Sample-to-Answer Detection of SARS-CoV-2 Viremia Using Thermally Responsive Alkane Partitions.

The diagnosis of bloodborne viral infections (viremia) is currently relegated to central laboratories because of the complex procedures required to detect viruses in blood samples. The development of point-of-care diagnostics for viremia would enable patients to receive a diagnosis and begin treatment immediately instead of waiting days for results. Point-of-care systems for viremia have been limited by the challenges of integrating multiple precise steps into a fully automated (i.e., sample-to-answer), compact, low-cost system. We recently reported the development of thermally responsive alkane partitions (TRAPs), which enable the complete automation of diagnostic assays with complex samples. Here we report the use of TRAPs for the sample-to-answer detection of viruses in blood using a low-cost portable device and easily manufacturable cassettes. Specifically, we demonstrate the detection of SARS-CoV-2 in spiked blood samples, and we show that our system detects viremia in COVID-19 patient samples with good agreement to conventional RT-qPCR. We anticipate that our sample-to-answer system can be used to rapidly diagnose SARS-CoV-2 viremia at the point of care, leading to better health outcomes for patients with severe COVID-19 disease, and that our system can be applied to the diagnosis of other life-threatening bloodborne viral diseases, including Hepatitis C and HIV.

SARS-CoV-2 Infection of Salivary Glands Compromises Oral Antifungal Innate Immunity and Predisposes to Oral Candidiasis.

Saliva contains antimicrobial peptides considered integral components of host innate immunity, and crucial for protection against colonizing microbial species. Most notable is histatin-5 which is exclusively produced in salivary glands with uniquely potent antifungal activity against the opportunistic pathogen Candida albicans. Recently, SARS-CoV-2 was shown to replicate in salivary gland acinar cells eliciting local immune cell activation. In this study, we performed mechanistic and clinical studies to investigate the implications of SARS-CoV-2 infection on salivary histatin-5 production and Candida colonization. Bulk RNA-sequencing of parotid salivary glands from COVID-19 autopsies demonstrated statistically significant decreased expression of histatin genes. In situ hybridization, coupled with immunofluorescence for co-localization of SARS-CoV-2 spike and histatin in salivary gland cells, showed that histatin was absent or minimally present in acinar cells with replicating viruses. To investigate the clinical implications of these findings, salivary histatin-5 levels and oral Candida burden in saliva samples from three independent cohorts of mild and severe COVID-19 patients and matched healthy controls were evaluated. Results revealed significantly reduced histatin-5 in SARS-CoV-2 infected subjects, concomitant with enhanced prevalence of C. albicans. Analysis of prospectively recovered samples indicated that the decrease in histatin-5 is likely reversible in mild-moderate disease as concentrations tended to increase during the post-acute phase. Importantly, salivary cytokine profiling demonstrated correlations between activation of the Th17 inflammatory pathway, changes in histatin-5 concentrations, and subsequent clearance of C. albicans in a heavily colonized subject. The importance of salivary histatin-5 in controlling the proliferation of C. albicans was demonstrated using an ex vivo assay where C. albicans was able to proliferate in COVID-19 saliva with low histatin-5, but not with high histatin-5. Taken together, the findings from this study provide direct evidence implicating SARS-CoV-2 infection of salivary glands with compromised oral innate immunity, and potential predisposition to oral candidiasis.

Long-term outcomes after treatment of delirium during critical illness with antipsychotics (MIND-USA): a randomised, placebo-controlled, phase 3 trial.

BACKGROUND: Delirium is common during critical illness and is associated with long-term cognitive impairment and disability. Antipsychotics are frequently used to treat delirium, but their effects on long-term outcomes are unknown. We aimed to investigate the effects of antipsychotic treatment of delirious, critically ill patients on long-term cognitive, functional, psychological, and quality-of-life outcomes. METHODS: This prespecified, long-term follow-up to the randomised, double-blind, placebo-controlled phase 3 MIND-USA Study was conducted in 16 hospitals throughout the USA. Adults (aged ≥18 years) who had been admitted to an intensive care unit with respiratory failure or septic or cardiogenic shock were eligible for inclusion in the study if they had delirium. Participants were randomly assigned-using a computer-generated, permuted-block randomisation scheme with stratification by trial site and age-in a 1:1:1 ratio to receive intravenous placebo, haloperidol, or ziprasidone for up to 14 days. Investigators and participants were masked to treatment group assignment. 3 months and 12 months after randomisation, we assessed survivors' cognitive, functional, psychological, quality-of-life, and employment outcomes using validated telephone-administered tests and questionnaires. This trial was registered with ClinicalTrials.gov, NCT01211522, and is complete. FINDINGS: Between Dec 7, 2011, and Aug 12, 2017, we screened 20 914 individuals, of whom 566 were eligible and consented or had consent provided to participate. Of these 566 patients, 184 were assigned to the placebo group, 192 to the haloperidol group, and 190 to the ziprasidone group. 1-year survival and follow-up rates were similar between groups. Cognitive impairment was common in all three treatment groups, with a third of survivors impaired at both 3-month and 12-month follow-up in all groups. More than half of the surveyed survivors in each group had cognitive or physical limitations (or both) that precluded employment at both 3-month and 12-month follow-up. At both 3 months and 12 months, neither haloperidol (adjusted odds ratio 1·22 [95% CI 0·73-2.04] at 3 months and 1·12 [0·60-2·11] at 12 months) nor ziprasidone (1·07 [0·59-1·96] at 3 months and 0·94 [0·62-1·44] at 12 months) significantly altered cognitive outcomes, as measured by the Telephone Interview for Cognitive Status T score, compared with placebo. We also found no evidence that functional, psychological, quality-of-life, or employment outcomes improved with haloperidol or ziprasidone compared with placebo. INTERPRETATION: In delirious, critically ill patients, neither haloperidol nor ziprasidone had a significant effect on cognitive, functional, psychological, or quality-of-life outcomes among survivors. Our findings, along with insufficient evidence of short-term benefit and frequent inappropriate continuation of antipsychotics at hospital discharge, indicate that antipsychotics should not be used routinely to treat delirium in critically ill adults. FUNDING: National Institutes of Health and the US Department of Veterans Affairs.

Nasal Intubation is not Associated with "Smoother" Emergence from General Anesthesia for Carotid Endarterectomy: A Case-Cohort Study.

BACKGROUND: Postoperative hematoma after carotid endarterectomy (CEA) is a devastating complication and may be more likely in patients with uncontrolled hypertension and coughing on emergence from anesthesia. We sought to determine if intubation with a nasal endotracheal tube (ETT)-instead of an oral ETT-is associated with "smoother" (i.e., less hemodynamic instability) emergence from general anesthesia for CEA. METHODS: Patients receiving CEA between December 2015 and September 2021 at a single tertiary academic medical center were included. We examined the electronic anesthesia records for 323 patients who underwent CEA during the 6-year study period and recorded consecutive systolic blood pressure (SBP) values during the 10 minutes before extubation as a surrogate for "smoothness" of the emergence. RESULTS: Intubation with a nasal ETT, when compared with intubation with an oral ETT, was not associated with any difference in maximum, minimum, average, median, or standard deviation of serial SBP values in the 10 minutes before extubation. The average SBP on emergence for patients with an oral ETT was 141 mm Hg and with a nasal ETT was 144 mm Hg (P = 0.562). The maximum SBP for patients with oral and nasal ETTs were 170 mm Hg and 174 mm Hg, respectively (P = 0.491). There were also no differences in the qualitative "smoothness" of emergence or in the percentage of patients who required an intravenous dose of 1 or more antihypertensive medications. The incidence of postoperative complications was similar between the 2 groups. CONCLUSIONS: When SBP is used as a surrogate for smoothness of emergence from general anesthesia for CEA, intubation with a nasal ETT was not associated with better hemodynamic stability compared to intubation with an oral ETT.

Drug disposal deserts: An assessment of receptacle availability in Kentucky community pharmacies.

PURPOSE: The purpose of this study was to describe the county-level availability of drug disposal receptacles in Kentucky community pharmacies and show the relationship between installed receptacles and opioid analgesic (OA)/controlled substance dispensing rates, stratifying where possible by urban-rural classification. METHODS: Using 2020 data from the Kentucky All Schedule Prescription Electronic Reporting program and disposal receptacle data from the US Drug Enforcement Agency, county-level comparisons were made between number of receptacles and OA/controlled substance dispensing rates. Logistic and negative binomial regression models were used to assess for differences between rural/urban county designation and odds of ≥1 disposal receptacle and compare the rates of receptacles per dispensed OA dose in rural/urban counties. FINDINGS: While rural counties saw higher OA and controlled substance dispensing rates, the majority (55.6%) of disposal receptacles were in urban locations. The odds of having at least 1 receptacle were higher in urban counties (OR 2.60, 95% CI: 1.15, 5.92) compared to rural. The estimated rate of disposal receptacles per million dispensed OA doses was found to be 0.47 (95% CI: 0.36, 0.61) in urban counties compared to 0.32 (95% CI: 0.25, 0.42) in rural counties, with an estimated rate ratio of 1.45 (95% CI: 1.01, 2.10). CONCLUSIONS: A mismatch between the availability of county-level disposal receptacles in community pharmacies and the volume of dispensed OAs/controlled substances exists, resulting in fewer receptacles per dispensed OA in rural counties compared to urban counties. Future efforts are necessary to increase access to convenient disposal receptacles located in community pharmacies, particularly in rural communities.

Examination of naloxone dosing patterns for opioid overdose by emergency medical services in Kentucky during increased fentanyl use from 2018 to 2021.

BACKGROUND: Fatal overdoses involving fentanyl/fentanyl analogs (F/FA) have increased in the US, raising questions about naloxone doses for F/FA overdose reversal. Emergency medical services (EMS) data provide an opportunity to examine naloxone administration changes as fentanyl increases in the illicit opioid supply. METHODS: Administered naloxone intranasal-equivalent total dose (INTD) in milligrams (mg) was calculated for Kentucky EMS suspected opioid overdose (SOO) encounters (n=33,846), 2018-2021, and patterns of administration were examined. County-level F/FA availability was measured as 1) proportion of fatal drug overdoses involving F/FA, and 2) F/FA police seizures. Linear mixed models estimated changes in INTD in relation to local F/FA availability accounting for patient characteristics. RESULTS: From 2018-2021, SOOs increased by 44% (6853 to 9888) with an average INTD increase from 4.5mg to 4.7mg, with more than 99% of encounters resulting in successful reversal each year. For SOO encounters examined by outcome at the scene (i.e., non-fatal fatal vs fatal), average INTD for non-fatal were 4.6mg compared to 5.9mg for fatal overdoses. Mixed modeling found no significant relationship between INTD and the two measures for local F/FA availability. CONCLUSION: As F/FA-involved overdose risk increased, we observed a modest increase in INTD administered in SOO EMS encounters - just slightly higher than the 4mg standard dose. The lack of significant relationship between F/FA and naloxone dose suggests that naloxone utilization in SOO with EMS involvement remains effective for overdose reversal, and that EMS naloxone dosing patterns have not changed substantially.

Spatial access to buprenorphine-waivered prescribers in the HEALing communities study: Enhanced 2-step floating catchment area analyses in Massachusetts, Ohio, and Kentucky.

INTRODUCTION: The opioid overdose epidemic continues to impact a large swath of the population in the US. Medications for opioid use disorders (MOUD) are an effective resource to combat the epidemic; however, there is limited research on MOUD treatment access that accounts for both supply of and demand for services. We aimed to examine access to buprenorphine prescribers in the HEALing Communities Study (HCS) Wave 2 communities in Massachusetts, Ohio, and Kentucky during 2021, and the association between buprenorphine access and opioid-related incidents, specifically fatal overdoses and opioid-related responses by emergency medical services (EMS). METHODS: We calculated Enhanced 2-Step Floating Catchment Area (E2SFCA) accessibility indices for each state, as well as Wave 2 communities in each state, based on the location of providers (buprenorphine-waivered clinicians from the US Drug Enforcement Agency Active Registrants database), population-weighted centroids at the census block group level, and catchment areas defined by the state or community's average commute time. In advance of intervention initiation, we quantified the opioid-related risk environment of communities. We assessed gaps in services by using bivariate Local Moran's I analysis, incorporating accessibility indices and opioid-related incident data. RESULTS: Massachusetts Wave 2 HCS communities had the highest rates of buprenorphine prescribers per 1000 patients (median: 165.8) compared to Kentucky (38.8) and Ohio (40.1). While urban centers in all three states had higher E2SFCA index scores compared to rural communities, we observed that suburban communities often had limited access. Through bivariate Local Moran's I analysis, we identified numerous locations with low buprenorphine access surrounded by high opioid-related incidents, particularly in communities that surrounded Boston, Massachusetts; Columbus, Ohio; and Louisville, Kentucky. CONCLUSION: Rural communities demonstrated a great need for additional access to buprenorphine prescribers. However, policymakers should also direct attention toward suburban communities that have experienced significant increases in opioid-related incidents.

Sustained Implementation of an Evidence-Based Extubation Checklist Reduced Extubation Failure in Trauma Patients.

Extubation failure remains a challenge in the perioperative setting. The aim of this intervention was to decrease the rate of perioperative extubation failure through the utilization of an extubation checklist. A five-item evidence-based extubation readiness checklist was implemented at a level I trauma center on all patients who were electively extubated in the operating room (OR). Extubation failure rates before and after implementation of the checklist were compared. Of 26,867 trauma patients extubated in the OR after the intervention, 84 cases (0.31%) failed extubation in the immediate postoperative period. A significant and sustained decrease in extubation failure rate per case performed was observed between the pre- and post-checklist period (OR, 0.33; 95% CI, 0.19, 0.56; P < 0.001). Partial (vs full) checklist completion, higher ASA physical status score, advanced age, and longer case length were independently associated with increased odds of extubation failure in the postintervention period.

Early Guided Palliative Care Communication for Patients With COVID-19 Receiving ECMO.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) combined with COVID-19 presents challenges (eg, isolation, anticipatory grief) for patients and families. OBJECTIVE: To (1) describe characteristics and outcomes of patients with COVID-19 receiving ECMO, (2) develop a practice improvement strategy to implement early, semistructured palliative care communication in ECMO acknowledgment meetings with patients' families, and (3) examine family members' experiences as recorded in clinicians' notes during these meetings. METHODS: Descriptive observation of guided, in-depth meetings with families of patients with COVID-19 receiving ECMO, as gathered from the electronic medical record of a large urban academic medical center. Most meetings were held within 3 days of initiation of ECMO. RESULTS: Forty-three patients received ECMO between March and October 2020. The mean patient age was 44 years; 63% of patients were Hispanic/Latino, 19% were Black, and 7% were White. Documentation of the ECMO acknowledgment meeting was completed for 60% of patients. Fifty-six percent of patients survived to hospital discharge. Family discussions revealed 7 common themes: hope, reliance on faith, multiple family members with COVID-19, helping children adjust to a new normal, visitation restrictions, gratitude for clinicians and care, and end-of-life discussions. CONCLUSION: Early and ongoing provision of palliative care is feasible and useful for highlighting a range of experiences related to COVID-19. Palliative care is also useful for educating patients and families on the benefits and limitations of ECMO therapy.

Impact of Pandemic Response on Training Experience of Anesthesiology Residents in an Academic Medical Center: A Retrospective Cohort Study.

Background The impact of the coronavirus disease 2019 (COVID-19) pandemic substantially altered operations at hospitals that support graduate medical education. We examined the impact of the pandemic on an anesthesiology training program with respect to overall case volume, subspecialty exposure, procedural skill experience, and approaches to airway management. Methods Data for this single center, retrospective cohort study came from an Institutional Review Board approved repository for clinical data. Date ranges were divided into the following phases in 2020: Pre-Pandemic (PP), Early Pandemic (EP), Recovery 1 (R1), and Recovery 2 (R2). All periods were compared to the same period from 2019 for case volume, anesthesia provider type, trainee exposure to Accreditation Council for Graduate Medical Education (ACGME) index case categories, airway technique, and patient variables. Results 15,087 cases were identified, with 5,598 (37.6%) in the PP phase, 1,570 (10.5%) in the EP phase, 1,451 (9.7%) in the R1 phase, and 6,269 (42.1%) in the R2 phase. There was a significant reduction in case volume during the EP phase compared to the corresponding period in 2019 (-55.3%; P < .001) that improved but did not return to baseline by the R2 phase (-17.6%; P < .001). ACGME required minimum cases were reduced during the EP phase compared to 2019 data for pediatric cases (age < 12 y, -72.1%; P < .001 and age < 3 y, -53.5%; P < .006) and cardiopulmonary bypass cases (52.3%, P < .003). Surgical subspecialty case volumes were significantly reduced in the EP phase except for transplant surgery. By the R2 phase, all subspecialty volumes had recovered except for plastic surgery (14.9 vs. 10.5 cases/week; P < .006) and surgical endoscopy (59.2 vs. 40 cases/week; P < .001). Use of video laryngoscopy (VL) and rapid sequence induction and intubation (RSII) also increased from the PP to the EP phase (24.6 vs. 79.6%; P < .001 and 10.3 vs. 52.3%; P < .001, respectively) and remained elevated into the R2 phase (35.2%; P < 0.001 and 23.1%; P < .001, respectively). Conclusions The COVID-19 pandemic produced significant changes in surgical case exposure for a relatively short period. The impact was short-lived, with sufficient remaining time to meet the annual ACGME program minimum case requirements and procedural experiences. The longer-term impact may be a shift towards the increased use of VL and RSII, which became more prevalent during the early phase of the pandemic.

Changing Trends in Drug Overdose Mortality in Kentucky: An Examination of Race and Ethnicity, Age, and Contributing Drugs, 2016-2020.

OBJECTIVES: Increased drug overdose mortality among non-Hispanic Black people in the United States in the past 5 years highlights the need for better tailored programs and services. We evaluated (1) changes in drug overdose mortality for various racial and ethnic groups and (2) drug involvement to inform drug overdose prevention efforts in Kentucky. METHODS: We used Kentucky death certificates and postmortem toxicology reports from 2016-2020 (provisional data) to estimate changes in age-adjusted drug overdose death rates per 100 000 standard population. RESULTS: The age-adjusted drug overdose death rate per 100 000 standard population among non-Hispanic Black residents doubled from 2016 (21.2) to 2020 (46.0), reaching the rate among non-Hispanic White residents in 2020 (48.7; P = .48). From 2016 to 2020, about 80% of these drug overdose deaths involved opioids; heroin involvement declined about 20 percentage points; fentanyl involvement increased about 30 percentage points. The number of psychostimulant-involved drug overdose deaths increased 513% among non-Hispanic Black residents and 191% among non-Hispanic White residents. Cocaine-involved drug overdose deaths increased among non-Hispanic Black residents but declined among non-Hispanic White residents. Drug overdose death rates were significantly lower among Hispanic residents than among non-Hispanic White residents. CONCLUSIONS: Increased opioid-involved overdose deaths among non-Hispanic Black residents in Kentucky in combination with rapidly expanding concomitant psychostimulant involvement require increased understanding of the social, cultural, and illicit market circumstances driving these rapid trend changes. Our findings underscore the urgent need to expand treatment and harm reduction services to non-Hispanic Black residents with substance use disorder.

Excessive platelet inhibition following Pipeline embolization of intracranial aneurysms.

BACKGROUND: High levels of platelet inhibition have been associated with hemorrhagic complications following Pipeline embolization of intracranial aneurysms. We therefore titrate clopidogrel dosing to maintain a moderate level of platelet inhibition using the VerifyNow P2Y12 assay. However, many patients demonstrate dramatic increases in platelet inhibition following treatment despite being on a consistent antiplatelet regimen. We therefore elected to explore the incidence of this phenomenon and possible predisposing factors. METHODS: All successful Pipeline aneurysm treatments performed at our institution from 2011 to 2019 with moderate procedure-day platelet inhibition levels as indicated by a VerifyNow PRU of 60-235 were included. Patients who received glycoprotein IIb/IIIa inhibitors and those treated for ruptured/symptomatic lesions were excluded. The incidence of excessive platelet inhibition defined by a PRU<60 within 8 weeks of treatment was noted. Multivariable logistic regression was performed to determined independent predictors of the phenomenon. RESULTS: Some 190 treatments were performed in 178 qualifying patients. A post-procedure PRU <60 occurred following 79% of treatments, documented on average after 8.5 (range 1-47) days. A higher procedure day hematocrit level (P=0.003, OR 1.09, 95% CI 1.029 to 1.152) was an independent predictor of reaching a PRU <60, while intra-procedural midazolam exposure (P=0.044, OR 0.44, 95% CI 0.201 to 0.980) and a higher procedure-day PRU (P=0.047, OR 0.99, 95% CI 0.982 to 1.000) were associated with a reduced odds. Time-since-procedure and hematocrit levels were associated with excessive platelet inhibition when excluding patients who initially demonstrated hyperresponse. CONCLUSION: Elevations in platelet inhibition were frequently observed following flow diversion with Pipeline.

Effects of SARS-CoV-2 Infection on Attention, Memory, and Sensorimotor Performance.

Background: Recovery after SARS-CoV-2 infection is extremely variable, with some individuals recovering quickly, and others experiencing persistent long-term symptoms or developing new symptoms after the acute phase of infection, including fatigue, poor concentration, impaired attention, or memory deficits. Many existing studies reporting cognitive deficits associated with SARS-CoV-2 infection are limited by the exclusive use of self-reported measures or a lack of adequate comparison groups. Methods: Forty-five participants, ages 18-70, (11 Long-COVID, 14 COVID, and 20 No-COVID) underwent behavioral testing with the NIH Toolbox Neuro-Quality of Life survey and selected psychometric tests, including a flanker interference task and the d2 Test of Attention. Results: We found greater self-reported anxiety, apathy, fatigue, emotional dyscontrol, sleep disturbance and cognitive dysfunction in COVID compared No-COVID groups. After categorizing COVID patients according to self-reported concentration problems, we observed declining performance patterns in multiple attention measures across No-COVID controls, COVID and Long-COVID groups. COVID participants, compared to No-COVID controls, exhibited worse performance on NIH Toolbox assessments, including the Eriksen Flanker, Nine-Hole Pegboard and Auditory Verbal Learning tests. Conclusion: This study provides convergent evidence that previous SARS-CoV-2 infection is associated with impairments in sustained attention, processing speed, self-reported fatigue and concentration. The finding that some patients have cognitive and visuomotor dysfunction in the absence of self-reported problems suggests that SARS-CoV-2 infection can have unexpected and persistent subclinical consequences.

A Retrospective Analysis of Respiratory Complications under General Anesthesia during EBUS-TBNA.

Background: EBUS-TBNA is an established technique for diagnostically sampling intrathoracic masses and lymph nodes. While the procedure is commonly conducted under general anesthesia (GA), little is known regarding the association between anesthetic management and perioperative respiratory complications. Here, we aim to evaluate this association among patients presenting for EBUS-TBNA. Methods: 586 patients receiving GA for EBUS-TBNA between 2012 and 2018 were retrospectively evaluated. The primary endpoint was the occurrence of perioperative respiratory complications and the secondary endpoint was procedure end to OR exit time (minutes). Respiratory complications were defined as episodes of severe (SpO2 <85%) or prolonged (SpO2<90% for >5 min) hypoxemia, bronchospasm, and postoperative ventilation that could not be directly attributed to procedural invasiveness. Results: Among all patients, 79 (13.5%) had respiratory complications. Four patient characteristics were associated with respiratory complications: home oxygen use (OR 2.39; 95% CI 1.26-4.45; P = 0.007), pre-existing respiratory disease (OR 2.01; CI 1.21-3.29; P = 0.005), ASA class (P = 0.03), and albuterol administration intra-operatively (OR 2.22; CI 1.23-3.92; P = 0.007). No anesthetic factors were found to be statistically significant. Procedures with respiratory complications had a longer duration (mean time 88.7 min vs. 111.8 min; P = 0.00009), prolonged time to extubation (mean time 11.9 min vs. 14.2 min; P = 0.039), and stayed in the room longer after extubation (mean time 18.4 min vs. 23.1 min; P = 0.0016). When comparing types of GA, there were no significant differences between volatile anesthetics versus TIVA (12.7% vs. 14.6%, P = 0.54). Conclusions: Pre-existing patient characteristics, as opposed to anesthetic factors, are associated with respiratory complications during EBUS-TBNA.

Platelet surface GPIbα, activated GPIIb-IIIa, and P-selectin levels in adult veno-arterial extracorporeal membrane oxygenation patients.

Our objective was to characterize platelet surface glycoprotein (GP)Ibα, activated GPIIb-IIIa, and P-selectin levels during and after extracorporeal membrane oxygenation (ECMO). We performed a single center cohort study of 10 adult patients on ECMO for cardiogenic shock. Patients had blood samples drawn on ECMO day 1 or 2, day 3, day 5, and 48-72 hours after ECMO decannulation. Platelets from untreated blood samples and samples treated with either adenosine diphosphate (ADP) or thrombin receptor agonist peptide (TRAP) had surface GPIbα, activated GPIIb-IIIa, and P-selectin levels measured using flow cytometry. Platelet surface GPIbα levels varied significantly by time on ECMO (p = .002) and were significantly higher on ECMO day 5 compared to ECMO day 1 (p = .01). GPIbα levels during ECMO did not differ significantly from levels after ECMO decannulation (p = .14). Activated GPIIb-IIIa levels did not change significantly during ECMO, but were significantly higher after ECMO decannulation (p = .04). There were no significant differences in P-selectin levels during ECMO (p = .87) or after ECMO decannulation (p = .41). Platelet surface GPIbα and P-selectin levels were similar during and after ECMO whereas activated GPIIb-IIIa levels were lower during ECMO, particularly in response to TRAP stimulation, potentially contributing to ECMO-induced coagulopathy.

Emergency Medical Services and Syndromic Surveillance: A Comparison With Traditional Surveillance and Effects on Timeliness.

OBJECTIVE: Traditional public health surveillance of nonfatal opioid overdose relies on emergency department (ED) billing data, which can be delayed substantially. We compared the timeliness of 2 new data sources for rapid drug overdose surveillance-emergency medical services (EMS) and syndromic surveillance-with ED billing data. METHODS: We used data on nonfatal opioid overdoses in Kentucky captured in EMS, syndromic surveillance, and ED billing systems during 2018-2019. We evaluated the time-series relationships between EMS and ED billing data and syndromic surveillance and ED billing data by calculating cross-correlation functions, controlling for influences of autocorrelations. A case example demonstrates the usefulness of EMS and syndromic surveillance data to monitor rapid changes in opioid overdose encounters in Kentucky during the COVID-19 epidemic. RESULTS: EMS and syndromic surveillance data showed moderate-to-strong correlation with ED billing data on a lag of 0 (r = 0.694; 95% CI, 0.579-0.782; t = 9.73; df = 101; P < .001; and r = 0.656; 95% CI, 0.530-0.754; t = 8.73; df = 101; P < .001; respectively) at the week-aggregated level. After the COVID-19 emergency declaration, EMS and syndromic surveillance time series had steep increases in April and May 2020, followed by declines from June through September 2020. The ED billing data were available for analysis 3 months after the end of a calendar quarter but closely followed the trends identified by the EMS and syndromic surveillance data. CONCLUSION: Data from EMS and syndromic surveillance systems can be reliably used to monitor nonfatal opioid overdose trends in Kentucky in near-real time to inform timely public health response.

The impact of the national stay-at-home order on emergency department visits for suspected opioid overdose during the first wave of the COVID-19 pandemic.

BACKGROUND: Although national syndromic surveillance data reported declines in emergency department (ED) visits after the declaration of the national stay-at-home order for COVID-19, little is known whether these declines were observed for suspected opioid overdose. METHODS: This interrupted time series study used syndromic surveillance data from four states participating in the HEALing Communities Study: Kentucky, Massachusetts, New York, and Ohio. All ED encounters for suspected opioid overdose (n = 48,301) occurring during the first 31 weeks of 2020 were included. We examined the impact of the national public health emergency for COVID-19 (declared on March 14, 2020) on trends in ED encounters for suspected opioid overdose. RESULTS: Three of four states (Massachusetts, New York and Ohio) experienced a statistically significant immediate decline in the rate of ED encounters for suspected opioid overdose (per 100,000) after the nationwide public health emergency declaration (MA: -0.99; 95 % CI: -1.75, -0.24; NY: -0.10; 95 % CI, -0.20, 0.0; OH: -0.33, 95 % CI: -0.58, -0.07). After this date, Ohio and Kentucky experienced a sustained rate of increase for a 13-week period. New York experienced a decrease in the rate of ED encounters for a 10-week period, after which the rate began to increase. In Massachusetts after a significant immediate decline in the rate of ED encounters, there was no significant difference in the rate of change for a 6-week period, followed by an immediate increase in the ED rate to higher than pre-COVID levels. CONCLUSIONS: The heterogeneity in the trends in ED encounters between the four sites show that the national stay-at-home order had a differential impact on opioid overdose ED presentation in each state.

Nasal Microbiota and Infectious Complications After Elective Surgical Procedures.

Importance: The association of the nasal microbiome with outcomes in surgical patients is poorly understood. Objective: To characterize the composition of nasal microbiota in patients undergoing clean elective surgical procedures and to examine the association between characteristics of preoperative nasal microbiota and occurrence of postoperative infection. Design, Setting, and Participants: Using a nested matched case-control design, 53 individuals who developed postoperative infection were matched (approximately 3:1 by age, sex, and surgical procedure) with 144 individuals who were not infected (ie, the control group). The 2 groups were selected from a prospective cohort of patients undergoing surgical procedures at 2 tertiary care university hospitals in Baltimore, Maryland, who were at high risk for postoperative infectious complications. Included individuals were aged 40 years or older; had no history of autoimmune disease, immunocompromised state, immune-modulating medication, or active infection; and were scheduled to undergo elective cardiac, vascular, spinal, or intracranial surgical procedure. Data were analyzed from October 2015 through September 2020. Exposures: Nasal microbiome cluster class served as the main exposure. An unsupervised clustering method (ie, grades of membership modeling) was used to classify nasal microbial samples into 2 groups based on features derived from 16S ribosomal RNA gene sequencing. The microbiome cluster groups were derived independently and agnostic of baseline clinical characteristics and infection status. Main Outcomes and Measures: Composite of surgical site infection, bacteremia, and pneumonia occurring within 6 months after surgical procedure. Results: Among 197 participants (mean [SD] age, 64.1 [10.6] years; 63 [37.7%] women), 553 bacterial taxa were identified from preoperative nasal swab samples. A 2-cluster model (with 167 patients in cluster 1 and 30 patients in cluster 2) accounted for the largest proportion of variance in microbial profiles using grades of membership modeling and was most parsimonious. After adjusting for potential confounders, the probability of assignment to cluster 2 was associated with 6-fold higher odds of infection after surgical procedure (odds ratio [OR], 6.18; 95% CI, 3.33-11.7; P < .001) independent of baseline clinical characteristics, including nasal carriage of Staphylococcus aureus. Intrasample (ie, α) diversity was inversely associated with infectious outcome in both clusters (OR, 0.57; 95% CI, 0.42-0.75; P < .001); however, probability of assignment to cluster 2 was associated with higher odds of infection independent of α diversity (OR, 4.61; 95% CI, 2.78-7.86; P < .001). Conclusions and Relevance: These findings suggest that the nasal microbiome was an independent risk factor associated with infectious outcomes among individuals who underwent elective surgical procedures and may serve as a biomarker associated with infection susceptibility in this population.