Occupation and SARS-CoV-2 seroprevalence studies: a systematic review.

OBJECTIVE: To describe and synthesise studies of SARS-CoV-2 seroprevalence by occupation prior to the widespread vaccine roll-out. METHODS: We identified studies of occupational seroprevalence from a living systematic review (PROSPERO CRD42020183634). Electronic databases, grey literature and news media were searched for studies published during January-December 2020. Seroprevalence estimates and a free-text description of the occupation were extracted and classified according to the Standard Occupational Classification (SOC) 2010 system using a machine-learning algorithm. Due to heterogeneity, results were synthesised narratively. RESULTS: We identified 196 studies including 591 940 participants from 38 countries. Most studies (n=162; 83%) were conducted locally versus regionally or nationally. Sample sizes were generally small (median=220 participants per occupation) and 135 studies (69%) were at a high risk of bias. One or more estimates were available for 21/23 major SOC occupation groups, but over half of the estimates identified (n=359/600) were for healthcare-related occupations. 'Personal Care and Service Occupations' (median 22% (IQR 9-28%); n=14) had the highest median seroprevalence. CONCLUSIONS: Many seroprevalence studies covering a broad range of occupations were published in the first year of the pandemic. Results suggest considerable differences in seroprevalence between occupations, although few large, high-quality studies were done. Well-designed studies are required to improve our understanding of the occupational risk of SARS-CoV-2 and should be considered as an element of pandemic preparedness for future respiratory pathogens.

Deploying wearable sensors for pandemic mitigation: A counterfactual modelling study of Canada's second COVID-19 wave.

Wearable sensors can continuously and passively detect potential respiratory infections before or absent symptoms. However, the population-level impact of deploying these devices during pandemics is unclear. We built a compartmental model of Canada's second COVID-19 wave and simulated wearable sensor deployment scenarios, systematically varying detection algorithm accuracy, uptake, and adherence. With current detection algorithms and 4% uptake, we observed a 16% reduction in the second wave burden of infection; however, 22% of this reduction was attributed to incorrectly quarantining uninfected device users. Improving detection specificity and offering confirmatory rapid tests each minimized unnecessary quarantines and lab-based tests. With a sufficiently low false positive rate, increasing uptake and adherence became effective strategies for scaling averted infections. We concluded that wearable sensors capable of detecting presymptomatic or asymptomatic infections have potential to help reduce the burden of infection during a pandemic; in the case of COVID-19, technology improvements or supporting measures are required to keep social and resource costs sustainable.

A proof of principle study of atomoxetine for the prevention of vasovagal syncope: the Prevention of Syncope Trial VI.

AIMS: There are few effective therapies for vasovagal syncope (VVS). Pharmacological norepinephrine transporter (NET) inhibition increases sympathetic tone and decreases tilt-induced syncope in healthy subjects. Atomoxetine is a potent and highly selective NET inhibitor. We tested the hypothesis that atomoxetine prevents tilt-induced syncope. METHODS AND RESULTS: Vasovagal syncope patients were given two doses of study drug [randomized to atomoxetine 40 mg (n = 27) or matched placebo (n = 29)] 12 h apart, followed by a 60-min drug-free head-up tilt table test. Beat-to-beat heart rate (HR), blood pressure (BP), and cardiac haemodynamics were recorded using non-invasive techniques and stroke volume modelling. Patients were 35 ± 14 years (73% female) with medians of 12 lifetime and 3 prior year faints. Fewer subjects fainted with atomoxetine than with placebo [10/29 vs. 19/27; P = 0.003; risk ratio 0.49 (confidence interval 0.28-0.86)], but equal numbers of patients developed presyncope or syncope (23/29 vs. 21/27). Of patients who developed only presyncope, 87% (13/15) had received atomoxetine. Patients with syncope had lower nadir mean arterial pressure than subjects with only presyncope (39 ± 18 vs. 69 ± 18 mmHg, P < 0.0001), and this was due to lower trough HRs in subjects with syncope (67 ± 30 vs. 103 ± 32 b.p.m., P = 0.006) and insignificantly lower cardiac index (2.20 ± 1.36 vs. 2.84 ± 1.05 L/min/m2, P = 0.075). There were no significant differences in stroke volume index (32 ± 6 vs. 35 ± 5 mL/m2, P = 0.29) or systemic vascular resistance index (2156 ± 602 vs. 1790 ± 793 dynes*s/cm5*m2, P = 0.72). CONCLUSION: Norepinephrine transporter inhibition significantly decreased the risk of tilt-induced syncope in VVS subjects, mainly by blunting reflex bradycardia, thereby preventing final falls in cardiac index and BP.

A functional cell-based bioassay for assessing adrenergic autoantibody activity in postural tachycardia syndrome.

BACKGROUND: Activating autoantibodies (AAb) to adrenergic receptors (AR) have previously been reported in patients with postural tachycardia syndrome (POTS). These AAb may contribute to a final common pathway for overlapping disease processes, reflecting a possible autoimmune contribution to POTS pathophysiology. In prior studies, measurement of AAb activity was inferred from costly, low-throughput, and laborious physiological assays. In the present study, we developed and validated an alternative cell-based bioassay for measuring AAb activity in serum by means of pre-treatment with monoamine oxidase (MAO). METHODS: A total of 37 POTS patients and 61 sex-matched healthy control participants were included. Serum was pre-treated with MAO to remove endogenous catecholamines that could falsely inflate AR activation by AAb. A receptor-transfected cell-based bioassay was used to detect presence of α1AR-AAb and ß1AR-AAb in serum. RESULTS: MAO effectively degraded catecholamines as demonstrated by suppression of norepinephrine-induced α1AR activation in POTS (6.4 â€‹± â€‹0.7 vs. 5.5 â€‹± â€‹0.9; P â€‹= â€‹0.044) and in controls (4.1 â€‹± â€‹0.5 vs. 3.9 â€‹± â€‹0.6; P â€‹= â€‹0.001). Mean activity values were greater in the POTS vs. Controls for α1AR-AAb (6.2 â€‹± â€‹1.2 vs. 5.3 â€‹± â€‹1.0; P â€‹< â€‹0.001) and ß1AR-AAb (5.7 â€‹± â€‹1.8 vs. 4.1 â€‹± â€‹0.9; P â€‹< â€‹0.001). Compared to controls, more POTS patients were positive for α1AR-AAb activity (22% vs 4%; P â€‹= â€‹0.007) and ß1AR-AAb activity (52% vs. 2%; P â€‹< â€‹0.001). CONCLUSIONS: The co-presence of norepinephrine in serum samples can artifactually elevate α1AR and ß1AR activity, which can be avoided by serum pre-treatment with MAO. Using this novel bioassay, we show that POTS patients have increased α1AR-AAb and ß1AR-AAb activity compared to healthy controls in the largest POTS cohort reported to-date.

Effects of a reminder to initiate oral anticoagulation in patients with atrial fibrillation/atrial flutter discharged from the emergency department: REMINDER study.

OBJECTIVE: Oral anticoagulation (OAC) reduces stroke risk in patients with atrial fibrillation (AF) or atrial flutter (AFL). However, OAC initiation rates in patients discharged directly from the emergency department (ED) are low. We aimed to address this care gap by implementing a quality improvement intervention. METHODS: The study was performed in four Canadian urban EDs between 2015 and 2016. Patients were included if they had an electrocardiogram (ECG) documenting AF/AFL in the ED, were directly discharged from the ED, and were alive after 90 days. Baseline rates of OAC initiation were determined prior to the intervention. Between June and December 2016, we implemented our intervention in two EDs (ED-intervention), with the remaining sites acting as controls (ED-control). The intervention included a reminder statement prompting OAC initiation according to guideline recommendations, manually added to ECGs with a preliminary interpretation of AF/AFL, along with a decision-support algorithm that included a referral sheet. The primary outcome was the rate of OAC initiation within 90 days of the ED visit. RESULTS: Prior to the intervention, 37.2% OAC-naïve patients with ECG-documented AF/AFL were initiated on OAC. Following implementation of the intervention, the rate of OAC initiation increased from 38.6% to 47.5% (absolute increase of 8.5%; 95% CI, 0.3% to 16.7%, p=0.04) among the ED-intervention sites, whereas the rate remained unchanged in ED-control sites (35.3% to 35.9%, p=0.9). CONCLUSIONS: Implementation of a quality improvement intervention consisting of a reminder and decision-support tool increased initiation of OAC in high-risk patients. This support package can be readily implemented in other jurisdictions to improve OAC rates for AF/AFL.