Prescribed psychostimulants and other pro-cognitive medications in bipolar disorder: A systematic review and meta-analysis of recurrence of manic symptoms.

OBJECTIVES: Clinicians are often hesitant to prescribe psychostimulants in bipolar disorder (BD) due to concerns of inducing (hypo)mania, despite limited published evidence on associations between prescribed psychostimulant use and recurrence of mood episodes in BD. The current systematic review and meta-analysis evaluated the emergence of (hypo)manic symptoms in patients with BD receiving prescribed psychostimulants or other pro-cognitive medications in euthymic or depressive states. METHODS: A systematic search was performed of MEDLINE, Embase, and PsychINFO from inception to April 5, 2023 and search of Clinicaltrials.gov and Clinicaltrialsregister.eu for unpublished data. References of included studies were hand-searched. Randomized trials and prospective longitudinal studies that evaluated psychostimulants and non-stimulant medications recommended for the treatment of ADHD by the Canadian ADHD practice guidelines were included. The review was reported in line with PRISMA guidelines and was preregistered on PROSPERO (CRD42022358588). RESULTS: After screening 414 unique records, we included 27 studies, of which five reported data that was quantitatively synthesized (n = 1653). The use of psychostimulants in BD was not associated with increased scores on the Young Mania Rating Scale in patients who were in a euthymic or depressed state (SMD IV -0.17; 95% CI, -0.40 to 0.06) compared to placebo. There was a high degree of study-level heterogeneity (I2 = 80%). A qualitative synthesis of studies revealed a limited risk of medication-induced manic symptoms. CONCLUSIONS: Our review provides preliminary evidence to suggest psychostimulants and non-stimulant ADHD medications have a limited risk of precipitating (hypo)mania symptoms. More extensive studies evaluating the safety and efficacy of these medications are warranted.

A systematic review and meta-analysis of neuroimaging studies examining synaptic density in individuals with psychotic spectrum disorders.

BACKGROUND: Psychotic disorders have long been considered neurodevelopmental disorders where excessive synaptic pruning and cortical volume loss are central to disease pathology. We conducted a systematic review of the literature to identify neuroimaging studies specifically examining synaptic density across the psychosis spectrum. METHODS: PRISMA guidelines on reporting were followed. We systematically searched MEDLINE, Embase, APA PsycINFO, Web of Science and The Cochrane Library from inception to December 8, 2023, and included all original peer-reviewed articles or completed clinical neuroimaging studies of any modality measuring synaptic density in participants with a diagnosis of psychosis spectrum disorder as well as individuals with psychosis-risk states. The NIH quality assessment tool for observational cohort and cross-sectional studies was used for the risk of bias assessment. RESULTS: Five studies (k = 5) met inclusion criteria, comprising n = 128 adults (psychotic disorder; n = 61 and healthy volunteers; n = 67 and specifically measuring synaptic density via positron emission tomography (PET) imaging of the synaptic vesicle glycoprotein 2 A (SV2A). Three studies were included in our primary meta-analysis sharing the same outcome measure of SV2A binding, volume of distribution (VT). Regional SV2A VT was reduced in psychotic disorder participants in comparison to healthy volunteers, including the occipital lobe (Mean Difference (MD)= -2.17; 95% CI: -3.36 to -0.98; P < 0.001 ), temporal lobe (MD: -2.03; 95% CI: -3.19 to -0.88; P < 0.001 ), parietal lobe (MD:-1.61; 95% CI: -2.85 to -0.37; P = 0.01), anterior cingulate cortex (MD= -1.47; 95% CI: -2.45 to -0.49; P = 0.003), frontal cortex (MD: -1.16; 95% CI: -2.18 to -0.15; P = 0.02), amygdala (MD: -1.36; 95% CI: -2.20 to -0.52, p = 0.002), thalamus (MD:-1.46; 95% CI:-2.46 to -0.46, p = 0.004) and hippocampus (MD= -0.96; 95% CI: -1.59 to -0.33; P = 0.003). CONCLUSIONS: Preliminary studies provide in vivo evidence for reduced synaptic density in psychotic disorders. However, replication of findings in larger samples is required prior to definitive conclusions being drawn. PROSPERO: CRD42022359018.

Explaining predictors of discharge destination assessed along the patients' acute stroke journey.

INTRODUCTION: Accurate prediction of outcome destination at an early stage would help manage patients presenting with stroke. This study assessed the predictive ability of three machine learning (ML) algorithms to predict outcomes at four different stages as well as compared the predictive power of stroke scores. METHODS: Patients presenting with acute stroke to the Canberra Hospital between 2015 and 2019 were selected retrospectively. 16 potential predictors and one target variable (discharge destination) were obtained from the notes. k-Nearest Neighbour (kNN) and two ensemble-based classification algorithms (Adaptive Boosting and Bootstrap Aggregation) were employed to predict outcomes. Predictive accuracy was assessed at each of the four stages using both overall and per-class accuracy. The contribution of each variable to the prediction outcome was evaluated by the ensemble-based algorithm and using the Relief feature selection algorithm. Various combinations of stroke scores were tested using the aforementioned models. RESULTS: Of the three ML models, Adaptive Boosting demonstrated the highest accuracy (90%) at Stage 4 in predicting death while the highest overall accuracy (81.7%) was achieved by kNN (k=2/City-block distance). Feature importance analysis has shown that the most important features are the 24-hour Scandinavian Stroke Scale (SSS) and 24-hour National Institutes of Health Stroke Scale (NIHSS) scores, dyslipidaemia, hypertension and premorbid mRS score. For the initial and 24-hour scores, there was a higher correlation (0.93) between SSS scores than for NIHSS scores (0.81). Reducing the overall four scores to InitSSS/24hrNIHSS increased accuracy to 95% in predicting death (Adaptive Boosting) and overall accuracy to 85.4% (kNN). Accuracies at Stage 2 (pre-treatment, 11 predictors) were not far behind those at Stage 4. CONCLUSION: Our findings suggest that even in the early stages of management, a clinically useful prediction regarding discharge destination can be made. Adaptive Boosting might be the best ML model, especially when it comes to predicting death. The predictors' importance analysis also showed that dyslipidemia and hypertension contributed to the discharge outcome even more than expected. Further, surprisingly using mixed score systems might also lead to higher prediction accuracies.

A cross-sectional study of cognitive performance in bipolar disorder across the lifespan: the cog-BD project.

BACKGROUND: Neuroprogressive models of the trajectory of cognitive dysfunction in patients with bipolar disorder (BD) have been proposed. However, few studies have explored the relationships among clinical characteristics of BD, cognitive dysfunction, and aging. METHODS: We conducted a cross-sectional analysis in euthymic participants with the MATRICS Cognitive Consensus Battery, the Trail Making Test B, the Stroop Test, and the Wechsler Test of Adult Reading. Age- and gender-equated control participants without a mental disorder ['Healthy Controls' - HC)] were assessed similarly. We compared cognitive performance both globally and in seven domains in four groups: younger BD (age ⩽49 years; n = 70), older BD (age ⩾50 years; n = 48), younger HC (n = 153), and older HC (n = 44). We also compared the BD and HC groups using age as a continuous measure. We controlled for relevant covariates and applied a Bonferroni correction. RESULTS: Our results support both an early impairment ('early hit') model and an accelerated aging model: impairment in attention/vigilance, processing speed, and executive function/working memory were congruent with the accelerated aging hypothesis whereas impairment in verbal memory was congruent with an early impairment model. BD and HC participants exhibited similar age-related decline in reasoning/problem solving and visuospatial memory. There were no age- or diagnosis-related differences in social cognition. CONCLUSION: Our findings support that different cognitive domains are affected differently by BD and aging. Longitudinal studies are needed to explore trajectories of cognitive performance in BD across the lifespan.

Associations between peripheral inflammation and clinical phenotypes of bipolar depression in a lower-middle income country.

OBJECTIVE: There has been increased interest in repurposing anti-inflammatories for the treatment of bipolar depression. Evidence from high-income countries suggests that these agents may work best for specific depressive symptoms in a subset of patients with biochemical evidence of inflammation but data from lower-middle income countries (LMICs) is scarce. This secondary analysis explored the relationship between pretreatment inflammatory markers and specific depressive symptoms, clinical measures, and demographic variables in participants with bipolar depression in Pakistan. METHODS: The current study is a cross-sectional secondary analysis of a randomized controlled trial of two anti-inflammatory medications (minocycline and celecoxib) for bipolar depression (n = 266). A series of logistic and linear regression models were completed to assess the relationship between C-reactive protein (CRP) (CRP > or < 3 mg/L and log10CRP) and clinical and demographic features of interest and symptoms of depression. Baseline clinical trial data was used to extract clinical and demographic features and symptoms of depression were assessed using the 24-item Hamilton Depression Rating Scale. RESULTS: The prevalence of low-grade inflammation (CRP > 3 mg/L) in the sample was 70.9%. After adjusting for baseline body mass index, socioeconomic status, age, gender, symptoms related to anhedonia, fatigue, and motor retardation were most associated with low-grade inflammation. CONCLUSIONS: Bipolar disorder (BD) patients from LMICs may experience higher rates of peripheral inflammation than have been reported in Western populations with BD. Future trials of repurposed anti-inflammatory agents that enrich for participants with these symptom profiles may inform the development of personalized treatment for bipolar depression in LMICs.

Generate Analysis-Ready Data for Real-world Evidence: Tutorial for Harnessing Electronic Health Records With Advanced Informatic Technologies.

Although randomized controlled trials (RCTs) are the gold standard for establishing the efficacy and safety of a medical treatment, real-world evidence (RWE) generated from real-world data has been vital in postapproval monitoring and is being promoted for the regulatory process of experimental therapies. An emerging source of real-world data is electronic health records (EHRs), which contain detailed information on patient care in both structured (eg, diagnosis codes) and unstructured (eg, clinical notes and images) forms. Despite the granularity of the data available in EHRs, the critical variables required to reliably assess the relationship between a treatment and clinical outcome are challenging to extract. To address this fundamental challenge and accelerate the reliable use of EHRs for RWE, we introduce an integrated data curation and modeling pipeline consisting of 4 modules that leverage recent advances in natural language processing, computational phenotyping, and causal modeling techniques with noisy data. Module 1 consists of techniques for data harmonization. We use natural language processing to recognize clinical variables from RCT design documents and map the extracted variables to EHR features with description matching and knowledge networks. Module 2 then develops techniques for cohort construction using advanced phenotyping algorithms to both identify patients with diseases of interest and define the treatment arms. Module 3 introduces methods for variable curation, including a list of existing tools to extract baseline variables from different sources (eg, codified, free text, and medical imaging) and end points of various types (eg, death, binary, temporal, and numerical). Finally, module 4 presents validation and robust modeling methods, and we propose a strategy to create gold-standard labels for EHR variables of interest to validate data curation quality and perform subsequent causal modeling for RWE. In addition to the workflow proposed in our pipeline, we also develop a reporting guideline for RWE that covers the necessary information to facilitate transparent reporting and reproducibility of results. Moreover, our pipeline is highly data driven, enhancing study data with a rich variety of publicly available information and knowledge sources. We also showcase our pipeline and provide guidance on the deployment of relevant tools by revisiting the emulation of the Clinical Outcomes of Surgical Therapy Study Group Trial on laparoscopy-assisted colectomy versus open colectomy in patients with early-stage colon cancer. We also draw on existing literature on EHR emulation of RCTs together with our own studies with the Mass General Brigham EHR.

A prospective comparison of total knee arthroplasty using ultra-congruent, condylar-stabilizing, and posterior-stabilized devices implanted with kinematic alignment: better 2-year outcomes with ultra-congruent.

PURPOSE: This study compared the 5-year results of posterior cruciate ligament (PCL)-sacrificing total knee arthroplasty (TKA) with either a post and cam posterior-stabilized (PS) device, a dished, congruent condylar-stabilizing (CS) device, or a deep-dished ultra-congruent (UC) device. The hypothesis was that the clinical and radiographic outcomes would be equivalent. CS and PS participants were part of a prospective, randomized trial, and UC participants were part of a separate prospective, non-randomized protocol that was otherwise identical. A kinematic alignment surgical technique was utilized. METHODS: Participants were assessed preoperatively, and postoperatively at 6 weeks, 6 months, and annually for 5 years by Knee Society Score (KSS), SF-36 v2, Lower Extremity Activity Scale (LEAS), and physical and radiographic evaluation. There were 116 CS/PS participants and 69 UC participants who participated in the study. RESULTS: Tourniquet (P = .02) and operative (P = .01) times for the CS and UC groups were significantly shorter than the PS group. KSS Function scores were better for the UC group than the CS and PS groups at 6 months (P = .04) and 1 year (P = .03), and better in the UC group vs. CS at 2 years (P = .04). The KSS Pain-only score was also better in the UC compared to PS at 6 months (P = .04). There were no significant differences for the KSS Pain/Motion scores, flexion, SF-36, and LEAS scores at any time. CONCLUSION: These data confirm the hypothesis that there are no clinically meaningful significant differences in outcomes between the three groups at a 5-year minimum follow-up, though there is a trend toward less pain and better function at earlier visits in the UC group. LEVEL OF EVIDENCE: II.

Validating a measure of motivational climate in health science courses.

PURPOSE: The aim of the study was to examine the validity evidence for the 19-item form of the MUSIC Model of Academic Motivation Inventory (College Student version) within health science schools in three different countries. The MUSIC Inventory includes five scales that assess the motivational climate by measuring students' perceptions related to five separate constructs: empowerment, usefulness, success, interest, and caring. BACKGROUND: The 26-item form of the MUSIC Inventory has been validated for use with undergraduate students and with students in professional schools, including students at a veterinary medicine school, a pharmacy school, and a medical school. A 19-item form of the MUSIC Inventory has also been validated for use with undergraduate students, but it has not yet been validated for use with medical school students. The purpose of this study was to provide validity evidence for the use of the 19-item form in heath science schools in three different countries to determine if this version is acceptable for use in different cultures. If validated, this shorter form of the MUSIC Inventory would provide more differentiation between the Interest and Usefulness scales and could reduce respondent fatigue. METHODOLOGY: Cook et al's [1] practical guidelines were followed to implement Kane's [2] validity framework as a means to examine the evidence of validity through scoring inferences, generalization inferences, and extrapolation inferences. Students (n = 667) in health science schools within three countries were surveyed. RESULTS: The results produced evidence to support all five hypotheses related to scoring, generalization, and extrapolation inferences. CONCLUSIONS: Scores from the 19-item form of the MUSIC Inventory are valid for use in health science courses within professional schools in different countries. Therefore, the MUSIC Inventory can be used in these schools to assess students' perceptions of the motivational climate.

Examining the Motivational Climate and Student Effort in Professional Competency Courses: Suggestions for Improvement.

The attainment of professional competencies leads to essential skills for successful and employable veterinarians. However, the inclusion of professional competencies in veterinary curricula is often underdeveloped, and it is sometimes less appreciated by students than the science/technical skill curricula. The aim of this study was to better understand students' motivation within professional competency courses (PC courses) by (a) comparing students' motivational perceptions in PC courses to those in science/technical skill courses (ST courses), (b) determining the extent to which students' motivational perceptions predict their course effort, and (c) identifying teaching strategies that could be used to improve PC courses. Participants included students from eight courses enrolled in their first or second year of a veterinary college at a large land-grant university in the United States. A partially mixed concurrent dominant status research design was used to collect quantitative and qualitative data. Students completed closed- and open-ended survey items regarding their effort and the motivational climate in their courses. Compared to ST courses, students put forth less effort in PC courses; rated PC courses lower on empowerment, usefulness, and interest; and had higher success expectancies in PC courses. Although students' perceptions of empowerment, usefulness, interest, and caring were significantly correlated with their effort, interest was the most significant predictor of effort in both PC and ST courses. Based on students' responses to the open-ended questions, specific motivational strategies are recommended to increase students' effort in PC courses, such as intentionally implementing strategies to increase students' interest and perceptions of usefulness and empowerment.

Accelerating diagnosis of Parkinson's disease through risk prediction.

BACKGROUND: Characterization of prediagnostic Parkinson's Disease (PD) and early prediction of subsequent development are critical for preventive interventions, risk stratification and understanding of disease pathology. This study aims to characterize the role of the prediagnostic period in PD and, using selected features from this period as novel interception points, construct a prediction model to accelerate the diagnosis in a real-world setting. METHODS: We constructed two sets of machine learning models: a retrospective approach highlighting exposures up to 5 years prior to PD diagnosis, and an alternative model that prospectively predicted future PD diagnosis from all individuals at their first diagnosis of a gait or tremor disorder, these being features that appeared to represent the initiation of a differential diagnostic window. RESULTS: We found many novel features captured by the retrospective models; however, the high accuracy was primarily driven from surrogate diagnoses for PD, such as gait and tremor disorders, suggesting the presence of a distinctive differential diagnostic period when the clinician already suspected PD. The model utilizing a gait/tremor diagnosis as the interception point, achieved a validation AUC of 0.874 with potential time compression to a future PD diagnosis of more than 300 days. Comparisons of predictive diagnoses between the prospective and prediagnostic cohorts suggest the presence of distinctive trajectories of PD progression based on comorbidity profiles. CONCLUSIONS: Overall, our machine learning approach allows for both guiding clinical decisions such as the initiation of neuroprotective interventions and importantly, the possibility of earlier diagnosis for clinical trials for disease modifying therapies.

What Every Reader Should Know About Studies Using Electronic Health Record Data but May Be Afraid to Ask.

Coincident with the tsunami of COVID-19-related publications, there has been a surge of studies using real-world data, including those obtained from the electronic health record (EHR). Unfortunately, several of these high-profile publications were retracted because of concerns regarding the soundness and quality of the studies and the EHR data they purported to analyze. These retractions highlight that although a small community of EHR informatics experts can readily identify strengths and flaws in EHR-derived studies, many medical editorial teams and otherwise sophisticated medical readers lack the framework to fully critically appraise these studies. In addition, conventional statistical analyses cannot overcome the need for an understanding of the opportunities and limitations of EHR-derived studies. We distill here from the broader informatics literature six key considerations that are crucial for appraising studies utilizing EHR data: data completeness, data collection and handling (eg, transformation), data type (ie, codified, textual), robustness of methods against EHR variability (within and across institutions, countries, and time), transparency of data and analytic code, and the multidisciplinary approach. These considerations will inform researchers, clinicians, and other stakeholders as to the recommended best practices in reviewing manuscripts, grants, and other outputs from EHR-data derived studies, and thereby promote and foster rigor, quality, and reliability of this rapidly growing field.

Faculty's attitudes and perceptions related to applying motivational principles to their teaching: a mixed methods study.

BACKGROUND: It is uncommon for faculty development professionals to assess faculty attitudes towards their teaching responsibilities and their perceived obstacles to teaching effectiveness. The purposes of this study were (a) to document faculty attitudes and practices related to applying motivation principles, and (b) to identify the perceived contextual factors that may shape these attitudes and practices. METHODS: A sequential explanatory mixed methods design was used. Faculty members (n = 272; 32% response rate) were surveyed about their responsibility for and application of the five motivational principles that are part of the MUSIC Model of Motivation: eMpowerment, Usefulness, Success, Interest, and Caring. Repeated measures ANOVAs and Student's t-tests were computed to detect differences. Subsequently, two focus groups of faculty members (n = 11) interpreted the survey results. We conducted a thematic analysis and used the focus group results to explain the survey results. RESULTS: Faculty rated their responsibilities for applying principles related to Usefulness, Interest, and Caring significantly higher than they did for Success and eMpowerment. Most faculty also reported that they actually applied Usefulness, Interest, and Caring strategies within the past year, whereas over half of the faculty applied Success strategies and about a third of faculty applied eMpowerment strategies. Focus group participants identified factors that affected their ability to apply eMpowerment strategies, (e.g., offering choices), including students lacking generic skills (e.g., critical thinking, problem-solving), a lack of confidence in their abilities to implement empowering strategies and meet the needs of students, passive students, and large lecture-type courses. Focus group participants cited obstacles to implementing Success strategies (e.g., providing feedback), including difficulty in providing feedback in large courses, lacking time and assistant teachers, limited knowledge of technologies, and lacking skills related to guiding effective student peer feedback. CONCLUSIONS: Faculty appear adequately prepared to implement some types of motivational strategies, but not others, in part due to contextual factors that can influence their attitudes and, ultimately, their application of these strategies. We discuss how these factors affect attitudes and application of motivational strategies and formulate suggestions based on the results.

Anticoagulant prescribing in patients with ischaemic stroke: what has changed over a decade?

A study at our institution conducted 10 years ago identified that warfarin was under-utilised in patients with atrial fibrillation. We replicated this study and compared the results. There was a significant increase in the proportion of patients appropriately anticoagulated (63% vs 9%, P < 0.001). Eighty-seven percent of eligible patients were appropriately anticoagulated on discharge (86% previously). Seventy-two percent of treated patients were prescribed a direct oral anticoagulant. Of these, 10% were discharged with a sub-therapeutic dose without obvious explanation.

Relative effectiveness of augmentation treatments for treatment-resistant depression: a systematic review and network meta-analysis.

Most interventions for treatment-resistant depression (TRD) are added as augmenters. We aimed to determine the relative effectiveness of augmentation treatments for TRD. This systematic review and network meta-analysis (NMA) sought all randomized trials of pharmacological and psychological augmentation interventions for adults meeting the most common clinical criteria for TRD. The NMA compared the intervention effectiveness of depressive symptoms for TRD augmentation. Of 36 included trials, 27 were suitable for inclusion in NMA, and no psychological trials could be included in the absence of a common comparator. Antipsychotics (13 trials), mood stabilizers (three trials), NMDA-targeting medications (five trials), and other mechanisms (3 trials) were compared against placebo. NMDA treatments were markedly superior to placebo (ES = 0.91, 95% CI 0.67 to 1.16) and head-to-head NMA suggested that NMDA therapies had the highest chance of being an effective treatment option compared to other pharmacological classes. This study provides the most comprehensive evidence of augmenters' effectiveness for TRD, and our GRADE recommendations can be used to guide guidelines to optimize treatment choices. Although conclusions are limited by paucity of, and heterogeneity between, trials as well as inconsistent reports of treatment safety. This work supports the use of NMDA-targeting medications such as ketamine.

Factors predicting identity as educators and openness to improve: an exploratory study.

CONTEXT: Researchers suggest that teachers' work environment affects their sense of connectedness and appreciation, which affects their educator identity. However, sessional (also known as adjunct, clinical, contingent and non-tenured) faculty members may struggle with their educator identity. The purpose of this exploratory study was to examine the extent to which perceived connectedness and received appreciation predicted identity as a medical (health care science) educator and openness to improve in tenure-track and sessional faculty members. METHODS: We utilised an 'identification with teaching' scale to measure medical educator identity. We developed scales to measure perceived connectedness to university department, openness to improve teaching, and appreciation as a motivation to try a new teaching method. We then hypothesised a path model between these constructs. We surveyed faculty members at a health sciences school and performed confirmatory factor analyses and structural equation modelling using data from a sample of 73 tenure-track and 146 sessional faculty members to explore support for the hypothesised model. RESULTS: Connectedness and appreciation predicted identity as a medical educator and openness to improve in different ways for sessional and tenure-track faculty members. For tenure-track faculty members, appreciation predicted medical educator identity and openness to improve, whereas a sense of connectedness trended towards predicting an openness to improve. For sessional faculty members, connectedness to their department predicted their identity as a medical educator, which acted as a mediator to predict an openness to improve. DISCUSSION: Our data supported the hypothesised model, but the sessional and tenure-track faculty models differed in strength and focus. We explore reasons for these differences based on the working environment of each teacher type. We suggest that the two models partially explain the transformation from 'a clinician who teaches' to a medical educator. Finally, we make suggestions for how identity as a medical educator and openness to improve may be encouraged in both types of teachers.

Needs, motivations, and identification with teaching: a comparative study of temporary part-time and tenure-track health science faculty in Iceland.

BACKGROUND: About 70% of teachers who instruct healthcare students are considered sessional (adjunct/temporary part-time) faculty and receive limited instruction in pedagogy. Sessional faculty may feel isolated and struggle with their teacher identity, and are often assumed to vary in their commitment, motivation, and ability to teach. However, research on teaching identity, motivations, and needs of sessional faculty is lacking. The aim of this study was to compare similarities and differences between sessional and tenure-track faculty across a health science school to guide faculty development for sessional faculty. METHODS: We developed an online needs assessment survey, based on informal interviews and literature reviews. Seventy-eight tenure-track faculty and 160 sessional faculty completed the survey (37, 25% response rate, respectively). We used validated scales to assess intrinsic motivation, identified regulated motivation, and identification with teaching, as well as developed scales (perceived connectedness, motivated by appreciation to try new teaching method) and single items. All scales demonstrated good internal consistency. We compared sessional and tenure-track faculty using t-tests/chi-square values. RESULTS: We found similarities between sessional and tenure-track faculty in intrinsic motivation, identified regulated motivation, and identification with teaching. However, sessional faculty perceived less department connectedness and were more motivated to improve instruction if shown appreciation for trying new teaching methods. Sessional faculty agreed more that they desired pedagogy instruction before starting to teach and that teachers should invest energy in improving their teaching. Admitting to less participation in activities to enhance teaching in the last year, sessional faculty were more interested in digital formats of faculty development. CONCLUSION: Our comparison suggested that sessional faculty value being a teacher as part of their self, similar to tenured faculty, but desired more appreciation for efforts to improve and perceived less connectedness to their university department than tenured faculty. They also preferred digital formats for pedagogy to improve accessibility, prior to and throughout their teaching career to support their development as teachers. Using this information as a guide, we provide suggestions for faculty development for sessional faculty. Supporting sessional faculty in the health sciences should improve the quality of teaching and positively affect student learning.

The Cost-Effectiveness of a Stroke Unit in Providing Enhanced Patient Outcomes in an Australian Teaching Hospital.

BACKGROUND: Stroke is one of the leading causes of disability and mortality. Patients who receive organized inpatient care in a stroke unit (SU) have better clinical outcomes. However, evidence on the cost analysis of an SU is lacking. The objective of this study was to assess the performance and analyze the cost-effectiveness of an SU. METHODS: A retrospective observational study was conducted comparing the acute stroke patient care in a 6-month period before and after the establishment of an acute SU at Calvary Hospital in 2013-2014. RESULTS: There were 103 patients included in the pre-SU period, as compared to 186 patients in the post-SU period. In the pre- and post-SU groups, 54 and 87 patients, respectively, had ischemic stroke, with significant trends in improved morbidity and mortality in the post-SU group (P = .01). The average length of stay (LOS) for patients was reduced from 9.7 days to 4.6 days in the post-SU group (P = .001). There was a reduction of cost per admission from $6382 Australian dollars (AUD) with conventional ward care as compared to $6061 (AUD) with SU care. CONCLUSION: This study confirmed that the establishment of an SU not only improves treatment outcomes but also shortens LOS, thereby achieving cost-effectiveness.

Redesigning a Neuroscience Laboratory Course for Multiple Sections: An Action Research Project to Engage Students.

The purpose of our action research project was to improve students' motivation in a multi-section introductory neuroscience laboratory course. In this paper, we present: (a) how we collected data related to students' motivation and engagement, (b) how we analyzed and used the data to make modifications to the courses, (c) the results of the course modifications, and (d) some possible explanations for our results. Our aim is not only to provide the results of our study, but also to explain the process that we used, with the hopes that other instructors can use similar approaches to improve students' motivation in their courses. Our attempts to improve students' motivation-related perceptions were successful in some instances, but not in others. Of particular note was our finding that some of the students' perceptions varied even though the course syllabus was the same across sections. We attributed this variation to the learning environment developed by the teaching assistants (TAs) who taught the different sections. We provide some strategies that faculty instructors can use to redesign courses with high enrollments and help TAs motivate their students.

Semi-supervised learning of the electronic health record for phenotype stratification.

Patient interactions with health care providers result in entries to electronic health records (EHRs). EHRs were built for clinical and billing purposes but contain many data points about an individual. Mining these records provides opportunities to extract electronic phenotypes, which can be paired with genetic data to identify genes underlying common human diseases. This task remains challenging: high quality phenotyping is costly and requires physician review; many fields in the records are sparsely filled; and our definitions of diseases are continuing to improve over time. Here we develop and evaluate a semi-supervised learning method for EHR phenotype extraction using denoising autoencoders for phenotype stratification. By combining denoising autoencoders with random forests we find classification improvements across multiple simulation models and improved survival prediction in ALS clinical trial data. This is particularly evident in cases where only a small number of patients have high quality phenotypes, a common scenario in EHR-based research. Denoising autoencoders perform dimensionality reduction enabling visualization and clustering for the discovery of new subtypes of disease. This method represents a promising approach to clarify disease subtypes and improve genotype-phenotype association studies that leverage EHRs.

Report on the international workshop on alternatives to the murine histamine sensitization test (HIST) for acellular pertussis vaccines: state of the science and the path forward.

Regulatory authorities require safety and potency testing prior to the release of each production lot of acellular pertussis (aP)-containing vaccines. Currently, the murine histamine sensitization test (HIST) is used to evaluate the presence of residual pertussis toxin in aP containing vaccines. However, the testing requires the use of a significant number of mice and results in unrelieved pain and distress. NICEATM, ICCVAM, their partners in the International Cooperation on Alternative Test Methods, and the International Working Group for Alternatives to HIST organized a workshop to discuss recent developments in alternative assays to the HIST, review data from an international collaborative study on non-animal alternative tests that might replace the HIST, and address the path toward global acceptance of this type of method. Currently, there are three potential alternative methods to HIST. Participants agreed that no single in vitro method was sufficiently developed for harmonized validation studies at this time. It is unlikely that any single in vitro method would be applicable to all aP vaccines without modification, due to differences between vaccines. Workshop participants recommended further optimization of cell-based assays under development. Participants agreed that the next international collaborative studies should commence in 2013 based on discussions during this workshop.