An implementation model for managing cloud-based longitudinal care plans for children with medical complexity.

OBJECTIVE: We aimed to iteratively refine an implementation model for managing cloud-based longitudinal care plans (LCPs) for children with medical complexity (CMC). MATERIALS AND METHODS: We conducted iterative 1-on-1 design sessions with CMC caregivers (ie, parents/legal guardians) and providers between August 2017 and March 2019. During audio-recorded sessions, we asked participants to walk through role-specific scenarios of how they would create, review, and edit an LCP using a cloud-based prototype, which we concurrently developed. Between sessions, we reviewed audio recordings to identify strategies that would mitigate barriers that participants reported relating to 4 processes for managing LCPs: (1) taking ownership, (2) sharing, (3) reviewing, and (4) editing. Analysis informed iterative implementation model revisions. RESULTS: We conducted 30 design sessions, with 10 caregivers and 20 providers. Participants emphasized that cloud-based LCPs required a team of owners: the caregiver(s), a caregiver-designated clinician, and a care coordinator. Permission settings would need to include universal accessibility for emergency providers, team-level permission options, and some editing restrictions for caregivers. Notifications to review and edit the LCP should be sent to team members before and after clinic visits and after hospital encounters. Mitigating double documentation barriers would require alignment of data fields between the LCP and electronic health record to maximize interoperability. DISCUSSION: These findings provide a model for how we may leverage emerging Health Insurance Portability and Accountability Act-compliant cloud computing technologies to support families and providers in comanaging health information for CMC. CONCLUSIONS: Utilizing these management strategies when implementing cloud-based LCPs has the potential to improve team-based care across settings.

User-centered design of a longitudinal care plan for children with medical complexity.

OBJECTIVE: To determine the content priorities and design preferences for a longitudinal care plan (LCP) among caregivers and healthcare providers who care for children with medical complexity (CMC) in acute care settings. MATERIALS AND METHODS: We conducted iterative one-on-one design sessions with CMC caregivers (ie, parents/legal guardians) and providers from 5 groups: complex care, primary care, subspecialists, emergency care, and care coordinators. Audio-recorded sessions included content categorization activities, drawing exercises, and scenario-based testing of an electronic LCP prototype. We applied inductive content analysis of session materials to elicit content priorities and design preferences between sessions. Analysis informed iterative prototype revisions. RESULTS: We conducted 30 design sessions (10 with caregivers, 20 with providers). Caregivers expressed high within-group variability in their content priorities compared to provider groups. Emergency providers had the most unique content priorities among clinicians. We identified 6 key design preferences: a familiar yet customizable layout, a problem-based organization schema, linked content between sections, a table layout for most sections, a balance between unstructured and structured data fields, and use of family-centered terminology. DISCUSSION: Findings from this study will inform enhancements of electronic health record-embedded LCPs and the development of new LCP tools and applications. The design preferences we identified provide a framework for optimizing integration of family and provider content priorities while maintaining a user-tailored experience. CONCLUSION: Health information platforms that incorporate these design preferences into electronic LCPs will help meet the information needs of caregivers and providers caring for CMC in acute care settings.

Two-Fluorophore Mobile Phone Imaging of Biplexed Real-Time NAATs Overcomes Optical Artifacts in Highly Scattering Porous Media.

Nucleic acid amplification tests (NAATs) are common in laboratory and clinical settings because of their low time to result and exquisite sensitivity and specificity. Laboratory NAATs include onboard positive controls to reduce false negatives and specialized hardware to enable real-time fluorescence detection. Recent efforts to translate NAATs into at-home tests sacrifice one or more of the benefits of laboratory NAATs, such as sensitivity, internal amplification controls (IACs), or time to result. In this manuscript, we describe a mobile-phone-based strategy for real-time imaging of biplexed NAATs in paper. The strategy consisted of: (1) using mobile phones with multipass excitation and emission filters on the flash and camera to image the signal from distinct fluorophore-labeled probe types in a biplexed NAAT in a glass fiber membrane; and (2) analyzing the differential fluorescence signal between the red and green color channels of phone images to overcome a strong evaporation-induced optical artifact in heated glass fiber pads due to changes in the refractive index. We demonstrated that differential fluorescence imaging enabled low limits of detection (316 copies of methicillin-resistant Staphylococcus aureus DNA) in our lab's "MD NAAT" platform, even in biplexed isothermal strand displacement amplification reactions containing 100k copies of coamplifying IAC DNA templates. These results suggest that two-fluorophore mobile phone imaging may enable translating the benefits of extant laboratory-based, real-time NAATs to the point of care.

Mobile Phone Ratiometric Imaging Enables Highly Sensitive Fluorescence Lateral Flow Immunoassays without External Optical Filters.

Paper-based diagnostic tests based on the lateral flow immunoassay concept promise low-cost, point-of-care detection of infectious diseases, but such assays suffer from poor limits of detection. One factor that contributes to poor analytical performance is a reliance on low-contrast chromophoric optical labels such as gold nanoparticles. Previous attempts to improve the sensitivity of paper-based diagnostics include replacing chromophoric labels with enzymes, fluorophores, or phosphors at the expense of increased fluidic complexity or the need for device readers with costly optoelectronics. Several groups, including our own, have proposed mobile phones as suitable point-of-care readers due to their low cost, ease of use, and ubiquity. However, extant mobile phone fluorescence readers require costly optical filters and were typically validated with only one camera sensor module, which is inappropriate for potential point-of-care use. In response, we propose to couple low-cost ultraviolet light-emitting diodes with long Stokes-shift quantum dots to enable ratiometric mobile phone fluorescence measurements without optical filters. Ratiometric imaging with unmodified smartphone cameras improves the contrast and attenuates the impact of excitation intensity variability by 15×. Practical application was shown with a lateral flow immunoassay for influenza A with nucleoproteins spiked into simulated nasal matrix. Limits of detection of 1.5 and 2.6 fmol were attained on two mobile phones, which are comparable to a gel imager (1.9 fmol), 10× better than imaging gold nanoparticles on a scanner (18 fmol), and >2 orders of magnitude better than gold nanoparticle-labeled assays imaged with mobile phones. Use of the proposed filter-free mobile phone imaging scheme is a first step toward enabling a new generation of highly sensitive, point-of-care fluorescence assays.

BIOPYDB: A Dynamic Human Cell Specific Biochemical Pathway Database with Advanced Computational Analyses Platform.

BIOPYDB: BIOchemical PathwaY DataBase is developed as a manually curated, readily updatable, dynamic resource of human cell specific pathway information along with integrated computational platform to perform various pathway analyses. Presently, it comprises of 46 pathways, 3189 molecules, 5742 reactions and 6897 different types of diseases linked with pathway proteins, which are referred by 520 literatures and 17 other pathway databases. With its repertoire of biochemical pathway data, and computational tools for performing Topological, Logical and Dynamic analyses, BIOPYDB offers both the experimental and computational biologists to acquire a comprehensive understanding of signaling cascades in the cells. Automated pathway image reconstruction, cross referencing of pathway molecules and interactions with other databases and literature sources, complex search operations to extract information from other similar resources, integrated platform for pathway data sharing and computation, etc. are the novel and useful features included in this database to make it more acceptable and attractive to the users of pathway research communities. The RESTful API service is also made available to the advanced users and developers for accessing this database more conveniently through their own computer programmes.

Ultrasonic-assisted continuous methanolysis of Jatropha curcas oil in the appearance of biodiesel used as an intermediate solvent.

A environmental friendly system for fast transesterification of Jatropha curcas oil was developed for the production of biodiesel using an ultrasonic-assisted continuous tank reactor in the presence of fatty acid methyl ester (FAMEs) used as a green (intermediate) solvent with potassium hydroxide used as a catalyst. This research provide a new biodiesel production process, the optimal condition for the reaction were established: reaction temperature 25°C oil to methanol molar ratio was 1:5, catalyst concentration 0.75wt% of oil, solvent concentration 7.5%, flow rate 241.68±0.80ml/min, ultrasonic amplitude 60% and ultrasonic cycles 0.7s, transesterification was completed within 1.09min (residence time). The purity and conversion of biodiesel was 98.75±0.50% analyzed by the reverse phase HPLC method.

Efficacy of agomelatine in major depressive disorder: meta-analysis and appraisal.

Agomelatine is the first approved antidepressant that mediates its activity through the melatoninergic pathway rather than the monoaminergic system. This meta-analysis aims to summarize an up-to-date report on the efficacy of agomelatine in major depressive disorder. Archives of published results in PubMed, CINAHL, Cochrane Library, EMBASE and PsycINFO databases were searched for randomized double-blind trials comparing agomelatine against placebo or antidepressant in major depressive disorder. Change in severity of depression as a result of intervention was the main outcome measure. Data necessary to compute the standardized mean difference (SMD) of this outcome and additional sample parameters that were likely to influence the main outcome were extracted for each selected studies. Summary effect sizes of various groups and subgroups were computed from SMDs between agomelatine and control (placebo or antidepressants) arms. There were nine trials involving 3943 severe cases of depression on agomelatine (n=2390) and either placebo (n=689) or antidepressants (n=864). Agomelatine (n=1274) stood superior to placebo (n=689) by a small margin (SMD -0.26, p=3.48×10-11) and the superiority of agomelatine (n=834, dose ≥ 25 mg/d) over antidepressants (paroxetine, fluoxetine, sertraline, venlafaxine; n=864) was even smaller (SMD -0.11, p=0.02). Although there is evidence of the superiority of agomelatine over placebo and selected antidepressants, it is questionable whether the magnitude of effect size is clinically significant and sample characteristics are relevant to the general patient population with major depressive disorder.

Meta-analysis of the efficacy of adjunctive NMDA receptor modulators in chronic schizophrenia.

BACKGROUND: Based on the glutamatergic NMDA receptor hypofunction theory of schizophrenia, NMDA receptor modulators (NMDARMs) may have therapeutic potential in the treatment of schizophrenia. OBJECTIVE: This meta-analysis aimed to evaluate the potential of modulators of the NMDA receptor as adjunctive therapy for schizophrenia, using the results from published trials. DATA SOURCES: A primary electronic search for controlled clinical trials using NMDARMs in schizophrenia was conducted on the PubMed, Cochrane Library, EMBASE, CINAHL® and PsycINFO databases. A secondary manual search of references from primary publications was also performed. STUDY SELECTION: Inclusion criteria were the application of an established method of diagnosis, randomized case assignment, comparison of NMDARM add-on therapy with placebo, and double-blind assessment of symptoms in chronic schizophrenia using standardized rating scales. Results were based on a total sample size of 1253 cases from 29 trials that fulfilled the specified criteria. DATA EXTRACTION: Scores on rating scales or on their relevant subscales were obtained for all selected studies from published results for the minimum dataset to compute the difference between post- and pre-trial scores and their pooled standard deviation for NMDARM add-on therapy and placebo groups for negative, positive and total symptoms. RESULTS: A negative standardized mean difference (SMD) indicates therapeutic benefit in favour of NMDARM add-on therapy and all SMD results mentioned here are statistically significant. The overall effect size for NMDARMs as a group was small for negative (SMD -0.27) and medium for total (SMD -0.40) symptoms of chronic schizophrenia. Subgroup analysis revealed medium effect sizes for D-serine and N-acetyl-cysteine (NAC) for negative (SMD -0.53 and -0.45, respectively) and total (SMD -0.40 and -0.64, respectively) symptoms, and for glycine (SMD -0.66) and sarcosine (SMD -0.41) for total symptoms. As adjuvants to non-clozapine antipsychotics, additional therapeutic benefits were observed for NMDARM as a group (SMD -0.14) and glycine (SMD -0.54) for positive symptoms; D-serine (SMD -0.54), NAC (SMD -0.45) and sarcosine (SMD -0.39) for negative symptoms; and NMDARM as a group (SMD -0.38), D-serine (SMD -0.40), glycine (SMD -1.12), NAC (SMD -0.64) and sarcosine (SMD -0.53) for total symptoms. When added to clozapine, none of the drugs demonstrated therapeutic potential, while addition of glycine (SMD +0.56) worsened positive symptoms. CONCLUSIONS: Taking into consideration the number of trials and sample size in subgroup analyses, D-serine, NAC and sarcosine as adjuncts to non-clozapine antipsychotics have therapeutic benefit in the treatment of negative and total symptoms of chronic schizophrenia. While glycine improves positive and total symptoms as an adjuvant to non-clozapine antipsychotics, it worsens them when added to clozapine.

Efficacy of antidepressants in treating the negative symptoms of chronic schizophrenia: meta-analysis.

BACKGROUND: Treatment of negative symptoms in chronic schizophrenia continues to be a major clinical issue. AIMS: To analyse the efficacy of add-on antidepressants for the treatment of negative symptoms of chronic schizophrenia. METHOD: Systematic review and meta-analysis of randomised controlled trials comparing the effect of antidepressants and placebo on the negative symptoms of chronic schizophrenia, measured through standardised rating scales. Outcome was measured as standardised mean difference between end-of-trial and baseline scores of negative symptoms. RESULTS: There were 23 trials from 22 publications (n = 819). The antidepressants involved were selective serotonin reuptake inhibitors, mirtazapine, reboxetine, mianserin, trazodone and ritanserin; trials on other antidepressants were not available. The overall standardised mean difference was moderate (-0.48) in favour of antidepressants and subgroup analysis revealed significant responses for fluoxetine, trazodone and ritanserin. CONCLUSIONS: Antidepressants along with antipsychotics are more effective in treating the negative symptoms of schizophrenia than antipsychotics alone.

Review and meta-analysis of usage of ginkgo as an adjunct therapy in chronic schizophrenia.

This study aimed to review the roles of antioxidants in the pathophysiology of schizophrenia, whether the properties of ginkgo can ameliorate symptoms of this illness, and evaluate available literature to test this assumption. This review is based upon published works on antioxidants and ginkgo. A primary electronic search for meta-analysis on the usage of ginkgo or its derived products in schizophrenia was conducted using Pubmed, Cochrane Library, EMBASE, CINAHL, PsycINFO and AMED. Inclusion criteria were: criteria-based diagnosis of schizophrenia, randomized case assignment, use of ginkgo as an add-on therapy, and assessment using standardized rating scales to measure the state of psychopathology for negative and total symptoms of schizophrenia. Additionally, a detailed review was undertaken to investigate if antioxidants are involved in development of psychotic symptoms in schizophrenia. The six studies that fulfilled the selection criteria were constituted of 466 cases on ginkgo and 362 cases on placebo. They all used the Scale for the Assessment of Negative Symptoms (SANS) to measure negative symptoms, and the Scale for the Assessment of Positive Symptoms (SAPS) or the Brief Psychiatric Rating Scale (BPRS) to measure total symptoms. Difference between ginkgo and control groups from their pre- and post-trial scores and its pooled standard deviation were used to compute standardized mean difference (SMD). Ginkgo as an add-on therapy to antipsychotic medication produced statistically significant moderate improvement (SMD=-0.50) in total and negative symptoms of chronic schizophrenia. Ginkgo as add-on therapy ameliorates the symptoms of chronic schizophrenia. The role of antioxidants in pathogenesis of schizophrenia has also been explored.