Sensory methods to evaluate perception of flavours in tobacco and other nicotine-containing products: a review.

OBJECTIVES: Sensory methods use human senses to evaluate product attributes. This review provides an overview of the types of sensory methods used to evaluate the perception of flavour in tobacco and other nicotine-containing (ToNic) products and to discuss how sensory data could inform flavoured ToNic product policy. DATA SOURCES: PubMed, Embase and Web of Science. STUDY SELECTION: All peer-reviewed studies evaluating ToNic products using a sensory method published before 23 May 2020. DATA EXTRACTION: Two independent coders completed title/abstract and full-text screening to choose articles for inclusion (Cohen's kappa=0.85, strong agreement). Each coder completed data extraction on half the articles, recording relevant information (eg, sensory methods used, results). The coders categorised sensory methods and generated overarching themes. DATA SYNTHESIS: Of 110 articles identified, we included 29 articles containing 35 studies that used sensory methods to investigate ToNic products. The sensory methods included analytic methods such as discrimination and descriptive tests and hedonic methods such as liking tests. Six themes emerged regarding how sensory methods can be used to understand consumer perception and liking of ToNic products and to inform ToNic product policy. CONCLUSIONS: The identified studies highlight that sensory data can inform ToNic product policy. Analytic and sensory hedonic ratings can be used to assess a ToNic product's ability to promote addiction in the user (ie, abuse liability). Lastly, hedonic ratings can provide information to assess potential use behaviours.

Exploring the potential neurotoxicity of vaping vitamin E or vitamin E acetate.

Serious adverse health effects have been reported with the use of vaping products, including neurologic disorders and e-cigarette or vaping product use-associated lung injury (EVALI). Vitamin E acetate, likely added as a diluent to cannabis-containing products, was linked to EVALI. Literature searches were performed on vitamin E and vitamin E acetate-associated neurotoxicity. Blood brain barrier (BBB) penetration potential of vitamin E and vitamin E acetate were evaluated using cheminformatic techniques. Review of the literature showed that the neurotoxic potential of inhalation exposures to these compounds in humans is unknown. Physico-chemical properties demonstrate these compounds are lipophilic, and molecular weights indicate vitamin E and vitamin E acetate have the potential for BBB permeability. Computational models also predict both compounds may cross the BBB via passive diffusion. Based on literature search, no experimental nonclinical studies and clinical information on the neurotoxic potential of vitamin E via inhalation. Neurotoxic effects from pyrolysis by-product, phenyl acetate, structurally analogous to vitamin E acetate, suggests vitamin E acetate has potential for central nervous system (CNS) impairment. Cheminformatic model predictions provide a theoretical basis for potential CNS permeability of these inhaled dietary ingredients suggesting prioritization to evaluate for potential hazard to the CNS.

Electronic nicotine delivery systems: overheating, fires and explosions.

BACKGROUND: Electronic nicotine delivery system (ENDS)-associated overheating, fire or explosion (OH/F/EXP) events have occurred since at least 2009. OBJECTIVE: To identify the number and nature of ENDS OH/F/EXP events in the USA. METHODS: Center for Tobacco Products (CTP) scientists searched for event reports among five US federal agencies, scientific literature and media outlets. FINDINGS: 100 reference sources identified 92 OH/F/EXP events in the USA, of which 45 (49%) injured 47 people, and 67 (73%) involved property damage beyond the product. Events were identified in media outlets (n=50; 54%) and reported to four agencies (n=42; 46%). The report rate peaked at an average of six reports per month in late 2013 with a smaller peak of three to four reports per month in the second quarter of 2015. All reports were incomplete and events exhibited variability. International events in three countries are mentioned, and international responses to events are summarised. CONCLUSIONS: The scope, causes and trajectory of ENDS OH/F/EXP events remain incompletely defined. Some events have resulted in life-threatening injury, permanent disfigurement or disability, and major property damage, suggesting the need for ongoing surveillance and risk mitigation. More comprehensive reporting could assist future analyses and may help to identify root causes and contributors to the OH/F/EXP events.

Early responses to adenoviral-mediated transfer of the aquaporin-1 cDNA for radiation-induced salivary hypofunction.

No conventional therapy exists for salivary hypofunction in surviving head and neck cancer patients with Radiation Therapy Oncology Group late grade 2-3 toxicity. We conducted a phase I clinical trial to test the safety and biologic efficacy of serotype 5, adenoviral-mediated aquaporin-1 cDNA transfer to a single previously irradiated parotid gland in 11 subjects using an open label, single-dose, dose-escalation design (AdhAQP1 vector; four dose tiers from 4.8 × 10(7) to 5.8 × 10(9) vector particles per gland). Treated subjects were followed at scheduled intervals. Multiple safety parameters were measured and biologic efficacy was evaluated with measurements of parotid salivary flow rate. Symptoms were assessed with a visual analog scale. All subjects tolerated vector delivery and study procedures well over the 42-d study period reported. No deaths, serious adverse events, or dose-limiting toxicities occurred. Generally, few adverse events occurred, and all were considered mild or moderate. No consistent changes were found in any clinical chemistry and hematology parameters measured. Objective responses were seen in six subjects, all at doses <5.8 × 10(9) vector particles per gland. Five of these six subjects also experienced subjective improvement in xerostomia. AdhAQP1 vector delivery to a single parotid gland was safe and transfer of the hAQP1 cDNA increased parotid flow and relieved symptoms in a subset of subjects.

Electronic cigarettes: incorporating human factors engineering into risk assessments.

OBJECTIVE: A systematic review was conducted to evaluate the impact of human factors (HF) on the risks associated with electronic cigarettes (e-cigarettes) and to identify research gaps. HF is the evaluation of human interactions with products and includes the analysis of user, environment and product complexity. Consideration of HF may mitigate known and potential hazards from the use and misuse of a consumer product, including e-cigarettes. METHODS: Five databases were searched through January 2014 and publications relevant to HF were incorporated. Voluntary adverse event (AE) reports submitted to the US Food and Drug Administration (FDA) and the package labelling of 12 e-cigarette products were analysed. RESULTS: No studies specifically addressing the impact of HF on e-cigarette use risks were identified. Most e-cigarette users are smokers, but data on the user population are inconsistent. No articles focused specifically on e-cigarette use environments, storage conditions, product operational requirements, product complexities, user errors or misuse. Twelve published studies analysed e-cigarette labelling and concluded that labelling was inadequate or misleading. FDA labelling analysis revealed similar concerns described in the literature. AE reports related to design concerns are increasing and fatalities related to accidental exposure and misuse have occurred; however, no publications evaluating the relationship between AEs and HF were identified. CONCLUSIONS: The HF impacting e-cigarette use and related hazards are inadequately characterised. Thorough analyses of user-product-environment interfaces, product complexities and AEs associated with typical and atypical use are needed to better incorporate HF engineering principles to inform and potentially reduce or mitigate the emerging hazards associated with e-cigarette products.

Implementing the SOHN-endorsed AORN guidelines for reprocessing reusable upper airway endoscopes.

This is a companion paper to two previous publications on recommended practices for cleaning and reprocessing flexible endoscopes used in Otolaryngology (Burlingame, Arcilla, & McDermott, 2008; Adams & Baker, 2010). In this paper we capture and expand upon the audience question and answer session in which the Society of Otorhinolaryngology and Head-Neck Nurse (SOHN)--endorsed the Association of periOperative Registered Nurses (AORN) recommended practices were presented to the SOHN membership (Adams & Waddington, September, 2010). We include additional background information to assist readers in understanding some of the science behind the recommendations and share successful implementation strategies from Otorhinolaryngology (ORL) outpatient nurses and published references.

Factors associated with changes in flavored tobacco products used: Findings from wave 2 and wave 3 (2014-2016) of the population assessment of tobacco and health (PATH) study.

INTRODUCTION: Flavored non-cigarette tobacco product use is widespread in the U.S. The availability of flavor options could be playing a role in recent increases in use, especially for non-cigarette tobacco products, among youth and young adults. Little is known about specific flavor preferences of youth and adult flavored tobacco product users, as well as how preferences may change over time. METHODS: This study analyzes PATH Study data from completed Wave 2 (2014-2015) and Wave 3 (2015-2016) youth (12-17 years), and adult (18 + years) interviews to estimate the prevalence of flavored non-cigarette tobacco product use. We assess flavor switching by examining changes between flavors and characteristics of those who changed flavors between waves. RESULTS: Across age groups, and at both waves, fruit-flavored products were the most frequently used flavor by past 30-day electronic nicotine delivery systems (ENDS), cigar, cigarillo, and hookah users. In the past 30 days, a higher proportion of youth and young adults used candy/sweets-flavored ENDS than adults. Among adult ENDS users, the odds of changing flavors were highest among younger users and decreased with increasing age. CONCLUSIONS: Flavored tobacco product use is prevalent across non-cigarette tobacco products. Stability in the number of flavors used, as well as specific flavors, is higher among adult tobacco users, while the use of multiple flavors, and change in specific flavor, is more prevalent among youth tobacco users. Additional longitudinal research can further examine the role flavors play in appeal, product trial, and switching.

Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen.

Gene therapy of human cancer using genetically engineered lymphocytes is dependent on the identification of highly reactive T-cell receptors (TCRs) with antitumor activity. We immunized transgenic mice and also conducted high-throughput screening of human lymphocytes to generate TCRs highly reactive to melanoma/melanocyte antigens. Genes encoding these TCRs were engineered into retroviral vectors and used to transduce autologous peripheral lymphocytes administered to 36 patients with metastatic melanoma. Transduced patient lymphocytes were CD45RA(-) and CD45RO(+) after ex vivo expansion. After infusion, the persisting cells displayed a CD45RA(+) and CD45RO(-) phenotype. Gene-engineered cells persisted at high levels in the blood of all patients 1 month after treatment, responding patients with higher ex vivo antitumor reactivity than nonresponders. Objective cancer regressions were seen in 30% and 19% of patients who received the human or mouse TCR, respectively. However, patients exhibited destruction of normal melanocytes in the skin, eye, and ear, and sometimes required local steroid administration to treat uveitis and hearing loss. Thus, T cells expressing highly reactive TCRs mediate cancer regression in humans and target rare cognate-antigen-containing cells throughout the body, a finding with important implications for the gene therapy of cancer. This trial was registered at www.ClinicalTrials.gov as NCI-07-C-0174 and NCI-07-C-0175.

Adverse Experience Reports of Seizures in Youth and Young Adult Electronic Nicotine Delivery Systems Users.

PURPOSE: Electronic nicotine delivery systems (ENDS) use poses significant and avoidable health risks to young people. Until recently, seizures were most often associated with cases of liquid nicotine ingestion. METHODS: We examined 122 voluntary reports of seizures (n = 114) and neurological symptoms (syncope, n = 7; and tremor, n = 1) in 123 ENDS users (one report contained information on two users) received by the Food and Drug Administration between December 1, 2010, and June 30, 2019. RESULTS: The median age (interquartile range) of users was 20 years (17-27); 67% of reports were in youth and young adults aged 14-24 years. Fifty-one (41%) reported other underlying medical conditions, including previous history of anxiety (n = 11), attention deficit hyperactivity disorder (n = 7), seizure (n = 6), and depression (n = 5). Of the 79 reports with available information, 67 (85%) reported seizure occurred within 24 hours of last use; 49 (62%) reported seizure within 30 minutes. The potential impact of concomitant use of marijuana or cannabidiol oil could not be evaluated from the eight reports that mentioned concomitant use. CONCLUSIONS: Findings suggest an association between ENDS use and seizures. Additional information will help to clarify the relationship between ENDS use and seizures and to understand how product attributes such as nicotine content, formulation, quantity, and other ingredients or contaminants may contribute to seizures. It is important that health care providers ask about ENDS use when evaluating neurological symptoms and that users, parents, school personnel, and health care providers report adverse experiences involving tobacco products to Food and Drug Administration via the Safety Reporting Portal (www.safetyreporting.hhs.gov).

The sounds of handheld audio players.

Hearing experts and public health organizations have longstanding hearing safety concerns about personal handheld audio devices, which are growing in both number and popularity. This paper reviews the maximum sound levels of handheld compact disc players, MP3 players, and an iPod. It further reviews device factors that influence the sound levels produced by these audio devices and ways to reduce the risk to hearing during their use.

Coding and insurance coverage for tobacco cessation services.

Tobacco cessation intervention is a primary therapy for treating many conditions encountered in an otolaryngology practice. This paper presents the latest billing, coding, and insurance information to use in providing tobacco cessation services. It further guides the appropriate applications of these codes to patient encounters.

Inhibition of nuclear factor-kappaB and target genes during combined therapy with proteasome inhibitor bortezomib and reirradiation in patients with recurrent head-and-neck squamous cell carcinoma.

PURPOSE: To examine the effects the proteasome inhibitor bortezomib (VELCADE) on transcription factor nuclear factor-kappaB (NF-kappaB) and target genes and the feasibility of combination therapy with reirradiation in patients with recurrent head-and-neck squamous cell carcinoma (HNSCC). METHODS AND MATERIALS: The tolerability and response to bortezomib 0.6 mg/m2 and 0.9 mg/m2 given twice weekly concurrent with daily reirradiation to 50-70 Gy was explored. Blood proteasome inhibition and NF-kappaB-modulated cytokines and factors were measured. Proteasome inhibition, nuclear localization of NF-kappaB phospho-p65, apoptosis, and expression of NF-kappaB-modulated mRNAs were compared in serial biopsies from accessible tumors. RESULTS: The maximally tolerated dose was exceeded, and study was limited to 7 and 2 patients, respectively, given bortezomib 0.6 mg/m2 and 0.9 mg/m2/dose with reirradiation. Grade 3 hypotension and hyponatremia were dose limiting. Mucositis was Grade 3 or less and was delayed. The mean blood proteasome inhibition at 1, 24, and 48 h after 0.6 mg/m2 was 32%, 16%, and 7% and after 0.9 mg/m2 was 56%, 26%, and 14%, respectively. Differences in proteasome and NF-kappaB activity, apoptosis, and expression of NF-kappaB-modulated cell cycle, apoptosis, and angiogenesis factor mRNAs were detected in 2 patients with minor tumor reductions and in serum NF-kappaB-modulated cytokines in 1 patient with a major tumor reduction. CONCLUSIONS: In combination with reirradiation, the maximally tolerated dose of bortezomib was exceeded at a dose of 0.6 mg/m2 and the threshold of proteasome inhibition. Although this regimen with reirradiation is not feasible, bortezomib induced detectable differences in NF-kappaB localization, apoptosis, and NF-kappaB-modulated genes and cytokines in tumor and serum in association with tumor reduction, indicating that other schedules of bortezomib combined with primary radiotherapy or reirradiation may merit future investigation.

Randomized, double-blind, placebo-controlled phase IIb trial of the cyclooxygenase inhibitor ketorolac as an oral rinse in oropharyngeal leukoplakia.

PURPOSE: Nonselective cyclooxygenase (COX) inhibitors have been reported to decrease the frequency of upper aerodigestive cancers. Ketorolac tromethamine oral rinse has been shown to resolve another COX-dependent process, periodontal disease, without incurring gastrointestinal side effects. This trial evaluated if a topically delivered oral rinse containing ketorolac was as safe as and more effective than oral rinse alone in reducing the area of oral leukoplakia. EXPERIMENTAL DESIGN: 57 patients were randomized (2:1 ratio) in a double-blind, placebo-controlled study of ketorolac (10 ml of a 0.1% ketorolac rinse solution; n = 38) or placebo (10 ml of rinse solution; n = 19) given twice daily for 30 s over 90 days. Primary end point was evaluated visually obtaining bidimensional measurement of the size of leukoplakia lesion(s) at entry and at 90 days. Secondary end point was histological assessment of the leukoplakia as sampled by serial punch biopsy and independently reviewed by three pathologists. RESULTS: The patients included 67% males, 11% non-Caucasian, and 86% used tobacco with no significant differences between the two arms. Both rinses were well tolerated with good compliance, and there was no significant difference in adverse events (P = 0.27). Major response rate (complete response and partial response) was 30% for ketorolac and 32% for the placebo arm. There was no significant difference in change in histology between the two arms. CONCLUSION: Local delivery of a COX-containing oral rinse was well tolerated but produced no significant reduction in the extent of leukoplakia compared with the placebo. However, the favorable response rate to placebo arm remains unexplained and additional investigation of the tissue penetration with ketorolac is warranted.

SOHN 2002 Web-based membership survey: results, analysis and recommendations.

In March, 2002, the Society of Otorhinolaryngology and Head-Neck Nurses, Inc. (SOHN) conducted a web-based survey of members' knowledge of and satisfaction with its portfolio of products and services. This paper reports on the process of developing and conducting the survey, as well as its findings. A new "Volunteer Agreement/Code of Conduct", piloted for this team's work is introduced. General and specific recommendations are put forth for SOHN members and leaders, including useful information to facilitate work for future survey teams.

Impact of tracheostomy or laryngectomy on spousal and caregiver relationships.

Caregiving is an important component in the management of patients with a tracheostomy or laryngectomy. The purpose of this integrative research literature review was to gain a better understanding of the impact of caregiving for adults and children with laryngectomy or tracheostomy on the patient, the family, and the caregiver. Patients who had undergone laryngectomy or tracheostomy included those with and without cancer. This integrated review of the literature on caregiving in this population demonstrates the dearth of studies on this subject. Despite the significance of the caregiving role, few studies have addressed caregiving, and those that have are primarily descriptive. Studies are needed that develop and test interventions to assist caregivers in adaptation to their role, identification of methods of decreasing caregiver burden and strain, and coordination of resources to support patients and caregivers of patients with tracheostomies and laryngectomies.