Development of an Emergency Medicine Pharmacy Intensity Score Tool

Purpose Emergency medicine pharmacists (EMPs) have been demonstrated to have a positive impact on patient outcomes in a variety of clinical scenarios in the emergency department (ED), yet their distribution across the nation is suboptimal. An emergency medicine pharmacy intensity score tool (EMPIST) would not only facilitate the quantification of EMP staffing needs and ideal resource deployment times, but would also allow practitioners to triage patient care activities. The purpose of this investigation was to develop an EMPIST and evaluate its relationship to EMP activities. Methods This was a multicenter, prospective, observational analysis of an EMPIST developed by practicing EMPs. EMPs prospectively documented their clinical activities during usual care for patients in their ED. Spearman’s rank-order correlation was used to determine any correlation between the EMPIST and pharmacist activities. Results In total, 970 EMP activities and 584 EMPIST items were documented in 352 patients by 7 EMPs across 7 different EDs. The most commonly documented EMP interventions performed were bedside monitoring (12.7%), initiation of nonantimicrobial therapy (12.6%), and antimicrobial therapy initiation and streamlining (10.6%). The total EMPIST was found to significantly correlate with EMP activities, and this correlation was consistent across both “diagnostic/presentation” and “medication” items (P \u3c 0.001 for all comparisons). Conclusion The EMPIST significantly correlated with EMP activities, with consistent correlation across all subgroups. Its utilization has the potential to enhance bedside clinical practice and optimize the deployment of limited EMP services. Additional investigations are needed to examine the validity of this tool and identify any relationship it may have to patient outcomes

Generation of tumor-initiating cells by exogenous delivery of OCT4 transcription factor

Abstract Introduction Tumor-initiating cells (TIC) are being extensively studied for their role in tumor etiology, maintenance and resistance to treatment. The isolation of TICs has been limited by the scarcity of this population in the tissue of origin and because the molecular signatures that characterize these cells are not well understood. Herein, we describe the generation of TIC-like cell lines by ectopic expression of the OCT4 transcription factor (TF) in primary breast cell preparations. Methods OCT4 cDNA was over-expressed in four different primary human mammary epithelial (HMEC) breast cell preparations from reduction mammoplasty donors. OCT4-transduced breast cells (OTBCs) generated colonies (frequency ~0.01%) in self-renewal conditions (feeder cultures in human embryonic stem cell media). Differentiation assays, immunofluorescence, immunohistochemistry, and flow cytometry were performed to investigate the cell of origin of OTBCs. Serial dilutions of OTBCs were injected in nude mice to address their tumorigenic capabilities. Gene expression microarrays were performed in OTBCs, and the role of downstream targets of OCT4 in maintaining self-renewal was investigated by knock-down experiments. Results OTBCs overcame senescence, overexpressed telomerase, and down-regulated p16INK4A . In differentiation conditions, OTBCs generated populations of both myoepithelial and luminal cells at low frequency, suggesting that the cell of origin of some OTBCs was a bi-potent stem cell. Injection of OTBCs in nude mice generated poorly differentiated breast carcinomas with colonization capabilities. Gene expression microarrays of OTBC lines revealed a gene signature that was over-represented in the claudin-low molecular subtype of breast cancer. Lastly, siRNA-mediated knockdown of OCT4 or downstream embryonic targets of OCT4, such as NANOG and ZIC1, suppressed the ability of OTBCs to self-renew. Conclusions Transduction of OCT4 in normal breast preparations led to the generation of cell lines possessing tumor-initiating and colonization capabilities. These cells developed high-grade, poorly differentiated breast carcinomas in nude mice. Genome-wide analysis of OTBCs outlined an embryonic TF circuitry that could be operative in TICs, resulting in up-regulation of oncogenes and loss of tumor suppressive functions. These OTBCs represent a patient-specific model system for the discovery of novel oncogenic targets in claudin-low tumors

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

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

Recommendations for nonantidote medications needed in the emergency department during a mass casualty incident

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time

Mobile Photoplethysmographic Technology to Detect Atrial Fibrillation

Background Low detection and nonadherence are major problems in current management approaches for patients with suspected atrial fibrillation (AF). Mobile health devices may enable earlier AF detection and improved AF management. Objectives This study sought to investigate the effectiveness of AF screening in a large population-based cohort using smart device–based photoplethysmography (PPG) technology, combined with a clinical care AF management pathway using a mobile health approach. Methods AF screening was performed with smart devices using PPG technology, which were made available for the population ≥18 years of age across China. Monitoring for at least 14 days with a wristband (Honor Band 4) or wristwatch (Huawei Watch GT, Honor Watch, Huawei Technologies Co., Ltd., Shenzhen, China) was allowed. The patients with “possible AF” episodes using the PPG algorithm were further confirmed by health providers among the MAFA (mobile AF app) Telecare center and network hospitals, with clinical evaluation, electrocardiogram, or 24-h Holter monitoring. Results There were 246,541 individuals who downloaded the PPG screening app, and 187,912 individuals used smart devices to monitor their pulse rhythm between October 26, 2018, and May 20, 2019. Among those with PPG monitoring (mean age 35 years, 86.7% male), 424 (of 187,912, 0.23%) (mean age 54 years, 87.0% male) received a “suspected AF” notification. Of those effectively followed up, 227 individuals (of 262, 87.0%) were confirmed as having AF, with the positive predictive value of PPG signals being 91.6% (95% confidential interval [CI]: 91.5% to 91.8%). Both suspected AF and identified AF markedly increased with age (p for trend <0.001), and individuals in Northeast China had the highest proportion of detected AF of 0.28% (95% CI: 0.20% to 0.39%). Of the individuals with identified AF, 216 (of 227, 95.1%) subsequently entered a program of integrated AF management using a mobile AF application; approximately 80% of high-risk patients were successfully anticoagulated. Conclusions Based on the present study, continuous home monitoring with smart device–based PPG technology could be a feasible approach for AF screening. This would help efforts at screening and detection of AF, as well as early interventions to reduce stroke and other AF-related complications. (Mobile Health [mHealth] Technology for Improved Screening, Patient Involvement and Optimizing Integrated Care in Atrial Fibrillation [MAFA II]; ChiCTR-OOC-17014138

Mobile Health Technology to Improve Care for Patients With Atrial Fibrillation

Background Current management of patients with atrial fibrillation (AF) is limited by low detection of AF, non-adherence to guidelines, and lack of consideration of patients’ preferences, thus highlighting the need for a more holistic and integrated approach to AF management. Objective The objective of this study was to determine whether a mobile health (mHealth) technology-supported AF integrated management strategy would reduce AF-related adverse events, compared with usual care. Methods This is a cluster randomized trial of patients with AF older than 18 years of age who were enrolled in 40 cities in China. Recruitment began on June 1, 2018 and follow-up ended on August 16, 2019. Patients with AF were randomized to receive usual care, or integrated care based on a mobile AF Application (mAFA) incorporating the ABC (Atrial Fibrillation Better Care) Pathway: A, Avoid stroke; B, Better symptom management; and C, Cardiovascular and other comorbidity risk reduction. The primary composite outcome was a composite of stroke/thromboembolism, all-cause death, and rehospitalization. Rehospitalization alone was a secondary outcome. Cardiovascular events were assessed using Cox proportional hazard modeling after adjusting for baseline risk. Results There were 1,646 patients allocated to mAFA intervention (mean age, 67.0 years; 38.0% female) with mean follow-up of 262 days, whereas 1,678 patients were allocated to usual care (mean age, 70.0 years; 38.0% female) with mean follow-up of 291 days. Rates of the composite outcome of ‘ischemic stroke/systemic thromboembolism, death, and rehospitalization’ were lower with the mAFA intervention compared with usual care (1.9% vs. 6.0%; hazard ratio [HR]: 0.39; 95% confidence interval [CI]: 0.22 to 0.67; p < 0.001). Rates of rehospitalization were lower with the mAFA intervention (1.2% vs. 4.5%; HR: 0.32; 95% CI: 0.17 to 0.60; p < 0.001). Subgroup analyses by sex, age, AF type, risk score, and comorbidities demonstrated consistently lower HRs for the composite outcome for patients receiving the mAFA intervention compared with usual care (all p < 0.05). Conclusions An integrated care approach to holistic AF care, supported by mHealth technology, reduces the risks of rehospitalization and clinical adverse events. (Mobile Health [mHealth] technology integrating atrial fibrillation screening and ABC management approach trial; ChiCTR-OOC-17014138)

Asian journal of andrology

The Argo Program has been implemented and sustained for almost two decades, as a global array of about 4000 profiling floats. Argo provides continuous observations of ocean temperature and salinity versus pressure, from the sea surface to 2000 dbar. The successful installation of the Argo array and its innovative data management system arose opportunistically from the combination of great scientific need and technological innovation. Through the data system, Argo provides fundamental physical observations with broad societally-valuable applications, built on the cost-efficient and robust technologies of autonomous profiling floats. Following recent advances in platform and sensor technologies, even greater opportunity exists now than 20 years ago to (i) improve Argo's global coverage and value beyond the original design, (ii) extend Argo to span the full ocean depth, (iii) add biogeochemical sensors for improved understanding of oceanic cycles of carbon, nutrients, and ecosystems, and (iv) consider experimental sensors that might be included in the future, for example to document the spatial and temporal patterns of ocean mixing. For Core Argo and each of these enhancements, the past, present, and future progression along a path from experimental deployments to regional pilot arrays to global implementation is described. The objective is to create a fully global, top-to-bottom, dynamically complete, and multidisciplinary Argo Program that will integrate seamlessly with satellite and with other in situ elements of the Global Ocean Observing System (Legler et al., 2015). The integrated system will deliver operational reanalysis and forecasting capability, and assessment of the state and variability of the climate system with respect to physical, biogeochemical, and ecosystems parameters. It will enable basic research of unprecedented breadth and magnitude, and a wealth of ocean-education and outreach opportunities