Urgent use of voxelotor in sickle cell disease when immediate transfusion is not safe.

The use of blood transfusions to improve anemia resulting from sickle cell disease (SCD) is often limited by alloimmunization, which occurs due to exposure to incompatible antigen present on donor red blood cells (RBCs). This complication occasionally manifests as delayed hemolytic transfusion reactions (DHTRs) that cause hemolysis of the recipient's own RBCs and can lead to fatal anemia. In this case study, we report a patient with SCD who experienced a DHTR following chronic transfusion and was successfully treated with voxelotor, an orally administered sickle hemoglobin (HbS) polymerization inhibitor for the treatment of SCD. Laboratory tests following admission indicated pan-reactivity in antigens, and a rare donor registry was used to locate acceptable units. The patient experienced the DHTR 3 days after admission, which limited laboratory tests due to profound hemolysis. Alternative treatments were limited, and phenotypically matched units were incompatible, so voxelotor was selected as a last-resort treatment. Following initiation of voxelotor 1500 mg, the patient's hemoglobin levels returned to baseline (6 g/dl) within 10 days, with clinical improvements. This report provides evidence regarding the use of voxelotor in the treatment of profound anemia where other treatments could be unsafe or unavailable.

Lessons Learned from Building a Pediatric-to-Adult Sickle Cell Transition Program.

OBJECTIVE: More effective transitions and transfers of young people with sickle cell disease (SCD) into the adult healthcare setting is a focus of both primary care and specialty care medical organizations. Effective transition and transfer requires six core elements: establishing a policy, tracking progress, administering transition readiness assessments, planning for adult care, transferring to adult care, and integrating into an adult practice. We developed a program using these six core elements. The objective of our report was to assess the development and implementation of this program. METHODS: We used the six core elements to develop and implement a program at Virginia Commonwealth University for children and adolescents with SCD to transition to adult health care. RESULTS: We assessed individuals' differences by age and grade, their independent living skills, their feelings about moving to adult care; tallied and analyzed several assessment scales; and assessed transfer success and patient retention. CONCLUSIONS: The principles and lessons we learned in developing and implementing this program over 5 years, accompanied by caring, flexible, and dedicated care team members, often can overcome even severe barriers to care transitions.

Effects of Electronic Cigarette Liquid Nicotine Concentration on Plasma Nicotine and Puff Topography in Tobacco Cigarette Smokers: A Preliminary Report.

INTRODUCTION: Electronic cigarettes (ECIGs) aerosolize a liquid that usually contains propylene glycol and/or vegetable glycerin, flavorants, and the dependence-producing drug nicotine in various concentrations. This study examined the extent to which ECIG liquid nicotine concentration is related to user plasma nicotine concentration in ECIG-naïve tobacco cigarette smokers. METHODS: Sixteen ECIG-naïve cigarette smokers completed four laboratory sessions that differed by the nicotine concentration of the liquid (0, 8, 18, or 36 mg/ml) that was placed into a 1.5 Ohm, dual coil "cartomizer" powered by a 3.3V battery. In each session, participants completed two, 10-puff ECIG use bouts with a 30-second inter-puff interval; bouts were separated by 60 minutes. Venous blood was sampled before and after bouts for later analysis of plasma nicotine concentration; puff duration, volume, and average flow rate were measured during each bout. RESULTS: In bout 1, relative to the 0mg/ml nicotine condition (mean = 3.8 ng/ml, SD = 3.3), plasma nicotine concentration increased significantly immediately after the bout for the 8 (mean = 8.8 ng/ml, SD = 6.3), 18 (mean = 13.2 ng/ml, SD = 13.2), and 36 mg/ml (mean = 17.0 ng/ml, SD = 17.9) liquid concentration. A similar pattern was observed after bout 2. Average puff duration in the 36 mg/ml condition was significantly shorter compared to the 0mg/ml nicotine condition. Puff volume increased during the second bout for 8 and 18 mg/ml conditions. CONCLUSIONS: For a given ECIG device, nicotine delivery may be directly related to liquid concentration. ECIG-naïve cigarette smokers can, from their first use bout, attain cigarette-like nicotine delivery profiles with some currently available ECIG products. IMPLICATIONS: Liquid nicotine concentration can influence plasma nicotine concentration in ECIG-naïve cigarette smokers, and, at some concentrations, the nicotine delivery profile of a 3.3V ECIG with a dual coil, 1.5-Ohm cartomizer approaches that of a combustible tobacco cigarette in this population. Finding a product that delivers nicotine as effectively as a tobacco cigarette, as we report here, may be essential for smokers who want to replace completely their combustible tobacco cigarettes with ECIGs.

Electronic cigarette nicotine delivery can exceed that of combustible cigarettes: a preliminary report.

INTRODUCTION: Electronic cigarettes (ECIGs) aerosolise a liquid that usually contains propylene glycol and/or vegetable glycerine, flavourants and the dependence-producing drug, nicotine, in various concentrations. This laboratory study examined the relationship between liquid nicotine concentration and plasma nicotine concentration and puffing behaviour in experienced ECIG users. METHODS: Sixteen ECIG-experienced participants used a 3.3-Volt ECIG battery attached to a 1.5-Ohm dual-coil 'cartomiser' loaded with 1 mL of a flavoured propylene glycol/vegetable glycerine liquid to complete four sessions, at least 2 days apart, that differed by nicotine concentration (0, 8, 18 or 36 mg/mL). In each session, participants completed two 10-puff ECIG-use bouts (30 s puff interval) separated by 60 min. Venous blood was sampled to determine plasma nicotine concentration. Puff duration, volume and average flow rate were measured. RESULTS: Immediately after bout 1, mean plasma nicotine concentration was 5.5 ng/mL (SD=7.7) for 0 mg/mL liquid, with significantly (p<0.05) higher mean concentrations observed for the 8 (mean=17.8 ng/mL, SD=14.6), 18 (mean=25.9 ng/mL, SD=17.5) and 36 mg/mL (mean=30.2 ng/mL; SD=20.0) concentrations; a similar pattern was observed for bout 2. For bout 1, at 36 mg/mL, the mean post- minus pre-bout difference was 24.1 ng/mL (SD=18.3). Puff topography data were consistent with previous results and revealed few reliable differences across conditions. DISCUSSION: This study demonstrates a relationship between ECIG liquid nicotine concentration and user plasma nicotine concentration in experienced ECIG users. Nicotine delivery from some ECIGs may exceed that of a combustible cigarette. The rationale for this higher level of nicotine delivery is uncertain.

Constraining electronic nicotine delivery systems (ENDS) nicotine dose by controlling nicotine flux at a limited puff duration.

Nicotine flux, the rate of electronic nicotine delivery system (ENDS) nicotine emission, is important in determining ENDS abuse liability. However, flux does not account for user behavior, including puff duration. Along with nicotine flux, puff duration limits the dose of nicotine that can be inhaled. Controlling both flux and puff duration allows regulators to constrain nicotine dose effectively. This study examined the effects of differing ENDS nicotine fluxes (by manipulating liquid nicotine concentration and holding device power constant), with user puff duration limited to 2 s. Participants (N = 32) completed four sessions, each session differing by nicotine flux (no flux, low flux, cigarettelike flux, and high flux conditions). Participants completed two ENDS use bouts in each session while puff duration was limited to 2 s. Plasma nicotine concentration, heart rate, and subjective effects were measured. At higher flux, higher plasma nicotine concentration and higher heart rate were observed. Moreover, higher fluxes decreased ratings of craving and urge to use nicotine and increased positive subjective effects, such as calmness. This study demonstrates that by manipulating nicotine flux and limiting puff duration, nicotine dose can be controlled. Subsequent research should demonstrate the effects of manipulating puff duration systematically. Results underscore the importance of targeting both flux and puff duration for ENDS regulation, intended to reduce abuse liability while maintaining the potential to facilitate transitions from cigarettes to ENDS. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Expanding on cross-price elasticity: Understanding tobacco product demand and substitution from the cross-price purchase task.

We examine whether cigarettes serve as substitutes for electronic nicotine delivery systems (ENDS) among ENDS users and demonstrate methodological extensions of data from a cross-price purchase task to inform policies and interventions. During a clinical laboratory study, n = 19 exclusive ENDS users and n = 17 dual cigarette/ENDS users completed a cross-price purchase task with cigarettes available at a fixed price while prices of own-brand ENDS increased. We estimated cross-price elasticity using linear models to examine substitutability. We defined five additional outcomes: nonzero cross-price intensity (purchasing cigarettes if ENDS were free), constant null demand (not purchasing cigarettes at any ENDS price), cross-product crossover point (first price where participants purchased more cigarettes than ENDS), dual-demand score (percentage of prices where both products were purchased), and dual-use break point (minimum relative price to force complete substitution). The cross-price elasticity results indicated that cigarettes could serve as substitutes for ENDS among ENDS users on average, but this average effect masked substantial heterogeneity in profiles of demand (here, a measure of the drug's reinforcement potential). Policies and regulations that increase ENDS prices appear unlikely to steer most exclusive ENDS users toward cigarette use, as most would not purchase cigarettes at any ENDS price, but they could prompt some dual users to substitute cigarettes completely while others remain dual users. This heterogeneity in consumer responses suggests additional indices of cross-product demand are useful to characterize the anticipated and unanticipated effects of tobacco price policies more fully.

Assessment of human abuse potential of an unflavored, sucralose-sweetened electronic cigarette in combustible cigarette smokers.

Despite the popularity of electronic cigarettes (ECIGs), limited research has examined the role of sweeteners, independent of other flavors, in shaping ECIG human abuse potential (HAP). This study examined the effects of sucralose and nicotine in unflavored ECIG liquid solutions to provide a basic understanding of the effects of sweeteners on ECIG HAP compared to combustible cigarettes. Individuals who smoked cigarettes daily (N = 14) completed five within-subject, Latin-square ordered study sessions that differed by product used: (a) own-brand combustible cigarettes (OB), (b) 0 mg/mL nicotine, unsweetened liquid, (c) 0 mg/mL nicotine, sucralose-sweetened liquid, (d) 15 mg/mL nicotine, unsweetened liquid, and (e) 15 mg/mL nicotine, sucralose-sweetened liquid. Participants completed subjective questionnaires and behavioral tasks following a 10-puff directed use bout during which puff topography was measured, and blood was sampled for later measurement of plasma nicotine concentration. On average, the OB condition had a greater increase in plasma nicotine concentration and produced more pronounced subjective effects compared to the ECIG conditions. The 15 mg/mL nicotine ECIGs delivered significantly more nicotine and produced greater drug effects and reductions in tobacco abstinence symptoms than the 0 mg/mL nicotine ECIGs. Sucralose-containing solutions increased ECIG product appeal, puff duration, and puff volume during the 10-puff directed bout. Findings revealed greater HAP for OB cigarettes relative to all ECIGs tested and suggest that adding sucralose and nicotine elevates ECIG HAP via different mechanisms; sucralose appears to influence HAP through product appeal, while nicotine influences HAP through drug effects and tobacco/nicotine abstinence symptom suppression. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Initial evidence of the acute effect of electronic nicotine delivery system use on energy intake.

Previous work has aimed to disentangle the acute effects of nicotine and smoking on appetite with mixed findings. Electronic nicotine delivery systems (ENDS) have yet to be examined in this regard despite evidence of use for weight control. The present study tested the influence of an ENDS on acute energy intake and associated subjective effects. Participants (n = 34; 18-65 years) with current ENDS use completed two randomly ordered clinical lab sessions after overnight abstinence from tobacco/nicotine/food/drinks (other than water). Sessions differed by the product administered over 20 min: active (20 puffs of a JUUL ENDS device; 5% nicotine tobacco-flavored pod) or control (access to an uncharged JUUL with an empty pod). About 40 min after product administration, participants were provided an ad lib buffet-style meal with 21 food/drink items. Subjective ratings were assessed at baseline, after product use, and before/after the meal. Energy intake (kcal) was calculated using pre-post buffet item weights. Repeated measures analyses of variance and pairwise comparisons were used to detect differences by condition and time (α < .05). Mean ± standard error of the mean energy intake did not differ significantly between active (1011.9 ± 98.8 kcal) and control (939.8 ± 88.4 kcal; p = .108) conditions. Nicotine abstinence symptoms significantly decreased after the active condition, while satiety significantly increased. Following the control condition, satiety remained constant while hunger significantly increased relative to baseline. Findings indicate that acute ENDS use did not significantly impact energy intake, but there was an ENDS-associated subjective increase in satiety and relative decrease in hunger. Results support further investigation of ENDS on appetite. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Interactive effects of protonated nicotine concentration and device power on ENDS nicotine delivery, puff topography, and subjective effects.

Electronic nicotine delivery systems (ENDSs) produce an aerosol by heating a liquid that often contains nicotine. The nicotine can be protonated that may make the aerosol easier to inhale than freebase nicotine. This study's purpose is to determine, in cigarette smokers and ENDS users, the effects of three concentrations of protonated nicotine aerosolized at two different power settings. Forty-five participants (22 cigarette smokers and 23 ENDS users) completed some or all of six sessions that varied by liquid nicotine concentration (10, 15, or 30 mg/ml protonated nicotine) and device power (15 or 30 W). Participants took 10 puffs from each product and then used each product for 90 min ad libitum. Plasma nicotine concentration, subjective effects, and puff topography were measured. Results showed increases in plasma nicotine concentration in all conditions, with greater plasma nicotine increases in higher watt, higher nicotine concentration conditions, as well as greater nicotine delivery for ENDS users compared to cigarette smokers. For puff topography, puff duration and volume decreased as nicotine concentration and power increased, and ENDS users took longer and larger puffs than cigarette smokers. Participants rated the higher watt, higher nicotine concentration conditions as harsher and with more throat hit. Overall, these results suggest that device characteristics and liquid constituents interact to influence users' plasma nicotine delivery and should be considered together when regulating ENDS. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The electronic nicotine delivery system (ENDS) purchase task: Are results sensitive to price framing?

Extension of the cigarette purchase task (CPT) to electronic nicotine delivery systems (ENDS) is complicated by the heterogeneous nature of this product class, as ambiguity exists regarding the appropriate price-frame (i.e., unit of the product being purchased). We explored correlations between ENDS purchase task (E-CPTs) outcomes featuring two common price-frames: 10 puffs and 1 mL of liquid. Adult exclusive ENDS users (N = 19) and dual users of ENDS and cigarettes (N = 16) completed two own-brand E-CPTs. One E-CPT used "10 puffs" as its price-frame; the other used "1 mL of liquid." Five outcomes were generated for each E-CPT: breakpoint, intensity, Omax, Pmax, and α. Exploratory Factor Analyses (EFA) considered how these outcomes captured latent structures of demand for ENDS. Spearman correlations in E-CPT outcomes assessed within-person variation between price-frames. Analyses also considered whether correlations differed by user group. E-CPT outcomes were highly correlated across price-frames (ρs > 0.57, ps < .001), and EFA revealed little difference in how outcomes from the tasks loaded onto two latent structures of demand ("Persistence" and "Amplitude") reported in the previous literature. The magnitude of correlations for E-CPT outcomes tended to be higher for exclusive ENDS users than for dual users. Participant responses to purchase task outcomes were similar across two E-CPT price-frames. Using "10 puffs" as a price-frame may be a generalizable approach among heterogenous groups of ENDS users, but researchers should consider their target population and structure the E-CPT to reflect participants' knowledge and purchasing behaviors. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Acute effects of flavored Black and mild cigars among young adult cigarette smokers.

The U.S. Food and Drug Administration proposed new product standards that would ban characterizing flavors (other than tobacco) in cigars. To inform this regulatory action, we compared physiological effects, use behavior, and subjective effects of four popular cigar flavors in cigar-naïve young adult cigarette smokers. Across five laboratory visits, participants (n = 25) used and evaluated own brand (OB) cigarettes or Black & Mild cigars (original, wine, apple, and cream flavors). Linear mixed models tested differences in saliva nicotine, exhaled carbon monoxide (CO), heart rate (HR), blood pressure (BP), puff topography, and subjective effects (p < .05). Compared to all cigars, OB resulted in higher nicotine boost (953 vs. < 300 ng/ml) and lower CO boost (4 vs. 8-9 ppm). Nicotine boost for original cigars (283 ng/ml) was significantly higher than wine (190 ng/ml). All products significantly increased HR/BP relative to baseline, but across time wine and apple cigars were associated with significantly lower HR than OB and BP effects varied. Relative to OB, participants took approximately 0.5 s longer puffs for all cigars and took significantly larger puffs (+ 21%-24%) of original, wine, and apple cigars. OB was rated more positively than all cigars, which had similar subjective effects. Wine cigars were disliked most and were less effective in reducing tobacco abstinence symptoms than OB; cream cigars were harsher and had stronger flavor intensity than original. The consistency in toxicant exposure, use behavior, and subjective effects across cigar flavors, including original, highlights the need for product standards to interpret characterizing flavors subject to prohibition broadly. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Improving the health of the homeless: advice for physicians.

Homeless individuals suffer from a constellation of health issues, experience barriers to medical care that are both recognizable and hidden, and score worse on measures of health outcomes than the general population. They differ to such an extent from the general population that homeless people should be viewed by clinicians as a unique patient population. Improving the health of this population is difficult for a number of reasons. This article explores those reasons. It describes common conditions affecting homeless people and discusses how patient-centered comprehensive primary care, collaboration between health care providers and social service organizations, and innovative delivery of medical respite services can result in better care for this population.

Feasibility and Quality Validation of a Mobile Application for Enhancing Adherence to Opioids in Sickle Cell Disease.

Prescription opioid nonadherence, specifically opioid misuse, has contributed to the opioid epidemic and opioid-related mortality in the US. Popular methods to measure and control opioid adherence have limitations, but mobile health, specifically smartphone applications, offers a potentially useful technology for this purpose. We developed, tested, and validated the OpPill application using the Mobile Applications Rating Scale (MARS), a validated tool for assessing the quality of mobile health apps. The MARS contains four scales (range of each scale = 0-4) that rate Engagement, Functionality, Aesthetics, and Information Quality. It also assesses subjective quality, relevance, and overall application impact. Our application was built to be a mobile monitoring and reporting system intended to enhance opioid adherence by collecting data and providing systematic feedback on pain and opioid use. Patients (n = 28) all had one of various SCD genotypes, were ages 19 to 59 years (mean 36.56), 53.6% were female, and 39.3% had completed some college. Patients rated the OpPill application highly on all four scales: Engagement, 3.93 ± 0.73; Functionality, 4.54 ± 0.66; Aesthetics, 3.92 ± 0.81; Information, 3.91 ± 0.87. The majority of patients found the application to be relevant for their care. A total of 96% reported the information within the app was complete, while 4% estimated the information to be minimal or overwhelming. Patients (91.7%) overwhelmingly reported that the quality of information as it pertained to SCD patients was relevant; only 8.3% found the application to be poorly relevant to SCD. Similarly, patients (91.7%) overwhelmingly rated both the application's performance and ease of use positively. The large majority of participants (85.7%) found the application to be interesting to use, while 74% found it entertaining. All users found the application's navigation to be logical and accurate with consistent and intuitive gestural design. We conclude that the OpPill application, specifically targeted to monitor opioid use and pain and opioid behavior in patients with Chronic Non-Cancer Pain, was feasible and rated by SCD patients as easy-to-use using a validated rating tool.

Real-world effectiveness of voxelotor for treating sickle cell disease in the US: a large claims data analysis.

BACKGROUND: Sickle cell disease (SCD) is a genetic disease that impacts patients' quality of life, healthcare costs, and life expectancy. Elevated sickle hemoglobin (HbS), which readily polymerizes, causes red blood cell sickling, leading to chronic hemolytic anemia and complications often requiring hospitalization and transfusions. In 2019, voxelotor, which inhibits HbS polymerization, was approved for SCD treatment. OBJECTIVES: This study uses real-world evidence to assess voxelotor's effectiveness in SCD patients in typical clinical practice from 2019 to 2021 using a national medical claims database (N = 3128). RESULTS: After initiating voxelotor, 60.8% of patients with available hemoglobin (Hb) laboratory data (n = 74) showed a Hb increase >1 g/dL. Mean transfusion rate per patient-year dropped 52% in patients with ≥1 transfusion before treatment (n = 190). In patients with ≥1 of the corresponding events (n = 1065), decreases were observed in mean vaso-occlusive crisis (VOC) frequency (-23%); mean VOC-related hospitalizations and length of stay (LOS) time (-34% and -30%, respectively); mean all-cause hospitalization and LOS time (-37% and -23%, respectively); outpatient visits (-10%); iron chelation use (-46%); and prescribed opioids (-13%). CONCLUSION: These data align with randomized controlled trial results showing voxelotor improvements and support that voxelotor may lower transfusion and VOC rates in clinical practice.

Behavioral economic assessment of abuse liability for Black & Mild cigar flavors among young adults.

Cigars are available in a variety of flavors that may impact uptake and use, but little is known about how different flavors affect abuse liability. This study used 3 behavioral economic tasks to examine abuse liability of Black & Mild cigars differing in flavor among young adult cigarette smokers. Participants were 25 cigar-naïve young adults (aged 18-25 years) who smoked ≥ 5 cigarettes/day. In 5 Latin square-ordered laboratory visits, participants completed 3 abuse liability tasks (drug purchase task, cross-price purchase task, and multiple-choice procedure) for each of 4 cigar flavors (original, cream, wine, or apple) and own-brand cigarettes. In the drug purchase task, relative to own-brand cigarettes, all cigar flavors were associated with lower abuse liability using most measures (intensity, breakpoint, maximum total tobacco expenditure for 1 day [ps < .05]), although only wine-flavored cigars scored significantly lower using 1 measure (price at maximum total tobacco expenditure for 1 day). When cigars and cigarettes were available concurrently in the cross-price purchase task, all cigar flavors functioned as substitutes for cigarettes. Using the multiple-choice procedure, crossover points for wine- (mean = $0.61) and apple-flavored cigars (mean = $0.71) were significantly lower than own-brand cigarettes (mean = $0.86) and original-flavored cigars (mean = $1.00); no significant differences existed between own-brand cigarettes and original-flavored cigars. Thus, whereas abuse liability may be highest for participants' own-brand cigarette, young adult smokers may be willing to use flavored cigars. Furthermore, abuse liability varies by cigar flavor, with original- and cream-flavored cigars appearing to have the highest abuse liability. Characterizing flavors and flavor additives in cigars represent an important tobacco regulatory target. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Tobacco-use behavior and toxicant exposure among current dual users of electronic cigarettes and tobacco cigarettes.

Electronic cigarette (e-cigarette) use continues to grow with most users reporting concurrent cigarette smoking, but few studies have focused on tobacco use and toxicant exposure among naturalistic dual-using populations. This controlled clinical laboratory study examined how dual versus exclusive use of e-cigarettes and cigarettes and no tobacco/nicotine affected behavioral, physiological, and subjective measures among current dual users. Twenty-two participants identifying as cigarette (≥ 10 cigarettes per day [CPD]) and e-cigarette (≥ 3 days/week) users of "cig-a-like" e-cigarettes completed four 5-day outpatient conditions, which differed by their own brand of products used ad libitum: (a) cigarette and e-cigarette (dual), (b) cigarette-only, (c) e-cigarette-only, and (d) no tobacco/nicotine. Primary outcomes included daily tobacco use, expired air carbon monoxide (CO), and urinary cotinine and NNAL. Linear mixed models with pairwise comparisons (Bonferroni corrected) were performed (p < .05). CPD did not differ significantly between dual and cigarette-only use, but e-cigarette use and liquid consumed increased significantly during e-cigarette-only relative to dual use. Relative to dual use, expired air CO did not differ during cigarette-only and was significantly lower during e-cigarette-only use. Urinary cotinine was significantly lower during e-cigarette-only use relative to dual and cigarette-only use, while urinary NNAL did not differ between the nicotine-containing conditions. In summary, among current dual users, e-cigarettes in combination with cigarettes did not reduce CPD relative to exclusive cigarette use or toxicant exposure relative to exclusive use of either product. However, exclusive e-cigarette use did reduce CO and cotinine, highlighting the benefits of cigarette cessation. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Variable Voltage, Tank-Style ENDS Do Not Always Deliver Nicotine.

OBJECTIVE: This study's objective was to characterize the nicotine delivery profile of a variable voltage, tank-style electronic nicotine delivery system (ENDS). METHODS: Ten cigarette smokers (8 men, 2 women) completed this within-subject study assessing effects of 2 device power settings (15 W, 45 W) and 3 liquid nicotine concentrations (0, 3, and 6 mg/ml) using a tank-style ENDS. Participants completed one directed (10 puffs) and one ad libitum use period for each condition, with blood sampled throughout. RESULTS: Plasma nicotine concentration did not increase significantly at 15 W regardless of liquid nicotine concentration. At 45 W, mean plasma nicotine increased (not significantly compared to 0 mg/ml) from 2.24 ng/ml (SD=0.2) at baseline to 3.4 ng/ml (SD=0.6) in the 3 mg/ml condition. In the 6 mg/ml, 45 W condition, mean plasma nicotine increased significantly (compared to 0 mg/ml) from 2.0 ng/ml (SD=0) at baseline to 5.96 ng/ml (SD=1.3) after 10 puffs. In general, puff duration and volume decreased as device power and nicotine concentration increased. CONCLUSIONS: Despite using a variable wattage, tank-style device, nicotine delivery was minimal. These results, when combined with results from other studies using tank-style devices, highlight ENDS performance heterogeneity. Regulation may play a role in standardizing ENDS nicotine delivery.

Abuse liability of electronic cigarettes in men who are experienced electronic cigarette users.

Most electronic cigarettes (e-cigs) aerosolize a nicotine-containing liquid that users inhale. Few experimental studies have examined e-cig abuse liability (the extent to which use of these products may lead to persistent and/or problematic use). In this study, 24 experienced male e-cig users completed 4 sessions that differed byproduct used: own e-cig (OWN), an eGo e-cig filled with participants' own brand/flavor liquid in 0 mg/mL nicotine (e-cig0), an eGo e-cig filled with the highest nicotine concentration available in participants' own brand/flavor (e-cighighest), and a U.S. Food and Drug Administration-approved nicotine inhaler (IN). Outcome measures included crossover point on the multiple-choice procedure, plasma nicotine delivery, and subjective effect profile. After 10 puffs, a significantly higher mean crossover point was observed for OWN at $1.35 (SD = 0.90) compared to e-cighighest at $0.88 (SD = 0.89), e-cig0 at $0.83 (SD = 0.79), and IN at $0.72 (SD = 0.84). Significant increases in mean plasma nicotine concentration were observed for OWN at 7.94 ng/mL (SD = 6.19) and e-cighighest at 7.51 ng/mL (SD = 5.39). Significant reductions in abstinence symptom suppression and higher ratings of satisfaction were observed for OWN and e-cighighest, with significantly less suppression and lower ratings of satisfaction for e-cig0 and IN. These findings suggest that human laboratory methods can be used to assess e-cig abuse liability and that nicotine-containing e-cigs have greater abuse liability than nicotine-free e-cigs and the IN. Potential regulations intended to limit e-cig abuse liability should be tested using these or similar procedures. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Development of a Severity Classification System for Sickle Cell Disease.

PURPOSE: There is no well-accepted classification system of overall sickle cell disease (SCD) severity. We sought to develop a system that could be tested as a clinical outcome predictor. PATIENTS AND METHODS: Using validated methodology (RAND/UCLA modified Delphi panel), 10 multi-disciplinary expert clinicians collaboratively developed 180 simplified patient histories and rated each on multiple axes (estimated clinician follow-up frequency, risk of complications or death, quality of life, overall disease severity). Using ratings on overall disease severity, we developed a 3-level severity classification system ranging from Class I (least severe) to Class III (most severe). RESULTS: The system defines patients as Class I who are 8-40 years with no end organ damage, no chronic pain, and ≤4 unscheduled acute care visits due to vaso-occlusive crises (VOC) in the last year. Patients <8 or >40 years with no end organ damage, no chronic pain, and <2 unscheduled acute care visits are also considered Class I. Patients any age with ≥5 unscheduled acute care visits and/or with severe damage to bone, retina, heart, lung, kidney, or brain are classified as Class III (except patients ≥25 years with severe retinopathy, no chronic pain, and 0-1 unscheduled acute care visits, who are considered Class II). Patients not meeting these Class I or III definitions are classified as Class II. CONCLUSION: This system consolidates patient characteristics into homogenous groups with respect to disease state to support clinical decision-making. The system is consistent with existing literature that increased unscheduled acute care visits and organ damage translate into clinically significant patient morbidity. Studies to further validate this system are planned.

Exercise Testing of Adolescents and Young Adults With Sickle Cell Disease: Perceptual Responses and the Gas Exchange Threshold.

For individuals with sickle cell disease (SCD), mild to moderate exercise is advised, but self-regulation of these intensities is difficult. To regulate intensity, one SCD recommendation is to stop exercising at the first perception of fatigue. However, perceived effort and affect (how one feels) are perceptual cues that are commonly used to guide exercise intensity. This study (a) examined perceived effort, affect, and fatigue in relation to metabolic state (gas exchange) in adolescents and young adults (AYAs) with SCD, (b) explored guidelines AYAs use to self-regulate exercise, and (c) compared perceived effort and affect at gas exchange threshold (GET) with healthy counterparts. Twenty-two AYAs with SCD completed an incremental cycle test. Perceived effort, affect, and fatigue were assessed every 2 minutes. A mixed-effects linear model was conducted to model changes in effort, affect, and fatigue across time. Mean scores of effort and affect at GET were compared with published data of healthy counterparts. Participants were queried about self-regulation exercise strategies. Findings indicated that both perceived fatigue and effort at GET was lower than expected. Perceived effort was lower (p < .0001), and perceived affect was significantly higher (p = .0009) than healthy counterparts. Interviews revealed that most participants (95%) do not stop exercising until fatigue is moderate to severe, and many (73%) do not stop until symptoms are severe (chest tightness, blurry vision). Nurses should review guidelines for safe exercise with AYAs with SCD. Exercise training may be beneficial to AYAs with SCD for learning how to interpret bodily responses to exercise to improve self-regulation.