Trends of Use and Outcomes Associated With Glycoprotein-IIb/IIIa Inhibitors in Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention.

Background: Glycoprotein IIb/IIIa inhibitors (GPIs) are a treatment option in the management of acute coronary syndromes (ACSs). Evidence supporting the use of GPIs predates trials establishing the benefits of P2Y12 inhibitors, routine early invasive therapy, and thrombectomy devices in patients with ACS. Objective: The aim of this study was to determine trends in GPI use and their associated outcomes in contemporary practice. Methods: We assessed GPI use in patients with ACS undergoing percutaneous coronary intervention (PCI) from the Melbourne Interventional Group registry (2005-2013). The primary endpoint was the 30-day incidence of major adverse cardiovascular events (MACE). The safety endpoint was in-hospital major bleeding. Results: GPIs were used in 40.5% of 12 357 patients with ACS undergoing PCI. GPI use decreased over the study period (P for trend <0.0001). Patients were more likely to receive GPIs if they were younger, presented with a ST-elevation myocardial infarction (STEMI), had more complex (B2/C-type) lesions, and when thrombectomy devices were used (all P < 0.0001). MACE were higher in patients receiving GPI (4.9% vs 4.1%, P = 0.03). Propensity score matching revealed no difference in 30-day mortality and 30-day MACE (odds ratio [OR] = 1.00; 95% CI = 0.99-1.004 and OR = 1.01; 95% CI = 0.99-1.02, respectively). GPI use was associated with more bleeding complications (3.6% vs 1.8%, P < 0.0001). Conclusion and Relevance: GPI use in ACS patients undergoing PCI has declined, and use appears to be dictated by ACS type and lesion complexity, as opposed to high-risk comorbidities. GPI use was associated with a doubling in bleeding complications.

Adherence to Antifungal Guidelines in Malignant Hematology Patients: A Review of the Literature.

Objective: To review the published literature assessing adherence rates to antifungal guidelines and reasons for nonadherence in the adult malignant hematology inpatient setting. Data sources: The databases Embase, MEDLINE, and PubMed (from data inception to May 2019) were searched using the terms hematology, oncology, antifungal, guidelines, adherence, and stewardship with the search limited to adult human subjects and published in English. This yielded 123 articles. From this list, studies that were published in peer-reviewed journals were extracted, leaving 10 citations that met the final inclusion criteria. Study Selection and Data Extraction: Ten studies were selected assessing adherence to consensus antifungal guidelines in the malignant hematology setting. These included studies investigating the introduction of antifungal stewardship programs in tertiary hospitals. Data Synthesis: Although the studies were heterogeneous, all focused on appropriateness of antifungal therapy in the inpatient setting. Adherence to antifungal guidelines for optimal antifungal prophylaxis and treatment was low in most studies, with rates of inappropriate antifungal therapy ranging from 25% to 70% of fungal prescriptions. Relevance to Patient Care and Clinical Practice: Adherence rates with guidelines for antifungal therapy are low in the hematology inpatient setting. This may affect infection rates influencing morbidity and mortality in this high-risk population. Conclusion: Given the prevalence of invasive fungal infections in malignant hematology inpatients, suboptimal adherence with antifungal guidelines is concerning. This demands a focus on education, antifungal stewardship, and updating guidelines to meet real-world scenarios. Adherence with antifungal guidelines in the outpatient hematology setting is unknown and requires further research.

Management of an unintentional enoxaparin overdose: A case report and literature review.

PURPOSE: The aim of this article is to describe a case in which protamine was used for a low-molecular-weight heparin (LMWH) overdose and present an up-to-date review of the literature on the management of LMWH overdose in adults. SUMMARY: An unintentional administration of enoxaparin 900 mg occurred in a 73-year-old man with coronavirus disease 2019-related pulmonary embolism. Management of the overdose included a protamine bolus followed by an infusion. Anti-factor Xa levels and activated partial thromboplastin time were monitored. Anti-factor Xa levels declined in a linear fashion irrespective of protamine administration. No bleeding or further thrombotic complications occurred in the patient. A review of the literature revealed that the optimal strategy to treat an LMWH overdose is unknown, with treatment of overdoses ranging from clinical observation to aggressive protamine dosing in reported cases. Although protamine effectively neutralizes unfractionated heparin, it is unable to completely reverse LMWH activity and has variable effects on laboratory measures of LMWH anticoagulant activity. CONCLUSION: The current case report provides additional data to previous literature suggesting that protamine may have a limited effect in decreasing anti-factor Xa levels in LMWH overdose. Continued reporting on the management of LMWH overdoses is warranted to clarify the optimal treatment strategy.

Precision fluid and vasoactive drug therapy for critically ill patients.

There are several clinical practice guidelines concerning the use of fluid and vasoactive drug therapies in critically ill adult patients, but the recommendations in these guidelines are often based on low-quality evidence. Further, some were compiled prior to the publication of landmark clinical trials, particularly in the comparison of balanced crystalloid and normal saline. An important consideration in the treatment of critically ill patients is the application of precision medicine to provide the most effective care to groups of patients most likely to benefit from the therapy. Although not currently widely integrated into these practice guidelines, the utility of precision medicine in critical illness is a recognized research priority for fluid and vasoactive therapy management. The purpose of this narrative review was to illustrate the evaluation and challenges of providing precision fluid and vasoactive therapies to adult critically ill patients. The review includes a discussion of important investigations published after the release of currently available clinical practice guidelines to provide insight into how recommendations and research priorities may change future guidelines and bedside care for critically ill patients.

Canadian Hospital Pharmacists' Perceptions of Workplace Preparedness and Personal Well-Being during the COVID-19 Pandemic.

Background: Little is known about hospital pharmacists' experiences during the COVID-19 pandemic, as studies to date have focused on community pharmacy practices. Objectives: To determine hospital pharmacists' perceptions of their workplace preparedness for the COVID-19 pandemic and to measure their mental well-being with the Warwick-Edinburgh Mental Well-being Scale (WEMWBS). Methods: Pharmacists working in Canadian hospital inpatient settings during the COVID-19 pandemic were invited to participate in a 2-part online survey. Part A was a 46-item survey containing statements related to directions and support from leadership, personal protective equipment practices, work environment, and emotions. Part B assessed respondents' mental well-being using the validated 14-item WEMWBS. Responses to both parts of the survey were based on Likert scales. The survey was open from July to September 2020. Descriptive analyses were applied. Results: A total of 432 hospital pharmacists consented to participate in the study. Most respondents were women (337/432, 78%), and most were 25 to 44 years old (293/432, 68%). Most respondents were confident that their workplace and pharmacy department were effectively managing patient demand (314/389, 81%) and the pandemic more generally (263/394, 67%). They also felt that their workplace teams were working well together (314/386, 81%). Interestingly, 22% (86/391) of the respondents did not agree that they had received training for COVID-19 infection prevention and control practices. The mean WEMWBS score was 48.9 (standard deviation 8.6), which indicated average mental well-being. Conclusions: After the initial wave of the COVID-19 pandemic, respondents perceived their hospitals and departments as being able to manage the pandemic and reported average mental well-being. Ensuring that all hospital pharmacists receive training for effective COVID-19 infection prevention and control practices is crucial. How their perceptions and well-being have changed since the time of the survey is unknown.

Contexte: On sait peu de choses sur les expériences des pharmaciens d'hôpitaux pendant la pandémie de COVID-19, car les études à ce jour se sont concentrées sur les pratiques de la pharmacie communautaire. Objectifs: Cerner les perceptions des pharmaciens d'hôpitaux quant à la préparation de leur lieu de travail à la pandémie de COVID-19 et mesurer leur bien-être mental à l'aide de l'échelle de bien-être mental Warwick-Edinburgh (WEMWBS). Méthodes: Les pharmaciens qui travaillaient en milieu hospitalier canadien pendant la pandémie de COVID-19 ont été invités à participer à un sondage en ligne en deux volets. Le volet A consistait en une enquête portant sur 46 éléments contenant des déclarations liées aux orientations et au soutien de la direction, aux pratiques en matière d'équipement de protection individuelle, à l'environnement de travail et aux émotions. Le volet B a quant à lui permis d'évaluer le bien-être mental des répondants à l'aide de l'échelle WEMWBS validée à 14 points. Les réponses aux deux volets de l'enquête se basaient sur des échelles de Likert. Le sondage était ouvert de juillet à septembre 2020. Des analyses descriptives ont été appliquées. Résultats: Au total, 432 pharmaciens d'hôpitaux ont accepté de participer à l'étude. La plupart des répondants étaient des femmes (337/432, 78 %), et la plupart avaient entre 25 et 44 ans (293/432, 68 %). La plupart des répondants étaient convaincus que leur lieu de travail et leur service de pharmacie géraient efficacement la demande des patients (314/389, 81 %) et la pandémie en général (263/394, 67 %). Ils ont aussi estimé que leurs équipes de travail travaillaient bien ensemble (314/386, 81 %). Fait intéressant : 22 % des répondants (86/391) convenaient ne pas avoir reçu de formation sur les pratiques de prévention et de contrôle des infections à la COVID-19. Le score moyen sur l'échelle WEMWBS était de 48,9 (écart type 8,6), ce qui indique un bien-être mental moyen. Conclusions: Après la première vague de la pandémie de COVID-19, les répondants ont perçu leurs hôpitaux et leurs services comme étant capables de gérer la pandémie et ont déclaré un bien-être mental moyen. Veiller à ce que tous les pharmaciens d'hôpitaux reçoivent une formation sur les pratiques efficaces de prévention et de contrôle des infections à la COVID-19 est crucial. On ne sait pas comment leurs perceptions et leur bien-être ont changé depuis le moment de l'enquête.

Subtherapeutic concentrations of posaconazole tablet: determining risk factors and effectiveness of a standardized dose adjustment in hematology inpatients.

Posaconazole is indicated for antifungal prophylaxis in hematology patients at high-risk of invasive fungal infections (IFI). Consensus guidelines recommend maintaining steady-state trough concentrations above 0.7 mg/L; however, upto one-third of patients return subtherapeutic concentrations which is associated with breakthrough IFI. This retrospective observational study of 496 concentrations from 90 hematology inpatients prescribed posaconazole tablet (PCZ-tab) between May 2017 and May 2019 identified 24% (n = 121) of posaconazole concentrations were subtherapeutic after the dosage of 300 mg daily. On multivariable analyses, diarrhea (p = 0.002), male gender (p = 0.018), and concurrent regular metoclopramide (p = 0.002) were significantly associated with subtherapeutic posaconazole concentrations. Eighty-nine percent of patients (n = 16) who underwent dose adjustment to 200 mg twice daily successfully achieved target posaconazole concentrations at first steady-state measurement. This study confirms that therapeutic drug monitoring of posaconazole remains necessary as subtherapeutic posaconazole concentrations are relatively common, and that dose adjustment of 200 mg twice daily, safely enabled achievement of therapeutic concentrations.

Pharmacist review of high-risk haematology outpatients to improve appropriateness of antifungal prophylaxis.

Background Patients with haematological malignancies are at high risk of invasive fungal infections. However, there is a lack of information about the utilisation of the recommended Australian antifungal prophylaxis guidelines in haematology outpatients. Objective To assess the impact of a weekly pharmacist review of high-risk adult haematology outpatients on the utilisation of appropriate antifungal prophylaxis. Setting Outpatient cancer centre, tertiary referral hospital in Sydney, Australia. Method A 3-month pre-and post-interventional study was conducted. A retrospective audit was conducted to obtain baseline utilisation of antifungal guidelines in adult haematology outpatients with acute myeloid leukemia, acute lymphoblastic leukemia and myelodysplastic syndrome receiving chemotherapy. This was followed by a weekly pharmacist review over a 3-month period of all eligible outpatients assessing the appropriateness of antifungal agent, dose, use of therapeutic drug monitoring and presence of drug-interactions/contraindications. Recommendations to physicians were conveyed weekly and outcomes recorded. Main outcome measure Appropriate utilisation of antifungal prophylaxis guidelines in outpatient haematology patients before and after implementation of a 3-month weekly pharmacist review service. Results Forty patients were included in the retrospective group, equating to 348 reviews, while 42 patients equating to 269 reviews were included in the prospective group. Appropriate utilisation of antifungal prophylaxis guidelines increased from 31 to 54% post implementation of a pharmacist review (Odds Ratio = 2.44, 95% Confidence Interval: 1.07-5.58, p = 0.0344). The most common reason for nonadherence to guidelines in both groups was lack of therapeutic drug monitoring and failure to prescribe antifungal prophylaxis where indicated. The percentage of appropriate use of antifungal prophylaxis in patients with acute myeloid leukemia increased from 13 to 46% (p value < 0.01) after pharmacist intervention. The pharmacist made 153 recommendations from 269 reviews, with a percentage uptake of 40%. Moderate to severe drug interactions were identified in 19 reviews from 10 patients. One major azole antifungal-chemotherapy interaction was avoided. Conclusions Appropriate utilisation of antifungal prophylaxis guidelines can be improved through a regular pharmacist review. Future studies should identify whether improving adherence to antifungal guidelines leads to improved patient outcomes.

Predictive Validity of a QTc Interval Prolongation Risk Score in the Intensive Care Unit.

BACKGROUND: Torsade de pointes is a form of polymorphic ventricular tachycardia associated with heart rate-corrected QT (QTc ) interval prolongation. With approximately 24-61% of critically ill patients experiencing QTc interval prolongation, a predictive tool to identify high-risk patients could assist in the monitoring and management in the intensive care unit (ICU). The Tisdale et al. Risk Score (TRS) is a predictive tool that was developed and validated in a cardiac critical care unit. OBJECTIVES: The objective of this study was to evaluate the predictive validity (sensitivity and specificity) and likelihood ratios of the TRS in a medical ICU. METHODS: This was a longitudinal, retrospective, cohort study of consecutive patients who met the inclusion criteria from October 2017 to June 2018 with a sample size of 264 patients. The sample size was derived based on the number of TRS covariates and an exploratory variable. Baseline characteristics and risk factors were documented from electronic health records. The first occurrence of QTc interval prolongation, defined as a QTc interval > 500 ms or an increase ≥ 60 ms above baseline, was the primary endpoint. MAIN RESULTS: The sensitivity and specificity of the TRS for low-risk patients against the moderate-risk and high-risk patients were 97% (95% CI 91-99%) and 16% (95% CI 11-23%), respectively. These results corresponded to a positive likelihood ratio of 1.15 (95% CI 1.07-1.24) and a negative likelihood ratio of 0.20 (95% CI 0.06-0.65). CONCLUSIONS: In conclusion, the TRS showed a high sensitivity, making it useful in identifying patients at risk of developing QTc interval prolongation. Furthermore, patients categorized as low risk by the tool can be considered as having minimal risk of developing QTc interval prolongation. Given the tool's low specificity, it does not reliably identify all patients at low risk of QTc interval prolongation.

Single antiplatelet therapy for patients with previous gastrointestinal bleeds.

OBJECTIVE: To determine whether aspirin plus a proton pump inhibitor (PPI) is preferable, from a gastrointestinal bleed (GIB) risk perspective, to clopidogrel in patients who have experienced a GIB while on aspirin and who require single antiplatelet therapy for secondary prevention of cardiovascular disease. DATA SOURCES: A literature search was conducted using EMBASE (1980-January 2008), PubMed (1966-January 2008), Google, and a manual search of the reference lists using the search terms gastrointestinal bleed, gastrointestinal hemorrhage, peptic ulcer hemorrhage, ASA, aspirin, Plavix, clopidogrel, and PPI. The search, limited to human and English studies, yielded 110 returns. STUDY SELECTION AND DATA EXTRACTION: Randomized trials that compared aspirin with clopidogrel, involved patients who had previously experienced a GIB, and provided detailed information on the type and dose of drugs used were included. Studies were required to provide information on the recurrence of GIB. DATA SYNTHESIS: Two randomized trials were reviewed to assess the safety of secondary prevention of cardiovascular disease with respect to previous GIB. These noninferiority trials compared aspirin plus a PPI with clopidogrel over 12 months following confirmed healing of an aspirin-induced ulcer. In both trials, the majority of the GIB recurrences were in the clopidogrel group (8.6% vs 0.7%; difference 7.9%; 95% CI 3.4 to 12.4; p = 0.001 and 13.6% vs 0%; difference 13.6%; 95% CI 6.3 to 20.9; p = 0.0019) and the difference in recurrence rates exceeded the a priori selected upper boundary. CONCLUSIONS: Findings reported in the limited literature available support that clopidogrel is not equivalent to the combination of aspirin plus a PPI in the patient population studied. Aspirin plus a PPI would be considered clinically superior and should be used in medically managed patients who require single antiplatelet therapy but have had a prior GIB while on aspirin. Further research regarding dual antiplatelet therapy and a PPI is required.

Intravenous warfarin as an alternative for anticoagulation.

Oral warfarin is the standard of care for patients requiring long-term anticoagulation due to venous thromboembolic disease. Patients with Crohn's disease may have reduced absorption in the small bowel due to loss of effective surface area secondary to chronic inflammation, ulcerative lesions, or resection. A 27-year-old Caucasian woman with end-stage Crohn's disease was hospitalized with an upper extremity thrombosis. In this complicated patient, who was resistant to oral warfarin and unable to receive subcutaneous low-molecular-weight heparin, therapeutic anticoagulation was achieved with intravenous warfarin. Intravenous warfarin provides an alternative administration route for patients who cannot receive the oral formulation and cannot be administered subcutaneous low-molecular-weight heparins due to adverse effects.