Market survey of disposable e-cigarette nicotine content and e-liquid volume.

Inaccurate labels on some e-cigarette products have prompted calls for routine testing to monitor product label integrity. The objective of this study was to compare label statements of commercial disposable/non-chargeable e-cigarette products for nicotine concentration and e-liquid volume with analytically verified levels. Commercial e-cigarette samples were analyzed for nicotine concentration (N = 51), e-liquid volume and total nicotine content (N = 39). Twenty-three of the 51 samples analyzed for nicotine deviated from their label statements by more than ± 10%. Deviations ranged from -50.1% to + 13.9%. Thirty of the 39 samples analyzed for e-liquid volume deviated from their label statements by more than ± 10%. Deviations ranged from -62.1% to + 13.3%. Only one brand listed total nicotine on the label. In thirty-one of the 39 samples, calculated total nicotine amount in e-liquid deviated from the amounts calculated from the label metrics by more than ± 10%. Deviations ranged from -66.8% to -1.43%. These findings underscore the need for regulatory enforcement of manufacturing quality control and product labeling practices to optimize the harm reduction potential and consumer experience associated with the use of e-cigarette products.

Examining patient activation and other factors associated with changes in pain and function following best evidence osteoarthritis care.

Objectives: The primary objective was to examine baseline patient activation as a prognostic factor for changes in pain and function following participation in an osteoarthritis management program. The secondary objective was to examine other prognostic factors from existing literature (e.g. employment, functional performance, depression, comorbidities). Method: One-hundred-and-eleven participants with knee osteoarthritis were assessed at 0-, 12- and 26-weeks in this prospective clinical cohort. Demographic variables, timed-up-and-go (TUG), patient activation measure (PAM-13), Depression Anxiety Stress Scale and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were collected. Multivariable linear regression examined relationships between prognostic factors and pain and function at 12- and 26-weeks. Results: Complete 12- and 26-week data were available for 89 and 74 participants respectively, 66 â€‹% female, 66.8 (SD 10.0) years, 74 â€‹% unemployed, 66 â€‹% finished high school or higher, 12 â€‹% on joint arthroplasty waitlists. Baseline PAM-13 scores were not associated with changes in pain or function at 12- or 26-weeks. Employment status (ߠ​= â€‹9.17 (95 â€‹% CI 2.11, 16.24), p â€‹= â€‹0.01) and TUG (ߠ​= â€‹-1.20 (95 â€‹% CI -1.91, -0.49), p â€‹< â€‹0.01) were associated with changes in pain at week-12. Employment status (ߠ​= â€‹11.60 (95 â€‹% CI 5.31, 17.90), p â€‹< â€‹0.01) and TUG (ߠ​= â€‹-1.10 (95%CI -1.78, -0.43), p â€‹< â€‹0.01) were associated with 12-week function. Baseline TUG (ߠ​= â€‹-1.32 (95 â€‹% CI -2.40, -0.23), p â€‹= â€‹0.02) was associated with week-26 WOMAC function. Conclusions: Baseline PAM-13 scores were not associated with changes in pain and function at any timepoint. Employment status and TUG were associated with changes in pain and function at 12-weeks, TUG was associated with 26-week function.

Comparison of Generic Drug Reviews for Marketing Authorization between Japan and Canada.

PURPOSE: Generic drugs are assuming an increasingly important role in sustaining modern healthcare systems, as the cost of healthcare, including drug usage, is gradually expanding around the world. To date, published articles comparing generic drug reviews between different countries are scarce. OBJECTIVE: The objective of this study was to examine generic drug reviews in Japan and Canada. METHODS: We surveyed generic drug reviews from Japan and Canada and compared the following points: general matter (application types, type of partial change or Supplement to an Abbreviated New Drug Submission, application and approval numbers, review period, application format, review report, responsibility for review), bioequivalence studies for solid oral dosage forms, and bioequivalence guidelines, guidance, or basic principles regarding various dosage forms. RESULTS: This survey described the many similarities and differences in generic drug reviews between the two countries and points that should be improved to promote better generic drug reviews. In particular, regulations for the definition of the same or different active pharmaceutical ingredients (APIs) are similar for both authorities. CONCLUSIONS: The results clarified the future challenges of generic drug reviews, and the differences highlighted by this survey will be important considerations for the future. This is the first article to present and discuss the details of generic drug reviews between Japan and Canada.

Time trends in never smokers in the relative frequency of the different histological types of lung cancer, in particular adenocarcinoma.

The increasing proportion of lung cancers classified as adenocarcinoma has been a topic of interest and research. The main objective of the analyses reported here is to summarize how the proportion of adenocarcinoma varies in never smokers by time, sex and region based on published evidence on the distribution of lung cancer types available from epidemiological studies. Based on 219 sex- and period-specific blocks of data drawn from 157 publications, there appears to be a clear time-related increase in the proportion of lung cancers in never smokers that are adenocarcinoma, which is evident in both sexes, and not specific to any region. It is seen whether the denominator of the proportion is made up of adenocarcinoma plus squamous cell carcinoma cases, cases of the four major types combined, or all lung cancer cases. The ratio of adenocarcinoma to squamous cell carcinoma rose continuously from 1950 to 69 to be almost 4 times higher for the data from 2000 onwards. We discuss factors that may have contributed to the observed findings, including changes in lung cancer classification. Our findings argue against the hypothesis that increases in the ratio arise from changes in cigarette design and composition.

Effect of cigarette design on biomarkers of exposure, puffing topography and respiratory parameters.

Despite the lack of evidence, many reports exist which have implied that smokers inhale low-yield cigarette smoke more deeply than that of high-yield cigarettes. The objective of this study was to investigate the effect of short-term switching between smoker's own brand and test cigarettes with different smoke yields on puffing topography, respiratory parameters and biomarkers of exposure. Participants were randomly assigned to smoke either a Test Cigarette-High Tar (TCH), for two days, and then switched to a Test Cigarette-Low Tar (TCL), for two days or the reverse order (n = 10 each sequence). Puffing topography (CReSS microdevice), respiratory parameters (inductive plethysmography) and biomarkers of exposure (BOE, urinary nicotine equivalents - NE and blood carboxyhemoglobin - COHb) were measured at baseline and on days 2 and 4. The average puffs per cigarette, puff volume and puff durations were statistically significantly lower, and inter-puff interval was significantly longer for the TCH compared to the TCL groups. Respiratory parameters were not statistically significantly different between the TCH and TCL groups. Post-baseline NE and COHb were statistically significantly lower in the TCL compared to the TCH groups. Under the conditions of this study, we found no indication of changes in respiratory parameters, particularly inhalation time and volume, between study participants smoking lower versus higher yield cigarettes. Likewise, the BOE provides no indication of deeper inhalation when smoking low- versus high-yield cigarettes. These findings are consistent with the published literature indicating smoking low-yield cigarettes does not increase the depth of inhalation.

TSNA exposure from cigarette smoking: 18 years of urinary NNAL excretion data.

The objective of this work was to characterize trends over time in urinary excretion of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) among cigarette smokers in the US. We identified 35 studies presenting data that either reported, or could be converted to, common units of total urinary NNAL excretion as pmol/mg creatinine. The studies spanned 18years, reported urinary NNAL excretion estimates for 61 defined populations, and included a combined total of 3941 study participants. Analyses show that urinary NNAL excretion trends downward with study publication year, and the trend is statistically significant. The trend does not appear to be accounted for by a reduction in cigarettes smoked per day by study participants over the same time period. This trend is consistent with reductions in tobacco specific nitrosamine (TSNA) levels in both cigarette tobacco filler and mainstream cigarette smoke observed over the past decade and with efforts by the tobacco industry and the agricultural community to reduce levels of TSNAs in tobacco and cigarette smoke.

TSNA levels in machine-generated mainstream cigarette smoke: 35 years of data.

This paper characterizes historical and current tobacco specific nitrosamine (TSNA) levels in mainstream (MS) cigarette smoke of US commercial cigarettes. To conduct this analysis, we gathered 35 years of published data of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N-nitrosonornicotine (NNN) levels in MS cigarette smoke. We also assessed internal data of MS smoke NNK and NNN levels generated from various market monitoring initiatives and from control cigarettes used in a multi-year program for testing cigarette ingredients. In all, we analyzed machine smoking data from 401 cigarette samples representing a wide range of products and design characteristics from multiple manufacturers and market leaders. There was no indication that TSNA levels systematically increased in cigarette MS smoke over the 35-year analysis period. In particular, TSNA levels expressed as either per cigarette or normalized for tar suggest a downward trend in MS smoke over the past 10 years. The apparent downward trend in TSNA levels in MS smoke may reflect industry and agricultural community efforts to reduce levels of TSNAs in tobacco and cigarette smoke.

Frequency and outcomes of accidental ingestion of tobacco products in young children.

This review assesses published literature related to frequency and outcomes associated with accidental ingestion of tobacco and pharmaceutical nicotine products among young children. Twenty-seven years of annual reports by American Association of Poison Control Centers (AAPCC) were analyzed for occurrence and outcomes associated with accidental ingestion events involving tobacco and pharmaceutical nicotine products among young children. Over a 27-year period, and of >50 million contacts for all categories combined, 217,340 contacts involving ingestion of tobacco products were reported. Approximately 89% involved children <6 years old. One fatality was reported, however the co-ingestion of both cigarettes and diazepam complicates an assessment of a contributory role of tobacco. The rate of major, non-fatal, outcomes was <0.1%. Data from AAPCC reports and other sources indicate the frequency of accidental poisoning events is relatively low for tobacco products compared with other products such as drugs, dietary supplements, cleaning products, and personal care products. These findings, along with those for pharmaceutical nicotine products, are consistent with published case reports and reviews, indicating that the frequency and severity of outcomes associated with accidental ingestion of tobacco products by young children appear to be relatively low. However, adults should keep tobacco products out of the reach of children.

Does dual use jeopardize the potential role of smokeless tobacco in harm reduction?

INTRODUCTION: The use of smokeless tobacco as part of a strategy to reduce the harm from cigarette smoking is a topic of debate within the tobacco control and public health communities. One concern voiced regarding endorsement of such a tactic is the possibility of actually increasing harm should current smokers adopt dual cigarette/smokeless tobacco use (dual use), which could lead to unintended consequences by perpetuating cigarette smoking, diminishing tobacco cessation, or increasing tobacco-related harm. METHODS: Here, we review the available literature on health effects and trajectories of use among dual users from a variety of U.S. and European epidemiological studies. RESULTS: These data suggest that there are not any unique health risks associated with dual use of smokeless tobacco products and cigarettes, which are not anticipated or observed from cigarette smoking alone. Furthermore, studies show that dual users smoke fewer cigarettes than exclusive smokers, and studies of tobacco use patterns over time (tobacco use trajectory data) indicate that dual users are more likely than exclusive cigarette smokers to cease smoking. CONCLUSIONS: Overall, the concern about dual use appears to be contradicted by the evidence in the literature that dual use of smokeless tobacco and cigarettes may result in reduction in smoking-related harm as smoking intensity is decreased and smoking cessation increases.

The effect of menthol containing cigarettes on adult smokers' exposure to nicotine and carbon monoxide.

UNLABELLED: There is limited information comparing biomarkers of exposure (BOE) to cigarette smoke in menthol (MS) and non-menthol cigarette smokers (NMS). OBJECTIVE: To compare BOE to nicotine and carbon monoxide in MS and NMS. METHODS: Cross-sectional, observational, ambulatory, multi-centre study in 3341 adult cigarette smokers. Nicotine equivalents (NE) in 24h urine, NE/cigarette, COHb and serum cotinine were measured. Statistical analyses included analysis of variance and Wilcoxon test. RESULTS: Analyses of variance revealed no statistically significant effects of mentholated cigarettes on NE/24h, COHb, serum cotinine and NE/cigarette. On average MS smoked 15.0 and NMS 16.8 cigarettes/day. The unadjusted mean differences were as follows: MS had lower NE/24h (5.4%) and COHb (3.2%), higher serum cotinine (3.0%) and NE/cigarette (5.7%) than NMS. African-Americans MS smoked 40% fewer cigarettes, showed lower NE/24h (24%) and COHb (10%) and higher NE/cig (29%) and serum cotinine (8%) levels than their White counterparts. CONCLUSIONS: Smoking mentholated cigarettes does not increase daily exposure to smoke constituents as measured by NE and COHb. These findings are consistent with the majority of epidemiological studies indicating no difference in smoking related risks between MS and NMS.

Heme oxygenase-derived carbon monoxide promotes arteriolar endothelial dysfunction and contributes to salt-induced hypertension in Dahl salt-sensitive rats.

Vascular tissues express heme oxygenase (HO), which metabolizes heme to form carbon monoxide (CO). Heme-derived CO inhibits nitric oxide synthase and promotes endothelium-dependent vasoconstriction. After 4 wk of high-salt diet, Dahl salt-sensitive (Dahl-S) rats display hypertension, increased vascular HO-1 expression, and attenuated vasodilator responses to ACh that can be completely restored by acute treatment with an inhibitor of HO. In this study, we examined the temporal development of HO-mediated endothelial dysfunction in isolated pressurized first-order gracilis muscle arterioles, identified the HO product responsible, and studied the blood pressure effects of HO inhibition in Dahl-S rats on a high-salt diet. Male Dahl-S rats (5-6 wk) were placed on high-salt (8% NaCl) or low-salt (0.3% NaCl) diets for 0-4 wk. Blood pressure increased gradually, and responses to an endothelium-dependent vasodilator, ACh, decreased gradually with the length of high-salt diet. Flow-induced dilation was abolished in hypertensive Dahl-S rats. Acute in vitro pretreatment with an inhibitor of HO, chromium mesoporphyrin (CrMP), restored endothelium-dependent vasodilation and abolished the differences between groups. The HO product CO prevented the restoration of endothelium-dependent dilation by CrMP. Furthermore, administration of an HO inhibitor lowered blood pressure in Dahl-S rats with salt-induced hypertension but did not do so in low-salt control rats. These results suggest that hypertension and HO-mediated endothelial dysfunction develop gradually and simultaneously in Dahl-S rats on high-salt diets. They also suggest that HO-derived CO underlies the impaired endothelial dysfunction and contributes to hypertension in Dahl-S rats on high-salt diets.

Heme oxygenase activity in placenta: direct dependence on oxygen availability.

Carbon monoxide (CO), which is formed endogenously from heme catalyzed by heme oxygenase (HO), is proposed to play a role in vascular control. The mRNA and protein expression of the inducible isoform of HO (HO-1) increases in response to hypoxia, and it has been assumed that HO activity also increases. This assumption requires evaluation because the catalytic activity of HO requires three molecules of O(2) for each molecule of CO formed from heme, and HO activity may be limited by O(2) availability. To test the hypothesis that low physiological O(2) concentrations limit HO activity, heme-derived CO formation by microsomal fractions of homogenates of chorionic villi of human placentas was determined after exposure to 0, 1, 5, or 21% O(2). Results revealed that HO activity was directly dependent on O(2) concentration. Thus, although hypoxia may increase HO protein and mRNA expression, there is a progressive decrease in HO activity with decreasing O(2) concentration and the dependence of HO activity on O(2) concentration is similar in chorionic villi from noninfarcted areas of preeclamptic and normotensive placenta.