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Computational prediction of proteotypic peptides for quantitative proteomics.

Mass spectrometry-based quantitative proteomics has become an important component of biological and clinical research. Although such analyses typically assume that a protein's peptide fragments are observed with equal likelihood, only a few so-called 'proteotypic' peptides are repeatedly and consistently identified for any given protein present in a mixture. Using >600,000 peptide identifications generated by four proteomic platforms, we empirically identified >16,000 proteotypic peptides for 4,030 distinct yeast proteins. Characteristic physicochemical properties of these peptides were used to develop a computational tool that can predict proteotypic peptides for any protein from any organism, for a given platform, with >85% cumulative accuracy. Possible applications of proteotypic peptides include validation of protein identifications, absolute quantification of proteins, annotation of coding sequences in genomes, and characterization of the physical principles governing key elements of mass spectrometric workflows (e.g., digestion, chromatography, ionization and fragmentation).

Algorithms↗

Sharable EHR systems in Finland.

In Finland, the shared record is a virtual electronic health record (EHR). It consists of health data generated, maintained and preserved by different health care service providers. Two different kinds of technologies for integrating regional EHR-systems are applied, but mainly by using a common middleware. Services provided by this middleware are EHR location services using a link repository and combining EHR-viewing services with security management services including consent management and identification services for health professionals. The Regional Health Information Organization (UUMA) approach is based on a stepwise implementation of integrated regional healthcare services to create a virtually borderless healthcare organization--a patient centered virtual workspace. In the virtual workspace multi-professional teams and patients collaborate and share information regardless of time and place. Presently the regional health information network (RHIN) is comprised of three integrated services between primary, secondary and tertiary care within the county of Uusimaa. The regional healthcare modules consist of an (1) eReferral network, (2) integrated EHR service between health care professionals and (3) PACS system. The eReferral between primary and secondary care not only speeds up the transfer, but also offers an option for communication in the form of eConsultation between general practitioners and hospital specialists. By sharing information and knowledge remote eConsultations create a new working environment for integrated delivery of eServices between the health care providers. Over 100,000 eReferral messages (40 %) were transferred between health care providers. Interactive eConsultations enable supervised care leading to the reduction of outpatient visits and more timely appointments. One third (10/31) of the municipal health centers are connected to the clinics in the Helsinki University Central Hospital by the eReferral system. The link directory service extends the dimensions of networking between organizations by combining legacy systems within regional primary and secondary care. The link directory is an interface to diverse patient information systems, like HUSpacs, containing links pointing to the actual patient data located in remote information systems. The original data including images can be viewed with a web browser, but data can be accessed only with the patient's informed consent. Currently the reference data base includes 9.5 million links from 1.4 million patients with over 2.000 daily users. We aim to create a new working environment for professionals by incorporation of innovative information and communication technology, new organization of work and re-engineering of workflows. In the near-future, the citizen will have an active role participating in decisions on his care, carrying out guided self-care and taking steps of pro-active prevention.

Computer Communication Networks↗

Enterprise-wide worklist management.

Radiologists in multi-facility health care delivery networks must serve not only their own departments but also departments of associated clinical facilities. We describe our experience with a picture archiving and communication system (PACS) implementation that provides a dynamic view of relevant radiological workload across multiple facilities. We implemented a distributed query system that permits management of enterprise worklists based on modality, body part, exam status, and other criteria that span multiple compatible PACSs. Dynamic worklists, with lesser flexibility, can be constructed if the incompatible PACSs support specific DICOM functionality. Enterprise-wide worklists were implemented across Generations Plus/Northern Manhattan Health Network, linking radiology departments of three hospitals (Harlem, Lincoln, and Metropolitan) with 1465 beds and 4260 ambulatory patients per day. Enterprise-wide, dynamic worklist management improves utilization of radiologists and enhances the quality of care across large multi-facility health care delivery organizations. Integration of other workflow-related components remain a significant challenge.

Community Networks↗

A Rapid Poly(ethylene glycol)-Assisted Magnetic Isolation Approach for High-Throughput Extracellular Vesicle Isolation and Subsequent Biomarker Analysis.

Extracellular vesicles (EVs) are crucial mediators of intercellular communication and have the potential to serve as biomarkers for disease diagnosis and therapeutic monitoring. However, most EV isolation methods often require large sample volumes and specialized instruments or involve trade-offs between purity, yield, cost, and scalability. We developed MagPEG, a workflow that combines poly(ethylene glycol) (PEG)-mediated EV aggregation with magnetic beads to provide a simple, reproducible alternative to ultracentrifugation, size-exclusion chromatography, and commercial precipitation kits. Our optimization experiments clarified the PEG concentration, ionic strength, and bead surface chemistry that collectively influence EV aggregation, capture efficiency, and contaminant coprecipitation, allowing us to define conditions that improve purity while maintaining high recovery. Compared with commonly used methods, MagPEG produced EVs with comparable size distribution, EV markers, and proteomic profiles while relying only on standard laboratory supplies. A key feature of the platform is that EVs and EV-associated DNA, RNA, and proteins can be sequentially extracted from the same bead-bound material, reducing sample loss and hands-on time and enabling multiomic analysis for limited clinical or small animal samples. MagPEG is compatible with downstream applications including proteomics, bead-based assays, and miRNA quantification. When applied to human serum, the method supported high-throughput EV proteomic profiling and enabled the identification of Alzheimer's disease-associated protein signatures, illustrating its utility for biomarker discovery. Overall, our results establish MagPEG as a powerful, rapid, scalable, and high-throughput solution for translational applications in biomarker discovery.

Polyethylene Glycols↗

Application of PathoChip to urine-derived nucleic acids for broad microbial profiling in men with suspected prostate cancer: setup of a methodological workflow and pilot feasibility study.

BACKGROUND: Urine-based liquid biopsy is an attractive non-invasive source of prostate cancer (PCa) biomarkers, but urinary microbiome studies have mainly relied on 16S rRNA sequencing or shotgun metagenomics. This pilot study optimized and evaluated a practical workflow using PathoChip - a broad-spectrum microarray designed to detect bacterial, viral, fungal, and parasitic signatures - for microbial profiling of urine sediments from men with suspected PCa, an application not previously established. METHODS: First-morning urine was collected without prostatic massage from 35 men scheduled for biopsy; 19 were diagnosed with PCa and 16 were biopsy-negative. Different urine volumes and extraction strategies were evaluated to optimize DNA/RNA recovery. A setup phase compared 25 ng versus 50 ng of urine DNA and RNA input. DNA/RNA isolated from human B cells was used as reference control. An analysis pipeline was developed to detect outlier probes and create a presence/absence matrix. Reproducibility was assessed via library yield, Pearson correlation, blank-control subtraction, outlier probe detection. Prevalence comparisons were performed between clinical groups. RESULTS: An 8 mL starting volume was chosen as consistently available from self-collected urine. Sequential DNA/RNA extraction using the AllPrep DNA/RNA Micro Kit from sediment provided the best balance between nucleic-acid recovery, purity, and clinical compatibility. Reducing the input from 50 ng to 25 ng preserved highly concordant hybridization profiles, with matched samples clustering together with strong correlations. Exploratory analysis revealed PCa- and grade-associated patterns involving Actinomycetaceae, Aerococcaceae, and Streptococcaceae, with Streptococcaceae enriched in PCa of higher grades (ISUP GG ≥ 2). Other signatures, including Mobiluncus, Prevotella, Rhodotorula, Hymenolepis, and JC polyomavirus, were broadly detected but not PCa-discriminating. CONCLUSIONS: PathoChip can be adapted to urine sediments, generating reproducible microbial profiles from limited DNA/RNA input without prostatic massage. This platform provides a quick and accessible approach to broad screening, extending beyond 16S rRNA sequencing by enabling simultaneous multi-kingdom detection. The observed PCa- and grade-associated patterns are hypothesis-generating and require validation in larger independent cohorts.

Pathochip↗

Clinical and Genetic Spectrum of Large AIP Deletions.

Familial isolated pituitary adenoma (FIPA) accounts for approximately 2%-5% of all pituitary adenomas, with inactivating variants of the aryl hydrocarbon receptor-interacting protein (AIP) gene representing the most frequent known genetic cause. Clinically, patients with AIP variants often have young-onset macroadenomas with growth hormone hypersecretion, although disease severity and penetrance are variable. Most reported AIP variants are point mutations, whereas large deletions are rare and potentially underdiagnosed. Accurate detection of AIP copy-number variants requires methods such as multiplex ligation-dependent probe amplification or validated copy-number analysis of next-generation sequencing data, as Sanger sequencing alone may fail to identify these alterations. Due to the rarity of the disease, it is unknown whether large deletions in the ubiquitously expressed AIP gene are associated with potentially more severe phenotype. Available data suggest that large deletions may occur in 8%-10% of AIP mutation-positive pedigrees, highlighting the importance of incorporating copy-number variant detection into AIP testing workflows. We analysed data from all published patients with large AIP deletions (n = 25) and report here two novel large AIP deletions (Exons 3-4 and Exons 2-6 deletions) and three additional three families, including an Albanian kindred associated with metastatic Hürthle cell thyroid carcinoma. No major differences compared with other AIP variants were found in age at diagnosis, tumour size, hormonal profile, sex distribution or presence of other tumours. A role for AIP variants in thyroid carcinogenesis is unlikely.

Humans↗

Current challenges in adherence to clinical guidelines for antibiotic prophylaxis in surgery.

UNLABELLED: To study the impact of guidelines on surgical antibiotic prophylaxis in clinical practice, barriers involved in adherence to guidelines and how to overcome the same. METHODS: Literature pertaining to prophylactic antibiotic usage was searched. Medscape, Medline, Cochrane, Surgical Infection Prevention (SIP) project databases were reviewed. Recent articles from relevant journals, texts, and standard guidelines were also studied. RESULTS: Local guidelines seem more likely to be accepted and followed than those developed nationally. Major barriers involved in adherence to guidelines include lack of awareness about the guidelines, general perception of guideline as a bureaucratic rather than educational tool. Some practitioners perceive guidelines as "cookbook medicine" that does not permit them to make their own medical decisions. Other barriers are complex, multi-step systems that create confusion, decrease accountability. Methods for guideline adherence include surveillance and data analysis, new systems to facilitate documentation and improving workflow, education regarding current evidence-based guidelines and promoting the development of local guidelines or protocol, development and implementation of reminders to facilitate adherence to the local guidelines. CONCLUSION: A multidisciplinary steering team of surgeons, infectious disease specialists, pharmacists, anesthesiologists, microbiologists and nurses should develop local guidelines suitable to their institution and methods for adherence to prevent the surgical site infections. The gap between evidence-based guidelines and practice must be addressed in order to achieve optimal practice in this domain.

Antibiotic Prophylaxis↗

The electronic patient record in community health services--paradoxes and adjustments in clinical work.

This case study explores the consequences of the introduction of an electronic patient record (EPR) system to support community health services in a Norwegian municipality. The EPR was envisaged as a key tool for developing integration between a nursing home and a home care organization to meet quality care goals and to increase the time available for patient care. This investigation takes a socio-technical approach, particularly drawing on "actor-network" theory and insights from "articulation work". The empirical data comes from structured interviews, participant observation and document review. The findings of the case study indicated reluctance by staff to use the EPR system. The management had eliminated traditional information and communication routines, such as oral handover and informal nursing notes, in a reorganization of duties associated with the EPR implementation. To prevent fragmentation of nursing work, and to maintain continuity of care, the nurses reintroduced these routines spontaneously and ad hoc. The reluctance to use the system and the reintroduction of abandoned routines can be understood by exploring the interaction between the EPR system's user interface, its ability to support nursing work, and the workflow in the new merged health service. So far, the introduction of the EPR has not led to the benefits expected from it.

Community Health Services↗

A Web-based telemedicine system for diabetic retinopathy screening using digital fundus photography.

The purpose was to design and implement a Web-based telemedicine system for diabetic retinopathy screening using digital fundus cameras and to make the software publicly available through Open Source release. The process of retinal imaging and case reviewing was modeled to optimize workflow and implement use of computer system. The Web-based system was built on Java Servlet and Java Server Pages (JSP) technologies. Apache Tomcat was chosen as the JSP engine, while MySQL was used as the main database and Laboratory of Neuro Imaging (LONI) Image Storage Architecture, from the LONI-UCLA, as the platform for image storage. For security, all data transmissions were carried over encrypted Internet connections such as Secure Socket Layer (SSL) and HyperText Transfer Protocol over SSL (HTTPS). User logins were required and access to patient data was logged for auditing. The system was deployed at Hubert H. Humphrey Comprehensive Health Center and Martin Luther King/Drew Medical Center of Los Angeles County Department of Health Services. Within 4 months, 1500 images of more than 650 patients were taken at Humphrey's Eye Clinic and successfully transferred to King/Drew's Department of Ophthalmology. This study demonstrates an effective architecture for remote diabetic retinopathy screening.

Diabetic Retinopathy↗

Integrating anatomical pathology to the healthcare enterprise.

For medical decisions, healthcare professionals need that all required information is both correct and easily available. We address the issue of integrating anatomical pathology department to the healthcare enterprise. The pathology workflow from order to report, including specimen process and image acquisition was modeled. Corresponding integration profiles were addressed by expansion of the IHE (Integrating the Healthcare Enterprise) initiative. Implementation using respectively DICOM Structured Report (SR) and DICOM Slide-Coordinate Microscopy (SM) was tested. The two main integration profiles--pathology general workflow and pathology image workflow--rely on 13 transactions based on HL7 or DICOM standard. We propose a model of the case in anatomical pathology and of other information entities (orders, image folders and reports) and real-world objects (specimen, tissue samples, slides, etc). Cases representation in XML schemas, based on DICOM specification, allows producing DICOM image files and reports to be stored into a PACS (Picture Archiving and Communication System.

Diagnostic Imaging↗

The role of primary care non-physician clinic staff in e-mail communication with patients.

BACKGROUND: Few studies have explicitly addressed how e-mail technology may affect non-physician clinic staff, even though these staff typically manage tasks well suited to e-mail communication such as requests for prescription renewals, laboratory and test results, and referral authorizations. GOAL: We conducted a survey of staff members at 10 primary care clinics in Boston to further evaluate non-physician staff attitudes towards e-mail use with patients. We subsequently re-surveyed staff at three of these clinics after the implementation of Patient Gateway, an application designed to facilitate secure electronic communication between patients and the clinics. RESULTS: Before Patient Gateway implementation, 88% of surveyed staff were already using e-mail at least once a day for work-related communication. Many of these staff members (24%) were already using e-mail with patients. Forty-eight percent of staff members thought that increasing e-mail use with patients could improve the quality of care their practices delivered. However, staff reported having some hesitations about increasing e-mail use with patients, mostly relating to security, confidentiality, and workload. After Patient Gateway implementation, users reported high satisfaction with the application and staff in general (users and non-users of Patient Gateway) felt more enthusiastic about increasing e-mail use with patients. CONCLUSIONS: In order to maximize the potential of staff-patient e-mail, it is important that concerns relating to security, confidentiality, and workflow are addressed, and patients must be given guidelines for the appropriate use of e-mail. Secure applications designed with these issues in mind are likely to be well received by staff members, and in turn physicians.

Adolescent↗

The public health dashboard: a surveillance model for bioterrorism preparedness.

The City of Milwaukee Health Department piloted a short-term, near real-time syndromic surveillance and communication tool by using an existing secure regional Internet infrastructure. Voluntary, active syndromic case reporting by hospital Emergency Departments was combined with other data streams, including clinical laboratory reports of communicable disease, hospital emergency room diversions, ambulance runs, medical examiner reports of unusual or suspicious deaths, poison control and nursing hotline call volumes, and pharmacy over-the-counter sales. These data were aggregated into a "Surveillance Dashboard" format that was used to communicate community syndromic health trends to hospitals, Emergency Departments, and other providers using a secure Internet technology. Emergency Departments at 8 area hospitals reported a total of 314 cases meeting syndromic criteria from 26,888 patient encounters. Participants were satisfied with data entry and communications. All participating Emergency Departments received e-mail and text pager alerts sent by the Milwaukee Health Department. No unexplained findings or suggestions of an early outbreak were reported through syndrome surveillance for the 4-week duration of the project. Similar surveillance and communications systems could provide multiple benefits to Emergency Department workflow and management, as well as to public health and emergency response.

Bioterrorism↗

Online guideline assist in intensive care medicine--is the login-authentication a sufficient trigger for reminders?

INTRODUCTION: Rising cost pressure due to the implementation of the DRG-System and quality assurance lead to an increased use of therapy standards and standard operating procedures (SOPs) in intensive care medicine. The intention of the German Scientific Society supported project "OLGA" (Online Guideline Assist) is to develop a prototype of a knowledge based system supporting physicians of an intensive care unit in recognizing the indication for and selecting a specific guideline or SOP. While the response of the prototype on user entries can be displayed as a signal on the used workstation itself, the location and time for a reminder of scheduled or missed procedures or reactions to imported information is a difficult issue. One possible approach to this task is the display of non acknowledged reminders or recommendations while logging on to a system. The objective of this study is to analyse user behaviour of the physicians working on the surgical intensive care unit to decide whether the login authentication is a sufficient trigger for clinical reminding. METHODS: The surgical intensive care unit examined in this study comprises 14 beds. Medical care is provided by physicians working in shifts 24 hours a day, 7 days a week, with two anaesthetists at a time and an additional senior consultant during daytime. The entire documentation (examinations, medication, orders, care) is performed using the patient data management system ICUData. The authentication process of the physicians was logged and analysed. RESULTS: Throughout the observation period from December 13th 2005 to January 11th 2006 3563 physician logins were counted in total. The mean span between logins was in 11.3 minutes (SD 14.4), the median 7 minutes. The 75% centile was 14 minutes, the 95% centile 38 min. Intervals greater than 60 minutes occurred in 75%, and greater than 90 minutes in 25% of the days. DISCUSSION: It seems reasonable that reminders sent during authentication are able to enforce workflow compliance. It is possible to send notifications caused by external events to the physician depending on the importance of the event. Serious events with high urgency should be reliably passed using wireless pager or handheld technology. It seems that after the implementation of the prototype guideline assist further investigation is needed to monitor changes in authentication behaviour and reactions to the guideline advisory. This is also required to investigate the influence of unit's size, medical specialty and actual ward workload.

Critical Care↗

[The use of flat-panel detectors for CT imaging].

Clinical CT has reached a very high performance level by now. The introduction of spiral scanning and of multirow detectors have allowed to image even large body sections in very short time and with isotropic, high spatial resolution of better than 1 mm. For further improvements with respect to detector technology the use of flat-panel detectors (FPD), which have been developed for radiographic applications, is currently under investigation. In this article we discuss the general demands on CT detectors and specifically the suitability of FPDs with respect to CT imaging. FPDs offer excellent performance for the imaging of high-contrast structures with high spatial resolution.Low-contrast resolution and dose efficiency, however, do not yet reach the level of performance of dedicated CT detectors; temporal resolution is also limited. FPDs appear primarily suited for special applications in CT as for example 3D angiography or intraoperative imaging which also allows for improvements in workflow. For standard diagnostic CT they are not to be recommended at present, last but not least for dose reasons. The respective technical developments will have to be reassessed constantly in the future. The development of detector systems which are equally suited for radiography and CT constitutes an attractive goal.

Angiography↗

Quasi-automatic 3D finite element model generation for individual single-rooted teeth and periodontal ligament.

The paper demonstrates how to generate an individual 3D volume model of a human single-rooted tooth using an automatic workflow. It can be implemented into finite element simulation. In several computational steps, computed tomography data of patients are used to obtain the global coordinates of the tooth's surface. First, the large number of geometric data is processed with several self-developed algorithms for a significant reduction. The most important task is to keep geometrical information of the real tooth. The second main part includes the creation of the volume model for tooth and periodontal ligament (PDL). This is realized with a continuous free form surface of the tooth based on the remaining points. Generating such irregular objects for numerical use in biomechanical research normally requires enormous manual effort and time. The finite element mesh of the tooth, consisting of hexahedral elements, is composed of different materials: dentin, PDL and surrounding alveolar bone. It is capable of simulating tooth movement in a finite element analysis and may give valuable information for a clinical approach without the restrictions of tetrahedral elements. The mesh generator of FE software ANSYS executed the mesh process for hexahedral elements successfully.

Algorithms↗

The role of perceptions of clinicians in their adoption of a web-based antibiotic approval system: do perceptions translate into actions?

PURPOSE: Computerized Decision Support Systems have been shown to improve clinicians' performance. Clinicians' adoption of these systems is crucial for their success. Studying clinicians' perceptions can provide an insight into the determinants of clinicians' adoption of such systems. The aim of this study was to measure clinicians' perceptions of ease of use and usefulness of a web-based antibiotic approval system, and to investigate the relationship between the reported perceptions and use of the system. METHODS: Potentially identifiable coded surveys were sent to a total of 70 senior and 150 junior medical staff, and 30 pharmacists all working at a tertiary care referral teaching hospital of Melbourne, Australia. Clinicians' perceptions of ease of use and usefulness of the antibiotic approval system; clinicians' general computer use; and clinicians' usage of the antibiotic approval system were measured. RESULTS: The overall response rate from the clinicians was 53.4%. The majority of the participants (70% and above) found it easy to obtain antibiotic approval using the system. More than 80% of the participants believed that the system will decrease the inappropriate use of antibiotics at the hospital. Clinicians who were more likely to use the system also found it easy to learn (Rho=0.392, p=0.001), easy to show others how to use the system (Rho=0.298, p=0.014), easy to find additional information (Rho=0.317, p=0.009), and easy to use it within their daily workflow (Rho=0.268, p=0.028). In addition, the clinicians were also more likely to use the system if they believed that it will improve their adherence to evidence-based practice (Rho=0.352, p=0.003). CONCLUSION: The majority of clinicians in an independent investigation of the antibiotic approval system found the system easy to use and useful to them. A number of clinicians' perceptions about the system were found to be correlated with the actual usage of the system by the clinicians.

Adult↗

[Identification of quality problems in the clinical information to hospital emergency department patients].

OBJECTIVES: To evaluate the comprehension level of the information provided to patients and relatives attending an emergency department and to know their satisfaction degree. METHODS: A cross-sectional descriptive study was designed. The selection of study patients was made by means of a simple randomized sampling and the total of patients was 213. At discharge, these patients and their relatives answered a written, anonymous questionnaire. To evaluate the comprehension of the information provided, the questionnaire responses were checked against the clinical records. RESULTS: The self-identification of the health care providers, information on the estimated length of stay at the ED, the explanation of complementary tests and their results significantly determined the satisfaction score on the provided information, which for the patients was 6.3 on a 10-point scale. The percentages of patients who were knowledgeable of the performed tests, diagnosis, and administered treatment were 61.5%, 50.7%, and 35.2%, respectively. Understanding the diagnosis and the administered treatment differed according to age (p < 0.001) and the assimilation of the information on recommendations at patients's discharge differed according to the education level (p < 0.05). CONCLUSIONS: The self-identification of health care personnel would allow for a better bi-directional information flow. Given the socio-cultural characteristics of our population, the information provided should be clear and concise. The transmission of information to most emergency department users would be best achieved with previous information of the workflow at the emergency department in the form of booklets at the entrance, and also establishing protocols for the informed consent on different diagnostic and treatment techniques inherent to emergency care.

Adolescent↗

Workflow management systems for guideline implementation.

The activities of care providers need to be coordinated within a process properly designed on the basis of available best practice medical knowledge. It requires a rethinking of the management of care processes within health-care organisations. The current workflow technology seems to offer the most convenient solution to build such cooperative systems. However, some of its present weaknesses still require an intense research effort to find solutions allowing its exploitation in real medical practice. This paper presents an approach to design and build evidence-based workflow management systems (WfMS). They can be viewed as components of a knowledge management infrastructure each health care organisation should be provided with, to increase its performance in delivering high-quality care, by efficiently exploiting the available knowledge resources. On the basis of a general methodology, we describe a WfMS implementation in the area of Stroke management; such a system, after intensive testing in our research laboratory, is now in the process of being transferred in a real working setting (a stroke unit) and integrated with an existing electronic patient record.

Database Management Systems↗