Clinical effectiveness and analytical quality of a national point-of-care testing network for sexually transmitted infections integrated into rural and remote primary care clinics in Australia, 2016-2022: an observational program evaluation.

Background: To address inequitable diagnostic access and improve time-to-treatment for First Nations peoples, molecular point-of-care (POC) testing for chlamydia, gonorrhoea and trichomonas was integrated into 49 primary care clinics across Australia. We conducted an observational evaluation to determine clinical effectiveness and analytical quality of POC testing delivered through this national program. Methods: We evaluated (i) implementation by measuring trends in mean monthly POC testing; ii) clinical effectiveness by comparing proportions of positive patients treated by historical control/intervention period and by test type, and calculated infectious days averted; (iii) analytical quality by calculating result concordance by test type, and proportion of unsuccessful POC tests. Findings: Between 2016 and 2022, 46,153 POC tests were performed; an increasing mean monthly testing trend was observed in the first four years (p < 0.0001). A greater proportion of chlamydia/gonorrhoea positives were treated in intervention compared with historical control periods (≤2 days: 37% vs 22% [RR 1.68; 95% CI 1.12, 2.53]; ≤7 days: 48% vs 30% [RR 1.6; 95% CI 1.10, 2.33]; ≤120 days: 79% vs 54% [RR 1.46; 95% CI 1.10, 1.95]); similarly for trichomonas positives and by test type. POC testing for chlamydia, gonorrhoea and trichomonas averted 4930, 5620 and 7075 infectious days, respectively. Results concordance was high [99.0% (chlamydia), 99.3% (gonorrhoea) and 98.9% (trichomonas)]; unsuccessful POC test proportion was 1.8% for chlamydia/gonorrhoea and 2.1% for trichomonas. Interpretation: Molecular POC testing was successfully integrated into primary care settings as part of a routinely implemented program achieving significant clinical benefits with high analytical quality. In addition to the individual health benefits of earlier treatment, fewer infective days could contribute to reduced transmissions in First Nations communities. Funding: This work was supported by an Australian National Health and Medical Research Council Partnership Grant (APP1092503), the Australian Government Department of Health, Western Australia and Queensland Departments of Health.

Increased Incidence of Vestibular Disorders in Patients With SARS-CoV-2.

Objective: Determine the incidence of vestibular disorders in patients with SARS-CoV-2 compared to the control population. Study Design: Retrospective. Setting: Clinical data in the National COVID Cohort Collaborative database (N3C). Methods: Deidentified patient data from the National COVID Cohort Collaborative database (N3C) were queried based on variant peak prevalence (untyped, alpha, delta, omicron 21K, and omicron 23A) from covariants.org to retrospectively analyze the incidence of vestibular disorders in patients with SARS-CoV-2 compared to control population, consisting of patients without documented evidence of COVID infection during the same period. Results: Patients testing positive for COVID-19 were significantly more likely to have a vestibular disorder compared to the control population. Compared to control patients, the odds ratio of vestibular disorders was significantly elevated in patients with untyped (odds ratio [OR], 2.39; confidence intervals [CI], 2.29-2.50; P < 0.001), alpha (OR, 3.63; CI, 3.48-3.78; P < 0.001), delta (OR, 3.03; CI, 2.94-3.12; P < 0.001), omicron 21K variant (OR, 2.97; CI, 2.90-3.04; P < 0.001), and omicron 23A variant (OR, 8.80; CI, 8.35-9.27; P < 0.001). Conclusions: The incidence of vestibular disorders differed between COVID-19 variants and was significantly elevated in COVID-19-positive patients compared to the control population. These findings have implications for patient counseling and further research is needed to discern the long-term effects of these findings.

Characteristics of High-Performing Hospitals in Cardiogenic Shock Following Acute Myocardial Infarction.

Cardiogenic shock after acute myocardial infarction (AMI-CS) carries significant mortality despite advances in revascularization and mechanical circulatory support. We sought to identify the process-based and structural characteristics of centers with lower mortality in AMI-CS. We analyzed 16,337 AMI-CS cases across 440 centers enrolled in the National Cardiovascular Data Registry's Chest Pain-MI Registry, a retrospective cohort database, between January 1, 2015, and December 31, 2018. Centers were stratified across tertiles of risk-adjusted in-hospital mortality rate (RAMR) for comparison. Risk-adjusted multivariable logistic regression was also performed to identify hospital-level characteristics associated with decreased mortality. The median participant age was 66 (interquartile range 57 to 75) years, and 33.0% (n = 5,390) were women. The median RAMR was 33.4% (interquartile range 26.0% to 40.0%) and ranged from 26.9% to 50.2% across tertiles. Even after risk adjustment, lower-RAMR centers saw patients with fewer co-morbidities. Lower-RAMR centers performed more revascularization (92.8% vs 90.6% vs 85.9%, p <0.001) and demonstrated better adherence to associated process measures. Left ventricular assist device capability (odds ratio [OR] 0.78 [0.67 to 0.92], p = 0.002), more frequent revascularization (OR 0.93 [0.88 to 0.98], p = 0.006), and higher AMI-CS volume (OR 0.95 [0.91 to 0.99], p = 0.009) were associated with lower in-hospital mortality. However, several such characteristics were not more frequently observed at low-RAMR centers, despite potentially reflecting greater institutional experience or resources. This may reflect the heterogeneity of AMI-CS even after risk adjustment. In conclusion, low-RAMR centers do not necessarily exhibit factors associated with decreased mortality in AMI-CS, which may reflect the challenges in performing outcomes research in this complex population.

A novel combined approach to placement of a double lumen endobronchial tube using a video laryngoscope and fiberoptic bronchoscope: a retrospective chart review.

BACKGROUND: The objective of this study was to evaluate a modern combined video laryngoscopy and flexible fiberoptic bronchoscope approach to placement of a double lumen endobronchial tube and further characterize potential strengths and weaknesses of this approach. METHODS: Retrospective chart review was conducted at our single institution, academic medical center, tertiary-care hospital. Patients aged 18 years of age or older were evaluated who underwent thoracic surgery and one-lung ventilation with placement of a double lumen endobronchial tube using a novel combined video laryngoscopy and flexible fiberoptic bronchoscope approach. No interventions were performed. RESULTS: Demographics and induction and intubation documentation were reviewed for 21 patients who underwent thoracic surgery and one-lung ventilation with placement of a double lumen endobronchial tube using a novel combined video laryngoscopy and flexible fiberoptic bronchoscope approach. First pass success using the combined approach was 86% (18/21). The five patients with an anticipated difficult airway had successful double lumen endobronchial tube placement on the first attempt. There were no instances of desaturation during double lumen endobronchial tube placement. No airway complications related to double lumen endobronchial tube placement were recorded. CONCLUSION: Use of a combined approach employing video laryngoscopy and a flexible fiberoptic bronchoscope may represent a reliable alternative approach to placement of double lumen endobronchial tubes.

Thiuram Disulfide Mediated Cu-Catalyzed Amidation of Terminal Alkynes: An Efficient Synthesis of Alkynyl Amides.

Terminal alkynes undergo a CO-free aminocarbonylation reaction mediated by thiuram disulfides. Thiuram disulfide acts as the source of the carbamoyl group in the amidation of terminal alkynes in the presence of copper-based reagent and catalyst. A series of alkynyl amides has been prepared with several structural variations following the current one-pot two-step protocol. The reaction proceeds through a mixed disulfide intermediate, which has been isolated and characterized by single-crystal XRD analysis.

Measles, mumps, rubella and varicella antibodies among international and domestic university students.

BACKGROUND: Vaccine-preventable infections are generally well controlled in Australia. However, gaps in immunity can lead to outbreaks and are important to identify. Young adults are a highly mobile population and a potential source of imported infections. We aimed to evaluate anti- measles, mumps, rubella and varicella (MMR&V) IgG seroprevalence and explore factors relating to antibody seropositivity. METHODS: A cross-sectional online survey was conducted among students from a large Australian university to collect demographic, vaccination, infection and travel characteristics. Blood samples were collected to measure MMR&V seroprevalence. Logistic regression was used to identify factors associated with seropositivity. RESULTS: Among 804 university students, seroprevalence (positive or equivocal) for measles was 82.3% (95% CI 79.6-84.8%), mumps 79.5% (95% CI 76.7-82.3%), rubella 91.5% (95% CI 89.6-93.5%) and varicella 86.2% (95% CI 84.1-88.8%), with 452 (56.2%, 95% CI 52.8-59.6) seropositive to all four viruses. Varicella seropositivity was highest in the older birth cohort (born 1988-1991). Measles seropositivity was higher for international students compared to domestic students. Among international students, mumps seroprevalence was significantly lower than measles and rubella seroprevalence. International travel in the previous 12 months was reported by 63.1% of students, but only 18.2% of travellers reported seeking pre-travel health advice prior to most recent international travel. CONCLUSIONS: Overall, this study suggests immunity to MMR&V is sub-optimal. We found the university student population to be highly mobile and unlikely to seek pre-travel advice; thus, they are a potential source of infection importation. The implementation of university immunization policies could address the gaps identified and our findings can inform the development of targeted vaccination campaigns.

Preoperative sleep apnea screening protocol reduces medical emergency team activation in patients with atrial fibrillation.

STUDY OBJECTIVES: The association of in-hospital medical emergency team activation (META) among patients with atrial fibrillation (AF) at risk for obstructive sleep apnea (OSA) is unclear. This study evaluates the performance of the DOISNORE50 sleep questionnaire as an OSA screener for patients with AF and determines the prevalence of META among perioperative patients with underlying AF who have a diagnosis or are at risk for OSA. METHODS: A prospective perioperative cohort of 2,926 patients with the diagnosis of AF was assessed for DOISNORE50 questionnaire screening. Propensity-score matching was used to match patients' physical characteristics, comorbidities, length of stay, and inpatient continuous positive airway pressure device usage. META and intensive care unit admissions during the surgical encounter, 30-day hospital readmissions, and 30-day emergency department visits were evaluated. RESULTS: A total of 1,509 out of 2,926 AF patients completed the DOISNORE50 questionnaire and were enrolled in the OSA safety protocol. Following propensity-score matching, there were reduced adjusted odds of META in the screened group of 0.69 (95% confidence interval: 0.48-0.98, P < .001) in comparison to the unscreened group. The adjusted odds of intensive care unit admissions and emergency department visits within 30 days of discharge were statistically lower for the screened group compared with the unscreened group. CONCLUSIONS: Among perioperative AF patients, evidence supports DOISNORE50 screening and implementation of an OSA safety protocol for reduction of META. This study identified decreased odds of META, intensive care unit admissions, and emergency department visits among the screened group. The high-risk and known OSA group showed reduced odds of META following the implementation of an OSA safety protocol. CITATION: Saha AK, Sheehan KN, Xiang KR, et al. Preoperative sleep apnea screening protocol reduces medical emergency team activation in patients with atrial fibrillation. J Clin Sleep Med. 2024;20(5):783-792.

Agreement between cardiac output estimation with a wireless, wearable pulse decomposition analysis device and continuous thermodilution in post cardiac surgery intensive care unit patients.

PURPOSE: Pulse Decomposition Analysis (PDA) uses integration of the systolic area of a distally transmitted aortic pulse as well as arterial stiffness estimates to compute cardiac output. We sought to assess agreement of cardiac output (CO) estimation between continuous pulmonary artery catheter (PAC) guided thermodilution (CO-CCO) and a wireless, wearable noninvasive device, (Vitalstream, Caretaker Medical, Charlottesville, VA), that utilizes the Pulse Decomposition Analysis (CO-PDA) method in postoperative cardiac surgery patients in the intensive care unit. METHODS: CO-CCO measurements were compared with post processed CO-PDA measurements in prospectively enrolled adult cardiac surgical intensive care unit patients. Uncalibrated CO-PDA values were compared for accuracy with CO-CCO via a Bland-Altman analysis considering repeated measurements and a concordance analysis with a 10% exclusion zone. RESULTS: 259.7 h of monitoring data from 41 patients matching 15,583 data points were analyzed. Mean CO-CCO was 5.55 L/min, while mean values for the CO-PDA were 5.73 L/min (mean of differences +- SD 0.79 ± 1.11 L/min; limits of agreement - 1.43 to 3.01 L/min), with a percentage error of 37.5%. CO-CCO correlation with CO-PDA was moderate (0.54) and concordance was 0.83. CONCLUSION: Compared with the CO-CCO Swan-Ganz, cardiac output measurements obtained using the CO-PDA were not interchangeable when using a 30% threshold. These preliminary results were within the 45% limits for minimally invasive devices, and pending further robust trials, the CO-PDA offers a noninvasive, wireless solution to complement and extend hemodynamic monitoring within and outside the ICU.

Child Opportunity Index and Pediatric Intensive Care Outcomes: A Multicenter Retrospective Study in the United States.

OBJECTIVES: To evaluate for associations between a child's neighborhood, as categorized by Child Opportunity Index (COI 2.0), and 1) PICU mortality, 2) severity of illness at PICU admission, and 3) PICU length of stay (LOS). DESIGN: Retrospective cohort study. SETTING: Fifteen PICUs in the United States. PATIENTS: Children younger than 18 years admitted from 2019 to 2020, excluding those after cardiac procedures. Nationally-normed COI category (very low, low, moderate, high, very high) was determined for each admission by census tract, and clinical features were obtained from the Virtual Pediatric Systems LLC (Los Angeles, CA) data from each site. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 33,901 index PICU admissions during the time period, median patient age was 4.9 years and PICU mortality was 2.1%. There was a higher percentage of admissions from the very low COI category (27.3%) than other COI categories (17.2-19.5%, p < 0.0001). Patient admissions from the high and very high COI categories had a lower median Pediatric Index of Mortality 3 risk of mortality (0.70) than those from the very low, low, and moderate COI groups (0.71) ( p < 0.001). PICU mortality was lowest in the very high (1.7%) and high (1.9%) COI groups and highest in the moderate group (2.5%), followed by very low (2.3%) and low (2.2%) ( p = 0.001 across categories). Median PICU LOS was between 1.37 and 1.50 days in all COI categories. Multivariable regression revealed adjusted odds of PICU mortality of 1.30 (95% CI, 0.94-1.79; p = 0.11) for children from a very low versus very high COI neighborhood, with an odds ratio [OR] of 0.996 (95% CI, 0.993-1.00; p = 0.05) for mortality for COI as an ordinal value from 0 to 100. Children without insurance coverage had an OR for mortality of 3.58 (95% CI, 2.46-5.20; p < 0.0001) as compared with those with commercial insurance. CONCLUSIONS: Children admitted to a cohort of U.S. PICUs were often from very low COI neighborhoods. Children from very high COI neighborhoods had the lowest risk of mortality and observed mortality; however, odds of mortality were not statistically different by COI category in a multivariable model. Children without insurance coverage had significantly higher odds of PICU mortality regardless of neighborhood.

A Quality Improvement Initiative to Reduce Adverse Effects of Transitions of Anesthesia Care on Postoperative Outcomes: A Retrospective Cohort Study.

BACKGROUND: An intraoperative transfer of care from one anesthesia provider to another, or handover, may result in information loss and contribute to adverse patient outcomes. In 2019 the authors undertook a quality improvement effort to increase the use of a structured intraoperative handover tool incorporated in the electronic medical record. The authors hypothesized that intraoperative handovers of anesthesia care would be associated with adverse patient outcomes, and that increased use of a structured tool would attenuate this effect. METHODS: This study included adult patients undergoing noncardiac surgery of at least 1 h duration performed during the period 2016 to 2021. Cases with a handover were identified if either there was a change of attending anesthesiologist or change of nurse anesthetist or resident for more than 35 min. The primary outcome was the occurrence of a composite of postoperative mortality and major postoperative morbidity. The effect of the intervention was analyzed by examining the quarterly change in odds ratio for the primary outcome for cases with and without a handover. RESULTS: A total of 121,077 cases, 40.4% of which had a handover, were included. After weighting, the composite outcome was statistically associated with handovers (3,517 of 48,986 [7.2%] in handover cases vs. 4,470 of 72,091 [6.2%] in nonhandover cases; odds ratio, 1.08; 95% CI, 1.04 to 1.12). Time series analysis showed a marked increase in usage of the structured tool after the initial intervention. The odds ratio for the composite outcome showed a significant decrease over time after the initial intervention (t = -3.97; P < 0.001), with the slope of the odds ratio versus time curve decreasing from 0.002 (95% CI, 0.001 to 0.004; P = 0.018) to -0.011 (95% CI, -0.01 to -0.018; P < 0.001). CONCLUSIONS: Intraoperative handovers are significantly associated with adverse outcomes even after controlling for multiple confounding variables. Use of a structured handover tool during anesthesia care may attenuate the adverse effect.

Lung Structure and Risk of Sleep Apnea in SPIROMICS.

Rationale: The SubPopulations and InteRmediate Outcome Measures in COPD Study (SPIROMICS) is a prospective cohort study that enrolled 2981 participants with the goal of identifying new chronic obstructive pulmonary disease (COPD) subgroups and intermediate markers of disease progression. Individuals with COPD and obstructive sleep apnea (OSA) experience impaired quality of life and more frequent exacerbations. COPD severity also associates with computed tomography scan-based emphysema and alterations in airway dimensions. Objectives: The objective was to determine whether the combination of lung function and structure influences the risk of OSA among current and former smokers. Methods: Using 2 OSA risk scores, the Berlin Sleep Questionnaire (BSQ), and the DOISNORE50 (Diseases, Observed apnea, Insomnia, Snoring, Neck circumference > 18 inches, Obesity with body mass index [BMI] > 32, R = are you male, Excessive daytime sleepiness, 50 = age ≥ 50) (DIS), 1767 current and former smokers were evaluated for an association of lung structure and function with OSA risk. Measurements and Main Results: The study cohort's mean age was 63 years, BMI was 28 kg/m2, and forced expiratory volume in 1 second (FEV1) was 74.8% predicted. The majority were male (55%), White (77%), former smokers (59%), and had COPD (63%). A high-risk OSA score was reported in 36% and 61% using DIS and BSQ respectively. There was a 9% increased odds of a high-risk DIS score (odds ratio [OR]=1.09, 95% confidence interval [CI]:1.03-1.14) and nominally increased odds of a high-risk BSQ score for every 10% decrease in FEV1 %predicted (OR=1.04, 95%CI: 0.998-1.09). Lung function-OSA risk associations persisted after additionally adjusting for lung structure measurements (%emphysema, %air trapping, parametric response mapping for functional small airways disease, , mean segmental wall area, tracheal %wall area, dysanapsis) for DIS (OR=1.12, 95%CI:1.03-1.22) and BSQ (OR=1.09, 95%CI:1.01-1.18). Conclusions: Lower lung function independently associates with having high risk for OSA in current and former smokers. Lung structural elements, especially dysanapsis, functional small airways disease, and tracheal %wall area strengthened the effects on OSA risk.

Impact of continuous and wireless monitoring of vital signs on clinical outcomes: a propensity-matched observational study of surgical ward patients.

BACKGROUND: Continuous and wireless vital sign monitoring is superior to intermittent monitoring in detecting vital sign abnormalities; however, the impact on clinical outcomes has not been established. METHODS: We performed a propensity-matched analysis of data describing patients admitted to general surgical wards between January 2018 and December 2019 at a single, tertiary medical centre in the USA. The primary outcome was a composite of in-hospital mortality or ICU transfer during hospitalisation. Secondary outcomes were the odds of individual components of the primary outcome, and heart failure, myocardial infarction, acute kidney injury, and rapid response team activations. Data are presented as odds ratios (ORs) with 95% confidence intervals (CIs) and n (%). RESULTS: We initially screened a population of 34,636 patients (mean age 58.3 (Range 18-101) yr, 16,456 (47.5%) women. After propensity matching, intermittent monitoring (n=12 345) was associated with increased risk of a composite of mortality or ICU admission (OR 3.42, 95% CI 3.19-3.67; P<0.001), and heart failure (OR 1.48, 95% CI 1.21-1.81; P<0.001), myocardial infarction (OR 3.87, 95% CI 2.71-5.71; P<0.001), and acute kidney injury (OR 1.32, 95% CI 1.09-1.57; P<0.001) compared with continuous wireless monitoring (n=7955). The odds of rapid response team intervention were similar in both groups (OR 0.86, 95% CI 0.79-1.06; P=0.726). CONCLUSIONS: Patients who received continuous ward monitoring were less likely to die or be admitted to ICU than those who received intermittent monitoring. These findings should be confirmed in prospective randomised trials.

Hypoxemia in School-age Children Undergoing One-lung Ventilation: A Retrospective Cohort Study from the Multicenter Perioperative Outcomes Group.

BACKGROUND: Risk factors for hypoxemia in school-age children undergoing one-lung ventilation remain poorly understood. The hypothesis was that certain modifiable and nonmodifiable factors may be associated with increased risk of hypoxemia in school-age children undergoing one-lung ventilation and thoracic surgery. METHODS: The Multicenter Perioperative Outcomes Group database was queried for children 4 to 17 yr of age undergoing one-lung ventilation. Patients undergoing vascular or cardiac procedures were excluded. The original cohort was divided into two cohorts: 4 to 9 and 10 to 17 yr of age inclusive. All records were reviewed electronically for the primary outcome of hypoxemia during one-lung ventilation, which was defined as an oxygen saturation measured by pulse oximetry (Spo2) less than 90% for 3 min or longer continuously, while severe hypoxemia was defined as Spo2 less than 90% for 5 min or longer. Potential modifiable and nonmodifiable risk factors associated with these outcomes were evaluated using separate multivariable least absolute shrinkage and selection operator regression analyses for each cohort. The covariates evaluated included age, extremes of weight, American Society of Anesthesiologists Physical Status of III or higher, duration of one-lung ventilation, preoperative Spo2 less than 98%, approach to one-lung ventilation, right operative side, video-assisted thoracoscopic surgery, lower tidal volume ventilation (defined as tidal volume of 6 ml/kg or less and positive end-expiratory pressure of 4 cm H2O or greater for more than 80% of the duration of one-lung ventilation), and procedure type. RESULTS: The prevalence of hypoxemia in the 4- to 9-yr-old cohort and the 10- to 17-yr-old cohort was 24 of 228 (10.5% [95% CI, 6.5 to 14.5%]) and 76 of 1,012 (7.5% [95% CI, 5.9 to 9.1%]), respectively. The prevalence of severe hypoxemia in both cohorts was 14 of 228 (6.1% [95% CI, 3.0 to 9.3%]) and 47 of 1,012 (4.6% [95% CI, 3.3 to 5.8%]). Initial Spo2 less than 98% was associated with hypoxemia in the 4- to 9-yr-old cohort (odds ratio, 4.20 [95% CI, 1.61 to 6.29]). Initial Spo2 less than 98% (odds ratio, 2.76 [95% CI, 1.69 to 4.48]), extremes of weight (odds ratio, 2.18 [95% CI, 1.29 to 3.61]), and right-sided cases (odds ratio, 2.33 [95% CI, 1.41 to 3.92]) were associated with an increased risk of hypoxemia in the older cohort. Increasing age (1-yr increment; odds ratio, 0.88 [95% CI, 0.80 to 0.97]) was associated with a decreased risk of hypoxemia. CONCLUSIONS: An initial room air oxygen saturation of less than 98% was associated with an increased risk of hypoxemia in all children 4 to 17 yr of age. Extremes of weight, right-sided cases, and decreasing age were associated with an increased risk of hypoxemia in children 10 to 17 yr of age.

Towards Allograft Longevity: Leveraging Omics Technologies to Improve Heart Transplant Outcomes.

PURPOSE OF REVIEW: Heart transplantation (HT) remains the optimal therapy for patients living with end-stage heart disease. Despite recent improvements in peri-transplant management, the median survival after HT has remained relatively static, and complications of HT, including infection, rejection, and allograft dysfunction, continue to impact quality of life and long-term survival. RECENT FINDINGS: Omics technologies are becoming increasingly accessible and can identify novel biomarkers for, and reveal the underlying biology of, several disease states. While some technologies, such as gene expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA), are routinely used in the clinical care of HT recipients, a number of emerging platforms, including pharmacogenomics, proteomics, and metabolomics, hold great potential for identifying biomarkers to aid in the diagnosis and management of post-transplant complications. Omics-based assays can improve patient and allograft longevity by facilitating a personalized and precision approach to post-HT care. The following article is a contemporary review of the current and future opportunities to leverage omics technologies, including genomics, transcriptomics, proteomics, and metabolomics in the field of HT.

Automated Electronic Frailty Index-Identified Frailty Status and Associated Postsurgical Adverse Events.

Importance: Electronic frailty index (eFI) is an automated electronic health record (EHR)-based tool that uses a combination of clinical encounters, diagnosis codes, laboratory workups, medications, and Medicare annual wellness visit data as markers of frailty status. The association of eFI with postanesthesia adverse outcomes has not been evaluated. Objective: To examine the association of frailty, calculated as eFI at the time of the surgical procedure and categorized as fit, prefrail, or frail, with adverse events after elective noncardiac surgery. Design, Setting, and Participants: This cohort study was conducted at a tertiary care academic medical center in Winston-Salem, North Carolina. The cohort included patients 55 years or older who underwent noncardiac surgery of at least 1 hour in duration between October 1, 2017, and June 30, 2021. Exposure: Frailty calculated by the eFI tool. Preoperative eFI scores were calculated based on available data 1 day prior to the procedure and categorized as fit (eFI score: ≤0.10), prefrail (eFI score: >0.10 to ≤0.21), or frail (eFI score: >0.21). Main Outcomes and Measures: The primary outcome was a composite of the following 8 adverse component events: 90-item Patient Safety Indicators (PSI 90) score, hospital-acquired conditions, in-hospital mortality, 30-day mortality, 30-day readmission, 30-day emergency department visit after surgery, transfer to a skilled nursing facility after surgery, or unexpected intensive care unit admission after surgery. Secondary outcomes were each of the component events of the composite. Results: Of the 33 449 patients (median [IQR] age, 67 [61-74] years; 17 618 females [52.7%]) included, 11 563 (34.6%) were classified as fit, 15 928 (47.6%) as prefrail, and 5958 (17.8%) as frail. Using logistic regression models that were adjusted for age, sex, race and ethnicity, and comorbidity burden, patients with prefrail (odds ratio [OR], 1.24; 95% CI, 1.18-1.30; P < .001) and frail (OR, 1.71; 95% CI, 1.58-1.82; P < .001) statuses were more likely to experience postoperative adverse events compared with patients with a fit status. Subsequent adjustment for all other potential confounders or covariates did not alter this association. For every increase in eFI of 0.03 units, the odds of a composite of postoperative adverse events increased by 1.06 (95% CI, 1.03-1.13; P < .001). Conclusions and Relevance: This cohort study found that frailty, as measured by an automatically calculated index integrated within the EHR, was associated with increased risk of adverse events after noncardiac surgery. Deployment of eFI tools may support screening and possible risk modification, especially in patients who undergo high-risk surgery.

Chymase in Plasma and Urine Extracellular Vesicles: Novel Biomarkers for Primary Hypertension.

BACKGROUND: Extracellular vesicles (EVs) have emerged as a promising liquid biopsy for various diseases. For the first time, using plasma and urinary EVs, we assessed the activity of renin-angiotensin system (RAS), a central regulator of renal, cardiac, and vascular physiology, in patients with control (Group I) or uncontrolled (Group II) primary hypertension. METHODS: EVs were isolated from 34 patients with history of hypertension, and characterized for size and concentration by nanoparticle tracking analyses, exosomal biomarkers by immunogold labeling coupled with transmission electron microscopy, flow cytometry and immunoblotting. EVs were analyzed for the hydrolytic activity of chymase, angiotensin converting enzyme (ACE), ACE2, and neprilysin (NEP) by HPLC. RESULTS: Plasma and urinary EVs were enriched for small EVs and expressed exosomal markers (CD63, CD9, and CD81). The size of urinary EVs (but not plasma EVs) was significantly larger in Group II compared to Group I. Differential activity of RAS enzymes was observed, with significantly higher chymase activity compared to ACE, ACE2, and NEP in plasma EVs. Similarly, urinary EVs exhibited higher chymase and NEP activity compared to ACE and ACE2 activity. Importantly, compared to Group I, significantly higher chymase activity was observed in urinary EVs (p = 0.03) from Group II, while no significant difference in activity was observed for other RAS enzymes. CONCLUSIONS: Bioactive RAS enzymes are present in plasma and urinary EVs. Detecting chymase in plasma and urinary EVs uncovers a novel mechanism of angiotensin II-forming enzyme and could also mediate cell-cell communication and modulate signaling pathways in recipient cells.

Flexible and Innovative Connectivity Solution to Support National Decentralized Infectious Diseases Point-of-Care Testing Programs in Primary Health Services: Descriptive Evaluation Study.

BACKGROUND: Molecular point-of-care (POC) testing for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Trichomonas vaginalis (TV) has been available in regional and remote primary health services in Australia as part of a decentralized POC testing program since 2016 and for SARS-CoV-2 from 2020. As there was no suitable existing connectivity infrastructure to capture and deliver POC test results to a range of end users, a new system needed to be established. OBJECTIVE: The aim of the study is to design, implement, and optimize a connectivity system to meet clinical management, analytical quality management, and public health surveillance needs. METHODS: We used commercially available e-messaging technology coupled with adapted proprietary software to integrate a decentralized molecular POC testing platform (GeneXpert) in primary health services and interface with end-user databases. This connectivity infrastructure was designed to overcome key barriers to the implementation, integration, and monitoring of these large multijurisdictional infectious disease POC testing networks. Test result messages were tailored to meet end-user needs. Using centrally captured deidentified data, we evaluated the time to receipt of test results and completeness of accompanying demographic data. RESULTS: From January 2016 to April 2020, we operationalized the system at 31 health services across 4 jurisdictions and integrated with 5 different patient management systems to support the real-time delivery of 29,356 CT/NG and TV test results to designated recipients (patient management system and local clinical and central program databases). In 2019, 12,105 CT/NG and TV results were delivered, and the median time to receipt of results was 3.2 (IQR 2.2-4.6) hours, inclusive of test runtime. From May 2020 to August 2022, we optimized the system to support rapid scale-up of SARS-CoV-2 testing (105 services; 6 jurisdictions; 71,823 tests) and additional sexually transmissible infection testing (16,232 tests), including the electronic disease-specific notifications to jurisdictional health departments and alerts for connectivity disruption and positive results. In 2022, 19,355 results were delivered with an overall median transmission time of 2.3 (IQR 1.4-3.1) hours, 2.2 (IQR 1.2-2.3) hours for SARS-CoV-2 (n=16,066), 3.0 (IQR 2.0-4.0) hours for CT/NG (n=1843), and 2.6 (IQR 1.5-3.8) hours for TV (n=1446). Demographic data (age, sex, and ethnicity) were completed for 99.5% of test results in 2022. CONCLUSIONS: This innovative connectivity system designed to meet end-user needs has proven to be sustainable, flexible, and scalable. It represents the first such system in Australia established independent of traditional pathology providers to support POC testing in geographically dispersed remote primary health services. The system has been optimized to deliver real-time test results and has proven critical for clinical, public health, and quality management. The system has significantly supported equitable access to rapid diagnostics for infectious diseases across Australia, and its design is suitable for onboarding other POC tests and testing platforms in the future.

Protective roles of vitamin C and 5-aminosalicylic acid on reproduction in acrylamide intoxicated male mice.

Context: Serious health risks have been connected to ongoing, escalating exposure to environmental toxins and one of them is acrylamide (ACR), an organic compound. Although there are many published reports on ACR toxicity, limited information is available regarding the use of two potential antioxidants against ACR-instigated reproductive toxicity. Aims: The study focused on investigating the protective effects of vitamin C and 5-ASA against ACR-incited reproductive toxicity. Methods: A total of 50 male mice aged 4 weeks old were treated for 90 days with different concentrations either of ACR or ACR and vitamin C or ACR and 5- ASA or ACR, vitamin C, and 5- ASA. Key results: ACR significantly reduced serum testosterone level (p = 0.0037), sperm concentration (p = 0.0004), and percentage of sperm motility (p = 0.003), as well as increased sperm abnormality; head (p = 0.0058), tail (p = 0.001), and midpiece (p = 0.0339). Besides, the weight (p = 0.0006) and length (p = 0.0105) of testes, as well as weight (p = 0.0001) and length (p = 0.0021) of epididymis were decreased along with atrophy of seminiferous tubules of the testis, and disintegration of the tubular epithelium of epididymis on ACR exposed mice which were improved by vitamin C and 5-ASA administration. Conclusions: Vitamin C and 5-ASA can potentially mitigate the negative effects of ACR on male reproduction; however, combined application is recommended for better performance. Implications: In Bangladesh, this work is anticipated to address the health benefits of vitamin C and 5-ASA, particularly in improving the reproductive health of males against ACR toxicity.