Neuropathology in an α-synuclein preformed fibril mouse model occurs independent of the Parkinson's disease-linked lysosomal ATP13A2 protein.

Loss-of-function mutations in the ATP13A2 (PARK9) gene are implicated in early-onset autosomal recessive Parkinson's disease (PD) and other neurodegenerative disorders. ATP13A2 encodes a lysosomal transmembrane P5B-type ATPase that is highly expressed in brain and specifically within the substantia nigra pars compacta (SNc). Recent studies have revealed its normal role as a lysosomal polyamine transporter, although its contribution to PD-related pathology remains unclear. Cellular studies report that ATP13A2 can regulate α-synuclein (α-syn) secretion via exosomes. However, the relationship between ATP13A2 and α-syn in animal models remains inconclusive. ATP13A2 knockout (KO) mice exhibit lysosomal abnormalities and reactive astrogliosis but do not develop PD-related neuropathology. Studies manipulating α-syn levels in mice lacking ATP13A2 indicate minimal effects on pathology. The delivery of α-syn preformed fibrils (PFFs) into the mouse striatum is a well-defined model to study the development and spread of α-syn pathology. In this study we unilaterally injected wild-type (WT) and homozygous ATP13A2 KO mice with mouse α-syn PFFs in the striatum and evaluated mice for neuropathology after 6 months. The distribution, spread and extent of α-syn aggregation in multiple regions of the mouse brain was largely independent of ATP13A2 expression. The loss of nigrostriatal pathway dopaminergic neurons and their nerve terminals induced by PFFs were equivalent in WT and ATP13A2 KO mice. Reactive astrogliosis was induced equivalently by α-syn PFFs in WT and KO mice but was already significantly higher in ATP13A2 KO mice due to pre-existing reactive gliosis. We did not identify asymmetric motor disturbances, microglial activation, or axonal damage induced by α-syn PFFs in WT or KO mice. Although α-syn PFFs induce an increase in lysosomal number in the SNc in general, TH-positive dopaminergic neurons did not exhibit either increased lysosomal area or intensity, regardless of genotype. Our study evaluating the spread of α-syn pathology reveals no exacerbation of α-syn pathology, neuronal loss, astrogliosis or motor deficits in ATP13A2 KO mice, suggesting that selective lysosomal abnormalities resulting from ATP13A2 loss do not play a major role in α-syn clearance or propagation in vivo.

Learning Outcomes and Educational Effectiveness of Social Media as a Continuing Professional Development Intervention for Practicing Surgeons: A Systematic Review and Narrative Synthesis.

Objective: The objective of this systematic review was to assess the learning outcomes and educational effectiveness of social media as a continuing professional development intervention for surgeons in practice. Background: Social media has the potential to improve global access to educational resources and collaborative networking. However, the learning outcomes and educational effectiveness of social media as a continuing professional development (CPD) intervention are yet to be summarized. Methods: We searched MEDLINE and Embase databases from 1946 to 2022. We included studies that assessed the learning outcomes and educational effectiveness of social media as a CPD intervention for practicing surgeons. We excluded studies that were not original research, involved only trainees, did not evaluate educational effectiveness, or involved an in-person component. The 18-point Medical Education Research Study Quality Instrument (MERSQI) was used for quality appraisal. Learning outcomes were categorized according to Moore's Expanded Outcomes Framework (MEOF). Results: A total of 830 unique studies revealed 14 studies for inclusion. The mean MERSQI score of the included studies was 9.0 ± 0.8. In total, 3227 surgeons from 105 countries and various surgical specialties were included. Twelve studies (86%) evaluated surgeons' satisfaction (MEOF level 2), 3 studies (21%) evaluated changes in self-reported declarative or procedural knowledge (MEOF levels 3A and 3B), 1 study (7%) evaluated changes in self-reported competence (MEOF level 4), and 5 studies (36%) evaluated changes in self-reported performance in practice (MEOF level 5). No studies evaluated changes in patient or community health (MEOF levels 6 and 7). Conclusions: The use of social media as a CPD intervention among practicing surgeons is associated with improved self-reported declarative and procedural knowledge, self-reported competence, and self-reported performance in practice. Further research is required to assess whether social media use for CPD in surgeons is associated with improvements in higher level and objectively measured learning outcomes.

Tricyclic and tetracyclic antidepressants upregulate VMAT2 activity and rescue disease-causing VMAT2 variants.

Vesicular monoamine transporter 2 (VMAT2) is an essential transporter that regulates brain monoamine transmission and is important for mood, cognition, motor activity, and stress regulation. However, VMAT2 remains underexplored as a pharmacological target. In this study, we report that tricyclic and tetracyclic antidepressants acutely inhibit, but persistently upregulate VMAT2 activity by promoting VMAT2 protein maturation. Importantly, the VMAT2 upregulation effect was greater in BE(2)-M17 cells that endogenously express VMAT2 as compared to a heterologous expression system (HEK293). The net sustained effect of tricyclics and tetracyclics is an upregulation of VMAT2 activity, despite their acute inhibitory effect. Furthermore, imipramine and mianserin, two representative compounds, also demonstrated rescue of nine VMAT2 variants that cause Brain Monoamine Vesicular Transport Disease (BMVTD). VMAT2 upregulation could be beneficial for disorders associated with reduced monoamine transmission, including mood disorders and BMVTD, a rare but often fatal condition caused by a lack of functional VMAT2. Our findings provide the first evidence that small molecules can upregulate VMAT2 and have potential therapeutic benefit for various neuropsychiatric conditions.

Examining the utility of near infrared light as pre-exposure therapy to mitigate temporary noise-induced hearing loss in humans.

Introduction: This study sought to determine the effect of Occupational Safety and Health Administration (OSHA) compliant noise on auditory health and assess whether pre-noise near infrared (NIR) light therapy can mitigate the effects of noise exposure. Methods: Over four visits, participants (n = 30, NCT#: 03834714) with normal hearing completed baseline hearing health assessments followed by exposure to open ear, continuous pink noise at 94 dBA for 15 min. Immediately thereafter, post-noise hearing tests at 3000, 4000, and 6000 Hz and distortion product otoacoustic emissions (DPOAEs) were conducted along with the Modified Rhyme Test (MRT), Masking Level Difference Test (MLD), and Fixed Level Frequency Tests (FLFT) [collectively referred to as the Central and Peripheral Auditory Test Battery (CPATB)] to acquire baseline noise sensitivity profiles. Participants were then randomized to either Active or Sham NIR light therapy for 30 min binaurally to conclude Visit 1. Visit 2 (≥24 and ≤ 48 h from Visit 1) began with an additional 30-min session of Active NIR light therapy or Sham followed by repeat CPATB testing and noise exposure. Post-noise testing was again conducted immediately after noise exposure to assess the effect of NIR light therapy. The remaining visits were conducted following ≥2 weeks of noise rest in a cross-over design (i.e., those who had received Active NIR light therapy in Visits 1 and 2 received Sham therapy in Visits 3 and 4). Results: Recovery hearing tests and DPOAEs were completed at the end of each visit. Participants experienced temporary threshold shifts (TTS) immediately following noise exposure, with a mean shift of 6.79 dB HL (±6.25), 10.61 dB HL (±6.89), and 7.30 dB HL (±7.25) at 3000, 4000, and 6000 Hz, respectively, though all thresholds returned to baseline at 3000, 4000, and 6000 Hz within 75 min of noise exposure. Paradoxically, Active NIR light therapy threshold shifts were statistically higher than Sham therapy at 3000 Hz (p = 0.04), but no other differences were observed at the other frequencies tested. An age sub-analysis demonstrated that TTS among younger adults were generally larger in the Sham therapy group versus Active therapy, though this was not statistically different. There were no differences in CPATB test results across Active or Sham groups. Finally, we observed no changes in auditory function or central processing following noise exposure, suggestive of healthy and resilient inner ears. Conclusion: In this study, locally administered NIR prior to noise exposure did not induce a significant protective effect in mitigating noise-induced TTS. Further exploration is needed to implement effective dosage and administration for this promising otoprotective therapy.

Lessons learned from bovine subclinical endometritis: A systematic review exploring its potential relevance to chronic endometritis in women.

Chronic endometritis (CE) in humans is asymptomatic inflammation of the endometrium, associated with poor reproductive outcomes. Similarly asymptomatic endometrial inflammation in cows, termed subclinical endometritis (SCE), is associated with adverse reproductive outcomes. While the pathophysiology and treatment options for CE in humans remains poorly defined, the financial implications of SCE in dairy cows mean it has been intensively researched. We performed a systematic review with an emergent theme thematic analysis of studies of SCE in cows, to determine potential areas of interest in human CE research. A literature search for studies of subclinical endometritis in cows published between 1990 and November 2021 was performed across Embase, Medline, Scopus and CINAHL. Studies of symptomatic or clinical endometritis were excluded. Thematic analysis across two broad themes were explored: diagnostic methods and pathophysiology of SCE. In total, 44 bovine studies were included. 12 studies reported on diagnostic methodology. The primary emergent theme was the use of cytology for the diagnosis of SCE. This method has a lower sensitivity than histopathology but is less invasive and more specific than alternative techniques of ultrasound, vaginoscopy, or metabolic markers. The subthemes related to pathophysiology were identified as type of endometritis, metabolic stress, artificial insemination, infective causes, and altered cellular pathways. Despite the lack of symptoms, cellular pathways of inflammation including NFkB, MAPK, and inflammasomes were found to be activated. The key themes related to the diagnosis and pathophysiology of SCE in cows identified in this systematic review highlight potential areas for future research into human CE.

Transferring care to enhance access to early-phase cancer clinical trials: Protocol to evaluate a novel program.

Involving diverse populations in early-phase (phase I and II) cancer clinical trials is critical to informed therapeutic development. However, given the growing costs and complexities of early-phase trials, trial activation and enrollment barriers may be greatest for these studies at healthcare facilities that provide care to the most diverse patient groups, including those in historically underserved communities (e.g., safety-net healthcare systems). To promote diverse and equitable access to early-phase cancer clinical trials, we are implementing a novel program for the transfer of care to enhance access to early-phase cancer clinical trials. We will then perform a mixed-methods study to determine perceptions and impact of the program. Specifically, we will screen, recruit, and enroll diverse patients from an urban, integrated safety-net healthcare system to open and active early-phase clinical trials being conducted in a university-based cancer center. To evaluate this novel program, we will: (1) determine program impact and efficiency; and (2) determine stakeholder experience with and perceptions of the program. To achieve these goals, we will conduct preliminary cost analyses of the program. We will also conduct surveys and interviews with patients and caregivers to elucidate program impact, challenges, and areas for improvement. We hypothesize that broadening access to early-phase cancer trials conducted at experienced centers may improve equity and diversity. In turn, such efforts may enhance the efficiency and generalizability of cancer clinical research.

Determinants of health as predictors for differential antibody responses following SARS-CoV-2 primary and booster vaccination in an at-risk, longitudinal cohort.

Post vaccine immunity following COVID-19 mRNA vaccination may be driven by extrinsic, or controllable and intrinsic, or inherent health factors. Thus, we investigated the effects of extrinsic and intrinsic on the peak antibody response following COVID-19 primary vaccination and on the trajectory of peak antibody magnitude and durability over time. Participants in a longitudinal cohort attended visits every 3 months for up to 2 years following enrollment. At baseline, participants provided information on their demographics, recreational behaviors, and comorbid health conditions which guided our model selection process. Blood samples were collected for serum processing and spike antibody testing at each visit. Cross-sectional and longitudinal models (linear-mixed effects models) were generated to assess the relationship between selected intrinsic and extrinsic health factors on peak antibody following vaccination and to determine the influence of these predictors on antibody over time. Following cross-sectional analysis, we observed higher peak antibody titers after primary vaccination in females, those who reported recreational drug use, younger age, and prior COVID-19 history. Following booster vaccination, females and Hispanics had higher peak titers after the 3rd and 4th doses, respectively. Longitudinal models demonstrated that Moderna mRNA-1273 recipients, females, and those previously vaccinated had increased peak titers over time. Moreover, drug users and half-dose Moderna mRNA-1273 recipients had higher peak antibody titers over time following the first booster, while no predictive factors significantly affected post-second booster antibody responses. Overall, both intrinsic and extrinsic health factors play a significant role in shaping humoral immunogenicity after initial vaccination and the first booster. The absence of predictive factors for second booster immunogenicity suggests a more robust and consistent immune response after the second booster vaccine administration.

Optimizing the consent process for emergent laparoscopic cholecystectomy using an interactive digital education platform: a randomized control trial.

BACKGROUND: Informed consent is essential for any surgery. The use of digital education platforms (DEPs) can enhance patient understanding of the consent discussion and is a method to standardize the consent process in elective, ambulatory settings. The use of DEP as an adjunct to standard verbal consent (SVC) has not been studied in an acute care setting. METHODS: We conducted a prospective randomized control trial with patients presenting to the emergency department of a tertiary care hospital with acute biliary pathology requiring a laparoscopic cholecystectomy (LC) between August 2021 and April 2023. Participants were randomized 1:1 to receive either a DEP module with SVC or SVC alone. Baseline procedure-specific knowledge and self-reported understanding of risks and benefits of LC were collected using a questionnaire. Primary outcome was immediate post-intervention knowledge assessed using a 21-question multiple choice questionnaire. Secondary outcomes were delayed procedure-specific knowledge and participants' satisfaction with the consent discussion. RESULTS: We recruited 79 participants and randomized them 1:1 into the intervention group (DEP + SVC, n = 40) and the control group (SVC, n = 39). Baseline demographics and baseline procedure-specific knowledge were similar between groups. The immediate post-intervention knowledge was significantly higher for participants in the intervention versus the control group with a Cohen's d effect size of 0.68 (85.2(10.6)% vs. 78.2(9.9)%; p = 0.004). Similarly, self-reported understanding of risks and benefits of LC was significantly greater for participants in the intervention versus the control group with a Cohen's effect size of 0.76 (68.5(16.4)% vs. 55.1(18.8)%; p = 0.001). For participants who completed the delayed post-intervention assessment (n = 29), there continued to be significantly higher retention of acquired knowledge in the intervention group with a Cohen's effect size of 0.61 (86.5(8.5)% vs. 79.8 (13.1)%; p = 0.024). There was no difference in participants' self-reported satisfaction with the consent discussion between groups (69.5(6.7)% vs. 67.2(7.7)%; p = 0.149). CONCLUSION: The addition of digital education platform to standard verbal consent significantly improves patient's early and delayed understanding of risks and benefits of LC in an acute care setting.

Trauma resident exposure in Canada and operative numbers (TraumaRECON): a national multicentre retrospective review of operative and nonoperative trauma teaching.

BACKGROUND: General surgeons play an important role in the provision of trauma care in Canada and the current extent of their trauma experience during training is unknown. We sought to quantify the operative and nonoperative educational experiences among Canadian general surgery trainees. METHODS: We conducted a multicentre retrospective study of major operative exposures experienced by general surgery residents, as identified using institutional trauma registries and subsequent chart-level review, for 2008-2018. We also conducted a site survey on trauma education and structure. RESULTS: We collected data on operative exposure for general surgery residents from 7 programs and survey data from 10 programs. Operations predominantly occurred after hours (73% after 1700 or on weekends) and general surgery residents were absent from a substantial proportion (25%) of relevant trauma operations. The structure of trauma education was heterogeneous among programs, with considerable site-specific variability in the involvement of surgical specialties in trauma care. During their training, graduating general surgery residents each experienced around 4 index trauma laparotomies, 1 splenectomy, 1 thoracotomy, and 0 neck explorations for trauma. CONCLUSION: General surgery residents who train in Canada receive variable and limited exposure to operative and nonoperative trauma care. These data can be used as a baseline to inform the application of competency-based medical education in trauma care for general surgery training in Canada.

The Impact of Limited English Proficiency on Healthcare Access and Outcomes in the U.S.: A Scoping Review.

A majority of individuals with limited English proficiency (LEP) in the U.S. are foreign-born, creating a complex intersection of language, socio-economic, and policy barriers to healthcare access and achieving good outcomes. Mapping the research literature is key to addressing how LEP intersects with healthcare. This scoping review followed PRISMA-ScR guidelines and included PubMed/MEDLINE, CINAHL, Sociological Abstracts, EconLit, and Academic Search Premier. Study selection included quantitative studies since 2000 with outcomes specified for adults with LEP residing in the U.S. related to healthcare service access or defined health outcomes, including healthcare costs. A total of 137 articles met the inclusion criteria. Major outcomes included ambulatory care, hospitalization, screening, specific conditions, and general health. Overall, the literature identified differential access to and utilization of healthcare across multiple modalities with poorer outcomes among LEP populations compared with English-proficient populations. Current research includes inconsistent definitions for LEP populations, primarily cross-sectional studies, small sample sizes, and homogeneous language and regional samples. Current regulations and practices are insufficient to address the barriers that LEP individuals face to healthcare access and outcomes. Changes to EMRs and other data collection to consistently include LEP status and more methodologically rigorous studies are needed to address healthcare disparities for LEP individuals.

Examining the Effect of SARS-CoV-2 Pandemic-Induced Stress and Anxiety on Humoral Immunity in Health Care Workers.

OBJECTIVE: The effect of stress on vaccine-induced humoral immunity and therapeutic interventions to mitigate pandemic-related stress remain underexplored. METHOD: Participants in a longitudinal cohort study ( n = 189) completed a validated measure, GAD-7, and 10-instrument stress measure to assess stress and anxiety after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Serum was collected to obtain SARS-CoV-2 antibody titer levels. RESULTS: Participants experienced increased stress due to the SARS-CoV-2 pandemic with a positive correlation between GAD-7 scores and peak antibody titers overall; however, there was a negative association with scores commensurate with severe anxiety. Health care workers and younger participants were more significantly affected by anxiety. CONCLUSIONS: Mild anxiety levels may have immune-enhancing effects, whereas severe anxiety may cause antibody generation reduction. Mental health-focused interventions are imperative for younger adults and health care workers. Young adults may be more resilient to increased stress levels.

Educational Effectiveness of Telementoring as a Continuing Professional Development Intervention for Surgeons in Practice: A Systematic Review.

Objective: We performed a systematic review to determine the educational effectiveness of telementoring as a continuing professional development (CPD) intervention for surgeons in practice. Background: Surgeons can mentor their peers in remote locations using videoconferencing communication, referred to as telementoring. Methods: We searched MEDLINE and EMBASE and included studies assessing the educational effectiveness of telementoring interventions used by surgeons in practice. We excluded studies involving only trainees and those not evaluating educational effectiveness. Two reviewers independently screened, extracted data, and assessed study quality using the Medical Education Research Study Quality Instrument (MERSQI; maximum score 18). Educational outcomes were categorized using Moore's Outcomes Framework. Results: We retrieved a total of 1351 records, and 252 studies were selected for full-text review. Twenty-eight studies were included with 1 randomized controlled trial, 19 cohort studies, 5 qualitative studies, and 3 case studies, totaling 178 surgeons and 499 cases. The average MERSQI score was 10.21 ± 2.2 out of 18. Educational outcomes included surgeons' satisfaction with telementoring interventions (Moore's Level 2) in 12 studies, improvement in surgeons' procedural knowledge (Level 3b) in 3 studies, improvements in surgeons' procedural competence in an educational setting (Level 4) in 4 studies, performance in a workplace-based setting (Level 5) in 23 studies, and patient outcomes (Level 6) in 3 studies. No studies reported community health outcomes (Level 7). Conclusions: Moderate-level evidence demonstrates the use of telementoring as effective in changing surgeons' knowledge and competence in both educational and workplace-based settings. Its use is also associated with changes in patient outcomes.

Frequency dependence of coordinated pupil and eye movements for binocular disparity tracking.

Introduction: Coordinated alignment of the eyes during gaze fixation and eye movements are an important component of normal visual function. We have previously described the coordinated behavior of convergence eye movements and pupillary responses using a 0.1 Hz binocular disparity-driven sine profile and a step profile. The goal of this publication is to further characterize ocular vergence-pupil size coordination over a wider range of frequencies of ocular disparity stimulation in normal subjects. Methods: Binocular disparity stimulation is generated by presentation of independent targets to each eye on a virtual reality display, while eye movements and pupil size are measured by an embedded video-oculography system. This design allows us to study two complimentary analyses of this motion relationship. First, a macroscale analysis describes the vergence angle of the eyes in response to binocular disparity target movement and pupil area as a function of the observed vergence response. Second, a microscale analysis performs a piecewise linear decomposition of the vergence angle and pupil relationship to permit more nuanced findings. Results: These analyses identified three main features of controlled coupling of pupil and convergence eye movements. First, a near response relationship operates with increasing prevalence during convergence (relative to the "baseline" angle); the coupling is higher with increased convergence in this range. Second, the prevalence of "near response"-type coupling decreases monotonically in the diverging direction; the decrease persists after the targets move (converge back) from maximum divergence toward the baseline positions, with a minimum prevalence of near response segments near the baseline target position. Third, an opposite polarity pupil response is infrequent, but tends to be more prevalent when the vergence angles are at maximum convergence or divergence for a sinusoidal binocular disparity task. Discussion: We suggest that the latter response is an exploratory "range-validation" when binocular disparity is relatively constant. In a broader sense, these findings describe operating characteristics of the near response in normal subjects and form a basis for quantitative assessments of function in conditions such as convergence insufficiency and mild traumatic brain injury.

Learning Outcomes and Educational Effectiveness of E-Learning as a Continuing Professional Development Intervention for Practicing Surgeons and Proceduralists: A Systematic Review.

BACKGROUND: Electronic learning (e-Learning) has become a prevalent mode of delivering medical education. We aimed to determine the learning outcomes and educational effectiveness of e-Learning as a continuing professional development (CPD) intervention for practicing surgeons and proceduralists. METHODS: We searched MEDLINE databases and included studies reporting learning outcomes of e-learning CPD interventions for practicing surgeons and physicians performing technical procedures. We excluded articles only studying surgical trainees and those not reporting learning outcomes. Two reviewers independently screened, extracted data, and assessed study quality using the Critical Appraisal Skills Programme (CASP) tools. Learning outcomes and educational effectiveness were categorized using Moore's Outcomes Framework (PROSPERO: CRD42022333523). RESULTS: Of 1307 identified articles, 12 were included- 9 cohort studies, one randomized controlled trial and 2 qualitative studies, with a total of 2158 participants. Eight studies were rated as moderate, five as strong, and 2 as weak in study quality. E-Learning CPD interventions included web-based modules, image recognition, videos, a repository of videos and schematics, and an online journal club. Seven studies reported participants' satisfaction with the e-Learning interventions (Moore's Level 2), 4 reported improvements in participants' declarative knowledge (Level 3a), 1 reported improvements in procedural knowledge (Level 3b) and five reported improvements in participants' procedural competence in an educational setting (Level 4). No studies demonstrated improvements in participants' workplace-based performance, the health of patients, or community health (Levels 5-7). CONCLUSIONS: E-Learning as a CPD educational intervention is associated with high satisfaction and improvements in knowledge and procedural competencies of practicing surgeons and proceduralists in an educational setting. Future research is required to investigate whether e-Learning is associated with higher-level learning outcomes.

Exaggerated postural sway improves orthostatic cardiovascular and cerebrovascular control.

Introduction: Healthy individuals with poor cardiovascular control, but who do not experience syncope (fainting), adopt an innate strategy of increased leg movement in the form of postural sway that is thought to counter orthostatic (gravitational) stress on the cardiovascular system. However, the direct effect of sway on cardiovascular hemodynamics and cerebral perfusion is unknown. If sway produces meaningful cardiovascular responses, it could be exploited clinically to prevent an imminent faint. Methods: Twenty healthy adults were instrumented with cardiovascular (finger plethysmography, echocardiography, electrocardiogram) and cerebrovascular (transcranial Doppler) monitoring. Following supine rest, participants performed a baseline stand (BL) on a force platform, followed by three trials of exaggerated sway (anterior-posterior, AP; mediolateral, ML; square, SQ) in a randomized order. Results: All exaggerated postural sway conditions improved systolic arterial pressure (SAP, p = 0.001) responses, while blunting orthostatic reductions in stroke volume (SV, p < 0.01) and cerebral blood flow (CBFv, p < 0.05) compared to BL. Markers of sympathetic activation (power of low-frequency oscillations in SAP, p < 0.001) and maximum transvalvular flow velocity (p < 0.001) were reduced during exaggerated sway conditions. Responses were dose-dependent, with improvements in SAP (p < 0.001), SV (p < 0.001) and CBFv (p = 0.009) all positively correlated with total sway path length. Coherence between postural movements and SAP (p < 0.001), SV (p < 0.001) and CBFv (p = 0.003) also improved during exaggerated sway. Discussion: Exaggerated sway improves cardiovascular and cerebrovascular control and may supplement cardiovascular reflex responses to orthostatic stress. This movement provides a simple means to boost orthostatic cardiovascular control for individuals with syncope, or those with occupations that require prolonged motionless standing.

Primary Intensivists and Nurses for Long-Stay Patients: A Survey of Practices and Perceptions at Academic PICUs.

OBJECTIVES: To determine the prevalence of the utilization of primary intensivists and primary nurses for long-stay patients in large, academic PICU and ascertain how these practices are operationalized and perceived. DESIGN: A cross-sectional survey. SETTING: U.S. PICUs with accredited Pediatric Critical Care Medicine fellowships. SUBJECTS: One senior physician and one senior nurse at each institution. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Separate but largely analogous questionnaires for intensivists and nurses were created using an iterative process to enhance content/face validity and readability. Sixty-seven intensivists (representing 93% of the 72 institutions with fellowship programs and their PICUs) and 59 nurses (representing 82%) responded. Twenty-four institutions utilize primary intensivists; 30 utilize primary nurses; and 13 utilize both. Most institutions use length of stay and/or other criteria (e.g., medical complexity) for eligibility. Commonly, not all patients that meet eligibility criteria receive primaries. Primary providers are overwhelmingly volunteers, and often only a fraction of providers participate. Primary intensivists at a large majority (>75%) of institutions facilitate information sharing and decision-making, attend family/team meetings, visit patients/families regularly, and are otherwise available upon request. Primary nurses at a similar majority of institutions provide consistent bedside care, facilitate information sharing, and attend family/team meetings. A large majority of respondents thought that primary intensivists increase patient/family satisfaction, reduce their stress, improve provider communication, and reduce conflict, whereas primary nurses similarly increase patient/family satisfaction. More than half of respondents shared that these practices can sometimes require effort (e.g., time and emotion), complicate decision-making, and/or reduce staffing flexibility. CONCLUSIONS: Primary practices are potential strategies to augment rotating PICU care models and better serve the needs of long-stay and other patients. These practices are being utilized to varying extents and with some operationalization uniformity at large, academic PICUs.

Predictors for reactogenicity and humoral immunity to SARS-CoV-2 following infection and mRNA vaccination: A regularized, mixed-effects modelling approach.

Introduction: The influence of pre-existing humoral immunity, inter-individual demographic factors, and vaccine-associated reactogenicity on immunogenicity following COVID vaccination remains poorly understood. Methods: Ten-fold cross-validated least absolute shrinkage and selection operator (LASSO) and linear mixed effects models were used to evaluate symptoms experienced by COVID+ participants during natural infection and following SARS-CoV-2 mRNA vaccination along with demographics as predictors for antibody (AB) responses to recombinant spike protein in a longitudinal cohort study. Results: In previously infected individuals (n=33), AB were more durable and robust following primary vaccination when compared to natural infection alone. Higher AB were associated with experiencing dyspnea during natural infection, as was the total number of symptoms reported during the COVID-19 disease course. Both local and systemic symptoms following 1st and 2nd dose (n=49 and 48, respectively) of SARS-CoV-2 mRNA vaccines were predictive of higher AB after vaccination. Lastly, there was a significant temporal relationship between AB and days since infection or vaccination, suggesting that vaccination in COVID+ individuals is associated with a more robust immune response. Discussion: Experiencing systemic and local symptoms post-vaccine was suggestive of higher AB, which may confer greater protection.