A pharmacist-led heart failure stewardship initiative for guideline-directed medical therapy in hospitalized patients with reduced ejection fraction.

Background: Heart failure with reduced ejection fraction (HFrEF) is a progressive disease with high rates of hospitalization and mortality. The Canadian Cardiovascular Society recommends treating patients with HFrEF with medications from 4 standard medication classes-this is known as guideline-directed medical therapy (GDMT). However, despite clear evidence and recommendations, GDMT agents are known to be underutilized in the HFrEF population. Objective: To determine if the implementation of a prescriber-alert stewardship tool for hospitalized patients with HFrEF will increase the frequency of GDMT prescribing with all classes during hospitalization. Methods: Utilization of GDMT in patients with HFrEF between admission and discharge pre- and post-implementation of a prescriber alert stewardship tool was compared. Patients admitted to a cardiology stepdown unit between January and April 2022 had a stewardship-alert tool placed on their chart for physician review, while those admitted during the same time frame 1 year prior did not. Results: Following the use of a prescriber alert, there was a statistically significant increase in prescribing for ß-blockers (38.1% to 95.2%; p < 0.001), mineralocorticoid receptor antagonists (9.5% to 66.7%; p < 0.001) and combination GDMT (9.5% to 52.4%; p = 0.004) from admission to discharge. A statistically significant increase in the prescribing of ß-blockers (47.6% to 76.2%; p = 0.004) and angiotensin-converting enzyme inhibitors (21.4% to 40.5%; p = 0.008) was still observed without the use of the prescriber alert. Conclusion: A pharmacist-led heart failure stewardship tool initiative increased uptake of GDMT in patients with HFrEF.

Tolypocaibols: Antibacterial Lipopeptaibols from a Tolypocladium sp. Endophyte of the Marine Macroalga Spongomorpha arcta.

Two new lipopeptaibols, tolypocaibols A (1) and B (2), and the mixed NRPS-polyketide-shikimate natural product maximiscin [(P/M)-3)] were isolated from a Tolypocladium sp. fungal endophyte of the marine alga Spongomorpha arcta. Analysis of NMR and mass spectrometry data revealed the amino acid sequences of the lipopeptaibols, which both comprise 11 residues with a valinol C-terminus and a decanoyl acyl chain at the N-terminus. The configuration of the amino acids was determined by Marfey's analysis. Tolypocaibols A (1) and B (2) showed moderate, selective inhibition against Gram-positive and acid-fast bacterial strains, while maximiscin [(P/M)-3)] showed moderate, broad-spectrum antibiotic activity.

Metformin Prevents Hyperglycemia-Associated, Oxidative Stress-Induced Vascular Endothelial Dysfunction: Essential Role for the Orphan Nuclear Receptor Human Nuclear Receptor 4A1 (Nur77).

Vascular pathology is increased in diabetes because of reactive-oxygen-species (ROS)-induced endothelial cell damage. We found that in vitro and in a streptozotocin diabetes model in vivo, metformin at diabetes-therapeutic concentrations (1-50 µM) protects tissue-intact and cultured vascular endothelial cells from hyperglycemia/ROS-induced dysfunction typified by reduced agonist-stimulated endothelium-dependent, nitric oxide-mediated vasorelaxation in response to muscarinic or proteinase-activated-receptor 2 agonists. Metformin not only attenuated hyperglycemia-induced ROS production in aorta-derived endothelial cell cultures but also prevented hyperglycemia-induced endothelial mitochondrial dysfunction (reduced oxygen consumption rate). These endothelium-protective effects of metformin were absent in orphan-nuclear-receptor Nr4a1-null murine aorta tissues in accord with our observing a direct metformin-Nr4a1 interaction. Using in silico modeling of metformin-NR4A1 interactions, Nr4a1-mutagenesis, and a transfected human embryonic kidney 293T cell functional assay for metformin-activated Nr4a1, we identified two Nr4a1 prolines, P505/P549 (mouse sequences corresponding to human P501/P546), as key residues for enabling metformin to affect mitochondrial function. Our data indicate a critical role for Nr4a1 in metformin's endothelial-protective effects observed at micromolar concentrations, which activate AMPKinase but do not affect mitochondrial complex-I or complex-III oxygen consumption rates, as does 0.5 mM metformin. Thus, therapeutic metformin concentrations requiring the expression of Nr4a1 protect the vasculature from hyperglycemia-induced dysfunction in addition to metformin's action to enhance insulin action in patients with diabetes. SIGNIFICANCE STATEMENT: Metformin improves diabetic vasodilator function, having cardioprotective effects beyond glycemic control, but its mechanism to do so is unknown. We found that metformin at therapeutic concentrations (1-50µM) prevents hyperglycemia-induced endothelial dysfunction by attenuating reactive oxygen species-induced damage, whereas high metformin (>250 µM) impairs vascular function. However, metformin's action requires the expression of the orphan nuclear receptor NR4A1/Nur77. Our data reveal a novel mechanism whereby metformin preserves diabetic vascular endothelial function, with implications for developing new metformin-related therapeutic agents.

Health Outcomes of Older Adults after a Hospitalization for a Hip Fracture.

Background: Hip fractures in older adults often lead to adverse health outcomes, which may be related to time to surgery and longer hospital stays. The experience of older adults with hip fractures in New Brunswick is not known. Methods: This was a retrospective observational study. All hip fracture patients 65 years of age and older admitted to one hospital designated as a Level One Trauma Centre between April 1, 2015 and March 31, 2019 comprised the sample. Results: The majority (86.5%) received surgery within 48 hours and those who had surgery beyond this time frame had a significantly longer stay in acute care (OR: 3.79, 95% CI: 2.05-7.15). The mean total length of stay (Total-LOS) for patients discharged after their acute care needs were met was 9.8 days (SD=8.1) compared to patients experiencing delays in discharge for nonmedical reasons which was 26.3 days (SD=33.7). An extended stay in acute care (OR: 1.93, 95% CI: 1.09-3.43) and increasing age (OR: 1.03, 95% CI: 1.001-1.06) were associated with a higher likelihood of death at one year post-discharge. Time to surgery beyond 24 hours (OR: 2.80, 95% CI: 1.13-7.38) was associated with a higher likelihood of death 30 days post-discharge. Conclusions: Most patients had surgery within the national benchmark of less than 48 hours. The Total-LOS increased 2.5-fold in patients who remained in hospital after their acute care needs were met. A better understanding of patient characteristics, such as frailty, may better predict patients at risk for longer hospital stays and adverse health outcomes.

Retrospective Use of the Pictorial Fit-Frail Scale for Determination of Frailty Level in Hospitalized Older Adults with a Hip Fracture.

The Pictorial Fit-Frail Scale (PFFS) is a frailty tool consisting of visual images to comprehensively assess frailty across 14 domains that can be completed by health professionals, patients, or caregivers. The objective of this study was to explore the feasibility of using the PFFS retrospectively to determine a patient's frailty level using data from the hospital electronic health records (EHRs) of older adults admitted with an isolated hip fracture. A random sample of 200 hip fracture patients admitted to a Level 1 Trauma Center hospital in New Brunswick was selected for review using the PFFS. The majority (94.5%) of hospital EHRs contained the clinical information needed to populate most of the 14 PFFS domains, allowing for determination of a frailty score. The mean raw PFFS frailty score was 9.7 (SD 6.6), consistent with moderate frailty. For all patients, a Frailty Index (FI) score was calculated, with the mean being 0.27 (SD 0.18), again consistent with moderate frailty. Comparing the PFFS score to the FI score, the percentage categorized as not frail or very mildly frail fell from 33.3% to 20.1%, and those considered severely frail rose from 30.7% to 34.9%. The PFFS can be successfully used retrospectively with hospital EHRs to determine the frailty level of older patients. When converted to the FI score, there was an increase in the frequency and severity of frailty. This tool may provide a useful way to stratify older adults by frailty that can be helpful in evaluating health outcomes based on frailty levels.

Telephone versus In-Person Pharmacist-Led Medication Reviews in Home Dialysis Patients: Evaluating Quality of Care and Patient Satisfaction.

The COVID-19 pandemic required pharmacists in a provincial Home Dialysis Clinic to adapt from in-person to telephone-based medication reviews. Studies have shown that in-person pharmacist interventions in patients with chronic kidney disease (CKD) lead to a reduction of drug therapy problems (DTPs), however, it's unknown if telephone interventions provide similar outcomes. The purpose of this study was to evaluate whether differences in quality of care exist between in-person vs. telephone medication reviews in home dialysis patients and to evaluate patient satisfaction with telephone medication reviews. Data from the two most recent in-person medication reviews was compared with the two most recent telephone medication reviews for each patient (n = 46). There were no statistically significant differences in DTPs identified between in-person and telephone medication reviews (p = 0.431). Physician acceptance of pharmacist recommendations was higher for in-person medication reviews (p = 0.009). Patients were satisfied with the care they received with pharmacist-led telephone medication reviews, however, 29% (n = 7) would prefer an in-person medication review once per year with telephone medication reviews the rest of the time. Overall, patients were satisfied with the care they received from telephone medication reviews.

Identification of cannabinoids in post-mortem blood samples from the province of New Brunswick before and after recreational cannabis legalization.

INTRODUCTION: Since recreational legalization of cannabis in Canada in 2018, self-reported use in New Brunswick (NB) has increased from 15.1% to 20.3%, the largest increase of any province. Current literature on the impact of recreational cannabis legislation in other jurisdictions is conflicting, though retail availability has often been delayed on enactment. Given the immediate availability of cannabis in NB after legalization, we sought to establish the effect this had on post-mortem cannabinoid detection. Furthermore, we wanted to investigate the impact that age, sex, and manner of death had on cannabis use. We also established if there were any increases in commonly detected drugs over the study period. METHODS: A retrospective chart review was conducted on all adult Coroner's cases with toxicology analysis in NB between January 2014 and May 2020 (n = 3060). Differences in the proportion of cannabinoid-positive samples pre- versus post-legalization in the overall cohort as well as within each demographic parameter were assessed using chi-square tests. The effects of demographic parameters on cannabis presence were further assessed by logistic regression. Lastly, chi-square tests for trend were performed to identify increasing trends in cannabis detection, as well as cocaine, ethanol, opiates/opioids, benzodiazepines, and amphetamines over the study period. RESULTS: After controlling for age, sex, and manner of death, participants that died after recreational legalization had higher odds of having cannabis present post-mortem than those that died pre-legalization. In addition, demographic sub-analysis identified a greater proportion of cannabinoid-positive samples post-legalization in 25- to 44-year-olds and in deaths classified as either suicide or accidental compared to pre-legalization. We also observed a significant increase in the presence of cocaine and amphetamines in post-mortem samples over the study period. CONCLUSION: This study demonstrates that cannabis use has increased post-legalization in NB, particularly within young adults and those dying by suicide or accidental means. It also highlights the need for future research into the impact that legalization has on cannabis use in other jurisdictions.

Burnout among Hospital Pharmacists in Canada: A Cross-Sectional Analysis.

Background: Burnout is a growing problem among health care professionals, with consequences for patient safety and personal satisfaction. The prevalence of burnout among hospital pharmacists in Canada is unknown; however, it has been documented at over 60% in other countries. Objectives: To assess the prevalence of burnout and variables associated with burnout among hospital pharmacists in Canada. Methods: This cross-sectional cohort study was based on a survey made available to more than 2600 Canadian hospital pharmacists from February 10 to April 2, 2020, through the Canadian Society of Hospital Pharmacists QID platform. The questionnaire collected data for the Maslach Burnout Inventory Human Services Survey for Medical Personnel (MBI-HSSMP), demographic data, employment characteristics, and workplace factors; it also included an open-ended question about burnout. Results: A total of 171 respondents provided data suitable for analysis. Of these, only 13 (7.6%) met the criteria for burnout on all 3 subscales of the burnout inventory; however, 105 respondents (61.4%) surpassed the threshold for burnout on the emotional exhaustion subscale. In univariate analyses, not working to one's full scope of practice was associated with meeting the criteria for burnout on all 3 scales. Linear regression highlighted associations between scores on the emotional exhaustion subscale and gender identity, perceived excessive on-call duties, area of practice, and positivity of workplace culture. Content analysis of the open-ended question supported the quantitative findings and pointed to 3 major themes: workload quantity, workload quality, and workplace culture. Conclusions: Results on the emotional exhaustion subscale of the MBI-HSSMP and responses to the open-ended question suggested a relatively high prevalence of burnout among Canadian hospital pharmacists, and indicated potential links between burnout and certain workplace characteristics.

Contexte: L'épuisement professionnel est un problème croissant chez les professionnels de la santé qui entraîne des conséquences sur la sécurité des patients et la satisfaction personnelle des professionnels. La prévalence de l'épuisement professionnel chez les pharmaciens d'hôpitaux au Canada est inconnue; cependant, il a été documenté à plus de 60 % dans d'autres pays. Objectifs: Évaluer la prévalence de l'épuisement professionnel et les variables associées à celui-ci chez les pharmaciens d'hôpitaux au Canada. Méthodes: Cette étude de cohorte transversale se basait sur un sondage distribué à plus de 2600 pharmaciens d'hôpitaux canadiens entre le 10 février et le 2 avril 2020 via la plateforme QID de la Société canadienne des pharmaciens d'hôpitaux. Le questionnaire a permis de recueillir des données pour le Maslach Burnout Inventory Human Services Survey for Medical Personnel (MBI-HSSMP; un inventaire de l'épuisement professionnel chez les professionnels de la santé), des données démographiques, des caractéristiques professionnelles et des facteurs liés au lieu de travail; il comprenait également une question ouverte sur l'épuisement professionnel. Résultats: Au total, 171 répondants ont fourni des données se prêtant à l'analyse. Parmi ceux-ci, seuls 13 (7,6 %) répondaient aux critères de l'épuisement professionnel des 3 sous-échelles de l'inventaire de l'épuisement professionnel; cependant, 105 répondants (61,4 %) ont dépassé le seuil d'épuisement professionnel de la sous-échelle d'épuisement émotionnel. Dans les analyses univariées, le fait de ne pas travailler dans l'ensemble de son champ d'exercice était associé au respect des critères d'épuisement professionnel sur les 3 sous-échelles. La régression linéaire a mis en évidence des associations entre les scores sur la sous-échelle d'épuisement émotionnel et l'identité de genre, les tâches de garde excessives perçues, le domaine de pratique et la positivité de la culture sur le lieu de travail. L'analyse du contenu de la question ouverte étayait les résultats quantitatifs et a souligné 3 thèmes principaux : la quantité et la qualité de la charge de travail, ainsi que la culture sur le lieu de travail. Conclusions: Les résultats relatifs à la sous-échelle d'épuisement émotionnel du MBI-HSSMP et les réponses à la question ouverte suggèrent une prévalence relativement élevée d'épuisement professionnel chez les pharmaciens d'hôpitaux canadiens et indiquent des liens potentiels entre l'épuisement professionnel et certaines caractéristiques du milieu de travail.

Polyketides from an Endophytic Aspergillus fumigatus Isolate Inhibit the Growth of Mycobacterium tuberculosis and MRSA.

The crude extract of Aspergillusfumigatus isolate AF3-093A, an endophyte of the brown alga Fucus vesiculosus, showed significant antimicrobial activity in initial bioactivity screens. Bioassay-guided fractionation of the extract led to the isolation of flavipin, chaetoglobosin A and chaetoglobosin B, all of which inhibited the growth of Staphylococcus aureus, methicillin-resistant S. aureus and Mycobacterium tuberculosis H37Ra. The antimycobacterial activity of these compounds has not been previously reported.

Antimycobacterial Natural Products from Endophytes of the Medicinal Plant Aralia nudicaulis.

Antimycobacterial extracts of a Penicillium sp. (isolate HL4-159-41B) and a Coniothyrium sp. (isolate HL6-097-027B) isolated from the rhizomes of the Canadian medicinal plant Aralia nudicaulis were found to contain palitantin (1) and botrallin (2), craterellin C (3), mycosporulone (4), spiromassaritone (5), and massarigenin D (6) respectively. Bioassays against Mycobacterium tuberculosis H37Ra revealed that 1 - 4 possess moderate antimycobacterial activity.

Synthesis and biological activity of arylspiroborate salts derived from caffeic Acid phenethyl ester.

Two novel boron compounds containing caffeic acid phenethyl ester (CAPE) derivatives have been prepared and characterized fully. These new compounds and CAPE have been investigated for potential antioxidant and antimicrobial properties and their ability to inhibit 5-lipoxygenase and whether chelation to boron improves their biological activity. Sodium salt 4 was generally more active than ammonium salt 5 in the biological assays and surpassed the radical scavenging ability of CAPE. Compounds 4 and 5 were more active than CAPE and Zileuton in human polymorphonuclear leukocytes. These results clearly show the effectiveness of the synthesized salts as transporter of CAPE.

Antimicrobials from the marine algal endophyte Penicillium sp.

An endophytic fungus identified as Penicillium sp. was isolated from the brown alga Fucus spiralis collected from the Shetland Islands, United Kingdom. Bioassay-guided fractionation of an extract of the fungus led to the isolation of cladosporin, epiepoformin, phyllostine, and patulin, all of which showed antimicrobial activity against either Staphylococcus aureus or Pseudomonas aeruginosa. Cladosporin has not previously been identified from a fungus of the genus Penicillium, and, despite being biosynthetically related, epiepoformin, phyllostine and patulin have not been previously reported from one source.

Macroalgal Endophytes from the Atlantic Coast of Canada: A Potential Source of Antibiotic Natural Products?

As the need for new and more effective antibiotics increases, untapped sources of biodiversity are being explored in an effort to provide lead structures for drug discovery. Endophytic fungi from marine macroalgae have been identified as a potential source of biologically active natural products, although data to support this is limited. To assess the antibiotic potential of temperate macroalgal endophytes we isolated endophytic fungi from algae collected in the Bay of Fundy, Canada and screened fungal extracts for the presence of antimicrobial compounds. A total of 79 endophytes were isolated from 7 species of red, 4 species of brown, and 3 species of green algae. Twenty of the endophytes were identified to the genus or species level, with the remaining isolates designated codes according to their morphology. Bioactivity screening assays performed on extracts of the fermentation broths and mycelia of the isolates revealed that 43 endophytes exhibited antibacterial activity, with 32 displaying antifungal activity. Endophytic fungi from Bay of Fundy macroalgae therefore represent a significant source of antibiotic natural products and warrant further detailed investigation.