A Resource Compendium for Embedding LGBTQIA+ Patient Care in the Professional Identity of Community Pharmacists.

OBJECTIVES: Cultural, clinical, social, and legally competent patient care for lesbian, gay, bisexual, transgender, queer, intersex, and asexual (LGBTQIA+) patients is currently scarcely incorporated in pharmacy curricula. Furthermore, clinical, legal, and socio-cultural training that prepares pharmacists on the job to provide LGBTQIA+ competent patient care is scant. Here, our objectives were to (1) systematically review the literature using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify trends in community pharmacists' professional identity development related to the provision of competent LGBTQIA+ patient care, and (2) create a reference guide for community pharmacists for self-directed learning. The literature search focused on 4 professional identity domains common to most pharmacists: academic and clinical competence, cultural sensitivity, knowledge of state and federal laws, and continuing professional development. FINDINGS: A total of 207 articles were identified, with 93 retrieved, of which 26 articles were included in the final analysis based on title and abstract and other inclusion criteria. SUMMARY: Overall, our search identified that the LGBTQIA+ health professions literature focused on the following themes: guidance for appropriate drug selection and therapy, creation of cultural sensitivity training curricula, community pharmacists' perceptions of their ability to provide LGBTQIA+ care, health system interventions, and Allyship education for advancing LGBTQIA+ care, the need for enhanced training of pharmacists for understanding the federal and state laws and requirements while providing care, and the need for a resource compendium to help community pharmacists access self-directed learning information, for which we have created a self-help resource guide for pharmacists in these 4 professional pharmacist identity domains.

A pharmacist-led community-based survey study: Determining the impact of the Covid-19 pandemic on actionable factors associated with worse cancer outcomes and cancer health disparities.

Purpose: The goals of this cross-sectional community-based survey study were to assess the impact of the Covid-19 pandemic on actionable factors which are known to contribute to worse cancer outcomes, and to determine whether race and ethnicity-based differences exist. Methods: A survey study which captured demographic information and changes in cancer outcomes-related factors since the start of the Covid-19 pandemic, was conducted at a public Covid-19 vaccination clinic over a period of 10 days during March 2021. Surveys were administered in multiple languages. Chi-square tests and ANOVA followed by post-hoc Dunnett testing assessed for race and ethnicity-based differences. Results: A total of 949 people participated (61.6% participation rate). Ninety-three surveys were removed based on inclusion criteria giving a final participant number of 856. Many participants reported postponing cancer screenings (17.8%) and cancellation of medical appointments (22.8% and 25.8% reported cancelled appointments by providers or themselves, respectively) due to the pandemic. Participants also reported decreased physical activity (44.7%) and increased tobacco and/or marijuana usage (7.0%). Conversely, participants reported consuming more fruits and vegetables (21.4%) and decreasing alcohol consumption (21.4%). Several race-related differences but no ethnicity-related differences were observed. Conclusion: Our data can be used to help guide pharmacist-led targeted outreach in our community which will help mitigate Covid-19 pandemic-driven changes in behaviors associated with worse cancer outcomes and exacerbation of cancer health disparities. To our knowledge, this is the first cancer outcomes-related study to be conducted at a public Covid-19 vaccination site and is the first pharmacist-led study in this area.

HAND1 knockdown disrupts trophoblast global gene expression.

Congenital heart disease (CHD) affects nearly 1% of births annually, and CHD pregnancies carry increased risk of developing pathologies of abnormal placentation. We previously reported significant developmental impacts of disrupting Hand1, a gene associated with CHD, expression in placenta trophoblast and endothelial cells in multiple mouse models. In this study, we aimed to build upon this knowledge and characterize the mechanistic impacts of disrupting HAND1 on human placenta trophoblast and vascular endothelial cell gene expression. HAND1 gene expression was silenced in BeWo cells, a choriocarcinoma model of human cytotrophoblasts, (n = 3-9 passages) and isolated human placental microvascular endothelial cells (HPMVEC; n = 3 passages), with HAND1 siRNA for 96 h. Cells were harvested, mRNA isolated and RNA sequencing performed using the Illumina NextSeq 550 platform. Normalization and differential gene expression analyses were conducted using general linear modeling in edgeR packages. Statistical significance was determined using a log2 fold change of >1.0 or < -1.0 and unadjusted p-value ≤0.05. Panther DB was used for overrepresentation analysis, and String DB for protein association network analysis. There was downregulation of 664 genes, and upregulation of 59 genes in BeWo cells with direct HAND1 knockdown. Overrepresentation analysis identified disruption to pathways including cell differentiation, localization, and cell projection organization. In contrast, only seven genes were changed with direct HAND1 knockdown in HPMVECs. Disruption to HAND1 expression significantly alters gene expression profile in trophoblast but not endothelial cells. This data provides further evidence that future studies on genetic perturbations in CHDs should consider the extra-embryonic tissue in addition to the fetal heart.

Effectiveness of an Advanced Naloxone Training, Simulation, and Assessment of Second-Year Pharmacy Students.

Background: Opioid overdoses continue to be one of the most urgent public health priorities. In 2020, reported overdose deaths in the United States reached a high of over 93,000 cases. As the COVID-19 pandemic and opioid crisis continues to be addressed, life-saving agents must be more widely accessible to those with a high overdose risk. An essential step to increasing access is to train student pharmacists to dispense naloxone. Once licensed, the number of personnel authorized to dispense naloxone can increase. Objectives: To design a training program to educate second-year pharmacy (P2) students on furnishing naloxone under a state protocol. Methods: A multi-phased curriculum-based naloxone training program was delivered to P2 students and included lecture-based education, team-based learning (TBL) applications, case-based scenarios, and summative assessments to improve student knowledge and confidence in furnishing naloxone. Students were surveyed on their knowledge and confidence with naloxone prior to training, after the in-class training and TBL applications and after three assessments. Assessments included simulated patient counseling, case-based scenarios, and proper dispensing of naloxone in a community pharmacy simulation lab. Results: A total of 185 student pharmacists completed the naloxone training program and 68 completed all three surveys. Average scores for naloxone assessments were 83% for the APPS lab patient case, 90.5% for the prescription label typed for the naloxone product, and 88.5% for patient counseling. Statistically significant increases in knowledge-based quiz-like scores (42.1% after training vs. 7.2% after assessment) and in the proportion of students affirmatively answering survey questions after training and assessment was observed. Conclusion: Multi-phase curriculum-based naloxone training program improved pharmacy student knowledge and confidence in furnishing naloxone under a state BOP protocol.

Analysis of commonly expressed genes between first trimester fetal heart and placenta cell types in the context of congenital heart disease.

Congenital heart disease (CHD) is often associated with fetal growth abnormalities. During the first trimester of pregnancy, the heart and placenta develop concurrently, and share key developmental pathways. It is hypothesized that defective morphogenesis of either organ is synergistically linked. However, many studies determined to understand the mechanisms behind CHD overlook the contribution of the placenta. In this study, we aimed to identify commonly expressed genes between first trimester heart and placenta cells using two publicly available single cell sequencing databases. Using a systematic computational approach, we identified 328 commonly expressed genes between heart and placenta endothelial cells and enrichment in pathways including Vasculature Development (GO:0001944, FDR 2.90E-30), and Angiogenesis (GO:0001525, FDR 1.18E-27). We also found, in comparison with fetal heart endothelial cells, 197 commonly expressed genes with placenta extravillous trophoblasts, 128 with cytotrophoblasts and 80 with syncytiotrophoblasts, and included genes such as FLT1, GATA2, ENG and CDH5. Finally, comparison of first trimester cardiomyocytes and placenta cytotrophoblasts revealed 53 commonly expressed genes and enrichment in biological processes integral to cellular function including Cellular Respiration (GO:0045333; FDR 5.05E-08), Ion Transport (GO:0006811; FDR 2.08E-02), and Oxidation-Reduction Process (GO:0055114; FDR 1.58E-07). Overall, our results identify specific genes and cellular pathways common between first trimester fetal heart and placenta cells which if disrupted may concurrently contribute to the developmental perturbations resulting in CHD.

COVID-19-Driven Improvements and Innovations in Pharmacy Education: A Scoping Review.

The COVID-19 pandemic led to many colleges of pharmacy having to make major changes relating to their infrastructure and delivery of their curriculum within a very short time frame, including the transition of many components to an online setting. This scoping review sought to summarize what is known about the impact of COVID-19 on pharmacy education and the effectiveness of adaptation strategies which were put in place. PubMed, Web of Science, OVID Medline, and MedEdPortal were searched to identify pharmacy education-related articles published since the beginning of the COVID-19 pandemic. For article inclusion, the following criteria had to be met: described original research, related directly to PharmD or PharmBS education, related to the impact of COVID-19 on pharmacy education, and was available in English. Out of a total of 813 articles, 50 primary research articles were selected for inclusion. Our review of these identified four domains relating to the impact of COVID-19 on pharmacy education and/or effectiveness of adaptation strategies: (1) lab-based courses and activities (including interprofessional education activities), (2) experiential education, (3) didactic education, and (4) student well-being. The key research findings are summarized and discussed. While the COVID-19 pandemic has clearly brought many challenges to pharmacy education, it has also led to key improvements and innovations.

Placental and fetal characteristics of the Ohia mouse line recapitulate outcomes in human hypoplastic left heart syndrome.

Congenital heart defects (CHDs) are the most common birth defect worldwide. The morbidity and mortality associated with these defects is compounded by increased frequency of fetal growth abnormalities. In the Ohia mouse model of hypoplastic left heart syndrome (HLHS), the double homozygous genotype is embryonically lethal at mid-pregnancy; a time in which optimal establishment of the placenta is crucial to fetal survival. We aimed to characterize placental and fetal growth and development in the double heterozygous genotype (Sap130m/+Pcdha9m/+). There was a shift in frequency of fetuses with reduced weight near term in the Sap130m/+Pcdha9m/+ fetuses compared to wildtype, driven by lower fetal weight in male fetuses compared to female. This shift in fetal weight distribution in the Sap130m/+Pcdha9m/+ fetuses was associated with reduced labyrinth region area (P < 0.001) and reduced fetal capillary density (P < 0.001) in the placentas, the latter being significantly lower in male Sap130m/+Pcdha9m/+ placentas compared to female. mRNA expression of several nutrient transporters was also lower in placentas from males compared to placentas from females, irrespective of genotype. Overall, this data shows that whilst the double heterozygous fetuses do not carry heart defects, placental development and function is impaired, particularly in males. Such differences are similar to findings in studies of human placentas and highlights the importance of this mouse model in continuing to understand the developmental links and disruptions to the heart-placenta axis.

Conditional Mutation of Hand1 in the Mouse Placenta Disrupts Placental Vascular Development Resulting in Fetal Loss in Both Early and Late Pregnancy.

Congenital heart defects (CHD) affect approximately 1% of all live births, and often require complex surgeries at birth. We have previously demonstrated abnormal placental vascularization in human placentas from fetuses diagnosed with CHD. Hand1 has roles in both heart and placental development and is implicated in CHD development. We utilized two conditionally activated Hand1A126fs/+ murine mutant models to investigate the importance of cell-specific Hand1 on placental development in early (Nkx2-5Cre) and late (Cdh5Cre) pregnancy. Embryonic lethality occurred in Nkx2-5Cre/Hand1A126fs/+ embryos with marked fetal demise occurring after E10.5 due to a failure in placental labyrinth formation and therefore the inability to switch to hemotrophic nutrition or maintain sufficient oxygen transfer to the fetus. Labyrinthine vessels failed to develop appropriately and vessel density was significantly lower by day E12.5. In late pregnancy, the occurrence of Cdh5Cre+;Hand1A126fs/+ fetuses was reduced from 29% at E12.5 to 20% at E18.5 and remaining fetuses exhibited reduced fetal and placental weights, labyrinth vessel density and placenta angiogenic factor mRNA expression. Our results demonstrate for the first time the necessity of Hand1 in both establishment and remodeling of the exchange area beyond early pregnancy and in patterning vascularization of the placental labyrinth crucial for maintaining pregnancy and successful fetal growth.

Abnormalities of placental development and function are associated with the different fetal growth patterns of hypoplastic left heart syndrome and transposition of the great arteries.

BACKGROUND: Birthweight is a critical predictor of congenital heart disease (CHD) surgical outcomes. Hypoplastic left heart syndrome (HLHS) is cyanotic CHD with known fetal growth restriction and placental abnormalities. Transposition of the great arteries (TGA) is cyanotic CHD with normal fetal growth. Comparison of the placenta in these diagnoses may provide insights on the fetal growth abnormality of CHD. METHODS: Clinical data and placental histology from placentas associated with Transposition of the Great Arteries (TGA) were analyzed for gross pathology, morphology, maturity and vascularity and compared to both control and previously analyzed HLHS placentas [1]. RNA was isolated from HLHS, TGA and control placentas and sequenced by Illumina HiSeq.Transcriptome analysis was performed using AltAnalyze. Immunohistochemistry was utilized to assess placental nutrient transporter expression in all three groups. RESULTS: Placental weight was reduced in TGA cases, and demonstrated reduced villous vasculature, immature terminal villi in the parenchyma compared to controls and reflected our previous data from HLHS placentas. However, birth weight was not reduced in TGA cases compared to controls in contrast to the HLHS cohort and birthweight:placental weight ratio was significantly increased in TGA cases but not HLHS compared to control. Transcriptomic and histologic analysis demonstrates reduced cell activity and nutrient transport capability in HLHS but not TGA placentas which appear to increase/maintain these mechanisms. CONCLUSIONS: Despite common vascular disturbances in placentas from HLHAs and TGA, these do not account for the disparities in birthweights frequently seen between these CHD subtypes, in contrast our transcriptomic and histologic analyses reveal differentially regulated mechanisms between the subtypes that may explain these disparities.

Fibrocyte accumulation in the lungs of cystic fibrosis patients.

BACKGROUND: Cystic fibrosis (CF) patients develop severe lung disease including chronic airway infections, neutrophilic inflammation, and progressive fibrotic remodeling in airways. However, cellular and molecular processes that regulate excessive collagen deposition in airways in these patients remain unclear. Fibrocytes are bone marrow (BM)-derived mesenchymal cells that express the hematopoietic cell marker CD45, and mesenchymal cell markers and implicated in collagen deposition in several fibrotic diseases. It is unknown whether fibrocytes accumulate in the lungs of CF patients, so the current study evaluates the presence of fibrocytes in the fibrotic lesions of airways in explanted CF lungs compared to non-CF unused donor lungs (control). METHODS: We used immunofluorescence staining to determine if fibrocytes accumulate in explanted CF lungs compared to healthy donor lungs. Simultaneously, we evaluated cells collected by bronchoalveolar lavage (BAL) in CF patients using multi-color flow cytometry. Finally, we analyzed transcripts differentially expressed in fibrocytes isolated from the explanted CF lungs compared to control to assess fibrocyte-specific pro-fibrotic gene networks. RESULTS: Our findings demonstrate fibrocyte accumulation in CF lungs compared to non-CF lungs. Additionally, fibrocytes were detected in the BAL of all CF children. Transcriptomic analysis of fibrocytes identified dysregulated genes associated with fibrotic remodeling in CF lungs. CONCLUSIONS: With significantly increased fibrocytes that show increased expression of pro-fibrotic gene transcripts compared to control, our findings suggest an intervention for fibrotic remodeling as a potential therapeutic target in CF.

The Role of Abnormal Placentation in Congenital Heart Disease; Cause, Correlate, or Consequence?

Congenital heart disease (CHD) is the most common birth defect, affecting ~1% of all live births (van der Linde et al., 2011). Despite improvements in clinical care, it is the leading cause of infant mortality related to birth defects (Yang et al., 2006) and burdens survivors with significant morbidity (Gilboa et al., 2016). Furthermore, CHD accounts for the largest proportion (26.7%) of birth defect-associated hospitalization costs-up to $6.1 billion in 2013 (Arth et al., 2017). Yet after decades of research with a primary focus on genetic etiology, the underlying cause of these defects remains unknown in the majority of cases (Zaidi and Brueckner, 2017). Unexplained CHD may be secondary to undiscovered roles of noncoding genetic, epigenetic, and environmental factors, among others (Russell et al., 2018). Population studies have recently demonstrated that pregnancies complicated by CHD also carry a higher risk of developing pathologies associated with an abnormal placenta including growth disturbances (Puri et al., 2017), preeclampsia (Auger et al., 2015; Brodwall et al., 2016), preterm birth (Laas et al., 2012), and stillbirth (Jorgensen et al., 2014). Both the heart and placenta are vascular organs and develop concurrently; therefore, shared pathways almost certainly direct the development of both. The involvement of placental abnormalities in congenital heart disease, whether causal, commensurate or reactive, is under investigated and given the common developmental window and shared developmental pathways of the heart and placenta and concurrent vasculature development, we propose that further investigation combining clinical data, in vitro, in vivo, and computer modeling is fundamental to our understanding and the potential to develop therapeutics.