The phenotypic landscape of essential human genes.

Understanding the basis for cellular growth, proliferation, and function requires determining the roles of essential genes in diverse cellular processes, including visualizing their contributions to cellular organization and morphology. Here, we combined pooled CRISPR-Cas9-based functional screening of 5,072 fitness-conferring genes in human HeLa cells with microscopy-based imaging of DNA, the DNA damage response, actin, and microtubules. Analysis of >31 million individual cells identified measurable phenotypes for >90% of gene knockouts, implicating gene targets in specific cellular processes. Clustering of phenotypic similarities based on hundreds of quantitative parameters further revealed co-functional genes across diverse cellular activities, providing predictions for gene functions and associations. By conducting pooled live-cell screening of ∼450,000 cell division events for 239 genes, we additionally identified diverse genes with functional contributions to chromosome segregation. Our work establishes a resource detailing the consequences of disrupting core cellular processes that represents the functional landscape of essential human genes.

Optical Pooled Screens in Human Cells.

Genetic screens are critical for the systematic identification of genes underlying cellular phenotypes. Pooling gene perturbations greatly improves scalability but is not compatible with imaging of complex and dynamic cellular phenotypes. Here, we introduce a pooled approach for optical genetic screens in mammalian cells. We use targeted in situ sequencing to demultiplex a library of genetic perturbations following image-based phenotyping. We screened a set of 952 genes across millions of cells for involvement in nuclear factor κB (NF-κB) signaling by imaging the translocation of RelA (p65) to the nucleus. Screening at a single time point across 3 cell lines recovered 15 known pathway components, while repeating the screen with live-cell imaging revealed a role for Mediator complex subunits in regulating the duration of p65 nuclear retention. These results establish a highly multiplexed approach to image-based screens of spatially and temporally defined phenotypes with pooled libraries.

De novo design of small beta barrel proteins.

Small beta barrel proteins are attractive targets for computational design because of their considerable functional diversity despite their very small size (<70 amino acids). However, there are considerable challenges to designing such structures, and there has been little success thus far. Because of the small size, the hydrophobic core stabilizing the fold is necessarily very small, and the conformational strain of barrel closure can oppose folding; also intermolecular aggregation through free beta strand edges can compete with proper monomer folding. Here, we explore the de novo design of small beta barrel topologies using both Rosetta energy-based methods and deep learning approaches to design four small beta barrel folds: Src homology 3 (SH3) and oligonucleotide/oligosaccharide-binding (OB) topologies found in nature and five and six up-and-down-stranded barrels rarely if ever seen in nature. Both approaches yielded successful designs with high thermal stability and experimentally determined structures with less than 2.4 Å rmsd from the designed models. Using deep learning for backbone generation and Rosetta for sequence design yielded higher design success rates and increased structural diversity than Rosetta alone. The ability to design a large and structurally diverse set of small beta barrel proteins greatly increases the protein shape space available for designing binders to protein targets of interest.

Well-Being Domains in U.S. Military Veterans: Identifying Modifiable Factors to Promote Whole Health.

The U.S. Department of Veterans Affairs is actively transitioning away from a disease-centric model of healthcare to one that prioritizes disease prevention and the promotion of overall health and well-being. Described as Whole Health, this initiative aims to provide personalized, values-centered care that optimizes physical, behavioral, spiritual, and socioeconomic well-being. To inform this initiative, we analyzed cross-sectional data from a nationally representative sample of primarily older U.S. military veterans to estimate levels of well-being across these domains, and identify sociodemographic, military, and potentially modifiable health and psychosocial correlates of them. Results revealed that, overall, veterans reported high domain-specific well-being (average scores ranging from 6.7 to 8.3 out of 10), with the highest levels in the socioeconomic domain and lowest in the physical domain. Several modifiable factors, including purpose in life, resilience, and social support, were strongly associated with the examined well-being domains. Interventions targeting these constructs may help promote well-being among U.S. veterans.

Multi-professional development of a competency framework for patients with a Port-a-Cath (PAC).

PURPOSE: In France, 40,000 Port-a-Cath (PAC) are inserted each year. These medical devices are prone to complications during their insertion or use. The education of patients wearing these devices could be a lever to reduce the risk of complications. The objective of this work was to develop, in a multi-professional and consensual manner, a unique and specific skills reference framework for patients with PAC and to propose it as a reference tool for health professionals. METHODS: A multidisciplinary working group was set up to draw up this reference framework of skills. The first stage of the work consisted of a reflection leading to an exhaustive list of competencies necessary for the patient. These skills were then classified according to three different fields of knowledge (theoretical, know-how and attitudes). Finally, the working group identified priority competencies and established a grid that can be used to evaluate the level of acquisition of these competencies. RESULTS: Fifteen competencies were identified: five relating to theoretical knowledge, six relating to know-how and four relating to attitudes. These competencies were broken down into sub-competences. Seven competencies or sub-competencies were selected to constitute the list of priority competencies. DISCUSSION: This competency framework provides a reference framework for the education of patients with PAC and will help to harmonise practices within the different teams that care for patients with PAC.

Surgery for Spinal Stenosis in Achondroplasia: Causes of Reoperation and Reduction of Risks.

BACKGROUND: Individuals with achondroplasia are prone to symptomatic spinal stenosis requiring surgery. Revision rates are thought to be high; however, the precise causes and rates of reoperation are unknown. The primary aim of this study is to investigate the causes of reoperation after initial surgical intervention in individuals with achondroplasia and spinal stenosis. In addition, we report on surgical techniques aimed at reducing the risks of these reoperations. METHODS: A retrospective review was conducted over an 8-year period of all patients with achondroplasia at a single institution that serves as a large referral center for patients with skeletal dysplasias. Patients with achondroplasia who underwent spinal surgery for stenosis were identified and the need for revision surgery was studied. Data collected included demographic, surgical, and revision details. Fisher exact test was used to determine if an association existed between construct type and the need for revisions. RESULTS: Thirty-three of the 130 (22%) patients with achondroplasia required spinal stenosis surgery. Twenty-four individuals who met the criteria were selected for analysis. The initial spine surgery was at an average age of 18.7 years (SD: 10.1 y). Nine patients (38%) required revision surgeries, and 3 required multiple revisions. Five of 9 (56%) of the revisions had primary surgery at an outside institution. Revision surgeries were due to caudal pseudarthrosis (the distal instrumented segment) (8), proximal junctional kyphosis (PJK) (7), and new neurological symptoms (7). There was a significant association found between construct type and the need for revision (P=0.0111). The pairwise comparison found that short fusions were significantly associated with the need for revision compared with the interbody group (P=0.0180). PJK was associated with short fusions when compared with the long fusion group (P=0.0294) and the interbody group (P=0.0300). Caudal pseudarthrosis was associated with short fusions when compared with the interbody group (P=0.0015). Multivariate logistic regression found long fusion with an interbody was predictive of and protective against the need for revision surgery (P=0.0246). To date, none of the initial cases that had long fusions with caudal interbody required a revision for distal pseudarthrosis. CONCLUSIONS: In patients with achondroplasia, the rate of surgery for spinal stenosis is 22% and the risk of revision is 38% and is primarily due to pseudarthrosis, PJK, and recurrent neurological symptoms. Surgeons should consider discussing spinal surgery as part of the patient's life plan and should consider wide decompression of the stenotic levels and long fusion with the use of an interbody cage at the caudal level in all patients to reduce risks of revision. LEVEL OF EVIDENCE: Level IV-Retrospective case series.

Design of Diverse Asymmetric Pockets in De Novo Homo-oligomeric Proteins.

A challenge for design of protein-small-molecule recognition is that incorporation of cavities with size, shape, and composition suitable for specific recognition can considerably destabilize protein monomers. This challenge can be overcome through binding pockets formed at homo-oligomeric interfaces between folded monomers. Interfaces surrounding the central homo-oligomer symmetry axes necessarily have the same symmetry and so may not be well suited to binding asymmetric molecules. To enable general recognition of arbitrary asymmetric substrates and small molecules, we developed an approach to designing asymmetric interfaces at off-axis sites on homo-oligomers, analogous to those found in native homo-oligomeric proteins such as glutamine synthetase. We symmetrically dock curved helical repeat proteins such that they form pockets at the asymmetric interface of the oligomer with sizes ranging from several angstroms, appropriate for binding a single ion, to up to more than 20 Å across. Of the 133 proteins tested, 84 had soluble expression in E. coli, 47 had correct oligomeric states in solution, 35 had small-angle X-ray scattering (SAXS) data largely consistent with design models, and 8 had negative-stain electron microscopy (nsEM) 2D class averages showing the structures coming together as designed. Both an X-ray crystal structure and a cryogenic electron microscopy (cryoEM) structure are close to the computational design models. The nature of these proteins as homo-oligomers allows them to be readily built into higher-order structures such as nanocages, and the asymmetric pockets of these structures open rich possibilities for small-molecule binder design free from the constraints associated with monomer destabilization.

Improving Clinical Care for Children With CKD: A Report From a National Kidney Foundation Scientific Workshop.

Development of clinical guidelines and recommendations to address the care of pediatric patients with chronic kidney disease (CKD) has rarely included the perspectives of providers from a variety of health care disciplines or the patients and parents themselves. Accordingly, the National Kidney Foundation hosted an in-person, one and a half-day workshop that convened a multidisciplinary group of physicians, allied health care professionals, and pediatric patients with CKD and their parents, with the goal of developing key clinical recommendations regarding best practices for the clinical management of pediatric patients living with CKD. The key clinical recommendations pertained to 5 broad topics: addressing the needs of patients and parents/caregivers; modifying the progression of CKD; clinical management of CKD-mineral and bone disorder and growth retardation; clinical management of anemia, cardiovascular disease, and hypertension; and transition and transfer of pediatric patients to adult nephrology care. This report describes the recommendations generated by the participants who attended the workshop.

Vitamin D and malabsorptive gastrointestinal conditions: A bidirectional relationship?

This paper is one of the outcomes of the 5th International Conference "Controversies in Vitamin D" held in Stresa, Italy from 15 to 18 September 2021 as part of a series of annual meetings which was started in 2017. The scope of these meetings is to discuss controversial issues about vitamin D. Publication of the outcomes of the meeting in international journals allows a wide sharing of the most recent data with the medical and academic community. Vitamin D and malabsorptive gastrointestinal conditions was one of the topics discussed at the meeting and focus of this paper. Participants to the meeting were invited to review available literature on selected issues related to vitamin D and gastrointestinal system and to present their topic to all participants with the aim to initiate a discussion on the main outcomes of which are reported in this document. The presentations were focused on the possible bidirectional relationship between vitamin D and gastrointestinal malabsorptive conditions such as celiac disease, inflammatory bowel diseases (IBDs) and bariatric surgery. In fact, on one hand the impact of these conditions on vitamin D status was examined and on the other hand the possible role of hypovitaminosis D on pathophysiology and clinical course of these conditions was also evaluated. All examined malabsorptive conditions severely impair vitamin D status. Since vitamin D has known positive effects on bone this in turn may contribute to negative skeletal outcomes including reduced bone mineral density, and increased risk of fracture which may be mitigated by vitamin D supplementation. Due to the immune and metabolic extra-skeletal effects there is the possibility that low levels of vitamin D may negatively impact on the underlying gastrointestinal conditions worsening its clinical course or counteracting the effect of treatment. Therefore, vitamin D status assessment and supplementation should be routinely considered in all patients affected by these conditions. This concept is strengthened by the existence of a possible bidirectional relationship through which poor vitamin D status may negatively impact on clinical course of underlying disease. Sufficient elements are available to estimate the desired threshold vitamin D level above which a favourable impact on the skeleton in these conditions may be obtained. On the other hand, ad hoc controlled clinical trials are needed to better define this threshold for obtaining a positive effect of vitamin D supplementation on occurrence and clinical course of malabsorptive gastrointestinal diseases.

Suicidal Thoughts and Behaviors in Older U.S. Military Veterans: Results From the National Health and Resilience in Veterans Study.

OBJECTIVE: To identify the prevalence and correlates associated with suicidal thoughts and behaviors (STBs) in a nationally representative sample of older (55+) US military veterans. METHODS: Data were analyzed from the 2019-2020 National Health and Resilience in Veterans Study (N = 3,356; mean age = 70.6). Self-report measures of past-year suicidal ideation (SI), lifetime suicide plan, lifetime suicide attempt(s), and future suicide intent were examined in relation to sociodemographic, neuropsychiatric, trauma, physical health, and protective factors. RESULTS: A total of 6.6% (95% CI = 5.7%-7.8%) of the sample endorsed past-year SI, 4.1% (CI = 3.3%-5.1%) a lifetime suicide plan, 1.8% (CI = 1.4%-2.3%) a lifetime suicide attempt, and 0.9% (CI = 0.5%-1.3%) future suicide intent. Higher levels of loneliness and lower levels of purpose in life were most strongly associated with past-year SI; lifetime history of major depressive disorder with suicide plan and suicide attempt; and frequency of past-year SI and more negative expectations regarding emotional aging with future suicide intent. CONCLUSION: These findings provide the most up-to-date nationally representative prevalence estimates of STBs among older military veterans in the United States. Several modifiable vulnerability factors were found to be associated with suicide risk in older US military veterans, suggesting that these factors may be targets for intervention in this population.

Purpose in life and physical health in older U.S. military veterans: Cross-sectional results from the National Health and Resilience in Veterans Study.

General population studies suggest purpose in life (PIL) is associated with a number of positive outcomes, including better mental and physical health. At present, however, scarce research has examined how PIL relates to these outcomes in veterans. The goal of this study was to determine the current prevalence of different levels of PIL and their associations with reported physical health in a nationally representative sample of predominantly older U.S. veterans. Cross-sectional data were analyzed from the 2019-2020 National Health and Resilience in Veterans Study (N = 4069; M(age) = 62.2). Veterans were classified into low, average, and high PIL. Self-report assessments were administered to assess physical health conditions and physical functioning. Results showed most veterans endorsed average PIL (71.7%), while 16.0% endorsed low PIL and 12.3% endorsed high PIL. Low PIL was associated with lower overall self-reported health and physical and cognitive functioning, as well as higher bodily pain, somatic symptoms, and physical role limitations (Cohen's d = 0.06-0.77). Low PIL was also associated with elevated rates of several physical health conditions, including sleep disorders, as well as obesity and disability with activities of daily living (i.e., ADLs) or instrumental activities of daily living (i.e., IADLs). These results suggest low PIL is associated with physical health difficulties, and underscore the importance of assessing and monitoring PIL, and evaluating whether interventions to promote PIL may help improve physical health and vice versa.

Identifying significant correlates of purpose in life in older US military veterans: results from the national health and resilience in veterans study.

OBJECTIVE: Perceived purpose in life (PIL) has been linked to a broad range of adverse physical, mental, and cognitive outcomes. However, limited research has examined factors associated with PIL that can be targeted in prevention and treatment efforts in aging populations at heightened risk of adverse outcomes. Using data from predominantly older US veterans, we sought to identify important correlates of PIL. METHODS: Cross-sectional data were analyzed from the 2019-2020 National Health and Resilience in Veterans Study, which surveyed a nationally representative sample of 4069 US military veterans (Mage = 62.2). Elastic net and relative importance analyses were conducted to evaluate sociodemographic, military, health, and psychosocial variables that were strongly associated with PIL. RESULTS: Of the 39 variables entered into an elastic net analysis, 10 were identified as significant correlates of PIL. In order of magnitude, these were resilience (18.7% relative variance explained [RVE]), optimism (12.1%), depressive symptoms (11.3%), community integration (10.7%), gratitude (10.2%), loneliness (9.8%), received social support (8.6%), conscientiousness (8.5%), openness to experience (5.4%), and intrinsic religiosity (4.7%). CONCLUSIONS: Several modifiable psychosocial factors emerged as significant correlates of PIL in US military veterans. Interventions designed to target these factors may help increase PIL and mitigate risk for adverse health outcomes in this population.

A Global Outlook on Child Sexual Abuse and Sexually Explicit Material Online During COVID-19: Trends and Interdisciplinary Prevention Methods.

This scoping review investigates the impact of COVID-19 on global and national trends in online child sexually explicit material (CSEM) trafficking and production in addition to online child sexual abuse (OCSA). Globally, CSEM consumption increased dramatically during the pandemic, as well as trafficking of self-generated material. The hypothesized reasons for the increase in OCSA and CSEM that guided this review included stay-at-home orders, COVID-19-related precautions, technology use increase, economic instability, and lack of available victim and legal resources. Current global and national law enforcement procedures to prevent the proliferation of online sexual abuse are reviewed with suggestions for preventing further increases in CSEM production, distribution, and consumption at the micro and macro levels.

Dispositional hope as a potential outcome parameter among patients with advanced malignancy: An analysis of the ENABLE database.

BACKGROUND: Hopefulness, whether inherently present (dispositional hope) or augmented (by enhancement techniques), may affect outcomes. This study was performed to determine the association of dispositional hope with survival among patients diagnosed with advanced cancer. METHODS: Data from ENABLE (Educate, Nurture, Advise, Before Life Ends), a palliative care intervention, were reanalyzed to determine the association of higher dispositional hope and patient survival. This was a secondary analysis of data combined from the ENABLE II and ENABLE III randomized controlled trials (RCTs) with respect to dispositional hope and survival. A dispositional hope index was created from 3 hope items from 2 validated baseline questionnaires. Dispositional hope and survival data were collected during the 2 RCTs. In ENABLE II, participants were randomly assigned to the ENABLE intervention or to usual care. In ENABLE III, participants were randomly assigned to receive the intervention immediately or 12 weeks after enrollment. RESULTS: In all, 529 persons were included in Cox proportional hazards regression analyses to model the effects of dispositional hope on survival. An initial analysis without covariates yielded a significant effect of hope (Wald statistic, 8.649; hazard ratio, 0.941; confidence interval, 0.904-0.980; P = .003), such that higher dispositional hope was associated with longer survival. In a subsequent analysis that included all covariates, the effect of dispositional hope approached statistical significance (Wald statistic, 2.96; hazard ratio, 0.933; confidence interval, 0.863-1.010; P = .085). CONCLUSIONS: Higher levels of dispositional hope were associated with longer survival in patients with advanced cancer. Prospective trials are needed to determine the effects of dispositional and augmented hope on the outcomes of patients with advanced cancer.

Improving Clinical Trials for Anticomplement Therapies in Complement-Mediated Glomerulopathies: Report of a Scientific Workshop Sponsored by the National Kidney Foundation.

Blocking the complement system as a therapeutic strategy has been proposed for numerous glomerular diseases but presents myriad questions and challenges, not the least of which is demonstrating efficacy and safety. In light of these potential issues and because there are an increasing number of anticomplement therapy trials either planned or under way, the National Kidney Foundation facilitated an all-virtual scientific workshop entitled "Improving Clinical Trials for Anti-Complement Therapies in Complement-Mediated Glomerulopathies." Attended by patient representatives and experts in glomerular diseases, complement physiology, and clinical trial design, the aim of this workshop was to develop standards applicable for designing and conducting clinical trials for anticomplement therapies across a wide spectrum of complement-mediated glomerulopathies. Discussions focused on study design, participant risk assessment and mitigation, laboratory measurements and biomarkers to support these studies, and identification of optimal outcome measures to detect benefit, specifically for trials in complement-mediated diseases. This report summarizes the discussions from this workshop and outlines consensus recommendations.

Developing an adolescent and adult Fontan Management Programme.

Patients with single-ventricle CHD undergo a series of palliative surgeries that culminate in the Fontan procedure. While the Fontan procedure allows most patients to survive to adulthood, the Fontan circulation can eventually lead to multiple cardiac complications and multi-organ dysfunction. Care for adolescents and adults with a Fontan circulation has begun to transition from a primarily cardiac-focused model to care models, which are designed to monitor multiple organ systems, and using clues from this screening, identify patients who are at risk for adverse outcomes. The complexity of care required for these patients led our centre to develop a multidisciplinary Fontan Management Programme with the primary goals of earlier detection and treatment of complications through the development of a cohesive network of diverse medical subspecialists with Fontan expertise.

Discovering Noncritical Organization: Statistical Mechanical, Information Theoretic, and Computational Views of Patterns in One-Dimensional Spin Systems.

We compare and contrast three different, but complementary views of "structure" and "pattern" in spatial processes. For definiteness and analytical clarity, we apply all three approaches to the simplest class of spatial processes: one-dimensional Ising spin systems with finite-range interactions. These noncritical systems are well-suited for this study since the change in structure as a function of system parameters is more subtle than that found in critical systems where, at a phase transition, many observables diverge, thereby making the detection of change in structure obvious. This survey demonstrates that the measures of pattern from information theory and computational mechanics differ from known thermodynamic and statistical mechanical functions. Moreover, they capture important structural features that are otherwise missed. In particular, a type of mutual information called the excess entropy-an information theoretic measure of memory-serves to detect ordered, low entropy density patterns. It is superior in several respects to other functions used to probe structure, such as magnetization and structure factors. ϵ-Machines-the main objects of computational mechanics-are seen to be the most direct approach to revealing the (group and semigroup) symmetries possessed by the spatial patterns and to estimating the minimum amount of memory required to reproduce the configuration ensemble, a quantity known as the statistical complexity. Finally, we argue that the information theoretic and computational mechanical analyses of spatial patterns capture the intrinsic computational capabilities embedded in spin systems-how they store, transmit, and manipulate configurational information to produce spatial structure.

Cholangiopathy After Severe COVID-19: Clinical Features and Prognostic Implications.

INTRODUCTION: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 virus, is a predominantly respiratory tract infection with the capacity to affect multiple organ systems. Abnormal liver tests, mainly transaminase elevations, have been reported in hospitalized patients. We describe a syndrome of cholangiopathy in patients recovering from severe COVID-19 characterized by marked elevation in serum alkaline phosphatase (ALP) accompanied by evidence of bile duct injury on imaging. METHODS: We conducted a retrospective study of COVID-19 patients admitted to our institution from March 1, 2020, to August 15, 2020, on whom the hepatology service was consulted for abnormal liver tests. Bile duct injury was identified by abnormal liver tests with serum ALP > 3x upper limit of normal and abnormal findings on magnetic resonance cholangiopacreatography. Clinical, laboratory, radiological, and histological findings were recorded in a Research Electronic Data Capture database. RESULTS: Twelve patients were identified, 11 men and 1 woman, with a mean age of 58 years. Mean time from COVID-19 diagnosis to diagnosis of cholangiopathy was 118 days. Peak median serum alanine aminotransferase was 661 U/L and peak median serum ALP was 1855 U/L. Marked elevations of erythrocyte sedimentation rate, C-reactive protein, and D-dimers were common. Magnetic resonance cholangiopacreatography findings included beading of intrahepatic ducts (11/12, 92%), bile duct wall thickening with enhancement (7/12, 58%), and peribiliary diffusion high signal (10/12, 83%). Liver biopsy in 4 patients showed acute and/or chronic large duct obstruction without clear bile duct loss. Progressive biliary tract damage has been demonstrated radiographically. Five patients were referred for consideration of liver transplantation after experiencing persistent jaundice, hepatic insufficiency, and/or recurrent bacterial cholangitis. One patient underwent successful living donor liver transplantation. DISCUSSION: Cholangiopathy is a late complication of severe COVID-19 with the potential for progressive biliary injury and liver failure. Further studies are required to understand pathogenesis, natural history, and therapeutic interventions.

MAA868, a novel FXI antibody with a unique binding mode, shows durable effects on markers of anticoagulation in humans.

A large unmet medical need exists for safer antithrombotic drugs because all currently approved anticoagulant agents interfere with hemostasis, leading to an increased risk of bleeding. Genetic and pharmacologic evidence in humans and animals suggests that reducing factor XI (FXI) levels has the potential to effectively prevent and treat thrombosis with a minimal risk of bleeding. We generated a fully human antibody (MAA868) that binds the catalytic domain of both FXI (zymogen) and activated FXI. Our structural studies show that MAA868 traps FXI and activated FXI in an inactive, zymogen-like conformation, explaining its equally high binding affinity for both forms of the enzyme. This binding mode allows the enzyme to be neutralized before entering the coagulation process, revealing a particularly attractive anticoagulant profile of the antibody. MAA868 exhibited favorable anticoagulant activity in mice with a dose-dependent protection from carotid occlusion in a ferric chloride-induced thrombosis model. MAA868 also caused robust and sustained anticoagulant activity in cynomolgus monkeys as assessed by activated partial thromboplastin time without any evidence of bleeding. Based on these preclinical findings, we conducted a first-in-human study in healthy subjects and showed that single subcutaneous doses of MAA868 were safe and well tolerated. MAA868 resulted in dose- and time-dependent robust and sustained prolongation of activated partial thromboplastin time and FXI suppression for up to 4 weeks or longer, supporting further clinical investigation as a potential once-monthly subcutaneous anticoagulant therapy.

Effect of COVID19 on prehospital pronouncements and ED visits for stroke and myocardial infarction.

OBJECTIVE: The Novel Coronavirus19 (COVID19) arrived in northern New Jersey (NJ) in early March 2020, peaked at the beginning of April, and then declined. Starting in March, some patients who called 911 and required advanced life support (ALS) may have decompensated more rapidly than would have been expected, possibly because of concomitant COVID19 infection and/or delays in seeking medical care because of fear of exposure to the virus, and social isolation. In this study, our goal was to determine if there was an increase in prehospital ALS pronouncements and a decrease in ED visits for potentially serious conditions such as MI and stroke during the peak of the COVID-19 pandemic in northern NJ. METHODS STUDY DESIGN: Retrospective cohort of prehospital patients pronounced dead by paramedics and patients with MI and stroke in the EDs of receiving hospitals of these paramedics. Study Setting and Population: Ten ground ALS units in northern NJ and nine receiving hospital EDs. Each ALS unit is staffed by two NJ-certified mobile intensive care paramedics and respond with a paramedic flycar in a two-tiered dispatch system. DATA ANALYSIS: We identified prehospital pronouncements using the EMSCharts electronic record (Zoll Medical, Chelmsford, Massachusetts). We tabulated the number of pronouncements by week from January 1 to June 30 in 2019 and 2020. We tabulated the combined total number of pronouncements and ED visits by month along with visits for MI and stroke and calculated the changes during the same timeframe. We used Chi-square to test for statistical significance for the monthly changes from 2019 to 2020. RESULTS: For January through June in 2019 and 2020, there were 12,210 and 13,200 ALS dispatches, and 366 and 555 prehospital pronouncements, respectively. In 2020, pronouncements rose from a weekly baseline of 13 in early March, reached a peak of 45 at the beginning of April, then returned to the baseline level by the end of May. April 2020, the month with the most pronouncements, had 183% more pronouncements than April 2019 but total ED visits and visits for MI and stroke were 49%, 46% and 42% less, respectively (p < 0.0001 for each of these changes). CONCLUSION: Following the arrival of the COVID-19 pandemic in northern NJ, we found pre-hospital ALS death pronouncements increased and ED visits for MI and stroke decreased. Although we have speculated about the reasons for these findings, further studies are needed to determine what the actual causes were.