Efficacy of Electronic Cigarettes vs Varenicline and Nicotine Chewing Gum as an Aid to Stop Smoking: A Randomized Clinical Trial.

Importance: Electronic cigarettes (ECs) are often used by smokers as an aid to stopping smoking, but evidence is limited regarding their efficacy compared with nicotine replacement therapy (NRT), and no evidence is available on how their efficacy compares with that of varenicline. Objective: To evaluate whether ECs are superior to NRT and noninferior to varenicline in helping smokers quit. Design, Setting, and Participants: This was a randomized clinical trial conducted at 7 sites in China and including participants who were smoking at least 10 cigarettes per day and motivated to quit, not using stop-smoking medications or EC, and willing to use any of the study products. Participants were first recruited in May 2021, and data analysis was conducted in December 2022. Interventions: A cartridge-based EC (30 mg/mL nicotine salt for 2 weeks and 50 mg/mL after that), varenicline (0.5 mg, once a day for 3 days; 0.5 mg, twice a day for 4 days; and 1 mg, twice a day, after that), and 2 mg (for smokers of ≤20 cigarettes per day) or 4 mg (>20 cigarettes per day) nicotine chewing gum, all provided for 12 weeks and accompanied by minimal behavioral support (an invitation to join a self-help internet forum). Main Outcomes and Measures: The primary outcome was sustained abstinence from smoking at 6 months as validated by an expired-air carbon monoxide reading (<8 parts per million). Participants lost to follow-up were included as nonabstainers. Results: Of 1068 participants, 357 (33.5%) were female, and the mean (SD) age was 33.9 (3.1) years. A total of 409 (38.3%), 409 (38.3%), and 250 (23.4%) participants were randomized to the EC, varenicline, and NRT arms, respectively. The 6-month biochemically validated abstinence rates were 15.7% (n = 64), 14.2% (n = 58), and 8.8% (n = 22) in the EC, varenicline, and NRT study arms, respectively. The quit rate in the EC arm was noninferior to the varenicline arm (absolute risk reduction, 1.47%; 95% CI, -1.41% to 4.34%) and higher than in the NRT arm (odds ratio, 1.92; 95% CI, 1.15-3.21). Treatment adherence was similar in all study arms during the initial 3 months, but 257 participants (62.8%) in the EC arm were still using ECs at 6 months, with no further use in the 2 other study arms. The most common adverse reactions were throat irritation (32 [7.8%]) and mouth irritation (28 [6.9%]) in the EC arm, nausea (36 [8.8%]) in the varenicline arm, and throat irritation (20 [8.0%]) and mouth irritation (22 [8.8%]) in the NRT arm. No serious adverse events were recorded. Conclusions and Relevance: The results of this randomized clinical trial found that when all treatments were provided with minimal behavior support, the efficacy of EC was noninferior to varenicline and superior to nicotine chewing gum. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2100048156.

Effects of tobacco smoking on cardiovascular disease in patients with systemic lupus erythematosus: A systematic review and meta-analysis.

Background: Patients with systemic lupus erythematosus (SLE) are at increased risk of cardiovascular disease (CVD) compared to the general population. However, little is known about the effects of tobacco smoking on CVD in patients with SLE. Objective: To systematically review and summarize the available literature regarding the effects of tobacco smoking on developing CVD in patients with SLE. Methods: We retrieved relevant studies from the following databases: PubMed, EMBASE, Web of Science and China National Knowledge Internet (CNKI) database. Two reviewers independently reviewed the eligible studies, assessed their validity, and extracted relevant data. Sensitivity and subgroup analyses were performed to distinguish sources of heterogeneity. Results: A total of 10 studies, which comprised 6984 participants, were included in the analysis. The overall quality of evidence was rated as moderate to low. The smoking prevalence among CVD patients was 39.28% (271/690), which was higher than 31.36% (1974/6294) among non-CVD patients. Compared with never-smokers, the risk of developing CVD in current smokers was 1.42 (95% CI: 1.21-1.66). No significant publication bias was found in our meta-analysis. Conclusions: In spite of the several negative results, this study found that current smokers with SLE have an increased risk of developing CVD, although most of the included studies were in low-to-moderate quality. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022338109.

[Evidence mapping of clinical research on traditional Chinese medicine in treatment of diabetic foot].

The present study comprehensively summarized the clinical randomized controlled trials(RCTs) and systematic reviews/Meta-analyses of traditional Chinese medicine(TCM) in the treatment of diabetic foot by evidence mapping and clarified the distribution of evidence in this field.CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Web of Science were searched for clinical RCTs and systematic reviews on TCM in the treatment of diabetic foot published in the past ten years.The evidence was analyzed and displayed in the form of text combined with figures and tables.AMSTAR was used for the quality evaluation of systematic reviews.A total of 1 037 clinical RCTs and 20 systematic reviews/Meta-analyses were included.The overall publishing trend was stable, and the scale of RCTs was small.TCM interventions for diabetic foot mainly included external application and foot bath.Much attention was paid to the outcome indicators including total effective rate, ankle brachial index(ABI), and TCM syndromes, while less attention to neuropathy scores, emotional psychology, and long-term prognosis.The overall quality of systematic reviews was low, and the majority of studies indicated that TCM had potential efficacy in treating diabetic foot, and there was still a lack of clear clinical evidence of efficacy.TCM has both advantages and problems in the treatment of diabetic foot.At present, there is still a lack of high-quality research, suggesting that more large-sample, multi-center RCTs should be launched in the future, and the quality of related systematic reviews/Meta-analyses should be improved to fully explore and give full play to the advantages of TCM in the treatment of diabetic foot, and promote the development of the clinical and evidence-based medicine of TCM in the treatment of diabetic foot.

The characteristics and patterns of e-cigarette use and its association with cigarette cessation intention in a Chinese smoking population: A mediation analysis.

INTRODUCTION: The use of e-cigarettes has become more common in China, but the research on e-cigarettes in China, while growing, is still limited. This study examined the characteristics and patterns of e-cigarette use, and analyzed the possible mediators between cigarette cessation intention and e-cigarette use in a Chinese smoking population. METHODS: This was a cross-sectional study conducted in mainland China. By convenience sampling method, the participants were recruited from 85 major commercial streets of several large cities in China. The study interviewers completed face-to-face interviews and uploaded the completed questionnaires into the online survey platform. The participants were contacted for clarification if any problems were detected. Logistic regression yielded adjusted odds ratios (ORs) for ever use of e-cigarettes. We further conducted a mediation analysis to estimate the effect of possible mediators. RESULTS: From July to August 2020, a total of 738 smokers were invited to participate in this study; 613 smokers were identified as eligible and 609 smokers were included in this analysis. Of them, 24 (3.94%) participants were currently using e-cigarettes, and 165 (27.09%) participants have ever used e-cigarettes. The participants with younger age were more likely to have ever used e-cigarettes, ranging from 37.5% in the 18-29 years age group to 6.5% in the 60-69 years age group. After controlling for demographic characteristics and nicotine dependence, the ever use of e-cigarettes was significantly associated with younger age, higher education level, higher monthly income, previous smoking cessation attempts and quitting intention. With the mediation analysis, the education level is confirmed as a mediating factor, and approximately 42.86% of the effects were mediated through the channel of higher socioeconomic status. CONCLUSIONS: This is the first study to examine the possible mediators between cigarette cessation intention and e-cigarette use in a Chinese smoking population. The findings revealed that high socioeconomic status, particularly higher education level, was a major mediating factor.

The clinical population pharmacokinetics, metabolomics and therapeutic analysis of alkaloids from Alstonia scholaris leaves in acute bronchitis patients.

BACKGROUND: Capsule of alkaloids from leaf of Alstonia scholaris (CALAS) is a new investigational botanical drug (No. 2011L01436) for respiratory disease. Clinical population pharmacokinetics (PK), metabolomics and therapeutic data are essential to guide dosing in patients. Previous research has demonstrated the potential therapeutic effect of CALAS on acute bronchitis. Further clinical trial data are needed to verify its clinical efficacy, pharmacokinetics behavior, and influence of dosage and other factors. PURPOSE: To verify the clinical efficacy and explore the potential biomarkers related to CALAS treatment for acute bronchitis. MATERIALS AND METHODS: Oral CALAS was assessed in a randomized, double-blind, placebo-controlled trial. Fifty-five eligible patients were randomly assigned to four cohorts to receive 20, 40 or 80 mg, of CALAS three times daily for seven days, or placebo. Each CALAS cohort included 15 subjects, and the placebo group included 10 subjects. A population PK model of CALAS was developed using plasma with four major alkaloid components. Metabolomics analysis was performed to identify biomarkers correlated with the therapeutic effect of CALAS, and efficacy and safety were assessed based on clinical symptoms and adverse events. RESULTS: The symptoms of acute bronchitis were alleviated by CALAS treatment without serious adverse events or clinically significant changes in vital signs, electrocardiography or upper abdominal Doppler ultrasonography. Moreover, one compartment model with first-order absorption showed that an increase in aspartate transaminase will reduce the clearance (CL) of scholaricine, and picrinine CL was inversely proportional to body mass index, while 19-epischolaricine and vallesamine CL increased with aging. The serum samples from acute bronchitis patients at different time points were analyzed using UPLC-QTOF in combination with the orthogonal projection to latent structures-discriminant analysis, which indicated higher levels of lysophosphatidylcholines, lysophosphatidylethanolamines and amino acids with CALAS treatment than with placebo. CONCLUSION: This is the first study to evaluate the clinical efficacy and explored the potential biomarkers related to CALAS therapeutic mechanism of acute bronchitis by means of clinical trial combined the metabolomics study. This exploratory study provides a basis for further research on clinical efficacy and optimal dosing regimens based on pharmacokinetics behavior. Additional acute bronchitis patients and CALAS PK samples collected in future studies may be used to improve model performance and maximize its clinical value.

The Effect of Cardiovascular Medications on Disease-Related Outcomes in Idiopathic Pulmonary Fibrosis: A Systematic Review and Meta-Analysis.

Background: Multiple studies have revealed that idiopathic pulmonary fibrosis (IPF) patients are more at risk for cardiovascular diseases and that many IPF patients receive cardiovascular medications like statins, angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), and anticoagulants. Existing studies have reported divergent findings on the link between cardiovascular medications and fibrotic disease processes. The aim of this study is to synthesize the evidence on the efficacy of cardiovascular medications in IPF. Methods: We searched studies reporting the effect of cardiovascular medications on IPF in the PubMed, Embase, Web of Science, Cochrane Library, and two Chinese databases (China National Knowledge Infrastructure database and China Wanfang database). We calculated survival data, forced vital capacity (FVC) decline, and IPF-related mortality to assess the efficacy of cardiovascular medications in IPF. We also estimated statistical heterogeneity by using I2 and Cochran Q tests, and publication bias was evaluated by risk of bias tools ROBINS-I. Results: A total of 12 studies were included in the analysis. The included studies had moderate-to-serious risk of bias. Statin use was associated with a reduction in mortality (hazard ratio (HR), 0.89; 95% CI 0.83-0.97). Meta-analysis did not demonstrate any significant relationship between statin use and the FVC decline (HR, 0.86; 95% CI 0.73-1.02), ACEI/ARB use, and survival data (HR, 0.92; 95% CI 0.73-1.15) as well as anticoagulant use and survival data (HR, 1.16; 95% CI 0.62-2.19). Conclusion: Our study suggested that there is a consistent relationship between statin therapy and survival data in IPF population. However, there is currently insufficient evidence to conclude the effect of ACEI, ARB, and anticoagulant therapy on IPF population especially to the disease-related outcomes in IPF.

Inhibition of Aspirin-Induced Gastrointestinal Injury: Systematic Review and Network Meta-Analysis.

Background: Administration of aspirin has the potential for significant side effects of gastrointestinal (GI) injury mainly caused by gastric acid stimulation, especially in long-term users or users with original gastrointestinal diseases. The debate on the optimal treatment of aspirin-induced gastrointestinal injury is ongoing. We aimed to compare and rank the different treatments for aspirin-induced gastrointestinal injury based on current evidence. Methods: We searched PubMed, EMBASE, Cochrane Library (Cochrane Central Register of Controlled Trials), and Chinese databases for published randomized controlled trials (RCTs) of different treatments for aspirin-induced gastrointestinal injury from inception to 1 May 2021. All of the direct and indirect evidence included was rated by network meta-analysis under a Bayesian framework. Results: A total of 10 RCTs, which comprised 503 participants, were included in the analysis. The overall quality of evidence was rated as moderate to high. Eleven different treatments, including omeprazole, lansoprazole, rabeprazole, famotidine, geranylgeranylacetone, misoprostol, ranitidine bismuth citrate, chili, phosphatidylcholine complex, omeprazole plus rebamipide, and placebo, were evaluated in terms of preventing gastrointestinal injury. It was suggested that omeprazole plus rebamipide outperformed other treatments, whereas geranylgeranylacetone and placebo were among the least treatments. Conclusion: This is the first systematic review and network meta-analysis of different treatments for aspirin-induced gastrointestinal injury. Our study suggested that omeprazole plus rebamipide might be considered the best option to treat aspirin-induced gastrointestinal injury. More multicenter, high quality, large sample size randomized controlled trials will confirm the advantages of these medicines in the treatment of aspirin-induced gastrointestinal injury in the future.

Combination of Xuesaitong and Aspirin Based on the Antiplatelet Effect and Gastrointestinal Injury: Study Protocol for a Randomized Controlled Noninferiority Trial.

BACKGROUND: Aspirin is the first-line medication for prevention and treatment of coronary heart disease (CHD). However, long-term use of aspirin resulting in gastrointestinal mucosal injury and bleeding limits the regularity of medication. Xuesaitong is a marketed Chinese medicine contained main active component in Panax notoginseng saponins (PNS), which can significantly inhibit platelet aggregation in patients with CHD. Our previous studies have already showed that PNS could reduce the gastrointestinal mucosal injury caused by aspirin in preclinical study. However, there is a need for further clinical studies to evaluate synergy and attenuation effect of the combination. METHODS: This trial is a prospectively planned, open-labeled, parallel-grouped, single-centered clinical trial. A total of eligible 480 participants will be randomly allocated into three groups: aspirin group, Xuesaitong group, and drug combination group at a ratio of 1 : 1 : 1. The primary outcome is the change of platelet aggregation rate and calprotectin activity. Secondary outcomes include PAC-1, P-selectin, P2Y12, I-FABP activity, and fecal occult blood. Discussion. The results of the study are expected to provide evidence of high methodological and reporting quality on the synergy function of Xuesaitong and aspirin upon the antiplatelet and anti-gastrointestinal injury effect for CHD. It also provides an experimental basis for clinical rational drug combination therapy. Trial Registration. This trial was registered in the Chinese Clinical Trail Registry, ChiCTR2000036311, on 22 August 2020, http://www.chictr.org.cn/edit.aspx?pid=58798&htm=4.

Pharmacokinetics and safety evaluation in healthy Chinese volunteers of alkaloids from leaf of Alstonia scholaris: A multiple doses phase I clinical trial.

BACKGROUND: Alstonia scholaris (Apocynaceae) was reported to be a rich source of indole alkaloids, which exhibited remarkably bioactivities. The leaf of A. scholaris has been used in 'dai' ethno-medicine for treatment of respiratory diseases, and the defined indole alkaloids from leaf of A. scholaris has been registered as investigational new botanical drug (No. 2011L01436) and was approved for phase I/II clinical trials by China Food and Drug Administration (CFDA). PURPOSE: The aim of the trial is to evaluate the safety and explore the relationship of dosing frequency and pharmacokinetics after oral administration of capsule of alkaloids from leaf of A. scholaris (CALAS) at different doses. METHODS: In this randomized, open-labelled, single-center clinical trial, the safety and pharmacokinetics of CALAS were assessed in eligible healthy Chinese volunteers after oral administration of different doses. Each volunteer (n = 10 per group) received single dose of CALAS from 20 mg, 40 mg, 80 mg to 120 mg orally. The pharmacokinetics of CALAS was investigated in healthy Chinese subjects' plasma by a fully-validated LC-MS/MS method. Safety was assessed biochemically and clinically throughout the study, and drug re-excitation research was conducted to verify the correlation between investigational product and minor adverse events. The trial was registered on August 26, 2015 (http://www.chictr.org.cn/showproj.aspx?proj=11736), number ChiCTR-IPR-15006976. RESULTS: 40 subjects completed the study, and as a result, vallesamine had the highest concentration in plasma of healthy volunteers, and the AUC exposure level in each compounds in turn is vallesamine > scholaricine > 19-epischolaricine > picrinine. For the safety evaluation of CALAS, two cases of minor adverse events were observed during the trial, but the drug re-excitation research indicated that these two adverse events were related to the individual's physiological variation. CONCLUSION: Pharmacokinetic characteristics of each ingredient showed different patterns. 19-epischolaricine, vallesamine and picrinine were match to the linear pharmacokinetic characteristics, but scholaricine conformed to the characteristics of nonlinear pharmacokinetics. The CALAS was safe in healthy subjects under the current dose regimen.