Fatal and Nonfatal Firearm Injury Rates by Race and Ethnicity in the United States, 2019 to 2020.

BACKGROUND: Racial disparities in firearm injury death in the United States are well established. Less is known about the magnitude of nonfatal and total firearm injury. OBJECTIVE: To combine health care data with death certificate data to estimate total firearm injuries in various racial and ethnic groups. DESIGN: Retrospective, cross-sectional study. SETTING: Fatal injury data were collected from the Centers for Disease Control and Prevention. Data on nonfatal injuries were collected from the Nationwide Emergency Department Sample (NEDS), a 20% stratified sample of U.S. emergency department visits, weighted to provide national estimates for the United States, 2019 to 2020. PARTICIPANTS: All firearm injuries and deaths in the United States. INTERVENTION: Race and ethnicity were classified into 5 mutually exclusive categories: Asian or Pacific Islander, Black, Hispanic, Native American, and White. International Classification of Diseases, 10th Revision codes were used to classify firearm injury intent. MEASUREMENTS: Incidence of fatal and nonfatal injury in the U.S. population and case-fatality ratios (CFRs). RESULTS: There were 252 376 total firearm injuries, including 84 908 deaths from firearm injures. Of all firearm injuries, 37.8% were unintentional, 37.3% were assault related, 21.0% were self-harm, and 1.3% were law enforcement associated. Self-harm had the highest CFRs (90.9% overall). Unintentional injuries accounted for just 1021 (1.2%) deaths but 94 433 (56.4%) of nonfatal injuries. Rates of self-harm were highest among White persons (11.0 per 100 000 population in 2020) followed by Native Americans (8.6 per 100 000). Rates of assault were highest among Black persons (70.1 per 100 000), as were unintentional injuries (56.1 per 100 000). LIMITATION: Findings are limited by the accuracy of discharge coding in NEDS, particularly regarding injury intent and patient race and ethnicity. CONCLUSION: From 2019 to 2020, the total burden of firearm injuries amounts to an average of 1 injury every 4 minutes and 1 death every 12 minutes in the United States. Racial disparities in firearm injury death are mirrored in nonfatal injury. PRIMARY FUNDING SOURCE: None.

Epigenetic patterns in Atlantic herring (Clupea harengus): Temperature and photoperiod as environmental stressors during larval development.

Understanding the molecular mechanisms underlying individual responses to environmental changes is crucial for species conservation and management. Pelagic fishes including Atlantic herring (Clupea harengus) are of particular interest because of their key ecological and economic roles and their susceptibility to a changing ocean from global warming. Temperature and photoperiod have been linked with spawning time and location in adult herring, but no study has thus far investigated the role of environmental factors on gene regulation during the vulnerable early developmental stages. Here, we examine DNA methylation patterns of larval herring bred under two temperatures (11°C and 13°C) and photoperiod (6 and 12 h) regimes in a 2 × 2 factorial design. We found consistently high levels of global methylation across all individuals and a decline in global methylation with increased developmental stage that was more pronounced at 13°C (p ≤ 0.007) than at 11°C (p ≥ 0.21). Most of the differentially methylated sites were in exon and promoter regions for genes linked to metabolism and development, some of which were hypermethylated at higher temperature. These results demonstrate the important role of DNA methylation during larval development and suggest that this molecular mechanism might be key in regulating early-stage responses to environmental stressors in Atlantic herring.

Viral Fitness Landscapes Based on Self-organizing Maps.

The creation of fitness maps from viral populations especially in the case of RNA viruses, with high mutation rates producing quasispecies, is complex since the mutant spectrum is in a very high-dimensional space. In this work, a new approach is presented using a class of neural networks, Self-Organized Maps (SOM), to represent realistic fitness landscapes in two RNA viruses: Human Immunodeficiency Virus type 1 (HIV-1) and Hepatitis C Virus (HCV). This methodology has proven to be very effective in the classification of viral quasispecies, using as criterium the mutant sequences in the population. With HIV-1, the fitness landscapes are constructed by representing the experimentally determined fitness on the sequence map. This approach permitted the depiction of the evolutionary paths of the variants subjected to processes of fitness loss and gain in cell culture. In the case of HCV, the efficiency was measured as a function of the frequency of each haplotype in the population by ultra-deep sequencing. The fitness landscapes obtained provided information on the efficiency of each variant in the quasispecies environment, that is, in relation to the entire spectrum of mutants. With the SOM maps, it is possible to determine the evolutionary dynamics of the different haplotypes.

Health Care Use Among Patients Retroactively Insured via a Hospital-Based Insurance Linkage Program.

OBJECTIVE: Over 25% of the 27 million uninsured individuals in the United States are eligible for Medicaid. Many hospitals have insurance linkage programs that assist eligible patients with enrollment, but little is known about the impact of these programs on care utilization. This research assessed health care utilization and health outcomes among patients enrolled in Medicaid via a hospital-based insurance linkage program. METHODS: This retrospective cohort study included adults aged 18-64 admitted to the hospital from 2016 to 2021. Those who obtained insurance retroactively via insurance linkage (RI) were compared with those who presented with Medicaid (MI) or remained uninsured (UI). The primary outcome was the presence of at least one visit with a primary care provider (PCP) in the 12 months following index admission. Secondary outcomes included having an assigned PCP, ED revisits, and hospital readmissions. For patients with diabetes and hypertension, 12-month hemoglobin A1c (HbA1c) and blood pressure (BP) readings were tracked. RESULTS: Of 3882 patients admitted with no insurance, 2905 (74.8%) were enrolled in insurance (RI). In multivariable analysis, RI patients were 14% more likely (OR 1.14, p = 0.020) to have completed at least one PCP visit by 12 months after index admission compared to those with preexisting Medicaid (MI), and uninsured patients were 29% less likely (OR 0.71, p = 0.003). MI and RI patients also had more ED revisits (p < 0.001) and greater 12-month reductions in blood pressure (p < 0.001) compared with uninsured patients. CONCLUSION: Hospital-based insurance linkage reached three-quarters of uninsured patients and was associated with increased utilization of acute and outpatient health care services. An acute care encounter represents an opportunity to connect patients to insurance, a key step toward improving their health outcomes.

Firearm violence and associated factors among young adults presenting to emergency departments in three cities: Baseline results from Project SPARK.

OBJECTIVE: Recent shifts in U.S. violence dynamics call for updated violence epidemiology among general emergency department (ED) samples of young adults. Using baseline data from a multi-site longitudinal study of firearm violence prediction, we describe violence rates and associated factors. METHODS: Staff approached age 18-24 entrants to Level-1 trauma centers in three cities (Flint, Seattle, Philadelphia; 7/2021-5/2023). Consenting participants completed a survey including validated measures of violence experience, firearm-related behaviors, substance use, mental health symptoms, peer/parental/familial behaviors, community violence, and attitudes/norms. We described the sample and examined factors associated with firearm assault (victimization/aggression, including threats). RESULTS: Across sites, 1506 participants enrolled (40.9 % Black; 34.3 % White; 60.1 % female). Half of participants self-reported past-six-month violent victimization and/or aggression; non-partner violence, and violent victimization were most common. Over half of participants self-reported high-risk substance use, and over half screened positive for post-traumatic stress disorder, depression, and/or anxiety. About 14.4 % self-reported past-six-month firearm assault, and 5.9 % self-reported firearm violence (excluding threats). Adjusted analysis showed community violence exposure was most strongly associated with firearm assault; each one-point-increase corresponded to a 13.7 % (95 %CI: 10.4 %-16.9 %) absolute increase in firearm assault prevalence. Drug misuse, mental health symptoms, firearm carrying, retaliatory attitudes, prosocial attitudes, and family conflict were also associated with firearm assault. CONCLUSIONS: Violence, including firearm assault, is common among young adults entering urban EDs, and is associated with several psychosocial factors. High rates of substance use and mental health symptoms underscore this as a high-need population. Leveraging this information could help tailor interventions and optimize resource allocation.

Association between patient-reported onset-to-door time and mortality in patients hospitalized with COVID-19 disease.

INTRODUCTION: Timely hospital presentation and treatment are critical for recovery from coronavirus disease (COVID-19). However, the relationship between symptom onset-to-door time and key clinical outcomes, such as inpatient mortality, has been poorly understood due to the difficulty of retrospectively measuring symptom onset in observational data. This study examines the association between patient-reported symptom onset-to-door time (ODT) and mortality among patients hospitalized and treated for COVID-19 disease. METHODS: We conducted a retrospective cohort study of emergency department (ED) encounters of patients with COVID-19 disease who were hospitalized and received remdesivir and/or dexamethasone between March 1, 2020, and March 1, 2022. The exposure was patient-reported ODT in days. The outcome of interest was inpatient mortality, including referral to hospice care. We used multivariable logistic regression to examine the association between ODT and mortality while adjusting for patient characteristics, hospital sites, and seasonality. We tested whether severe illness on hospital presentation modified the association between ODT and mortality. Severe illness was defined by Emergency Severity Index triage level 1 or 2 and hypoxia (SpO2 < 94%). RESULTS: Of the 3451 ED hospitalizations included, 439 (12.7%) resulted in mortality, and 1693 (49.1%) involved patients with severe illness on hospital presentation. Greater ODT was significantly associated with lower odds of inpatient mortality (adjusted odds ratio (AOR) = 0.96, 95% CI = 0.93-1.00, P = 0.023). There was a statistically significant interaction between ODT and severe illness at hospital arrival on mortality, suggesting the negative association between ODT and mortality specifically pertained to patients who were not severely ill upon ED presentation (AOR = 0.93, 95% CI = 0.87-1.00, P = 0.035). The adjusted probability of mortality was significantly lower for non-severely ill, hospitalized patients who presented on days 8-14 (5.2%-3.3%) versus days 0-3 (9.4%-7.5%) after symptom onset. CONCLUSION: More days between symptom onset and hospital arrival were associated with lower mortality among hospitalized patients treated for COVID-19 disease, particularly if they did not have severe illness at ED presentation. However, onset-to-door time was not associated with mortality among hospitalized patients with severe illness at ED presentation. Collectively, these results suggest that non-severely ill COVID-19 patients who require hospitalization are less likely to decompensate with each passing day without severe illness. These findings may continue to guide clinical care delivery for hospitalized COVID-19 patients.

Does the loss of diadromy imply the loss of salinity tolerance? A gene expression study with replicate nondiadromous populations of Galaxias maculatus.

The recurrent colonization of freshwater habitats and subsequent loss of diadromy is a major ecological transition that has been reported in many ancestrally diadromous fishes. Such residency is often accompanied by a loss of tolerance to seawater. The amphidromous Galaxias maculatus has repeatedly colonized freshwater streams with evidence that freshwater-resident populations exhibit stark differences in their tolerance to higher salinities. Here, we used transcriptomics to gain insight into the mechanisms contributing to reduced tolerance to higher salinities in freshwater resident populations. We conducted an acute salinity challenge (0 ppt to 23-25 ppt) and measured osmoregulatory ability (muscle water content) over 48 h in three populations: diadromous, saltwater intolerant resident (Toltén), and saltwater tolerant resident (Valdivia). RNA sequencing of the gills identified genes that were differentially expressed in association with the salinity change and associated with the loss of saltwater tolerance in the Toltén population. Key genes associated with saltwater acclimation were characterized in diadromous G. maculatus individuals, some of which were also expressed in the saltwater tolerant resident population (Valdivia). We found that some of these "saltwater acclimation" genes, including the cystic fibrosis transmembrane conductance regulator gene (CFTR), were not significantly upregulated in the saltwater intolerant resident population (Toltén), suggesting a potential mechanism for the loss of tolerance to higher salinities. As the suite of differentially expressed genes in the diadromous-resident comparison differed between freshwater populations, we hypothesize that diadromy loss results in unique evolutionary trajectories due to drift, so the loss of diadromy does not necessarily lead to a loss in upper salinity tolerance.

La colonización recurrente de hábitats de agua dulce y la subsecuente pérdida de diadromía es una transición ecológica importante que ha sido reportada en varias especies de peces con ancestros diádromos. Esta residencia está acompañada frecuentemente por la pérdida de tolerancia a ambientes de agua salada. Galaxias maculatus, especie anfídroma, ha colonizado ríos repetidamente y existe evidencia que las poblaciones residentes presentan diferencias respecto a la tolerancia al agua salada. En este estudio, usamos transcriptómica para dilucidar los mecanismos que contribuyen a la reducida tolerancia a altas salinidades en las poblaciones residentes de agua dulce. Realizamos un desafío agudo de salinidad (0 ppt a 23-2 ppt) y medimos la habilidad osmoreguladora (contenido de agua en músculo) por 48 horas en individuos de tres poblaciones: una diádroma, una intolerante a agua salada (Toltén) y una tolerante a agua salada (Valdivia). Con el secuenciamiento de ARN de las branquias identificamos los genes expresados diferencialmente al cambio de salinidad y cuales están asociados a la pérdida de tolerancia a agua salada en la población de Toltén. Genes claves asociados a la aclimatación al agua salada fueron caracterizados en individuos diádromos, algunos de ellos también se expresaron en la población residente tolerante al agua salada (Valdivia). Sin embargo, algunos genes involucrados en la aclimatación al agua salada, incluyendo el gen regulador de la conductancia transmembrana de la fibrosis quística (CFTR), no se diferenciaron significativamente en la población residente intolerante al agua salada (Toltén), sugiriendo un mecanismo potencial de la pérdida de tolerancia a ambientes con salinidad elevada. Como el conjunto de genes expresados difiere entre las dos poblaciones residentes al compararse con la población diádroma, hipotetizamos que la pérdida de diadromía resulta en trayectorias evolutivas únicas debido a deriva génica, por lo que la pérdida de la diadromía no necesariamente conlleva a la pérdida de la tolerancia a aguas saladas.

A Prato Tour on Carbon Nanotubes: Raman Insights.

The functionalisation of carbon nanotubes has been instrumental in broadening its application field, allowing especially its use in biological studies. Although numerous covalent and non-covalent functionalisation methods have been described, the characterisation of the final materials has always been an added challenge. Among the various techniques available, Raman spectroscopy is one of the most widely used to determine the covalent functionalisation of these species. However, Raman spectroscopy is not a quantitative technique, and no studies are reported comparing its performance when the same number of functional groups are added but using completely different reactions. In this work, we have experimentally and theoretically studied the functionalisation of carbon nanotubes using two of the most commonly used reactions: 1,3-dipolar cycloaddition of azomethylene ylides and diazonium-based radical addition. The number of groups introduced onto the tubes by these reactions has been determined by different characterisation techniques. The results of this study support the idea that data obtained by Raman spectra are only helpful for comparing functionalisations produced using the same type of reaction. However, they should be carefully analysed when comparing functionalisations produced using different reaction types.

Extended π-Conjugation and Structural Planarity Effects of Symmetrical D-π-A-π-D Naphthalene and Perylene Diimide Semiconductors on n-type Electrical Properties.

A series of donor-π-acceptor-π-donor (D-π-A-π-D) compounds based on naphthalendiimide (NDI) and perylenediimide (PDI) central cores combined with triphenylamine and phenylcarbazole donor groups have been synthesized, characterized and tested in top-contact/bottom gate organic field-effect transistors (OFETs). The results showed high electron mobilities, up to 0.3 cm2 V-1 s-1 , in the case of NDI derivatives and moderate values of around 10-3  cm2 V-1 s-1 for PDI-based semiconductors. Quantum chemical calculations were performed in order to support the experimental data. The results suggest that adequate molecular characteristics and larger crystalline domains in NDI vs. PDI semiconducting films may be the reasons behind the enhanced electrical properties of NDI derivatives. Furthermore, when the lateral donor substituents are triphenylamine groups, the mobilities were slightly higher in comparison to phenylcarbazole donor groups due to an improved electron-donating character. Other characterization techniques, such as AFM, X-ray diffraction or spectroelectrochemistry, among others, have been performed to analyze supramolecular order, charge carriers' nature and stability, parameters closely related to charge transport characteristics.

Limited mitochondrial permeabilization causes DNA damage and genomic instability in the absence of cell death.

During apoptosis, the mitochondrial outer membrane is permeabilized, leading to the release of cytochrome c that activates downstream caspases. Mitochondrial outer membrane permeabilization (MOMP) has historically been thought to occur synchronously and completely throughout a cell, leading to rapid caspase activation and apoptosis. Using a new imaging approach, we demonstrate that MOMP is not an all-or-nothing event. Rather, we find that a minority of mitochondria can undergo MOMP in a stress-regulated manner, a phenomenon we term "minority MOMP." Crucially, minority MOMP leads to limited caspase activation, which is insufficient to trigger cell death. Instead, this caspase activity leads to DNA damage that, in turn, promotes genomic instability, cellular transformation, and tumorigenesis. Our data demonstrate that, in contrast to its well-established tumor suppressor function, apoptosis also has oncogenic potential that is regulated by the extent of MOMP. These findings have important implications for oncogenesis following either physiological or therapeutic engagement of apoptosis.

Association of ICU Admission and Outcomes in Sepsis and Acute Respiratory Failure.

Rationale: Many decisions to admit patients to the ICU are not grounded in evidence regarding who benefits from such triage, straining ICU capacity and limiting its cost-effectiveness. Objectives: To measure the benefits of ICU admission for patients with sepsis or acute respiratory failure. Methods: At 27 United States hospitals across two health systems from 2013 to 2018, we performed a retrospective cohort study using two-stage instrumental variable quantile regression with a strong instrument (hospital capacity strain) governing ICU versus ward admission among high-acuity patients (i.e., laboratory-based acute physiology score v2 ⩾ 100) with sepsis and/or acute respiratory failure who did not require mechanical ventilation or vasopressors in the emergency department. Measurements and Main Results: Among patients with sepsis (n = 90,150), admission to the ICU was associated with a 1.32-day longer hospital length of stay (95% confidence interval [CI], 1.01-1.63; P < 0.001) (when treating deaths as equivalent to long lengths of stay) and higher in-hospital mortality (odds ratio, 1.48; 95% CI, 1.13-1.88; P = 0.004). Among patients with respiratory failure (n = 45,339), admission to the ICU was associated with a 0.82-day shorter hospital length of stay (95% CI, -1.17 to -0.46; P < 0.001) and reduced in-hospital mortality (odds ratio, 0.75; 95% CI, 0.57-0.96; P = 0.04). In sensitivity analyses of length of stay, excluding, ignoring, or censoring death, results were similar in sepsis but not in respiratory failure. In subgroup analyses, harms of ICU admission for patients with sepsis were concentrated among older patients and those with fewer comorbidities, and the benefits of ICU admission for patients with respiratory failure were concentrated among older patients, highest-acuity patients, and those with more comorbidities. Conclusions: Among high-acuity patients with sepsis who did not require life support in the emergency department, initial admission to the ward, compared with the ICU, was associated with shorter length of stay and improved survival, whereas among patients with acute respiratory failure, triage to the ICU compared with the ward was associated with improved survival.

Variability in opioid use disorder clinical presentations and treatment in the emergency department: A mixed-methods study.

BACKGROUND: There is strong evidence for emergency department (ED)-initiated treatment of opioid use disorder (OUD). However, implementation is variable, and ED management of OUD may differ by clinical presentation. Our aim was to use mixed methods to explore variation in ED-based OUD care by patient clinical presentation and understand barriers and facilitators to ED implementation of OUD treatment across scenarios. METHODS: We analyzed treatment outcomes in OUD-related visits within three urban, academic EDs from 12/2018 to 7/2020 following the implementation of interventions to increase ED-initiated OUD treatment. We assessed differences in treatment with medications for OUD (MOUDs) by clinical presentation (overdose, withdrawal, others). These data were integrated with results from 5 focus groups conducted with 28 ED physicians and nurses January to April 2020 to provide a richer understanding of clinician perspectives on caring for ED patients with OUD. RESULTS: Of the 1339 total opioid-related visits, there were 265 (20%) visits for overdose, 123 (9%) for withdrawal, and 951 (71%) for other OUD-related conditions. 23% of patients received MOUDs during their visit or at discharge. Treatment with MOUDs was least common in overdose presentations (6%) and most common in withdrawal presentations (69%, p < 0.001). Buprenorphine was prescribed at discharge in 15% of visits, including 42% of withdrawal visits, 14% of other OUD-related visits, and 5% of overdose visits (p < 0.001). In focus groups, clinicians highlighted variation in ED presentations among patients with OUD. Clinicians also highlighted key aspects necessary for successful treatment initiation including perceived patient receptivity, provider confidence, and patient clinical readiness. CONCLUSIONS: ED-based treatment of OUD differed by clinical presentation. Clinician focus groups identified several areas where targeted guidance or novel approaches may improve current practices. These results highlight the need for tailored clinical guidance and can inform health system and policy interventions seeking to increase ED-initiated treatment for OUD.

Patient and clinician perspectives of a remote monitoring program for COVID-19 and lessons for future programs.

COVID Watch is a remote patient monitoring program implemented during the pandemic to support home dwelling patients with COVID-19. The program conferred a large survival advantage. We conducted semi-structured interviews of 85 patients and clinicians using COVID Watch to understand how to design such programs even better. Patients and clinicians found COVID Watch to be comforting and beneficial, but both groups desired more clarity about the purpose and timing of enrollment and alternatives to text-messages to adapt to patients' preferences as these may have limited engagement and enrollment among marginalized patient populations. Because inclusiveness and equity are important elements of programmatic success, future programs will need flexible and multi-channel human-to-human communication pathways for complex clinical interactions or for patients who do not desire tech-first approaches.

Are There Differences in Postoperative Opioid Prescribing Across Racial and Ethnic Groups? Assessment of an Academic Health System.

BACKGROUND: Previous studies have demonstrated racial disparities in opioid prescribing in emergency departments and after surgical procedures. Orthopaedic surgeons account for a large proportion of dispensed opioid prescriptions, yet there are few data investigating whether racial or ethnic disparities exist in opioid dispensing after orthopaedic procedures. QUESTIONS/PURPOSES: (1) Are Black, Hispanic or Latino, or Asian or Pacific Islander (PI) patients less likely than non-Hispanic White patients to receive an opioid prescription after an orthopaedic procedure in an academic United States health system? (2) Of the patients who do receive a postoperative opioid prescription, do Black, Hispanic or Latino, or Asian or PI patients receive a lower analgesic dose than non-Hispanic White patients when analyzed by type of procedure performed? METHODS: Between January 2017 and March 2021, 60,782 patients underwent an orthopaedic surgical procedure at one of the six Penn Medicine healthcare system hospitals. Of these patients, we considered patients who had not been prescribed an opioid within 1 year eligible for the study, resulting in 61% (36,854) of patients. A total of 40% (24,106) of patients were excluded because they did not undergo one of the top eight most-common orthopaedic procedures studied or their procedure was not performed by a Penn Medicine faculty member. Missing data consisted of 382 patients who had no race or ethnicity listed in their record or declined to provide a race or ethnicity; these patients were excluded. This left 12,366 patients for analysis. Sixty-five percent (8076) of patients identified as non-Hispanic White, 27% (3289) identified as Black, 3% (372) identified as Hispanic or Latino, 3% (318) identified as Asian or PI, and 3% (311) identified as another race ("other"). Prescription dosages were converted to total morphine milligram equivalents for analysis. Statistical differences in receipt of a postoperative opioid prescription were assessed with multivariate logistic regression models within procedure, adjusted for age, gender, and type of healthcare insurance. Kruskal-Wallis tests were used to assess for differences in the total morphine milligram equivalent dosage of the prescription, stratified by procedure. RESULTS: Almost all patients (95% [11,770 of 12,366]) received an opioid prescription. After risk adjustment, we found no differences in the odds of Black (odds ratio 0.94 [95% confidence interval 0.78 to 1.15]; p = 0.68), Hispanic or Latino (OR 0.75 [95% CI 0.47 to 1.20]; p = 0.18), Asian or PI (OR 1.00 [95% CI 0.58 to 1.74]; p = 0.96), or other-race patients (OR 1.33 [95% CI 0.72 to 2.47]; p = 0.26) receiving a postoperative opioid prescription compared with non-Hispanic White patients. There were no race or ethnicity differences in the median morphine milligram equivalent dose of postoperative opioid analgesics prescribed (p > 0.1 for all eight procedures) based on procedure. CONCLUSION: In this academic health system, we did not find any differences in opioid prescribing after common orthopaedic procedures by patient race or ethnicity. A potential explanation is the use of surgical pathways in our orthopaedic department. Formal standardized opioid prescribing guidelines may reduce variability in opioid prescribing. LEVEL OF EVIDENCE: Level III, therapeutic study.

Comparative Effectiveness of an Automated Text Messaging Service for Monitoring COVID-19 at Home.

BACKGROUND: Although most patients with SARS-CoV-2 infection can be safely managed at home, the need for hospitalization can arise suddenly. OBJECTIVE: To determine whether enrollment in an automated remote monitoring service for community-dwelling adults with COVID-19 at home ("COVID Watch") was associated with improved mortality. DESIGN: Retrospective cohort analysis. SETTING: Mid-Atlantic academic health system in the United States. PARTICIPANTS: Outpatients who tested positive for SARS-CoV-2 between 23 March and 30 November 2020. INTERVENTION: The COVID Watch service consists of twice-daily, automated text message check-ins with an option to report worsening symptoms at any time. All escalations were managed 24 hours a day, 7 days a week by dedicated telemedicine clinicians. MEASUREMENTS: Thirty- and 60-day outcomes of patients enrolled in COVID Watch were compared with those of patients who were eligible to enroll but received usual care. The primary outcome was death at 30 days. Secondary outcomes included emergency department (ED) visits and hospitalizations. Treatment effects were estimated with propensity score-weighted risk adjustment models. RESULTS: A total of 3488 patients enrolled in COVID Watch and 4377 usual care control participants were compared with propensity score weighted models. At 30 days, COVID Watch patients had an odds ratio for death of 0.32 (95% CI, 0.12 to 0.72), with 1.8 fewer deaths per 1000 patients (CI, 0.5 to 3.1) (P = 0.005); at 60 days, the difference was 2.5 fewer deaths per 1000 patients (CI, 0.9 to 4.0) (P = 0.002). Patients in COVID Watch had more telemedicine encounters, ED visits, and hospitalizations and presented to the ED sooner (mean, 1.9 days sooner [CI, 0.9 to 2.9 days]; all P < 0.001). LIMITATION: Observational study with the potential for unobserved confounding. CONCLUSION: Enrollment of outpatients with COVID-19 in an automated remote monitoring service was associated with reduced mortality, potentially explained by more frequent telemedicine encounters and more frequent and earlier presentation to the ED. PRIMARY FUNDING SOURCE: Patient-Centered Outcomes Research Institute.

Wildlife health surveillance: gaps, needs and opportunities.

Disease emergence represents a global threat to public health, economy and biological conservation. Most emerging zoonotic diseases have an animal origin, most commonly from wildlife. To prevent their spread and to support the implementation of control measures, disease surveillance and reporting systems are needed, and due to globalisation, these activities should be carried out at the global level. To define the main gaps affecting the performance of wildlife health surveillance and reporting systems globally, the authors analysed data from a questionnaire sent to National Focal Points of the World Organisation for Animal Health that inquired on structure and limits of wildlife surveillance and reporting systems in their territories. Responses from 103 Members, covering all areas of the globe, revealed that 54.4% have a wildlife disease surveillance programme and 66% have implemented a strategy to manage disease spread. The lack of dedicated budget affected the possibility of outbreak investigations, sample collection and diagnostic testing. Although most Members maintain records relating to wildlife mortality or morbidity events in centralised databases, data analysis and disease risk assessment are reported as priority needs. The authors' evaluation of surveillance capacity found an overall low level, with marked variability among Members that was not restricted to a specific geographical area. Increased wildlife disease surveillance globally would help in understanding and managing risks to animal and public health. Moreover, consideration of the influence of socio-economic, cultural and biodiversity aspects could improve disease surveillance under a One Health approach.

L'émergence de maladies représente une menace pour la santé publique, l'économie et la conservation de la biodiversité au niveau mondial. La plupart des maladies émergentes sont d'origine animale et proviennent de la faune sauvage. Afin de prévenir leur propagation et de soutenir la mise en oeuvre de mesures de contrôle, une surveillance des maladies et des systèmes de notification sont nécessaires - et ce à l'échelle internationale, en raison de la mondialisation. En vue de définir les lacunes principales affectant les performances de la surveillance et de la notification sanitaire relative à la faune sauvage au niveau mondial, les auteurs ont analysé les données d'un questionnaire envoyé aux Points focaux nationaux de l'Organisation mondiale de la santé animale et traitant de la structure et des limites des systèmes de surveillance et de notification applicables à la faune sauvage sur leur territoire. Selon les réponses des 103 Membres, qui représentaient toutes les régions du monde, 54,4 % disposent d'un programme de surveillance et 66 % ont mis en oeuvre une stratégie visant à gérer la propagation de maladies. L'absence de budgets dédiés affecte la possibilité d'enquêter sur l'apparition d'épidémies, de prélever des échantillons et d'effectuer des tests diagnostiques. Bien que la majorité des Membres consignent dans des bases de données centralisées les événements de mortalité et de morbidité affectant la faune sauvage, l'analyse des données et l'évaluation des risques sanitaires ont été mentionnées comme étant des besoins prioritaires. Les auteurs ont évalué les capacités de surveillance qui se situent, selon eux, à un niveau faible et se caractérisent par une grande variabilité entre les Membres, indépendamment des zones géographiques dont il s'agit. Une meilleure surveillance sanitaire de la faune sauvage au niveau mondial permettrait d'améliorer la compréhension et la gestion des risques pour la santé animale et publique. Par ailleurs, une réflexion sur l'influence des aspects socio-économiques, culturels et liés à la biodiversité améliorerait la surveillance sanitaire mise en place dans le cadre de l'approche Une seule santé.

La aparición de enfermedades representa una amenaza de dimensión mundial para la salud pública, la economía y la conservación de los recursos biológicos. La mayor parte de las enfermedades zoonóticas tienen un origen animal, por lo general localizado en la fauna silvestre. Para evitar que estas enfermedades se propaguen y apoyar la aplicación de medidas de lucha hacen falta sistemas de vigilancia y notificación de enfermedades, sistemas que, teniendo en cuenta las dinámicas de la mundialización, deben declinarse a escala planetaria. Con objeto de determinar las principales carencias que lastran el buen funcionamiento de los sistemas de vigilancia y notificación de enfermedades de la fauna silvestre a escala mundial, los autores analizaron datos extraídos de un cuestionario distribuido entre los puntos focales nacionales de la Organización Mundial de Sanidad Animal, en el cual se les preguntaba por la estructura y los límites que presentaban en su territorio dichos sistemas. Las respuestas recibidas de 103 Miembros de todas las zonas del globo pusieron de relieve que un 54,4% de ellos cuenta con un programa de vigilancia sanitaria de la fauna silvestre y que un 66% tiene implantada una estrategia para contener la propagación de enfermedades. La falta de un presupuesto asignado específicamente a estas tareas limita la posibilidad de investigar eventuales brotes, obtener muestras y practicar pruebas de diagnóstico. Aunque la mayoría de los Miembros lleva un registro de los episodios de mortalidad y morbilidad de animales salvajes en bases de datos centralizadas, el análisis de datos y la determinación del riesgo de enfermedad son dos de los aspectos mencionados como necesidad prioritaria. La evaluación de la capacidad de vigilancia realizada por los autores puso de manifiesto un nivel en general bajo, con una marcada heterogeneidad entre los Miembros que no se circunscribía a una zona geográfica en particular. Una mayor vigilancia de las enfermedades de la fauna silvestre a escala mundial ayudaría a aprehender y manejar mejor los riesgos que estas presentan para la sanidad animal y la salud pública. Además, el hecho de tener en cuenta la influencia de factores socioeconómicos, culturales y ligados a la diversidad biológica podría traducirse en una más eficaz vigilancia sanitaria en clave de Una sola salud.

Update on citric acid use in endodontic treatment: a systematic review.

This systematic review aims to analyse the available evidence concerning the use of citric acid (CA) in endodontics treatment and to assess its results in terms of different considerations: effect on smear layer removal, influence on sealer bond strength, activation effect by means of sonic or ultrasonic devices, effects on dentine surface, antibacterial activity, and effectiveness boost for regenerative procedures, releasing growth factors from dentin. To evaluate the results of CA as a final irrigant and compare them to other chelating agents. This review followed the PRISMA checklist. An electronic search was conducted in MEDLINE (OVID), Scopus (Elsevier) and the Web of Science (Thomson Reuters) databases. Risk of bias of included studies was evaluated using the modified CONSORT checklist and the PRIRATE checklist 2020 guidelines. 39 studies fulfilled the eligibility criteria to be included in this review: 27 in vitro studies using extracted human teeth, 10 in vitro studies using human dentin disks, and 2 RCT. Citric acid has proven to be effective in smear layer removal, showing better results in coronal and middle root thirds, improving its effect when combined with manual dynamic activation. There is no agreement regarding citric acid effect on sealer adhesion and adaptation to root canal walls due to heterogeneity within studies. Citric acid irrigation can decrease dentine microhardness and cause decalcification and erosion, especially when used before NaOCl. Citric acid has proven to be beneficial in regenerative endodontic procedures due to higher TGF-ß1 release.Trial registration: Prospero database CRD42021267055.

New Insights into Acylhydrazones E/Z Isomerization: An Experimental and Theoretical Approach.

A family of acylhydrazones have been prepared and characterized with the aim of investigating their potential as information storage systems. Their well-established synthetic methodologies allowed for the preparation of seven chemically stable acylhydrazones in excellent yields that have been photophysically and photochemically characterized. In addition, DFT and TD-DFT calculations have been performed to gain more insights into the structural, energetic and photophysical properties of the E/Z isomers. Our results reveal that E/Z configurational isomerization upon irradiation is highly dependent on the stabilization of the E or Z isomers due to the formation of intramolecular H bonds and the electronic/steric effects intrinsically related to their structures. In addition, Raman spectroscopy is also used to confirm the molecular structural changes after the formation of hydrogen bonds in the isomers.

Optimal Thresholds for Fracton Codes and Random Spin Models with Subsystem Symmetry.

Fracton models provide examples of novel gapped quantum phases of matter that host intrinsically immobile excitations and therefore lie beyond the conventional notion of topological order. Here, we calculate optimal error thresholds for quantum error correcting codes based on fracton models. By mapping the error-correction process for bit-flip and phase-flip noises into novel statistical models with Ising variables and random multibody couplings, we obtain models that exhibit an unconventional subsystem symmetry instead of a more usual global symmetry. We perform large-scale parallel tempering Monte Carlo simulations to obtain disorder-temperature phase diagrams, which are then used to predict optimal error thresholds for the corresponding fracton code. Remarkably, we found that the X-cube fracton code displays a minimum error threshold (7.5%) that is much higher than 3D topological codes such as the toric code (3.3%), or the color code (1.9%). This result, together with the predicted absence of glass order at the Nishimori line, shows great potential for fracton phases to be used as quantum memory platforms.

Sustained Implementation of a Multicomponent Strategy to Increase Emergency Department-Initiated Interventions for Opioid Use Disorder.

STUDY OBJECTIVE: There is strong evidence supporting emergency department (ED)-initiated buprenorphine for opioid use disorder, but less is known about how to implement this practice. Our aim was to describe implementation, maintenance, and provider adoption of a multicomponent strategy for opioid use disorder treatment in 3 urban, academic EDs. METHODS: We conducted a retrospective analysis of electronic health record data for adult patients with opioid use disorder-related visits before (March 2017 to November 2018) and after (December 2018 to July 2020) implementation. We describe patient characteristics, clinical treatment, and process measures over time and conducted an interrupted time series analysis using a patient-level multivariable logistic regression model to assess the association of the interventions with buprenorphine use and other outcomes. Finally, we report provider-level variation in prescribing after implementation. RESULTS: There were 2,665 opioid use disorder-related visits during the study period: 28% for overdose, 8% for withdrawal, and 64% for other conditions. Thirteen percent of patients received medications for opioid use disorder during or after their ED visit overall. Following intervention implementation, there were sustained increases in treatment and process measures, with a net increase in total buprenorphine of 20% in the postperiod (95% confidence interval 16% to 23%). In the adjusted patient-level model, there was an immediate increase in the probability of buprenorphine treatment of 24.5% (95% confidence interval 12.1% to 37.0%) with intervention implementation. Seventy percent of providers wrote at least 1 buprenorphine prescription, but provider-level buprenorphine prescribing ranged from 0% to 61% of opioid use disorder-related encounters. CONCLUSION: A combination of strategies to increase ED-initiated opioid use disorder treatment was associated with sustained increases in treatment and process measures. However, adoption varied widely among providers, suggesting that additional strategies are needed for broader uptake.