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.

Menthol versus tobacco e-liquid flavor: Impact on acute subjective effects, puff patterns, and intentions for use among Black and White menthol smokers.

BACKGROUND: The proposed FDA product standard to prohibit menthol as a characterizing flavor in combustible cigarettes has the potential to significantly reduce tobacco-related health disparities. Whether a menthol e-liquid product standard would improve or hinder public health is unknown. No known research has directly examined the impact of menthol vs. tobacco flavored e-liquid use on acute e-cigarette use patterns, subjective experience, behavioral intentions, and craving and withdrawal among menthol cigarette smokers. METHODS: Black (n = 47) and White (n = 4) nicotine-deprived menthol smokers with limited e-cigarette experience completed two counterbalanced in-laboratory 30-minute ad libitum vaping sessions with menthol and tobacco nicotine salt-based e-liquid in a randomized crossover pilot trial design. Questionnaires assessed reductions in craving and withdrawal and post-session subjective experience and behavioral intentions. Puff topography was measured continuously throughout each vaping session. RESULTS: Measures of puff topography did not differ significantly by e-liquid flavor (all p > .40). Similarly, menthol and tobacco flavored e-cigarettes were both rated positively in terms of subjective effects and behavioral intentions (all p > .10) and about 40 % of participants reported a preference for the tobacco-flavored e-liquid. Finally, participants showed comparable reductions in craving (p = .210) and withdrawal (p = .671) from pre- and post-session regardless of e-liquid flavor. CONCLUSIONS: Among menthol smokers in a lab-based setting, findings suggest that menthol vs tobacco e-liquid flavor has little impact on acute changes in puff patterns, subjective experience, behavioral intentions, or craving and withdrawal.

Modification of the PM2.5- and extreme heat-mortality relationships by historical redlining: a case-crossover study in thirteen U.S. states.

BACKGROUND: Redlining has been associated with worse health outcomes and various environmental disparities, separately, but little is known of the interaction between these two factors, if any. We aimed to estimate whether living in a historically-redlined area modifies the effects of exposures to ambient PM2.5 and extreme heat on mortality by non-external causes. METHODS: We merged 8,884,733 adult mortality records from thirteen state departments of public health with scanned and georeferenced Home Owners Loan Corporation (HOLC) maps from the University of Richmond, daily average PM2.5 from a sophisticated prediction model on a 1-km grid, and daily temperature and vapor pressure from the Daymet V4 1-km grid. A case-crossover approach was used to assess modification of the effects of ambient PM2.5 and extreme heat exposures by redlining and control for all fixed and slow-varying factors by design. Multiple moving averages of PM2.5 and duration-aware analyses of extreme heat were used to assess the most vulnerable time windows. RESULTS: We found significant statistical interactions between living in a redlined area and exposures to both ambient PM2.5 and extreme heat. Individuals who lived in redlined areas had an interaction odds ratio for mortality of 1.0093 (95% confidence interval [CI]: 1.0084, 1.0101) for each 10 µg m-3 increase in same-day ambient PM2.5 compared to individuals who did not live in redlined areas. For extreme heat, the interaction odds ratio was 1.0218 (95% CI 1.0031, 1.0408). CONCLUSIONS: Living in areas that were historically-redlined in the 1930's increases the effects of exposures to both PM2.5 and extreme heat on mortality by non-external causes, suggesting that interventions to reduce environmental health disparities can be more effective by also considering the social context of an area and how to reduce disparities there. Further study is required to ascertain the specific pathways through which this effect modification operates and to develop interventions that can contribute to health equity for individuals living in these areas.

Dietary Intake Assessment Using a Novel, Generic Meal-Based Recall and a 24-Hour Recall: Comparison Study.

BACKGROUND: Dietary intake assessment is an integral part of addressing suboptimal dietary intakes. Existing food-based methods are time-consuming and burdensome for users to report the individual foods consumed at each meal. However, ease of use is the most important feature for individuals choosing a nutrition or diet app. Intakes of whole meals can be reported in a manner that is less burdensome than reporting individual foods. No study has developed a method of dietary intake assessment where individuals report their dietary intakes as whole meals rather than individual foods. OBJECTIVE: This study aims to develop a novel, meal-based method of dietary intake assessment and test its ability to estimate nutrient intakes compared with that of a web-based, 24-hour recall (24HR). METHODS: Participants completed a web-based, generic meal-based recall. This involved, for each meal type (breakfast, light meal, main meal, snack, and beverage), choosing from a selection of meal images those that most represented their intakes during the previous day. Meal images were based on generic meals from a previous study that were representative of the actual meal intakes in Ireland. Participants also completed a web-based 24HR. Both methods were completed on the same day, 3 hours apart. In a crossover design, participants were randomized in terms of which method they completed first. Then, 2 weeks after the first dietary assessments, participants repeated the process in the reverse order. Estimates of mean daily nutrient intakes and the categorization of individuals according to nutrient-based guidelines (eg, low, adequate, and high) were compared between the 2 methods. P values of less than .05 were considered statistically significant. RESULTS: In total, 161 participants completed the study. For the 23 nutrient variables compared, the median percentage difference between the 2 methods was 7.6% (IQR 2.6%-13.2%), with P values ranging from <.001 to .97, and out of 23 variables, effect sizes for the differences were small for 19 (83%) variables, moderate for 2 (9%) variables, and large for 2 (9%) variables. Correlation coefficients were statistically significant (P<.05) for 18 (78%) of the 23 variables. Statistically significant correlations ranged from 0.16 to 0.45, with median correlation of 0.32 (IQR 0.25-0.40). When participants were classified according to nutrient-based guidelines, the proportion of individuals who were classified into the same category ranged from 52.8% (85/161) to 84.5% (136/161). CONCLUSIONS: A generic meal-based method of dietary intake assessment provides estimates of nutrient intake comparable with those provided by a web-based 24HR but with varying levels of agreement among nutrients. Further studies are required to refine and improve the generic recall across a range of nutrients. Future studies will consider user experience including the potential feasibility of incorporating image recognition of whole meals into the generic recall.

Visibility of inflicted bruises by alternate light: Results of a randomized controlled trial.

Difficulty visualizing bruises resulting from interpersonal violence, especially in individuals with dark skin, contributes to disparities in access to justice. The purpose of this analysis was to compare bruise visibility of detected injuries using white light versus alternate light sources (ALS). Visibility was assessed using the 5-point Bruise Visibility Scale (BVS) for white light and the ALS Visibility Scale (AVS) for ALS. Bruises were induced using controlled application of a paintball to the upper arm on 157 healthy adults across six skin color categories. Using a crossover design, the light source used first to assess the bruise (white light or ALS) was randomized. Each bruise was examined up to 21 times over 4 weeks using white light and 10 combinations of wavelengths (350 nanometer [nm] - 535 nm) and colored filters (yellow, orange, and red). Multilevel modeling was used to analyze the repeated measures data with a total 20,103 bruise assessments. Results revealed 415 nm with yellow filter resulted in an almost 0.5-point increase in BVS/AVS score across all skin colors (Estimate = 0.46; 95% CI: 0.43, 0.49; p < 0.001), a clinically significant improvement in ability to visualize bruises. Conversely, 515 nm (Estimate = -0.80; 95% CI: -0.84, -0.76; p < 0.001) and 535 nm (Estimate = -0.64, 95% CI: -0.67, -0.60; p < 0.001) with red filter resulted in more than 0.5-point decrease in BVS/AVS score. The use of ALS is supported by the data and results in improved bruise visibility during medical forensic examinations.

Exploring various measures of the area under the curve for the assessment of dose-proportionality and estimation of bioavailability.

OBJECTIVE: In pharmacokinetics, the area under the concentration versus time curve (AUC) extrapolated to infinity (AUC0-∞) is the preferred metric but it is not always possible to have a reliable estimate of the terminal phase half-life. Here we sought to explore the accuracy of three different area measures to accurately identify dose proportionality and bioavailability. METHODS: One to three compartment model simulations with different doses for dose-proportionality or different rates and/or extents of bioavailability. Area measures evaluated were AUC0-∞, to the last quantifiable concentration (AUCtlast), and to a common time value (AUCt'). RESULTS: Under linear pharmacokinetics, AUCt' provided the most accurate measure of dose proportionality. Except for the one compartment model where AUC0-∞ provided the best predictor of the true measure, there was no clear advantage to the use of either of the three measures of AUC. CONCLUSION: With uncertainty about the terminal phase half-life, the use of AUCt' can be a very useful and even the preferred measure of exposure for use in assessing proportionality in exposure between doses. The choice of AUC measure in bioavailability is less clear and may depend on compartmental nature of the drug, and study parameters including assay sensitivity and sampling protocols.

Reduction of discrepancies between students and instructors in the assessment of practical tasks through structured evaluation sheets and peer feedback.

The aim of this study was to reduce discrepancies between students and instructors in a preclinical dental course by employing structured peer feedback based on a detailed evaluation sheet. In a crossover study of dental students (n = 32), which compared peer feedback using an evaluation sheet (test) with the traditional method (control), participants completed tasks involving cavity and partial crown preparation. The practical tasks were scored numerically on a scale ranging from one (excellent) to six (failure). The amount of feedback provided by the instructor was also recorded. Statistical analysis was conducted using Wilcoxon signed-rank tests (p < 0.05). Regarding cavity preparation, no statistically significant difference was observed (median (25th-75th percentile)) between the grades received by the test (2.00 (1.50-3.00)) and control groups (2.25 (2.00-3.00)). However, the grades pertaining to partial crown preparation exhibited a statistically significant difference between the test (2.25 (2.00-2.50)) and control (2.50 (2.00-3.00)) groups. LimeSurvey and five-finger feedback were used to assess satisfaction with the new method, revealing that most students found the evaluation sheet and peer feedback to be effective. Within the limitations of this study, structured peer feedback using the evaluation sheet positively impacted grades pertaining to partial crown preparation, requiring less instructor feedback.

Ambient Heat and Risk of Serious Hypoglycemia in Older Adults With Diabetes Using Insulin in the U.S. and Taiwan: A Cross-National Case-Crossover Study.

OBJECTIVE: To measure the association between ambient heat and hypoglycemia-related emergency department visit or hospitalization in insulin users. RESEARCH DESIGN AND METHODS: We identified cases of serious hypoglycemia among adults using insulin aged ≥65 in the U.S. (via Medicare Part A/B/D-eligible beneficiaries) and Taiwan (via National Health Insurance Database) from June to September, 2016-2019. We then estimated odds of hypoglycemia by heat index (HI) percentile categories using conditional logistic regression with a time-stratified case-crossover design. RESULTS: Among ∼2 million insulin users in the U.S. (32,461 hypoglycemia case subjects), odds ratios of hypoglycemia for HI >99th, 95-98th, 85-94th, and 75-84th percentiles compared with the 25-74th percentile were 1.38 (95% CI, 1.28-1.48), 1.14 (1.08-1.20), 1.12 (1.08-1.17), and 1.09 (1.04-1.13) respectively. Overall patterns of associations were similar for insulin users in the Taiwan sample (∼283,000 insulin users, 10,162 hypoglycemia case subjects). CONCLUSIONS: In two national samples of older insulin users, higher ambient temperature was associated with increased hypoglycemia risk.

Evaluating the effects of nicotine concentration on the appeal and nicotine delivery of oral nicotine pouches among rural and Appalachian adults who smoke cigarettes: A randomized cross-over study.

BACKGROUND AND AIMS: Oral nicotine pouches (ONPs) probably offer reduced harm compared with cigarettes, but independent data concerning their misuse liability are lacking. We compared nicotine delivery and craving relief from ONPs with different nicotine concentrations to cigarettes. DESIGN: This was a single-blind, three-visit (≥ 48-hour washout), randomized-cross-over study. Participants were encouraged to complete all study visits in less than 1 month. SETTING: The study took place in Rural/Appalachian Ohio. PARTICIPANTS: Participants comprised 30 adults who smoke cigarettes. Participants (meanage = 34.5) were 60% men and 90% White. INTERVENTION: Participants who were ≥ 12-hour tobacco-abstinent used: (1) a 3-mg nicotine concentration ONP, (2) a 6-mg nicotine concentration ONP and (3) usual brand cigarette in separate visits. ONPs (wintergreen Zyn) were used for 30 minutes; cigarettes were puffed every 30 sec for 5 minutes. MEASUREMENTS: Plasma nicotine and self-reported craving were assessed at t = 0, 5, 15, 30, 60 and 90 minutes. The primary outcome was plasma nicotine concentration at t = 30 minutes. A secondary outcome was craving relief at t = 5 minutes. FINDINGS: At t = 30, mean [95% confidence interval (CI)] plasma nicotine was 9.5 ng/ml (95% CI = 7.1, 11.9 ng/ml) for the 3 mg nicotine ONP, 17.5 ng/ml (95% CI = 13.7, 21.3) for the 6 mg nicotine ONP and 11.4 ng/ml (95% CI = 9.2, 13.6 ng/ml) for the cigarette. Mean plasma nicotine at t = 30 minutes differed between the 3- and 6-mg nicotine ONPs (P = 0.001) and between the 6-mg nicotine ONP and cigarette (P = 0.002). Mean (95% CI) craving at t = 5 minutes was lower for the cigarette (mean = 1.00, 95% CI = 0.61, 1.39) than either the 3 mg (mean = 2.25, 95% CI = 1.68, 2.82; P < 0.0001) or 6 mg nicotine (mean = 2.19, 95% CI = 1.60, 2.79; P < 0.0001) ONP. CONCLUSIONS: Among adult smokers, using 6-mg nicotine concentration oral nicotine pouches (ONPs) was associated with greater plasma nicotine delivery at 30 minutes than 3-mg ONPs or cigarettes, but neither ONP relieved craving symptoms at 5 minutes as strongly as a cigarette. Accelerating the speed of nicotine delivery in ONPs might increase their misuse liability relative to cigarettes.

Drug-induced immune hemolytic anemia: detection of new signals and risk assessment in a nationwide cohort study.

ABSTRACT: More than 130 drugs have been suspected to induce immune hemolytic anemia. Comparative studies measuring the risk of drug-induced immune hemolytic anemia (DIIHA) are lacking. We aimed (1) to detect new signals of DIIHA, excluding vaccines, and (2) to assess the association between all suspected drugs and the occurrence of immune hemolytic anemia in a nationwide comparative study. The new signals were identified using a disproportionality study (case/noncase design) in the World Pharmacovigilance Database, Vigibase, among the cases of adverse drug reactions reported up to February 2020 (>20 million). We then conducted a comparative study in the French National health database that links sociodemographic, out-of-hospital, and hospital data for the entire population (67 million individuals). Associations between exposure to drugs (those already reported as DIIHA, plus new signals identified in Vigibase) and incident cases of immune hemolytic anemia (D59.0 and D59.1 diagnosis codes of the International Classification of Diseases, version 10) from 2012 to 2018 were assessed with case-control and case-crossover designs. In Vigibase, 3371 cases of DIIHA were recorded. Fifty-nine new signals were identified resulting in a final list of 112 drugs marketed in France and measurable in the nationwide cohort (n = 4746 patients with incident immune hemolytic anemia included in the case-control analysis matched with 22 447 controls from the general population). We identified an association between immune hemolytic anemia occurrence and some antibiotics, antifungal drugs, ibuprofen, acetaminophen, furosemide, azathioprine, and iomeprol.

Acute Ingestion of a Ketone Monoester without Co-ingestion of Carbohydrate Improves Running Economy in Male Endurance Runners.

PURPOSE: Acute ingestion of a ketone monoester, with and without co-ingestion of carbohydrate, was investigated for effects on running economy (RE), time to exhaustion (TTE), and other related indices of endurance running performance. METHODS: Using a three condition, placebo-controlled, randomized crossover design, 11 male middle- and long-distance runners ran at five submaximal speeds (10-14 km·h -1 ) on a motorized treadmill for 8 min each, immediately followed by a ramp test to volitional exhaustion. Participants consumed either a 10% carbohydrate solution (CHO), a 10% carbohydrate solution with 750 mg·kg -1 body mass of an ( R )-3-hydroxybutyl ( R )-3-hydroxybutyrate ketone monoester (CHO + KE), or 750 mg·kg -1 body mass of the ketone monoester in flavored water (KE) before (two-thirds of the dose) and during (one-third of the dose) exercise. RESULTS: ß-hydroxybutyrate concentration averaged 1.8 ± 0.3 and 2.1 ± 0.3 mM during exercise in CHO + KE and KE, respectively. RE was lower at each submaximal running speed (effect size = 0.48-0.98) by an average of 4.1% in KE compared with CHO, but not between CHO + KE and CHO. TTE did not differ between CHO (369 ± 116 s), CHO + KE (342 ± 99 s), or KE (333 ± 106 s) ( P = 0.093). CONCLUSIONS: Acute ingestion of a ketone monoester without carbohydrate, but not when coingested with carbohydrate, improved RE in middle- and long-distance runners at a range of submaximal running speeds and did not alter TTE in a short-duration ramp test to volitional exhaustion. Further investigation is required to examine if these differences translate into positive performance outcomes over longer durations of exercise.

Randomized trial of dyadic-report vs proxy-report and self-report symptom assessment for pediatric patients receiving cancer treatments.

BACKGROUND: We validated different approaches to symptom assessment for pediatric cancer patients based on the Symptom Screening in Pediatrics Tool (SSPedi) for self-report (SSPedi and mini-SSPedi), proxy-report (proxy-SSPedi), and structured dyadic-report (co-SSPedi). The objective was to compare co-SSPedi scores vs proxy-report (proxy-SSPedi) and self-report (SSPedi or mini-SSPedi) scores for pediatric patients receiving cancer treatments. METHODS: This was a single-center, randomized crossover study enrolling English-speaking dyads of pediatric patients with cancer or hematopoietic cell transplant recipients 4-18 years old and their guardians. Dyads were randomized to first complete the dyadic-report (co-SSPedi) or self-report (patients: SSPedi or mini-SSPedi) and proxy-report (guardians: proxy-SSPedi). Dyads then crossed over to the alternate approach. Primary analysis compared total SSPedi scores between randomized groups. RESULTS: We enrolled 420 dyads that were randomized to co-SSPedi first (n = 213) or proxy-SSPedi and self-report SSPedi first (n = 207). Mean total SSPedi scores (± standard deviation) were co-SSPedi (9.6 ± 7.1), proxy-SSPedi (9.7 ± 7.5; P = .950 for comparison vs co-SSPedi), and self-report SSPedi (9.7 ± 8.2; P = .981 for comparison vs co-SSPedi). Co-SSPedi scores were significantly different from proxy-SSPedi for feeling disappointed or sad, feeling cranky or angry, feeling tired, mouth sores, and changes in taste. Co-SSPedi scores were significantly different from self-report SSPedi scores for problems with thinking or remembering things, feeling tired, mouth sores, tingly or numb hands or feet, and diarrhea. CONCLUSIONS: Total co-SSPedi scores were not significantly different compared with proxy-report or self-report scores, although there were differences in specific symptom scores. If different reporter types are used during clinical implementation, specifying reporter type will be important. The study was registered at clinicaltrials.gov (NCT #05012917). Symptoms are common and frequently severely bothersome in pediatric patients with cancer and hematopoietic cell transplant (HCT) recipients (1). To measure the extent of bothersome symptoms, the Symptom Screening in Pediatrics Tool (SSPedi) suite of symptom assessment tools was developed for pediatric patients receiving cancer treatments and currently consists of multiple validated instruments. SSPedi was developed for self-report by patients 8-18 years of age (2,3). Mini-SSPedi was developed for self-report by patients 4 to 7 years of age (4). Proxy-SSPedi was developed for proxy-report by guardians of pediatric patients 2-18 years of age (5). These 3 instruments can be categorized as either self-report (SSPedi or mini-SSPedi) or proxy-report (proxy-SSPedi).

Influence of different midsole foam in advanced footwear technology use on running economy and biomechanics in trained runners.

BACKGROUND: Ethylene and vinyl acetate (EVA) and polyether block amide (PEBA) are recently the most widely used materials for advanced footwear technology (AFT) that has been shown to improve running economy (RE). This study investigated the effects of these midsole materials on RE and biomechanics, in both fresh and worn state (after 450 km). METHODS: Twenty-two male trained runners participated in this study. Subjects ran four 4-min trials at 13 km‧h-1 with both fresh EVA and PEBA AFT and with the same models with 450 km of wear using a randomized crossover experimental design. We measured energy cost of running (W/kg), spatiotemporal, and neuromuscular parameters. RESULTS: There were significant differences in RE between conditions (p = 0.01; n2 = 0.17). There was a significant increase in energy cost in the worn PEBA condition compared with new (15.21 ± 1.01 and 14.87 ± 0.99 W/kg; p < 0.05; ES = 0.54), without differences between worn EVA (15.13 ± 1.14 W/kg; p > 0.05), and new EVA (15.15 ± 1.13 w/kg; ES = 0.02). The increase in energy cost between new and worn was significantly higher for the PEBA shoes (0.32 ± 0.38 W/kg) but without significant increase for the EVA shoes (0.06 ± 0.58 W/kg) (p < 0.01; ES = 0.51) with changes in step frequency and step length. The new PEBA shoes had lower energy cost than the new EVA shoes (p < 0.05; ES = 0.27) with significant differences between conditions in contact time. CONCLUSION: There is a clear RE advantage of incorporating PEBA versus EVA in an AFT when the models are new. However, after 450 km of use, the PEBA and EVA shoes had similar RE.

Exercise-Induced Cell-Free DNA Correlates with Energy Expenditure in Multiple Exercise Protocols.

PURPOSE: Exercise-induced cell-free DNA (ei-cfDNA) has been studied in response to various types of exercise. Its correlation with exercise intensity and duration has been observed consistently. However, comprehensive measurements and exploration of the tissue of origin are lacking. The aim of this study is to establish precise connections between exercise variables and the distribution of tissue of origin, aiming to provide further evidence supporting its use as a biomarker for exercise. METHODS: Twelve self-identified active adults (six men and six women) performed a crossover study starting with either endurance testing or resistance testing under different intensities and protocols. We obtained blood before and after each exercise session and measured the levels of cfDNA and determined its tissue of origin utilizing cell type-specific DNA methylation patterns in plasma. RESULTS: We found that when duration and intensity are fixed, ei-cfDNA fold change correlates with energy expenditure ( P = 0.001) in endurance testing and years trained ( P = 0.001) in resistance testing. Most of the ei-cfDNA comes from increases in white blood cells (~95%) where neutrophils make up the majority (~74%) and the distribution is different between exercise modalities and protocols. CONCLUSIONS: This study highlights the potential of exercise-induced cfDNA as a biomarker for exercise, showing correlations with energy expenditure and a consistent pattern of tissue origin. Additional research is needed to investigate potential sex differences in the response of cfDNA to exercise, further exploring its clinical implications.

Post hoc analysis of food costs associated with Dietary Approaches to Stop Hypertension diet, whole food, plant-based diet, and typical baseline diet of individuals with insulin-treated type 2 diabetes mellitus in a nonrandomized crossover trial with meals provided.

BACKGROUND: Americans consume diets that fall short of dietary recommendations, and the cost of healthier diets is often cited as a barrier to dietary change. We conducted a nonrandomized crossover trial with meals provided utilizing 2 diets: Dietary Approaches to Stop Hypertension (DASH) and whole food, plant-based (WFPB), and thus had intake data from baseline and both intervention diets. OBJECTIVES: Using actual diet records, describe food costs of baseline diets of individuals with type 2 diabetes (T2DM) as well as therapeutic DASH and WFPB diets. METHODS: Three-day food records were collected and analyzed for each 7-d diet phase: baseline, DASH, and WFPB. Nutrient content was analyzed using the Nutrient Data System for Research and cost was determined using Fillet, an application to manage menu pricing. Food costs were calculated for each diet as consumed and adjusted to a standardized 1800 kcal/d. Ingredient-only costs of food away from home (FAFH) were approximated and analyzed. Costs were analyzed using linear mixed-effect models as a function of diet. RESULTS: Fifteen subjects enrolled; 12 completed all dietary phases. The baseline, DASH, and WFPB diets, as consumed, cost $15.72/d (95% CI; $13.91, $17.53), $12.74/d ($11.23, $14.25), and $9.78/d ($7.97, $11.59), respectively. When adjusted to an 1800 kcal/d intake, the baseline, DASH, and WFPB diets cost $15.69/d ($13.87, $17.52), $14.92/d ($13.59, $16.26), and $11.96/d ($10.14, $13.78), respectively. When approximated ingredient-only costs of FAFH were analyzed, as consumed baseline [$11.01 ($9.53, $12.49)] and DASH diets [$11.81 ($10.44, $13.18)] had similar costs; WFPB diet [$8.83 ($7.35, $10.31)] cost the least. CONCLUSIONS: In this short-term study with meals provided, the food costs of plant-predominant diets offering substantial metabolic health benefits were less than or similar to baseline food costs of adults with insulin-treated T2DM. Longer-term data without meal provision are needed for more generalizable results. This trial was registered at clinicaltrials.gov as NCT04048642.

Quantifying energy expenditure in Göttingen Minipigs with the 13C-bicarbonate method under basal and drug-treated conditions.

Effective treatments of obesity focusing on energy expenditure (EE) are needed. To evaluate future EE-modulating drug candidates, appropriate animal models and methods to assess EE are needed. This study aimed to evaluate the stable isotope 13C-bicarbonate method (13C-BM) for estimating EE in Göttingen minipigs under basal and drug-treated conditions. Four experiments (Expt.1-4) were conducted to assess: 1) the 13C-BM reproducibility using breath sample collection (n = 8), on two consecutive days, 2) the effect of two dose levels (5 and 10 mg/kg body weight (BW)) of the mitochondrial uncoupler dinitrophenol (DNP) in a crossover design (n = 8), 3) sampling method agreement; blood vs. exhaled air (n = 6) and 4) 13C-BM using constant isotope infusion compared with indirect calorimetry (IC) (n = 3). Results correlated significantly (p < 0.001) between days (Expt.1), with an average coefficient of variance of 5.4 ± 2.3%. Administration of 10 mg DNP/kg BW increased (p < 0.01) EE by 33.2 ± 6.4% (Expt.2). Results based on different sampling methods correlated significantly (p < 0.001) and EE increased after 10 mg DNP/kg BW (p < 0.05) in Expt.3. However, results based on blood sampling were significantly higher (p < 0.01) than those of exhaled air. No effect of DNP and significantly different EE results (p < 0.05) was observed in a limited number of animals, when constant isotope infusion and blood sampling was compared with IC (Expt.4). In conclusion, the 13C-BM is useful for investigating treatment effects on EE in minipigs. However, further validation under standardized conditions is needed to provide accurate estimates of the 13C recovery factor and respiratory quotient, both of decisive importance when using the 13C-BM.

A guaranteed income intervention to improve the health and financial well-being of low-income black emerging adults: study protocol for the Black Economic Equity Movement randomized controlled crossover trial.

Background: Economic inequity systematically affects Black emerging adults (BEA), aged 18-24, and their healthy trajectory into adulthood. Guaranteed income (GI)-temporary, unconditional cash payments-is gaining traction as a policy solution to address the inequitable distribution of resources sewn by decades of structural racism and disinvestment. GI provides recipients with security, time, and support to enable their transition into adulthood and shows promise for improving mental and physical health outcomes. To date, few GI pilots have targeted emerging adults. The BEEM trial seeks to determine whether providing GI to BEA improves financial wellbeing, mental and physical health as a means to address health disparities. Methods/design: Using a randomized controlled crossover trial design, 300 low-income BEA from San Francisco and Oakland, California, are randomized to receive a $500/month GI either during the first 12-months of follow-up (Phase I) or during the second 12-months of a total of 24-months follow-up (Phase II). All participants are offered enrollment in optional peer discussion groups and financial mentoring to bolster financial capability. Primary intention-to-treat analyzes will evaluate the impact of GI at 12 months among Phase I GI recipients compared to waitlist arm participants using Generalized Estimating Equations (GEE). Primary outcomes include: (a) financial well-being (investing in education/training); (b) mental health status (depressive symptoms); and (c) unmet need for mental health and sexual and reproductive health services. Secondary analyzes will examine effects of optional financial capability components using GEE with causal inference methods to adjust for differences across sub-strata. We will also explore the degree to which GI impacts dissipate after payments end. Study outcomes will be collected via surveys every 3 months throughout the study. A nested longitudinal qualitative cohort of 36 participants will further clarify how GI impacts these outcomes. We also discuss how anti-racism praxis guided the intervention design, evaluation design, and implementation. Discussion: Findings will provide the first experimental evidence of whether targeted GI paired with complementary financial programming improves the financial well-being, mental health, and unmet health service needs of urban BEA. Results will contribute timely evidence for utilizing GI as a policy tool to reduce health disparities. Clinical trial registration: https://clinicaltrials.gov, identifier NCT05609188.

Impact of telemedicine on disease activity assessment: A case-crossover study nested within a cohort of patients with systemic lupus erythematosus.

INTRODUCTION: The utilisation of telemedicine has been rapidly growing among patients with rheumatic diseases, especially following the corona virus disease 2019 pandemic. Ease and convenience appear to dominate the reasons for this growth. However, the effects of this approach in patients with systemic lupus erythematosus (SLE) are yet to be revealed. In this study, we examined the effect of telemedicine on disease activity assessment and damage scores in patients with SLE. METHODS: This case-crossover study was nested within a national prospective cohort of patients with SLE in Saudi Arabia. Patients with SLE were included if they fulfilled the Systemic Lupus International Collaborating Clinics classification criteria between March 2020 and March 2021 and were assessed at three time points with 3 months between assessments, according to the standardised protocol of this cohort. Telemedicine was conducted for the first evaluation, while in-person assessments were used at the second and third visits. The primary outcome was the difference in the SLE disease activity index 2000 (SLEDAI-2K) score. The primary analysis was conducted using the repeated measure model and adjusted for potential confounders, including demographics, medications, and changes in steroid doses. Several sensitivity analyses were conducted to mitigate selection and time-varying confounders. RESULTS: A total of 92 participants were included in this study. Most patients were females (88%), with a mean (±standard deviation [SD]) age of 36 (±13) years. The mean (±SD) disease activity scores at baseline were as follows: SLEDAI-2K, 5 (±5); SLE responder index, 3.8 (±3.5); Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index, 1 (±1). The mean difference in SLEDAI-2K score was -1.641 (95% confidence interval -2.773 to -0.510, p = 0.005*) between telemedicine and follow-up visits. The results were consistent in all sensitivity analyses. CONCLUSION: We found that telemedicine assessment was associated with a much higher disease activity score than subsequent assessments, which may suggest an overestimation of disease activity and later assessment accuracy. Cautious adoption has been suggested for SLE patients with active disease.

Sex differences in the effects of inorganic nitrate supplementation on exercise economy and endurance capacity in healthy young adults.

Dietary nitrate (NO3-) is a widely used supplement purported to provide beneficial effects during exercise. Most studies to date include predominantly males. Therefore, the present study aimed to investigate if there is a sex-dependent effect of NO3- supplementation on exercise outcomes. We hypothesized that both sexes would exhibit improvements in exercise economy and exercise capacity following NO3- supplementation, but males would benefit to a greater extent. In a double-blind, randomized, crossover study, twelve females (24 ± 4 yr) and fourteen males (23 ± 4 yr) completed two 4-min moderate-intensity (MOD) exercise bouts followed by a time-to-exhaustion (TTE) task after following 3 days of NO3- supplementation (beetroot juice or BRJ) or NO3--depleted placebo (PL). Females were tested during the early follicular phase of the menstrual cycle. During MOD exercise, BRJ reduced the steady-state V̇o2 by ∼5% in males (M: Δ -87 ± 115 mL·min-1; P < 0.05) but not in females (F: Δ 6 ± 195 mL·min-1). Similarly, BRJ extended TTE by ∼15% in males (P < 0.05) but not in females. Dietary NO3- supplementation improved exercise economy during moderate-intensity exercise and exercise capacity during severe-intensity TTE in males but not in females. These differences could be related to estrogen levels, antioxidant capacity, nitrate-reducing bacteria, or a variety of known physiologic differences such as skeletal muscle calcium handling, and/or fiber type. Overall, our data suggests the ergogenic benefits of oral NO3- supplementation found in studies predominantly on male subjects may not be applicable to females.NEW & NOTEWORTHY While inorganic nitrate (NO3-) supplementation has increased in popularity as an ergogenic aid to improve exercise performance, the role of sex in NO3- supplementation on exercise outcomes is lacking despite known physiological differences during exercise between sex. This study revealed that males, but not females, improved exercise economy during submaximal exercise and exercise capacity during exercise within the severe-intensity domain following NO3- supplementation.

Bioequivalence evaluation and blood concentration estimation of generic and branded tacrolimus in healthy subjects under fasting: A randomized, four-periods, two-sequences, complete repeated, crossover study.

OBJECTIVE: The demand for generic tacrolimus is enormous. Our randomized trial was an open-label single-dose testing with four-periods and two-sequences; we aimed to evaluate the bioequivalence between a generic and branded tacrolimus by establishing their area under concentration-time curve (AUC) predictive equations. For better comparison, each tacrolimus served either as test vs. reference in sequence 1 or vice versa as reference vs. test in sequence 2. METHODS: Forty healthy subjects were randomized into two groups, namely a sequence 1 group (N = 20 in test-reference-test-reference) or sequence 2 (N = 20, reference-test-reference-test) received a test tacrolimus (Ruibeirong®; Chengdu Shengdi Medicine Co., Ltd.) and a reference tacrolimus (Astagraf XL®, Astellas Ireland Co., Ltd.) under the fasting condition with a wash-out period of ≥14 days between every two phases. Blood samples were collected sequentially until 120 h after oral administration of tacrolimus. RESULTS: A 95% upper confidence bound was -0.05% for the peak concentration (Cmax), -0.02% for the AUC from 0 to the last time point (AUC0-t), and - 0.02% for the AUC from 0 to infinity (AUC0-∞). The geometric least square means ratio (test/reference) with 90% of confidence interval (CI)) was 96.10% (90.58%-101.95%) for Cmax, 93.80% (88.52%-99.39%) for AUC0-t, and 94.34% (89.20%-99.77%) for AUC0-∞. Meanwhile, the ratio of within-subject standard deviation of test/reference (σWT/WR) with 90% CI was 0.66 (0.50-0.86) for Cmax, 0.73 (0.55-0.96) for AUC0-t, and 0.75 (0.57-0.98) for AUC0-∞. These results fulfilled the bioequivalence criteria by the Food and Drug Administration. Both products showed acceptable safety. Moreover, the AUC predictive equations (by linear regression plus limited sampling strategy) with 2-5 sampling time point showed the high performance (all R > 0.970, predictive error (PE) >0.5%, absolute PE <5.1%, which were interchangeable between test and reference products. CONCLUSION: Generic tacrolimus (Ruibeirong®) is bioequivalent to branded tacrolimus (Astagraf XL®) with tolerable safety, which AUC predictive equations work well and are interchangeable between the two products.