Evidence for a bifactor structure of the Scales of Psychological Well-being using exploratory structural equation modeling

This research investigates the much-debated factor structure of the 54-item version of Ryff’s (1989) Scales of Psychological Well-being (SPWB). Using two samples (n1 = 573; n2 = 449) of undergraduate university students, we apply confirmatory factor analysis (CFA) along with recently developed exploratory structural equation modeling (ESEM) techniques to evaluate several unidimensional and multidimensional models identified in previous research, as well as a new bifactor model. In a bifactor model, items load directly on both a global and a specific factor; when tested using ESEM, cross-loadings on other specific factors are also permitted and are targeted to be as close to zero as possible. After comparing various ESEM and traditional CFA models, the results indicate that a bifactor model estimated using ESEM provided the best fit to the data. Most items were found to reflect the global factor, but some items failed to reflect the intended specific factor. Thus, the 54-item version of the SPWB appears to be a good measure of overall psychological well-being, but may need refinement as a measure of the intended specific factors, at least among young adults. The benefits of applying ESEM to investigate the factor structure of the SPWB in other populations are discussed

Evaluating Student Performance and Perception of a Workshop Integrating Pharmacy Practice and a Pharmaceutics Lab

  Objective: Evaluating Student Performance and Perception of a Workshop Integrating Pharmacy Practice and a Pharmaceutics Lab Innovation: Common methods for curricular integration are often time and faculty-intensive. An innovative approach to integration was developed and utilized in an introductory compounding workshop. Faculty members collaborated with a compounding pharmacist to design and facilitate a pharmaceutics workshop for first-year pharmacy students.  The workshop was composed of four major sections, an introduction to pharmaceutical compounding and the regulations surrounding manufacturing and sterility, a case discussion involving a pediatric patient and the need to develop an appropriate drug delivery system, a short review of pharmaceutical calculations and labeling requirements, and then an introduction to logistics and active learning in a lab setting. Critical Analysis: After taking part in the workshop, students indicated a significantly higher comfort level going into the pharmaceutics lab (3.48±0.83 to 4.04±0.70) and in the compounding process (3.06±0.83 to 3.71±0.80). Their views of the clinical application of the lab and the need to use knowledge gained from other courses in the lab were also significantly improved (4.36±0.68 to 4.61±0.49 and 3.71±0.77 to 4.26±0.74, respectively). In addition, their perceptions of how they will utilize the skills developed as a practicing pharmacist, and their feelings towards the safety procedures involved in compounding, were also positively affected (3.96±0.87 to 4.45±0.59 and 3.28±0.92 to 3.91±0.72, respectively). Finally, students’ average quiz score in Spring 2016, when the workshop was instituted, significantly increased from Spring 2015 (90.154±4.98 versus 85.89±10.87, respectively). Article Type:  Not

Mapping alterations to the endogenous elemental distribution within the lateral ventricles and choroid plexus in brain disorders using X-ray fluorescence imaging

The choroid plexus and cerebral ventricles are critical structures for the production of cerebral spinal fluid (CSF) and play an important role in regulating ion and metal transport in the brain, however many aspects of its roles in normal physiology and disease states, such as psychiatric illness, remain unknown. The choroid plexus is difficult to examine in vivo, and in situ ex vivo, and as such has typically been examined indirectly with radiolabeled tracers or ex vivo stains, making measurements of the endogenous K+, Cl-, and Ca+ distributions unreliable. In the present study, we directly examined the distribution of endogenous ions and biologically relevant transition metals in the choroid plexus and regions surrounding the ventricles (ventricle wall, cortex, corpus callosum, striatum) using X-ray fluorescence imaging (XFI). We find that the choroid plexus was rich in Cl- and Fe while K+ levels increase further from the ventricle as Cl- levels decrease, consistent with the known role of ion transporters in the choroid plexus CSF production. A polyI:C offspring displayed enlarged ventricles, elevated Cl- surrounding the ventricles, and intraventricular calcifications. These observations fit with clinical findings in patients with schizophrenia and suggest maternal treatment with polyI:C may lead to dysfunctional ion regulation in offspring. This study demonstrates the power of XFI for examining the endogenous elemental distributions of the ventricular system in healthy brain tissue as well as disease models

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Perceptions of prescription warning labels within an underserved population

Objective: To understand whether underserved populations attend to prescription warning label (PWL) instructions, examine the importance of PWL instructions to participants and describe the challenges associated with interpreting the information on PWLs.Methods: Adults from an underserved population (racial and ethnic minorities, individuals with low income, older adults) who had a history of prescription medication use and were able to understand English took part in semi-structured interviews. Participants were presented with eight different prescription bottles with an attached PWL. Participants were asked, “If this prescription was yours, what information would you need to know about the medicine?” The number of participants who attended to the warning labels was noted. Other questions assessed the importance of PWLs, the challenges with understanding PWLs, and ways a pharmacist could help participant understanding of the PWL.Results: There were 103 participants. The mean age was 50.25 years (SD=18.05). Majority attended to the PWL. Participants not currently taking medications and who had limited health literacy were likely to overlook the warning labels. Majority rated the warning instructions to be extremely important (n=86, 83.5 %), wanted the pharmacist to help them understand PWLs by counseling them on the information on the label (n=63, 61.2%), and thought the graphics made the label information easy to understand.Conclusions: PWLs are an important method of communicating medication information, as long as they are easily comprehensible to patients. In addition to placing PWLs on prescription bottles, health care providers need to counsel underserved populations on medication warnings, especially individuals with limited health literacy who are not currently using a prescription medication

A Pharmacokinetic and Pharmacodynamic Investigation of an ε-Aminocaproic Acid Regimen Designed for Cardiac Surgery With Cardiopulmonary Bypass

Objective: To investigate the pharmacokinetics and pharmacodynamics of an ε-aminocaproic acid (EACA) regimen designed for cardiac surgery with cardiopulmonary bypass (CPB). Design: Prospective observational study requiring blood sampling to measure EACA concentrations and fibrinolysis markers (fibrinogen, D-dimer, α2-antiplasmin, and tissue plasminogen activator-plasminogen activator inhibitor [tPA-PAI-1] complex). Setting: Single-center, tertiary medical center. Participants: Patients who underwent cardiac surgery with CPB between 2018 and 2019 for aortic or mitral valve replacement/repair or coronary artery bypass grafting. Previous sternotomy patients were included. Intervention: None. Measurements and Main Results: The pharmacokinetics of EACA, during CPB, were described by a 3-compartment disposition model. EACA concentrations were greater than 130 mg/L in all patients after CPB and in most patients during CPB. The D-dimer level trended up and reached a peak median level of 1.35 mg/L of fibrinogen equivalence units (FEU) at 15 minutes after protamine administration. The median change in D-dimer (ΔD-dimer) from baseline to 15 minutes after protamine was 0.34 (–0.48 to 3.81) mg/L FEU. ΔD-dimer did not correlate with EACA concentration intraoperatively, urine output, body weight, glomerular filtration rate, cell salvage volume, and ultrafiltration volume. The median 24-hour chest tube output was 445 (180-1,011) mL. Conclusion: This regimen provided maximum EACA concentrations near the time of protamine administration, with a total perioperative dose of 15 g. Most patients had EACA concentrations greater than the target during CPB. ΔD-dimer did not correlate with EACA concentration. The median 24-hour chest tube output compared well to similar studies that used higher doses of EACA