RESUMO
Pharmacokinetic (PK) studies can provide essential information on abuse liability of nicotine and tobacco products but are intrusive and must be conducted in a clinical environment. The objective of the study was to explore whether changes in plasma nicotine levels following use of an e-cigarette can be predicted from real time monitoring of physiological parameters and mouth level exposure (MLE) to nicotine before, during, and after e-cigarette vaping, using wearable devices. Such an approach would allow an -effective pre-screening process, reducing the number of clinical studies, reducing the number of products to be tested and the number of blood draws required in a clinical PK study Establishing such a prediction model might facilitate the longitudinal collection of data on product use and nicotine expression among consumers using nicotine products in their normal environments, thereby reducing the need for intrusive clinical studies while generating PK data related to product use in the real world.An exploratory machine learning model was developed to predict changes in plasma nicotine levels following the use of an e-cigarette; from real time monitoring of physiological parameters and MLE to nicotine before, during, and after e-cigarette vaping. This preliminary study identified key parameters, such as heart rate (HR), heart rate variability (HRV), and physiological stress (PS) that may act as predictors for an individual's plasma nicotine response (PK curve). Relative to baseline measurements (per participant), HR showed a significant increase for nicotine containing e-liquids and was consistent across sessions (intra-participant). Imputing missing values and training the model on all data resulted in 57% improvement from the original'learning' data and achieved a median validation R2 of 0.70.The study is in its exploratory phase, with limitations including a small and non-diverse sample size and reliance on data from a single e-cigarette product. These findings necessitate further research for validation and to enhance the model's generalisability and applicability in real-world settings. This study serves as a foundational step towards developing non-intrusive PK models for nicotine product use.
RESUMO
Recurrent pharyngo-tonsillar infections caused by group A beta-hemolytic streptococci (GABHS) occur frequently in young children, and the treatment of these infections contributes substantially to the total current requirement for antibiotic prescribing. Our study goal was to assess through a retrospective observational analysis whether the administration of the oral probiotic, Streptococcus salivarius K12 (SsK12), could reduce the occurrence of GABHS pharyngo-tonsillar infections in children who had a recent history of recurrent episodes of these infections. Twelve primary care pediatricians identified, through their databases, a total of 130 children who had experienced recurrent GABHS pharyngo-tonsillar infections over a period of at least 6-12 months prior to their inclusion in the study. Of these children, 76 then undertook a 90-day program requiring once-a-day dosing with a commercially available (Bactoblis) lozenge containing SsK12. No probiotic supplement was given to the remaining 54 (control) children. Each subject was monitored for the occurrence of GABHS pharyngo-tonsillitis and also for acute otitis media, bronchitis, sinusitis, and bronchopneumonia for at least 12 months following their entry to the study. Even 9 months after the use of SsK12 had been stopped, the probability of new GABHS infections was significantly lower (P>0.001) when compared to the period before dosing commenced. When compared to the untreated children, those taking SsK12 appear to have had significantly fewer GABHS infections both during the 90-day period of prophylaxis and during the following 9 months (P<0.001). These observations are supportive of the use of probiotic SsK12 for the control of recurrent GABHS pharyngo-tonsillar infections in children, and as an associated benefit, the use of this probiotic could lead to reduced antibiotic consumption. Follow-up controlled prospective studies should now be initiated in order to further establish the efficacy of this newly emerging prophylactic strategy.