Dosing strategies for switching from oral risperidone to paliperidone palmitate: Effects on clinical outcomes.

IntroductionThere are currently no guidelines for switching patients from oral risperidone to paliperidone palmitate (Invega Sustenna®). Furthermore, the paliperidone long-acting injectable (LAI) package insert does not recommend bridging with oral antipsychotics, which may result in inadequate serum concentrations in patients on ≥4 mg/d risperidone.MethodsThis study evaluated the effects of suboptimal dosing and bridging in patients switched from oral risperidone to paliperidone LAI on hospitalization days, emergency department (ED)/mental health urgent care visits, and no-shows/cancellations to mental health appointments. Patients were categorized into optimal or suboptimal dosing based on their loading and maintenance paliperidone doses. Patients on risperidone ≥4 mg/d were categorized as bridged if they received risperidone for ≥7 days after the first paliperidone injection.ResultsThere were no significant differences in outcomes between optimally and suboptimally dosed patients. There were statistically significant reductions in hospitalization days in patients who were bridged compared with patients who were not bridged. There were statistically significant reductions in hospitalization days and ED/mental health urgent care visits after switching to paliperidone LAI.DiscussionThe results of this study indicate that bridging patients who are on ≥4 mg/d risperidone, when converting to paliperidone LAI, is associated with reductions in hospitalization days. However, more research is required to determine the optimal dose and duration of the bridge. The results also indicate that switching patients from oral risperidone to paliperidone LAI, even if the dose is suboptimal, is associated with reductions in hospitalization days and ED/mental health urgent care visits

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Combination nicotine replacement therapy: strategies for initiation and tapering.

Several studies and meta-analyses have demonstrated the efficacy of combination nicotine replacement therapy (NRT) for patients who wish to quit smoking. However, there is limited guidance with respect to initiation and tapering of combination NRT. We attempt to review the evidence and rationale behind combination NRT, present the dosing used in combination NRT studies, and propose a step-down approach for tapering of combination NRT with integration of behavioral strategies

Implementation and Evaluation of a 10-Week Health Equity Curriculum for Pharmacy Students.

Objective To describe a health equity curriculum created for pharmacy students and evaluate students' perceptions and structural competency after completion of the curriculum.Methods A health equity curriculum based on transformative learning and structural competency frameworks was implemented as a 10-week mandatory component of the pass-no pass neuropsychiatric theme for second year pharmacy students. Each week, students reviewed materials around a neuropsychiatric-related health equity topic and responded to discussion prompts through asynchronous forums or synchronous online video discussions. The effectiveness of the health equity curriculum was evaluated through assessment of structural competency through a validated instrument, an objective structured clinical examination (OSCE), and a questionnaire.Results All enrolled second year pharmacy students (n=124) participated in the health equity curriculum. Of the 75 students who completed the structural competency instrument, 46 (61%) were able to identify structural determinants of health, explain how structures contribute to health disparities, or design structural interventions. Ninety-six of the 124 students (77%) were able to address their OSCE standardized patient's mistrust in the health care system. Thematic analysis of student comments elucidated three themes: allyship, peer connection, and self-awareness. Students rated asynchronous discussion forums as significantly less effective than online video discussions and patient cases for achieving curricular objectives.Conclusion A mandatory curriculum delivered remotely throughout the didactic pharmacy curriculum using a blended learning approach was an effective way to incorporate health equity content and conversations into existing courses. Implementation of this or similar curriculums could be an important step in training pharmacy students to be advocates for social justice

Student Performance Outcomes and Perceptions in Two Content Areas in Conventional Versus Integrated Pharmacy Curricula.

Objective. To compare student performance measures and perceptions of learning in 2 content areas, conventional and integrated pharmacy curricula, at a single institution.Methods. Prospective cohort study of pharmacy students enrolled in either conventional (cohort C) or integrated (cohort I) curricula. Summative examination performance in the neuropsychiatric and infectious diseases courses, student self-rating of confidence and comfort in integrating and applying knowledge, and performance on a delayed knowledge assessment were compared between cohorts.Results. Cohort I students performed significantly lower on summative assessments compared to cohort C (78.4±9.1 vs 84.5±8.3, respectively). Prior to the integrated course, cohort I students rated themselves as significantly less confident and comfortable in knowledge integration, application, and communication compared to cohort C students; these differences were attenuated in a follow-up survey, although some remained significant. There was no difference between cohorts in performance on objective structured clinical examinations (OSCEs) or on a delayed knowledge assessment of neuropsychiatric and infectious diseases content.Conclusion. Pharmacy students in an integrated curriculum initially performed modestly worse in summative assessments and self-assessed their baseline knowledge as lower than did students in a conventional curriculum. However, differences in self-rated knowledge decreased at follow-up, and performance of the two cohorts on OSCEs and a delayed examination was similar. As pharmacy curricula shift towards integrated models, institutions should also consider evaluating experiential performance outcomes and student motivation to fully assess the impact of these transitions

Characterizing Participant Perceptions about Smoking-Cessation Pharmacotherapy and E-Cigarettes from Facebook Smoking-Cessation Support Groups.

The prevalence of smoking among young adults aged 19-28 years old in the United States persists at rates of 14.3%. Young adults underutilize pharmacotherapy for smoking cessation, and the use of e-cigarettes has increased. We analyzed comments from online smoking-cessation support groups to understand young-adult smokers' views of pharmacotherapy and e-cigarettes, to provide a more in-depth insight into the underutilization of pharmacotherapy. A qualitative analysis was performed on comments about pharmacotherapy and e-cigarettes from participants enrolled in online smoking-cessation support groups in 2016-2020. A codebook was developed with a deductive approach to code the comments, followed by thematic analysis. Eighteen themes were identified, with four dominant themes: interest, benefit, knowledge, and flavor. Participants expressed less interest in both nicotine-replacement therapy and e-cigarettes; moreover, they expressed unfamiliarity with and misconceptions about pharmacotherapy, and recognized the enticing flavors of e-cigarettes. Participants often felt e-cigarettes were not useful for smoking cessation, but the flavors of e-cigarettes were appealing for use. Participants had mixed opinions about the use of e-cigarettes for smoking cessation, but predominantly felt e-cigarettes were not useful for smoking cessation. The use of social media may be an effective way to address misconceptions about pharmacotherapy for smoking cessation and increase willingness to accept assistance

Incidence of postoperative seizures in neonates following cardiac surgery with regional cerebral perfusion and deep hypothermic circulatory arrestCentral MessagePerspective

Objectives: Historically, our center has primarily used deep hypothermic circulatory arrest, but in recent years some surgeons have selectively used regional cerebral perfusion as an alternative. We aimed to compare the incidence of postoperative electroencephalographic seizure incidence in neonates undergoing surgery with regional cerebral perfusion and deep hypothermic circulatory arrest. Methods: A retrospective analysis was performed in neonates who underwent surgery between 2012 and 2022 with either deep hypothermic circulatory arrest or regional cerebral perfusion with routine postoperative continuous electroencephalography monitoring for 48 hours. Propensity matching was performed to compare postoperative seizure risk between the 2 groups. Results: Among 1136 neonates undergoing cardiac surgery with cardiopulmonary bypass, regional cerebral perfusion was performed in 99 (8.7%) and deep hypothermic circulatory arrest in 604 (53%). The median duration of regional cerebral perfusion was 49 minutes (interquartile range, 38-68) and deep hypothermic circulatory arrest was 41 minutes (interquartile range, 31-49). The regional cerebral perfusion group had significantly longer total support, cardiopulmonary bypass, and aortic crossclamp times. Overall seizure incidence was 11% (N = 76) and 13% (N = 35) in the most recent era (2019-2022). The unadjusted seizure incidence was similar in neonates undergoing regional cerebral perfusion (N = 12, 12%) and deep hypothermic circulatory arrest (N = 64, 11%). After propensity matching, the seizure incidence was similar in neonates undergoing regional cerebral perfusion (N = 12, 12%) and deep hypothermic circulatory arrest (N = 37, 12%) (odds ratio, 0.97; 95% CI, 0.55-1.71; P = .92). Conclusions: In this contemporary single-center experience, the incorporation of regional cerebral perfusion did not result in a change in seizure incidence in comparison with deep hypothermic circulatory arrest. However, unmeasured confounders may have impacted these findings. Further studies are needed to determine the impact, if any, of regional cerebral perfusion on postoperative seizure incidence