Background: Rapid and early detection of SARS-CoV-2 infections, especially during the pre- or asymptomatic phase, could aid in reducing virus spread. Physiological parameters measured by wearable devices can be efficiently analysed to provide early detection of infections. The COVID-19 Remote Early Detection (COVID-RED) trial investigated the use of a wearable device (Ava bracelet) for improved early detection of SARS-CoV-2 infections in real-time. Trial design: Prospective, single-blinded, two-period, two-sequence, randomised controlled crossover trial. Methods: Subjects wore a medical device and synced it with a mobile application in which they also reported symptoms. Subjects in the experimental condition received real-time infection indications based on an algorithm using both wearable device and self-reported symptom data, while subjects in the control arm received indications based on daily symptom-reporting only. Subjects were asked to get tested for SARS-CoV-2 when receiving an app-generated alert, and additionally underwent periodic SARS-CoV-2 serology testing. The overall and early detection performance of both algorithms was evaluated and compared using metrics such as sensitivity and specificity. Results: A total of 17,825 subjects were randomised within the study. Subjects in the experimental condition received an alert significantly earlier than those in the control condition (median of 0 versus 7 days before a positive SARS-CoV-2 test). The experimental algorithm achieved high sensitivity (93.8–99.2%) but low specificity (0.8–4.2%) when detecting infections during a specified period, while the control algorithm achieved more moderate sensitivity (43.3–46.4%) and specificity (66.4–65.0%). When detecting infection on a given day, the experimental algorithm also achieved higher sensitivity compared to the control algorithm (45–52% versus 28–33%), but much lower specificity (38–50% versus 93–97%). Conclusions: Our findings highlight the potential role of wearable devices in early detection of SARS-CoV-2. The experimental algorithm overestimated infections, but future iterations could finetune the algorithm to improve specificity and enable it to differentiate between respiratory illnesses. Trial registration: Netherlands Trial Register number NL9320.

Introduction Patients are seeking greater involvement in their healthcare. It therefore may be beneficial to provide guidance on initial oral sumatriptan dose selection for the treatment of acute migraine in nontraditional settings, such as telehealth and other remote forms of medical care. We sought to determine whether clinical or demographic factors are predictive of oral sumatriptan dose preference. Methods This was a post hoc analysis of two clinical studies designed to determine preference for 25, 50, or 100 mg oral sumatriptan. Patients were aged 18–65 years with at least a 1 year history of migraine and experienced, on average, between one and six severe or moderately severe migraine attacks per month, with or without aura. Predictive factors were demographic measures, medical history, and migraine characteristics. Possibly predictive factors were identified using three analyses: classification and regression tree analysis, marginal significance (P < 0.1) within a full-model logistic regression, and/or selection within a forward-selection procedure in a logistic regression. A reduced model containing the variables identified in the preliminary analyses was developed. Due to differences in study design, data were not combined. Results A dose preference was expressed by 167 patients in Study 1 and 222 patients in Study 2. Gender and medical history of urologic and/or psychological conditions in Study 1 and duration of migraine history, height, and medical history of endocrine or neurologic disease and headache severity in Study 2 were identified as possibly predictive. The predictive model showed low positive predictive value (PPV; 23.8%) and low sensitivity (21.7%) for Study 1. For Study 2, the model showed moderate PPV (60.0%) but low sensitivity (10.9%). Conclusions No clinical or demographic characteristics alone or in combination were consistently or strongly associated with preference for oral sumatriptan dose level. Trial Registration The studies on which this paper is based were conducted before trial registration indexes were introduced.

Purpose: Synovitis, the inflammation of joint synovia, is a prominent feature of osteoarthritis (OA) manifested by enhanced synovial vascularity, endothelial leakage, and perivascular oedema. In this pilot study, we assessed the effect of topical diclofenac in hand OA (HOA) using the established semi-quantitative methods Magnetic Resonance Imaging (MRI) and Ultrasonography (US), and compared them with Fluorescent Optical Imaging (FOI), an emerging imaging modality. Patients and Methods: Ten patients with symptomatic and diagnosed HOA used topical diclofenac for 14 days, with FOI, MRI, US, and subjective pain assessed at Baseline and after 7 (Day 8), and 14 (Day 15) days of treatment. Changes in synovitis were assessed for all 10 joints of the hand (via sum scores), and separately for the two joints most affected by synovitis. A new, fully quantitative approach for objective synovitis assessment based on the FOI images was also developed and applied. Results: The semi-quantitative analysis of the sum scores showed a small decrease in synovitis throughout the treatment duration across the different imaging modalities. The effect of the treatment was more prominent on the two most affected joints, with a synovitis reduction vs Baseline of 21.1% and 34.2% on Day 8 and Day 15, respectively, in the FOI. The quantitative FOI pixel analysis further strengthened the evidence for this effect, with observed reduction of 17.8% and 42.4% for Days 8 and 15, respectively. A similar trend was observed for subjective pain perception, with a reduction of 7.2 and 13.3 mm on Days 8 and 15. Conclusion: This pilot study evidenced the effect of topical diclofenac on reducing synovitis in hand OA in semi- and fully quantitative analyses, with the effect being stronger in the most affected joints. Further, supporting studies are needed to probe the accuracy of the quantitative pixel analysis of FOI images.

Objective: To evaluate the bioequivalence and safety of the test and reference formulations of ibuprofen arginine granules (400 mg) in healthy Chinese adult subjects under fasting and fed conditions. Methods: This was a randomized, open-label, single-center, single-dose, two-treatment, two-sequence, two-period crossover bioequivalence study conducted in separate fasting and fed cohorts. A total of 84 healthy Chinese adults were enrolled, including 34 subjects in the fasting cohort and 50 subjects in the fed cohort. Subjects were randomized to receive either the test formulation followed by the reference formulation or the reverse sequence, with a washout period of at least 2 days between treatments. Plasma ibuprofen concentrations were measured using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Pharmacokinetic parameters were calculated using non-compartmental analysis, and bioequivalence was assessed based on geometric mean ratios (GMRs) and corresponding 90% confidence intervals (CIs) for Cmax, AUC0-t, and AUC0-∞. Results: Under fasting conditions, the GMRs (90% CIs) of the test versus reference formulation for AUC0-t, AUC0-∞, and Cmax were 1.0008 (0.9698– 1.0327), 1.0023 (0.9710– 1.0346), and 0.9825 (0.9383– 1.0288), respectively. Under fed conditions, the corresponding values were 0.9916 (0.9755– 1.0081), 0.9776 (0.9432– 1.0133), and 0.9982 (0.9431– 1.0567). All 90% CIs were within the predefined bioequivalence acceptance range of 80.00%-125.00%. No serious adverse events, deaths, or study discontinuations due to adverse events occurred. All treatment-emergent adverse events were mild and resolved without sequelae. Conclusion: The test and reference formulations of ibuprofen arginine granules were bioequivalent under both fasting and fed conditions in healthy Chinese adult subjects. Both formulations were generally safe and well tolerated, with comparable safety profiles.

Objective: The objective of the current post hoc analysis is to evaluate whether the combination of acetaminophen, aspirin, and caffeine (AAC) is more effective than placebo in relieving the pain intensity for and improving the quality-of-life (QoL) of subjects with menstrual migraine (MM). Methods: This analysis evaluated the impact of AAC (n = 85) versus placebo (n = 100) in relieving the pain intensity for and improving the QoL of subjects with MM during baseline and at 0.5, 1, 2, 3, 4, and 6 h post treatment. Subjects reported their pain intensity using a 4-point scale and QoL using a 5-point scale. A lower score indicates reduced pain intensity and improved QoL. Results: A statistically significant difference between the AAC and placebo groups (p ≤ 0.001) was observed in pain relief after 1 h (40% vs. 14%), 2 h (56.5% vs. 24%), 3 h (63.5% vs. 31%), 4 h (65.9% vs. 34%), and 6 h (64.7% vs. 31%) post treatment. Similarly, a significantly higher proportion of subjects reported improved QoL at 1 h (48.2% vs. 28.0%; p ≤ 0.005), 2 h (61.2% vs. 40.0%; p ≤ 0.005), 3 h (68.2% vs. 44.0%; p ≤ 0.001), 4 h (67.9% vs. 39.0%; p ≤ 0.001), and 6 h (64.3% vs. 37.0%; p ≤ 0.001) post treatment. The mean pain intensity and QoL scores reduced, while the relative pain intensity and QoL (difference between the AAC and placebo groups) increased with time and was sustained for 6 h. Conclusions: The rapid onset and sustained effect of AAC make it a potential option for managing headaches and other symptoms, and to improve the QoL of subjects with MM.