Characterizing the patterns of electronic health record-integrated secure messaging use: Cross-sectional study

BACKGROUND: Communication among health care professionals is essential for the delivery of safe clinical care. Secure messaging has rapidly emerged as a new mode of asynchronous communication. Despite its popularity, relatively little is known about how secure messaging is used and how such use contributes to communication burden. OBJECTIVE: This study aims to characterize the use of an electronic health record-integrated secure messaging platform across 14 hospitals and 263 outpatient clinics within a large health care system. METHODS: We collected metadata on the use of the Epic Systems Secure Chat platform for 6 months (July 2022 to January 2023). Information was retrieved on message volume, response times, message characteristics, messages sent and received by users, user roles, and work settings (inpatient vs outpatient). RESULTS: A total of 32,881 users sent 9,639,149 messages during the study. Median daily message volume was 53,951 during the first 2 weeks of the study and 69,526 during the last 2 weeks, resulting in an overall increase of 29% (P=.03). Nurses were the most frequent users of secure messaging (3,884,270/9,639,149, 40% messages), followed by physicians (2,387,634/9,639,149, 25% messages), and medical assistants (1,135,577/9,639,149, 12% messages). Daily message frequency varied across users; inpatient advanced practice providers and social workers interacted with the highest number of messages per day (median 19). Conversations were predominantly between 2 users (1,258,036/1,547,879, 81% conversations), with a median of 2 conversational turns and a median response time of 2.4 minutes. The largest proportion of inpatient messages was from nurses to physicians (972,243/4,749,186, 20% messages) and physicians to nurses (606,576/4,749,186, 13% messages), while the largest proportion of outpatient messages was from physicians to nurses (344,048/2,192,488, 16% messages) and medical assistants to other medical assistants (236,694/2,192,488, 11% messages). CONCLUSIONS: Secure messaging was widely used by a diverse range of health care professionals, with ongoing growth throughout the study and many users interacting with more than 20 messages per day. The short message response times and high messaging volume observed highlight the interruptive nature of secure messaging, raising questions about its potentially harmful effects on clinician workflow, cognition, and errors

Structural analysis of a trimeric assembly of the mitochondrial dynamin-like GTPase Mgm1.

The fusion of inner mitochondrial membranes requires dynamin-like GTPases, Mgm1 in yeast and OPA1 in mammals, but how they mediate membrane fusion is poorly understood. Here, we determined the crystal structure of Saccharomyces cerevisiae short Mgm1 (s-Mgm1) in complex with GDP. It revealed an N-terminal GTPase (G) domain followed by two helix bundles (HB1 and HB2) and a unique C-terminal lipid-interacting stalk (LIS). Dimers can form through antiparallel HB interactions. Head-to-tail trimers are built by intermolecular interactions between the G domain and HB2-LIS. Biochemical and in vivo analyses support the idea that the assembly interfaces observed here are native and critical for Mgm1 function. We also found that s-Mgm1 interacts with negatively charged lipids via both the G domain and LIS. Based on these observations, we propose that membrane targeting via the G domain and LIS facilitates the in cis assembly of Mgm1, potentially generating a highly curved membrane tip to allow inner membrane fusion

Anesthesia clinical workload estimated from electronic health record documentation vs billed relative value units

IMPORTANCE: Accurate measurements of clinical workload are needed to inform health care policy. Existing methods for measuring clinical workload rely on surveys or time-motion studies, which are labor-intensive to collect and subject to biases. OBJECTIVE: To compare anesthesia clinical workload estimated from electronic health record (EHR) audit log data vs billed relative value units. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study of anesthetic encounters occurring between August 26, 2019, and February 9, 2020, used data from 8 academic hospitals, community hospitals, and surgical centers across Missouri and Illinois. Clinicians who provided anesthetic services for at least 1 surgical encounter were included. Data were analyzed from January 2022 to January 2023. EXPOSURE: Anesthetic encounters associated with a surgical procedure were included. Encounters associated with labor analgesia and endoscopy were excluded. MAIN OUTCOMES AND MEASURES: For each encounter, EHR-derived clinical workload was estimated as the sum of all EHR actions recorded in the audit log by anesthesia clinicians who provided care. Billing-derived clinical workload was measured as the total number of units billed for the encounter. A linear mixed-effects model was used to estimate the relative contribution of patient complexity (American Society of Anesthesiology [ASA] physical status modifier), procedure complexity (ASA base unit value for the procedure), and anesthetic duration (time units) to EHR-derived and billing-derived workload. The resulting β coefficients were interpreted as the expected effect of a 1-unit change in each independent variable on the standardized workload outcome. The analysis plan was developed after the data were obtained. RESULTS: A total of 405 clinicians who provided anesthesia for 31 688 encounters were included in the study. A total of 8 288 132 audit log actions corresponding to 39 131 hours of EHR use were used to measure EHR-derived workload. The contributions of patient complexity, procedural complexity, and anesthesia duration to EHR-derived workload differed significantly from their contributions to billing-derived workload. The contribution of patient complexity toward EHR-derived workload (β = 0.162; 95% CI, 0.153-0.171) was more than 50% greater than its contribution toward billing-derived workload (β = 0.106; 95% CI, 0.097-0.116; P \u3c .001). In contrast, the contribution of procedure complexity toward EHR-derived workload (β = 0.033; 95% CI, 0.031-0.035) was approximately one-third its contribution toward billing-derived workload (β = 0.106; 95% CI, 0.104-0.108; P \u3c .001). CONCLUSIONS AND RELEVANCE: In this cross-sectional study of 8 hospitals, reimbursement for anesthesiology services overcompensated for procedural complexity and undercompensated for patient complexity. This method for measuring clinical workload could be used to improve reimbursement valuations for anesthesia and other specialties

Investigating the impact of delivery system design on the efficacy of self-amplifying RNA vaccines

Messenger RNA (mRNA)-based vaccines combine the positive attributes of both live-attenuated and subunit vaccines. In order for these to be applied for clinical use, they require to be formulated with delivery systems. However, there are limited in vivo studies which compare different delivery platforms. Therefore, we have compared four different cationic platforms: (1) liposomes, (2) solid lipid nanoparticles (SLNs), (3) polymeric nanoparticles (NPs) and (4) emulsions, to deliver a self-amplifying mRNA (SAM) vaccine. All formulations contained either the non-ionizable cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) or dimethyldioctadecylammonium bromide (DDA) and they were characterized in terms of physico-chemical attributes, in vitro transfection efficiency and in vivo vaccine potency. Our results showed that SAM encapsulating DOTAP polymeric nanoparticles, DOTAP liposomes and DDA liposomes induced the highest antigen expression in vitro and, from these, DOTAP polymeric nanoparticles were the most potent in triggering humoral and cellular immunity among candidates in vivo

High-throughput analysis reveals novel maternal germline RNAs crucial for primordial germ cell preservation and proper migration

During oogenesis, hundreds of maternal RNAs are selectively localized to the animal or vegetal pole, including determinants of somatic and germline fates. Although microarray analysis has identified localized determinants, it is not comprehensive and is limited to known transcripts. Here, we utilized high-throughput RNA sequencing analysis to comprehensively interrogate animal and vegetal pole RNAs in the fully grown Xenopus laevis oocyte. We identified 411 (198 annotated) and 27 (15 annotated) enriched mRNAs at the vegetal and animal pole, respectively. Ninety were novel mRNAs over 4-fold enriched at the vegetal pole and six were over 10-fold enriched at the animal pole. Unlike mRNAs, microRNAs were not asymmetrically distributed. Whole-mount in situ hybridization confirmed that all 17 selected mRNAs were localized. Biological function and network analysis of vegetally enriched transcripts identified protein-modifying enzymes, receptors, ligands, RNA-binding proteins, transcription factors and co-factors with five defining hubs linking 47 genes in a network. Initial functional studies of maternal vegetally localized mRNAs show that sox7 plays a novel and important role in primordial germ cell (PGC) development and that ephrinB1 (efnb1) is required for proper PGC migration. We propose potential pathways operating at the vegetal pole that highlight where future investigations might be most fruitful.Fil: Owens, Dawn A.. University of Miami; Estados UnidosFil: Butler, Amanda M.. University of Miami; Estados UnidosFil: Agüero, Tristán Horacio. University of Miami; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Newman, Karen M.. University of Miami; Estados UnidosFil: Van Booven, Derek. University of Miami; Estados UnidosFil: King, Mary Lou. University of Miami; Estados Unido

The accuracy of anal Self- and Companion Exams among Sexual Minority Men and Transgender Women: a Prospective analysis

BACKGROUND: Squamous cell carcinoma of the anus (SCCA) annual incidence among sexual minority men with and without HIV is 85/100,000 and 19/100,000 persons, respectively, which is significantly higher than the overall incidence (2/100,000). Incidence may also be higher in transgender women. Since SCCA tumours average ≥30 mm at diagnosis, we assessed the accuracy of individuals to self-detect smaller anal abnormalities. METHODS: Using convenience sampling, the study enrolled sexual minority men and transgender women, aged 25-81 years, in Chicago, Illinois and Houston, Texas, USA, during 2020-2022. Individuals were taught the anal self-examination and anal companion examination (ASE/ACE). Then, a clinician performed a digital anal rectal examination (DARE) before participants conducted the ASE or ACE. The sensitivity, specificity and concordance of the ASE/ACE to detect an abnormality were measured along with factors associated with ASE/ACE and DARE concordance. FINDINGS: Among 714 enrolled individuals, the median age was 40 years (interquartile range, 32-54), 36.8% (259/703) were living with HIV, and 47.0% (334/710), 23.4% (166/710), and 23.0% (163/710) were non-Hispanic white, non-Hispanic Black, and Hispanic, respectively. A total of 94.1% (671/713) identified as cisgendered men, and 5.9% (42/713) as gender minorities. A total of 658 participants completed an ASE and 28 couples (56 partners) completed an ACE. Clinicians detected abnormalities in 34.3% (245/714) of individuals. The abnormalities were a median of 3 mm in diameter. Sensitivity and specificity of the ASE/ACE was 59.6% (95% CI 53.5-65.7%) and 80.2% (95% CI 76.6-83.8%), respectively. Overall concordance was 0.73 (95% CI 0.70-0.76) between ASE/ACE and DARE and increased with increasing anal canal lesion size (p = 0.02). Concordance was lower when participants were older and received ASE/ACE training from a lay person rather than a clinician. INTERPRETATION: Sexual minority men/transgender women may self-detect SCCA when malignant lesions are much smaller than the current mean dimension at presentation of ≥30 mm. FUNDING: National Cancer Institute

To look or not to look during vaccination: A pilot randomized trial

Background: Clinicians commonly advise patients to look away from the needle during vaccinations; however, this recommendation is not evidence based. Aim: The aim of this study was to determine whether looking at the needle versus looking away affects pain and fear during vaccinations in adults. Methods: This was a pilot randomized two-group parallel trial with university students receiving influenza vaccinations. Participants were stratified according to their initial needle-looking preference and randomly assigned to either look at versus away from the needle. Participants self-reported their pain and fear during vaccination. Results: Of the 184 subjects who agreed to participate, 160 were enrolled; 66% were female. A three-way analysis of variance (ANOVA; Looking allocation assignment × Looking preference × Sex) revealed a significant main effect of looking allocation assignment on fear (P = 0.025); those who were randomized to look had higher fear scores than those who were randomized to look away. There was also a significant main effect of looking preference on fear (P \u3c 0.001); those who preferred to look away had higher fear scores than those who preferred to look. There was no evidence of an effect of looking allocation assignment or looking preference on pain. There was a significant main effect of sex on fear and pain, with females reporting higher pain and fear scores than males (P = 0.017 and P = 0.001, respectively). There were no significant interactions. Conclusion: These preliminary findings suggest that advising individuals to look away from the needle reduces fear. A larger trial including more individuals and a different population is recommended to confirm the results

The molecular basis of ATM-dependent dimerization of the Mdc1 DNA damage checkpoint mediator

Mdc1 is a large modular phosphoprotein scaffold that maintains signaling and repair complexes at double-stranded DNA break sites. Mdc1 is anchored to damaged chromatin through interaction of its C-terminal BRCT-repeat domain with the tail of γH2AX following DNA damage, but the role of the N-terminal forkhead-associated (FHA) domain remains unclear. We show that a major binding target of the Mdc1 FHA domain is a previously unidentified DNA damage and ATM-dependent phosphorylation site near the N-terminus of Mdc1 itself. Binding to this motif stabilizes a weak self-association of the FHA domain to form a tight dimer. X-ray structures of free and complexed Mdc1 FHA domain reveal a ‘head-to-tail’ dimerization mechanism that is closely related to that seen in pre-activated forms of the Chk2 DNA damage kinase, and which both positively and negatively influences Mdc1 FHA domain-mediated interactions in human cells prior to and following DNA damage

Identification and characterization of a novel testis-specific gene CKT2, which encodes a substrate for protein kinase CK2

Protein kinase CK2 is a serine/threonine kinase known to phosphorylate numerous substrates. CK2 is implicated in several physiologic and pathologic processes, particularly in cancer biology. CK2 is comprised of several subunits, including CK2α, CK2α′ and CK2β. Inactivation of CK2α′ leads to chromatin degeneration of germ cells, resulting in male sterility. To identify additional targets of CK2α′ in testes and to determine the role of CK2α′ in germ cell nuclear integrity, GST pull-down and protein–protein interaction assays were conducted. A novel testis-specific gene, CKT2 (CK2 Target protein 2), was found whose product interacts with and is phosphorylated by CK2 in vitro and in vivo. CKT2 is a 30.2 kDa protein with one coiled-coil domain and six putative phosphorylation sites. High expression of CKT2 correlated with chromatin condensation of spermatids in murine testes. Findings reported herein demonstrate that CKT2 is a target protein of native CK2α′ in testes and suggest that CKT2 plays a role in chromatin regulation of male germ cells