Citations

Abstract Purpose No consistent recommendations exist on how best to educate pharmacists to facilitate implementation of new evidence-based practices. This study aimed to determine whether spaced learning was more effective than traditional education when learning a new evidence-based practice (β-lactam therapeutic drug monitoring, or TDM). Summary β-lactam TDM was implemented in a phased fashion at Mayo Clinic in Rochester. Two go-lives took place, separated by 6 months, which allowed for a natural experiment to test education delivery methods (traditional education in the first go-live group of pharmacists vs spaced learning in the second go-live group of pharmacists). Each group received the same base educational package, with pharmacists in the spaced learning group also offered monthly in-person sessions for 6 months before go-live to discuss key considerations and cases with experts. There was no difference between the spaced learning group and the traditional education group when assessing appropriate use of TDM as defined by (1) appropriate patient selection; (2) correct ordering of laboratory testing; (3) appropriate clinical action; and (4) completed documentation. Assessments of secondary knowledge transfer also showed no difference between the groups. Pharmacists in the different education groups had similar satisfaction scores related to the effect and utility of the education. Both spaced learning and traditional education were part of a comprehensive implementation plan for β-lactam TDM, which might have influenced the outcomes. Spaced learning for future pharmacist education efforts needs further study. Conclusion As part of a greater β-lactam TDM implementation effort, altering the education delivery method did not impact the degree of knowledge transfer.

Abstract Aims Patients with end-stage renal disease (ESRD) and atrial fibrillation present a challenge for thromboembolic prevention, given their elevated risks of both thromboembolism and bleeding. Anticoagulants carry a higher bleeding risk in this population without clear evidence of thromboembolic benefit. This study aims to define the role of left atrial appendage occlusion (LAAO) as a preventive strategy for patients with ESRD. Methods and results A systematic literature review was conducted to identify studies reporting outcomes in patients with ESRD who underwent LAAO. Meta-analyses of aggregate and individual patient data were performed to evaluate acute and long-term outcomes and compare them with those of patients without ESRD. Seventeen studies reporting data from 24 127 patients, including 1047 with ESRD, were included. Procedural complications were more common in patients with ESRD (RR 2.23; P = 0.02), with a pooled rate of 4% (95% CI, 1–9%). There was no significant difference in thromboembolic event rates during follow-up between the groups (IRR 1.44; P = 0.16), but major bleeding incidence was higher among patients with ESRD (IRR 1.84; P < 0.01). Individual patient-level data from seven studies comprising 4745 patients (268 with ESRD) were obtained and analysed. Similarly, there was no significant association between ESRD and stroke/TIA incidence (HR, 1.22; 95% CI, 0.66–2.26), but major bleeding was higher on patients with ESRD (HR, 1.65; 95% CI, 1.01–2.69). Conclusion LAAO represents a feasible option for thromboembolic prevention in patients with ESRD, although these patients have an increased risk of complications and bleeding.

Introduction: Reversible and irreversible nephrotoxicity are known complications of tacrolimus. Approaches to reduce the incidence of nephrotoxicity include the reduction or avoidance of tacrolimus but must be weighed against risk of rejection. Infrequently, basiliximab has been used outside of the induction period to facilitate temporary tacrolimus cessation in the setting of acute kidney injury (AKI). Objective: The primary objective of this study was to describe renal recovery after temporary tacrolimus cessation with non-induction basiliximab (NIB) compared to a matched cohort. Methods: We conducted a single-center study of adult cardiothoracic transplant recipients that received basiliximab beyond post-operative day 7 for temporary tacrolimus cessation in the setting of AKI between January 2019 and November 2023 and matched them to acontrol cohort. Results: Twelve patients underwent temporary tacrolimus cessation with NIB. In total, 7 (58%) patients achieved initial renal recovery at tacrolimus resumption compared to 15 (42%) patients in the matched cohort at an equivalent time point. No difference between treated rejection (17% vs. 19%, p = 0.80) or infection (75% vs. 50%, p = 0.32) was observed between tacrolimus cessation and its matched cohort. Conclusions: The use of NIB for tacrolimus cessation can allow for potential renal recovery after an AKI or in patients at risk of AKI. This approach does not appear to significantly increase the risk of rejection but may increase the risk of infection in the long term.

Acute respiratory distress syndrome (ARDS) is a common and highly heterogeneous condition in the critically ill. The association between hyper- and hypo-inflammatory subphenotypes and clinical outcomes has generated significant interest in precise ARDS management. The value of identifying biomarkers to guide treatment and enrollment in future ARDS trials is undisputable. We describe multiple factors complicating the search for subphenotypes and their treatable traits. The observed heterogeneity seen in the clinical course of ARDS is dynamic and influenced by factors beyond lung pathophysiology, including variations in the delivery of best critical care practices, patient comorbidities, and functional status, and patient or family preferences. Current subphenotype definitions lack strong biological plausibility and without clear evidence of benefit from targeted treatments, their use in clinical practice is currently unwarranted.

ABSTRACTBackgroundRecent data demonstrate increased incidence of Infantile hemangioma (IH) over the past several decades. However, little is known about current trends in healthcare utilization and medication prescribing in patients with IH in the United States (US), particularly since the discovery and uptake of beta‐blockers as standard of care treatment.MethodsWe examined US ambulatory visits in infants (age ≤ 1 years) with any hemangioma (International Classification of Diseases [ICD] 9th Revision codes 228.00, 228.01, or 228.09 in the National Ambulatory Medical Care Survey [NAMCS] 2009–2015, and ICD 10th Revision code D18.0 in the NAMCS 2016–2019). We further trended the prescription of topical and systemic IH treatments during this period.ResultsYears of visit were bundled into 5‐year bins to minimize standard errors for the trend tests. The number of visits related to IH significantly increased from 878,725 (95% CI: 439,376–1,318,074) in 2009–2013 to 1,431,913 (95% CI: 940,036–1,923,790, p = 0.022) in 2014–2019. The number of visits with resulting timolol prescription concurrently significantly increased from 16,279 (95% CI: 0–40,600) to 424,845 (95% CI: 380,786–468,903, p < 0.001), while the increase in the number of propranolol prescriptions was nonsignificant (from 162,323 [95% CI: 0–331,537] to 208,139 [95% CI: 0–558,709], p = 0.652).ConclusionsThe US healthcare utilization for IH has been on the rise between 2009 and 2019, likely owing to increased awareness, earlier diagnosis, and enhanced therapies. While topical beta‐blocker prescriptions have significantly increased during that period of time, systemic beta‐blocker prescription rates have not.

Background: Breast cancer is the most common cancer that causes death among women worldwide. In Ethiopia, though there has not been an adequate study, the incidence of new cases of breast cancer is currently increasing and has become one of the most common cancer types, causing high rates of morbidity and mortality. Mutation in the BRCA1 gene in 5832insC regions has been demonstrated as the most common genetic factor that increases the occurrence of breast cancer. Thus, this study aimed to detect the frequency of 5832insC gene polymorphism in the BRCA1 gene and its associated risk factors among breast cancer-positive patients visiting the study sites. Materials and Methods: A cross-sectional study was conducted on 100 blood samples of females with breast cancer. Following genomic DNA isolation, PCR amplification was done using specific primer pairs for 5832insC BRCA1 regions. The amplified products were digested with restriction enzymes (HinfI) to detect 5382insC polymorphism. Results: Based on the findings of this study, family history was the only variable that had a significant association (P = 0.001) with 5382insC mutation in the BRCA1 gene. On the other hand, alcohol consumption (P = 0.542), age (P = 0.376), and residence zone (P = 0.856) of the participant did not show any association for this mutation. The total frequency of 5382insC BRCA1 gene mutations in the study participants was found to be 6%. Conclusion: The present study confirmed that 5382insC was the potential BRCA1 alterations that have been encountered in most breast cancer patients in the study area. The use of molecular techniques for early breast cancer detection is highly recommended to improve treatment efficiency and minimize the rate of mortality.

Background/Objectives: GaBHA syndrome (gastric bypass hyperammonemia) is an emerging new syndrome primarily in women who had prior Roux-en-Y gastric bypass surgery (RYGB) and then developed non-cirrhotic hyperammonemia with a high case–fatality ratio. Genetic and nutritional deficiencies have been implicated in the pathogenesis of this clinical condition, but none has been proven. We present an illustrative case and do a scoping review of the current literature in 58 patients with this diagnosis. Methods: A retrospective scoping literature review was utilized to identify patients who fulfilled 1. RYGB surgery, and 2. Hyperammonemic encephalopathy following the PRISMA extended checklist. We searched PubMed, MedLine, SCOPUS, and Web of Science databases. Results: We described the classic presenting symptoms and laboratory findings of this syndrome. We confirmed the female predominance (93%) and the high case–fatality ratio (32%). We then presented a novel hypothesis contending that arginine deficiency ultimately leads to a functional deficiency of the ornithine transcarbamolyase (OTC) enzyme, leading to the non-cirrhotic life-threatening hyperammonemia. Our hypothesis may also explain the high incidence of hypoglycemia found in these patients as we found in our search. Our proposed hypothesis may also be relevant to the occurrence of hyperammonemia in some solid organ transplant recipients. Conclusions: GaBHA syndrome is emerging as an important potential adverse outcome after RYGB surgery. It has a female predominance and a high case–fatality ratio. Arginine deficiency may explain the emergence of a functional OTC deficiency, which then leads to the severe hyperammonemia, and may also explain the frequent occurrence of hypo-glycemia in these patients.

Sindbis virus (SINV), a prototype of the Alphavirus genus (family Togaviridae), is a globally distributed arbovirus causing febrile rash and debilitating arthritis in humans. Viral structural proteins—capsid (C), E1, and E2—are fundamental to the virion’s architecture, mediating all stages from assembly to host cell entry and pathogenesis, thus representing critical targets for study. This review consolidates the historical and current understanding of SINV structural biology, tracing progress from early microscopy to recent high-resolution cryo-electron microscopy (cryo-EM) and X-ray crystallography. We detail the virion’s precise T = 4 icosahedral architecture, composed of a nucleocapsid core and an outer glycoprotein shell. Key functional roles tied to protein structure are examined: the capsid’s dual capacity as a serine protease and an RNA-packaging scaffold that interacts with the E2 cytoplasmic tail; the E1 glycoprotein’s function as a class II fusion protein driving membrane fusion; and the E2 glycoprotein’s primary role in receptor binding, which dictates cellular tropism and serves as the main antigenic target. Furthermore, we connect these molecular structures to viral evolution and disease, analyzing how genetic variation among SINV genotypes, particularly in the E2 gene, influences host adaptation, immune evasion, and the clinical expression of arthritogenic and neurovirulent disease. In conclusion, the wealth of structural data on SINV offers a powerful paradigm for understanding alphavirus biology. However, critical gaps persist, including the high-resolution visualization of dynamic conformational states during viral entry and the specific molecular determinants of chronic disease. Addressing these challenges through integrative structural and functional studies is paramount. Such knowledge will be indispensable for the rational design of next-generation antiviral therapies and broadly protective vaccines against the ongoing threat posed by SINV and related pathogenic alphaviruses.

Introduction: Endovascular thrombectomy (EVT) is an effective treatment for basilar artery occlusion (BAO) stroke in select patients. While there is a growing body of literature suggesting that advanced imaging modalities such as computed tomography perfusion (CTP) and magnetic resonance (MR) may not be necessary for selecting anterior circulation large vessel occlusion stroke patients for EVT, whether advanced imaging may be superior to conventional imaging (non-contrast CT and CT angiography) in identifying good treatment candidates among BAO patients is less clear. Patients and methods: This was a multicenter retrospective cohort study of BAO EVT patients treated from 2013 to 2022 in the Stroke Thrombectomy and Aneurysm Registry. Patients selected for EVT by advanced imaging (CTP or MR) were matched with those selected by conventional imaging using propensity score matching (PSM) accounting for possible confounders. Primary outcome was functional independence at 90 days. Other outcomes include bedridden state or death at 90-days and symptomatic intracranial hemorrhage (sICH). Results: 268 patients were included. 150 patients were selected for BAO EVT by conventional imaging, 86 by CTP, and 32 by MR. Patients selected by advanced imaging were significantly older than those selected by conventional imaging (median age 71 vs 64 years, p = 0.001); patient characteristics were otherwise similar between cohorts. After PSM, 90-day outcomes were similar between the two cohorts ( p = 0.56), with similar rates of functional independence (39.4% vs 35.1%, p = 0.65), bedridden state or death (40.4% vs 44.7%, p = 0.66), and sICH (3.3% vs 5.7%, p = 0.49) for conventional and advanced imaging groups, respectively. Results were similar across treatment time windows (all p > 0.05). Conclusions: Selecting patients for basilar EVT using conventional versus advanced imaging did not result in different clinical outcomes, regardless of treatment time windows. Conventional imaging appears sufficient as a first-line tool for selecting basilar EVT patients in routine clinical practice.