Longitudinal progression of diabetes mellitus in Wolfram syndrome: The Washington University Wolfram Research Clinic experience.

OBJECTIVE: (1) Describe the progression of diabetes mellitus over time in an observational study of Wolfram syndrome, a rare, genetic, neurodegenerative disorder, which often includes diabetes mellitus and is typically diagnosed during childhood or adolescence. (2) Determine whether C-peptide could be used as a marker of diabetes progression in interventional trials for Wolfram syndrome. METHODS: N = 44 (25F/19M) participants with genetically confirmed Wolfram syndrome attended the Washington University Wolfram Research Clinic annually from 2010 to 2019. Medical history, physical examinations, blood sampling, and questionnaires were used to collect data about diabetes mellitus and other components of Wolfram syndrome. Beta-cell function was assessed by determination of C-peptide during a mixed meal tolerance test. Random coefficients models evaluated the rate of progression of C-peptide over time, and power analyses were used to estimate the number of subjects needed to detect a change in C-peptide decline during an intervention trial. RESULTS: 93.2% of patients had diabetes mellitus. Mean HbA1c across all study visits was 7.9%. C-peptide significantly decreased with increasing duration of diabetes mellitus (p < 0.0001); an optimal break point in C-peptide decline was identified to occur between 0.1 and 2.3 years after diabetes mellitus diagnosis. Twenty patients per group (active vs. control) were estimated to be needed to detect a 60% slowing of C-peptide decline during the first 2.3 years following diabetes diagnosis. CONCLUSION: C-peptide declines over time in Wolfram syndrome and could potentially be used as a marker of diabetes progression in interventional studies for Wolfram syndrome, especially within the first 2 years after diabetes diagnosis.

The effect of expectation on transcranial direct current stimulation (tDCS) to suppress food craving and eating in individuals with overweight and obesity.

Transcranial direct current stimulation (tDCS) is a neuromodulation technique with potential to treat eating disorders and obesity. As for any potential treatment, it is important to assess the degree to which expectation effects contribute to its reported efficacy. This study assessed the effect of tDCS on amount of food craving and eating while tightly controlling treatment expectation. N = 74 adults with overweight or obesity were informed of the known effects of tDCS to suppress craving and eating. Once electrodes were on the head, half of the participants were told they were receiving real, and the other half sham tDCS. Within these groups, approximately half actually received real and the other half sham tDCS. Stimulation parameters used were those previously found to reduce craving and eating, including in our lab: 2 mA, anode right/cathode left targeting the dorsolateral prefrontal cortex for 20 min (real), or only for the first and last minute (sham). Analyses controlled for demographics, hunger, trait impulsiveness, eating motives, dieting, binge eating, suggestibility, and baseline craving and eating. Participants told they were receiving real tDCS craved and ate less than participants told they were receiving sham tDCS (both p < 0.01), regardless of tDCS condition administered. There was no main effect of real vs. sham tDCS on craving or eating or an interaction between tDCS condition and expectation. The scientific validation of tDCS as a treatment for eating-related conditions hinges on controlling for the powerful effects of expectation. This can include the type of information provided on consent forms and participants' ability to guess real from sham conditions.

Baseline motives for eating palatable food: racial differences and preliminary utility in predicting weight loss.

PURPOSE: Behavioral predictors of weight-loss program (WLP) outcomes are needed and important because they can be modified. Eating calorie-dense palatable foods (PFs) outside of hunger contributes to obesity. This study assessed if habitual motives to consume PFs could predict weight-loss outcomes. METHODS: N = 171 Black and N = 141 White adults in a reduced-calorie program completed the Palatable Eating Motives Scale (PEMS). Body weight and body mass index (BMI) lost after 3 and 6 months were analyzed controlling for initial BMI and demographics. Greater PEMS motive scores meant more frequent habitual intake of PFs for that motive. RESULTS: Whites vs. Blacks had higher scores on most of the PEMS motives: Social, Coping, and Reward Enhancement. In Whites at 3 months, greater Reward Enhancement scores and initial BMI predicted more BMI loss (p < 0.05). At 6 months, greater Reward Enhancement and lower Conformity scores predicted more weight (p < 0.05) and BMI loss (Conformity: p < 0.05; Reward Enhancement: p = 0.05). PEMS motives did not predict outcomes for Blacks. CONCLUSION: The results provide preliminary evidence for the PEMS to predict WLP outcomes. White patients who eat PFs primarily for their rewarding properties and less to conform should fare better in Lifestyle programs while group or family-based interventions may be more efficacious when conformity is the main motive. Lower motive scores among Blacks suggest that eating PFs outside of hunger may go unrecognized or underreported and warrants further investigation. The findings highlight the motive-based heterogeneity of obesity and how it may be used to predict outcomes and customize interventions to improve WLP outcomes. LEVEL OF EVIDENCE: Level IV, multiple time series.

The critical role of cognitive-based trait differences in transcranial direct current stimulation (tDCS) suppression of food craving and eating in frank obesity.

Obesity remains a major public health concern and novel treatments are needed. Transcranial direct current stimulation (tDCS) is a neuromodulation technique shown to reduce food craving and consumption, especially when targeting the dorsolateral prefrontal cortex (DLPFC) with a right anode/left cathode electrode montage. Despite the implications to treat frank (non-bingeeating) obesity, no study has tested the right anode/left cathode montage in this population. Additionally, most tDCS appetite studies have not controlled for differences in traits under DLPFC control that may influence how well one responds to tDCS. Hence, N = 18 (10F/8M) adults with frank obesity completed the Dutch Eating Behavior Questionnaire-Restraint and Barratt Impulsiveness Scale, and received 20 min of 2 mA active tDCS and control tDCS session. Craving and eating was assessed at both sessions with a food photo "wanting" test and in-lab measures of total, preferred, and less-preferred kilocalories consumed of three highly palatable snack foods. While main effects of tDCS vs. control were not found, significant differences emerged when trait scores were controlled. tDCS reduced food craving in females with lower attention-type impulsiveness (p = 0.047), reduced preferred-food consumption in males with lower intent to restrict calories (p = 0.024), and reduced total food consumption in males with higher non-planning-type impulsiveness (p = 0.009) compared to control tDCS. This is the first study to find significant reductions in food craving and consumption in a sample with frank obesity using the most popular tDCS montage in appetite studies. The results also highlight the cognitive-based heterogeneity of individuals with obesity and the importance of considering these differences when evaluating the efficacy of DLPFC-targeted tDCS in future studies aimed at treating obesity.

Initial Employment Plans of PharmD Graduates from Ten Public Colleges/Schools of Pharmacy, 2018-2022.

OBJECTIVE: Since 2009, the Big Ten Pharmacy Assessment Collaborative has surveyed their Doctor of Pharmacy (PharmD) graduates regarding their first employment plans. The current study updates the results from 2013-2017, since which the nationwide demand for pharmacists decreased, then increased again due to COVID-19. METHODS: Quantitative first-position employment data from 2018-2022 were tracked among 6687 Big Ten PharmD graduates. Outcomes included job/residency/fellowship placement; satisfaction with placement; salary; time spent searching; and perceived difficulty finding placement. RESULTS: Over the study period, 5276 usable surveys were received (survey participation rate 79%). Respondents who reported applying for employment (2699) spent nearly 3 months searching for a position, although 64% had received employment offers before graduation. Annual salaries in pharmacy positions of at least 32 h per week (excluding residencies or fellowships) trended downward from $113,754 in 2018 to $99,175 in 2021, rebounding to $114,097 in 2022. Approximately 42% of respondents who applied for jobs reported difficulty finding a position in 2018 and 2019, decreasing to 20% in 2022. In total, 73% of respondents were satisfied with the offers they received, with 72% finding positions in their preferred job setting. An average of 57% applied for residencies from 2018 to 2022, nearly 10% higher than 2013-2017, with 76% of applicants matching. An additional 19% planned to pursue additional academic degrees, fellowship training, or both. CONCLUSION: From 2018 to 2022, Big Ten PharmD graduates found pharmacy-related first positions to the same extent as did Big Ten PharmD graduates from 2013-2017, at similar salaries.

Perception and Awareness of Diabetes Risk and Reported Risk-Reducing Behaviors in Adolescents.

Importance: Lifestyle change is central to diabetes risk reduction in youth with overweight or obesity. Feeling susceptible to a health threat can be motivational in adults. Objective: To evaluate associations between diabetes risk perception and/or awareness and health behaviors in youth. Design, Setting, and Participants: This cross-sectional study analyzed data from the US National Health and Nutrition Examination Survey 2011 to 2018. Participants included youths aged 12 to 17 years with body mass index (BMI) in the 85th percentile or higher without known diabetes. Analyses were conducted from February 2022 to February 2023. Main Outcomes and Measures: Outcomes included physical activity, screen time, and attempted weight loss. Confounders included age, sex, race and ethnicity, and objective diabetes risk (BMI, hemoglobin A1c [HbA1c]). Exposures: Independent variables included diabetes risk perception (feeling at risk) and awareness (told by clinician), as well as potential barriers (eg, food insecurity, household size, insurance). Results: The sample included 1341 individuals representing 8 716 794 US youths aged 12 to 17 years with BMI in the 85th percentile or higher for age and sex. The mean age was 15.0 years (95% CI, 14.9-15.2 years) and mean BMI z score was 1.76 (95% CI 1.73-1.79). Elevated HbA1c was present in 8.6% (HbA1c 5.7%-6.4%: 8.3% [95% CI, 6.5%-10.5%]; HbA1c ≥6.5%: 0.3% [95% CI, 0.1%-0.7%]). Nearly one-third of youth with elevated HbA1c reported risk perception (30.1% [95% CI, 23.1%-38.1%), while one-quarter (26.5% [95% CI, 20.0%-34.2%]) had risk awareness. Risk perception was associated with increased TV watching (ß = 0.3 hours per day [95% CI, 0.2-0.5 hours per day]) and approximately 1 less day per week with at least 60 minutes of physical activity (ß = -1.2 [95% CI, -2.0 to -0.4) but not with nutrition or weight loss attempts. Awareness was not associated with health behaviors. Potential barriers had mixed associations: larger households (≥5 members vs 1-2) reported lower consumption of non-home-prepared meals (OR 0.4 [95% CI, 0.2-0.7]) and lower screen time (ß = -1.1 hours per day [95% CI, -2.0 to -0.3 hours per day), while public insurance (vs private) was associated with approximately 20 fewer minutes per day of physical activity (ß = -20.7 minutes per day [95% CI, 35.5 to -5.8 minutes per day]). Conclusions and Relevance: In this cross-sectional study including a US-representative sample of adolescents with overweight or obesity, diabetes risk perception and awareness were not associated with greater engagement in risk-reducing behaviors in youth. These findings suggest the need to address barriers to engagement in lifestyle change, including economic disadvantage.

Longitudinal associations between weight indices, cognition, and mental health from childhood to early adolescence.

Childhood obesity has been associated with lower cognitive performance and worse mental health in cross-sectional studies. However, it is unclear whether these findings extend longitudinally and in what causal direction. Using data from the Adolescent Brain Cognitive Development (ABCD) Study (maximum analytical n = 6671, 48.3% girls, 42.8% non-White), we examined how body mass index (BMI) at baseline (ages 9-11) relate prospectively to changes in cognition or psychopathology across the 2 years thereafter, and vice versa. Cognitive tests included the National Institutes of Health Toolbox Cognition Battery, Little Man Task of mental rotation, and Rey Auditory Verbal Learning Test. Psychopathology was assessed using caregiver-reported Child Behavior Checklist. Linear mixed models adjusted for sociodemographic and developmental covariates indicated that lower baseline performance on most cognitive tests was associated with greater longitudinal BMI gain (eg, 1 point lower than median on Picture Vocabulary corresponded to 0.012 kg/m2 [1.6%; 95% CI, 0.008 to 0.016 kg/m2] more annual BMI gain, PFDR < .001), whereas baseline BMI was unrelated to longitudinal changes in cognition (PFDR ≥ .12; including after considering practice effects). Greater broad-spectrum psychopathology at baseline was associated with increased BMI gain (eg, each endorsement of externalizing problems than none corresponded to 0.015 kg/m2 [2.2%; 95% CI, 0.009 to 0.021 kg/m2] more annual BMI gain, PFDR < .001) and, reciprocally, greater baseline BMI was linked specifically to more longitudinal withdrawn/depressed and depression problems (0.010 [22%; 95% CI, 0.004 to 0.016] and 0.011 [15%; 95% CI, 0.004 to 0.017] more problems annually per 1 kg/m2 above median BMI, PFDR = .003 and .008). The associations did not differ in boys vs. girls (PFDR ≥ .40), and remained stable with waist circumference as the weight index and in subgroups of participants without weight-altering medications or common baseline psychiatric diagnoses. Our longitudinal findings expand previous cross-sectional works and highlight the importance of cognitive and mental health to children's weight development and links between weight and depression.

NAPLEX Preparation Program Characteristics and Resources Associated With First-Time Exam Pass Rates.

OBJECTIVE: Pharmacy colleges and schools invest substantial faculty effort and financial resources in North America Pharmacist Licensure Exam (NAPLEX) preparation, including vendor products purported to improve NAPLEX pass rates. The objective of this project was to examine NAPLEX preparation program characteristics associated with first-time pass rates. METHODS: A national survey investigated which pharmacy schools provided a formal NAPLEX preparation program in the 2021/2022 academic year, and what resources students were required to use. Pharmacy school characteristics and the unique resources provided in NAPLEX preparation programs were separately analyzed for association with 2022 NAPLEX first-time pass rates. RESULTS: The survey response rate was 71% (100 pharmacy schools). Of the 6 pharmacy school characteristics analyzed, offering a formal NAPLEX preparation program and private status were both weakly correlated with a decrease in the 2022 NAPLEX pass rate, while founding year of 2000 or earlier was weakly correlated with an increase in the pass rate. In a generalized linear model, a decrease in 2022 NAPLEX pass rate was associated with offering a formal NAPLEX preparation program (-5.90% [-11.55 to -0.23]) and with a 3-year accelerated curriculum (-9.15% [-15.55 to -2.75]). Of 12 resources required in NAPLEX preparation programs, 3 were weakly correlated with a decrease in 2022 pass rate: a vendor question bank, vendor review book/materials, and a live, synchronous faculty-led review. In a generalized linear model, a decrease in 2022 NAPLEX pass rate was associated with a live, synchronous faculty-led review (-6.62% [-11.16 to -2.08]). Among schools without a formal preparation program, NAPLEX pass rates consistently exceeded the national average in 2020, 2021, and 2022, while the proportion of schools with NAPLEX preparation programs and first-time pass rates above the national average dropped from 59% in 2021 and 58% in 2020 to 44% in 2022. CONCLUSION: Simply implementing a NAPLEX preparation program is insufficient to overcome other systemic/programmatic influences of successfully passing the NAPLEX; programs should invest earlier resources to address NAPLEX competencies.

A Description of NAPLEX and MPJE Preparation Strategies Among US Colleges and Schools of Pharmacy.

OBJECTIVE: The purpose of this study was to describe the different strategies used to supplement North American Pharmacist Licensure Examination (NAPLEX) and Multistate Pharmacy Jurisprudence Examination (MPJE) preparation in the US pharmacy programs. METHODS: An online survey was developed to gather information from 141 accredited schools/colleges of pharmacy about the preparation methods used during the 2021-22 academic year. The questionnaire contained 19 NAPLEX- and 10 MPJE-specific questions related to timing, content, use of commercial products and programs, faculty involvement, and whether these activities were required or recommended. Characteristics of schools/colleges were compared based on the presence or absence of preparation programs; preparation programs were descriptively reported. RESULTS: The response rate was 71%. Most schools (87/100 respondents) provided NAPLEX preparation programs starting in the advanced pharmacy practice experiential year, required students to participate, and focused on reviewing the content instead of assessing students' examination readiness. Similar elements were reported among 61 schools providing MPJE preparation programs. Schools used a variety of resources including access to vendor-based question banks or review materials, and completing live, proctored, NAPLEX-like examinations. Characteristics of schools or colleges did not differ significantly based on presence or absence of a preparation program. CONCLUSION: Schools/colleges of pharmacy use a variety of strategies to prepare students for licensing examinations. Many require student participation in vendor-based preparation programs for NAPLEX, and homegrown programs for MPJE preparation. The next step will be to determine the effectiveness of various approaches used by the schools/colleges on first-time licensure examination attempts.

Childhood obesity is linked to putative neuroinflammation in brain white matter, hypothalamus, and striatum.

Neuroinflammation is both a consequence and driver of overfeeding and weight gain in rodent obesity models. Advances in magnetic resonance imaging (MRI) enable investigations of brain microstructure that suggests neuroinflammation in human obesity. To assess the convergent validity across MRI techniques and extend previous findings, we used diffusion basis spectrum imaging (DBSI) to characterize obesity-associated alterations in brain microstructure in 601 children (age 9-11 years) from the Adolescent Brain Cognitive DevelopmentSM Study. Compared with children with normal-weight, greater DBSI restricted fraction (RF), reflecting neuroinflammation-related cellularity, was seen in widespread white matter in children with overweight and obesity. Greater DBSI-RF in hypothalamus, caudate nucleus, putamen, and, in particular, nucleus accumbens, correlated with higher baseline body mass index and related anthropometrics. Comparable findings were seen in the striatum with a previously reported restriction spectrum imaging (RSI) model. Gain in waist circumference over 1 and 2 years related, at nominal significance, to greater baseline RSI-assessed restricted diffusion in nucleus accumbens and caudate nucleus, and DBSI-RF in hypothalamus, respectively. Here we demonstrate that childhood obesity is associated with microstructural alterations in white matter, hypothalamus, and striatum. Our results also support the reproducibility, across MRI methods, of findings of obesity-related putative neuroinflammation in children.

Detection of Academic Early Warning Signs and Effective Intervention "Takes a Village".

Early intervention for students at risk of academic difficulty can be more effectively accomplished using a team-based approach that capitalizes on the expertise of many in a pharmacy education community. Authored by members of the Big Ten Alliance Pharmacy Assessment Collaborative, this commentary advocates for better integration of assessment professionals, pharmacy faculty, and student support services to capture academic, accountability, and behavior-related data that might signal student intellectual and/or behavioral challenges and manifest as marginal academic performance. Assessment professionals can assist with creating data dashboards/monitoring systems, recognizing trends within the data, refining formulas to identify at-risk students, and measuring the impact of interventions to determine which approaches positively and significantly influence outcomes. Effective early warning and intervention takes a village and should go beyond narrowly focused attempts that fail to account for the complexity of students as individuals or fail to acknowledge the multifaceted skill set students are expected to develop to become competent and responsible pharmacists.

Technological Ecological Momentary Assessment Tools to Study Type 1 Diabetes in Youth: Viewpoint of Methodologies.

Type 1 diabetes (T1D) is one of the most common chronic childhood diseases, and its prevalence is rapidly increasing. The management of glucose in T1D is challenging, as youth must consider a myriad of factors when making diabetes care decisions. This task often leads to significant hyperglycemia, hypoglycemia, and glucose variability throughout the day, which have been associated with short- and long-term medical complications. At present, most of what is known about each of these complications and the health behaviors that may lead to them have been uncovered in the clinical setting or in laboratory-based research. However, the tools often used in these settings are limited in their ability to capture the dynamic behaviors, feelings, and physiological changes associated with T1D that fluctuate from moment to moment throughout the day. A better understanding of T1D in daily life could potentially aid in the development of interventions to improve diabetes care and mitigate the negative medical consequences associated with it. Therefore, there is a need to measure repeated, real-time, and real-world features of this disease in youth. This approach is known as ecological momentary assessment (EMA), and it has considerable advantages to in-lab research. Thus, this viewpoint aims to describe EMA tools that have been used to collect data in the daily lives of youth with T1D and discuss studies that explored the nuances of T1D in daily life using these methods. This viewpoint focuses on the following EMA methods: continuous glucose monitoring, actigraphy, ambulatory blood pressure monitoring, personal digital assistants, smartphones, and phone-based systems. The viewpoint also discusses the benefits of using EMA methods to collect important data that might not otherwise be collected in the laboratory and the limitations of each tool, future directions of the field, and possible clinical implications for their use.

Examining the interdependence of parent-child dyads: Effects on weight loss and maintenance.

BACKGROUND: This study aimed to further elucidate correlated weight changes in parent-child dyads enrolled in family-based treatment (FBT) by modeling the interdependence of weight changes during treatment. METHODS: Parent-child dyads (n = 172) with overweight/obesity (child mean zBMI = 2.16 ± 0.39; parent mean BMI = 37.9 ± 9.4 kg/m2 ) completed 4 months of FBT and were randomized to one of three 8-month maintenance interventions (Social Facilitation Maintenance [SFM]-high dose, SFM-low dose or control). Weight/height was measured at 0, 4 and 12 months. Structural equation models simultaneously estimated the effect that an individual had on their own (actor effect) and on one another's (partner effect) weight-status across time using the actor-partner interdependence model. RESULTS: Actor paths were significant over time for parent and child. Partner paths were significant for child zBMI predicting parent BMI at 4 and 12 months. Maintenance condition moderated actor/partner paths in the model. CONCLUSIONS: Child weight change may motivate parents to make environmental and behavioural changes that impact their own weight. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00759746.

Leveraging a required e-portfolio course to meet multiple needs: Student assessment, curriculum improvement, and accreditation.

BACKGROUND: Learning portfolios enable student pharmacists to connect program outcomes and related learning experiences to future practice as healthcare providers. Assessment programs also require data to inform decisions regarding curriculum quality and maintain program accreditation. Our goal was to create a portfolio meeting multiple needs, including learning improvement, curricular assessment, and accreditation. EDUCATIONAL ACTIVITY: In this required, longitudinal, learning e-portfolio course, students upload artifacts and reflect on how the corresponding learning experiences link to program outcomes and their own continuous professional development. Baseline and annual self-assessment ratings and guided reflections document progress toward learning outcome attainment. Individualized formative feedback from pharmacist reviewers develops student capacity for reflection, improves ability to assess their own strengths and weaknesses, and promotes lifelong learning. De-identified quantitative and qualitative data is shared with stakeholders for purposes of improvement. CRITICAL ANALYSIS OF THE EDUCATIONAL ACTIVITY: Through deliberate design of the course, a corresponding plan for assessment, and modification of portfolio software platform reporting capabilities, the program has been able to acquire rich quantitative and qualitative data regarding individual student and cohort performance. This has enabled us to review these data to make improvements in individual learning experiences and make informed decisions regarding curricular effectiveness and accreditation requirements as part of the collegiate assessment plan. This course provides a wealth of opportunity for student growth and generation of assessment data, but it is best suited for programs with ample support resources to maintain its integrity as designed.

Considerations for the incorporation of mindfulness into pharmacy education.

INTRODUCTION: A range of approaches are needed to bolster the mental health and well-being of pharmacists and student pharmacists. COMMENTARY: In recent years, medical and nursing educators have been training students to use mindfulness-oriented meditation (MOM) techniques such as Mindfulness-Based Stress Reduction (MBSR) for mental health, wellness, and greater attention and presence. MOM training should be considered for incorporation into pharmacy education. Mindfulness can be included in the pharmacy curriculum in a variety of ways. These include introducing students to the topic didactically, encouraging and facilitating students to take an MBSR course, workshop, or online self-study, and integrating mindfulness through mindful moments during critical educational activities like product verification and communication assessments. IMPLICATIONS: Mindfulness may be a valuable skill for student pharmacists, thus we encourage schools to expose students to the concepts of mindfulness and MOM techniques like MBSR. Additionally, more robust and rigorous research is needed to better understand the effects of MOM in different settings and contexts.