LTP induction by structural rather than enzymatic functions of CaMKII.

Learning and memory are thought to require hippocampal long-term potentiation (LTP), and one of the few central dogmas of molecular neuroscience that has stood undisputed for more than three decades is that LTP induction requires enzymatic activity of the Ca2+/calmodulin-dependent protein kinase II (CaMKII)1-3. However, as we delineate here, the experimental evidence is surprisingly far from conclusive. All previous interventions inhibiting enzymatic CaMKII activity and LTP4-8 also interfere with structural CaMKII roles, in particular binding to the NMDA-type glutamate receptor subunit GluN2B9-14. Thus, we here characterized and utilized complementary sets of new opto-/pharmaco-genetic tools to distinguish between enzymatic and structural CaMKII functions. Several independent lines of evidence demonstrated LTP induction by a structural function of CaMKII rather than by its enzymatic activity. The sole contribution of kinase activity was autoregulation of this structural role via T286 autophosphorylation, which explains why this distinction has been elusive for decades. Directly initiating the structural function in a manner that circumvented this T286 role was sufficient to elicit robust LTP, even when enzymatic CaMKII activity was blocked.

Publisher Correction: A planet within the debris disk around the pre-main-sequence star AU Microscopii.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A planet within the debris disk around the pre-main-sequence star AU Microscopii.

AU Microscopii (AU Mic) is the second closest pre-main-sequence star, at a distance of 9.79 parsecs and with an age of 22 million years1. AU Mic possesses a relatively rare2 and spatially resolved3 edge-on debris disk extending from about 35 to 210 astronomical units from the star4, and with clumps exhibiting non-Keplerian motion5-7. Detection of newly formed planets around such a star is challenged by the presence of spots, plage, flares and other manifestations of magnetic 'activity' on the star8,9. Here we report observations of a planet transiting AU Mic. The transiting planet, AU Mic b, has an orbital period of 8.46 days, an orbital distance of 0.07 astronomical units, a radius of 0.4 Jupiter radii, and a mass of less than 0.18 Jupiter masses at 3σ confidence. Our observations of a planet co-existing with a debris disk offer the opportunity to test the predictions of current models of planet formation and evolution.

Derivation of a minimal functional XIST by combining human and mouse interaction domains.

X-inactive specific transcript (XIST) is a 17-19 kb long non-coding ribonucleic acid (RNA) critical for X-chromosome inactivation. Tandem repeats within the RNA serve as functional domains involved in the cis-limited recruitment of heterochromatic changes and silencing. To explore the sufficiency of these domains while generating a functional mini-XIST for targeted silencing approaches, we tested inducible constructs integrated into 8p in a male cell line. Previous results suggested silencing could be accomplished with a transgene comprised of the repeat A, which is highly conserved and critical for silencing; the repeat F that overlaps regulatory elements and the repeat E that contributes to XIST localization by binding proteins such as CIZ1 (AFE). As polycomb-repressive complex 1 (PRC1) is recruited through HNRNPK binding of repeats B-C-D, we included a second 'mini-XIST' comprising AFE with the mouse Polycomb Interaction Domain (PID), a 660-nucleotide region known to recruit PRC1. Silencing of an adjacent gene was possible with and without PID; however, silencing more distally required the addition of PID. The recruitment of heterochromatic marks, evaluated by immunofluorescence combined with RNA fluorescence in situ hybridization, revealed that the AFE domains were sufficient only for CIZ1 recruitment. However, mini-XIST transgene recruited all marks, albeit not to full XIST levels. The ability of the PID domain to facilitate silencing and heterochromatic mark recruitment was unexpected, and inhibition of PRC1 suggested that many of these are PRC1 independent. These results suggest that the addition of this small region allowed the partial recruitment of all the features induced by a full XIST, demonstrating the feasibility of finding a minimal functional XIST.

Short-term CaMKII inhibition with tatCN19o does not erase pre-formed memory in mice and is neuroprotective in pigs.

The Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a central regulator of learning and memory, which poses a problem for targeting it therapeutically. Indeed, our study supports prior conclusions that long-term interference with CaMKII signaling can erase pre-formed memories. By contrast, short-term pharmacological CaMKII inhibition with the neuroprotective peptide tatCN19o interfered with learning in mice only mildly and transiently (for less than 1 h) and did not at all reverse pre-formed memories. These results were obtained with ≥500-fold of the dose that protected hippocampal neurons from cell death after a highly clinically relevant pig model of transient global cerebral ischemia: ventricular fibrillation followed by advanced life support and electrical defibrillation to induce the return of spontaneous circulation. Of additional importance for therapy development, our preliminary cardiovascular safety studies in mice and pig did not indicate any concerns with acute tatCN19o injection. Taken together, although prolonged interference with CaMKII signaling can erase memory, acute short-term CaMKII inhibition with tatCN19o did not cause such retrograde amnesia that would pose a contraindication for therapy.

Independent domains for recruitment of PRC1 and PRC2 by human XIST.

XIST establishes inactivation across its chromosome of origin, even when expressed from autosomal transgenes. To identify the regions of human XIST essential for recruiting heterochromatic marks we generated a series of overlapping deletions in an autosomal inducible XIST transgene present in 8p of the HT1080 male fibrosarcoma cell line. We examined the ability of each construct to enrich its unified XIST territory with the histone marks established by PRC1 and PRC2 as well as the heterochromatin factors MacroH2A and SMCHD1. Chromatin enrichment of ubH2A by PRC1 required four distinct regions of XIST, and these were completely distinct from the two domains crucial for enrichment of H3K27me3 by PRC2. Both the domains required, as well as the impact of PRC1 and PRC2 inhibitors, suggest that PRC1 is required for SMCHD1 while PRC2 function is necessary for MacroH2A recruitment, although incomplete overlap of regions implicates roles for additional factors. This cooperativity between factors contributes to the requirement for multiple separate domains being required for each feature examined. The independence of the PRC1/PRC2 pathways was observed when XIST was expressed both autosomally or from the X chromosome suggesting that these observations are not purely a result of the context in which XIST operates. Although independent domains were required for the PRC1 and PRC2 pathways overall all regions tested were important for some aspect of XIST functionality, demonstrating both modularity and cooperativity across the XIST lncRNA.

X-linked neonatal-onset epileptic encephalopathy associated with a gain-of-function variant p.R660T in GRIA3.

The X-linked GRIA3 gene encodes the GLUA3 subunit of AMPA-type glutamate receptors. Pathogenic variants in this gene were previously reported in neurodevelopmental diseases, mostly in male patients but rarely in females. Here we report a de novo pathogenic missense variant in GRIA3 (c.1979G>C; p. R660T) identified in a 1-year-old female patient with severe epilepsy and global developmental delay. When exogenously expressed in human embryonic kidney (HEK) cells, GLUA3_R660T showed slower desensitization and deactivation kinetics compared to wildtype (wt) GLUA3 receptors. Substantial non-desensitized currents were observed with the mutant but not for wt GLUA3 with prolonged exposure to glutamate. When co-expressed with GLUA2, the decay kinetics were similarly slowed in GLUA2/A3_R660T with non-desensitized steady state currents. In cultured cerebellar granule neurons, miniature excitatory postsynaptic currents (mEPSCs) were significantly slower in R660T transfected cells than those expressing wt GLUA3. When overexpressed in hippocampal CA1 neurons by in utero electroporation, the evoked EPSCs and mEPSCs were slower in neurons expressing R660T mutant compared to those expressing wt GLUA3. Therefore our study provides functional evidence that a gain of function (GoF) variant in GRIA3 may cause epileptic encephalopathy and global developmental delay in a female subject by enhancing synaptic transmission.

A 20-year population study of peripartum cardiomyopathy.

BACKGROUND AND AIMS: The epidemiology of peripartum cardiomyopathy (PPCM) in Europe is poorly understood and data on long-term outcomes are lacking. A retrospective, observational, population-level study of validated cases of PPCM in Scotland from 1998 to 2017 was conducted. METHODS: Women hospitalized with presumed de novo left ventricular systolic dysfunction around the time of pregnancy and no clear alternative cause were included. Each case was matched to 10 controls. Incidence and risk factors were identified. Morbidity and mortality were examined in mothers and children. RESULTS: The incidence of PPCM was 1 in 4950 deliveries. Among 225 women with PPCM, obesity, gestational hypertensive disorders, and multi-gestation were found to be associated with having the condition. Over a median of 8.3 years (9.7 years for echocardiographic outcomes), 8% of women with PPCM died and 75% were rehospitalized for any cause at least once. Mortality and rehospitalization rates in women with PPCM were ∼12- and ∼3-times that of controls, respectively. The composite of all-cause death, mechanical circulatory support, or cardiac transplantation occurred in 14%. LV recovery occurred in 76% and, of those who recovered, 13% went on to have a decline in LV systolic function despite initial recovery. The mortality rate for children born to women with PPCM was ∼5-times that of children born to controls and they had an ∼3-times greater incidence of cardiovascular disease over a median of 8.8 years. CONCLUSIONS: PPCM affected 1 in 4950 women around the time of pregnancy. The condition is associated with considerable morbidity and mortality for the mother and child. There should be a low threshold for investigating at-risk women. Long term follow-up, despite apparent recovery, should be considered.

A narrative review of the well-being and burnout of U.S. community pharmacists.

OBJECTIVES: The purpose of this narrative review is to summarize the literature on well-being and burnout among community pharmacists in the U.S. and provide recommendations for future research. METHODS: Relevant literature was identified by searching PubMed for combinations of keywords such as "burnout" and "well-being" combined with "pharmacists." Titles and abstracts were reviewed for relevancy, and full text articles were reviewed when applicable. RESULTS: While burnout is defined by its 3 core symptoms of emotional exhaustion, depersonalization, and low personal accomplishment, well-being is more challenging to define and measure, which has led to it being less studied. Community pharmacists faced high rates of burnout, low quality of life (QOL), and extreme fatigue prior to the COVID-19 pandemic, a situation that has likely only worsened. Factors such as workload, the type of community pharmacy, the level of education or training of the pharmacist, and stress may be some of the contributors to high rates of burnout. Clinician burnout may be related to high rates of mental health disorders seen in pharmacists, may impact patient safety and satisfaction, and may affect productivity and costs to employers and the healthcare system overall. There has been no research into interventions or strategies to support well-being and reduce burnout among community pharmacists, but having a workplace that is perceived as supporting well-being may have some impact. Recommendations for future research include the following: (1) define well-being, (2) explore why various factors support well-being or contribute to burnout, (3) determine the impact of community pharmacists experiencing well-being or burnout, and (4) develop strategies to support well-being and reduce burnout that are specific to community pharmacy. CONCLUSION: There is a sparsity of evidence regarding community pharmacist well-being and burnout. Further research is needed to generate the evidence needed to support interventions that are specific to the unique work setting of community pharmacists.

Pregnancy-related risk factors and receipt of postpartum care among Texas Medicaid pregnant enrollees: Opportunities for pharmacist services.

BACKGROUND: The United States (US) experiences the highest rate of maternal mortality of similar countries. Postpartum care (PPC) focused on chronic disease management is potentially lifesaving, especially among pregnancies complicated by risk factors such as diabetes, hypertension, and mental health conditions (MHCs), which are conditions in which pharmacists can have an impact. OBJECTIVE: To evaluate the prevalence of maternal mortality risk factors and their relationships with receipt of PPC among Texas Medicaid enrollees. METHODS: A retrospective study included women with a delivery between 3/25/2014-11/1/2019 who were continuously enrolled in Texas Medicaid during the study period from 84 days pre-delivery to 60 days post-delivery. PPC was defined as ≥1 visit associated with postpartum follow-up services. Maternal mortality risk factors (diabetes, hypertension, and MHCs) during and after pregnancy were identified using diagnoses and medication utilization. Age, race/ethnicity, cesarean delivery, and preterm birth served as covariates. Multivariable logistic regression was used to address the study objective. RESULTS: The sample (N = 617,010) was 26.5±5.7 years, primarily (52.8%) Hispanic, and 33.0% had cesarean deliveries and 9.3% had preterm births. Risk factor prevalence included: diabetes (14.0%), hypertension (14.3%), and MHCs during (6.3%) and after (9.1%) pregnancy. A majority (77.9%) had a PPC visit within 60 days of delivery. The odds of receiving PPC were 1.2 times higher for patients with diabetes (OR = 1.183; 95% CI = 1.161-1.206; P < 0.0001), 1.1 times higher for patients with hypertension (OR = 1.109; 95% CI= 1.089-1.130; P < 0.0001), and 1.1 times higher for patients with MHCs (OR=1.138; 95% CI = 1.108-1.170; P < 0.0001) than patients without, respectively. CONCLUSION: Over three-quarters of Texas Medicaid pregnant enrollees received PPC within 60 days of delivery and risk factors were prevalent and predictive of receipt of PPC. Pharmacists can have a positive impact on maternal health by addressing hypertension, diabetes, and MHC risk factors.

Provider perceptions of barriers to biosimilar utilization in community oncology practices.

BACKGROUND: Biosimilars reduce the burden of cost on patients and payers, and so doing, increase access to life-saving care. However, biosimilar uptake in the US has been inconsistent. OBJECTIVES: This study assessed provider perceptions of barriers to biosimilar use and their relationships to utilization rates in a large, national oncology network and examined if perceptions differed by demographic and practice characteristics. METHODS: A 28-item survey was administered to 400 network physicians, pharmacists, nurses, and administrators, spanning 25 provider groups, and measured 1) barriers to use categorized into 4 subscales-payer-related, provider-related, operational, and patient-related, using a Likert scale ranging from Never (1) to Always (5); and 2) demographic and practice characteristics. Utilization rates were assessed using aggregated patient-level drug administration data found in the electronic health record system. Descriptive and inferential statistics were used to describe responses and assess relationships between variables. RESULTS: A total of 46 responses were analyzed, with a response rate of 11.5%. Most respondents were female (55.6%), physicians (52.2%), with over 6 years of experience (67%). A majority worked in practices participating in the Oncology Care Model (86.7%) and received continuing education on biosimilars (84.8%). Overall scale score was moderately low (mean=2.31), indicating low levels of perceived barriers. The lowest subscale score was operational barriers (mean=2.21), while payer-related barriers was the highest (mean=2.78). Perceptions of barriers did not differ based on demographic and practice characteristics. The average biosimilar utilization rate was 66.2%, with practices in the West administering biosimilars most frequently (71.8%). Utilization was not impacted by perceptions of barriers. CONCLUSION: Perceived barriers to biosimilar utilization were not common and not associated with utilization. Infrequent impediments to utilization may be associated with network-wide emphasis on continuing education and a value-based care environment. Future research should consider other practice- and patient-level factors that may impact biosimilar utilization.

The smallest likely pathogenic duplication of a SOX9 enhancer identified to date in a family with 46,XX testicular differences of sex development.

Copy number variants that duplicate distal upstream enhancer elements of the SOX9 gene cause 46,XX testicular differences of sex development (DSD) which is characterized by a 46,XX karyotype in an individual presenting with either ambiguous genitalia or genitalia with varying degrees of virilization, including those resembling typical male genitalia. Reported duplications in this region range in size from 24 to 780 kilobases (kb). Here we report a family with two affected individuals, the proband and his maternal uncle, harboring a 3.7 kb duplication of a SOX9 enhancer identified by clinical genome sequencing. Prior fluorescence in situ hybridization (FISH) for SRY and a multi-gene panel for ambiguous genitalia were non-diagnostic. The unaffected mother also carries this duplication, consistent with previously described incomplete penetrance. To our knowledge, this is the smallest duplication identified to-date, most of which resides in a 5.2 kb region that has been previously shown to possess enhancer activity that promotes the expression of SOX9. The duplication was confirmed by quantitative-PCR and shown to be in tandem by bidirectional Sanger sequencing breakpoint analysis. This finding highlights the importance of non-coding variant interrogation in suspected genetic disorders.

Assessing the association of stigma and HIV service and prevention uptake among men who have sex with men and transgender women in South Africa.

HIV prevention for gay, bisexual, and other men who have sex with men (GBMSM) and transgender women (TGW) is critical to reducing health disparities and population HIV prevalence. To understand if different types of stigma impact engagement with HIV prevention services, we assessed associations between stigmas and use of HIV prevention services offered through an HIV prevention intervention. This analysis included 201 GBMSM and TGW enrolled in a prospective cohort offering a package of HIV prevention interventions. Participants completed a baseline survey that included four domains of sexual identity/behavior stigma, HIV-related stigma, and healthcare stigma. Impact of stigma on PrEP uptake and the number of drop-in visits was assessed. No domain of stigma was associated with PrEP uptake. In bivariate analysis, increased enacted sexual identity stigma increased number of drop-in visits. In a logistic regression analysis constrained to sexual identity stigma, enacted stigma was associated with increased drop-in visits (aIRR = 1.30, [95% CI: 1.02, 1.65]). Participants reporting higher enacted stigma were modestly more likely to attend additional services and have contact with the study clinics and staff. GBMSM and TGW with higher levels of enacted stigma may seek out sensitized care after negative experiences in their communities or other healthcare settings.

Acoustic Change Complex Recorded in Hybrid Cochlear Implant Users.

INTRODUCTION: Expanding cochlear implant (CI) candidacy criteria and advances in electrode arrays and soft surgical techniques have increased the number of CI recipients who have residual low-frequency hearing. Objective measures such as obligatory cortical auditory-evoked potentials (CAEPs) may help clinicians make more tailored recommendations to recipients regarding optimal listening mode. As a step toward this goal, this study investigated how CAEPs measured from hybrid CI users differ in two listening modes: acoustic alone (A-alone) versus acoustic plus electric (A + E). METHODS: Eight successful hybrid CI users participated in this study. Two CAEPs, the P1-N1-P2 and the acoustic change complex (ACC), were measured simultaneously in response to the onset and change of a series of different and spectrally complex acoustic signals, in each of the two listening modes (A-alone and A + E). We examined the effects of listening mode and stimulus type on the onset and ACC N1-P2 amplitudes and peak latencies. RESULTS: ACC amplitudes in hybrid CI users significantly differed as a function of listening mode and stimulus type. ACC responses in A + E were larger than those in the A-alone mode. This was most evident for stimuli involving a change from low to high frequency. CONCLUSIONS: Results of this study showed that the ACC varies as a function of listening mode and stimulus type. This finding suggests that the ACC can be used as a physiologic, objective measure of the benefit of hybrid CIs, potentially supporting clinicians in making clinical recommendations on individualized listening mode, or to document subjective preference for a given listening mode. Further research into this potential clinical application in a range of hybrid recipients and/or long electrode users who have residual low-frequency hearing is warranted.

Acoustically Evoked Compound Action Potentials Recorded From Cochlear Implant Users With Preserved Acoustic Hearing.

OBJECTIVES: Less traumatic intracochlear electrode design and the introduction of the soft surgery technique allow for the preservation of low-frequency acoustic hearing in many cochlear implant (CI) users. Recently, new electrophysiologic methods have also been developed that allow acoustically evoked peripheral responses to be measured in vivo from an intracochlear electrode. These recordings provide clues to the status of peripheral auditory structures. Unfortunately, responses generated from the auditory nerve (auditory nerve neurophonic [ANN]) are somewhat difficult to record because they are smaller than the hair cell responses (cochlear microphonic). Additionally, it is difficult to completely segregate the ANN from the cochlear microphonic, complicating the interpretation and limiting clinical applications. The compound action potential (CAP) is a synchronous response of multiple auditory nerve fibers and may provide an alternative to ANN where the status of the auditory nerve is of primary interest. This study is a within-subject comparison of CAPs recorded using traditional stimuli (clicks and 500 Hz tone bursts) and a new stimulus (CAP chirp). We hypothesized that the chirp stimulus might result in a more robust CAP than that recorded using traditional stimuli, allowing for a more accurate assessment of the status of the auditory nerve. DESIGN: Nineteen adult Nucleus L24 Hybrid CI users with residual low-frequency hearing participated in this study. CAP responses were recorded from the most apical intracochlear electrode using a 100 µs click, 500 Hz tone bursts, and chirp stimuli presented via the insert phone to the implanted ear. The chirp stimulus used in this study was CAP chirp generated using parameters from human-derived band CAPs ( Chertoff et al. 2010 ). Additionally, nine custom chirps were created by systematically varying the frequency sweep rate of the power function used to construct the standard CAP chirp stimulus. CAPs were recorded using all acoustic stimuli, allowing for within-subject comparisons of the CAP amplitude, threshold, percentage of measurable CAP responses, and waveform morphology. RESULTS: Considerable variation in response morphology was apparent across stimuli and stimulation levels. Clicks and CAP chirp significantly evoked identifiable CAP response more compared to 500 Hz tone bursts. At relatively high stimulation levels, the chirp-evoked CAPs were significantly larger in amplitude and less ambiguous in morphology than the click-evoked CAPs. The status of residual acoustic hearing at high frequencies influenced the likelihood that a CAP could be reliably recorded. Subjects with better preserved hearing at high frequencies had significantly larger CAP amplitudes when CAP chirp was used. Customizing the chirp stimulus by varying the frequency sweep rates significantly affected the CAP amplitudes; however, pairwise comparisons did not show significant differences between chirps. CONCLUSIONS: CAPs can be measured more effectively using broadband acoustic stimuli than 500 Hz tone bursts in CI users with residual low-frequency acoustic hearing. The advantage of using CAP chirp stimulus relative to standard clicks is dependent on the extent of preserved acoustic hearing at high frequencies and the stimulus level. The chirp stimulus may present an attractive alternative to standard clicks or tone bursts for this CI population when the goal is to record robust CAP responses.

Longitudinal Electrocochleography as an Objective Measure of Serial Behavioral Audiometry in Electro-Acoustic Stimulation Patients.

OBJECTIVE: Minimally traumatic surgical techniques and advances in cochlear implant (CI) electrode array designs have allowed acoustic hearing present in a CI candidate prior to surgery to be preserved postoperatively. As a result, these patients benefit from combined electric-acoustic stimulation (EAS) postoperatively. However, 30% to 40% of EAS CI users experience a partial loss of hearing up to 30 dB after surgery. This additional hearing loss is generally not severe enough to preclude use of acoustic amplification; however, it can still impact EAS benefits. The use of electrocochleography (ECoG) measures of peripheral hair cell and neural auditory function have shed insight into the pathophysiology of postimplant loss of residual acoustic hearing. The present study aims to assess the long-term stability of ECoG measures and to establish ECoG as an objective method of monitoring residual hearing over the course of EAS CI use. We hypothesize that repeated measures of ECoG should remain stable over time for EAS CI users with stable postoperative hearing preservation. We also hypothesize that changes in behavioral audiometry for EAS CI users with loss of residual hearing should also be reflected in changes in ECoG measures. DESIGN: A pool of 40 subjects implanted under hearing preservation protocol was included in the study. Subjects were seen at postoperative visits for behavioral audiometry and ECoG recordings. Test sessions occurred 0.5, 1, 3, 6, 12 months, and annually after 12 months postoperatively. Changes in pure-tone behavioral audiometric thresholds relative to baseline were used to classify subjects into two groups: one group with stable acoustic hearing and another group with loss of acoustic hearing. At each test session, ECoG amplitude growth functions for several low-frequency stimuli were obtained. The threshold, slope, and suprathreshold amplitude at a fixed stimulation level was obtained from each growth function at each time point. Longitudinal linear mixed effects models were used to study trends in ECoG thresholds, slopes, and amplitudes for subjects with stable hearing and subjects with hearing loss. RESULTS: Preoperative, behavioral audiometry indicated that subjects had an average low-frequency pure-tone average (125 to 500 Hz) of 40.88 ± 13.12 dB HL. Postoperatively, results showed that ECoG thresholds and amplitudes were stable in EAS CI users with preserved residual hearing. ECoG thresholds increased (worsened) while ECoG amplitudes decreased (worsened) for those with delayed hearing loss. The slope did not distinguish between EAS CI users with stable hearing and subjects with delayed loss of hearing. CONCLUSIONS: These results provide a new application of postoperative ECoG as an objective tool to monitor residual hearing and understand the pathophysiology of delayed hearing loss. While our measures were conducted with custom-designed in-house equipment, CI companies are also designing and implementing hardware and software adaptations to conduct ECoG recordings. Thus, postoperative ECoG recordings can potentially be integrated into clinical practice.

Evaluating the relationship between patient activation and health-related quality of life (HRQOL) in patients with pancreatic cancer (PwPC).

PURPOSE: Advanced pancreatic cancer is synonymous with a high mortality rate, debilitating symptom profile, and minimal prolongation in overall survival. Therefore, health-related quality of life (HRQOL) is important in patients with pancreatic cancer (PwPC). In chronic conditions, patient activation is positively associated and higher HRQOL. However, no known study has evaluated patient activation, HRQOL, and their association in PwPC. METHODS: A 43-item cross-sectional survey assessed patient activation and HRQOL of patients with locally advanced and metastatic pancreatic cancer undergoing chemotherapy. Variables were analyzed descriptively, and relationships were assessed using bivariate statistics (sig p < 0.05). RESULTS: Fifty-six patients participating in the study had an average age of 69.5 ± 11.1 years, and the majority were females (51.8%), Caucasians (61.8%), married/partnered (64.3%), and had at least a college degree (59%). Almost half were at stage 4 (48.2%), and most were newly diagnosed (66.1%). Mean patient activation score was 63.5 ± 17.2 (scale range: 0-100), with most at higher activation levels of 3 or 4 (66.7%). Mean HRQOL score of 41.0 ± 12.7 (scale range: 0-72) was low. Patient activation levels, age, education level, and gender explained 21% of variation in overall HRQOL scores. Patients at activation level 4 had significantly higher overall HRQOL versus those at lower activation (level 1 or 2). Higher patient activation was significantly associated with having either private insurance only or multiple insurances and being partnered. CONCLUSION: Patient activation significantly predicted HRQOL in PwPC despite the low sample size. Initiatives to increase patient activation should focus on patients of low socioeconomic status and those without partner support.

An examination of the emerging field of community paramedicine: a national cross-sectional survey of community paramedics.

BACKGROUND: Community Paramedicine is an evolving community-based model that expands paramedic roles from emergency and transport care to a focus on non-emergent and preventive health services tailored to local community needs. Though community paramedicine is a growing field and acceptance is gradually increasing, there is limited information on community paramedics (CPs) perceptions of their expanded roles. The study's aim is to assess CPs' perceptions about their training, roles, role clarity, role readiness, role satisfaction, professional identity, interprofessional collaboration, and the future of the community paramedicine care model. METHODS: Using the National Association of Emergency Medical Technicians-mobile integrated health (NAEMT-MIH) listserv, a cross-sectional survey was conducted in July/August 2020 using a 43-item web-based questionnaire. Thirty-nine questions evaluated CPs' training, roles, role clarity, role readiness, role satisfaction, professional identity, interprofessional collaboration, and program/work characteristics. Four open-ended questions examined perceptions of the future of community paramedicine care models and challenges/opportunities encountered during the COVID-19 pandemic. Data was analyzed using Spearman's correlation, Wilcoxon Mann-Whitney U, and Kruskal-Wallis tests. Open-ended questions were analyzed using qualitative content analyses. RESULTS: Responses from fifty-seven CPs were analyzed. Most (80%) completed didactic and/or clinical training. Nearly all respondents (96.5%) performed health assessments; only 38.6% administered vaccines. Overall, participants were neutral about their role readiness with a mean score of 3.3/5.0. The mean role clarity was 15.5 (range 4-29; higher scores = higher clarity), professional identity was 46.8 (range 30-55; higher scores = higher identity), role satisfaction was 4.4/5 with 5 = very satisfied, and interprofessional collaboration was 9.5/10 (10 = very important). Role clarity training (rho = 0.4, p = 0.0013) and higher interprofessional collaboration (rho = 0.4, p = 0.0015) were found to be significantly associated with the enhancement of professional identity. Respondents who completed training showed higher role satisfaction compared to those who did not (p = 0.0114). COVID-19 challenges included keeping up with emerging policies/procedures, CPs' well-being, and inadequate funding to meet service needs; opportunities identified included service delivery expansion and CPs meeting community needs in a flexible manner. Respondents reported that sustainable payment models, expanding services, and geographic reach were important to the future of community paramedicine. CONCLUSIONS: Interprofessional collaboration is important to fulfill CPs roles. Role clarity and readiness could be improved, which aligns with the emerging nature of community paramedicine. The future of the community paramedicine care model is dependent on funding and expanding reach of services.

Perceived discrimination in the community pharmacy: A cross-sectional, national survey of adults.

BACKGROUND: Discrimination experiences have been documented in various health care settings; little is known about discrimination experiences in the community pharmacy setting. OBJECTIVES: This study aimed to (1) describe perceived everyday discrimination, including racial discrimination, in community pharmacies, (2) examine factors associated with perceived everyday discrimination, (3) examine the relationship between perceived racial discrimination and delays in picking up prescriptions, and (4) examine the relationship between perceived racial discrimination and forgoing prescriptions. METHODS: A cross-sectional survey was conducted in 2021 with a U.S. Qualtrics research panel. The 9-item Everyday Discrimination Scale (EDS) was used to assess perceived discrimination (range 9-45, higher scores indicate higher perceived discrimination). One question asked whether respondents perceived racial discrimination. Two questions asked whether respondents delayed or forwent getting a prescription(s) in the past year. Descriptive statistics were calculated for all variables. A generalized linear model examined factors associated with perceived discrimination; logistic regression examined the relationships between perceived racial discrimination and delays in getting or forgoing prescription(s). RESULTS: Participants (n = 578) were 40.2 (±16.5) years old. Most were white (55.5%), 24.4% were black, and 29.4% were Hispanic or Latino. The mean EDS score was 16.5 (±8.8); 18.7% perceived racial discrimination. Overall, 36.3% and 33.0% reported a delay in getting and forgoing their prescriptions, respectively. Age (P < 0.0001), sexual identity or orientation (P = 0.010), ethnicity (P = 0.049), annual income (P = 0.012), and prescription insurance (P = 0.008) were associated with perceived discrimination. Those with perceived racial discrimination had significantly higher odds of a delay in getting their prescription(s) than those without perceived racial discrimination (odds ratio 2.6 [95% CI 1.3-5.3]). CONCLUSIONS: Study findings elucidate discrimination experiences in the community pharmacy and the impact of racial discrimination on individuals' decision in obtaining their medications in a timely manner. Community pharmacy staff need to recognize their implicit biases and obtain training on best practices that promote equitable treatment of diverse patients.

Independent community pharmacists' attitudes and intentions toward dispensing buprenorphine/naloxone for opioid use disorder.

BACKGROUND: Buprenorphine/naloxone (BUP/NX) for opioid use disorder (OUD) is associated with positive health outcomes; however, challenges accessing prescribed BUP/NX at community pharmacies have been identified. OBJECTIVE: The theory of planned behavior was applied to determine whether independent community pharmacists' attitudes toward dispensing BUP/NX for OUD predict intentions to dispense. METHODS: A 40-item survey was administered to 185 Texas Community Pharmacy Enhanced Services Network pharmacists. The survey assessed intentions to dispense BUP/NX (3 items), attitudes toward BUP/NX (24 items), current barriers to dispensing BUP/NX (2 items), and demographics (10 items). Inferential statistics determined associations among pharmacists' attitudes, practice setting characteristics, and intentions to dispense BUP/NX. Regression analysis determined whether attitude predicted intention to dispense BUP/NX, controlling for practice setting and demographic characteristics. RESULTS: Responses were obtained from 82 community independent pharmacists (response rate = 44%). Respondents were predominantly non-Hispanic white (45.8%) and women (56.6%) and practiced in pharmacies with an average 1129.1 (± 1034.5) dispensed prescriptions/week. Pharmacists had positive intentions (6.2 ± 3.5) and attitudes (14.4 ± 24.9) toward dispensing BUP/NX and attitudes did not predict intentions to dispense (P = 0.330). Positive drivers of attitude were related to improving patient outcomes, fulfilling a community need, and absence of conflicts with pharmacists' personal and religious beliefs. A negative driver of attitude was financial reimbursement/loss. Pharmacists dispensing 2000 or more prescriptions/week had higher intentions (b = 3.22, P = 0.014) to dispense than those dispensing less than 500 prescriptions/week. The most common barrier to dispense BUP/NX was "refill was too soon" (54.8%). CONCLUSION: Community independent pharmacists had positive attitudes toward and intentions of dispensing BUP/NX for OUD. However, attitudes did not predict intentions to dispense. Negative drivers of attitudes were related to factors not within pharmacists' control, such as time to refill or financial reimbursement.Future studies focused on community pharmacy-based access to BUP/NX are warranted to elucidate issues that are impactful in improving pharmacists' dispensing intentions and behavior.