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Introduction: The incidence of sexually transmitted infections (STI) increased in the United States between 2017–2021. There is limited data describing STI co-testing practices and the prevalence of STI co-infections in emergency departments (ED). In this study, we aimed to describe the prevalence of co-testing and co-infection of HIV, hepatitis C virus (HCV), syphilis, gonorrhea, and chlamydia, in a large, academic ED. Methods: This was a single-center, retrospective cross-sectional study of ED patients tested for HIV, HCV, syphilis, gonorrhea or chlamydia between November 27, 2018–May 26, 2019. In 2018, the study institution implemented an ED-based infectious diseases screening program in which any patient being tested for gonorrhea/chlamydia was eligible for opt-out syphilis screening, and any patient 18–64 years who was having blood drawn for any clinical purpose was eligible for opt-out HIV and HCV screening. Weanalyzed data from all ED patients ≥13 years who had undergone STI testing. The outcomes of interest included prevalence of STI testing/co-testing and the prevalence of STI infection/co-infection. We describe data with simple descriptive statistics. Results: During the study period there were 30,767 ED encounters for patients ≥13 years (mean age: 43 ± 14 years, 52% female), and 7,866 (26%) were tested for at least one of HIV, HCV, syphilis, gonorrhea, or chlamydia. We observed the following testing frequencies (and prevalence of infection): HCV, 7,539 (5.0%); HIV, 7,359 (0.9%); gonorrhea, 574 (6.1%); chlamydia, 574 (9.8%); and syphilis, 420 (10.5%). Infectious etiologies with universal testing protocols (HIV and HCV) made up the majority of STI testing. In patients with syphilis, co-infection with chlamydia (21%, 9/44) and HIV (9%, 4/44) was high. In patients with gonorrhea, co-infection with chlamydia (23%, 8/35) and syphilis (9%, 3/35) was high, and in patients with chlamydia, co-infection with syphilis (16%, 9/56) and gonorrhea (14%, 8/56) was high. P

PURPOSE: Triple-negative breast cancer (TNBC) often metastasizes to the central nervous system (CNS) and has the highest propensity among breast cancer subtypes to develop leptomeningeal disease (LMD). LMD is a spread of cancer into leptomeningeal space that speeds up the disease progression and severely aggravates the prognosis. LMD has limited treatment options. We sought to test whether the common anti-helminthic drug mebendazole (MBZ) may be effective against murine TNBC LMD. METHODS: A small-molecule screen involving TNBC cell lines identified benzimidazoles as potential therapeutic agents for further study. In vitro migration assays were used to evaluate cell migration capacity and the effect of MBZ. For in vivo testing, CNS metastasis was introduced into BALB/c athymic nude mice through internal carotid artery injections of brain-tropic MDA-MB-231-BR or MCF7-BR cells. Tumor growth and spread was monitored by bioluminescence imaging and immunohistochemistry. MBZ was given orally at 50 and 100 mg/kg doses. MBZ bioavailability was assayed by mass spectrometry. RESULTS: Bioinformatic analysis and migration assays revealed higher migratory capacity of TNBC compared to other breast cancer subtypes. MBZ effectively slowed down migration of TNBC cell line MDA-MB-231 and its brain tropic derivative MDA-MB-231-BR. In animal studies, MBZ reduced leptomeningeal spread, and extended survival in brain metastasis model produced by MDA-MB-231-BR cells. MBZ did not have an effect in the non-migratory MCF7-BR model. CONCLUSIONS: We demonstrated that MBZ is a safe and effective oral agent in an animal model of TNBC CNS metastasis. Our findings are concordant with previous efforts involving MBZ and CNS pathology and support the drugs potential utility to slow down leptomeningeal spread.

OBJECTIVES: To determine the predictive value of social determinants of health (SDoH) variables on 30-day readmission following a sepsis hospitalization as compared with traditional clinical variables. DESIGN: Multicenter retrospective cohort study using patient-level data, including demographic, clinical, and survey data. SETTINGS: Thirty-five hospitals across the United States from 2017 to 2021. PATIENTS: Two hundred seventy-one thousand four hundred twenty-eight individuals in the AllofUs initiative, of which 8909 had an index sepsis hospitalization. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Unplanned 30-day readmission to the hospital. Multinomial logistic regression models were constructed to account for survival in determination of variables associate with 30-day readmission and are presented as adjusted odds rations (aORs). Of the 8909 sepsis patients in our cohort, 21% had an unplanned hospital readmission within 30 days. Median age (interquartile range) was 54 years (41-65 yr), 4762 (53.4%) were female, and there were self-reported 1612 (18.09%) Black, 2271 (25.49%) Hispanic, and 4642 (52.1%) White individuals. In multinomial logistic regression models accounting for survival, we identified that change to nonphysician provider type due to economic reasons (aOR, 2.55 [2.35-2.74]), delay of receiving medical care due to lack of transportation (aOR, 1.68 [1.62-1.74]), and inability to afford flow-up care (aOR, 1.59 [1.52-1.66]) were strongly and independently associated with a 30-day readmission when adjusting for survival. Patients who lived in a ZIP code with a high percentage of patients in poverty and without health insurance were also more likely to be readmitted within 30 days (aOR, 1.26 [1.22-1.29] and aOR, 1.28 [1.26-1.29], respectively). Finally, we found that having a primary care provider and health insurance were associated with low odds of an unplanned 30-day readmission. CONCLUSIONS: In this multicenter retrospective cohort, several SDo

Case Presentation: A 22-year-old male with a history of anti-neutrophil cytoplasmic antibody vasculitis, renal transplant, hypertension, and no known family history of sudden cardiac death suffered a witnessed cardiac arrest. An initial rhythm strip recorded by emergency medical services revealed ventricular fibrillation. Return of spontaneous circulation was achieved after three rounds of cardiopulmonary resuscitation, defibrillation, and intravenous epinephrine. The patient was brought to the emergency department and admitted to the intensive care unit. He was diagnosed with Brugada syndrome, and an automatic implantable cardioverter-defibrillator (AICD) was placed after discharge. Discussion: Brugada syndrome is characterized electrocardiographically by ≥2 millimeters (mm) ST-segment elevation in leads V1–V2 with either “coved type” (type 1) or “saddleback” (type 2) ST-segment morphology, or ≤2 mm ST-segment elevation in V1–V2 with either “coved” or “saddleback” morphology (type 3). The absence of these patterns on isolated electrocardiograms (ECG) does not exclude the diagnosis, as dynamic fluctuations in ECG patterns are well-documented and can be induced by various physiologic stressors. This case provides an uncommon, complete electrocardiographic history of Brugada syndrome, from out-of-hospital cardiac arrest to AICD placement and depicts dynamic fluctuations between Brugada patterns and normal ECGs. This highlights the importance of serial ECGs in diagnosis, as sudden cardiac death is often the first or only presentation of Brugada syndrome.

Machine learning presents opportunities for tracking evidence on climate change adaptation, including text-based methods from natural language processing. In theory, such tools can analyse more data in less time, using fewer resources and with less risk of bias. However, the first generation of adaptation studies have delivered only proof of concepts. Reviewing these first studies, we argue that future efforts should focus on creating more diverse datasets, investigating concrete hypotheses, fostering collaboration and promoting ‘machine learning literacy’, including understanding bias. More fundamentally, machine learning enables a paradigmatic shift towards automating repetitive tasks and makes interactive ‘living evidence’ platforms possible. Broadly, the adaptation community is failing to prepare for this shift. Flagship projects of organizations such as the IPCC could help to lead the way.

Climate change adaptation policies are urgently needed, but the large volume and variety of evidence limits the ability of practitioners to make informed decisions. Here, we create an evidence map of adaptation policy research, selecting and categorizing 8,691 documents using state-of-the-art transformers-based machine learning models. We combine policy-relevant categories, such as the NATO-typology and governance levels, with automatically extracted locations and a structural topic model to provide a detailed global assessment of the tools governments are using to address climate change risks and impacts. We find that international-level policies, as well as policies in North America and much of the Global South, emphasize financial instruments, whereas national policies, particularly in Europe and Oceania, favor authority-based legislation. Collaborative approaches are most common at the local level. Despite a rapidly expanding evidence base overall, we note persistent geographic inequalities and limited evidence on information-based policies, policy implementation, and structural reforms.

The N-methyl-d-aspartate (NMDA) receptor is a glutamate-activated cation channel that is critical to many processes in the brain. Genome-wide association studies suggest that glutamatergic neurotransmission and NMDA receptor-mediated synaptic plasticity are important for body weight homeostasis1. Here we report the engineering and preclinical development of a bimodal molecule that integrates NMDA receptor antagonism with glucagon-like peptide-1 (GLP-1) receptor agonism to effectively reverse obesity, hyperglycaemia and dyslipidaemia in rodent models of metabolic disease. GLP-1-directed delivery of the NMDA receptor antagonist MK-801 affects neuroplasticity in the hypothalamus and brainstem. Importantly, targeting of MK-801 to GLP-1 receptor-expressing brain regions circumvents adverse physiological and behavioural effects associated with MK-801 monotherapy. In summary, our approach demonstrates the feasibility of using peptide-mediated targeting to achieve cell-specific ionotropic receptor modulation and highlights the therapeutic potential of unimolecular mixed GLP-1 receptor agonism and NMDA receptor antagonism for safe and effective obesity treatment.

The N-methyl-d-aspartate (NMDA) receptor is a glutamate-activated cation channel that is critical to many processes in the brain. Genome-wide association studies suggest that glutamatergic neurotransmission and NMDA receptor-mediated synaptic plasticity are important for body weight homeostasis1. Here we report the engineering and preclinical development of a bimodal molecule that integrates NMDA receptor antagonism with glucagon-like peptide-1 (GLP-1) receptor agonism to effectively reverse obesity, hyperglycaemia and dyslipidaemia in rodent models of metabolic disease. GLP-1-directed delivery of the NMDA receptor antagonist MK-801 affects neuroplasticity in the hypothalamus and brainstem. Importantly, targeting of MK-801 to GLP-1 receptor-expressing brain regions circumvents adverse physiological and behavioural effects associated with MK-801 monotherapy. In summary, our approach demonstrates the feasibility of using peptide-mediated targeting to achieve cell-specific ionotropic receptor modulation and highlights the therapeutic potential of unimolecular mixed GLP-1 receptor agonism and NMDA receptor antagonism for safe and effective obesity treatment.

BackgroundWe aimed to evaluate the feasibility of implementing an emergency department (ED)-based Coronavirus Disease of 2019 (COVID-19) vaccination protocol in a population of unhoused patients.MethodsOn June 10, 2021, a best practice alert (BPA) was implemented that fired when an ED provider opened the charts of unhoused patients and prompted the provider to order COVID-19 vaccination for eligible patients. We downloaded electronic medical record data of patients who received a COVID-19 vaccine in the ED between June 10, 2021 and August 26, 2021. The outcomes of interest were the number of unhoused, and the total number of patients vaccinated for COVID-19 during the study period. Data were described with simple descriptive statistics.ResultsThere were 25,871 patient encounters in 19,992 unique patients (mean 1.3 visits/patient) in the emergency department during the study period. There were 1,474 (6% of total ED population) visits in 1,085 unique patients who were unhoused (mean 1.4 visits/patient). The BPA fired in 1,046 unhoused patient encounters (71% of PEH encounters) and was accepted in 79 (8%). Forty-three unhoused patients were vaccinated as a result of the BPA (4% of BPA fires) and 18 unhoused patients were vaccinated without BPA prompting. An additional 76 domiciled patients were vaccinated in the ED.ConclusionsImplementing an ED-based COVID-19 vaccination program is feasible, however, only a small number of patients underwent COVID-19 vaccination. Further studies are needed to explore the utility of using the ED as a setting for COVID-19 vaccination.

To further the understanding of post-COVID conditions, and provide a more nuanced description of symptom progression, resolution, emergence, and reemergence after SARS-CoV-2 infection or COVID-like illness, analysts examined data from the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE), a prospective multicenter cohort study. This report includes analysis of data on self-reported symptoms collected from 1,296 adults with COVID-like illness who were tested for SARS-CoV-2 using a Food and Drug Administration-approved polymerase chain reaction or antigen test at the time of enrollment and reported symptoms at 3-month intervals for 12 months. Prevalence of any symptom decreased substantially between baseline and the 3-month follow-up, from 98.4% to 48.2% for persons who received a positive SARS-CoV-2 test results (COVID test-positive participants) and from 88.2% to 36.6% for persons who received negative SARS-CoV-2 test results (COVID test-negative participants). Persistent symptoms decreased through 12 months; no difference between the groups was observed at 12 months (prevalence among COVID test-positive and COVID test-negative participants = 18.3% and 16.1%, respectively; p>0.05). Both groups reported symptoms that emerged or reemerged at 6, 9, and 12 months. Thus, these symptoms are not unique to COVID-19 or to post-COVID conditions. Awareness that symptoms might persist for up to 12 months, and that many symptoms might emerge or reemerge in the year after COVID-like illness, can assist health care providers in understanding the clinical signs and symptoms associated with post-COVID-like conditions.

ObjectiveTo evaluate the impact of implementing clinical decision support (CDS) tools for outpatient antibiotic prescribing in the emergency department (ED) and clinic settings.DesignWe performed a before-and-after, quasi-experimental study that employed an interrupted time-series analysis.SettingThe study institution was a quaternary, academic referral center in Northern California.ParticipantsWe included prescriptions for patients in the ED and 21 primary-care clinics within the same health system.InterventionWe implemented a CDS tool for azithromycin on March 1, 2020, and a CDS tool for fluoroquinolones (FQs; ie, ciprofloxacin, levofloxacin, and moxifloxacin) on November 1, 2020. The CDS added friction to inappropriate ordering workflows while adding health information technology (HIT) features to easily perform recommended actions. The primary outcome was the number of monthly prescriptions for each antibiotic type, by implementation period (before vs after).ResultsImmediately after azithromycin-CDS implementation, monthly rates of azithromycin prescribing decreased significantly in both the ED (-24%; 95% CI, -37% to -10%; P < .001) and outpatient clinics (-47%; 95% CI, -56% to -37%; P < .001). In the first month after FQ-CDS implementation in the clinics, there was no significant drop in ciprofloxacin prescriptions; however, there was a significant decrease in ciprofloxacin prescriptions over time (-5% per month; 95% CI, -6% to -3%; P < .001), suggesting a delayed effect of the CDS.ConclusionImplementing CDS tools was associated with an immediate decrease in azithromycin prescriptions, in both the ED and clinics. CDS may serve as a valuable adjunct to existing antimicrobial stewardship programs.

High rates of asymptomatic infections with COVID-19 have been reported. We aimed to describe an asymptomatic COVID-19 testing protocol in a pediatric emergency department (ED). This was a retrospective cohort study of pediatric patients (younger than 18 years) who were tested for COVID-19 via the asymptomatic testing protocol at a single urban pediatric ED between May 2020 and January 2021. This included all pediatric patients undergoing admission, urgent procedures, and psychiatric facility placement. The primary outcome was the percentage of positive COVID-19 tests. COVID-19 testing was performed via real-time polymerase chain reaction RNA assay testing. County-level COVID-19 data were used to estimate local daily COVID-19 cases/100,000 individuals (from all ages). Data were described with simple descriptive statistics. There were 1459 children tested for COVID-19 under the asymptomatic protocol. Mean ± standard deviation age was 8.2 ± 5.8 years. Two tests were inconclusive and 29 (2.0%; 95% confidence interval [CI] 1.3-2.8%) were positive. Of the 29 positive cases, 14 (48%; 95% CI 29-67%) had abnormal vital signs or signs and symptoms of COVID-19, on retrospective review. A total of 15 truly asymptomatic infections were identified. On the days that asymptomatic cases were identified, the lowest average daily community rate was 7.67 cases/100,000 individuals. Asymptomatic COVID-19 positivity rates in the pediatric ED were low when the average daily community rate was fewer than 7.5 cases/100,000 individuals. In the current pandemic, ED clinicians should assess for signs and symptoms of COVID-19, even when children present to the ED with unrelated chief symptoms.

In 2020, Centers for Disease Control and Prevention (CDC) released guidelines recommending HCV screening in all adults 18 years and older. In the current study, we aimed to identify risk factors for HCV infection in an ED population. We performed a retrospective analysis of ED patients ≥ 18 years who were screened for HCV between 28 November 2018, and 27 November 2019, at a single urban, quaternary referral academic hospital. An HCV-antibody immunoassay (HCV-Ab) was used for screening; positive results were confirmed by measuring HCV ribonucleic acid (RNA). The outcome of interest was the number of new HCV diagnoses (presence of viremia by HCV RNA testing). Multiple logistic regression models were used to identify risk factors associated with a new HCV diagnosis. 16,722 adult patients were screened for HCV (mean age: 46 ± 15 years; 51% female). HCV seroprevalence was 5%. Independent risk factors for HCV included increasing age [10-year aOR 1.26 (95% CI 1.23, 1.30)], male sex [aOR 1.25 (95% CI 1.03, 1.51)], undomiciled housing status [aOR 2.8 (95% CI 2.3, 3.5)], history of tobacco use [aOR 3.0 (95% CI 2.3, 3.9)], history of illicit drug use [aOR 3.6 (95% CI 2.9, 4.5)], Medicaid insurance status [aOR 4.0 (95% CI 2.9, 5.5)] and Medicare insurance status [aOR 1.6 (95% CI 1.1, 2.2)].The ED services a high-risk population with regards to HCV infection. These data support universal screening of ED patients for HCV. Risk factor profiles could improve targeted screening at institutions without universal testing protocols.

BackgroundHigh rates of asymptomatic infections with COVID-19 have been reported.ObjectiveWe aimed to describe an asymptomatic COVID-19 testing protocol in a pediatric emergency department (ED).MethodsThis was a retrospective cohort study of pediatric patients (younger than 18 years) who were tested for COVID-19 via the asymptomatic testing protocol at a single urban pediatric ED between May 2020 and January 2021. This included all pediatric patients undergoing admission, urgent procedures, and psychiatric facility placement. The primary outcome was the percentage of positive COVID-19 tests. COVID-19 testing was performed via real-time polymerase chain reaction RNA assay testing. County-level COVID-19 data were used to estimate local daily COVID-19 cases/100,000 individuals (from all ages). Data were described with simple descriptive statistics.ResultsThere were 1459 children tested for COVID-19 under the asymptomatic protocol. Mean ± standard deviation age was 8.2 ± 5.8 years. Two tests were inconclusive and 29 (2.0%; 95% confidence interval [CI] 1.3-2.8%) were positive. Of the 29 positive cases, 14 (48%; 95% CI 29-67%) had abnormal vital signs or signs and symptoms of COVID-19, on retrospective review. A total of 15 truly asymptomatic infections were identified. On the days that asymptomatic cases were identified, the lowest average daily community rate was 7.67 cases/100,000 individuals.ConclusionsAsymptomatic COVID-19 positivity rates in the pediatric ED were low when the average daily community rate was fewer than 7.5 cases/100,000 individuals. In the current pandemic, ED clinicians should assess for signs and symptoms of COVID-19, even when children present to the ED with unrelated chief symptoms.

The prevalence of cardiovascular disease (CVD) is rising among people with HIV (PWH) in sub-Saharan Africa (SSA). Despite the utility of the electrocardiogram (ECG) in screening for CVD, there is limited data regarding longitudinal ECG changes among PWH in SSA. In this study, we aimed to describe ECG changes over a 6-month period in a cohort of PWH in northern Tanzania. Between September 2020 and March 2021, adult PWH were recruited from Majengo HIV Care and Treatment Clinic (MCTC) in Moshi, Tanzania. Trained research assistants surveyed participants and obtained a baseline ECG. Participants then returned to MCTC for a 6-month follow-up, where another ECG was obtained. Two independent physician adjudicators interpreted baseline and follow-up ECGs for rhythm, left ventricular hypertrophy (LVH), bundle branch blocks, ST-segment changes, and T-wave inversion, using standardized criteria. New ECG abnormalities were defined as those that were absent in a patients baseline ECG but present in their 6-month follow-up ECG. Of 500 enrolled participants, 476 (95.2%) completed follow-up. The mean (± SD) age of participants was 45.7 (± 11.0) years, 351 (73.7%) were female, and 495 (99.8%) were taking antiretroviral therapy. At baseline, 248 (52.1%) participants had one or more ECG abnormalities, the most common of which were LVH (n = 108, 22.7%) and T-wave inversion (n = 89, 18.7%). At six months, 112 (23.5%) participants developed new ECG abnormalities, including 40 (8.0%) cases of new T-wave inversion, 22 (4.6%) cases of new LVH, 12 (2.5%) cases of new ST elevation, and 11 (2.3%) cases of new prolonged QTc. Therefore, new ECG changes were common over a relatively short 6-month period, which suggests that subclinical CVD may develop rapidly in PWH in Tanzania. These data highlight the need for additional studies on CVD in PWH in SSA and the importance of routine CVD screening in this high-risk population.

Transportation systems in northern Canada are highly sensitive to climate change. We project how access to semi-permanent trails on land, water, and sea ice might change this century in Inuit Nunangat (the Inuit homeland in northern Canada), using CMIP6 projections coupled with trail access models developed with community members. Overall trail access is projected to diminish, with large declines in access for sea ice trails which play a central role for Inuit livelihoods and culture; limits to adaptation in southern regions of Inuit Nunangat within the next 40 years; a lengthening of the period when no trails are accessible; and an unequal distribution of impacts according to the knowledge, skills, equipment, and risk tolerance of trail users. There are opportunities for adaptation through efforts to develop skillsets and confidence in travelling in more marginal environmental conditions, which can considerably extend the envelope of days when trails are accessible and months when this is possible. Such actions could reduce impacts across emissions scenarios but their potential effectiveness declines at higher levels of global warming, and in southern regions only delays when sea ice trails become unusable.

Introduction: In 2019 the United States Preventive Services Task Force (USPSTF) released draft guidelines recommending universal hepatitis C virus (HCV) screening for individuals aged 18-79. We aimed to assess the efficacy of an Emergency Department-based HCV screening program, by comparing screening practices before and after its implementation.Methods: We performed a retrospective cohort analysis of two temporally-matched, 11-month study periods, corresponding to before and after the implementation of a best practice advisory (BPA). Patients were screened for anti-HCV antibody (Ab) and positive results were followed by HCV viral load (VL) testing. The primary implementation outcome was ED testing volume (number of tests performed/month). The primary screening outcomes were the seroprevalence of anti-HCV Ab and HCV VL. Data were described with simple descriptive statistics.Results: The median age of patients was similar between periods (pre: 50 years [IQR 34-62], post: 47 years [IQR 33-59]). Patients screened were more likely to be males in the pre-BPA period (Male, pre:60%, post: 49%). During the pre-BPA study period, a total of 69,604 patients were seen in the ED, and 218 unique patients were screened for HCV (mean 19.8 tests/month). During the post-BPA study period, a total of 68,225 patients were seen in the ED, and 14, 981 unique patients were screened for HCV (mean 1,361.9 tests/month). Anti-HCV Ab seroprevalence was 23% (51/218) and 9% (1,340/14,981) in the pre-BPA and post-BPA periods, respectively. In the pre-BPA period, six patients with a positive anti-HCV Ab level had follow-up viral load testing (three were detectable). In the post-BPA period, reflex VL testing was performed in most patients (91%, 1,225/1,340), and there were 563 patients with detectable VLs.Conclusion: Our study shows that utilizing a universal BPA-driven screening protocol can dramatically increase the number of patients screened for HCV and increase the number of new HCV diagnoses.

Introduction: In 2019 the United States Preventive Services Task Force (USPSTF) released draft guidelines recommending universal hepatitis C virus (HCV) screening for individuals aged 18-79. We aimed to assess the efficacy of an Emergency Department-based HCV screening program, by comparing screening practices before and after its implementation.Methods: We performed a retrospective cohort analysis of two temporally-matched, 11-month study periods, corresponding to before and after the implementation of a best practice advisory (BPA). Patients were screened for anti-HCV antibody (Ab) and positive results were followed by HCV viral load (VL) testing. The primary implementation outcome was ED testing volume (number of tests performed/month). The primary screening outcomes were the seroprevalence of anti-HCV Ab and HCV VL. Data were described with simple descriptive statistics.Results: The median age of patients was similar between periods (pre: 50 years [IQR 34-62], post: 47 years [IQR 33-59]). Patients screened were more likely to be males in the pre-BPA period (Male, pre:60%, post: 49%). During the pre-BPA study period, a total of 69,604 patients were seen in the ED, and 218 unique patients were screened for HCV (mean 19.8 tests/month). During the post-BPA study period, a total of 68,225 patients were seen in the ED, and 14, 981 unique patients were screened for HCV (mean 1,361.9 tests/month). Anti-HCV Ab seroprevalence was 23% (51/218) and 9% (1,340/14,981) in the pre-BPA and post-BPA periods, respectively. In the pre-BPA period, six patients with a positive anti-HCV Ab level had follow-up viral load testing (three were detectable). In the post-BPA period, reflex VL testing was performed in most patients (91%, 1,225/1,340), and there were 563 patients with detectable VLs.Conclusion: Our study shows that utilizing a universal BPA-driven screening protocol can dramatically increase the number of patients screened for HCV and increase the number of new HCV diagnoses.

Introduction: There is a growing body of literature detailing coronavirus 2019 (COVID-19) cardiovascular complications and hypercoagulability, although little has been published on venous or arterial thrombosis risk.Case Report: In this report, we present a single case of cardioembolic stroke in the setting of COVID-19 related myocarditis, diagnosed via cardiac magnetic resonance imaging and echocardiography. COVID-19 infection was confirmed via a ribonucleic acid polymerase chain reaction assay.Conclusion: Further research is needed to evaluate the hypercoagulable state of patients with COVID-19 to determine whether prophylactic anticoagulation may be warranted to prevent intracardiac thrombi and cardioembolic disease in patients with COVID-19 related myocarditis.

Introduction: There is a growing body of literature detailing coronavirus 2019 (COVID-19) cardiovascular complications and hypercoagulability, although little has been published on venous or arterial thrombosis risk.Case Report: In this report, we present a single case of cardioembolic stroke in the setting of COVID-19 related myocarditis, diagnosed via cardiac magnetic resonance imaging and echocardiography. COVID-19 infection was confirmed via a ribonucleic acid polymerase chain reaction assay.Conclusion: Further research is needed to evaluate the hypercoagulable state of patients with COVID-19 to determine whether prophylactic anticoagulation may be warranted to prevent intracardiac thrombi and cardioembolic disease in patients with COVID-19 related myocarditis.

Sea level rise (SLR) will increase adaptation needs along low-lying coasts worldwide. Despite centuries of experience with coastal risk, knowledge about the effectiveness and feasibility of societal adaptation on the scale required in a warmer world remains limited. This paper contrasts end-century SLR risks under two warming and two adaptation scenarios, for four coastal settlement archetypes (Urban Atoll Islands, Arctic Communities, Large Tropical Agricultural Deltas, Resource-Rich Cities). We show that adaptation will be substantially beneficial to the continued habitability of most low-lying settlements over this century, at least until the RCP8.5 median SLR level is reached. However, diverse locations worldwide will experience adaptation limits over the course of this century, indicating situations where even ambitious adaptation cannot sufficiently offset a failure to effectively mitigate greenhouse-gas emissions.

Introduction: New evidence suggests that emergency department (ED)-based infectious diseases screening programs have utility. We aimed to compare clinic-based and ED-based hepatitis C virus (HCV) screening programs within a single health system, to identify key differences in HCV antibody (Ab) positivity and chronic HCV, as well as population demographics.Methods: In the clinic-based program, adults in the birth cohort (born 1945-1965) were screened for HCV. In the ED-based program, non-targeted HCV screening of all adults was conducted. We included patients screened between June 2019–June 2020. Patients were screened for anti-HCV Ab, and positive results were followed by HCV viral load (VL) testing. Our primary outcomes were seroprevalence of HCV Ab and HCV VL.Results: There were 1,296 and 12,778 patients screened for HCV in the clinics and the ED, respectively. In the clinic setting, 13 patients (1%) screened positive for HCV Ab and nine (69%) completed VL testing, which was positive in one patient (11%). In the ED, 1,053 patients (8%) screened positive for HCV Ab and 847 (80%) underwent reflex VL testing, which was positive in 381 patients (45%). In an ED birth cohort sub-analysis, Hepatitis C virus Ab seroprevalence was 15% (675/4521).Conclusion: In this study of patients in a single healthcare system, ED-based HCV screening was higher yield than clinic-based screening.

Introduction: New evidence suggests that emergency department (ED)-based infectious diseases screening programs have utility. We aimed to compare clinic-based and ED-based hepatitis C virus (HCV) screening programs within a single health system, to identify key differences in HCV antibody (Ab) positivity and chronic HCV, as well as population demographics.Methods: In the clinic-based program, adults in the birth cohort (born 1945-1965) were screened for HCV. In the ED-based program, non-targeted HCV screening of all adults was conducted. We included patients screened between June 2019–June 2020. Patients were screened for anti-HCV Ab, and positive results were followed by HCV viral load (VL) testing. Our primary outcomes were seroprevalence of HCV Ab and HCV VL.Results: There were 1,296 and 12,778 patients screened for HCV in the clinics and the ED, respectively. In the clinic setting, 13 patients (1%) screened positive for HCV Ab and nine (69%) completed VL testing, which was positive in one patient (11%). In the ED, 1,053 patients (8%) screened positive for HCV Ab and 847 (80%) underwent reflex VL testing, which was positive in 381 patients (45%). In an ED birth cohort sub-analysis, Hepatitis C virus Ab seroprevalence was 15% (675/4521).Conclusion: In this study of patients in a single healthcare system, ED-based HCV screening was higher yield than clinic-based screening.

Chronic pain has become a global health problem contributing to years lived with disability and reduced quality of life. Advances in the clinical management of chronic pain have been limited due to incomplete understanding of the multiple risk factors and molecular mechanisms that contribute to the development of chronic pain. The Acute to Chronic Pain Signatures (A2CPS) Program aims to characterize the predictive nature of biomarkers (brain imaging, high-throughput molecular screening techniques, or "omics," quantitative sensory testing, patient-reported outcome assessments and functional assessments) to identify individuals who will develop chronic pain following surgical intervention. The A2CPS is a multisite observational study investigating biomarkers and collective biosignatures (a combination of several individual biomarkers) that predict susceptibility or resilience to the development of chronic pain following knee arthroplasty and thoracic surgery. This manuscript provides an overview of data collection methods and procedures designed to standardize data collection across multiple clinical sites and institutions. Pain-related biomarkers are evaluated before surgery and up to 3 months after surgery for use as predictors of patient reported outcomes 6 months after surgery. The dataset from this prospective observational study will be available for researchers internal and external to the A2CPS Consortium to advance understanding of the transition from acute to chronic postsurgical pain.

IntroductionCoronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has killed nearly 800,000 Americans since early 2020. The disease has disproportionately affected older Americans, men, persons of color, and those living in congregate living facilities. Sacramento County (California USA) has used a novel Mobile Integrated Health Unit (MIH) to test hundreds of patients who dwell in congregate living facilities, including skilled nursing facilities (SNF), residential care facilities (ie, assisted living facilities [ALF] and board and care facilities [BCF]), and inpatient psychiatric facilities (PSY), for SARS-CoV-2.MethodsThe MIH was authorized and rapidly created at the beginning of the COVID-19 pandemic as a joint venture between the Sacramento County Department of Public Health (SCDPH) and several fire-based Emergency Medical Services (EMS) agencies within the county to perform SARS-CoV-2 testing and surveillance in a prehospital setting at a number of congregate living facilities. All adult patients (≥18 years) who were tested for SARS-CoV-2 infection by the MIH from March 31, 2020 through April 30, 2020 and lived in congregate living facilities were included in this retrospective descriptive cohort. Demographic and laboratory data were collected to describe the cohort of patients tested by the MIH.ResultsDuring the study period, the MIH tested a total of 323 patients from 15 facilities in Sacramento County. The median age of patients tested was 66 years and the majority were female (72%). Overall, 72 patients (22%) tested positive for SARS-CoV-2 in congregate living settings, a higher rate of positivity than was measured across the county during the same time period.ConclusionThe MIH was a novel method of epidemic surveillance that succeeded in delivering effective and efficient testing to patients who reside in congregate living facilities and was able to accurately identify pockets of infection within other

TP53 mutation is the most frequent genetic event in head and neck squamous cell carcinoma (HNSCC), found in more than 80% of patients with human papillomavirus-negative disease. As mutations in the TP53 gene are associated with worse outcomes in HNSCC, novel therapeutic approaches are needed for patients with TP53-mutated tumors. The National Cancer Institute sponsored a Clinical Trials Planning Meeting to address the issues of identifying and developing clinical trials for patients with TP53 mutations. Subcommittees, or breakout groups, were tasked with developing clinical studies in both the locally advanced and recurrent and/or metastatic (R/M) disease settings as well as considering signal-seeking trial designs. A fourth breakout group was focused on identifying and standardizing biomarker integration into trial design; this information was provided to the other breakout groups prior to the meeting to aid in study development. A total of 4 concepts were prioritized to move forward for further development and implementation. This article summarizes the proceedings of the Clinical Trials Planning Meeting with the goal of developing clinical trials for patients with TP53-mutant HNSCC that can be conducted within the National Clinical Trials Network.

[This corrects the article DOI: 10.1371/journal.pone.0054014.].

CCP6 assesses the climate change impacts and risks to ecosystems and human systems in Polar Regions, as well as options for adaptation and climate resilient development.

CCP6 assesses the climate change impacts and risks to ecosystems and human systems in Polar Regions, as well as options for adaptation and climate resilient development.

Assessing global progress on human adaptation to climate change is an urgent priority. Although the literature on adaptation to climate change is rapidly expanding, little is known about the actual extent of implementation. We systematically screened >48,000 articles using machine learning methods and a global network of 126 researchers. Our synthesis of the resulting 1,682 articles presents a systematic and comprehensive global stocktake of implemented human adaptation to climate change. Documented adaptations were largely fragmented, local and incremental, with limited evidence of transformational adaptation and negligible evidence of risk reduction outcomes. We identify eight priorities for global adaptation research: assess the effectiveness of adaptation responses, enhance the understanding of limits to adaptation, enable individuals and civil society to adapt, include missing places, scholars and scholarship, understand private sector responses, improve methods for synthesizing different forms of evidence, assess the adaptation at different temperature thresholds, and improve the inclusion of timescale and the dynamics of responses.

Assessing global progress on human adaptation to climate change is an urgent priority. Although the literature on adaptation to climate change is rapidly expanding, little is known about the actual extent of implementation. We systematically screened >48,000 articles using machine learning methods and a global network of 126 researchers. Our synthesis of the resulting 1,682 articles presents a systematic and comprehensive global stocktake of implemented human adaptation to climate change. Documented adaptations were largely fragmented, local and incremental, with limited evidence of transformational adaptation and negligible evidence of risk reduction outcomes. We identify eight priorities for global adaptation research: assess the effectiveness of adaptation responses, enhance the understanding of limits to adaptation, enable individuals and civil society to adapt, include missing places, scholars and scholarship, understand private sector responses, improve methods for synthesizing different forms of evidence, assess the adaptation at different temperature thresholds, and improve the inclusion of timescale and the dynamics of 536 responses.

Assessing global progress on human adaptation to climate change is an urgent priority. Although the literature on adaptation to climate change is rapidly expanding, little is known about the actual extent of implementation. We systematically screened >48,000 articles using machine learning methods and a global network of 126 researchers. Our synthesis of the resulting 1,682 articles presents a systematic and comprehensive global stocktake of implemented human adaptation to climate change. Documented adaptations were largely fragmented, local and incremental, with limited evidence of transformational adaptation and negligible evidence of risk reduction outcomes. We identify eight priorities for global adaptation research: assess the effectiveness of adaptation responses, enhance the understanding of limits to adaptation, enable individuals and civil society to adapt, include missing places, scholars and scholarship, understand private sector responses, improve methods for synthesizing different forms of evidence, assess the adaptation at different temperature thresholds, and improve the inclusion of timescale and the dynamics of responses.

Constraints and limits to adaptation are critical to understanding the extent to which human and natural systems can successfully adapt to climate change. We conduct a systematic review of 1,682 academic studies on human adaptation responses to identify patterns in constraints and limits to adaptation for different regions, sectors, hazards, adaptation response types, and actors. Using definitions of constraints and limits provided by the Intergovernmental Panel on Climate Change (IPCC), we find that most literature identifies constraints to adaptation but that there is limited literature focused on limits to adaptation. Central and South America and Small Islands generally report greater constraints and both hard and soft limits to adaptation. Technological, infrastructural, and ecosystem-based adaptation suggest more evidence of constraints and hard limits than other types of responses. Individuals and households face economic and socio-cultural constraints which also inhibit behavioral adaptation responses and may lead to limits. Finance, governance, institutional, and policy constraints are most prevalent globally. These findings provide early signposts for boundaries of human adaptation and are of high relevance for guiding proactive adaptation financing and governance from local to global scales.

Growing evidence suggests that climate adaptation responses that do not incorporate equity considerations may worsen inequality and increase vulnerability. Using data from a systematic review of peer-reviewed empirical research on adaptation responses to climate change (n = 1,682), we present an assessment of how social equity is considered in adaptation across regions, sectors, and social groups. Roughly 60% of peer-reviewed literature on adaptation responses considers social equity by reporting on which marginalized groups were involved in planning or implementation. Articles on responses in Africa and Asia and those focusing on poverty reduction most frequently considered social equity. Equity was less likely to be considered in adaptation responses in Europe, Australasia, and North America, as well as in literature focused on cities. Income-based inequity was more frequently considered than gender, age, or Indigenous status. Ethnic and racial minorities, migrants, and people with disabilities were rarely considered. Attention to the levels and forms in which equity is integrated into adaptation research and practice is needed to ensure just adaptation.

We conducted a global systematic literature review of climate change adaptation in fisheries. We addressed three specific questions: (i) What are fisheries adapting to? (ii) How are fisheries adapting? and (iii) What research gaps need to be addressed? We identified, characterized and examined case studies published between 1990 and 2019 that lie at the intersection of the domains of climate change, adaptation and fisheries. We characterized the documented climate change effects in fisheries that are being adapted to multiple stressors, general climate impacts, extreme events, ocean conditions, marine system shifts, climate variability, fishery dynamics, species distribution and atmospheric warming. Three categories of adaptive responses came to light: coping mechanisms (e.g. changing fishing location, use of traditional knowledge); adaptive strategies (e.g. livelihood diversification, incorporation of technology); and management responses (e.g. adaptive management, adaptation planning). We identified key potential areas for future research, including studies on the limits and barriers for adaptation, studies using specific conceptual and methodological approaches, and studies focussing on the top-producing countries such as China, Indonesia, Peru and Russia. This analysis gives broader insights to the fisheries industry and to climate change adaptation research to proceed in the face of new global challenges.

Key findings: • Climate change is impacting the subsistence harvestbased livelihoods of many small Arctic communities, affecting the quality or supply of traditional food and drinking water, including availability of species to be harvested, and altering transportation access. • Rain-on-snow, extreme snowfall, and variable freezethaw cycles have resulted in severe impacts for reindeer herders. In 2020, multiple snowstorms combined with a late spring thaw resulted in high newborn calf mortality and, together with other social stresses related to Covid-19, created severe crises for reindeer herders in Fennoscandia. • Commercial fisheries are expanding in Arctic shelf ecosystems with warmer oceans and less sea ice. This could benefit local economies and job creation, but may also challenge traditional livelihoods and culture and impact vulnerable Arctic ecosystems. Large uncertainties are associated with the effects of ocean acidification, which could potentially counteract increased commercial fishing opportunities. Commercial fishing is currently prohibited by international agreement in the Central Arctic Ocean. • Warmer water is enabling a northward expansion of salmon farming in the ice-free European Arctic. The aquaculture industry brings employment opportunities and positive ripple effects for local economies, but also has environmental and societal costs that need to be considered in marine spatial planning and regulatory measures. • Arctic cruise tourism is increasing and is attracted to the wildlife associated with the marginal ice zone. Although increased cruise tourism brings the potential for local economic development, adverse local impacts have been reported, including impacts on culture, local hunting and fishing, crowding, and revenue largely benefitting foreign-based individuals and corporations. • Permafrost thaw, flooding, and coastal erosion are causing damage to buildings, roads, and other infrastructure, and pose serious financial and health risks

[This corrects the article DOI: 10.1371/journal.pone.0054014.].

Constraints and limits to adaptation are critical to understanding the extent to which human and natural systems can successfully adapt to climate change. We conduct a systematic review of 1,682 academic studies on human adaptation responses to identify patterns in constraints and limits to adaptation for different regions, sectors, hazards, adaptation response types, and actors. Using definitions of constraints and limits provided by the Intergovernmental Panel on Climate Change (IPCC), we find that most literature identifies constraints to adaptation but that there is limited literature focused on limits to adaptation. Central and South America and Small Islands generally report greater constraints and both hard and soft limits to adaptation. Technological, infrastructural, and ecosystem-based adaptation suggest more evidence of constraints and hard limits than other types of responses. Individuals and households face economic and socio-cultural constraints which also inhibit behavioral adaptation responses and may lead to limits. Finance, governance, institutional, and policy constraints are most prevalent globally. These findings provide early signposts for boundaries of human adaptation and are of high relevance for guiding proactive adaptation financing and governance from local to global scales.

Growing evidence suggests that climate adaptation responses that do not incorporate equity considerations may worsen inequality and increase vulnerability. Using data from a systematic review of peer-reviewed empirical research on adaptation responses to climate change (n = 1,682), we present an assessment of how social equity is considered in adaptation across regions, sectors, and social groups. Roughly 60% of peer-reviewed literature on adaptation responses considers social equity by reporting on which marginalized groups were involved in planning or implementation. Articles on responses in Africa and Asia and those focusing on poverty reduction most frequently considered social equity. Equity was less likely to be considered in adaptation responses in Europe, Australasia, and North America, as well as in literature focused on cities. Income-based inequity was more frequently considered than gender, age, or Indigenous status. Ethnic and racial minorities, migrants, and people with disabilities were rarely considered. Attention to the levels and forms in which equity is integrated into adaptation research and practice is needed to ensure just adaptation.

Assessing global progress on human adaptation to climate change is an urgent priority. Although the literature on adaptation to climate change is rapidly expanding, little is known about the actual extent of implementation. We systematically screened >48,000 articles using machine learning methods and a global network of 126 researchers. Our synthesis of the resulting 1,682 articles presents a systematic and comprehensive global stocktake of implemented human adaptation to climate change. Documented adaptations were largely fragmented, local and incremental, with limited evidence of transformational adaptation and negligible evidence of risk reduction outcomes. We identify eight priorities for global adaptation research: assess the effectiveness of adaptation responses, enhance the understanding of limits to adaptation, enable individuals and civil society to adapt, include missing places, scholars and scholarship, understand private sector responses, improve methods for synthesizing different forms of evidence, assess the adaptation at different temperature thresholds, and improve the inclusion of timescale and the dynamics of responses.

We conducted a global systematic literature review of climate change adaptation in fisheries. We addressed three specific questions: (i) What are fisheries adapting to? (ii) How are fisheries adapting? and (iii) What research gaps need to be addressed? We identified, characterized and examined case studies published between 1990 and 2019 that lie at the intersection of the domains of climate change, adaptation and fisheries. We characterized the documented climate change effects in fisheries that are being adapted to multiple stressors, general climate impacts, extreme events, ocean conditions, marine system shifts, climate variability, fishery dynamics, species distribution and atmospheric warming. Three categories of adaptive responses came to light: coping mechanisms (e.g. changing fishing location, use of traditional knowledge); adaptive strategies (e.g. livelihood diversification, incorporation of technology); and management responses (e.g. adaptive management, adaptation planning). We identified key potential areas for future research, including studies on the limits and barriers for adaptation, studies using specific conceptual and methodological approaches, and studies focussing on the top-producing countries such as China, Indonesia, Peru and Russia. This analysis gives broader insights to the fisheries industry and to climate change adaptation research to proceed in the face of new global challenges.