A Risk Analysis Method to Evaluate the Impact of a Computerized Provider Order Entry System on Patient Safety

Objectives: Quantitative evaluation of safety after the implementation of a computerized provider order entry (CPOE) system, stratification of residual risks to drive future developments. Design: Comparative risk analysis of the drug prescription process before and after the implementation of CPOE system, according to the Failure Modes, Effects and Criticality Analysis (FMECA) method. Measurements: The failure modes were defined and their criticality indices calculated on the basis of the likelihood of occurrence, potential severity for patients, and detection probability. Criticality indices of handwritten and electronic prescriptions were compared, the acceptability of residual risks was discussed. Further developments were proposed and their potential impact on the safety was estimated. Results: The sum of criticality indices of 27 identified failure modes was 3813 for the handwritten prescription, 2930 (−23%) for CPOE system, and 1658 (−57%) with 14 enhancements. The major safety improvements were observed for errors due to ambiguous, incomplete or illegible orders (−245 points), wrong dose determination (−217) and interactions (−196). Implementation of targeted pop-ups to remind treatment adaptation (−189), vital signs (−140), and automatic edition of documents needed for the dispensation (−126) were the most promising proposed improvements. Conclusion: The impact of a CPOE system on patient safety strongly depends on the implemented functions and their ergonomics. The use of risk analysis helps to quantitatively evaluate the relationship between a system and patient safety and to build a strategy for continuous quality improvement, by selecting the most appropriate improvements to the syste

North Atlantic Midlatitude Surface-Circulation Changes Through the Plio-Pleistocene Intensification of Northern Hemisphere Glaciation

The North Atlantic Current (NAC) transports warm salty water to high northern latitudes, with important repercussions for ocean circulation and global climate. A southward displacement of the NAC and Subarctic Front, which separate subpolar and subtropical water masses, is widely suggested for the Last Glacial Maximum (LGM) and may have acted as a positive feedback in glacial expansion at this time. However, the role of the NAC during the intensification of Northern Hemisphere glaciation (iNHG) at ~3.5 to 2.5 Ma is less clear. Here we present new records from Integrated Ocean Drilling Program Site U1313 (41°N) spanning ~2.8–2.4 Ma to trace the influence of Subarctic Front waters above this mid‐latitude site. We reconstruct surface and permanent pycnocline temperatures and seawater δ18O using paired Mg/Ca‐δ18O measurements on the planktic foraminifers Globigerinoides ruber and Globorotalia crassaformis and determine abundances of the subpolar foraminifer Neogloboquadrina atlantica. We find that the first significant glacial incursions of Subarctic Front surface waters above Site U1313 did not occur until ~2.6 Ma. At no time during our study interval was (sub)surface reorganization in the midlatitude North Atlantic analogous to the LGM. Our findings suggest that LGM‐like processes sensu stricto cannot be invoked to explain interglacial‐glacial cycle amplification during iNHG. They also imply that increased glacial productivity at Site U1313 during iNHG was not only driven by southward deflections of the Subarctic Front. We suggest that nutrient injection from cold‐core eddies and enhanced glacial dust delivery may have played additional roles in increasing export productivity in the midlatitude North Atlantic from 2.7 Ma.t. Funding for this research was provided by IODP France (C. T. B.) and the German Research Foundation (DFG) (grant OF 2544/2 to O. F.). I. B. is grateful to the UK IODP for financial support for shipboard and post-cruise participation in IODP Exp. 306. C. T. B., K. T., T. D. G., L. V., C. S., and M. E. acknowledge OSU Pythéas. M. M. R. acknowledges support by the USGS Land Change Science Program

Rhythmic Relating : Bidirectional support for social timing in autism therapies

We propose Rhythmic Relating for autism: a system of supports for friends, therapists, parents, and educators; a system which aims to augment bidirectional communication and complement existing therapeutic approaches. We begin by summarizing the developmental significance of social timing and the social-motor-synchrony challenges observed in early autism. Meta-analyses conclude the early primacy of such challenges, yet cite the lack of focused therapies. We identify core relational parameters in support of social-motor-synchrony and systematize these using the communicative musicality constructs: pulse; quality; and narrative. Rhythmic Relating aims to augment the clarity, contiguity, and pulse-beat of spontaneous behavior by recruiting rhythmic supports (cues, accents, turbulence) and relatable vitality; facilitating the predictive flow and just-ahead-in-time planning needed for good-enough social timing. From here, we describe possibilities for playful therapeutic interaction, small-step co-regulation, and layered sensorimotor integration. Lastly, we include several clinical case examples demonstrating the use of Rhythmic Relating within four different therapeutic approaches (Dance Movement Therapy, Improvisational Music Therapy, Play Therapy, and Musical Interaction Therapy). These clinical case examples are introduced here and several more are included in the Supplementary Material (Examples of Rhythmic Relating in Practice). A suite of pilot intervention studies is proposed to assess the efficacy of combining Rhythmic Relating with different therapeutic approaches in playful work with individuals with autism. Further experimental hypotheses are outlined, designed to clarify the significance of certain key features of the Rhythmic Relating approach

Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information

Funding Information: This work was supported by the National Institute of Mental Health / U.S. Army Medical Research and Development Command (Grant No. R01MH106595 [to CMN, IL, MBS, KJRe, and KCK], National Institutes of Health (Grant No. 5U01MH109539 to the Psychiatric Genomics Consortium ), and Brain & Behavior Research Foundation (Young Investigator Grant [to KWC]). Genotyping of samples was provided in part through the Stanley Center for Psychiatric Genetics at the Broad Institute supported by Cohen Veterans Bioscience . Statistical analyses were carried out on the LISA/Genetic Cluster Computer ( https://userinfo.surfsara.nl/systems/lisa ) hosted by SURFsara. This research has been conducted using the UK Biobank resource (Application No. 41209). This work would have not been possible without the financial support provided by Cohen Veterans Bioscience, the Stanley Center for Psychiatric Genetics at the Broad Institute, and One Mind. Funding Information: MBS has in the past 3 years received consulting income from Actelion, Acadia Pharmaceuticals, Aptinyx, Bionomics, BioXcel Therapeutics, Clexio, EmpowerPharm, GW Pharmaceuticals, Janssen, Jazz Pharmaceuticals, and Roche/Genentech and has stock options in Oxeia Biopharmaceuticals and Epivario. In the past 3 years, NPD has held a part-time paid position at Cohen Veterans Bioscience, has been a consultant for Sunovion Pharmaceuticals, and is on the scientific advisory board for Sentio Solutions for unrelated work. In the past 3 years, KJRe has been a consultant for Datastat, Inc., RallyPoint Networks, Inc., Sage Pharmaceuticals, and Takeda. JLM-K has received funding and a speaking fee from COMPASS Pathways. MU has been a consultant for System Analytic. HRK is a member of the Dicerna scientific advisory board and a member of the American Society of Clinical Psychopharmacology Alcohol Clinical Trials Initiative, which during the past 3 years was supported by Alkermes, Amygdala Neurosciences, Arbor Pharmaceuticals, Dicerna, Ethypharm, Indivior, Lundbeck, Mitsubishi, and Otsuka. HRK and JG are named as inventors on Patent Cooperative Treaty patent application number 15/878,640, entitled “Genotype-guided dosing of opioid agonists,” filed January 24, 2018. RP and JG are paid for their editorial work on the journal Complex Psychiatry. OAA is a consultant to HealthLytix. All other authors report no biomedical financial interests or potential conflicts of interest. Funding Information: This work was supported by the National Institute of Mental Health/ U.S. Army Medical Research and Development Command (Grant No. R01MH106595 [to CMN, IL, MBS, KJRe, and KCK], National Institutes of Health (Grant No. 5U01MH109539 to the Psychiatric Genomics Consortium), and Brain & Behavior Research Foundation (Young Investigator Grant [to KWC]). Genotyping of samples was provided in part through the Stanley Center for Psychiatric Genetics at the Broad Institute supported by Cohen Veterans Bioscience. Statistical analyses were carried out on the LISA/Genetic Cluster Computer (https://userinfo.surfsara.nl/systems/lisa) hosted by SURFsara. This research has been conducted using the UK Biobank resource (Application No. 41209). This work would have not been possible without the financial support provided by Cohen Veterans Bioscience, the Stanley Center for Psychiatric Genetics at the Broad Institute, and One Mind. This material has been reviewed by the Walter Reed Army Institute of Research. There is no objection to its presentation and/or publication. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting true views of the U.S. Department of the Army or the Department of Defense. We thank the investigators who comprise the PGC-PTSD working group and especially the more than 206,000 research participants worldwide who shared their life experiences and biological samples with PGC-PTSD investigators. We thank Mark Zervas for his critical input. Full acknowledgments are in Supplement 1. MBS has in the past 3 years received consulting income from Actelion, Acadia Pharmaceuticals, Aptinyx, Bionomics, BioXcel Therapeutics, Clexio, EmpowerPharm, GW Pharmaceuticals, Janssen, Jazz Pharmaceuticals, and Roche/Genentech and has stock options in Oxeia Biopharmaceuticals and Epivario. In the past 3 years, NPD has held a part-time paid position at Cohen Veterans Bioscience, has been a consultant for Sunovion Pharmaceuticals, and is on the scientific advisory board for Sentio Solutions for unrelated work. In the past 3 years, KJRe has been a consultant for Datastat, Inc. RallyPoint Networks, Inc. Sage Pharmaceuticals, and Takeda. JLM-K has received funding and a speaking fee from COMPASS Pathways. MU has been a consultant for System Analytic. HRK is a member of the Dicerna scientific advisory board and a member of the American Society of Clinical Psychopharmacology Alcohol Clinical Trials Initiative, which during the past 3 years was supported by Alkermes, Amygdala Neurosciences, Arbor Pharmaceuticals, Dicerna, Ethypharm, Indivior, Lundbeck, Mitsubishi, and Otsuka. HRK and JG are named as inventors on Patent Cooperative Treaty patent application number 15/878,640, entitled ?Genotype-guided dosing of opioid agonists,? filed January 24, 2018. RP and JG are paid for their editorial work on the journal Complex Psychiatry. OAA is a consultant to HealthLytix. All other authors report no biomedical financial interests or potential conflicts of interest. Publisher Copyright: © 2021 Society of Biological PsychiatryBackground: Posttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) information could enhance the discovery power of PTSD genome-wide association studies (GWASs). Methods: A GWAS on PTSD symptoms was performed in 51 cohorts followed by a fixed-effects meta-analysis (N = 182,199 European ancestry participants). A GWAS of LTE burden was performed in the UK Biobank cohort (N = 132,988). Genetic correlations were evaluated with linkage disequilibrium score regression. Multivariate analysis was performed using Multi-Trait Analysis of GWAS. Functional mapping and annotation of leading loci was performed with FUMA. Replication was evaluated using the Million Veteran Program GWAS of PTSD total symptoms. Results: GWASs of PTSD symptoms and LTE burden identified 5 and 6 independent genome-wide significant loci, respectively. There was a 72% genetic correlation between PTSD and LTE. PTSD and LTE showed largely similar patterns of genetic correlation with other traits, albeit with some distinctions. Adjusting PTSD for LTE reduced PTSD heritability by 31%. Multivariate analysis of PTSD and LTE increased the effective sample size of the PTSD GWAS by 20% and identified 4 additional loci. Four of these 9 PTSD loci were independently replicated in the Million Veteran Program. Conclusions: Through using a quantitative trait measure of PTSD, we identified novel risk loci not previously identified using prior case-control analyses. PTSD and LTE have a high genetic overlap that can be leveraged to increase discovery power through multivariate methods.publishersversionpublishe