Creating a pharmacy elective course in Indigenous health.

BACKGROUND AND PURPOSE: There is a critical need for greater Indigenous health education and cultural safety training for pharmacists. The objective of this paper is to describe the creation, development, and impact of Canada's first offering of an undergraduate elective course specific to pharmaceutical care in Indigenous health. EDUCATIONAL ACTIVITY AND SETTING: A three-credit elective course was developed and offered to bachelor of science pharmacy students at the University of British Columbia. A variety of pedagogical approaches including reflection, educational trips, video conferencing with Indigenous communities, and Indigenous community-based projects were used. Evaluation of student learning impact included quantitative and qualitative post-course survey data, student enrollment, and student work. FINDINGS: From course inception in 2012 to 2017, 101 students participated. Survey respondents rated an average of 4.7 out of 5 on the five core elements of the curriculum design and pedagogical practice (i.e. learning objectives, instructional methods, assessments, organization, and workload). Thematic analysis identified three themes: 1) the qualities of the course instructors, 2) the unique curriculum design and pedagogical practices, and 3) significant personal and professional impact on students. SUMMARY: This course is one of few opportunities for pharmacy students to learn about cultural safety as it relates to the pharmaceutical care of Indigenous peoples. Extensive engagement with stakeholders and utilization of various teaching and assessment techniques were beyond the expected requirements of course offerings. Students highly rated this course as having personal and professional impact. This course plays a critical role in the overall Indigenization of pharmacy curricula.

Impact of choice of coping strategies and family functioning on psychosocial function of young people with epilepsy.

Both medical and psychological factors have an important impact upon the psychosocial functioning of young people with epilepsy. The purpose of this study was to identify factors that distinguish young people with epilepsy and high psychosocial functioning from those with lower levels. The participants were 114 young people (40 males, 74 females) with active epilepsy and a mean age of 17.92years (SD=3.90) who completed either a paper (60.5%) or a web-based survey (39.5%) comprising demographic, medical, and psychosocial measures. Psychosocial measures included family functioning, adolescent coping, anxiety, depression, and quality of life. A latent class analysis produced two psychosocial functioning groups based on participants' scores for anxiety, depression, and quality of life. Young people were more likely to be members of the group with poor psychosocial functioning if they had a seizure in the last month (Wald=5.63, p<.05), came from families with lower levels of communication and problem solving (Wald=5.28, p<.05), and made greater use of non-productive (emotion-focused) coping strategies such as wishful thinking, withdrawal, and worry (Wald=12.00, p<.01). The findings suggest that, in addition to standard medical treatment, clinicians may promote better outcomes by strengthening family functioning and encouraging less use of nonproductive coping strategies.

Functional genomics of attention-deficit/hyperactivity disorder (ADHD) risk alleles on dopamine transporter binding in ADHD and healthy control subjects.

BACKGROUND: The main aim of this study was to examine the relationship between dopamine transporter (DAT) binding in the striatum in individuals with and without attention-deficit/hyperactivity disorder (ADHD), attending to the 3'-untranslated region of the gene (3'-UTR) and intron8 variable number of tandem repeats (VNTR) polymorphisms of the DAT (SLC6A3) gene. METHODS: Subjects consisted of 68 psychotropic (including stimulant)-naïve and smoking-naïve volunteers between 18 and 55 years of age (ADHD n = 34; control subjects n = 34). Striatal DAT binding was measured with positron emission tomography with 11C altropane. Genotyping of the two DAT (SLC6A3) 3'-UTR and intron8 VNTRs used standard protocols. RESULTS: The gene frequencies of each of the gene polymorphisms assessed did not differ between the ADHD and control groups. The ADHD status (t = 2.99; p<.004) and 3'-UTR of SLC6A3 9 repeat carrier status (t = 2.74; p<.008) were independently and additively associated with increased DAT binding in the caudate. The ADHD status was associated with increased striatal (caudate) DAT binding regardless of 3'-UTR genotype, and 3'-UTR genotype was associated with increased striatal (caudate) DAT binding regardless of ADHD status. In contrast, there were no significant associations between polymorphisms of DAT intron8 or the 3'-UTR-intron8 haplotype with DAT binding. CONCLUSIONS: The 3'-UTR but not intron8 VNTR genotypes were associated with increased DAT binding in both ADHD patients and healthy control subjects. Both ADHD status and the 3'-UTR polymorphism status had an additive effect on DAT binding. Our findings suggest that an ADHD risk polymorphism (3'-UTR) of SLC6A3 has functional consequences on central nervous system DAT binding in humans.

Importance of pharmacokinetic profile and timing of coadministration of short- and long-acting formulations of methylphenidate on patterns of subjective responses and abuse potential.

OBJECTIVE: Subjective responses (ie, liking, disliking) to stimulants are thought to be proxies for abuse potential. Greater subjective responses have been documented in formulations that are more rapidly absorbed. However, repeat dosing has not been examined. METHODS: Subjective responses on the Drug Rating Questionnaire were compared in 26 healthy adults after administration of short- (immediate-release [IR] methylphenidate [MPH]) and long- (osmotically controlled-release oral delivery system [OROS] MPH) acting stimulant formulations. The second dose was administered 4 hours after initial dosing. All subjects received all 5 conditions (ie, placebo to placebo; IR-MPH to IR-MPH; IR-MPH to OROS-MPH; OROS-MPH to IR-MPH; or OROS-MPH to OROS-MPH) in a double-blind, counter-balanced design on 5 separate days. RESULTS: Plasma levels and subjective patterns of detection were higher when an IR formulation was administered during the ascending phase of a first-administered long-acting dose (OROS). CONCLUSION: These results emphasize the critical role that formulation type (IR vs OROS) and timing of administration (ascending vs descending phase) play when short- and long-acting formulations are coadministered. Such knowledge provides important information for clinicians about the safety and tolerability of the timing of repeat dosing of various permutations of coadministration of MPH formulations.

Understanding the central pharmacokinetics of spheroidal oral drug absorption system (SODAS) dexmethylphenidate: a positron emission tomography study of dopamine transporter receptor occupancy measured with C-11 altropane.

OBJECTIVE: Pediatric studies of the long-acting formulation (spheroidal oral drug absorption system [SODAS]) of the isomer dexmethylphenidate have shown a dose-dependent efficacy through 12 hours. However, there are no studies of central nervous system (CNS) dopamine transporter occupancies. METHOD: Eighteen healthy volunteers underwent positron emission tomography (PET) imaging with C-11 altropane before and after administration of oral doses of SODAS dexmethylphenidate. Each group of 6 subjects received 1 of 3 doses (20 mg, 30 mg, 40 mg) before PET imaging at 1, 8, 10, 12 (20 mg and 30 mg), or 1, 8, 10, and 14 (40 mg) hours after dosing. Transporter occupancy was calculated by standard methods. The study was conducted from January 2007 through December 2007. RESULTS: For all doses, plasma dexmethylphenidate levels and CNS dopamine transporter occupancies were greatest at 8 hours and decreased over time at 10, 12, and 14 hours. Plasma dexmethylphenidate levels were correlated to dose (P < .003). Mean plasma levels were ≥ 6 ng/mL to at least 8 hours with 20 mg (5.7 ng/mL), 10 hours with 30 mg, and 12 hours (extrapolated) with 40 mg. Dopamine transporter occupancies in the right caudate were 47% at 8 hours with 20 mg, 42% at hour 10 with 30 mg, and 46% (extrapolated) at hour 12 with 40 mg. Dopamine transporter occupancy was significantly correlated with plasma concentration of dexmethylphenidate (P < .001). CONCLUSIONS: These results confirm the study hypothesis that central dopamine transporter occupancy parallels peripheral pharmacokinetic findings in orally administered long-acting dexmethylphenidate in later hours after administration. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00593138.

Toward defining deficient emotional self-regulation in children with attention-deficit/hyperactivity disorder using the Child Behavior Checklist: a controlled study.

OBJECTIVE: Deficient emotional self-regulation (DESR) is characterized by deficits in self-regulating the physiological arousal caused by strong emotions. We examined whether a unique profile of the Child Behavior Checklist (CBCL) would help identify DESR in children with attention-deficit/hyperactivity disorder (ADHD). METHODS: Subjects included 197 children with ADHD and 224 children without ADHD. We defined DESR if a child had an aggregate cut-off score of > 180 but < 210 on the Anxiety/Depression, Aggression, and Attention scales of the CBCL (CBCL-DESR). This profile was selected because of: 1) its conceptual congruence with the clinical concept of DESR; and 2) because its extreme (> 210) form has been previously associated with severe forms of mood and behavioral dysregulation in children with ADHD. All subjects were comprehensively assessed with structured diagnostic interviews and a wide range of functional measures. RESULTS: Forty-four percent of children with ADHD had a positive CBCL-DESR profile versus 2% of controls (P < 0.001). The CBCL-DESR profile was associated with elevated rates of anxiety and disruptive behavior disorders, as well as significantly more impairments in emotional and interpersonal functioning. CONCLUSIONS: The CBCL-DESR profile helped identify a subgroup of children with ADHD who had a psychopathological and functional profile consistent with the clinical concept of DESR.

Predictors of persistent ADHD: an 11-year follow-up study.

OBJECTIVE: Despite the existence of several follow-up studies of children with ADHD followed up into adulthood, there is limited information on whether patterns of persistence and remission in ADHD can be predicted over the long term. The main aim of this study was to evaluate predictors of persistence of ADHD in a large sample of boys with and without ADHD followed prospectively for 11 years into young adulthood. METHOD: Subjects were Caucasian, non-Hispanic boys with (N = 110) and without (N = 105) ADHD who were 6-17 years old at the baseline assessment (mean age 11 years) and 15 to 31 years old at the follow-up assessment (mean age 22 years). Subjects were comprehensively and blindly assessed with structured diagnostic interviews and assessments of cognitive, social, school, and family functioning. RESULTS: At the 11-year follow-up, 78% of children with ADHD continued to have a full (35%) or a partial persistence (subsyndromal (22%), impaired functioning (15%), or remitted but treated (6%)). Predictors of persistence were severe impairment of ADHD, psychiatric comorbidity, and exposure to maternal psychopathology at baseline. CONCLUSIONS: These findings prospectively confirm that persistence of ADHD over the long term is predictable from psychosocial adversity and psychiatric comorbidity ascertained 11 years earlier.

A positron emission tomography study examining the dopaminergic activity of armodafinil in adults using [¹¹C]altropane and [¹¹C]raclopride.

BACKGROUND: Armodafinil, prescribed principally to treat narcolepsy, is undergoing assessment of therapeutic potential for other neuropsychiatric disorders and medical conditions. The neurochemical substrates and mechanisms of armodafinil are unresolved. We investigated the hypothesis that armodafinil enhances wakefulness by modulating the activities of the dopamine transporter (DAT). With positron emission tomography imaging, we determined DAT occupancy and changes in extracellular dopamine by armodafinil in vivo. METHODS: Twelve subjects were enrolled. Plasma armodafinil levels were obtained. In vivo armodafinil occupancy of the DAT in striatum was detected by [¹¹C]altropane and changes in extracellular dopamine were detected by indirect displacement of [¹¹C]raclopride in human subjects at different times after drug administration. RESULTS: Armodafinil (100 mg by mouth [PO]) occupied striatal DAT (34.0 ± 9.0% at 1 hour, 40.4 ± 9.5% at 2.5 hours, n = 6) and 250 mg occupied striatal DAT (60.5 ± 7.4% at 1 hour, 65.2 ± 6.1% at 2.5 hours, n = 6). In addition, armodafinil was associated with changes in extracellular dopamine (17.8 ± 30.1% [100 mg PO] and 7.0 ± 8.6% [250 mg PO] at 2.5 hours, n = 6). CONCLUSIONS: Occupancy of the DAT and changes in extracellular dopamine in vivo further implicates the actions of armodafinil on DAT as a potential candidate for its therapeutic improvement of wakefulness and other conditions.

Familial risk analysis of the association between attention-deficit/hyperactivity disorder and psychoactive substance use disorder in female adolescents: a controlled study.

BACKGROUND: A robust and bi-directional comorbidity between attention-deficit/hyperactivity disorder (ADHD) and psychoactive substance use disorder (PSUD, alcohol or drug abuse, or dependence) has been consistently reported in the literature. However, this literature has been based almost exclusively on male only samples and, therefore, the findings may not generalize to females. METHODS: First-degree relatives from a large sample of pediatrically and psychiatrically referred girls with (123 probands, 403 relatives) and without ADHD (112 probands, 359 relatives) were comprehensively assessed by blind raters with structured diagnostic interviews. Familial risk analysis examined the risks in first-degree relatives for ADHD and PSUD (alcohol or drug abuse or dependence) after stratifying probands by the presence and absence of these disorders. RESULTS: ADHD in the proband significantly increased the risk for ADHD in relatives independently of the comorbidity with PSUD. PSUD in the proband was associated with a significantly increased risk for PSUD in relatives regardless of ADHD status. There was no evidence of co-segregation or non-random mating in the families of probands with ADHD and PSUD. CONCLUSIONS: Patterns of familial risk analysis suggest that the association between ADHD and PSUD in adolescent females is most consistent with the hypothesis that these disorders are independently transmitted, although the hypothesis of variable expressivity could not be ruled out. These findings are consistent with previously reported patterns of familial associations between ADHD and PSUD found in adolescent males. Longer follow-up periods are needed to more fully clarify the relationship between ADHD and PSUD, as well as provide adequate power for separate analyses of alcohol and drug use.