Digitization of Measurement-Based Care Pathways in Mental Health Through REDCap and Electronic Health Record Integration: Development and Usability Study.

BACKGROUND: The delivery of standardized self-report assessments is essential for measurement-based care in mental health. Paper-based methods of measurement-based care data collection may result in transcription errors, missing data, and other data quality issues when entered into patient electronic health records (EHRs). OBJECTIVE: This study aims to help address these issues by using a dedicated instance of REDCap (Research Electronic Data Capture; Vanderbilt University)-a free, widely used electronic data capture platform-that was established to enable the deployment of digitized self-assessments in clinical care pathways to inform clinical decision making. METHODS: REDCap was integrated with the primary clinical information system to facilitate the real-time transfer of discrete data and PDF reports from REDCap into the EHR. Both technical and administrative components were required for complete implementation. A technology acceptance survey was also administered to capture physicians' and clinicians' attitudes toward the new system. RESULTS: The integration of REDCap with the EHR transitioned clinical workflows from paper-based methods of data collection to electronic data collection. This resulted in significant time savings, improved data quality, and valuable real-time information delivery. The digitization of self-report assessments at each appointment contributed to the clinic-wide implementation of the major depressive disorder integrated care pathway. This digital transformation facilitated a 4-fold increase in the physician adoption of this integrated care pathway workflow and a 3-fold increase in patient enrollment, resulting in an overall significant increase in major depressive disorder integrated care pathway capacity. Physicians' and clinicians' attitudes were overall positive, with almost all respondents agreeing that the system was useful to their work. CONCLUSIONS: REDCap provided an intuitive patient interface for collecting self-report measures and accessing results in real time to inform clinical decisions and an extensible backend for system integration. The approach scaled effectively and expanded to high-impact clinics throughout the hospital, allowing for the broad deployment of complex workflows and standardized assessments, which led to the accumulation of harmonized data across clinics and care pathways. REDCap is a flexible tool that can be effectively leveraged to facilitate the automatic transfer of self-report data to the EHR; however, thoughtful governance is required to complement the technical implementation to ensure that data standardization, data quality, patient safety, and privacy are maintained.

Modeling development of frontal electroencephalogram (EEG) asymmetry: Sex differences and links with temperament.

Asymmetric patterns of frontal brain electrical activity reflect approach and avoidance tendencies, with stability of relative right activation associated with withdrawal emotions/motivation and left hemisphere activation linked with approach and positive affect. However, considerable shifts in approach/avoidance-related lateralization have been reported for children not targeted because of extreme temperament. In this study, dynamic effects of frontal electroencephalogram (EEG) power within and across hemispheres were examined throughout early childhood. Specifically, EEG indicators at 5, 10, 24, 36, 48, and 72 months-of-age (n = 410) were analyzed via a hybrid of difference score and panel design models, with baseline measures and subsequent time-to-time differences modeled as potentially influencing all subsequent amounts of time-to-time change (i.e., predictively saturated). Infant sex was considered as a moderator of dynamic developmental effects, with temperament attributes measured at 5 months examined as predictors of EEG hemisphere development. Overall, change in left and right frontal EEG power predicted declining subsequent change in the same hemisphere, with effects on the opposing neurobehavioral system enhancing later growth. Infant sex moderated the pattern of within and across-hemisphere effects, wherein for girls more prominent left hemisphere influences on the right hemisphere EEG changes were noted and right hemisphere effects were more salient for boys. Largely similar patterns of temperament prediction were observed for the left and the right EEG power changes, with limited sex differences in links between temperament and growth parameters. Results were interpreted in the context of comparable analyses using parietal power values, which provided evidence for unique frontal effects.

The CAMH Neuroinformatics Platform: A Hospital-Focused Brain-CODE Implementation.

Investigations of mental illness have been enriched by the advent and maturation of neuroimaging technologies and the rapid pace and increased affordability of molecular sequencing techniques, however, the increased volume, variety and velocity of research data, presents a considerable technical and analytic challenge to curate, federate and interpret. Aggregation of high-dimensional datasets across brain disorders can increase sample sizes and may help identify underlying causes of brain dysfunction, however, additional barriers exist for effective data harmonization and integration for their combined use in research. To help realize the potential of multi-modal data integration for the study of mental illness, the Centre for Addiction and Mental Health (CAMH) constructed a centralized data capture, visualization and analytics environment-the CAMH Neuroinformatics Platform-based on the Ontario Brain Institute (OBI) Brain-CODE architecture, towards the curation of a standardized, consolidated psychiatric hospital-wide research dataset, directly coupled to high performance computing resources.

Paternal influences on infant temperament: effects of father internalizing problems, parenting-related stress, and temperament.

Temperament ratings were obtained from 98 fathers when their infants were 4 and 6 months of age to examine effects of paternal characteristics on infant temperament. Parental stress, internalizing symptoms, and father's temperament were considered as factors possibly contributing to differences in their child's temperament.

Mechanisms of contextual risk for adolescent self-injury: invalidation and conflict escalation in mother-child interactions.

According to developmental theories of self-injury, both child characteristics and environmental contexts shape and maintain problematic behaviors. Although progress has been made toward identifying biological vulnerabilities to self-injury, mechanisms underlying psychosocial risk have received less attention. In the present study, we compared self-injuring adolescents (n = 17) with typical controls (n = 20) during a mother-child conflict discussion. Dyadic interactions were coded using both global and microanalytic systems, allowing for a highly detailed characterization of mother-child interactions. We also assessed resting state psychophysiological regulation, as indexed by respiratory sinus arrhythmia (RSA). Global coding revealed that maternal invalidation was associated with adolescent anger. Furthermore, maternal invalidation and coerciveness were both related to adolescent opposition/defiance. Results from the microanalytic system indicated that self-injuring dyads were more likely to escalate conflict, suggesting a potential mechanism through which emotion dysregulation is shaped and maintained over time. Finally, mother and teen aversiveness interacted to predict adolescent resting RSA. Low-aversive teens with highly aversive mothers had the highest RSA, whereas teens in high-high dyads showed the lowest RSA. These findings are consistent with theories that emotion invalidation and conflict escalation are possible contextual risk factors for self-injury.

The effects of allostatic load on neural systems subserving motivation, mood regulation, and social affiliation.

The term allostasis, which is defined as stability through change, has been invoked repeatedly by developmental psychopathologists to describe long-lasting and in some cases permanent functional alterations in limbic-hypothalamic-pituitary-adrenal axis responding following recurrent and/or prolonged exposure to stress. Increasingly, allostatic load models have also been invoked to describe psychological sequelae of abuse, neglect, and other forms of maltreatment. In contrast, neural adaptations to stress, including those incurred by monoamine systems implicated in (a) mood and emotion regulation, (b) behavioral approach, and (c) social affiliation and attachment, are usually not included in models of allostasis. Rather, structural and functional alterations in these systems, which are exquisitely sensitive to prolonged stress exposure, are usually explained as stress mediators, neural plasticity, and/or programming effects. Considering these mechanisms as distinct from allostasis is somewhat artificial given overlapping functions and intricate coregulation of monoamines and the limbic-hypothalamic-pituitary-adrenal axis. It also fractionates literatures that should be mutually informative. In this article, we describe structural and functional alterations in serotonergic, dopaminergic, and noradrenergic neural systems following both acute and prolonged exposure to stress. Through increases in behavioral impulsivity, trait anxiety, mood and emotion dysregulation, and asociality, alterations in monoamine functioning have profound effects on personality, attachment relationships, and the emergence of psychopathology.

Association of alpha4beta2 nicotinic receptor and heavy smoking in schizophrenia.

INTRODUCTION: Previously we suggested that the CHRNA7 polymorphism in nicotinic receptor genes, in particular the D15S1360 in CHRNA7, is associated with smoking in schizophrenia. Schizophrenia patients are usually heavy smokers. In this study we hypothesized that high-affinity nicotinic receptors are associated with smoking in such patients. OBJECTIVE: To investigate the role of alpha4 (Ch 20) and beta2 (Ch 1) genes in conferring a risk for smoking and for smoking a large number of cigarettes daily in subjects with schizophrenia. METHODS: Our study sample consisted of 241 white European schizophrenia patients (157 smokers and 84 nonsmokers) from the Toronto area. Current smoking status was assessed by the medical history. We investigated 4 markers located in the CHRNA4 gene and 3 markers located in the CHRNB2 gene. RESULTS: There was no difference in age or ethnicity between the 2 groups and the population was not stratified (lambda=0.4527). We found a significant association between the CHRNA4 rs3746372 allele 1 and a large number of cigarettes smoked daily (p=0.0203). The intragenic interaction between rs3787116 and rs3746372 (p = 0.0050) in CHRNA4 showed a significant interaction for the number of cigarettes smoked. CONCLUSION: Although our findings suggest an association between rs3746372 allele 1 and heavy smoking, further study is warranted to investigate the relation between smoking and high-affinity nicotinic receptor genes in schizophrenia.

Association analyses of the DAOA/G30 and D-amino-acid oxidase genes in schizophrenia: further evidence for a role in schizophrenia.

A number of linkage studies have previously implicated the region of chromosome 13q34 in schizophrenia. Chumakov and colleagues (2002) identified a gene complex called G72 (now termed D-amino acid oxidase activator: DAOA)/G30 in this region and performed association analyses of the DAOA/G30 as well as the D-amino-acid oxidase (DAAO) gene with schizophrenia. DAAO oxidizes D-serine, a potent activator of the N-methyl-D-aspartate (NMDA) type glutamate receptor in the human brain whereas the DAOA protein is considered an activator of DAAO. The interaction of these two genes has thus been implicated in the NMDA receptor regulation pathway in schizophrenia. To date, several studies have shown a relatively consistent positive association between schizophrenia and DAOA/G30, but not with DAAO. The aim of our study was to further evaluate the contributions of these genes to the susceptibility to schizophrenia using two different sample sets. Our sample consisted of 168 matched case-control pairs as well as a family-based sample (n=113) for transmission disequilibrium test. Significant associations between the DAOA/G30 M-7 and M-18 polymorphisms and schizophrenia were observed in our case-control sample whereas no associations were observed for DAAO markers. We also observed significant or suggestive transmission disequilibrium for DAOA/G30 M-7, M-23, and M-24 to probands with schizophrenia in our family-based sample. Subsequent analysis of haplotypes made up of four DAOA/G30 markers, one marker selected from each of two linkage disequilibrium blocks that were observed in our sample as well as both ends (M-7 and M-25), were also associated with schizophrenia. Our data provide further evidence that the DAOA/G30 locus may play a role in the pathophysiology of schizophrenia. Although no direct link to genetic polymorphism in these genes and NMDA receptor function has been revealed, the present findings support previous reports implicating DAOA/G30 as susceptibility genes for schizophrenia. Further research is warranted to determine the functional variation underlying these findings and to relate this to the pathophysiology of schizophrenia.

Genetic association analysis of the glutathione peroxidase (GPX1) gene polymorphism (Pro197Leu) with tardive dyskinesia.

A possible involvement of oxidative stress in the pathophysiology of tardive dyskinesia (TD) has previously been proposed (reviewed in [Andreassen, O.A., Jorgensen, H.A., 2000. Neurotoxicity associated with neuroleptic-induced oral dyskinesias in rats. Implications for tardive dyskinesia? Progress in Neurobiology 61, 525-541.]). Long-term administration of neuroleptics alters dopaminergic turnover, which results in increased formation of reactive oxygen species (ROS). This is hypothesized to lead to TD through neuronal toxicity as a consequence of oxidative stress. In the present study, the relationship between TD and a possible functional polymorphism of the human glutathione peroxidase (GPX1) gene (an important antioxidant enzyme) was studied in 68 chronic treatment-refractory patients with schizophrenia. A proline (Pro) to leucine (Leu) substitution at codon 197 (Pro197Leu) in the GPX1 gene was genotyped. No significant difference in total Abnormal Involuntary Movements Scale (AIMS) scores was observed among patients in the three genotype groups. Moreover, no significant differences in genotype or allele frequencies were observed between subjects with and without TD. Our results suggest that the GPX1 gene polymorphism does not confer increased susceptibility to TD, although further studies are warranted before a conclusion can be drawn.

Intraoperative correction of induced astigmatism after spherical correction of hyperopia with conductive keratoplasty.

PURPOSE: To evaluate the treatment of surgically induced astigmatism intraoperatively during conductive keratoplasty (CK) for correcting hyperopia. METHODS: Conductive keratoplasty uses radiofrequency energy applied to the peripheral corneal stroma to shrink the collagen and alter the central cornea to correct hyperopia. Nineteen consecutive patients (27 eyes) who underwent CK for hyperopia and were treated intraoperatively for induced astigmatism were examined. By using automated keratometric readings taken during the procedure, additional spots were applied at the minus cylinder or flat axis at the 7-mm zone until the intraoperative astigmatism was 2 diopters (D) or less. RESULTS: The intraoperative treatment reduced the astigmatism by an average of 2.30 +/- 1.32 D (P=0.00001). The mean induced astigmatism was 3.33 +/- 0.14 D for eyes that received eight spots, 4.12 +/- 1.13 D for eyes that received 16 spots, 4.43 +/- 0.82 D for eyes that received 24 spots, and 4.60 +/- 1.08 D for eyes that received 32 spots. Additional spots reduced astigmatism in most patients to less than 2 D. CONCLUSIONS: Intraoperative treatment of astigmatism through the addition of more spots at the minus cylinder or flat axis reduced the degree of induced astigmatism. Surgically induced astigmatism was observed more frequently in patients who received 32 treatment spots and 6-mm treatment zone application.

Effects of topical antiglaucoma medications on the ocular surface.

The side effects of topical antiglaucoma medications and their preservatives range from ocular discomfort to sight-threatening alterations of the ocular surface. Conjunctival hyperemia, decreased tear production and function, and superficial punctate keratitis are among the most common signs seen on routine clinical examination. Squamous cell metaplasia and changes in cell morphology have been demonstrated by impression cytology studies and evaluation of biopsy specimens, and inflammatory effects are documented by the presence of inflammatory markers. The adverse effects of topical antiglaucoma eyedrops interfere with the treatment of glaucoma on two levels: first, the discomfort produced by the eye drops discourages patient compliance; and, second, long-term treatment with eyedrops is associated with a higher failure of filtration surgery. The detailed mechanism of inflammatory response and/or direct toxicity of eye drops has yet to be determined, but it may vary with the different classes of eye drops, different preservatives, and durations of treatments. Upcoming multicenter trials for new antiglaucoma eye drops should specifically evaluate ocular surface effects.

Corneal topography in corneal refractive therapy (CRT): a 1-month follow-up.

PURPOSE: To evaluate visual outcome and corneal shape change during the first month of wearing corneal refractive therapy (CRT) reshaping contact lenses to correct myopia in otherwise healthy eyes. METHODS: Twenty-nine eyes were fit with Paragon CRT contact lenses, which were worn nightly. Before and after CRT fitting, uncorrected visual acuity was measured, and corneal topography was performed and evaluated with the Holladay Diagnostic Summary EyeSys 2000 Videokeratoscope. To evaluate the visual outcome, refractive yield (achieved/attempted correction) was calculated and accounted for distance or monovision. RESULTS: Uncorrected visual acuity improved in all patients. In 1 month, refractive yield was 96.7%. Corneal uniformity index and predicted corneal acuity index were maintained, and the Q value changed from -0.08 to +0.38 (P < 0.05). CONCLUSIONS: CRT lenses are effective in improving visual acuity. They significantly changed the corneal from prolate to oblate while maintaining corneal quality.

No association between the Pro197Leu polymorphism in the glutathione peroxidase (GPX1) gene and schizophrenia.

OBJECTIVE: Oxidative stress such as free radical-mediated neuronal dysfunction may be involved in the pathophysiology of schizophrenia. The human glutathione peroxidase (GPX1) is a selenium-dependent enzyme, which plays an important role in the detoxification of free radicals. We therefore hypothesized that the GPX1 gene, which is located on chromosome 3p21.3, may be involved in the pathophysiology of schizophrenia. The aim of this study is to examine whether a potentially functional polymorphism, a proline (Pro) to leucine (Leu) substitution at codon 197 (Pro197Leu) of the human GPX1 gene, is associated with susceptibility to schizophrenia. METHODS: We genotyped the Pro197Leu polymorphism in a total of 113 nuclear families that had a proband with schizophrenia. Genetic association was tested using the transmission disequilibrium test (TDT), the sib transmission disequilibrium test (STDT), and the family-based association test (FBAT). RESULTS: The minor allele (Leu) frequency was calculated to be 0.282. We could not find significant transmission disequilibrium of the alleles for the Pro197Leu polymorphism in the GPX1 gene in association with the presence of schizophrenia in our family sample (TDT, chi2=0.03, degrees of freedom=1, P=0.86; combined TDT-STDT, Z'=-0.052, P=0.47; FBAT, Z=0.000, P=1.000). CONCLUSION: The results of this study suggest that the GPX1 polymorphism is unlikely to be associated with susceptibility to schizophrenia.