Pharmacogenomic Profiling of Pediatric Patients on Psychotropic Medications in an Emergency Department.

OBJECTIVE: The aim of the study was to evaluate the ability of a combinatorial pharmacogenomic test to predict medication blood levels and relative clinical improvements in a selected pediatric population. METHODS: This study enrolled patients between ages 3 to 18 years who presented to a pediatric emergency department with acute psychiatric, behavioral, or mental health crisis and/or concerns, and had previously been prescribed psychotropic medications. Patients received combinatorial pharmacogenomic testing with medications categorized according to gene-drug interactions (GDIs); medications with a GDI were considered "incongruent," and medications without a GDI were considered "congruent." Blood levels for escitalopram, fluoxetine, aripiprazole, and clonidine were evaluated according to level of GDI. Relative clinical improvements in response to the prescribed psychotropic medications were measured using a parent-rated Clinical Global Impression of Improvement (CGI-I) assessment, where lower scores corresponded with greater improvement. RESULTS: Of the 100 patients enrolled, 73% reported taking ≥1 incongruent medication. There was no significant difference in CGI-I scores between patients prescribed congruent versus incongruent medications (3.37 vs 3.68, P = 0.343). Among patients who presented for depression or suicidal ideation, those prescribed congruent medications had significantly lower CGI-I scores compared with those taking incongruent medications ( P = 0.036 for depression, P = 0.018 for suicidal ideation). There was a significant association between medication GDI and blood levels for aripiprazole (n = 15, P = 0.01) and escitalopram (n = 10, P = 0.01). CONCLUSIONS: Our preliminary findings suggest that combinatorial pharmacogenomic testing can predict medication blood levels and relative outcomes based on medication congruency in children presenting to an emergency department with acute psychiatric/behavioral crises. Additional studies will be needed to confirm these findings.

Exploring the experience of a cognitive rehabilitation intervention for cancer-related cognitive change in people living with cancer: An interpretative phenomenological analysis.

OBJECTIVES: Some cancer patients experience cancer-related cognitive change (CRCC). Cognitive rehabilitation interventions (CRIs) have recently been developed to help mitigate the impact of CRCC, which, untreated, can impact resumption of daily life post-cancer treatment. The experience of participants is important to understand but largely absent within research literature. This study aimed to explore how those with CRCC experience the phenomenon following completion of a CRI. METHODS: This study comprised a qualitative phenomenological approach. This involved conducting in-depth, semi-structured interviews with 6 self-referred participants from one CRI. Participants were invited to discuss their experience of CRCC and what the CRI therefore meant to them. Interviews were analyzed using interpretative phenomenological analysis. RESULTS: Analysis of the findings revealed 4 key themes. (1) "Experiencing and addressing isolation" comprises reflections on posttreatment perceived abandonment and consequent feelings of belonging through CRI participation. (2) "Identity" explores participants' reflections around perceived loss-of-self and feelings of empowerment from the intervention. (3) "Cognitive and physical balance" comprises the planning and choices participants make, supported by both their own and CRI coping strategies as they seek acceptance of cognitive change. (4) "Course reflections" explore reflections on intervention structure, format, and delivery, focusing on 2 subthemes of accessibility, flexibility and inclusivity, and communication. All participants reflected positively on their experience. SIGNIFICANCE OF RESULTS: Results support further dissemination among health professionals and implementation of this CRI to better support self-reported CRCC concerns within this population. Future qualitative research should explore the long-term impact of CRI interventions.

Development of a questionnaire to assess student behavioral confidence to undertake interprofessional education activities.

Measurement of the impact of interprofessional education (IPE) is the golden chalice educationalists chase. We undertook the development of a scale to measure IPE Academic Behavioral Confidence (IPE-ABC) in allied health, nursing, and social work pre-registration students. This work formed part of the evaluation of a large IPE framework embedded across two Scottish universities. General ABC has been shown to influence student perceptions of study experiences and it is thus reasonable to postulate that ABC could influence student perceptions of IPE. This research developed a questionnaire to ascertain health and social care students' confidence to engage in IPE, utilizing a mixed method approach. Fifteen different professional groups of pre-registration students (n = 565) participated in the assessment of the 38 item questionnaire. Exploratory factor analysis identified three factors: 1/interprofessional teamwork, 2/behaviors underpinning collaboration, and 3/interprofessional communication collectively accounting for 38.2% of the variance. Internal consistency of the overall scale (Cronbach's α = .93) was very good with subscales demonstrating very good internal consistency, 1 (α = .89), or respectable consistency 2 (α = .78) and 3 (α = .79). We conclude the IPE-ABC questionnaire could be utilized to enhance and assess the success of IPE related activities.

An online module evaluation of the role and effectiveness of wikis in fostering collaborative practice skills in interprofessional education: a short report.

This short report focuses on student feedback relating to the use of online group wikis as a means of a summative assessment intended to foster skills in collaborative practice for a large interprofessional education (IPE) module. Electronic feedback from 112 (72.2% response rate) students suggested wikis were a key area of the module. Open text comments relating to the wikis were extracted and categorized initially as positive or negative, with sub-themes then identified within these two broad categories. Findings showed that students valued the experience of a novel type of assessment but felt the amount of work required was too great. We concluded that digital capabilities need to be part of the developmental skill set of students. This raises important issues for further research to consider whether wikis themselves as a computer supported collaborative learning tool are appropriate for large scale IPE delivery.

Distinct periods of developmental sensitivity to the effects of 3,4-(±)-methylenedioxymethamphetamine (MDMA) on behaviour and monoamines in rats.

Previous findings showed allocentric and egocentric learning deficits in rats after MDMA treatment from postnatal days (PD) 11-20 but not after treatment from PD 1-10. Shorter treatment periods (PD 1-5, 6-10, 11-15, or 16-20) resulted in allocentric learning deficits averaged across intervals but not for any interval individually and no egocentric learning deficits individually or collectively. Whether this difference was attributable to treatment length or age at the start of treatment was unclear. In the present experiment rat litters were treated on PD 1-10, 6-15, or 11-20 with 0, 10, or 15 mg/kg MDMA q.i.d. at 2-h intervals. Two male/female pairs/litter received each treatment. One pair/litter received acoustic startle with prepulse inhibition, straight channel swimming, Cincinnati water maze (CWM), and conditioned fear in a latent inhibition paradigm. The other pair/litter received locomotor activity, straight channel swimming, Morris water maze (MWM), and locomotor activity retest with MK-801 challenge. MDMA impaired CWM learning following PD 6-15 or 11-20 exposure. In MWM acquisition, all MDMA-treated groups showed impairment. During reversal and shift, the PD 6-15 and PD 11-20 MDMA-treated groups were significantly impaired. Reductions in locomotor activity were most evident after PD 6-15 treatment while increases in acoustic startle were most evident after PD 1-10 treatment. After MK-801 challenge, MDMA-treated offspring showed less locomotion compared to controls. Region-specific changes in brain monoamines were also observed but were not significantly correlated with behavioural changes. The results show that PD 11-20 exposure to MDMA caused the largest long-term cognitive deficits followed by PD 6-15 exposure with PD 1-10 exposure least affected. Other effects, such as those upon MK-801-stimulated locomotion showed greatest effects after PD 1-10 MDMA exposure. Hence, each effect has a different window of developmental susceptibility.

Beyond tingles: An exploratory qualitative study of the Autonomous Sensory Meridian Response (ASMR).

This qualitative exploratory study investigated the embodied experiences and the meanings of Autonomous Sensory Meridian Response (ASMR) from the viewer's perspective. ASMR research has been sparse and largely quantitative, assuming it to be a predominantly fixed physiological response of "tingles", despite the acronym being rooted in pseudoscience. A qualitative research design was adopted to facilitate the exploratory nature of the study in this under-researched area. In contrast to the mostly survey-based research on ASMR, this study employed semi-structured interviews as a means to understand the lived experience of ASMR and to promote participant agency. Six self-identifying ASMR consumers were recruited using a mixture of snowball and opportunity sampling. Semi-structured interviews were conducted both in person and using Skype to facilitate transnational data collection. Interview transcripts were analysed using an inductive, data-driven approach to thematic analysis. The analysis suggests that ASMR is felt to provide a social environment of comfort rather than a solely physiological-based experience. Three key themes emerged: who and what defines ASMR? (reflecting the variety of what was classed as ASMR and what content was consumed to produce the response); "real" intimacy tailored to me (reflecting the idiosyncratic perception of intimacy made possible through ASMR); and emotional relief on my terms (reflecting the role of ASMR in self-soothing). The present data reflect a rich, complex experience of the ASMR consumer, pointing to potential wider applications and informing further research.

Developmental treatment with the dopamine D2/3 agonist quinpirole selectively impairs spatial learning in the Morris water maze.

Developmental exposure to the dopamine D2/3 receptor agonist quinpirole is reported to induce D2 priming, impair Morris water maze performance, reduce acoustic startle prepulse inhibition (PPI), and alter locomotor activity. We treated rats from postnatal days 1-21 with the dose reported to induce these effects, 1.0 mg/kg/day, and two higher doses, 2.0 and 4.0 mg/kg/day, or saline. Offspring were tested in the Morris water maze, PPI, exploratory locomotor activity, activity after quinpirole and (+)-methamphetamine challenge, elevated zero maze, light-dark box, marble burying, straight channel swimming, and Cincinnati water maze. In the Morris water maze, all quinpirole groups had longer latencies on test days 3-5 of acquisition, but no effects on reversal or shifted-reduced platform trials. The quinpirole 4.0 mg/kg group had significantly reduced mean search distances on probe trials when combined across the 3 phases of testing but not separately. The male 4.0 mg/kg quinpirole group showed a greater increase in methamphetamine-stimulated activity during the first 10 min after drug challenge but not in the remainder of the 2 h test. No quinpirole effects were found for light-dark box, marble burying, exploratory locomotor activity, straight channel, Cincinnati water maze, or locomotor activity after quinpirole challenge. No effects were found on most measures in the elevated zero maze however the quinpirole 4.0 mg/kg females had longer latencies to enter an open quadrant. The results partially support prior Morris maze deficits induced by developmental quinpirole treatment but little evidence of dopamine D2/3 priming was found using locomotor activity with quinpirole or methamphetamine challenge or acoustic startle/PPI. The limited comparability to published data using developmental quinpirole exposure may be attributable to differences in experimental procedures or may be the result of quinpirole having limited effects. The data suggest that caution is warranted concerning the developmental efficacy of quinpirole.

Impact of pharmacogenomics on clinical outcomes in major depressive disorder in the GUIDED trial: A large, patient- and rater-blinded, randomized, controlled study.

Current prescribing practices for major depressive disorder (MDD) produce limited treatment success. Although pharmacogenomics may improve outcomes by identifying genetically inappropriate medications, studies to date were limited in scope. Outpatients (N = 1167) diagnosed with MDD and with a patient- or clinician-reported inadequate response to at least one antidepressant were enrolled in the Genomics Used to Improve DEpression Decisions (GUIDED) trial - a rater- and patient-blind randomized controlled trial. Patients were randomized to treatment as usual (TAU) or a pharmacogenomics-guided intervention arm in which clinicians had access to a pharmacogenomic test report to inform medication selections (guided-care). Medications were considered congruent ('use as directed' or 'use with caution' test categories) or incongruent ('use with increased caution and with more frequent monitoring' test category) with test results. Unblinding occurred after week 8. Primary outcome was symptom improvement [change in 17-item Hamilton Depression Rating Scale (HAM-D17)] at week 8; secondary outcomes were response (≥50% decrease in HAM-D17) and remission (HAM-D17 ≤ 7) at week 8. At week 8, symptom improvement for guided-care was not significantly different than TAU (27.2% versus 24.4%, p = 0.107); however, improvements in response (26.0% versus 19.9%, p = 0.013) and remission (15.3% versus 10.1%, p = 0.007) were statistically significant. Patients taking incongruent medications prior to baseline who switched to congruent medications by week 8 experienced greater symptom improvement (33.5% versus 21.1%, p = 0.002), response (28.5% versus 16.7%, p = 0.036), and remission (21.5% versus 8.5%, p = 0.007) compared to those remaining incongruent. Pharmacogenomic testing did not significantly improve mean symptoms but did significantly improve response and remission rates for difficult-to-treat depression patients over standard of care (ClinicalTrials.gov NCT02109939).

Hematopoietic cells from bone marrow have the potential to differentiate into cardiomyocytes in vitro.

Recent studies have indicated that hematopoietic progenitor cells (HPCs) have the capacity to form cardiomyocytes. In the present study, we further examined the cardiac competence of HPCs by asking whether these cells by themselves can be provoked to undergo cardiac differentiation. Our data indicate that in response to growth factor treatment, HPCs from avian bone marrow (BM) can undergo cardiac differentiation, as indicated by their expression of multiple cardiac transcription factors and sarcomeric proteins. Furthermore, coculture experiments with adult mouse BM cells and embryonic heart tissue confirmed that HPCs are able to both integrate into cardiac tissue and differentiate into cardiomyocytes. In an additional set of experiments, we investigated whether other hematopoietic populations might possess cardiac potential by examining whether blood cells that normally are recruited to damaged tissue might act as a source of newly generated cardiomyocytes. Remarkably, macrophages cocultured with cardiac explants also demonstrated an ability to integrate into contractile heart tissue and undergo cardiac differentiation. Thus, our data suggest that the capacity of blood cells to transdifferentiate into cardiomyocytes is not limited to classically defined hematopoietic progenitors.

Chlorhexidine bathing and microbial contamination in patients' bath basins.

BACKGROUND: Research has demonstrated the hazards associated with patients' bath basins and microbial contamination. In a previous study, soap and water bath basins in 3 acute care hospitals were found to be reservoirs for bacteria and potentially associated with the development of hospital-acquired infections. Bacteria grew in 98% of the basin samples; the most common were enterococci (54%), and 32% were gram-negative organisms. OBJECTIVE: To assess the presence of bacterial contaminants in wash basins when chlorhexidine gluconate solution is used in place of standard soap and water to wash patients. METHODS: Bathing with chlorhexidine gluconate is the standard of practice for all patients in intensive care units at St Vincent Hospital. Specimens from 90 bath basins used for 5 days or more were cultured for bacterial growth to assess contamination of basins when chlorhexidine gluconate is used. RESULTS: Of the 90 basins cultured, only 4 came back positive for microbial growth; all 4 showed growth of gram-positive organisms. Three of the 4 organisms were identified as coagulase-negative staphylococcus, which is frequently found on the skin. This translates into a 95.5% reduction in bacterial growth when chlorhexidine gluconate is used as compared with soap and water in the previous study (Fisher exact test, P < .001). The only factor that was related to positive cultures of samples from basins was the sex of the patient. DISCUSSION: Compared with the previous study examining microbial contamination of basins when soap and water was used to bathe patients, bacterial growth in patients' bath basins decreased significantly with the use of chlorhexidine gluconate, drastically reducing the risk for hospital-acquired infections. Such reduced risk is especially important for critically ill patients at high risk for bacterial infection.