose of this study was to compare student and faculty perceptions of strength of residency candidacy and to identify student preferences and perceptions that influence the process of being selected by a residency program beyond standard application materials. METHODS: A 31-item questionnaire was administered to third-year and fourth-year pharmacy students to collect information regarding factors deemed important for successful residency program candidacy. Global assessment of strength of residency candidacy was self-rated by students and a group of clinical faculty blinded to student responses. Interrater reliability for student-to-faculty and faculty-to-faculty perceptions of strength of residency candidacy was determined. RESULTS: Students generally reported good academic metrics and participation in a wide variety of scholarly activities deemed important in attaining a residency position. Students rated overall strength of residency candidacy as "above average" (n = 54, 37.2%), "average" (n = 60, 41.4%), and "below average" (n = 31, 21.3%), and self-perception increased with matriculation. Student self-assessment of strength of residency candidacy compared to faculty assessment showed poor agreement (mean [SD] kappa = 0.27 [0.08]). Faculty concordance in assessment of strength of residency candidacy was moderate (α = 0.55). CONCLUSIONS: Concordance in self-assessment of strength of residency candidacy of students compared to faculty was poor. In contrast, agreement among faculty was moderate with generally lower ratings compared to student self-rating, suggesting that students are overconfident in this regard. These findings support residency preparedness training in pharmacy curricula which should include formal assessment of strength of residency candidacy to identify gaps.

Stop tempting your students to cheat.

INTRODUCTION: Maintaining academic integrity is paramount for educators, and even more so for health science educators, where the health of patients is potentially at stake. However, as more content and assessments are pushed into an online forum, more hurdles are being placed in the path of keeping everyone honest without requiring significant financial resources for online proctoring of every assessment. This commentary explores the suggestion of re-evaluating the need for graded course assessments as a way to uphold academic integrity. COMMENTARY: One reason pharmacy students participate in academic dishonesty is the nature of the assessments employed, with students more likely to cheat on higher stakes assessments (i.e. graded assessments). There is an established difference between learning and performance, where a learning environment encourages mistakes and graded assessments lead more to performance. While the use of retrieval practice can facilitate learning, this can be done with ungraded formative assessments without decline in summative assessment scores. IMPLICATIONS: Transitioning formative assessments from graded to ungraded while keeping them closed-book and at an appropriate level of difficulty allows for learners to make mistakes, utilize retrieval practice, and ultimately, learn. This transition also allows the pharmacy program to spend their financial resources on proctoring summative assessments only. Making this change strikes a balance between learning and performance while still making strides to maintain academic integrity.

Impact of Supplemental Material Use on Student Metacognitive Monitoring and Calibration.

Objective. To determine whether third year Doctor of Pharmacy students' self-reported use of optional supplemental material impacted their ability to accurately predict their performance on a low-stakes assessment.Methods. An instructor created optional supplemental material in the form of an online quiz. Students were asked to report whether they used the supplemental material and to predict and postdict their performance on an in-class assessment. The relative accuracy of the predictions and postdictions as well as the assessment grades and overall course grades were compared between students who reported using the supplemental material and those who reported not using the supplemental material.Results. More than half of the students (60%) reported using the supplemental material. Most students underpredicted their performance on the in-class assessment, but there was no difference in the accuracy of predictions based on supplemental material use or non-use (-1.2 vs -1.0) or on the postdictions (-1.3 vs. -1.0). Students who reported using the supplemental material performed better on both the low-stakes assessment (7.7 vs 7.2 out of 10) and overall in the course (87.0% vs 84.9%).Conclusion. Pharmacy students' self-reported use of optional supplemental material does not appear to impact their ability to accurately predict their performance on a low-stakes assessment.

Recent Updates in Antimicrobial Stewardship in Outpatient Parenteral Antimicrobial Therapy.

PURPOSE OF REVIEW: Antimicrobial stewardship within acute care is common and has been expanding to outpatient areas. Some inpatient antimicrobial stewardship tactics apply to outpatient parenteral antimicrobial therapy (OPAT) and complex outpatient antimicrobial therapy (COpAT) management, but differences do exist. RECENT FINDINGS: OPAT/COpAT is a growing area of practice and research with its own unique considerations for antimicrobial stewardship. Potential ideas for antimicrobial stewardship in the OPAT/COpAT setting include redesigning the regimen to COpAT instead of OPAT, ensuring the use of the shortest effective duration of antimicrobial therapy; using antimicrobials dosed less frequently, such as long-acting glycopeptides; optimizing antimicrobial susceptibility testing reporting for common OPAT/COpAT drugs; and establishing routine laboratory and safety monitoring. Future consensus is needed to determine validated OPAT program metrics and outcomes. SUMMARY: As more focus is placed on outpatient antimicrobial stewardship, clinicians practicing in OPAT should publish more data regarding OPAT program methods and outcomes as they relate to antimicrobial stewardship. These can involve patient clinical outcomes, OPAT readmission rates, OPAT therapy completion, and central line-related complications.

The use of all-oral direct-acting antivirals in hepatitis C virus-infected patients with substance use disorders.

BACKGROUND: There is evidence that barriers exist for the initiation of direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) for those with substance use disorders (SUDs). However, real world clinical evidence of DAA treatment initiation following receipt of a prescription and continuation among those with SUDs and HCV is lacking. OBJECTIVES: To (1) compare HCV treatment initiation (prescription fill) rates and early discontinuation rates between HCV-infected patients with and without SUDs in the DAA era, and (2) identify patient-level factors associated with HCV treatment initiation and early discontinuation in patients with SUDs. METHODS: A retrospective cohort analysis of the MarketScan databases (January 2012-December 2018) was conducted for newly diagnosed treatment naïve HCV-infected patients (age ≥ 18) with and without SUDs. We used multivariable Cox regression to estimate adjusted hazard ratios (aHRs) with 95% confidence intervals of treatment initiation and early discontinuation in those with SUDs versus those without. RESULTS: We identified a total of 29,228 newly diagnosed HCV-infected patients (6,385 with SUDs and 22,843 without SUDs). Overall, DAA treatment initiation for patients with SUDs was significantly lower than that for those without SUDs (24% vs 34%; P < 0.01). After adjusting for demographics and clinical characteristics, patients with SUDs were less likely to initiate DAA treatments than those without SUDs (aHR, 0.87 [0.82-0.92]). There was no difference in discontinuation of DAA treatment between those with and without SUDs (4% vs 3%: aHR, 1.13 [0.81-1.60]). Among patients with SUDs (n = 6,385), lower rates of initiating DAA treatment was associated with younger age, and comorbidities including alcoholic liver disease (ALD; aHR, 0.44 [0.33-0.57), chronic kidney disease (CKD) (aHR, 0.52 [0.36-0.75]), and hepatitis B virus (HBV; aHR, 0.64 [0.44-0.92]). DAA treatment discontinuation was associated with younger age, ribavirin (RBV) therapy (aHR, 3.78 [2.21-6.47]), and cirrhosis diagnosis (aHR, 2.42 [1.21-4.84]) but not SUD treatment (aHR, 0.68 [0.34-1.34]). CONCLUSIONS: HCV-infected patients with SUDs had significantly lower treatment initiation rates, especially in young females and those with ALD, CKD, and HBV. No difference was found in DAA discontinuation. However, younger patients with RBV treatment and/or cirrhosis were more likely to stop treatment. Interventions directed towards these groups are needed to enhance DAA initiation and treatment maintenance among HCV-infected patients with SUDs. DISCLOSURES: Research reported in this publication was supported in part by the National Institute on Drug Abuse of the National Institutes of Health under award number K01DA045618 (to Park). The other authors have nothing to disclose that may present a potential conflict of interest.

Profile of sofosbuvir/velpatasvir/voxilaprevir in the treatment of hepatitis C.

The treatment of chronic hepatitis C has been revolutionized with the introduction of direct-acting antivirals (DAAs). However, some patients are not cured with first-line treatment. Sofosbuvir/velpatasvir/voxilaprevir is a fixed-dose combination of a polymerase inhibitor, an NS5A inhibitor, and a protease inhibitor with activity against strains of the hepatitis C virus that show resistance to other first-line antiviral regimens. Sofosbuvir/velpatasvir/voxilaprevir has been studied in four Phase III randomized trials: POLARIS-1, -2, -3, and -4, which enrolled both treatment naïve and experienced patients with and without compensated cirrhosis. In these trials, at least 95% of patients treated with sofosbuvir/velpatasvir/voxilaprevir achieved sustained virological response (SVR). This includes favorable treatment outcomes in patients who had previously failed a regimen containing sofosbuvir or an NS5A inhibitor. Patient-reported outcomes also improved during and after treatment with sofosbuvir/velpatasvir/voxilaprevir. Treatment with sofosbuvir/velpatasvir/voxilaprevir is well tolerated, with the most commonly reported adverse events being headache, fatigue, diarrhea, and nausea. The approval of sofosbuvir/velpatasvir/voxilaprevir allows a treatment option for patients who have failed treatment with certain DAA regimens.