Evidence of the long-term efficacy of digital therapies for smoking cessation that include a smartphone application (app) is limited. In this multi-center randomized controlled trial, we tested the efficacy of a novel digital therapy for smoking cessation: the “CureApp Smoking Cessation (CASC)” system, including a CASC smartphone app, a web-based patient management PC software for primary physicians, and a mobile exhaled carbon monoxide (CO) checker. A total of 584 participants with nicotine dependence were recruited from October 2017 to January 2018, and allocated 1:1 to the CASC intervention group or the control group. Both groups received a standard smoking cessation treatment with pharmacotherapy and counseling for 12 weeks. Meanwhile, the intervention group used the CASC system, and the control group used a control-app without a mobile CO checker, each for 24 weeks. The primary outcome was the biochemically validated continuous abstinence rate (CAR) from weeks 9 to 24. The main secondary outcome was an extended CAR from weeks 9 to 52. Except for 12 participants who did not download or use the apps, 285 participants were assigned to the intervention group, and 287, to the control. CAR from weeks 9 to 24 in the intervention group was significantly higher than that in the control group (63.9% vs. 50.5%; odds ratio [OR], 1.73; 95% confidence interval [CI], 1.24 to 2.42;P = 0.001). The CAR from weeks 9 to 52 was also higher in the intervention group than that in the control group (52.3% vs. 41.5%; OR, 1.55; 95% CI, 1.11 to 2.16;P = 0.010). No specific adverse events caused by the CASC system were reported. Augmenting standard face-to-face counseling and pharmacotherapy with a novel smartphone app, the CASC system significantly improved long-term CARs compared to standard treatment and a minimally supportive control app.

Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). Background: Mobile applications have been considered to provide active and continuous support for smoking cessation. However, it is yet to be known whether a smoking cessation smartphone application improves long-term abstinence rates in nicotine-dependent patients. Objective: We aim to evaluate the long-term abstinence effect of a novel smartphone application, CureApp Smoking Cessation (CASC), in patients with nicotine dependence. Methods: This study was a prospective, interventional, multicenter, single-arm study. We provided the CASC application to all the participants, who used it daily for 24 weeks. The CASC application includes features to maximize the therapeutic effect of pharmacological therapies and counseling at outpatient clinics for smoking cessation. The primary endpoint was a continuous abstinence rate (CAR) from weeks 9 to 24, while secondary endpoints were CARs from weeks 9 to 12 and 9 to 52. Results: Of the 56 adult smokers recruited, one did not download the application; therefore, 55 participants constituted the full analysis sample. The CAR from weeks 9 to 24 was 63.6% (35/55; 95% confidence interval [CI]: 51.3% – 76.0%), while the CARs from weeks 9 to 12 and 9 to 52 were 76.4% (42/55; 95% CI: 65.2% – 87.5%) and 58.2% (32/55; 95% CI: 45.6% – 70.8%), respectively. These CARs were better than the results of the national survey on outpatient clinics with regard to smoking cessation under the National Health Insurance Program and that of the varenicline phase Ⅲ trial in Japan and the United States. There was only one participant who dropped out during the 12 weeks of the treatment period. This treatment decreased the scores related to withdrawal and craving symptoms. Conclusions: The addition of CASC to usual smoking cessation therapies resulted in high CARs, high patient retention rates, and improvement of cessation-related symptoms. The smartphone application CASC is a feasible and useful tool to help long-term continuous abstinence that can be combined with a standard smoking cessation treatment program. Clinical Trial: University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN ID: UMIN000020123).

• Cycle threshold values were associated with the time to negative qPCR of SARS-CoV-2. • Olfactory and taste disorders occurred after development of fever and sore throat. • Fever and olfactory and taste disorders were correlated with higher viral burden. • Assessment of olfactory and taste disorders may be important to prevent transmission.

Group 2 innate lymphoid cells (ILC2s) play an important role in the pathophysiology of asthma via the robust production of type 2 cytokines. Recent studies have demonstrated that TLR7 (Toll-like receptor 7) signaling skews toward a type 1 inflammatory response in asthma, which may lead to the development of novel treatment strategies. However, the effect of TLR7 signaling on ILC2-dependent nonallergic eosinophilic inflammation remains unclear. In this study, we investigated the effects of R848, a TLR7 agonist, in a mouse model of IL-33–induced eosinophilic airway inflammation. Intranasal administration of R848 decreased infiltration of airway eosinophils and ILC2s, mucus production in epithelial cells, and type 2 cytokine production. Flow cytometric analysis identified an increased number of interstitial macrophages (IMs) expressing a high level of TLR7 in the lung upon IL-33 stimulation. IL-33–induced IMs also expressed high levels of alternatively activated (M2)-type genes and chemokines (CCL17 and CCL24). However, R848 stimulation modified these gene expressions and elicited the production of IL-27. Coculture experiments revealed that IL-33–induced IMs directly suppressed ILC2 activation in response to R848. In addition, the inhibitory effects of R848 on ILC2-induced type 2 inflammation were defective in WSX-1–deficient mice lacking the IL-27 receptor. Taken together, these findings indicate that R848 stimulates IL-33–induced IMs to suppress ILC2-mediated type 2 airway inflammation via IL-27. These findings highlight the therapeutic potential of TLR7 agonists and/or IL-27 cascades in nonallergic asthma.

This cross-sectional study investigated the relationship between the aminolevulinate dehydrogenase (ALAD) genotype and blood lead levels among 101 Japanese workers. Blood lead concentration measurement, biomarkers, and genotyping were performed. The minor allele frequency (MAF) for ALAD (ALAD2) was 0.08. Although the blood lead level in the subjects with heterozygous GC genotype was significantly higher than those with homozygous GG genotype, there were no significant differences for hemoglobin, hematocrit, serum and urinary ALA levels among genotypes. ALAD2 genotype was significantly associated with the blood lead concentration, even in the environmental lead exposed subjects. Further confirmation with a large sample size is needed.