A Review of Concordance and Quality in Clinical Guidelines for Hormonal Contraceptives to Mitigate Drug-Drug Interactions in Women With Epilepsy.

PURPOSE: Concomitant use of hormonal contraceptive agents (HCAs) and enzyme-inducting antiepileptic drugs (EIAEDs) may lead to contraceptive failure and unintended pregnancy. This review identified and evaluated concordance and quality of clinical treatment guidelines related to the use of HCAs in women with epilepsy (WWE) receiving EIAEDs. METHODS: Relevant clinical guidelines were identified across four databases and were independently evaluated for quality utilizing the AGREE-II protocol instrument. Quality in this context is defined as the rigor and transparency of the methodologies used to develop the guideline. Guidelines were further assessed in terms of concordance and discordance with the latest body of knowledge concerning the use of hormonal contraception in the presence of EIAEDs. RESULTS: A total of n = 5 guidelines were retrieved and evaluated. Overall guideline scores ranged from 17% to 92%, while individual domain scores ranged from 0% to 100%. Contraceptive guidelines consistently recommended the use of intrauterine systems and long-acting injectables in the presence of EIAEDs, recommended against the use of oral, transdermal, and vaginal ring contraceptives, and differed regarding recommendations related to implants. Guidelines agreed regarding recommendations that women treated with EIAEDs should receive intrauterine systems and long-acting injectables; however, the suggested frequency of administration of injectable contraceptives differed. The use of intrauterine systems in this population is supported by evidence, but there is uncertainty surrounding the use of long-acting injectables and contraceptive implants. CONCLUSIONS: To mitigate the risk of unintended pregnancy and its consequences, recommendations related to implants and long-acting injectable contraceptives should be evidence-based.

PSCA-CAR T cell therapy in metastatic castration-resistant prostate cancer: a phase 1 trial.

Despite recent therapeutic advances, metastatic castration-resistant prostate cancer (mCRPC) remains lethal. Chimeric antigen receptor (CAR) T cell therapies have demonstrated durable remissions in hematological malignancies. We report results from a phase 1, first-in-human study of prostate stem cell antigen (PSCA)-directed CAR T cells in men with mCRPC. The starting dose level (DL) was 100 million (M) CAR T cells without lymphodepletion (LD), followed by incorporation of LD. The primary end points were safety and dose-limiting toxicities (DLTs). No DLTs were observed at DL1, with a DLT of grade 3 cystitis encountered at DL2, resulting in addition of a new cohort using a reduced LD regimen + 100 M CAR T cells (DL3). No DLTs were observed in DL3. Cytokine release syndrome of grade 1 or 2 occurred in 5 of 14 treated patients. Prostate-specific antigen declines (>30%) occurred in 4 of 14 patients, as well as radiographic improvements. Dynamic changes indicating activation of peripheral blood endogenous and CAR T cell subsets, TCR repertoire diversity and changes in the tumor immune microenvironment were observed in a subset of patients. Limited persistence of CAR T cells was observed beyond 28 days post-infusion. These results support future clinical studies to optimize dosing and combination strategies to improve durable therapeutic outcomes. ClinicalTrials.gov identifier NCT03873805 .

Facilitating rural access to quality health information through Little Free Libraries.

Background: In 2020 the Health Science Center Libraries (HSCL) at the University of Florida collaborated with the Okeechobee County Public library (OCPL) on their plan to install Little Free Libraries (LFLs) within their community. It was agreed that the HSCL would provide consumer health-related materials for the Little Free Libraries and training with the goal of improving health literacy, precision medicine, and increasing rural access to consumer health materials and services. Case Presentation: Using census data, the County Health Improvement Plan, and OCPL circulation data the team identified minority population groups, potential accessibility issues, and local consumer health information needs and barriers to select appropriate resources. Additionally, partnerships were created with the local Health Department, Parks and Recreation services, the Rotary Club, and other local organizations to make the project a success. A total of 424 books were selected for the LFLs and 40 unique online resources were selected, printed, and shipped to OCPL to be used during LFL reference sessions. Technology was purchased to assist OCPL with their planned community health reference outreach sessions. HSCL created and provided online training on facilitating consumer health outreach, conducting health information reference services, and promoting community engagement for OCPL. Discussion: LFLs have become an important resource for lower-income rural families in Okeechobee. There are 7 LFLs in Okeechobee County, with a goal of eventually establishing 15 total to provide vital health resources and books. Over 2,456 items have been circulated among the 7 LFLs since May 2020. Overall, the project has been successful with positive feedback received from the community and with OCPL planning to continue to expand the project.

Antigen-dependent IL-12 signaling in CAR T cells promotes regional to systemic disease targeting.

Chimeric antigen receptor (CAR) T cell therapeutic responses are hampered by limited T cell trafficking, persistence, and durable anti-tumor activity in solid tumors. However, these challenges can be largely overcome by relatively unconstrained synthetic engineering strategies. Here, we describe CAR T cells targeting tumor-associated glycoprotein-72 (TAG72), utilizing the CD28 transmembrane domain upstream of the 4-1BB co-stimulatory domain as a driver of potent anti-tumor activity and IFNγ secretion. CAR T cell-mediated IFNγ production facilitated by IL-12 signaling is required for tumor cell killing, which is recapitulated by engineering an optimized membrane-bound IL-12 (mbIL12) molecule in CAR T cells. These T cells show improved antigen-dependent T cell proliferation and recursive tumor cell killing in vitro, with robust in vivo efficacy in human ovarian cancer xenograft models. Locoregional administration of mbIL12-engineered CAR T cells promotes durable anti-tumor responses against both regional and systemic disease in mice. Safety and efficacy of mbIL12-engineered CAR T cells is demonstrated using an immunocompetent mouse model, with beneficial effects on the immunosuppressive tumor microenvironment. Collectively, our study features a clinically-applicable strategy to improve the efficacy of locoregionally-delivered CAR T cells engineered with antigen-dependent immune-modulating cytokines in targeting regional and systemic disease.

Integrating diversity, equity, and inclusion principles into instruction: Case studies from the University of Florida's Health Science Center Libraries.

Librarians at the University of Florida Health Science Center Libraries have begun to intentionally incorporate diversity, equity, and inclusion (DEI) principles into teaching during design, implementation, and evaluation. This article uses four case studies to provide an overview of the librarians' approaches to inclusive teaching (1) an annual workshop for Physical Therapy students on the intersection between DEI, health literacy, and patient education; (2) a librarian-taught one-credit course for public health students, which was revised to create a more inviting syllabus and integrate elements of universal design; (3) an annual project for first year medical students highlighting health disparities and community resources; and (4) piloting the application of critical librarianship principles in library standalone sessions on database searching and reference management. Suggestions are provided for other librarians who are interested in developing a culture of inclusive teaching in their own libraries.

Telerehabilitation service impact on physical function and adherence compared to face-to-face rehabilitation in patients with stroke: A systematic review and meta-analysis.

OBJECTIVES: The purposes of this systematic review and meta-analysis were to (1) appraise the available evidence of telerehabilitation program effects on functional outcomes, adherence, and patient satisfaction compared to face-to-face programs after stroke; and (2) provide direction for future outcome measure selection and development for clinical research purposes. TYPE: Systematic review and meta analysis of randomized controlled trials. LITERATURE SURVEY: MEDLINE, CINAHL, Embase, Scopus, Proquest Theses and Dissertations, Physiotherapy Evidence Database (PEDro), and Clinicaltrials.gov were searched for studies published in English from 1964 to the end of April 2022. METHODOLOGY: A total of 6450 studies were identified, 13 were included in the systematic review, and 10 with at least 3 reported similar outcomes were included the meta-analysis. Methodological quality of results was evaluated using the PEDro checklist. SYNTHESIS: Telerehabilitation demonstrated equivalency in outcomes across several domains and was favored compared to conventional face to face alone or when paired with semisupervised physical therapy on Wolf Motor Function performance score (mean difference [MD] 1.69 points, 95% confidence interval [CI] 0.21-3.17) and time score (MD 2.07 seconds, 95% CI -4.04 to -0.10, Q test = 30.27, p < .001, I2 = 93%), and Functional Mobility Assessment in the upper extremities (MD 3.32 points, 95% CI 0.90-5.74, Q test = 5.60, p = .23, I2 = 29% alone or when paired with semisupervised physical therapy). The Barthel Index participation measures of function demonstrated improvement (MD 4.18 points, 95% CI, 1.79-6.57, Q test = 3.56, p = .31, I2 = 16%). Over half of summarized study ratings were determined to be of good to excellent quality (PEDro score 6.6 ± 2.3 points). Adherence varied in available studies from 75%-100%. Satisfaction levels of telerehabilitation were highly variable. CONCLUSIONS: Telerehabilitation can improve functional outcomes and promote therapy adherence after stroke. Therapy protocols and functional assessments need substantial refinement and standardization to improve interpretation and clinical outcomes.

Deprescribing Strategies for Opioids and Benzodiazepines with Emphasis on Concurrent Use: A Scoping Review.

While the Food and Drug Administration's black-box warnings caution against concurrent opioid and benzodiazepine (OPI-BZD) use, there is little guidance on how to deprescribe these medications. This scoping review analyzes the available opioid and/or benzodiazepine deprescribing strategies from the PubMed, EMBASE, Web of Science, Scopus, and Cochrane Library databases (01/1995-08/2020) and the gray literature. We identified 39 original research studies (opioids: n = 5, benzodiazepines: n = 31, concurrent use: n = 3) and 26 guidelines (opioids: n = 16, benzodiazepines: n = 11, concurrent use: n = 0). Among the three studies deprescribing concurrent use (success rates of 21-100%), two evaluated a 3-week rehabilitation program, and one assessed a 24-week primary care intervention for veterans. Initial opioid dose deprescribing rates ranged from (1) 10-20%/weekday followed by 2.5-10%/weekday over three weeks to (2) 10-25%/1-4 weeks. Initial benzodiazepine dose deprescribing rates ranged from (1) patient-specific reductions over three weeks to (2) 50% dose reduction for 2-4 weeks, followed by 2-8 weeks of dose maintenance and then a 25% reduction biweekly. Among the 26 guidelines identified, 22 highlighted the risks of co-prescribing OPI-BZD, and 4 provided conflicting recommendations on the OPI-BZD deprescribing sequence. Thirty-five states' websites provided resources for opioid deprescription and three states' websites had benzodiazepine deprescribing recommendations. Further studies are needed to better guide OPI-BZD deprescription.

Antigen-dependent IL-12 signaling in CAR T cells promotes regional to systemic disease targeting.

Chimeric antigen receptor (CAR) T cell therapeutic responses are hampered by limited T cell trafficking, persistence, and durable anti-tumor activity in solid tumor microenvironments. However, these challenges can be largely overcome by relatively unconstrained synthetic engineering strategies, which are being harnessed to improve solid tumor CAR T cell therapies. Here, we describe fully optimized CAR T cells targeting tumor-associated glycoprotein-72 (TAG72) for the treatment of solid tumors, identifying the CD28 transmembrane domain upstream of the 4-1BB co-stimulatory domain as a driver of potent anti-tumor activity and IFNγ secretion. These findings have culminated into a phase 1 trial evaluating safety, feasibility, and bioactivity of TAG72-CAR T cells for the treatment of patients with advanced ovarian cancer ( NCT05225363 ). Preclinically, we found that CAR T cell-mediated IFNγ production facilitated by IL-12 signaling was required for tumor cell killing, which was recapitulated by expressing an optimized membrane-bound IL-12 (mbIL12) molecule on CAR T cells. Critically, mbIL12 cell surface expression and downstream signaling was induced and sustained only following CAR T cell activation. CAR T cells with mbIL12 demonstrated improved antigen-dependent T cell proliferation and potent cytotoxicity in recursive tumor cell killing assays in vitro and showed robust in vivo anti-tumor efficacy in human xenograft models of ovarian cancer peritoneal metastasis. Further, locoregional administration of TAG72-CAR T cells with antigen-dependent IL-12 signaling promoted durable anti-tumor responses against both regional and systemic disease in mice and was associated with improved systemic T cell persistence. Our study features a clinically-applicable strategy to improve the overall efficacy of locoregionally-delivered CAR T cells engineered with antigen-dependent immune-modulating cytokines in targeting both regional and systemic disease.

Predictive Modeling for Suicide-Related Outcomes and Risk Factors among Patients with Pain Conditions: A Systematic Review.

Suicide is a leading cause of death in the US. Patients with pain conditions have higher suicidal risks. In a systematic review searching observational studies from multiple sources (e.g., MEDLINE) from 1 January 2000-12 September 2020, we evaluated existing suicide prediction models' (SPMs) performance and identified risk factors and their derived data sources among patients with pain conditions. The suicide-related outcomes included suicidal ideation, suicide attempts, suicide deaths, and suicide behaviors. Among the 87 studies included (with 8 SPM studies), 107 suicide risk factors (grouped into 27 categories) were identified. The most frequently occurring risk factor category was depression and their severity (33%). Approximately 20% of the risk factor categories would require identification from data sources beyond structured data (e.g., clinical notes). For 8 SPM studies (only 2 performing validation), the reported prediction metrics/performance varied: C-statistics (n = 3 studies) ranged 0.67-0.84, overall accuracy(n = 5): 0.78-0.96, sensitivity(n = 2): 0.65-0.91, and positive predictive values(n = 3): 0.01-0.43. Using the modified Quality in Prognosis Studies tool to assess the risk of biases, four SPM studies had moderate-to-high risk of biases. This systematic review identified a comprehensive list of risk factors that may improve predicting suicidal risks for patients with pain conditions. Future studies need to examine reasons for performance variations and SPM's clinical utility.

Corrigendum: Hyperammonemia After Lung Transplantation: Systematic Review and a Mini Case Series.

[This corrects the article DOI: 10.3389/ti.2022.10433.].

Developing a Culture of Inclusivity through a Library Diversity, Equity, and Inclusion Team. Part 2: Team Activities.

The Health Science Center Libraries at the University of Florida formalized, focused, and expanded their diversity, equity, and inclusion-related activities by creating a Diversity, Equity, and Inclusion Team. This paper describes the activities of the Team from 2018 to 2020, including efforts related to assessment, programming, promotion, and space. Future plans are also discussed. The Team activities described here can serve as models for other health science libraries with a commitment to diversity, equity, and inclusion.

Hyperammonemia After Lung Transplantation: Systematic Review and a Mini Case Series.

Background: Hyperammonemia after lung transplantation (HALT) is a rare but serious complication with high mortality. This systematic review delineates possible etiologies of HALT and highlights successful strategies used to manage this fatal complication. Methods: Seven biomedical databases and grey literature sources were searched using keywords relevant to hyperammonemia and lung transplantation for publications between 1995 and 2020. Additionally, we retrospectively analyzed HALT cases managed at our institution between January 2016 and August 2018. Results: The systematic review resulted in 18 studies with 40 individual cases. The mean peak ammonia level was 769 µmol/L at a mean of 14.1 days post-transplant. The mortality due to HALT was 57.5%. In our cohort of 120 lung transplants performed, four cases of HALT were identified. The mean peak ammonia level was 180.5 µmol/L at a mean of 11 days after transplantation. HALT in all four patients was successfully treated using a multimodal approach with an overall mortality of 25%. Conclusion: The incidence of HALT (3.3%) in our institution is comparable to prior reports. Nonetheless, ammonia levels in our cohort were not as high as previously reported and peaked earlier. We attributed these significant differences to early recognition and prompt institution of multimodal treatment approach.

Trends in the Management of Headache Disorders in US Emergency Departments: Analysis of 2007-2018 National Hospital Ambulatory Medical Care Survey Data.

We examined trends in management of headache disorders in United States (US) emergency department (ED) visits. We conducted a cross-sectional study using 2007−2018 National Hospital Ambulatory Medical Care Survey data. We included adult patient visits (≥18 years) with a primary ED discharge diagnosis of headache. We classified headache medications by pharmacological group: opioids, butalbital, ergot alkaloids/triptans, acetaminophen/nonsteroidal anti-inflammatory drugs (NSAIDs), antiemetics, diphenhydramine, corticosteroids, and intravenous fluids. To obtain reliable estimates, we aggregated data into three time periods: 2007−2010, 2011−2014, and 2015−2018. Using multivariable logistic regression, we examined medication, neuroimaging, and outpatient referral trends, separately. Among headache-related ED visits, opioid use decreased from 54.1% in 2007−2010 to 28.3% in 2015−2018 (Ptrend < 0.001). There were statistically significant increasing trends in acetaminophen/NSAIDs, diphenhydramine, and corticosteroids use (all Ptrend < 0.001). Changes in butalbital (6.4%), ergot alkaloid/triptan (4.7%), antiemetic (59.2% in 2015−2018), and neuroimaging (37.3%) use over time were insignificant. Headache-related ED visits with outpatient referral for follow-up increased slightly from 73.3% in 2007−2010 to 79.7% in 2015−2018 (Ptrend = 0.02). Reflecting evidence-based guideline recommendations for headache management, opioid use substantially decreased from 2007 to 2018 among US headache-related ED visits. Future studies are warranted to identify strategies to promote evidence-based treatment for headaches (e.g., sumatriptan, dexamethasone) and appropriate outpatient referral and reduce unnecessary neuroimaging orders in EDs.

Dosing profiles of concurrent opioid and benzodiazepine use associated with overdose risk among US Medicare beneficiaries: group-based multi-trajectory models.

BACKGROUND AND AIMS: One-third of opioid (OPI) overdose deaths involve concurrent benzodiazepine (BZD) use. Little is known about concurrent opioid and benzodiazepine use (OPI-BZD) most associated with overdose risk. We aimed to examine associations between OPI-BZD dose and duration trajectories, and subsequent OPI or BZD overdose in US Medicare. DESIGN: Retrospective cohort study. SETTING: US Medicare. PARTICIPANTS: Using a 5% national Medicare data sample (2013-16) of fee-for-service beneficiaries without cancer initiating OPI prescriptions, we identified 37 879 beneficiaries (age ≥ 65 = 59.3%, female = 71.9%, white = 87.6%, having OPI overdose = 0.3%). MEASUREMENTS: During the 6 months following OPI initiation (i.e. trajectory period), we identified OPI-BZD dose and duration patterns using group-based multi-trajectory models, based on average daily morphine milligram equivalents (MME) for OPIs and diazepam milligram equivalents (DME) for BZDs. To label dose levels in each trajectory, we defined OPI use as very low (< 25 MME), low (25-50 MME), moderate (51-90 MME), high (91-150 MME) and very high (>150 MME) dose. Similarly, we defined BZD use as very low (< 10 DME), low (10-20 DME), moderate (21-40 DME), high (41-60 DME) and very high (> 60 DME) dose. Our primary analysis was to estimate the risk of time to first hospital or emergency department visit for OPI overdose within 6 months following the trajectory period using inverse probability of treatment-weighted Cox proportional hazards models. FINDINGS: We identified nine distinct OPI-BZD trajectories: group A: very low OPI (early discontinuation)-very low declining BZD (n = 10 598; 28.0% of the cohort); B: very low OPI (early discontinuation)-very low stable BZD (n = 4923; 13.0%); C: very low OPI (early discontinuation)-medium BZD (n = 4997; 13.2%); D: low OPI-low BZD (n = 5083; 13.4%); E: low OPI-high BZD (n = 3906; 10.3%); F: medium OPI-low BZD (n = 3948; 10.4%); G: very high OPI-high BZD (n = 1371; 3.6%); H: very high OPI-very high BZD (n = 957; 2.5%); and I: very high OPI-low BZD (n = 2096; 5.5%). Compared with group A, five trajectories (32.3% of the study cohort) were associated with increased 6-month OPI overdose risks: E: low OPI-high BZD [hazard ratio (HR) = 3.27, 95% confidence interval (CI) = 1.61-6.63]; F: medium OPI-low BZD (HR = 4.04, 95% CI = 2.06-7.95); G: very high OPI-high BZD (HR = 6.98, 95% CI = 3.11-15.64); H: very high OPI-very high BZD (HR = 4.41, 95% CI = 1.51-12.85); and I: very high OPI-low BZD (HR = 6.50, 95% CI = 3.15-13.42). CONCLUSIONS: Patterns of concurrent opioid and benzodiazepine use most associated with overdose risk among fee-for-service US Medicare beneficiaries initiating opioid prescriptions include very high-dose opioid use (MME > 150), high-dose benzodiazepine use (DME > 40) or medium-dose opioid with low-dose benzodiazepine use.

Developing a Culture of Inclusivity through a Library Diversity, Equity, and Inclusion Team. Part 1: Team Formation.

Health science libraries are ideally suited for proactive Diversity, Equity, and Inclusion (DEI) efforts, as their work and spaces transcend disciplinary boundaries. In 2018, a DEI Team was created by the Health Science Center Libraries at the University of Florida, with the purpose of improving the library's climate for its diverse patrons and employees. This article provides an overview of the Team's formation and development, including its charge, culture, structure, teamwork, leadership, and reporting processes. Recommendations are offered for other libraries seeking to establish similar committees.

Identifying diversity, equity, and inclusion enhancement opportunities through an online mixed methods library survey.

Objective: A mixed methods survey was conducted at a health sciences library to assess patrons' perceptions of the library's digital and physical environments in relation to diversity, equity, and inclusion (DEI). Methods: Developed by the library's DEI Team and preceded by a pilot assessment, the survey posed 17 Likert Scale questions and 2 free-text response questions on the topics of belonging, inclusivity, equitability, emotional and physical safety, and commitment to DEI. The survey was created in Qualtrics, pilot tested, and launched in February 2020 for approximately 12 weeks. Results: Objective question responses were received from 101 individuals, with 24 open-ended responses. The quantitative findings showed largely positive perceptions of the DEI climate. Questions about feeling welcome and feeling physically safe were among those with the highest responses. The three lower-scoring questions indicate areas for improvement, including services for people whose native language is not English, for individuals with disabilities, and for families. The qualitative findings indicate the library's strengths include its exhibitions, welcoming atmosphere, and LGBTQ+ inclusivity initiatives. In contrast, opportunities for enhancement encompass non-English language resources, website updates, and accessibility to some physical spaces. Conclusion: The DEI Team is using the online survey data to enhance library services, staffing, programming, policies, and spaces. These improvements include looking into providing a space for patrons with families, expanding services for individuals whose first language is not English, assessing library accessibility for people with physical disabilities, and enhancing the physical space with quiet areas, improved lighting, and meditation spaces. Employee DEI training is ongoing, using results from a training needs survey to identify knowledge gaps. The library has a history of successful partnerships with campus entities, which will help the DEI Team to move forward with their work.

A Scoping Review on the Relationship between Race/Ethnicity and the Receipt of Supportive Care Medications during Cancer Treatment: Implications for the Clinical Pharmacist.

There is surmounting levels of evidence on the health disparities within cancer treatment in the United States (US). Most of the research focused on cancer specific factors including anticancer incidence, screening, treatment and follow-up, and clinical outcomes such as overall survival (OS). Less is known about the disparities present with supportive care medication use in cancer patients. Supportive care utilization during cancer treatment has been linked to improved quality of life (QoL) and OS among patients. The goal of this scoping review is to summarize findings of current literature on the relationship between race and ethnicity and the receipt of supportive care medications during cancer treatment for pain and chemotherapy-induced nausea and vomiting (CINV). This scoping review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA-ScR) guidelines. Our literature search included quantitative studies, qualitative studies, and grey literature written in the English language with clinically relevant outcomes pertaining to pain and CINV management in cancer treatment published from 2001-2021. Articles that met the predefined inclusion criteria were considered for inclusion in the analysis. The initial search yielded 308 studies. Following de-duplication and screening, 14 studies met the predefined inclusion criteria, with majority of the studies being quantitative studies (n=13). Collectively, results were mixed results regarding the presence of racial disparities for supportive care medication use. Half of the studies (n=7) supported this finding whereas, the other half (n=7) did not identify any racial disparities. In our review, multiple studies illustrate the existence of disparities in the use of supportive care medications in some cancer types. Clinical pharmacists should strive to eliminate supportive medication use disparities as part of a multidisciplinary team. In order to develop strategies to prevent supportive care medication use disparities in this population, further research and analysis of external factors that influence them are needed.

Evaluating the use of prescription sequence symmetry analysis as a pharmacovigilance tool: A scoping review.

BACKGROUND: The (prescription) sequence symmetry analysis (PSSA) design has been used to identify potential prescribing cascade signals by assessing the prescribing sequence of an index drug relative to a marker drug presumed to treat an adverse drug event provoked by the index drug. OBJECTIVES: This review aimed to explore the use of the PSSA design as a pharmacovigilance tool with a particular focus on the breadth of identified signals and advances in PSSA methodology. METHODS: We searched Embase, PubMed/Medline, Google Scholar, Web of Science and grey literature to identify studies that used the PSSA methodology. Two reviewers independently extracted relevant data for each included article. Study characteristics including signals identified, exposure time window, stratified analyses, and use of controls were extracted. RESULTS: We identified 53 studies which reported original results obtained using PSSA methodology or quantified the validity of components of the PSSA design. Of those, nine studies provided validation metrics showing reasonable sensitivity and high specificity of PSSA to identify prescribing cascade signals. We identified 340 unique index drug - marker drug signals published in the PSSA literature, representing 281 unique index - marker pharmacological class dyads (i.e., unique fourth-level Anatomical Therapeutic Chemical [ATC] classification dyads). Commonly observed signals were identified for index drugs acting upon the nervous system (34%), cardiovascular system (21%), and blood and blood-forming organs (15%), and many marker drugs were related to the nervous system (25%), alimentary tract and metabolism (23%), cardiovascular system (17%), and genitourinary system and sex hormones (14%). Negative controls and positive controls were utilized in 21% and 13% of studies, respectively. CONCLUSIONS: The PSSA methodology has been used in 53 studies worldwide to detect and evaluate over 300 unique prescribing cascades signals. Researchers should consider sensitivity analyses incorporating negative and/or positive controls and additional time windows to evaluate time-varying biases when designing PSSA studies.

A Mapping Literature Review of Medical Cannabis Clinical Outcomes and Quality of Evidence in Approved Conditions in the USA from 2016 to 2019.

In 2017, a National Academies of Sciences, Engineering, and Medicine (NASEM) report comprehensively evaluated the body of evidence regarding cannabis health effects through the year 2016. The objectives of this study are to identify and map the most recently (2016-2019) published literature across approved conditions for medical cannabis and to evaluate the quality of identified recent systematic reviews, published following the NASEM report. Following the literature search from 5 databases and consultation with experts, 11 conditions were identified for evidence compilation and evaluation: amyotrophic lateral sclerosis, autism, cancer, chronic noncancer pain, Crohn's disease, epilepsy, glaucoma, human immunodeficiency virus/AIDS, multiple sclerosis (MS), Parkinson's disease, and posttraumatic stress disorder. A total of 198 studies were included after screening for condition-specific relevance and after imposing the following exclusion criteria: preclinical focus, non-English language, abstracts only, editorials/commentary, case studies/series, and non-U.S. study setting. Data extracted from studies included: study design type, outcome definition, intervention definition, sample size, study setting, and reported effect size. Few completed randomized controlled trials (RCTs) were identified. Studies classified as systematic reviews were graded using the Assessing the Methodological Quality of Systematic Reviews-2 tool to evaluate the quality of evidence. Few high-quality systematic reviews were available for most conditions, with the exceptions of MS (9 of 9 graded moderate/high quality; evidence for 2/9 indicating cannabis improved outcomes; evidence for 7/9 indicating cannabis inconclusive), epilepsy (3 of 4 graded moderate/high quality; 3 indicating cannabis improved outcomes; 1 indicating cannabis inconclusive), and chronic noncancer pain (12 of 13 graded moderate/high quality; evidence for 7/13 indicating cannabis improved outcomes; evidence from 6/7 indicating cannabis inconclusive). Among RCTs, we identified few studies of substantial rigor and quality to contribute to the evidence base. However, there are some conditions for which significant evidence suggests that select dosage forms and routes of administration likely have favorable risk-benefit ratios (i.e., epilepsy and chronic noncancer pain). The body of evidence for medical cannabis requires more rigorous evaluation before consideration as a treatment option for many conditions, and evidence necessary to inform policy and treatment guidelines is currently insufficient for many conditions.

Experiential education for the deaf or hard of hearing learner in a pharmacy curriculum.

INTRODUCTION: Pharmacy educators are responsible for providing appropriate resources for students of all abilities to eliminate barriers to accessible learning. This commentary focuses on the need for schools of pharmacy to provide equally accessible learning for students who are deaf/hard of hearing, including within the area of experiential education, while highlighting the potential challenges and areas for opportunity. COMMENTARY: Experiential education settings present unique challenges for students who are deaf/hard of hearing and their pharmacy educators due to the variety of educational settings and different learning logistics associated with experiential education in contrast to the learning environment of the classroom. Pandemic conditions have brought additional challenges since masks have limited the ability for students to lip read. The team has identified several resources to assist in the experiential setting. IMPLICATIONS: In order to provide equally accessible experiential education for students who are deaf/hard of hearing, it is imperative that pharmacy educators work together with other stakeholders such as disability resource centers, experiential site preceptors, and information technology departments to address associated challenges. Lack of literature concerning students with disabilities and experiential education programs in the health sciences shows that this is an area in need of further research and study in order to advance understanding and provide accessible learning for students with diverse needs.