Estimating human pharmacokinetic parameters forelectronic nicotine delivery system products from chemical analyses of their aerosols.

The ability of Electronic Nicotine Delivery Systems (ENDS) to deliver nicotine is central to their function to substitute for cigarettes, allowing people who smoke to switch away from smoking, thus reducing their exposure to harmful chemicals in cigarette smoke. The nicotine concentration in ENDS e-liquid has proved to be a poor predictor of nicotine uptake in users. Using meta-analytic methods to analyze 12 pharmacokinetic studies of nicotine-salt closed-system ENDS, this paper examines whether the mass of nicotine/puff of aerosol can predict Cmax in pharmacokinetic studies. Cmax values were available for 38 products, in 58 use conditions (including both controlled [3 s] and ad libitum puffing), comprising 1769 participant observations. Nicotine/puff data reflected chemical analyses of aerosol obtained under nonintense (3 s) or intense (6 s) machine puffing. Meta-regression analyses (weighted by reliability of Cmax estimate) assessed the relationship of nicotine/puff to Cmax. In some models, empirical data were used to impute the variation in Cmax or the nicotine/puff value under intense puffing. In simple linear models, Cmax was significantly associated with nicotine/puff under all combinations of intense/nonintense and controlled/ad-libitum conditions, with R2 values of 0.71-0.77. More complex models based on quadratic effects or log[nicotine/puff] did not generally improve upon more parsimonious linear models. Application of the model illustrates the divergence between nicotine concentration in e-liquids and expected Cmax when other ENDS parameters vary. The meta-analytic model may have utility in settings where clinical pharmacokinetic data are not available, including product development.

A Practical Framework for Novel Electronic Nicotine Delivery System Evaluation: Chemical and Toxicological Characterization of JUUL2 Aerosol and Comparison with Reference Cigarettes.

Electronic nicotine delivery systems (ENDSs) are designed as a non-combustible alternative to cigarettes, aiming to deliver nicotine without the harmful byproducts of tobacco combustion. As the category evolves and new ENDS products emerge, it is important to continually assess the levels of toxicologically relevant chemicals in the aerosols and characterize any related toxicology. Herein, we present a proposed framework for characterizing novel ENDS products (i.e., devices and formulations) and determining the reduced risk potential utilizing analytical chemistry and in vitro toxicological studies with a qualitative risk assessment. To demonstrate this proposed framework, long-term stability studies (12 months) analyzing relevant toxicant emissions from six formulations of a next-generation product, JUUL2, were conducted and compared to reference combustible cigarette (CC) smoke under both non-intense and intense puffing regimes. In addition, in vitro cytotoxicity, mutagenicity, and genotoxicity assays were conducted on aerosol and smoke condensates. In all samples, relevant toxicants under both non-intense and intense puffing regimes were substantially lower than those observed in reference CC smoke. Furthermore, neither cytotoxicity, mutagenicity, nor genotoxicity was observed in aerosol condensates generated under both intense and non-intense puffing regimes, in contrast to results observed for reference cigarettes. Following the proposed framework, the results demonstrate that the ENDS products studied in this work generate significantly lower levels of toxicants relative to reference cigarettes and were not cytotoxic, mutagenic, or genotoxic under these in vitro assay conditions.

Determination of chemical constituent yields in e-cigarette aerosol using partial and whole pod collections, a comparative analysis.

Literature reports the chemical constituent yields of electronic nicotine delivery systems (ENDS) aerosol collected using a range of aerosol collection strategies. The number of puffs to deplete an ENDS product varies widely, but collections often consist of data from the first 50-100 puffs. However, it is not clear whether these discrete puff blocks are representative of constituent yields over the life of a pod. We aimed to assess the effect of differing aerosol collection strategies on reported yields for select chemical constituents in the aerosol of closed pod-based ENDS products. Constituents analyzed were chosen to reflect important classes of compounds from the Final Premarket Tobacco Product Application Guidance. Yields were normalized to total device mass loss (DML). Collection strategies that consisted of partial pod collection were valid for determining yields of constituents whose DML normalized yields were consistent for the duration of pod life. These included primary aerosol constituents, such as propylene glycol, glycerol, and nicotine, and whole pod yields could be determined from initial puff blocks. However, changes were observed in the yields of some metals, some carbonyl compounds, and glycidol over pod life in a chemical constituent and product dependent manner. These results suggest that collection strategies consisting of initial puff block collections require validation per chemical constituent/product and are not appropriate for chemical constituents with variable yields over pod life. Whole pod collection increased sensitivity and accuracy in determining metal, carbonyl, and glycidol yields compared to puff block-based collection methodologies for all products tested.

A 10-year retrospective cohort study of the management of toxic epidermal necrolysis and Stevens-Johnson syndrome in a New South Wales state referral hospital from 2006 to 2016.

IMPORTANCE: Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are life-threatening severe cutaneous drug reactions. There have been no Australian data published since 2007. OBJECTIVE: To explore whether there is an association between prognosis and the type of systemic immune-modulation treatment administered in a cohort of patients with SJS, SJS-TEN overlap, and TEN at the New South Wales State SJS/TEN referral center - Concord Repatriation General Hospital. METHODS: This is a retrospective, single center, cohort study of patients admitted with SJS/TEN from January 1, 2006, to December 31, 2016, at Concord Repatriation General Hospital. Data on demographic information, the causative agent, treatment, and final survival outcome were analyzed. RESULTS: Forty-two patients included: 26 (62%) with TEN, six (14%) with SJS/TEN overlap, and 10 (24%) with SJS. Overall mortality was 19% (n = 8), and seven suffered TEN. The average age of those who died was 60 years. Eighty-one percent of patients were managed within the burn unit. Twenty-nine patients (70%) received IVIG within this group; 13 individuals also received systemic corticosteroids. Seven (17%) were managed with corticosteroid therapy alone. The incidence of death was 0% in the combined IVIG and corticosteroid group. CONCLUSION: This series of 42 patients contributes valuable information to a serious condition with low global incidence and high mortality. There appears to be an apparent reduced mortality in the group of SJS/TEN patients managed with combined IVIG and corticosteroid. Larger cohorts are required to validate this relationship due to the risk of bias inherent to the retrospective study design and small sample size.

Female pattern hair loss.

BACKGROUND: Female pattern hair loss (FPHL) is a commonly encountered clinical presentation in primary care. Patterned hair loss in women is characterised by diffuse hair thinning and often becomes an ongoing cause of psychosocial distress. OBJECTIVE: The aim of this article is to present a practical approach for the clinical assessment of female hair loss and to review the up-to-date treatment modalities. DISCUSSION: Alopecia can be the first symptom of systemic illness. It is therefore crucial for the primary care physician to be able to differentiate between FPHL and more concerning causes of hair loss. Treatment options often involve a combination of non-androgenic and androgenic therapy. The use of oral minoxidil in combination with oral spironolactone is a novel therapy with promising results. The role of the general practitioner is paramount in establishing the diagnosis, setting achievable therapeutic goals and navigating the psychosocial comorbidity associated with this chronic condition.

Acral pseudolymphomatous angiokeratoma of children (APACHE).

13-year-old girl presented with a 10-year history of multiple discrete red firm papules situated on her right upper arm. The histopathology examination revealed a massive subepidermal lymphohistiocytic infiltrate, consistent with acral pseudolymphomatous angiokeratoma of children. Treatment with topical application of mometasone furoate 0.1% cream once daily for 6 months improved the lesions partially. However, these papules returned to their pretreatment appearance and consistency within 6 months after the cessation of the topical corticosteroid. The authors prefer the term 'papular angiolymphoid hyperplasia' for this entity, based on the absence of histological angiokeratomatous features, the benign nature of the lesion and the previously reported cases from adults and non-acral sites.