Longitudinal passive cough monitoring and its implications for detecting changes in clinical status.

Research question: What is the impact of the duration of cough monitoring on its accuracy in detecting changes in the cough frequency? Materials and methods: This is a statistical analysis of a prospective cohort study. Participants were recruited in the city of Pamplona (Northern Spain), and their cough frequency was passively monitored using smartphone-based acoustic artificial intelligence software. Differences in cough frequency were compared using a one-tailed Mann-Whitney U test and a randomisation routine to simulate 24-h monitoring. Results: 616 participants were monitored for an aggregated duration of over 9 person-years and registered 62 325 coughs. This empiric analysis found that an individual's cough patterns are stochastic, following a binomial distribution. When compared to continuous monitoring, limiting observation to 24 h can lead to inaccurate estimates of change in cough frequency, particularly in persons with low or small changes in rate. Interpretation: Detecting changes in an individual's rate of coughing is complicated by significant stochastic variability within and between days. Assessing change based solely on intermittent sampling, including 24-h, can be misleading. This is particularly problematic in detecting small changes in individuals who have a low rate and/or high variance in cough pattern.

Acoustic surveillance of cough for detecting respiratory disease using artificial intelligence.

Research question: Can smartphones be used to detect individual and population-level changes in cough frequency that correlate with the incidence of coronavirus disease 2019 (COVID-19) and other respiratory infections? Methods: This was a prospective cohort study carried out in Pamplona (Spain) between 2020 and 2021 using artificial intelligence cough detection software. Changes in cough frequency around the time of medical consultation were evaluated using a randomisation routine; significance was tested by comparing the distribution of cough frequencies to that obtained from a model of no difference. The correlation between changes of cough frequency and COVID-19 incidence was studied using an autoregressive moving average analysis, and its strength determined by calculating its autocorrelation function (ACF). Predictors for the regular use of the system were studied using a linear regression. Overall user experience was evaluated using a satisfaction questionnaire and through focused group discussions. Results: We followed-up 616 participants and collected >62 000 coughs. Coughs per hour surged around the time cohort subjects sought medical care (difference +0.77 coughs·h-1; p=0.00001). There was a weak temporal correlation between aggregated coughs and the incidence of COVID-19 in the local population (ACF 0.43). Technical issues affected uptake and regular use of the system. Interpretation: Artificial intelligence systems can detect changes in cough frequency that temporarily correlate with the onset of clinical disease at the individual level. A clearer correlation with population-level COVID-19 incidence, or other respiratory conditions, could be achieved with better penetration and compliance with cough monitoring.

The effect of ivermectin alone and in combination with cobicistat or elacridar in experimental Schistosoma mansoni infection in mice.

Schistosoma mansoni is less susceptible to the antiparasitic drug ivermectin than other helminths. By inhibiting the P-glycoprotein or cytochrome P450 3A in mice host or parasites in a murine model, we aimed at increasing the sensitivity of S. mansoni to the drug and thus preventing infection. We assigned 124 BALB/c mice to no treatment, treatment with ivermectin only or a combination of ivermectin with either cobicistat or elacridar once daily for three days before infecting them with 150 S. mansoni cercariae each. The assignment was done by batches without an explicit randomization code. Toxicity was monitored. At eight weeks post-infection, mice were euthanized. We determined number of eggs in intestine and liver, adult worms in portal and mesenteric veins. Disease was assessed by counting granulomas/cm2 of liver and studying organ weight indices and total weight. IgG levels in serum were also considered. No difference between groups treated with ivermectin only or in combination with cobicistat or elacridar compared with untreated, infected controls. Most mice treated with ivermectin and elacridar suffered severe neurological toxicity. In conclusion, systemic treatment with ivermectin, even in the presence of pharmacological inhibition of P-glycoprotein or cytochrome P450 3A, did not result in effective prophylaxis for S. mansoni infection in an experimental murine model.

Digital acoustic surveillance for early detection of respiratory disease outbreaks in Spain: a protocol for an observational study.

INTRODUCTION: Cough is a common symptom of COVID-19 and other respiratory illnesses. However, objectively measuring its frequency and evolution is hindered by the lack of reliable and scalable monitoring systems. This can be overcome by newly developed artificial intelligence models that exploit the portability of smartphones. In the context of the ongoing COVID-19 pandemic, cough detection for respiratory disease syndromic surveillance represents a simple means for early outbreak detection and disease surveillance. In this protocol, we evaluate the ability of population-based digital cough surveillance to predict the incidence of respiratory diseases at population level in Navarra, Spain, while assessing individual determinants of uptake of these platforms. METHODS AND ANALYSIS: Participants in the Cendea de Cizur, Zizur Mayor or attending the local University of Navarra (Pamplona) will be invited to monitor their night-time cough using the smartphone app Hyfe Cough Tracker. Detected coughs will be aggregated in time and space. Incidence of COVID-19 and other diagnosed respiratory diseases within the participants cohort, and the study area and population will be collected from local health facilities and used to carry out an autoregressive moving average analysis on those independent time series. In a mixed-methods design, we will explore barriers and facilitators of continuous digital cough monitoring by evaluating participation patterns and sociodemographic characteristics. Participants will fill an acceptability questionnaire and a subgroup will participate in focus group discussions. ETHICS AND DISSEMINATION: Ethics approval was obtained from the ethics committee of the Centre Hospitalier de l'Université de Montréal, Canada and the Medical Research Ethics Committee of Navarre, Spain. Preliminary findings will be shared with civil and health authorities and reported to individual participants. Results will be submitted for publication in peer-reviewed scientific journals and international conferences. TRIAL REGISTRATION NUMBER: NCT04762693.