Assessment of abuse liability and switching potential of menthol-flavored pod-based electronic nicotine delivery systems among US adults who smoke cigarettes.

BACKGROUND: Menthol-flavored electronic nicotine delivery systems (ENDS) are a focus of public health and regulatory policy considerations. The abuse liability of five menthol-flavored pod-based ENDS was compared to combustible cigarettes, and switching potential of ENDS was also evaluated. METHODS: 215 US adults who smoke cigarettes (34.4% female; mean age[SD]=29.60[8.75]; 40.9% non-Hispanic White; mean cigarettes/day[SD]=12.04[8.52]) completed a randomized 6-arm within-person cross-over product-use study. Participants used five pod-based menthol-flavored ENDS (JUUL2 Polar Menthol 1.5%, JUUL2 Prototype Fresh Menthol 3.0%, JUUL Menthol 5.0%, Vuse Alto Menthol 5.0%, NJOY Ace Menthol 5.0%) and their usual brand (UB) cigarette for 20minutes ad libitum. After each product use, subjective reinforcing effects relevant to abuse liability and associated with switching away from cigarettes (e.g., satisfaction, product liking) were assessed. RESULTS: All ENDS products were rated substantially and statistically significantly lower than UB cigarette on measures of subjective reinforcing effects (ps<0.001). Satisfying effects of JUUL2 1.5% were rated significantly higher than other ENDS products. JUUL2 Prototype 3.0% and Vuse Alto 5.0% did not significantly differ (ps>0.05), and both were rated significantly higher than JUUL 5.0% and NJOY Ace 5.0% (ps<0.05). Differences in subjective responses to study products did not significantly differ by preference for menthol cigarettes or by current ENDS use. CONCLUSIONS: Abuse liability of all menthol-flavored ENDS in this study was substantially lower than combustible cigarettes. Abuse liability of JUUL2 1.5% was within the range of currently marketed pod-based menthol-flavored ENDS products. JUUL2 1.5% likely has high potential for facilitating switching among US adults who smoke.

Comparing Adult Smokers Who Switched to JUUL versus Continuing Smokers: Biomarkers of Exposure and of Potential Harm and Respiratory Symptoms.

OBJECTIVES: Real-world evidence on exposure to harmful and potentially harmful constituents (HPHCs) and on biological effects in cigarette smokers who switch to electronic nicotine delivery systems (ENDS) can inform the health effects of switching. AIMS AND METHODS: This cross-sectional, observational study assessed adults who had smoked ≥10 cigarettes/day for ≥10 years, comparing 124 continuing cigarette smokers (Smokers) to 140 former smokers who switched to JUUL-brand ENDS exclusively for ≥6 months (Switchers). Assessments included biomarkers of exposure (BOEs) to select HPHCs, biomarkers of potential harm (BOPHs) related to smoking-related diseases, psychometric assessments of dependence on cigarettes and ENDS, respectively, and respiratory symptoms. Planned analyses compared geometric means, adjusted for demographic covariates; further analyses adjusted for additional lifestyle and smoking history covariates. RESULTS: Nicotine levels were significantly higher in Switchers (median time switched = 3 years), who were unusually heavy users of JUUL. All other BOEs, including NNAL and HPMA3 (primary endpoints), were significantly lower in Switchers than Smokers. Most BOPHs (sICAM-1 [primary], and eg, white blood cell count, MCP1, HbA1c) were significantly lower in Switchers than Smokers; HDL was significantly higher. Switchers reported significantly lower dependence on JUUL than Smokers did on cigarettes, and respiratory symptom scores were significantly lower among Switchers than Smokers. CONCLUSIONS: Compared to continuing smokers, smokers who switched to JUUL had substantially lower exposures to multiple HPHCs, favorable differences in markers of inflammation, endothelial function, oxidative stress, and cardiovascular risk, and fewer respiratory symptoms. These findings suggest that switching from cigarettes to JUUL likely reduces smokers' health risks. IMPLICATIONS: Short-term confinement studies and randomized clinical trials demonstrate that adult smokers who switch completely to ENDS experience substantial reductions in exposure to many smoking-related toxicants. This study extends those findings to longer periods of switching to JUUL-brand ENDS (almost 3 years on average) under naturalistic use conditions in real-world settings and also found that switching to JUUL resulted in favorable differences in BOPHs more proximally related to smoking-induced disease, as well as in respiratory symptoms. Smokers who switch to ENDS reduce their exposure to toxicants, likely reducing their disease risk.

Comparison of biomarkers of exposure among US adult smokers, users of electronic nicotine delivery systems, dual users and nonusers, 2018-2019.

The harm caused by cigarette smoking is overwhelmingly due to byproducts of tobacco combustion. Electronic Nicotine Delivery Systems (ENDS) provide nicotine to users without combustion, and may support tobacco harm reduction among cigarette smokers who would not otherwise quit in the near term. Analyses of Wave 5 of the Population Assessment of Tobacco and Health (PATH) Study compared biomarkers of exposure (BOE) levels for nicotine, 3 metals, 2 tobacco-specific nitrosamines and 14 smoking-related volatile organic compounds in 151 exclusive ENDS users, 1341 exclusive cigarette smokers, 115 dual users (cigarettes and ENDS), and 1846 past 30-day nonusers of tobacco, adjusting for demographics. Nicotine exposure in ENDS users and dual users did not significantly differ from smokers. Among ENDS users, 16 of 18 other BOEs were significantly lower than smokers'; 9 BOEs were not significantly different from nonusers. Among dual users smoking < 10 cigarettes/day, 15 of 18 non-nicotine BOEs were significantly lower than smokers', whereas in dual users smoking ≥ 10 cigarettes per day none of the BOEs significantly differed from smokers'. In this representative sample of US adults, exclusive use of ENDS (vs. cigarette smoking) was associated with much lower exposures to many harmful chemicals associated with smoking-related disease. BOE levels in dual users were directly related to their cigarette consumption. These BOE data provide further evidence that ENDS expose users to substantially lower levels of toxicants than combustible cigarettes, confirming their potential for harm reduction.

A New Questionnaire to Assess Respiratory Symptoms (The Respiratory Symptom Experience Scale): Quantitative Psychometric Assessment and Validation Study.

BACKGROUND: Smokers often experience respiratory symptoms (eg, morning cough), and those who stop smoking, including those who do so by switching completely to electronic nicotine delivery systems (ENDS), may experience reductions in symptoms. Existing respiratory symptom questionnaires may not be suitable for studying these changes, as they are intended for patient populations, such as those with chronic obstructive pulmonary disease (COPD). OBJECTIVE: This study aimed to develop a respiratory symptom questionnaire appropriate for current smokers and for assessing changes when smokers stop smoking. METHODS: The Respiratory Symptom Experience Scale (RSES) was derived from existing instruments and subject matter expert input and refined through cognitive debriefing interviews (n=49). Next, for purposes of the quantitative psychometric evaluation, the RSES was administered to smokers (n=202), former smokers (no tobacco use in >6 months; n=200), and switchers (n=208, smokers who switched to ENDS for >6 months), all of whom had smoked for at least 10 years (mean age 33 years). Participants, who averaged 62 (SD 12) years of age, included 28% (173/610) with respiratory allergy symptoms and 17% (104/610) with COPD. Test-retest reliability was assessed by repeat assessment after 1 week in 128 participants. RESULTS: A generalized partial credit model confirmed that the response options were ordered, and a parallel analysis using principal components confirmed that the scale was unidimensional. With allowance for 2 sets of correlated errors between pairs of items, a 1-factor graded response model fit the data. Discrimination parameters were approximately 1 or greater for all items. Scale reliability was 0.80 or higher across a broad range of severity (standardized scores -0.40 to 3.00). Test-retest reliability (absolute intraclass correlation) was good, at 0.89. RSES convergent validity was supported by substantial differences (Cohen d=0.74) between those with and without a diagnosis of respiratory disease (averaging 0.57 points, indicating that differences of this size or smaller represent meaningful differences). RSES scores also strongly differentiated those with and without COPD (d=1.52). Smokers' RSES scores were significantly higher than former smokers' scores (P<.001). Switchers' RSES scores were significantly lower than smokers' scores (P<.001) and no different from former smokers' scores (P=.34). CONCLUSIONS: The RSES fills an important gap in the existing toolkit of respiratory symptom questionnaires; it is a reliable and valid tool to assess respiratory symptoms in adult current and former smokers, including those who have switched to noncombusted nicotine products. This suggests that the scale is sensitive to respiratory symptoms that develop in smokers and to their remission when smokers quit or switch to noncombusted nicotine products intended to reduce the harm of smoking. The findings also suggest that switching from cigarettes to ENDS may improve respiratory health.

Assessment of psychological functioning in retired firefighters.

The past decade has witnessed increased clinical and investigative attention directed to the mental health of active-duty firefighters. Yet, to our knowledge, no investigations have focused on the well-being of retired firefighters, despite awareness of retirement posing significant challenges for many older adults in general, and, in particular, first responders. The purpose of this study was to (a) conduct an initial assessment of psychological functioning in 315 retired firefighters, (b) examine the relationship between overall psychological functioning and self-concept clarity (i.e., the extent to which an individual's self-concept is clearly defined, internally consistent, and temporally stable), and (c) determine whether self-concept clarity moderates and/or mediates relationships between psychological functioning and relevant demographic and personal variables. Results indicated firefighters suffer from mental health symptoms associated with psychological disorders, such as depression and posttraumatic stress disorder, at higher rates than their same-aged counterparts in the general population. Furthermore, results showed that factors like age, length of time on active duty, and length of time retired, each significantly correlated with overall psychological functioning. Finally, results suggested that self-concept clarity both mediates and moderates the association between overall psychological functioning and personal factors such as daily levels of pain, feelings of financial stability, and access to affordable health care. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Understanding heterogeneity among individuals who smoke cigarettes and vape: assessment of biomarkers of exposure and potential harm among subpopulations from the PATH Wave 1 Data.

INTRODUCTION: People who both smoke cigarettes and vape are often considered as a homogenous group even though multiple subgroups may exist. We examined biomarkers of exposure (BOE) and biomarkers of potential harm (BOPH) to differentiate between subgroups of people who smoke and vape based on PATH Study Wave 1 (2013-2014) data. METHODS: We compared people who only smoke cigarettes everyday (Group A, n = 2442) and people who only vape everyday (Group C, n = 169) against people who smoke and vape segmented into subgroups of people who frequently smoke and vape (Group B1, n = 169), frequently smoke and infrequently vape (Group B2, n = 678), frequently vape and infrequently smoke (Group B3, n = 57), and infrequently smoke and vape (Group B4, n = 66). Eighteen BOEs (representing exposure to TSNAs, nicotine, heavy metals, PAHs, and volatile organic compounds) and four BOPHs (representing inflammation and oxidative stress) were compared within the subgroups. RESULTS: Levels of many BOEs/BOPHs were higher among Group B2 relative to Groups B1, B3, and B4. Compared to Group A, many BOEs were significantly lower in Groups B3 (15/18) and B4 (17/18), and some BOEs were higher among B2 (4/18). Compared to Group C, significantly lower BOEs were observed for Group B4 (2/18). CONCLUSIONS: Overall, the levels of BOEs and BOPHs in people who smoke and vape are associated with frequency of cigarette smoking. Our findings indicate that not all people who smoke and vape are the same, and tobacco product use frequency should be considered when categorizing people who smoke and vape.

A Behavioral-Analytic Model for Assessing Stress in Firefighters.

Research has documented a number of acute and chronic stressors unique to the fire service. Due to the rise in mental health concerns in firefighters, there has been increased awareness of the negative effects of unmanaged stress. The present study employed a behavioral-analytic model to construct a brief screening measure of stress for this population: the Firefighter Assessment of Stress Test (FAST). Psychometric properties of the FAST were evaluated using data from active-duty firefighters throughout the United States. Results indicated the FAST has good internal reliability (α = 0.89), as well as good convergent and discriminant validity. Also, the factor structure of the FAST revealed three significant subscales reflective of stress associated with responding to calls, administrative difficulties, and being overworked. Scoring and interpretation guidelines were established to suggest when further assessment is warranted. The FAST offers a brief and valid method of self-assessment of current stress levels in firefighters. Information obtained from the FAST (i.e., overall stress level and domains) has the potential to facilitate more immediate identification and recognition of stress in firefighters than what has been possible to date. Moreover, heightened awareness of stress and its effects will hopefully culminate in expanded efforts directed toward stress reduction and intervention for firefighters and their families.

Comparison of Screw Quantity and Placement of Metacarpal Fracture Fixation: A Biomechanical Study.

BACKGROUND: It is recommended to have 6 bicortical screws for plate fixation of long bone fractures; however, many metacarpal fractures do not allow 6 screws due to size limitations and proximity of crucial anatomical structures. The purpose of this biomechanical study was to determine whether the mechanical properties of a 4-screw nonlocking construct are noninferior to those of a 6-screw nonlocking construct. METHODS: Metacarpal sawbones were used to simulate a midshaft, transverse fracture. Nonlocking bicortical screws were placed in the 6-hole plate, and the metacarpals were randomly assigned to 2 equal study groups: (1) 4 screws, 2 on either side of the fracture (4S); and (2) 6 screws, 3 on either side of the fracture (6S). The metacarpals were tested in a cyclic loading mode and load to failure in a cantilever bending mode. RESULTS: Maximum deflection was significantly higher for 4S compared with 6S. Cyclic root mean square (RMS) was also significantly greater for 4S at 70 and 100 N. There were no statistically significant differences observed between the 2 constructs for maximum bending load, bending stiffness, and cyclic RMS at 40 N. The maximum bending load in 4S and 6S was 245.6 ± 37.9 N and 230.8 ± 41.9 N, respectively; 4S was noninferior and not superior to 6S. Noninferiority testing was inconclusive for bending stiffness. CONCLUSIONS: A 4-screw bicortical nonlocking construct is noninferior to a 6-screw bicortical nonlocking construct for fixation of metacarpal fractures, which may be advantageous to minimize disruption of soft tissues while maintaining sufficient construct stability.

Development and validation of behavioral intention measures of an E-vapor product: intention to try, use, dual use, and switch.

BACKGROUND: The harm caused by tobacco use is primarily attributable to cigarette smoking. Switching completely to non-combustible products may reduce disease risks in adult cigarette smokers who are unable or unwilling to quit. Before a new tobacco product can enter the market or can be marketed as a modified risk tobacco product, the manufacturer must determine the impact that the product will have on the likelihood of changes in tobacco use behavior among both tobacco users and nonusers. One way to estimate change in tobacco use behavior is to assess tobacco users' and nonusers' behavioral intentions toward the product and its marketing, including intentions to try, use, dual use, and switch to the product from cigarettes. The purpose of this study was to develop and validate behavioral intention metrics appropriate for use with current, former, and never adult tobacco users. METHODS: Preliminary items were subjected to cognitive testing with adult (1) smokers planning to quit cigarettes in the next 30 days, (2) smokers not planning to quit cigarettes in the next 30 days, (3) e-vapor users, (4) former tobacco users, and (5) never tobacco users. Items were iteratively revised based on feedback during cognitive testing, and surviving items were administered to a large sample of adults (N = 2943) representing the aforementioned sub-groups. Rating scale functioning, reliability, validity, bias, and ability to detect change were evaluated. RESULTS: Examination of the response category thresholds generated by the Rasch model provided evidence that the rating scales were functioning appropriately. Results revealed good stability and excellent internal consistency and person reliability and provided evidence of unidimensionality and convergent validity. Estimates of reliability and validity were similar across sub-groups. A cross-validation sample generally confirmed findings from the validation sample. No items were discarded due to differential item function. Exploratory analyses provided support for ability to detect change. CONCLUSIONS: Results from this rigorous, empirical evaluation using large validation and cross-validation samples provide strong support for the psychometric properties of the Intention to Try, Use, Dual Use, and Switch scales with current, former, and never adult tobacco users.

Estimating the Population Health Impact of Recently Introduced Modified Risk Tobacco Products: A Comparison of Different Approaches.

INTRODUCTION: Various approaches have been used to estimate the population health impact of introducing a Modified Risk Tobacco Product (MRTP). AIMS AND METHODS: We aimed to compare and contrast aspects of models considering effects on mortality that were known to experts attending a meeting on models in 2018. RESULTS: Thirteen models are described, some focussing on e-cigarettes, others more general. Most models are cohort-based, comparing results with or without MRTP introduction. They typically start with a population with known smoking habits and then use transition probabilities either to update smoking habits in the "null scenario" or joint smoking and MRTP habits in an "alternative scenario". The models vary in the tobacco groups and transition probabilities considered. Based on aspects of the tobacco history developed, the models compare mortality risks, and sometimes life-years lost and health costs, between scenarios. Estimating effects on population health depends on frequency of use of the MRTP and smoking, and the extent to which the products expose users to harmful constituents. Strengths and weaknesses of the approaches are summarized. CONCLUSIONS: Despite methodological differences, most modellers have assumed the increase in risk of mortality from MRTP use, relative to that from cigarette smoking, to be very low and have concluded that MRTP introduction is likely to have a beneficial impact. Further model development, supplemented by preliminary results from well-designed epidemiological studies, should enable more precise prediction of the anticipated effects of MRTP introduction. IMPLICATIONS: There is a need to estimate the population health impact of introducing modified risk nicotine-containing products for smokers unwilling or unable to quit. This paper reviews a variety of modeling methodologies proposed to do this, and discusses the implications of the different approaches. It should assist modelers in refining and improving their models, and help toward providing authorities with more reliable estimates.

The impact of cigarette and e-cigarette use history on transition patterns: a longitudinal analysis of the population assessment of tobacco and health (PATH) study, 2013-2015.

BACKGROUND: Population models have been developed to evaluate the impact of new tobacco products on the overall population. Reliable input parameters such as longitudinal tobacco use transitions are needed to quantify the net population health impact including the number of premature deaths prevented, additional life years, and changes in cigarette smoking prevalence. METHODS: This secondary analysis assessed transition patterns from PATH wave 1 (2013-14) to wave 2 (2014-15) among adult exclusive cigarette smokers, exclusive e-cigarette users, and dual users. Transition probabilities were calculated by taking into account factors including cigarette smoking and e-cigarette use histories and experimental or established use behaviors. Multinomial logistic regression models were constructed to further evaluate factors associated with transition patterns. RESULTS: Differential transition probabilities emerged among study subgroups when taking into account cigarette smoking and e-cigarette use histories and experimental or established use behaviors. For example, overall 45% of exclusive e-cigarette users in wave 1 continued using e-cigarettes exclusively in wave 2. However, we observed approximately 11 to 14% of wave 1 exclusive experimental e-cigarette users continued to use e-cigarette exclusively in wave 2, compared to about 62% of exclusive established e-cigarette users. The history of cigarette smoking and e-cigarette use is another important factor associated with transition patterns. Among experimental e-cigarette users, 7.5% of individuals without a history of cigarette smoking transitioned to exclusive cigarette smoking, compared to 30% of individuals with a history of cigarette smoking. Additionally, 1.3% of exclusive cigarette smokers in wave 1 transitioned to exclusive e-cigarette use, with the highest transition probability (3.7%) observed in the established cigarette smoker with a history of e-cigarette use subgroup. CONCLUSIONS: Product use histories and current use behaviors are important factors influencing transitions between product use states. Given that experimental users' transition behaviors may be more variable and more influenced by tobacco use history, long-term predictions made by population models could be improved by the use of transition probabilities from established users. As transition patterns might be changing over time, long-term transition patterns can be examined through analysis of future waves of PATH data.

Development of a Leader Tool for Assessing and Mitigating Suicide Risk Factors.

INTRODUCTION: Despite efforts in prevention, suicide rates in the US military remain unchanged. This article describes the development of a tool for leaders to identify and mitigate suicide risk factors. METHODS: A seven-item measure, the Leader Suicide Risk Assessment Tool (LSRAT), was constructed to allow leaders to assess and mitigate suicide drivers. During a 6-mo pilot, unit leaders completed the LSRAT for 161 at-risk soldiers. The LSRAT data were compared to clinical data from a subset of these soldiers. RESULTS: The LSRAT showed good test-retest reliability. The LSRAT scores showed significant correlations with both clinical and screening measures of suicidality. Command actions mitigated or partially mitigated 89% of risk factors identified on the LSRAT. CONCLUSIONS: This study provides initial psychometric data on a tool that prescribes concrete responses to mitigate risk. The LSRAT may be a valid and feasible tool to assist front-line commanders in identifying potential area's risk mitigation. Synchronization efforts between commanders, clinicians, and support services are crucial to ensure effective intervention to prevent suicide behavior.

Smokeless tobacco mortality risks: an analysis of two contemporary nationally representative longitudinal mortality studies.

BACKGROUND: Assessments supporting smokeless tobacco (SLT) disease risk are generally decades old. Newer epidemiological data may more accurately represent the health risks associated with contemporary US-based SLT products, many of which contain lower levels of hazardous and potentially hazardous chemicals compared to previously available SLT products. METHODS: Data from two longitudinal datasets (National Longitudinal Mortality Study-NLMS, and the National Health Interview Survey-NHIS) were analyzed to determine potential associations between SLT use and/or cigarette smoking and all-cause and disease-specific mortality. Mortality hazard ratios (HR) were estimated using a Cox proportional hazards regression model applied to various groups, including never users of any tobacco or SLT product, and current and former SLT users and/or cigarette smokers. RESULTS: The two datasets yielded consistent findings with similar patterns evident for the specific causes of death measured. All-cause mortality risk for exclusive SLT users was significantly lower than that observed for exclusive cigarette smokers and dual SLT/cigarette users. Similar trends were found for mortality from diseases of the heart, chronic lower respiratory diseases, and malignant neoplasms. Mortality risk for lung cancer in exclusive cigarette smokers was increased by about 12-fold over never-tobacco users but was rarely present in exclusive SLT users in either survey (NHIS, < 5 cases/1,563 observations; NLMS, 3 cases/1,863 observations). While the data in the surveys are limited, SLT use by former cigarette smokers was not associated with an increase in the lung cancer risk HR compared to that by former cigarette smokers who never used SLT. CONCLUSIONS: Emerging epidemiological data provides a new perspective on the health risks of SLT use compared to risks associated with cigarette smoking. HR estimates derived from two current US datasets, which include data on contemporary tobacco products, demonstrate a clear mortality risk differential between modern SLT products and cigarettes. Cigarette smokers had an increased overall mortality risk and risk for several disease-specific causes of death, while SLT users consistently had lower mortality risks.

A Computational Model for Assessing the Population Health Impact of Introducing a Modified Risk Claim on an Existing Smokeless Tobacco Product.

Computational models are valuable tools for predicting the population effects prior to Food and Drug Administration (FDA) authorization of a modified risk claim on a tobacco product. We have developed and validated a population model using best modeling practices. Our model consists of a Markov compartmental model based on cohorts starting at a defined age and followed up to a specific age accounting for 29 tobacco-use states based on a cohort members transition pathway. The Markov model is coupled with statistical mortality models and excess relative risk ratio estimates to determine survival probabilities from use of smokeless tobacco. Our model estimates the difference in premature deaths prevented by comparing Base Case ("world-as-is") and Modified Case (the most likely outcome given that a modified risk claim is authorized) scenarios. Nationally representative transition probabilities were used for the Base Case. Probabilities of key transitions for the Modified Case were estimated based on a behavioral intentions study in users and nonusers. Our model predicts an estimated 93,000 premature deaths would be avoided over a 60-year period upon authorization of a modified risk claim. Our sensitivity analyses using various reasonable ranges of input parameters do not indicate any scenario under which the net benefit could be offset entirely.

A Modular Health-Related Quality of Life Instrument for Electronic Assessment and Treatment Monitoring: Web-Based Development and Psychometric Validation of Core Thrive Items.

BACKGROUND: Patient-reported outcome (PRO) measures describe natural history, manage disease, and measure the effects of interventions in trials. Patients themselves increasingly use Web-based PRO tools to track their progress, share their data, and even self-experiment. However, existing PROs have limitations such as being: designed for paper (not screens), long and burdensome, negatively framed, under onerous licensing restrictions, either too generic or too specific. OBJECTIVE: This study aimed to develop and validate the core items of a modular, patient-centric, PRO system (Thrive) that could measure health status across a range of chronic conditions with minimal burden. METHODS: Thrive was developed in 4 phases, largely consistent with Food and Drug Administration guidance regarding PRO development. First, preliminary core items (common across multiple conditions: core Thrive items) were developed through literature review, analysis of approximately 20 existing PROs on PatientsLikeMe, and feedback from psychometric and content experts. Second, 2 rounds of cognitive interviews were iteratively conducted with patients (N=14) to obtain feedback on the preliminary items. Third, core Thrive items were administered electronically along with comparator measures, including 20-item Short-Form General Health Survey (SF)-20 and Patient Health Questionnaire (PHQ)-9, to a large sample (N=2002) of adults with chronic diseases through the PatientsLikeMe platform. On the basis of theoretical and empirical rationale, items were revised or removed. Fourth, the revised core Thrive items were administered to another sample of patients (N=704) with generic and condition-specific comparator measures. A psychometric evaluation, which included both modern and classical test theory approaches, was conducted on these items, and several more items were removed. RESULTS: Cognitive interviews helped to remove confusing or redundant items. Empirical testing of subscales revealed good internal consistency (Cronbach alpha=.712-.879), test-retest reliability (absolute intraclass correlations=.749-.912), and convergent validity with legacy PRO scales (eg, Pearson r=.5-.75 between Thrive subscales and PHQ-9 total). The finalized instrument consists of a 19-item core including 5 multi-item subscales: Core symptoms, Abilities, Mobility, Sleep, and Thriving. Results provide evidence of construct (content, convergent) validity, high levels of test-retest and internal consistency reliability, and the ability to detect change over time. The items did not exhibit bias based on gender or age, and the items generally functioned similarly across conditions. These results support the use of Thrive Core items across diverse chronic patient populations. CONCLUSIONS: Thrive appears to be a useful approach for capturing important domains for patients with chronic conditions. This core set serves as a foundation to begin developing modular condition-specific versions in the near future. Cross-walking against traditional PROs from the PatientsLikeMe platform is underway, in addition to clinical validation and comparison with biomarkers. Thrive is licensed under Creative Commons Attribution ShareAlike 4.0.

Measurement of Quality of Life in Patients with Mycosis Fungoides/Sézary Syndrome Cutaneous T-Cell Lymphoma: Development of an Electronic Instrument.

BACKGROUND: Although the quality of life (QoL) plays an important role in treatment decision making and clinical management of mycosis fungoides (MF) or Sézary syndrome (SS) subtypes of cutaneous T-cell lymphomas (MF/SS-CTCLs), an MF- or SS-specific measure of QoL does not exist. OBJECTIVE: The objective of this research was to develop and validate the first QoL instrument for MF/SS-CTCL using a patient-centered approach. METHODS: A conceptual framework for the MF/SS-CTCL QoL was developed through a literature review and interviews with key opinion leaders. Concept elicitation with patients was utilized to refine the conceptual model and generate preliminary items. The items were then revised based on qualitative and quantitative feedback obtained through cognitive debriefing surveys and interviews with patients. Next, participants (N=126) completed the preliminary MF/SS-CTCL QoL and a comparator measure of health-related QoL (Skindex-29) through the PatientsLikeMe Open Research Exchange. The MF/SS-CTCL QoL was completed again 5 days later by 66 participants for the purposes of evaluating test-retest reliability. The MF/SS-CTCL QoL was finalized based on results from an empirical evaluation, which included both classical and modern test theory approaches. Specifically, this included evaluation of (1) the optimal item response theory measurement model; (2) item fit; (3) unidimensionality; (4) rating scale performance; (5) reliability; (6) test information (precision); (7) person-to-item map; (8) convergent and discriminant validity; and (9) presence of bias via differential item function. RESULTS: Results from the comprehensive psychometric evaluation utilizing a Rasch-Grouped Rating Scale model yielded a final 12-item instrument. The rating scale functioned as expected, and the instrument exhibited adequate person reliability (.87), good to excellent test-retest reliability (r=.89, P<.001), high levels of measurement precision, and good person-to-item targeting. The correlation between the MF/SS-CTCL QoL and the Skindex-29 (r=.852, P<.001) was significantly greater than the correlation between the MF/SS-CTCL QoL and syndrome stage (r=.260, P<.001), providing support for convergent and discriminant validity. Items did not show significant bias based on gender, age, or race. Rasch scores were converted to scaled scores with qualitative descriptive categories for ease of interpretation. CONCLUSIONS: Empirical evaluation demonstrated strong evidence of excellent psychometric properties. Utilizing a patient-centered measure development approach ensures that this QoL instrument captures the information that is most meaningful and clinically relevant to patients.

Development of a Brief Version of the Current Opioid Misuse Measure (COMM): The COMM-9.

Objective: The Current Opioid Misuse Measure (COMM) is a commonly used self-report instrument to identify and monitor aberrant opioid-related behavior in chronic pain patients on opioid therapy. However, the length of the COMM may limit its clinical utility. Additionally, this paper-and-pencil screener requires hand scoring, which increases paperwork and staff burden. Therefore, the current study presents development of the "COMM-9," a brief electronically administered form of the COMM. Methods: Patients (N = 517) with chronic noncancer pain on opioid therapy completed the COMM. Patients were classified as either being positive or negative for aberrant drug-related behavior based on self-report data from a structured interview, physician-report data, and urine toxicology screen (the Aberrant Drug Behavior Index [ADBI]). COMM items with the strongest classification accuracy were identified using the LASSO method as the selection criterion in conjunction with the leave-one-out cross-validation method as the stop criterion. A sub-set of patients (n=55) completed a second administration of the COMM one week later to evaluate test-retest reliability. Results: Nine items were identified before the selection criterion stopped, and logistic regression was utilized to predict probabilities of positive ADBI from the 9 COMM items using all data and the cross-validation procedure. Receiver operating characteristic curves revealed high levels of classification accuracy that were essentially equivalent to the full COMM. Cut-points were identified to classify patients as having no/low risk, moderate risk, and high risk for aberrant opioid-related behavior. Test-retest reliability of the COMM-9 was comparable to the full 17-item COMM. Conclusions: This study presents the successful development of a brief electronic screener to identify current aberrant opioid-related behavior in chronic pain patients on long-term opioid therapy.

Osteogenic Sarcoma in an Adolescent With Cystic Fibrosis: Successful Treatment Despite Significant Obstacles.

Introduction: We describe the case of a 16-year old male with cystic fiborosis (CF) who presented with an osteosarcoma of his right distal tibia. Case Report: Treatment consisted of neoadjuvant chemotherapy of cisplatin, doxorubicin and high dose methotrexate followed by distal tibial resection and free fibula flap reconstruction and consolidation chemotherapy. Treatment was complicated by a pulmonary exacerbation, where Pseudomonas aeruginosa (PsA) and Staphylococcus aureus were grown on sputum culture which was treated with a 2-week course of intravenous piptazobactam and tobramycin. Mycobacterium intracellulare and Mycobacterium abscessus were also cultured following commencement of chemotherapy and successfully treated with a 6-month course of oral azithromycin, ethambutol, and moxifloxacin along with a 1-month course of inhaled amikacin. Pulmonary function improved during his treatment from baseline FEV1 of 3.8 l (93.9%) to 4.15 l (102.3% predicted) whilst nutritional status remained stable. Discussion: The combination of CF and osteosarcoma is rare with only one previous case reported (1). Our case is instructive as the patient faced the challenge of chronic PsA and the first reported culturing and successful treatment of non-tuberculous mycobacterium (NTM) during chemotherapy. Fatal outcomes have been reported previously for CF patients during immunosuppression (2). In concordance with our findings, a recent report noted an improvement in respiratory function in a child treated for leukemia (3). The anti-inflammatory nature of some chemotherapy agents could be responsible for the observed clinical improvement in CF with low dose methotrexate having been shown to increase FEV1 in adolescents with advanced CF (4). Whilst doxorubicin could improve pulmonary outcomes through increased total cellular CFTR protein expression and CFTR associated chloride secretion (5). It is hypothesized that the improved pulmonary function in patients with CF who require chemotherapy could be due to increased production of Multi-Drug Resistance Proteins (MDR) and Multi-Drug Resistant Associated Proteins (MRP) that may complement the depleted CFTR protein (6). Concluding Remarks: We report the well-tolerated management of osteosarcoma in a patient with CF including the first reported identification and eradication of NTM during chemotherapy. The observed positive pulmonary outcome following chemotherapy highlights several potential cellular mechanisms that deserve to be explored.

Evaluation of the Relative Abuse of an OROS Extended-release Hydromorphone HCI Product: Results From 3 Postmarket Surveillance Studies.

OBJECTIVE: Formulating prescription opioids to limit abuse remains a priority. OROS extended-release (ER) hydromorphone HCl (EXALGO) may have lower abuse potential than many other opioid products. Three postmarketing studies of the relative abuse liability of OROS hydromorphone ER were conducted. METHODS: Estimates of abuse, unadjusted, and adjusted for prescription volume, were generated for OROS hydromorphone ER and comparators from Q2 2010 through Q2 2014 for a high-risk, substance abuse treatment population and the general population using poison control center data. Comparators were selected for compound, market penetration, and route of administration (ROA) profile. ROA comparisons were made among the substance abuse treatment population. Internet discussion was examined to determine abusers' interest in and desire for the OROS formulation. RESULTS: Examination of abuse prevalence among adults within substance abuse treatment, intentional poison exposures, and Internet discussion levels generally support the hypothesis that OROS hydromorphone ER may have lower abuse potential than many other opioid products. OROS hydromorphone ER also seems to be abused less often by alternate ROAs (eg, snorting and injection). Lower levels of online discussion were observed along with relatively low endorsement for abuse. DISCUSSION: Abuse of OROS hydromorphone ER was observed in high-risk substance abuse and general population samples but at a very low relative prevalence compared to comparators. Evidence suggests it may be less often abused by alternate ROAs than some comparators. Online data did not find evidence of high levels of desire for OROS hydromorphone ER by recreational abusers. Continued monitoring of this product's abuse liability is warranted.

Psychometric evaluation of the PainCAS Interference with Daily Activities, Psychological/Emotional Distress, and Pain scales.

PURPOSE: The PainCAS is a web-based clinical tool for assessing and tracking pain and opioid risk in chronic pain patients. Despite evidence for its utility within the clinical setting, the PainCAS scales have never been subject to psychometric evaluation. The current study is the first to evaluate the psychometric properties of the PainCAS Interference with Daily Activities, Psychological/Emotional Distress, and Pain scales. METHODS: Patients (N = 4797) from treatment centers and hospitals in 16 different states completed the PainCAS as part of routine clinical assessment. A subsample (n = 73) from two hospital-based treatment centers also completed comparator measures. Rasch Rating Scale Models were employed to evaluate the Interference with Daily Activities and Psychological/Emotional Distress scales, and empirical evaluation included assessment of dimensionality, discrimination, item fit, reliability, information, and person-to-item targeting. Additionally, convergent and discriminant validity were evaluated through classical test theory approaches. Convergent validity of the Pain scales was evaluated through correlations with corresponding comparator items. RESULTS: One Interference with Daily Activities item was removed due to poor functioning and discrimination. The retained items from the Interference with Daily Activities and Psychological/Emotional Distress scales conformed to unidimensional Rasch measurement models, yielding satisfactory item fit, reliability, precision, and coverage. Further, results provided support for the convergent and discriminant validity of these two scales. Convergent validity between the PainCAS Pain and BPI Pain items was also strong. CONCLUSION: Taken together, results provide strong psychometric support for these PainCAS Pain scales. Strengths and limitations of the current study are discussed.