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A case study: business process re-engineering (BPR) of the order-/delivery process at the pediatric clinic at the University Hospital of Lund.

The traditional order and delivery activities have been characterized by manual routines and a paper-based workflow management. Problems such as the time consuming processes in which a laboratory service order is created or that of getting the laboratory service report with results from the requested investigations from the laboratories and the entry of the same information by different persons at different points in the workflow with the possibilities of transfer errors are well known. The development of modern information technology, along with the developing of standards for communication protocols and the message structure for the electronic interchange of information (EDI) gives us the tools to change the way we work and manage workflow. An important input to the business process reengineering process is a thorough knowledge of the context within which the order-/delivery activities exist. One has to take into account that the activities are: 1) heavily integrated in the whole treatment and care process, 2) together with routines and the taking of samples and related requests many times are a part of the daily work of a ward, and 3) many decisions about the treatment of a patient are based on the results in the laboratory service report from the laboratories.

Hospital Information Systems↗

Functional screening of ZIP8 naturally occurring variants identifies pathogenic mutations and trafficking defects.

The rapid expansion of human genomic data has revealed a large number of naturally occurring variants, creating a major challenge for functional annotation. The human metal transporter SLC39A8 (ZIP8) is a clinically important divalent metal transporter, yet most of its documented variants remain uncharacterized. Here, we developed a workflow to functionally evaluate ZIP8 variants by integrating laser ablation inductively coupled plasma time-of-flight mass spectrometry (LA-ICP-TOF-MS) with scaled-up cell-based transport assays. Using this method, we systematically analyzed 33 naturally occurring missense variants located in the extracellular domain (ECD) of ZIP8. The assay enables direct quantification of intracellular metal accumulation with substantially improved throughput (∼150 samples per hour). Functional screening identified 14 potential pathogenic variants with significantly reduced transport activity. Comparison with computational predictions revealed a moderate correlation between activity and AlphaMissense pathogenicity scores (R2 = 0.423), while an error rate of ∼20% for AlphaMissense underscores the need for experimental validation. Flow cytometry analysis showed that most loss-of-function variants exhibit impaired trafficking of the protein to the cell surface possibly due to mutation-caused protein misfolding or instability. Structural mapping of activity-compromised variants, together with functional assessment of the ZIP8-ECD, highlights the importance of this domain in ZIP8 expression and intracellular protein trafficking. Together, this work establishes a scalable approach for functional screening of metal transporter variants and provides new insights into the structure-function relationships of ZIP8.

Journal Article↗

Disseminating medical knowledge: the PROforma approach.

Medical knowledge is traditionally disseminated via the publication of documents and through participation in clinical practice. Information technology offers to extend both modes of dissemination, via electronic publishing and virtual reality training, for example. AI promises even more radical changes through the possibility of publishing clinical expertise in the form of expert systems, which assist patient care through active decision support and workflow management. PROforma is a knowledge representation language that is designed to support this new mode of dissemination. It is based on an intuitive model of the processes of care and well-understood logical semantics. This paper provides a description of the language and associated software tools, and discusses its potential roles in, and implications for, medical knowledge publishing.

Artificial Intelligence↗

Mass spectrometry-based ligand binding assays in biomedical research.

INTRODUCTION: Ligand binding assays combining immunoaffinity enrichment steps with mass spectrometry (MS) readout have gained attention as a highly specific and sensitive tool for protein quantification. These techniques typically combine enzymatic fragmentation of the sample or enriched protein with capture on the protein or peptide-level for quantification. Antibodies ensure specific target recognition, while MS offers quantitative accuracy with isotopically labeled internal standards. This dual approach supports a broad dynamic range, enabling protein measurements from picomolar to nanomolar levels. These methods have diverse applications, from quantifying signaling proteins in basic research to biomarker monitoring in clinical trials and analyzing the pharmacokinetics of therapeutic proteins. AREAS COVERED: This review delves into the diverse workflows of immunoaffinity-MS, shedding light on the innovative strategies employed, their practical applications, efficacy, and inherent limitations in the realm of protein quantification. EXPERT OPINION: Immunoaffinity-MS has transformed protein analysis, but widespread adoption is hindered by complex workflows, high instrument costs, and limited capture molecule availability. Efforts to enhance automation, standardize workflows, and advance technological innovation aim to overcome these barriers. Improvements in mass spectrometer sensitivity, advances in recombinant capture technologies, and support from public initiatives are poised to further improve the reliability and accessibility of this method.

Mass Spectrometry↗

Anticoagulation management: a new approach.

Anticoagulation therapy has been identified as an area in which new approaches to treatment and monitoring may allow for significant improvements in healthcare quality and costs. We evaluated the potential benefits of a new approach to anticoagulation therapy, utilizing decision support software, point-of-service testing, and workflow redesign. We performed an intervention study in the setting of a university-affiliated primary care clinic, involving 40 patients receiving chronic anticoagulation therapy. Study measurement included anticoagulation control, complications of therapy and related costs, as well as clinic revenue and overhead costs. After implementation of the new approach, the frequency of international normalized ratio (INR) results within therapeutic range increased from 34% to 67%. During a 1-year follow-up period, complications related to anticoagulation therapy were reduced by 91% (p < 0.01). Labor-related overhead costs decreased from approximately 12,600 to 3,100 US dollars. During the same period, the clinic generated approximately 35,000 US dollars in new revenue. For every dollar spent on clinic implementation and maintenance, over 25 US dollars was returned from cost containment and new revenue production. This approach allows a clinic to show improved anticoagulation control and complication rates while simultaneously improving financial performance.

Adult↗

Application of qualifying variants for genomic analysis.

MOTIVATION: Qualifying variants (QVs) are genomic alterations selected by defined criteria within analysis pipelines. Although crucial for both research and clinical diagnostics, QVs are often seen as simple filters rather than dynamic elements that influence the entire workflow. In practice these rules are embedded within pipelines, which hinders transparency, audit, and reuse across tools. A unified, portable specification for QV criteria is needed. RESULTS: Our aim is to embed the concept of a "QV" into the genomic analysis vernacular, moving beyond its treatment as a single filtering step. By decoupling QV criteria from pipeline variables and code, the framework enables clearer discussion, application, and reuse. It provides a flexible reference model for integrating QVs into analysis pipelines, improving reproducibility, interpretability, and interdisciplinary communication. Validation across diverse applications confirmed that QV based workflows match conventional methods while offering greater clarity and scalability. AVAILABILITY AND IMPLEMENTATION: The source code and data are accessible at the Zenodo repository https://doi.org/10.5281/zenodo.17414191. Manuscript files are available at https://github.com/DylanLawless/qvApp2025lawless. The QV framework is available under the MIT licence, and the dataset will be maintained for at least two years following publication.

Genomics↗

Prenatal diagnosis of recurrent Kagami-Ogata syndrome inherited from a mother affected by Temple syndrome: a case report and literature review.

BACKGROUND: Kagami-Ogata syndrome (KOS) and Temple syndrome (TS) are two imprinting disorders characterized by the absence or reduced expression of maternal or paternal genes in the chromosome 14q32 region, respectively. We present a rare prenatally diagnosed case of recurrent KOS inherited from a mother affected by TS. CASE PRESENTATION: The woman's two affected pregnancies exhibited recurrent manifestations of prenatal overgrowth, polyhydramnios, and omphalocele, as well as a small bell-shaped thorax with coat-hanger ribs postnatally. Prenatal genetic testing using a single-nucleotide polymorphism array detected a 268.2-kb deletion in the chromosome 14q32 imprinted region inherited from the mother, leading to the diagnosis of KOS. Additionally, the woman carried a de novo deletion in the paternal chromosome 14q32 imprinted region and presented with short stature and small hands and feet, indicating a diagnosis of TS. CONCLUSIONS: Given the rarity of KOS as an imprinting disorder, accurate prenatal diagnosis of this rare imprinting disorder depends on two factors: (1) increasing clinician recognition of the clinical phenotype and related genetic mechanism, and (2) emphasizing the importance of imprinted regions in the CMA workflow for laboratory analysis.

Humans↗

Improving override rates for computerized prescribing alerts in ambulatory care.

Computerized drug prescribing alerts can improve patient safety, but are often overridden because of poor specificity and alert overload. We developed a selective knowledge base of only clinically significant drug alerts and designated only critical-high severity alerts to be interruptive to clinician workflow (a tiered approach). Using this approach, we were able to achieve a 67% clinician accept rate for ambulatory computerized prescribing alerts.

Ambulatory Care Information Systems↗

Role of the director of pharmacy: the first six months.

PURPOSE: Interviewing for a director of pharmacy position is discussed, and recommended activities for a pharmacy director's first six months on the job are described. SUMMARY: A prospective pharmacy director should first target the specific positions available that best fit his or her skills. The individual should tour the hospital and the pharmacy for each position of interest. Interviews should include the pharmacy staff, the nursing staff, the direct-report manager, and the medical staff. The hospital's financial condition should be assessed and a postinterview analysis conducted. Once hired, the new director should devote the first three months to an assessment of pharmacy services, staff, and customers; a regulatory and accreditation review; and assessments of organizational leadership, information systems, and clinical services. In addition, key documents, such as hospital policies and procedures, should be reviewed. At the end of the first three months, two documents, a summary of the new director's initial assessments and a chart showing current workflow, should be completed. Tasks for the first six months on the job include devising a work plan to address issues, developing reporting systems and metrics, setting priorities, creating staffing and clinical plans, promoting staff development creating and revising procedures, and evaluating outsourcing needs. The director should take a moment from time to time to celebrate successes with the staff. CONCLUSION: The director of pharmacy has one of the most complex jobs in the hospital. Planning, communicating, networking, writing, listening, leading, and motivating are skills necessary for success.

Humans↗

Implementing patient safety practices in small ambulatory care settings.

BACKGROUND: Improving patient safety in the outpatient setting poses unique challenges for patient safety leaders in clinics and hospitals. Even though ambulatory care may be less technologically complex than inpatient care, it is often more complex logistically. METHODS AND MATERIALS: From October 2002 to May 2003, Gundersen Lutheran Medical Center developed a tool kit of best practices and conducted a collaborative to institute these best practices within a regional health care network. All clinics evaluated patient safety standards and enhanced medication-related practices. RESULTS: Improvements were demonstrated in medication list accuracy. A number of policies were instituted, and medical and nursing staffs were educated in patient safety issues. Improvements were sustained after one year. DISCUSSION: The collaborative model of improvement efforts was an effective model for improving patient safety in small group practices. Structural and process changes often do not require major changes in workflow or large technology installations. Many of the projects allowed for, or required, local assessment and management. However, within a large system of clinics, some of the improvements in this study--verbal order policy, methodology and/or technology for assessment of medication and allergy list accuracy, warfarin care--required systemwide efforts. The degree of difficulty of achieving improvements was surprisingly low and barriers were minimal.

Ambulatory Care Facilities↗

Weaving the Web into legacy information systems.

For many years, client-server systems were developed as the backbone of clinical computing in leading hospitals around the country. Beth Israel Deaconess Medical Center now faces the challenge of bridging the technology gap between such systems and the Internet. While developing Web interfaces to legacy clinical systems gives a taste of the future, it is clear that complete institutional migration to the Web is not imminent. Asking clinicians to utilize two different systems, Web-based and legacy, in the interim phase is just one of the difficulties in such transition. This paper describes "Mbridge", a solution that allows legacy system users to exploit the benefits of the Internet in a fashion that does not interfere with their workflow and is both simple and affordable to implement. The service allows clinicians to work on the legacy platform while context-sensitive clinical content is streamed to the browser without their intervention. Using the system, we can gradually expose clinicians to new Web-based applications and resources without forcing them to operate two computing environments simultaneously. The service achieves these goals by means of linkage and coordination rather than by code-translation, data exchange or replication.

Computer Systems↗

[Modern operating room management in the workflow of surgery. Spectrum of tasks and challenges of the future].

The operating unit is one of the cost-intensive facilities in a surgical clinic with a pacemaking function for most of the internal procedures. The power of performance of the operating unit is based on the cooperation of all disciplines and professions involved. The key to management of the operating unit is not only to coordinate the daily procedures, but also to interact with support personnel. To ensure successful OR management, the internal structure of the OR must fit the clinical tasks and the available quantity of personnel in each profession must be coordinated. Sufficient utilization of resources and equipment must be guaranteed without cost-intensive over-capacities and patient flow must be orientated to OR capacities. The development of such a business structure requires the management to clearly define the goal, to know the actual on-site data in detail with regard to the idiosyncratic workings of each specialty and to clearly assign the competence of each member of the team working in the OR. Coordination of the operating unit is the main task of OR management, which must ensure the following: transparent and coordinated schedule management in the various operative specialties, goal-directed changes of the schedule with incorporation of emergencies, as well as effective organization of staff. In order to realize these tasks, it is reasonable to implement interdisciplinary rules of procedures. In addition, the assignment of a neutral decision-making body within the OR and the creation of an information center for all OR personnel. The challenge of OR organization in the future is to implement more effective documentation systems and active controlling within the OR. One can ensure adequate utilization of resources in the OR with prospectively oriented planning. Better transparency of operations in the OR contributes to increased efficiency. Implementation of quality management is the foundation for a successfully operating surgical hospital. Not only the productivity of individual members of the staff, but also the precise documentation of the quality of results will become important parameters in a successful surgical hospital, whose nucleus is the OR.

Appointments and Schedules↗

RESCUE: An end-to-end multi-agent LLM system for proactive rare-disease patient screening in the EHR.

BACKGROUND: Rare diseases affect a significant portion of the global population, yet patients often endure a lengthy diagnostic odyssey, frequently missing the opportunity for timely diagnoses with exome or genome sequencing (ES/GS). Existing informatics tools often rely on pre-identified patients or rigid, institution-specific rule sets, failing to address the broader operational question of clinical utility and feasibility. METHODS: We introduce RESCUE (Rare Disease Detection and Escalation Support via a Learning Health System), an end-to-end, multi-agent LLM-powered workflow designed for proactive rare-disease diagnosis across the entire electronic health record (EHR). RESCUE utilizes a team of specialized agents including Ontology, Modeling, Screening, and Review, to automate the screening process to identify candidates for diagnostic testing based on their clinical features. The Ontology Agent classifies clinical data into a four-tier genetic-evidence taxonomy; the Modeling Agent builds a positive-unlabeled (PU) XGBoost classifier to identify potential cases; the Screening Agent applies these models across the EHR population; and the Review Agent evaluates candidates by sampling clinical notes to ensure medical necessity and operational feasibility for genomic testing. RESULTS: Using electronic medical record data from a pediatric hospital, our retrospective evaluation on a holdout set (n=12,591) demonstrates strong discrimination between patients who received diagnostic genomic testing and those who did not (AUC 0.808). Of nearly 500,000 patients in the institutional base, 175,842 met inclusion criteria for screening; among these, RESCUE-flagged candidates were 7.4-fold more likely to receive subsequent genomic assessments compared to controls. Blinded manual chart reviews confirmed that RESCUE identifies previously missed, medically appropriate patients for ES/GS with 80% precision, while simultaneously accounting for prior testing history. CONCLUSIONS: By decoupling expert roles into modular agents, RESCUE offers a flexible, scalable, and adaptable framework for screening patients for rare-disease diagnostic genomic testing. This approach overcomes the limitations of traditional rule-based methods and provides a reproducible, agentic pathway to reduce diagnostic delays and improve patient care at an institutional scale.

Journal Article↗

[Implementation of modern operating room management -- experiences made at an university hospital].

Caused by structural changes in health care the general need for cost control is evident for all hospitals. As operating room is one of the most cost-intensive sectors in a hospital, optimisation of workflow processes in this area is of particular interest for health care providers. While modern operating room management is established in several clinics yet, others are less prepared for economic challenges. Therefore, the operating room statute of the Charité university hospital useful for other hospitals to develop an own concept is presented. In addition, experiences made with implementation of new management structures are described and results obtained over the last 5 years are reported. Whereas the total number of operation procedures increased by 15 %, the operating room utilization increased more markedly in terms of time and cases. Summarizing the results, central operating room management has been proved to be an effective tool to increase the efficiency of workflow processes in the operating room.

Cost Control↗

Implementing evidence-based psychosocial practices: lessons learned from statewide implementation of two practices.

OBJECTIVE: As part of this national project, we examined barriers and strategies to implementation of two evidence-based practices (EBPs) in Indiana. BACKGROUND: Despite many advances in the knowledge base regarding mental health treatment, the implementation of EBPs in real-world setting remains poorly understood. The National EBP Project is a multi-state study of factors influencing implementation of EBPs. METHODS: Over a 15-month period we observed eight assertive community treatment (ACT) programs and six integrated dual disorders treatment (IDDT) programs and noted pertinent actions taken by the state mental health agency influencing implementation. We created a database containing summaries of monthly visits to each program and interviews with key leaders. Using this database and clinical impressions, we rated barriers and strategies at each site on seven factors: Attitudes, Mastery, Leadership, Staffing, Policies, Workflow, and Program Monitoring. RESULTS: At the site level, the most frequently observed barriers were in the areas of leadership, staffing and policies for ACT, and mastery and leadership for IDDT. Overall, barriers were more evident for IDDT than for ACT. Strategies were less frequently noted but generally paralleled the areas noted for barriers. However, our central finding was that ACT was generally more successfully implemented than IDDT throughout the state, and that this difference could be traced in large part to state-level factors relating to historical preparation for the practice, establishment of standards, formation of a technical assistance center, and funding. CONCLUSION: In this case study, both state-level and site-specific factors influenced success of implementation of EBPs. To address these factors, the field needs systematic strategies to anticipate and overcome these barriers if full implementation is to be realized.

Community Mental Health Services↗

Computer decision support systems.

Computer decision support systems are computer applications designed to aid clinicians in making diagnostic and therapeutic decisions in patient care. They can simplify access to data needed to make decisions, provide reminders and prompts at the time of a patient encounter, assist in establishing a diagnosis and in entering appropriate orders, and alert clinicians when new patterns in patient data are recognized. Decision support systems that present patient-specific recommendations in a form that can save clinicians time have been shown to be highly effective, sustainable tools for changing clinician behavior. Designing and implementing such systems is challenging because of the computing infrastructure required, the need for patient data in a machine-processible form, and the changes to existing workflow that may result. Despite these difficulties, there is substantial evidence from trials in a wide range of clinical settings that computer decision support systems help clinicians do a better job caring for patients. As computer-based records and order-entry systems become more common, automated decision support systems will be used more broadly.

Computer Systems↗

Functional screening of ZIP8 naturally occurring variants identifies pathogenic mutations and trafficking defects.

The rapid expansion of human genomic data has revealed a large number of naturally occurring variants, creating a major challenge for functional annotation. The human metal transporter SLC39A8 (ZIP8) is a clinically important, promiscuous divalent metal transporter, yet most of its documented variants remain uncharacterized. Here, we developed a workflow to functionally evaluate ZIP8 variants by integrating laser ablation inductively coupled plasma time-of-flight mass spectrometry (LA-ICP-TOF-MS) with scaled-up cell-based transport assays. Using this method, we systematically analyzed 33 naturally occurring missense variants located in the extracellular domain (ECD) of ZIP8. The assay enables direct quantification of intracellular metal accumulation with substantially improved throughput (~150 samples per hour). Functional screening identified 14 potential pathogenic variants with significantly reduced transport activity. Comparison with computational predictions revealed a moderate correlation between activity and AlphaMissense pathogenicity scores (R2 = 0.423), while an error rate of ~20% underscores the need for experimental validation. Flow cytometry analysis showed that most loss-of-function variants exhibit impaired trafficking of the protein to the cell surface possibly due to mutation-caused protein misfolding or instability. Structural mapping of activity-compromised variants, together with functional assessment of the ZIP8-ECD, highlights the importance of this domain in ZIP8 expression and intracellular trafficking. Together, this work establishes a scalable approach for functional screening of metal transporter variants and provides new insights into the structure-function relationships of ZIP8.

Journal Article↗

Body area network--a key infrastructure element for patient-centered telemedicine.

The Body Area Network (BAN) extends the range of existing wireless network technologies by an ultra-low range, ultra-low power network solution optimised for long-term or continuous healthcare applications. It enables wireless radio communication between several miniaturised, intelligent Body Sensor (or actor) Units (BSU) and a single Body Central Unit (BCU) worn at the human body. A separate wireless transmission link from the BCU to a network access point--using different technology--provides for online access to BAN components via usual network infrastructure. The BAN network protocol maintains dynamic ad-hoc network configuration scenarios and co-existence of multiple networks.BAN is expected to become a basic infrastructure element for electronic health services: By integrating patient-attached sensors and mobile actor units, distributed information and data processing systems, the range of medical workflow can be extended to include applications like wireless multi-parameter patient monitoring and therapy support. Beyond clinical use and professional disease management environments, private personal health assistance scenarios (without financial reimbursement by health agencies / insurance companies) enable a wide range of applications and services in future pervasive computing and networking environments.

Artificial Intelligence↗