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Immediate benefits realized following implementation of physician order entry at an academic medical center.

OBJECTIVE: To evaluate the benefits of computerized physician order entry (POE) and electronic medication administration record (eMAR) on the delivery of health care. DESIGN: Inpatient nursing units in an academic health system were the setting for the study. The study comprised before-and-after comparisons between phase 1, pre-implementation of POE (pre-POE) and phase 2, post-implementation of POE (post-POE) and, within phase 2, a comparison of POE and the combination of POE plus eMAR. Length of stay and cost were compared pre- and post-POE for a period of 10 to 12 months across all services in the respective hospitals. MEASUREMENTS: Comparisons were made pre- and post-POE for the time intervals between initiation and completion of pharmacy (pre-POE, n=46; post-POE, n=70), radiology (pre-POE, n=11; post-POE, n=54), and laboratory orders (without POE, n=683; with POE, n=1,142); timeliness of countersignature of verbal order (University Hospitals [OSUH]: pre-POE, n=605; post-POE, n=19,225; James Cancer Hospital (James): pre-POE, n=478; post-POE, n=10,771); volume of nursing transcription errors (POE with manual MAR, n=888; POE with eMAR, n=396); length of stay and total cost (OSUH: pre-POE, n=8,228; post-POE, n=8,154; James: (pre-POE, n=6,471; post-POE, n=6,045). RESULTS: Statistically significant reductions were seen following the implementation of POE for medication turn-around times (64 percent, from 5:28 hr to 1:51 hr; p<0.001), radiology procedure completion times (43 percent, from 7:37 hr to 4:21 hr; p<0.05), and laboratory result reporting times (25 percent, from 31:3 min to 23:4 min; p=0.001). In addition, POE combined with eMAR eliminated all physician and nursing transcription errors. There were 43 and 26 percent improvements in order countersignature by physicians in OSUH and James, respectively. Severity-adjusted length of stay decreased in OSUH (pre-POE, 3.91 days; post-POE, 3.71 days; p=0.002), but not significantly in James (pre-POE, 3.68 days; post-POE, 3.61 days; p=0.356). Although total cost per admission decreased significantly in selected services, it did not change significantly across either institution (OSUH: pre-POE, 5,697 dollars; post-POE, 5,661 dollars; p=0.687; James: pre-POE, 6,427 dollars; post-POE, 6,518 dollars; p=0.502). CONCLUSION: Physician order entry and eMAR provided the framework for improvements in patient safety and in the timeliness of care. The significant cultural and workflow changes that accompany the implementation of POE did not adversely affect acuity-adjusted length of stay or total cost. The reductions in transcription errors, medication turn-around times, and timely reporting of results supports the view that POE and eMAR provide a good return on investment.

Academic Medical Centers↗

Implementation of a radiology electronic imaging network: the community teaching hospital experience.

Because of their typically small in-house computer and network staff, non-university hospitals often hesitate to consider picture archiving and communication system (PACS) as a solution to the very demanding financial, clinical, and technological needs of today's Radiology Department. This article presents the experiences of the 3-year process for the design and implementation of the Radiology Electronic Imaging Network (REIN) in the Department of Radiology at The Western Pennsylvania Hospital (WPH). WPH embarked on this project in late 1994 to find a solution to the very pressing demands to reduce operating costs and improve service to primary care clinicians, both on-site and at WPH-affiliated clinics. A five-member committee consisting of in-house medical, administrative, information services, and medical physics staff was formed to design a network that would satisfy specific needs of WPH by using a phased mini-PACS approach and to select the various vendors to implement it. Suppliers for individual mini-PACS were selected to provide modality-specific solutions. For the backbone network, vendors were evaluated based on their technological progress, competence and resources, the commitment of the company to the imaging network business, and their willingness to embark on a mid-sized PACS project such as this. Based on patient volume, workflow patterns, and image quality requirements, the committee produced proposals detailing number and location of workstations, short- and long-term memory requirements, and so on. Computed tomography/magnetic resonance imaging, computer radiography, ultrasound, nuclear medicine, digital fluoroscopy, and angiography mini-PACS have been implemented over the past 2 years, and most of these are already integrated into the main REIN. This article presents detailed information concerning the design, selection and implementation processes, including storage requirement calculations. This indicates that PACS implementation is achievable for community hospitals with small computer, networking, and physics departments. Also presented are recommendations concerning design and vendor selection, that may be helpful for similar institutions.

Computer Communication Networks↗

Population-scale detection of methylation outliers from long-read genome sequencing.

BACKGROUND: Aberrant DNA methylation can mediate the functional effects of rare genetic variation and contribute to imprinting disorders, repeat expansion diseases, and other pathogenic regulatory mechanisms. Long-read sequencing technologies now enable genome-wide detection of CpG methylation alongside genetic variation from a single assay. However, methods for systematic identification and interpretation of methylation outliers from long-read sequencing data remain limited. METHODS: We developed METAFORA, a computational workflow for detecting methylation outlier regions from PacBio and Oxford Nanopore long-read sequencing data. METAFORA constructs population-level methylation references, segments the genome into correlated CpG blocks, infers technical and biological sources of variation through hidden factor estimation, models uncertainty due to variable depth sequencing, and computes covariate-adjusted methylation outlier scores for individual samples. We applied METAFORA across large long-read sequencing cohorts and integrated methylation outliers with multi-omic data. METAFORA is implemented as a snakemake workflow available at https://github.com/tjense25/METAFORA. RESULTS: METAFORA identified methylation outlier regions associated with rare structural variants, tandem repeat expansions, and imprinting abnormalities. We found outlier regions were enriched for molecular outliers across transcriptomic and chromatin accessibility datasets, supporting their functional relevance in gene regulation. In a representative case, METAFORA identified an imprinting defect affecting the GNAS locus associated with an STX16 deletion. CONCLUSIONS: METAFORA enables scalable detection and interpretation of methylation outliers from long-read sequencing data and provides a framework for integrating epigenetic outliers with genomic and multi-omic analyses. These approaches may improve interpretation of rare regulatory variation and support discovery of clinically relevant epigenetic abnormalities in genomic medicine.

DNA methylation↗

LCM-Enriched Proteomic Characterization of Antibody-Mediated Glomerular Damage and Complement Activation in Pre-Clinical Models.

Biologics, lipid nanoparticles, and other therapeutic modalities can result in adverse events, often detected as lesions during preclinical pathology assessments. Characterization of these lesions provides valuable information during drug development to contextualize mechanisms of injury and assess species translatability. Here, we investigated the utility of a laser capture microdissection (LCM)-enriched mass spectrometry proteomics approach to analyze two well-characterized preclinical models of regional (glomerular) injury: Passive Heyman Nephritis in rats and bovine gamma globulin-induced glomerular injury in nonhuman primates (NHPs). Using LCM-enriched proteomics, glomeruli were isolated from formalin-fixed paraffin-embedded kidney tissue in the rat model, enabling identification of 4,661 proteins and quantification of 3,410. Proteinuria measurements were compared with digital pathology metrics of glomerular morphology and proteomics results, with all modalities yielding concordant evidence of glomerular injury and proteomics confirming the role of complement activation. The same LCM- enriched proteomics workflow was applied to an NHP model of induced glomerular damage, identifying 4,623 proteins, quantifying 3,000, and confirming qualitative concordance with established features of complement-mediated glomerular injury. Together, these findings illustrate the applicability of LCM-enriched proteomics for region-specific characterization of antibody-mediated tissue injury and support its use as a hypothesis-generating platform in translational toxicologic pathology.

Animals↗

Patient safety and computerized medication ordering at Brigham and Women's Hospital.

BACKGROUND: Medications are important therapeutic tools in health care, yet creating safe medication processes is challenging for many reasons. Computerized physician order entry (CPOE), one important way that technology can be used to improve the medication process, has been in place at Brigham and Women's Hospital (BWH; Boston) since 1993. CPOE AT BWH: The CPOE application, designed and developed internally by the BWH information systems team, allows physicians and other clinicians to enter all patient orders into the computer. Physicians enter 85% of orders, with the remainder entered electronically by other clinicians. CPOE AND SAFE MEDICATION USE: The CPOE application at BWH includes several features designed to improve medication safety--structural features (for example, required fields, use of pick lists), enhanced workflow features (order sets, standard scales for insulin and potassium), alerts and reminders (drug-drug and drug-allergy interaction checking), and adjunct features (the pharmacy system, access to online reference information). RESULTS AT BWH: Studies of the impact of CPOE on physician decision making and patient safety at BWH include assessment of CPOE's impact on the serious medication error and the preventable adverse drug event rate, the impact of computer guidelines on the use of vancomycin, the impact of guidelines on the use of heparin in patients at bed rest, and the impact of dosing suggestions on excessive dosing. CONCLUSION: CPOE and several forms of clinical decision support targeted at increasing patient safety have substantially decreased the frequency of serious medication errors and have had an even bigger impact on the overall medication error rate.

Clinical Pharmacy Information Systems↗

Case study: improving efficiency in a large hospital laboratory.

Saint Francis Health System (SFHS) consists of three hospitals and one clinic: Saint Francis Hospital (SFH); Broken Arrow Medical Center; Laureate Psychiatric Hospital; and Warren Clinic. SFHS has 670 physicians on staff and serves medical (oncology, orthopedic, neurology, and renal), surgical, cardiac, women and infant, pediatric, transplant, and trauma patients in Tulsa County, Oklahoma, which has a population of 660,000. SFH incorporates 706 staffed beds, including 126 pediatric beds and 119 critical care beds. Each year, the health system averages 38,000 admissions, 70,000 emergency department visits, 25,000 surgeries, and 3,500 births. Saint Francis Laboratory is located within the main hospital facility (SFH) and functions as a core lab for the health system. The lab also coordinates lab services with Saint Francis Heart Hospital, a physician-system joint venture. The Optimal Equipment Configuration (OEC) Project was designed by the Clinical Laboratory Services division of Premier, a group purchasing organization, with the goal of determining whether laboratories could improve efficiency and decrease unit cost by using a single-source vendor. Participants included seven business partners (Abbott, Bayer, Beckman/Coulter, Dade/Behring, J&J/ Ortho, Olympus, and Roche) and 21 laboratory sites (a small, mid-sized, and large site for each vendor). SFH laboratory staff embraced Premier's concept and viewed the OEC project as an opportunity to "energize" laboratory operations. SFH partnered with Abbott, their primary equipment vendor, for the project. Using resources and tools made available through the project, the laboratory was re-engineered to simplify workflow, increase productivity, and decrease costs by adding automation and changing to centralized specimen processing. Abbott and SFH shared a common vision for the project and enhanced their partnership through increased communication and problem solving. Abbott's area representatives provided for third-party design expertise and quarterly metric reporting through Argent Consulting. Abbott incorporated lessons learned from the SFH OEC project with organizational changes to improve the way they work with customers. Following is a step-by-step description of the OEC project to allow others to benefit from the experience (Figure 1).

Efficiency, Organizational↗

Computerising a guideline for the management of diabetes.

This paper reports an experience of computerising a clinical guideline for the management of non-insulin-dependent diabetes mellitus (NIDDM). The guideline, designed by the European NIDDM Policy Group is being used in a National Programme for Diabetes supported by the Portuguese Ministry of Health, who is keen to supporting its widespread use by general practitioners, namely in computerised form. The paper presents the main characteristics of the prototype that was implemented within the European project Prestige, and was developed according to the Prestige Protocol Model. The model is briefly described, together with the generic architecture that supports it. Then the main design decisions of the prototype are explained, regarding the modelling of a general practitioner workflow during a typical consultation and the user interface, two key issues for obtaining acceptance from the users. The limitations of the system are discussed and a number of directions are outlined in order to circumvent such limitations, and broaden the scope of applicability of the system.

Diabetes Mellitus, Type 2↗

Wireless home monitoring and health care activity management through the Internet in patients with chronic diseases.

A project was developed for the creation of an Internet-based network aimed at improved management of home care activities in brain-injured children. At the patient's side, a home care unit was provided, made of a portable medical device, and a tablet PC. Measured clinical data were blood oxygen saturation, heart rate, breath rate and quantity of movement. Thanks to device portability, the patient was free to move while measurements were taken. At prescribed time intervals, measured data were automatically transmitted to the tablet PC via Bluetooth. From the tablet PC, data were transmitted remotely to a Service Centre (via ADSL or GPRS) and made available for consultation by health care professionals through the project Web portal. At the portal, other functionalities were also available, both for patients and families, and for professionals (such as weekly planning agenda, access to relevant information resources, communication tools). Information was delivered for the right participant through a workflow engine. A first trial involving nine patients was performed for two months. At the end, although some improvements were suggested, good acceptance was detected, and 78% of patients and families claimed to be interested in further use of the platform.

Brain Injuries↗

Automatic repositioning of single voxels in longitudinal 1H MRS studies.

An automatic procedure, allowing the prospective registration of brain MRI images and the acquisition of nearly identical brain volumes (coverage and orientation) in longitudinal exams, is presented. This procedure, based on a fast registration algorithm and a tailored pulse sequence, is used to reposition single voxels for 1H MRS data acquired in vivo. The impact of the repositioning method on the extent of voxel overlap and on the reproducibility of metabolite concentration measurements is studied. A statistically significant increase in voxel overlap and generally decreased short-term measurement variability (decreased coefficients of variation and increased reproducibility coefficients) are observed. Differences in the long-term variances of metabolite concentrations and concentration ratios measured using the eye and automatic repositioning scheme, however, do not reach statistical significance. The improved workflow associated with the use of the automatic repositioning process, which obviates the need for skilled operator intervention for voxel repositioning, suggests that approaches similar to the one presented here may be a standard element in tomorrow's longitudinal MRI and MRS exams.

Algorithms↗

SynchroSep-MS: Parallel LC Separations for Multiplexed Proteomics.

Achieving high throughput remains a challenge in MS-based proteomics for large-scale applications. We introduce SynchroSep-MS, a novel method for parallelized, label-free proteome analysis that leverages the rapid acquisition speed of modern mass spectrometers. This approach employs multiple liquid chromatography columns, each with an independent sample, simultaneously introduced into a single mass spectrometer inlet. A precisely controlled retention time offset between sample injections creates distinct elution profiles, facilitating unambiguous analyte assignment. We modified the DIA-NN workflow to effectively process these unique parallelized data, accounting for retention time offsets. Using a dual-column setup with mouse brain peptides, SynchroSep-MS detected approximately 16,700 unique protein groups, nearly doubling the peptide information obtained from a conventional single proteome analysis. The method demonstrated excellent precision and reproducibility (median protein %RSDs less than 4%) and high quantitative linearity (median R2 greater than 0.96) with minimal matrix interference. SynchroSep-MS represents a new paradigm for data collection and the first example of label-free multiplexed proteome analysis via parallel LC separations, offering a direct strategy to accelerate throughput for demanding applications such as large-scale clinical cohorts and single-cell analyses without compromising peak capacity or causing ionization suppression.

Proteomics↗

MRDagent: iterative and adaptive parameter optimization for stable ctDNA-based MRD detection in heterogeneous samples.

MOTIVATION: Minimal residual disease (MRD) as critical biomarker for cancer prognosis and management plays a crucial role in improving patient outcomes. However, detecting MRD via next-generation sequencing-based circulating tumor DNA variant calling remains unstable due to the extremely low variant allele frequency and significant inter- and intra-sample heterogeneity. Although parameter optimization can theoretically enhance the detection performance of variants, achieving stable MRD detection remains challenging due to three key factors: (i) the necessity for individualized parameter tuning across numerous heterogeneous genomic intervals within each sample, (ii) the tightly interdependent parameter requirements across different stages of variant detection workflows, and (iii) the limitations of current automated parameter optimization methods. RESULTS: In this study, we propose MRDagent, a novel variant detection tool designed specifically for MRD detection. MRDagent incorporates an iterative and self-adaptive optimization framework capable of handling unknown objectives, varying constraints, and highly coupled parameters across stages. A key innovation of MRDagent is the integration of a convolutional neural network-based meta-model, trained on historical data to enable rapid parameter prediction. This significantly enhances computational efficiency and generalization performance. Extensive evaluations on simulated and real-world datasets demonstrate MRDagent's superior and stable performance, providing an efficient, reliable solution for MRD detection in clinical and high-throughput research applications. AVAILABILITY AND IMPLEMENTATION: MRDagent is freely available at https://github.com/aAT0047/MRDagent.git. The corresponding dataset and software archive are available at Zenodo: https://doi.org/10.5281/zenodo.15458496.

Circulating Tumor DNA↗

Case-oriented computer-based-training in radiology: concept, implementation and evaluation.

BACKGROUND: Providing high-quality clinical cases is important for teaching radiology. We developed, implemented and evaluated a program for a university hospital to support this task. METHODS: The system was built with Intranet technology and connected to the Picture Archiving and Communications System (PACS). It contains cases for every user group from students to attendants and is structured according to the ACR-code (American College of Radiology) 2. Each department member was given an individual account, could gather his teaching cases and put the completed cases into the common database. RESULTS: During 18 months 583 cases containing 4136 images involving all radiological techniques were compiled and 350 cases put into the common case repository. Workflow integration as well as individual interest influenced the personal efforts to participate but an increasing number of cases and minor modifications of the program improved user acceptance continuously. 101 students went through an evaluation which showed a high level of acceptance and a special interest in elaborate documentation. CONCLUSION: Electronic access to reference cases for all department members anytime anywhere is feasible. Critical success factors are workflow integration, reliability, efficient retrieval strategies and incentives for case authoring.

Computer Communication Networks↗

Automation and high through-put for a DNA database laboratory: development of a laboratory information management system.

Automation and high through-put production of DNA profiles has become a necessity in every DNA database unit. In our laboratory we developed a Laboratory Information Management System (LIMS) controlled workflow architecture, which comprises a robotic DNA extraction- and pipetting-system and a capillary electrophoresis unit. This allows a through-put of 4,000 samples per person per year. Improved sample handling and data management, full sample- and batch-histories, and software-aided supervision of result data, with a consequent average turn-around time of 8 days, are the main features of our new system.

Austria↗

Value of HCC surveillance in a landscape of emerging surveillance options: Perspectives of a multi-stakeholder modified Delphi panel.

HCC surveillance is recommended by liver professional societies but lacks broad acceptance by several primary care and cancer societies due to limitations in the existing data. We convened a diverse multidisciplinary group of cancer screening experts to evaluate current and future paradigms of HCC prevention and early detection using a rigorous Delphi panel approach. The experts had high agreement on 21 statements about primary prevention, HCC surveillance benefits, HCC surveillance harms, and the evaluation of emerging surveillance modalities. The experts agreed that current data have methodologic limitations as well as unclear generalizability to Western populations. Although a randomized clinical trial of surveillance versus no surveillance is unlikely feasible, they concurred that alternative designs, such as a comparison of 2 surveillance modalities, could provide indirect evidence of surveillance efficacy. The panel acknowledged the presence of surveillance harms, but concurred the overall value of surveillance appears high, particularly given a greater emphasis on benefits over harms by both patients and clinicians. The experts underscored the importance of a framework for measuring both benefits and harms when evaluating emerging surveillance strategies. The panel acknowledged performance metrics of emerging methods may differ from other cancer screening programs given differences in populations, including higher risk of cancer development and competing risk of morality, and differences in diagnostic workflow in patients at risk of HCC. These data provide insights into the perceived value of HCC surveillance in an era of emerging blood- and imaging-based surveillance strategies.

Humans↗

FACS-Proteomics strategy toward extracellular vesicles single-phenotype characterization in biological fluids: exploring the role of leukocyte-derived EVs in multiple sclerosis.

BACKGROUND: The isolation and proteomics characterization of extracellular vesicles (EVs) from body fluids is challenging due to their vast heterogeneity. We have recently demonstrated that Fluorescence-activated Cell Sorting (FACS) efficiently isolates the whole EV circulating compartment directly from untouched body fluids enabling a comprehensive EV proteomics analysis. RESULTS: Here, we characterized, for the first time, a single-phenotype EV subset by sorting leukocyte-derived EVs (Leuko EVs) from peripheral blood and tears of healthy volunteers.&#xa0;Using an optimized and patented staining protocol of the whole EV compartment we identified and excluded non-EV particles, debris and damaged EVs. We further isolated, using an anti-CD45 antibody, Leuko EVs (CD45+&#x2009;EVs), reaching a high level of purity (>&#x2009;90%). Purified Leuko EVs were characterized using atomic force microscopy, nanoparticle tracking, and shotgun proteomics analysis revealing a similar coded protein cargo in both biological fluids. Subsequently, the same workflow was applied to tears from Relapsing-Remitting Multiple Sclerosis (RRMS) patients, revealing a Leuko EVs protein cargo enrichment that reflects the neuroinflammatory condition characteristics of RRMS. This enrichment was evidenced by the activation of upstream regulators TGFB1 and NFE2L2, which are associated with inflammatory responses. Additionally, the analysis identified markers indicative of endothelial cell proliferation and the development of enhanced vascular networks, with AGNPT2 and VEGF emerging as activated upstream regulators. These findings indicate the complex interplay between inflammation and angiogenesis in RRMS. CONCLUSIONS: In conclusion, our combined FACS-Proteomics strategy offers a promising approach for biomarker discovery, analysing cell-specific EV phenotypes directly from untouched body fluids, advancing the clinical value of tears EVs and improving the understanding of EV-mediated processes in vivo. Data are available via ProteomeXchange with the identifier PXD049036 and in EV-TRACK knowledgebase with ID: EV240150.

Humans↗

Intraoperative Iso-C C-arm navigation in craniospinal surgery: the first 60 cases.

OBJECTIVE: The intraoperative Iso-C C-arm (Siremobil Iso-C 3D; Siemens Medical Solutions, Erlangen, Germany) provides a unique ability to acquire and view multiplanar three-dimensional images of intraoperative anatomy. Registration for intraoperative surgical navigation may be automated, thus simplifying the operative workflow. METHODS: Iso-C C-arm intraoperative fluoroscopy acquires 100 images, each of which must be 1.8 degrees in a circumferential fashion about an "isocentric" point in space. The system generates a high-resolution isotropic three-dimensional data set that is available immediately after the 90-second C-arm rotation. The data set is ported to the image-guided workstation, registration is immediate and automated, and the surgeon can navigate with millimetric accuracy. The authors prospectively examined data from the initial 60 patients examined with the Iso-C, among whom were cases of anterior and posterior spinal instrumentation from the occiput to the sacrum. Percutaneous and minimally invasive spinal and cranial procedures were also included. RESULTS: Automated registration for image-guided navigation was attainable for anterior and posterior cases from the cranial base and entire spine. In most cases, intraoperative postprocedural imaging with the Iso-C mitigated the need for postoperative imaging. CONCLUSION: Intraoperative Iso-C three-dimensional scanning allows real-time feedback during cranial base and spinal surgery and during procedures involving instrumentation. In most cases, it obviates the need for postoperative computed tomography. Its usefulness is in its simplicity, and it can be easily adapted to the operating room workflow. When coupled with intraoperative navigation, this new technology facilitates complex neurosurgical procedures by improving the accuracy, safety, and time of surgery.

Adolescent↗

Cassette based digital X-ray systems: evaluating the Konica Minolta Xpress CR.

Cassette-based digital x-ray systems--also called computed radiography (CR) systems--are flexible and affordable, qualities that have secured their continued use in clinical settings. In this follow-up to our August 2001 Evaluation of CR systems, we examine the Konica Minolta Xpress CR. Our testing examines the ability of the Xpress CR to provide at least the same amount of diagnostic information as screen-film systems, while significantly increasing the overall efficiency of a radiology department. This article also includes updated information on the new products now offered by the suppliers whose CR systems we examined in August 2001. In addition, it describes the general developments that have occurred in CR technology. These developments include the use of new phosphor types to increase image quality and the wider implementation of wall-mounted touchscreens to improve workflow.

Equipment Design↗

ActiveGuidelines: integrating Web-based guidelines with computer-based patient records.

Use of the World Wide Web provides an efficient means to disseminate guidelines, but integrating them into the workflow at the point of care remains elusive. We developed a method, ActiveGuidelines (AGL), of integrating web-based guidelines with computer-based patient record (CPR) systems. An ActiveGuideline is an HTML document containing special tags that are interpreted by a CPR as actions (e.g., medication order, test order, referral, patient instructions). In our usage scenario, the CPR automatically displays ActiveGuidelines relevant to the current patient context. After reviewing the guideline, the user selects recommended orders directly from the ActiveGuideline. The selected orders are automatically transmitted to the CPR and executed as regular orders. An ActiveGuideline editor facilitates easy conversion of existing HTML-formatted guidelines into ActiveGuidelines. We believe that integrating patient-specific ActiveGuidelines within a CPR system will improve utilization of clinical guidelines in routine patient care.

Computer Systems↗