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The increasing use of patient-reported outcome (PRO) measures is forcing clinicians and health care systems to decide which to select and how to incorporate them into their records and clinical workflows. This overview addresses 3 topics related to these concerns. First, a literature review summarizes key psychometric and practical factors (such as reliability, responsiveness, computer adaptive testing, and interpretability) in choosing PROs for clinical practice. Second, 3 clinical decision support issues are highlighted: gathering PROs, electronic health record effect on providers, and incorporating PROs into clinical decision support design and implementation. Lastly, the salience of crosscutting domains as well as 9 key pragmatic decisions are reviewed. Crosscutting domains are those that are relevant across most medical and mental health conditions, such as the SPADE symptom pentad (sleep problems, pain, anxiety, depression, low energy/fatigue) and physical functioning. The 9 pragmatic decisions include (1) generic vs disease-specific scales; (2) single- vs multidomain scales; (3) universal scales vs user-choice selection; (4) number of domains to measure; (5) prioritization of domains when multiple domains are assessed; (6) action thresholds; (7) clinical purpose (screening vs monitoring); as well as the (8) frequency and (9) logistical aspects of PRO administration.

Objective To identify the appropriate treatment in the tonsillar region's infections, a distinction between tonsillitis with or without abscess formation is essential. Ultrasound proved to be a valuable method in identifying abscess formation in the head and neck region. However, no report described the assessment of the tonsil region. This study aims to determine the feasibility of transcervical ultrasound for abscess visualization in the palatal tonsillar region. Methods Retrospective analysis of 354 patients presenting with clinical suspicion of tonsillar abscess to a tertiary referral center and university hospital. All patients received a transcervical ultrasound to establish a primary diagnosis. The existence of an abscess was confirmed by puncture and incision, or final tonsillectomy. If no abscess could be delineated, non-abscessing tonsillitis was supposed, and conservative primary therapy and closed follow-up examinations were performed. Results After the first diagnostic ultrasound examination, in 257 cases (72.59%), the diagnosis of an abscess could be established, but in 97 cases (27.40%), due to missing abscess formation criteria, non-abscessing tonsillitis was documented. Overall, ultrasonography demonstrated an overall accuracy of 78.8% in this selected cohort. The sensitivity, specificity, PPV, and NPV after the first ultrasound examination were calculated with 75.1%, 88.6%, 94.6%, and 57.3%, respectively. Conclusion The presented data confirm that an abscess formation due to tonsillitis can be detected by transcervical ultrasound, enabling prompt, adequate management. As transcervical ultrasound can be conducted fast and is not associated with radiation, it can be regarded as a first-line diagnostic tool in this condition.

Background For Hepatocellular carcinoma (HCC) surgery either through resection or transplantation often provides the only chance for cure. Since hepatocarcinogenesis and postsurgical prognosis is not only dependent on cirrhosis but also on immune activation and exhaustion, many studies have investigated tumor infiltrating leukocyte (TIL) subsets. This systematic review and meta-analysis aims at describing the cell groups and their predictive power regarding overall (OS), disease free (DFS) and recurrence free survival (RFS). Material and methods A systematic search of the PubMed database was conducted (PROSPERO 172324). Data on CD3+, CD8+, Treg, B cells, macrophages, neutrophil and NK-cells were collected from Pubmed and related references up to December 2018. Overall (OS), disease-free (DFS) and recurrence free survival (RFS) in dependence of high vs. low infiltration rates were compared using a random effects meta-analysis. Results Altogether data from 3541 patients enrolled in 20 publications were included. Except for Tregs and Neutrophils, heterogeneity analysis was found to be moderate to high across the studies. High CD3+, CD8+, NK-cell infiltration predicted better survival (OS, DFS and RFS; p Discussion As with other solid tumors immune infiltration has a great influence on survival after resection. However, a considerable publication bias cannot be ruled out in mostly retrospective analyses. Nevertheless, in light of novel immune modulatory treatments this opens a new avenue towards effective and well-tolerated adjuvant treatment.

Purpose EAU guidelines recommend multiparametric MRI of the prostate (mpMRI) prior to biopsy to increase accuracy and reduce biopsies. Whether biopsy can be avoided in case of negative mpMRI remains unclear. Aim of this study is to evaluate predictors of overall prostate cancer (PCa) in negative mpMRI. Methods A total of 216 patients from 2018 to 2020 with suspicion of PCa and negative mpMRI (PI-RADS ≤ 2) were interviewed by telephone about outcome and further follow-up. Clinically significant PCa (csPCa) was defined as ISUP ≥ 2. Patients with vs. without biopsy and with vs. without PCa were compared. Univariate and multivariate analyses were performed to evaluate predictors of PCa occurrence in patients with negative mpMRI. Results 15.7% and 5.1% of patients with PI-RADS ≤ 2 on mpMRI showed PCa and csPCa, respectively. PCa patients had higher PSAD (0.14 vs. 0.09 ng/ml2; p = 0.001) and lower prostate volume (50.5 vs. 74.0 ml; p = 0.003). Patients without biopsy (25%) after MRI were older (69 vs. 65.5 years; p = 0.027), showed lower PSA (5.7 vs. 6.73 ng/ml; p = 0.033) and lower PSA density (0.09 vs. 0.1 ng/ml2; p = 0.027). Multivariate analysis revealed age (OR 1.09 [1.02–1.16]; p = 0.011), prostate volume (OR 0.982 [0.065; 0.997]; p = 0.027), total PSA level (OR 1.22 [1.01–1.47], p = 0.033), free PSA (OR 0.431 [0.177; 0.927]; p = 0.049) and no PI-RADS lesion vs PI-RADS 1–2 lesion (OR 0.38 [0.15–0.91], p = 0.032.) as predictive factors for the endpoint presence of PCa. Conclusions Biopsy for selected patient groups (higher age, prostate volume and free PSA as well as lower PSA-Density) with negative mpMRI can be avoided, if sufficient follow-up care is guaranteed. Detailed counseling regarding residual risk for undetected prostate cancer should be mandatory.

In social networks, individuals' decisions are strongly influenced by recommendations from their friends, acquaintances, and favorite renowned personalities. The popularity of online social networking platforms makes them the prime venues to advertise products and promote opinions. The Influence Maximization (IM) problem entails selecting a seed set of users that maximizes the influence spread, i.e., the expected number of users positively influenced by a stochastic diffusion process triggered by the seeds. Engineering and analyzing IM algorithms remains a difficult and demanding task due to the NP-hardness of the problem and the stochastic nature of the diffusion processes. Despite several heuristics being introduced, they often fail in providing enough information on how the network topology affects the diffusion process, precious insights that could help researchers improve their seed set selection. In this paper, we present VAIM, a visual analytics system that supports users in analyzing, evaluating, and comparing information diffusion processes determined by different IM algorithms. Furthermore, VAIM provides useful insights that the analyst can use to modify the seed set of an IM algorithm, so to improve its influence spread. We assess our system by: (i) a qualitative evaluation based on a guided experiment with two domain experts on two different data sets; (ii) a quantitative estimation of the value of the proposed visualization through the ICE-T methodology by Wall et al. (IEEE TVCG - 2018). The twofold assessment indicates that VAIM effectively supports our target users in the visual analysis of the performance of IM algorithms.

Background Non-resectability is common in patients with pancreatic ductal adenocarcinoma (PDAC) due to local invasion or distant metastases. Then, biliary or gastroenteric bypasses or both are often established despite associated morbidity and mortality. The current study explores outcomes after palliative bypass surgery in patients with non-resectable PDAC. Methods From the prospectively maintained German StuDoQ|Pancreas registry, all patients with histopathologically confirmed PDAC who underwent non-resective pancreatic surgery between 2013 and 2018 were retrospectively identified, and the influence of the surgical procedure on morbidity and mortality was analyzed. Results Of 389 included patients, 127 (32.6%) underwent explorative surgery only, and a biliary, gastroenteric or double bypass was established in 92 (23.7%), 65 (16.7%) and 105 (27.0%). After exploration only, patients had a significantly shorter stay in the intensive care unit (mean 0.5 days [SD 1.7] vs. 1.9 [3.6], 2.0 [2.8] or 2.1 [2.8]; P Conclusions In patients with non-resectable PDAC, biliary, gastroenteric or double bypass surgery is associated with relevant morbidity and mortality. Although surgical palliation is indicated if interventional alternatives are inapplicable, or life expectancy is high, less invasive options should be considered.

Although lung cancer is the leading cause of cancer deaths worldwide, the mechanisms how lung cancer cells evade the immune system remain incompletely understood. Here, we discovered IL-9-dependent signaling mechanisms that drive immune evasion in non-small cell lung cancer (NSCLC). We found increased IL-9 and IL-21 production by T cells in the tumoral region of the lung of patients with NSCLC, suggesting the presence of Th9 cells in the lung tumor microenvironment. Moreover, we noted IL-9 producing Tregs in NSCLC. IL-9 target cells in NSCLC consisted of IL-9R+ tumor cells and tumor-infiltrating lymphocytes. In two murine experimental models of NSCLC, andin vitro, IL-9 prevented cell death and controlled growth of lung adenocarcinoma cells. Targeted deletion of IL-9 resulted in successful lung tumor rejectionin vivoassociated with an induction of IL-21 and reduction of Treg cells. Finally, anti-IL-9 antibody immunotherapy resulted in suppression of tumor development even in established experimental NSCLC and was associated with reduced IL-10 production in the lung. In conclusion, our findings indicate that IL-9 drives immune escape of lung tumor cellsviaeffects on tumor cell survival and tumor infiltrating T cells. Thus, strategies blocking IL-9 emerge as a new approach for clinical therapy of lung cancer.

Surgical resection improves survival in pancreatic ductal adenocarcinoma (PDAC) and adjuvant chemotherapy adds an additional survival-benefit. While surgical technique has improved in recent years, it remains unclear whether these improvements translate into a survival benefit independent of adjuvant chemotherapy. Thus, we aimed to clarify whether survival of patients who were treated with either Gemcitabine (GEM) or who were observed only in randomized controlled trials on adjuvant chemotherapy of PDAC improved over time.A systematic search of MEDLINE/PubMed was performed to identify randomized controlled trials on adjuvant chemotherapy of PDAC. The search was limited to studies with arms on GEM monotherapy or postoperative observation and studies were grouped by the median year of enrolment and the use of GEM. Subsequently, a meta-regression on the effect of the median year of enrolment on patient survival was performed.A total of 13 studies with 2469 patients was included, with median years of enrollment ranging from 1996 to 2015. While disease-free survival decreased in patients with postoperative observation (18.0 vs. 5.0 months, p = 0.001), median survival improved over time in patients with postoperative observation (15.8 vs. 18.4 months, p = 0.01) and in patients treated with adjuvant GEM (22.8 vs. 35.0 months, p 0.001). One- (p ≤ 0.01) and two-year survival (p = 0.056) improved in both patients treated with adjuvant GEM and those observed only.Survival after surgical resection of PDAC has improved since 1996, even in patients who did not receive adjuvant chemotherapy. Improved surgical technique and postoperative management are likely to be causative factors.

Primary care physicians (general practitioners (GPs)) are burdened for various reasons and are particularly affected by stress-related complaints and an increasing prevalence of burnout. Thus, the prevention of physician burnout has become a major interest for health care services. Although many studies have addressed this issue in recent years, little seems to be known about the work strain and burnout rates in GP trainees. Therefore the objective of this article is to review the psychosocial burden and relevant prevention strategies for GPs with a special emphasis on GP trainees. Regardless of the specialty, burnout is more prevalent among medical trainees and so-called 'early career' physicians than among the age-matched population. Accordingly, burnout seems to be frequent among GP trainees, although there is some evidence that there are fewer doctors working in general medicine who were already heavily burdened at the time of choosing their career. The sudden assumption of responsibility in patient care as well as the fear of showing imperfection in front of their supervisors, or lack of recognition from senior doctors, the medical team, or patients might be stressors typical to this career stage. GP trainees might also feel burdened by the new level of personal involvement and thus have to develop or increase their individual level of professionality to deal with the patients' medical and personal problems. In conclusion, interventions to promote physical and mental health of GP trainees are a necessity to ensure passionate GPs in the future and should therefore be integrated into any postgraduate training curriculum in general practice.

Patient order management (POM) is a mission-critical task for perioperative workflow. Interface complexity within different EHR systems result in poor usability, increasing documentation burden. POM interfaces were compared across two systems prior to (Cerner SurgiNet) and subsequent to an EHR conversion (Epic). Here we employ a navigational complexity framework useful for examining differences in EHR interface systems. The methodological approach includes 1) expert-based methods—specifically, functional analysis, keystroke level model (KLM) and cognitive walkthrough, and 2) quantitative analysis of observed interactive user behaviors. We found differences in relation to navigational complexity with the SurgiNet interface displaying a higher number of unused POM functions, with 12 in total whereas Epic displayed 7 total functions. As reflected in all measures, Epic facilitated a more streamlined task-focused user experience. The approach enabled us to scrutinize the impact of different EHR interfaces on task performance and usability barriers subsequent to system implementation.

The impact of EHRs conversion on clinicians’ daily work is crucial to evaluate the success of the intervention for Hospitals and to yield valuable insights into quality improvement. To assess the impact of different EHR systems on the preoperative nursing workflow, we used a structured framework combining quantitative time and motion study and qualitative cognitive analysis to characterize, visualize and explain the differences before and after an EHR conversion. The results showed that the EHR conversion brought a significant decrease in the patient case time and a reduced percentage of time using EHR. PreOp nurses spent a higher proportion of time caring for the patient, while the important tasks were completed in a more continuous pattern after the EHR conversion. The workflow variance was due to different nurse’s cognitive process and the task time change was reduced because of some new interface features in the new EHR systems.

Rapid ethnography and data mining approaches have been used individually to study clinical workflows, but have seldom been used together to overcome the limitations inherent in either type of method. For rapid ethnography, how reliable are the findings drawn from small samples? For data mining, how accurate are the discoveries drawn from automatic analysis of big data, when compared with observable data? This paper explores the combined use of rapid ethnography and process mining, aka ethno-mining, to study and compare metrics of a typical clinical documentation task, vital signs charting. The task was performed with different electronic health records (EHRs) used in three different hospital sites. The individual methods revealed substantial discrepancies in task duration between sites. Specifically, means of 159.6(78.55), 38.2(34.9), and 431.3(283.04) seconds were captured with rapid ethnography. When process mining was used, means of 518.6(3,808), 345.5(660.6), and 119.74(210.3) seconds were found. When ethno-mining was applied instead, outliers could be identified, explained and removed. Without outliers, mean task duration was similar between sites (78.1(66.7), 72.5(78.5), and 71.7(75) seconds). Results from this work suggest that integrating rapid ethnography and data mining into a single process may provide more meaningful results than a siloed approach when studying of workflow.

Background The importance of platelets in the pathogenesis of metastasis formation is increasingly recognized. Although evidence from epidemiologic studies suggests positive effects of aspirin on metastasis formation, there is little clinical data on the perioperative use of this drug in pancreatic cancer patients. Methods From all patients who received curative intent surgery for pancreatic cancer between 2014 and 2016 at our institution, we identified 18 patients that took aspirin at time of admission and continued to throughout the inpatient period. Using propensity score matching, we selected a control group of 64 patients without aspirin intake from our database and assessed the effect of aspirin medication on overall, disease-free, and hematogenous metastasis-free survival intervals as endpoints. Results Aspirin intake proved to be independently associated with improved mean overall survival (OS) (46.5 vs. 24.6 months, *p = 0.006), median disease-free survival (DFS) (26 vs. 10.5 months, *p = 0.001) and mean hematogenous metastasis-free survival (HMFS) (41.9 vs. 16.3 months, *p = 0.005). Three-year survival rates were 61.1% in patients with aspirin intake vs. 26.3% in patients without aspirin intake. Multivariate cox regression showed significant independent association of aspirin with all three survival endpoints with hazard ratios of 0.36 (95% CI 0.15–0.86) for OS (*p = 0.021), 0.32 (95% CI 0.16–0.63) for DFS (**p = 0.001), and 0.36 (95% CI 0.16–0.77) for HMFS (*p = 0.009). Conclusions Patients in our retrospective, propensity-score matched study showed significantly better overall survival when taking aspirin while undergoing curative surgery for pancreatic cancer. This was mainly due to a prolonged metastasis-free interval following surgery.

Human-centered approaches are of particular importance when analyzing urban spaces in technology-driven fields, because understanding how people perceive and react to their environments depends on several dynamic and static factors, such as traffic volume, noise, safety, urban configuration, and greenness. Analyzing and interpreting emotions against the background of environmental information can provide insights into the spatial and temporal properties of urban spaces and their influence on citizens, such as urban walkability and bikeability. In this study, we present a comprehensive mixed-methods approach to geospatial analysis that utilizes wearable sensor technology for emotion detection and combines information from sources that correct or complement each other. This includes objective data from wearable physiological sensors combined with an eDiary app, first-person perspective videos from a chest-mounted camera, and georeferenced interviews, and post-hoc surveys. Across two studies, we identified and geolocated pedestrians&rsquo, and cyclists&rsquo, moments of stress and relaxation in the city centers of Salzburg and Cologne. Despite open methodological questions, we conclude that mapping wearable sensor data, complemented with other sources of information&mdash, all of which are indispensable for evidence-based urban planning&mdash, offering tremendous potential for gaining useful insights into urban spaces and their impact on citizens.

Clinician task performance is significantly impacted by the navigational efficiency of the system interface. Here we propose and evaluate a navigational complexity framework useful for examining differences in electronic health record (EHR) interface systems and their impact on task performance. The methodological approach includes 1) expert-based methods—specifically, representational analysis (focused on interface elements), keystroke level modeling (KLM), and cognitive walkthrough; and 2) quantitative analysis of interactive behaviors based on video-captured observations. Medication administration record (MAR) tasks completed by nurses during preoperative (PreOp) patient assessment were studied across three Mayo Clinic regional campuses and three different EHR systems. By analyzing the steps executed within the interfaces involved to complete the MAR tasks, we characterized complexities in EHR navigation. These complexities were reflected in time spent on task, click counts, and screen transitions, and were found to potentially influence nurses’ performance. Two of the EHR systems, employing a single screen format, required less time to complete (mean 101.5, range 106–97 s), respectively, compared to one system employing multiple screens (176 s, 73% increase). These complexities surfaced through trade-offs in cognitive processes that could potentially influence nurses’ performance. Factors such as perceptual-motor activity, visual search, and memory load impacted navigational complexity. An implication of this work is that small tractable changes in interface design can substantially improve EHR navigation, overall usability, and workflow.

We studied the medication reconciliation (MedRec) task through analysis of computer logs and ethnographic data. Time spent by healthcare providers performing MedRec was compared between two different EHR systems used at four different regional perioperative settings. Only one of the EHRs used at two settings generated computer logs that supported automatic discovery of the MedRec task. At those two settings, 53 providers generated 383 MedRec instances. Findings from the computer logs were validated with ethnographic data, leading to the identification and removal of 47 outliers. Without outliers, one of the settings had slightly smaller mean (SD) time in seconds 67.3 (40.2) compared with the other, 92.1 (25). The difference in time metrics was statistically significant (p

Preoperative care is a critical, yet complex, time-sensitive process. Optimization of workflow is challenging for many reasons, including a lack of standard workflow analysis methods. We sought to comprehensively characterize electronic health record-mediated preoperative nursing workflow. We employed a structured methodological framework to investigate and explain variations in the workflow. Video recording software captured 10 preoperative cases at Arizona and Florida regional referral centers. We compared the distribution of work for electronic health record tasks and off-screen tasks through quantitative analysis. Suboptimal patterns and reasons for variation were explored through qualitative analysis. Although both settings used the same electronic health record system, electronic health record tasks and off-screen tasks time distribution and patterns were notably different across two sites. Arizona nurses spent a longer time completing preoperative assessment. Electronic health record tasks occupied a higher proportion of time in Arizona, while off-screen tasks occupied a higher proportion in Florida. The contextual analysis helped to identify the variation associated with the documentation workload, preparation of the patient, and regional differences. These findings should seed hypotheses for future optimization efforts and research supporting standardization and harmonization of workflow across settings, post-electronic health record conversion.

Background Reporting of adverse events is an important aspect of patient safety management in hospitals, which may help to prevent future adverse events. Yet, only a small proportion of such events is actually reported in German hospitals. Therefore, it is crucial to evaluate attitudes of clinical staff towards reporting of adverse events. The aim of this study was to translate the Reporting of Clinical Adverse Events Scale (RoCAES) developed by Wilson, Bekker and Fylan (2008) and validate it in a sample of German-speaking health professionals. Methods The questionnaire covers five factors (perceived blame, perceived criteria for identifying events that should be reported, perceptions of colleagues’ expectations, perceived benefits of reporting, and perceived clarity of reporting procedures) and was translated into German language according to translation guidelines. Within a cross-sectional study in a sample of 120 health professionals in German hospitals, internal consistency (omega) and construct validity (confirmatory factor analysis) of the German scale RoCAES-D was assessed. Results The reliability was high (omega = 0.87) and the factor analysis showed a poor model fit (RMSEA: 0.074, χ2/df: 1.663, TLI: 0.690). Resulting from lower model fit of the original model (RMSEA: 0.082, χ2/df: 1.804, TLI: 0.606), one item was deleted due to low factor loadings and a low R2 (0.001), and two items were reallocated from the factor ‘perceived benefits’ to ‘perceived blame’. Conclusion The successful translation and initial validation of the RoCAES-D might be a good starting point for further research. A cultural adaptation of the scale needs to be done to initiate a large-scale usage of the questionnaire.

Introduction Rapid diagnosis accompanied by appropriate treatment is essential in the therapy of sepsis. However, there is no blood marker available, which reliably predicts sepsis and associated mortality. Therefore, the aim of the present study was to evaluate presepsin and endotoxin in comparison with established blood markers in patients undergoing emergency visceral surgery for abdominal infection. Patients and methods This prospective study included 31 patients with abdominal infection undergoing emergency surgery between March and August 2014. The Sepsis-2 and Sepsis-3 definitions of sepsis were used. Blood markers (presepsin, endotoxin, C-reactive protein, procalcitonin (PCT), interleukin 6 (IL-6), white blood count) were analyzed preoperatively and correlated with the clinical course and mortality. Additionally, a combination of the three markers, which performed best, was tested. Results Twenty patients (64.5%) in the analyzed cohort developed sepsis from an abdominal focus according to the latest sepsis definition. Out of the analyzed blood markers, presepsin exhibited the highest area under the curve, sensitivity, and specificity for the prediction of the development of sepsis. Moreover, presepsin had the highest predictive value for mortality as opposed to both endotoxin and previously established blood markers (i.e., PCT, IL-6). The multimarker approach, which included PCT, IL-6, and presepsin, showed no additional predictive value over presepsin alone. Conclusion The present study suggests that presepsin is a novel predictor of sepsis and mortality from sepsis in patients undergoing surgery for intra-abdominal infections. The findings of the present study should be validated in a larger cohort.

Purpose 68Ga-PSMA-11-PET/CT is increasingly used in early-stage biochemical recurrence of prostate cancer to detect potential lesions for an individualized radiotherapy concept. However, subtle findings especially concerning small local recurrences can still be challenging to interpret and are prone to variability between different readers. Thus, we analyzed interobserver variability, detection rate, and lesion patterns systematically in a homogeneous patient population with low-level biochemical recurrence. Methods We analyzed 68Ga-PSMA-11-PET/CTs in 116 patients with status post-prostatectomy and PSA levels up to 0.6 ng/ml. None of them received ADT or radiotherapy beforehand. Images were interpreted and blinded by two nuclear medicine physicians (R1 and R2). Findings were rated using a 5-point scale concerning local recurrence, lymph nodes, bone lesions, and other findings (1: definitely benign, 2: probably benign, 3: equivocal, 4: probably malignant, 5: definitely malignant). In findings with substantial discrepancies of 2 or more categories and/or potentially leading to differences in further patient management, a consensus reading was done with a third reader (R3). Interobserver agreement was measured by Cohens Kappa analysis after sub-categorizing our classification system to benign (1 + 2), equivocal (3), and malignant (4 + 5). Time course of PSA levels after salvage treatment of patients rated as positive (4 + 5) was analyzed. Results The overall detection rate (categories 4 and 5) was 50% (R1/R2, 49%/51%) and in the PSA subgroups 0–0.2 ng/ml, 0.21–0.3 ng/ml, and 0.31–0.6 ng/ml 24%/27%, 57%/57%, and 65%/68%, respectively. Local recurrence was the most common lesion manifestation followed by lymphatic and bone metastases. The overall agreement in the Cohens Kappa analysis was 0.74 between R1 and R2. For local, lymphatic, and bone sites, the agreement was 0.76, 0.73, and 0.58, respectively. PSA levels of PSMA PET/CT-positive patients after salvage treatment decreased in 75% (27/36) and increased in 25% (9/36). A decrease of PSA, although more frequent in patients with imaging suggesting only local tumor recurrence (86%, 18/21), was also observed in 67% (10/15) of patients with findings of metastatic disease. Conclusions In a highly homogeneous group of prostate cancer patients with early-stage biochemical recurrence after radical prostatectomy, we could show that 68Ga-PSMA-11-PET/CT has a good detection rate of 50% which is in accordance with literature, with clinically relevant findings even in patients with PSA

EHRs transform work practices in ways that enhance or impede the quality of care. There is a need for in-depth analysis of EHR workflows, particularly in complex clinical environments. We investigated EHR-basedpre-operative workflows by combining findings from 18 interviews, 7 days of observations, and process mining of EHR interactions from 31 personnel caring for 375 patients at one tertiary referral center. We provided high-definition descriptions of workflows and personnel roles. One third (32.2%) of the time with each patient was spent interacting with the EHR and 4.2% using paper-based artifacts. We also mined personnel social networks validating observed personnel’s EHR-interactions. When comparing workflows between two similar pre-operative settings at different hospitals, we found significant differences in physical organization, patient workflow, roles, use of EHR, social networks and time efficiency. This study informs Mayo Clinic’s enterprise-wide conversion to a single EHR and will guide before and after workflow comparisons.

Vital sign documentation is an essential part of perioperative workflow. Health information technology can introduce complexity into all facets of documentation and burden clinicians with high cognitive load(3-4). The Mayo Clinic enterprise is in the process of documenting current EHR-mediated workflow prior to a system-wide EHR conversion. We compared and evaluated three different vital sign documentation interfaces in pre-operative nursing assessments at three different Mayo Clinic sites. The interfaces differed in their modes of interaction, organization of patient information and cognitive support. Analyses revealed that accessing displays and the organization of interface elements are often unintuitive and inefficient, creating unnecessary complexities when interacting with the system. These differences surface through interface workflow models and interactive behavior measures for accessing, logging and reviewing patient information. Different designs differentially mediate task performance, which can ultimately mitigate errors for complex cognitive tasks, risking patient safety. Identifying barriers to interface usability and bottlenecks in EHR-mediated workflow can lead to system redesigns that minimize cognitive load while improving patient safety and efficiency.

For the evaluation of infectious-diseases interventions, the transmissible nature of such diseases plays a central role. Agent-based models (ABM) allow for dynamic transmission modeling but publications are limited. We aim to provide an overview of important characteristics of ABM for decision-analytic modeling of infectious diseases. A case study of dengue epidemics illustrates model characteristics, conceptualization, calibration and model analysis. First, major characteristics of ABM are outlined and discussed based on ISPOR and ISPOR-SMDM Good Practice guidelines. Second, in our case study, we modeled a dengue outbreak in Cebu City (Philippines) to assess the impact interventions to control the relative growth of the mosquito population. Model outcomes include prevalence and incidence of infected persons. The modular ABM simulates persons and mosquitoes over an annual time horizon considering daily time steps. The model was calibrated and validated. ABM is a dynamic, individual-level modeling approach that is capable to reproduce direct and indirect effects of interventions for infectious diseases. The ability to replicate emerging behavior and to include human behavior or the behavior of other agents is a distinguishing modeling characteristic (e.g., compared to Markov models). Modeling behavior may, however, require extensive calibration and validation. The analyzed hypothetical effectiveness of dengue interventions showed that a reduced human-mosquito ratio of 1:2.5 during rainy seasons leads already to a substantial decrease of infected persons. ABM can support decision-analyses for infectious diseases including disease dynamics, emerging behavior, and providing a high level of reusability due to modularity.

A number of studies have investigated different ways of visualizing uncertainty. However, in the temporal dimension, it is still an open question how to best represent uncertainty, since the special characteristics of time require special visual encodings and may provoke different interpretations. Thus, we have conducted a comprehensive study comparing alternative visual encodings of intervals with uncertain start and end times: gradient plots, violin plots, accumulated probability plots, error bars, centered error bars, and ambiguation. Our results reveal significant differences in error rates and completion time for these different visualization types and different tasks. We recommend using ambiguation - using a lighter color value to represent uncertain regions - or error bars for judging durations and temporal bounds, and gradient plots - using fading color or transparency - for judging probability values.

Information technologies have transformed healthcare delivery and promise to improve efficiency and quality of care. However, in-depth analysis of EHR-mediated workflows is challenging. Our goal was to apply process mining, in combination with observational techniques, to understand EHR-based workflows. We reviewed nearly 76,000 event logs from 15 providers and supporting staff, and 142 patients in a pre-operative setting and we inspected 3 weeks of interviews and video observations. We found that on average 44 minutes were spent per patient interacting with the EHR, 55% of the time of the patient visit was spent by personnel interacting with the EHR and for over 5% of the time personnel used or reviewed paper-based artifacts. We also discovered the handover-of-care network and compared frequency of interactions between personnel. This study suggests that applying process mining in combination with observational techniques has vast potential for informing Mayo Clinic in the forthcoming EHR conversion.

Background Patients with inflammatory rheumatic diseases are at higher risk for influenza and current guidelines recommend vaccination for this group of patients. The aim of this study was to evaluate the vaccination coverage and predictors for influenza vaccination among patients with inflammatory rheumatic diseases. Methods This survey was conducted at the outpatient rheumatology clinic at the Medical University of Vienna between July and October 2017. All patients diagnosed with an inflammatory rheumatic disease and receiving immunosuppressive therapy were asked to complete a questionnaire about their influenza vaccination status for 2016/17. Results 490 patients with rheumatic diseases completed a questionnaire (33% male, mean age 55.3 years). The influenza vaccination rate for the previous season was 25.3% (n = 124/490). Predictors for a positive influenza vaccination status were higher age (Adjusted Odds Ratio 5.0, 95% Confidence Interval 2.4–10.4) and treatment with biological disease-modifying antirheumatic drugs (AOR 2.0, 95% CI 1.3–3.1). Patients who received a recommendation for influenza vaccination by their general practitioner were significantly more likely to be vaccinated than those who did not (57% vs. 15%, AOR 6.6, 95% CI 4.1–10.8); even more so if they received a recommendation by their rheumatologist (62% vs. 19%, AOR 9.0, 95% CI 4.9–16.5). The main reasons for patients to decline influenza vaccination were fear of side effects (36%), concerns that vaccination might not be effective due to their immunosuppressed condition (38%) or that it might worsen the rheumatic disease (20%). Conclusions A moderate influenza vaccination rate of 25.3% was detected among patients with inflammatory rheumatic diseases. Recommendation of the influenza vaccine by a physician exerts the most effective impact on a positive vaccination status.

Background Disease Management Programmes (DMPs) aim to improve effectiveness and equity of care but may suffer from selective enrolment. We analysed social disparities in DMP enrolment among elderly patients with coronary heart disease (CHD) in Germany, taking into account contextual effects at municipality and primary care practice levels. Methods Cross-sectional analysis of effects of educational attainment and regional deprivation on physician-reported DMP enrolment in a subsample of a large population-based cohort study in Germany, adjusting for individual-level, practice-level and area-level variables. We calculated OR and their 95% CIs (95% CI) in cross-classified, multilevel logistic regression models. Results Among N=1280 individuals with CHD (37.3% women), DMP enrolment rates were 22.2% (women) and 35% (men). The odds of DMP enrolment were significantly higher for male patients (OR=1.98 (1.50 to 2.62)), even after adjustment for potential confounding by individual-level, practice-level and area-level variables (range: OR=1.60 (1.08 to 2.36) to 2.16 (1.57 to 2.98)). Educational attainment was not significantly associated with DMP enrolment. Compared to patients living in least-deprived municipalities, the adjusted propensity of DMP enrolment was statistically significantly lower for patients living in medium-deprived municipalities (OR=0.41 (0.24 to 0.71)), and it also tended to be lower for patients living in the most-deprived municipalities (OR=0.70 (0.40 to 1.21)). Models controlling for the social situation (instead of health-related behaviour) yielded comparable effect estimates (medium-deprived/most-deprived vs least-deprived areas: OR=0.45 (0.26 to 0.78)/OR=0.68 (0.33 to 1.19)). Controlling for differences in comorbidity attenuated the deprivation effect estimates. Conclusions We found evidence for marked gender, but not educational disparities in DMP enrolment among patients with CHD. Small-area deprivation was associated with DMP enrolment, but the effects were partly explained by differences in comorbidity. Future studies on DMPs should consider contextual effects when analysing programme effectiveness or impacts on equity and efficiency. &nbsp

Data from the health care domain is often reused to create and parameterize simulation models for example to support life science business in the evaluation of new products. Data quality assessments play an important part to help model users in interpreting simulation results by showing deficiencies in the raw data used in the model building and offers model builders a comparison of data quality amongst the used data assets.Assess data quality in raw data prior to creating simulation models and prepare results for model users.Using a literature review and documentation of previous models created, we searched data quality criteria. For eligible criteria we formulated questions and viable answers to be used in a questionnaire to assess data quality of a data asset.We developed a web tool to evaluate data assets using a generic data model. Percentage results are visualized using a radar chart.Data quality assessment with questionnaires offers model builders a framework to critically analyse raw data and to detect deficiencies early in the modelling process. The summarized results can help model users to better interpret simulation results.

Implant failures are primarily related to bacterial infections and inflammation. Nanocoating of implant devices with organic molecules is a method used for improving their integration into host tissues and limiting inflammation. Bioengineered plant-derived rhamnogalacturonan-Is (RG-Is) from pectins improve tissue regeneration and exhibit anti-inflammatory properties. Therefore, the aim of this study is to evaluate the in vitro effect of RG-I nanocoating on human gingival primary fibroblast (HGF) activity and proinflammatory response following Porphyromonas gingivalis (P. gingivalis) infection. Infected HGFs were incubated on tissue culture polystyrene (TCPS) plates coated with unmodified RG-I isolated from potato pectin (PU) and dearabinanated RG-I (PA). HGF morphology, proliferation, metabolic activity, and expression of genes responsible for extracellular matrix (ECM) turnover and proinflammatory response were examined. Following the P. gingivalis infection, PU and PA significantly promoted HGF proliferation and metabolic activity. Moreover, gene expression levels of IL1B, IL8, TNFA, and MMP2 decreased in the infected cells cultured on PU and PA, whereas the expression of COL1A1, FN1, and FGFR1 was upregulated. The results indicate that RG-Is are promising candidates for nanocoating of an implant surface, can reduce inflammation, and enhance implant integration, particularly in medically compromised patients with chronic inflammatory diseases such as periodontitis and rheumatoid arthritis. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3475-3481, 2017.

An electronic health record (EHR) can assist the delivery of high-quality patient care, in part by providing the capability for a broad range of clinical decision support, including contextual references (e.g., Infobuttons), alerts and reminders, order sets, and dashboards. All of these decision support tools are based on clinical knowledge; unfortunately, the mechanisms for managing rules, order sets, Infobuttons, and dashboards are often unrelated, making it difficult to coordinate the application of clinical knowledge to various components of the clinical workflow. Additional complexity is encountered when updating enterprise-wide knowledge bases and delivering the content through multiple modalities to different consumers. We present the experience of Mayo Clinic as a case study to examine the requirements and implementation challenges related to knowledge management across a large, multi-site medical center. The lessons learned through the development of our knowledge management and delivery platform will help inform the future development of interoperable knowledge resources.

Compelling evidence for the existence of somatic stem cells in the heart of different mammalian species has been provided by numerous groups; however, so far it has not been possible to maintain these cells as self-renewing and phenotypically stable clonal cell lines in vitro. Thus, we sought to identify a surrogate stem cell niche for the isolation and persistent maintenance of stable clonal cardiovascular progenitor cell lines, enabling us to study the mechanism of self-renewal and differentiation in these cells. Using postnatal murine hearts with a selectable marker as the stem cell source and embryonic stem cells and leukemia inhibitory factor (LIF)-secreting fibroblasts as a surrogate niche, we succeeded in the isolation of stable clonal cardiovascular progenitor cell lines. These cell lines self-renew in an LIF-dependent manner. They express both stemness transcription factors Oct4, Sox2, and Nanog and early myocardial transcription factors Nkx2.5, GATA4, and Isl-1 at the same time. Upon LIF deprivation, they exclusively differentiate to functional cardiomyocytes and endothelial and smooth muscle cells, suggesting that these cells are mesodermal intermediates already committed to the cardiogenic lineage. Cardiovascular progenitor cell lines can be maintained for at least 149 passages over 7 years without phenotypic changes, in the presence of LIF-secreting fibroblasts. Isolation of wild-type cardiovascular progenitor cell lines from adolescent and old mice has finally demonstrated the general feasibility of this strategy for the isolation of phenotypically stable somatic stem cell lines.

We demonstrate qualitative dissociations of brightness processing in visuomotor priming and conscious vision. Speeded keypress responses to the brighter of two luminance targets were performed in the presence of preceding dark and bright primes (clearly visible and flanking the targets) whose apparent brightness values were enhanced or attenuated by a visual illusion. Response times to the targets were greatly affected by consistent versus inconsistent arrangements of the primes, relative to the targets (response priming). Priming effects could systematically contradict subjective brightness matches, such that one prime could appear brighter than the other but could prime as if it were darker. Systematic variation of the illusion showed that response-priming effects depended only on local flanker-background contrast, not on the subjective appearance of the flankers. Our findings suggest that speeded motor responses, as opposed to conscious perceptual judgments, access an early phase of lightness and brightness processing prior to full lightness constancy.

Background. As part of a trial aiming to improve care for patients with chronic (systolic) heart failure, a standardized, multifaceted case management approach was evaluated in German general practices. It consisted of regular telephone monitoring, home visits, health counselling, diagnostic screening and booklets for patients. Practice-based doctors’ assistants (equivalent to a nursing role) adopted these new tasks and reported regularly to the employing general practitioner (GP). Objective. To explore GPs’ perceptions of case management, subsequent changes in relationships within the practice team and the potential future role. Method. Twenty-four GPs participated in five moderated, semi-structured, audio-taped focus groups. Full transcription and thematic content analysis was undertaken. Results. GPs rated all elements and instruments of case management conducted by doctors’ assistants feasible, except for the geriatric assessment as patients had not been at risk. GPs perceived difficulties in their own role in delivering health behaviour counselling. Relationships between doctors’ assistants and patients and between GPs and patients or doctors’ assistants remained stable or improved. All GPs perceived a variety of role changes in doctors’ assistants including more in-depth medical knowledge and higher responsibilities yielding more recognition by patients and GPs. Some GPs suggested transferring the case management programme to other chronic conditions and that it should form part of a further education curriculum for doctors’ assistants. Conclusion. This primary care-based case management model characterized by the orchestrated delegation of tasks to doctors’ assistants offers a promising strategy of enhanced chronic illness care, but it needs further adaptation and evaluation.

Objective: Clinical practice guidelines (CPGs) are means to provide evidence-based medical knowledge. In order to make up-to-date ''best'' scientific evidence available these documents need to be updated on an ongoing basis. An effective method to accomplish this aim is offered by the so-called ''living guidelines'': Living guidelines are documents presenting up-to-date and state-of-the-art knowledge to practitioners. To have guidelines implemented by computer-support they have to be formalized in a computer-interpretable form in a first step. Due to the complexity of such formats the formalization process is burdensome and time-consuming. Automating parts of the modeling process and, consequently, modeling updates of these guideline documents are demanded. Methods and material: The LASSIE methodology supports this task by formalizing guidelines in several steps from the textual form to the guideline representation language Asbru using a document-centric approach. LASSIE uses information extraction techniques to semi-automatically accomplish these steps. We apply LASSIE to support the implementation of living guidelines. Results: Based on a living guideline published by the Scottish Intercollegiate Guidelines Network (SIGN) we show that adaptations of previously formalized guidelines can be accomplished easily and fast. Thereby, the different versions of guideline documents are compared and updates are identified. Due to the traceable formalization method of linking text parts and their corresponding formal models, we are able to inherit unchanged models from previously formalized versions. Thus, we only need to formalize updated text parts using the semi-automatic formalization method LASSIE. Conclusion: We propose a simple, time-saving, but effective method called LASSIE to formalize new guideline versions of previously formalized CPGs. Furthermore, models that have been added or modified by knowledge engineers in previous versions can also be transferred easily. This will result in a faster implementation of new guideline versions also known as living guidelines to provide up-to-date knowledge necessary for accomplishing the daily work of health care professionals.

In this paper, a retrospective study was performed to find out whether the introduction of early nasal continuous positive airway pressure (nCPAP) as a new standard regime of very low birthweight infants will lead to a decreasing tracheal intubation and ventilation rate, as well as to a lower incidence of bronchopulmonary dysplasia in a tertiary-level perinatal centre. Ninety-three infants (study group) with early nCPAP as the first respiratory support were compared to 63 infants (historical control group) born before the use of early nCPAP. No statistically significant differences were found in the baseline characteristics. The main results of the study include reduced intubation mainly in infants with a birthweight

An acidic domain (AD) of gp130 was previously found to interact with the Src family kinase (SFK) Hck. Here, the influence of myristoylated peptides derived from this AD was assessed in the mouse myeloma cell line, 7TD1. The IL-6-dependent growth of 7TD1 cells was reduced by approximately 75%, if 100 microM of myristoylated 18mer peptide (18AD) was included in the growth medium, but was unaffected by a control peptide with scrambled sequence (18sc). A similar differential inhibition by peptides 18AD and 18sc was observed for the erythropoietin-dependent growth of BaF-EH cells expressing chimeric erythropoietin receptor-gp130 and human Hck and for the human myeloma cell line INA-6. While the peptide 18AD concentration inhibiting 50% was approximately 30 microM in 7TD1 and BaF-EH cells, peptide 18AD did not significantly inhibit growth of IL-6-independent MM1.S myeloma and OKT1 hybridoma cells or of BaF-EH cells supplied with IL-3. Treatment with 100 microM peptide 18AD caused the same degree or 60% of apoptosis induction as IL-6 deprivation in 7TD1 or INA-6 cells, respectively. Co-immunoprecipitation experiments revealed that peptide 18AD interfered with the association of Hck and gp130 in 7TD1 lysates in a concentration-dependent manner. IL-6-treatment of INA-6 cells induced the kinase activities of Fyn, Lyn and Hck, but not Src, and the IL-6-induced SFK activities were inhibited by peptide 18AD. Expression in 7TD1 cells of a kinase-inactive Hck mutant (K269R) elicited a dominant-negative effect on cell number increases providing further evidence that SFKs are required for gp130 signalling in myeloma cells.

Background Family caregivers play a key role in palliative care at home, and understanding the interdependencies in the constellation of patient, family caregivers and service providers is important. As few longitudinal studies have examined the influence of patient quality of life (QoL) in palliative care on burden of family caregivers, the aim of this study was to identify correlations between changing patient QoL and changing burden of family caregivers that need consideration in patient management. Methods Palliative patients with cancer in primary care evaluated their QoL (Quality of Life Questionnaire Core 15 Palliative Care, QLQ-C15-PAL). They were assessed monthly for an interval of 6 months or until death of the patient. Family caregivers reported the burden they perceived while supporting the patient (Short form of the Burden Scale for Family Caregivers, BSFC). Longitudinal data were analysed for all patients with at least 3 available assessments, considering the most recent data for participants with more than 3 assessments. Changes in patient QoL were analysed using the Friedman test. In a stepwise regression analysis, influences of change in patient QoL on changing caregiver burden were investigated. Results One hundred patients (63 men, 37 women; average age: 68 years) were enrolled in the study. The most common primary diagnoses were colon, lung or breast cancer. In 58 cases, assessments were available from both patients and caregivers. Patients reported overall quality of life increasing towards end of life, although reporting that physical functioning deteriorated. Symptoms of pain and fatigue bothered patients most. Caregiver burden was moderate and on average did not change over time. In a stepwise regression model, the difference in emotional functioning and the difference in dyspnoea showed an influence on the development of caregiver burden (explained variance of 19.3 %). Conclusions Patients’ dyspnoea, feelings of depression and anxiety impacted on the perceived burden of family caregivers, but are manageable symptoms. Our results corroborate the need of regular assessment of patients’ needs taking into account caregiver burden. In this way, general practice teams can intervene early and may more likely meet patients’ needs in the end of life care process. Trial registration Current Controlled Trials ISRCTN78021852, assigned on 04/04/2007

Background Disease Management Programmes (DMPs) have been introduced in Germany ten years ago with the aim to improve effectiveness and equity of care, but little is known about the degree to which enrolment in the programme meets the principles of equity in health care. We aimed to analyse horizontal equity in DMP enrolment among patients with coronary heart disease (CHD). Methods Cross-sectional analysis of horizontal inequities in physician-reported enrolment in the DMP for CHD in a large population-based cohort-study in Germany (2008–2010). We calculated horizontal inequity indices (HII) and their 95% confidence intervals [95%CI] for predicted need-standardised DMP enrolment across two measures of socio-economic status (SES) (educational attainment, regional deprivation) stratified by sex. Need-standardised DMP enrolment was predicted in multi-level logistic regression models. Results Among N = 1,280 individuals aged 55–84 years and diagnosed with CHD, DMP enrolment rates were 22.2% (women) and 35.0% (men). Education-related inequities in need-standardised DMP enrolment favoured groups with lower education, but HII estimates were not significant. Deprivation-related inequities among women significantly favoured groups with higher SES (HII = 0.086 [0.007 ; 0.165]. No such deprivation-related inequities were seen among men (HII = 0.014 [−0.048 ; 0.077]). Deprivation-related inequities across the whole population favoured groups with higher SES (HII estimates not significant). Conclusion Need-standardised DMP enrolment was fairly equitable across educational levels. Deprivation-related inequities in DMP enrolment favoured women living in less deprived areas relative to those living in areas with higher deprivation. Further research is needed to gain a better understanding of the mechanisms that contribute to deprivation-related horizontal inequities in DMP enrolment among women. Electronic supplementary material The online version of this article (doi:10.1186/s12939-015-0155-1) contains supplementary material, which is available to authorized users.

Objective: Currently, visualization support for patient data analysis is mostly limited to the representation of directly measured data. Contextual information on performed treatment steps is an important source to find reasons and explanations for certain phenomena in the measured patient data, but is mostly spared out in the analysis process. This work aims to fill this gap via integrating classical data visualization and visualization of treatment information. Methods and material: We considered temporal as well as logical data aspects and applied a user-centered development approach that was guided by user input gathered via a user study, design reviews, and prototype evaluations. Furthermore, we investigated the novel PlanningLine glyph, that is used to represent plans in the temporal domain, via a comparative empirical user study. Results: Our interactive visualization approach CareVis provides multiple simultaneous views to cover different aspects of the complex underlying data structure of treatment plans and patient data. The tightly coupled views use visualization methods well-known to domain experts and are designed to facilitate users' tasks. The views are based on the concepts of clinical algorithm maps and LifeLines which have been extended in order to cope with the powerful and expressive plan representation language Asbru. Initial feedback of physicians was encouraging and is accompanied by empirical evidence which verifies that PlanningLines are well suited to manage temporal uncertainty. Conclusion: The interactive integration of different visualization methods forms a novel way of combining, relating, and analyzing different kinds of medical data and information that otherwise would be separated.

Fresh beef products, such as steaks, may become contaminated with potential specified risk materials (SRMs), such as central nervous system tissue, during the fabrication of bone-in loin subprimals. The objective of this study was to evaluate current and alternative cutting methods that could be used to minimize the transfer of nervous system tissue (NST) tissue during preparation of steaks from bone-in short loins. Bone-in short loins were cut according to three methods. (i) Cutting method I-The vertebral column bones were removed prior to cutting the loin into steaks from the medial (vertebral column) to lateral (flank) side. (ii) Cutting method II--The loin was cut into steaks from the vertebral column side to the flank side prior to removal of the vertebral column bones. (iii) Cutting method III--The loin was cut into steaks from the flank side to the vertebral column side prior to removal of the vertebral column bones. Results indicated that surface areas along the vertebral column cutting line had detectable (0.10 and 0.22% NST/100 cm2) and, thus, higher potential SRM contamination than resulting steak surfaces or the cutting blade. Overall, there were no detectable (0.10% NST/100 cm2) differences in NST contamination of steaks produced by the three cutting methods. Immunohistochemical evaluation of areas on excised and ground steak surfaces indicated that regardless of cutting method, there was generally "no" to "moderate" staining, suggesting that detectable (0.137 to 0.201% NST) contamination from these samples was most likely due to peripheral nerve detection. These results imply that steaks may be cut from bone-in short loins prior to removal of the vertebral column bones without affecting the transfer of NST to resulting steaks at concentrations0.10% NST/100 cm2.

OBJECTIVES: During the last decade, evidence-based medicine has given rise to an increasing number of medical practice guidelines and protocols. However, the work done on developing and distributing protocols outweighs the efforts on guaranteeing their quality. Indeed, anomalies like ambiguity and incompleteness are frequent in medical protocols. Recent efforts have tried to address the problem of protocol improvement, but they are not sufficient since they rely on informal processes and notations. Our objective is to improve the quality of medical protocols.APPROACH: The solution we suggest to the problem of quality improvement of protocols consists in the utilisation of formal methods. It requires the definition of an adequate protocol representation language, the development of techniques for the formal analysis of protocols described in that language and, more importantly, the evaluation of the feasibility of the approach based on the formalisation and verification of real-life medical protocols. For the first two aspects we rely on earlier work from the fields of knowledge representation and formal methods. The third aspect, i.e. the evaluation of the use of formal methods in the quality improvement of protocols, constitutes our main objective. The steps with which we have carried out this evaluation are the following: (1) take two real-life reference protocols which cover a wide variety of protocol characteristics; (2) formalise these reference protocols; (3) check the formalisation for the verification of interesting protocol properties; and (4) determine how many errors can be uncovered in this way.RESULTS: Our main results are: a consolidated formal language to model medical practice protocols; two protocols, each both modelled and formalised; a list of properties that medical protocols should satisfy; verification proofs for these protocols and properties; and perspectives of the potentials of this approach. Our results have been evaluated by a panel of medical experts, who judged that the problems we detected in the protocols with the help of formal methods were serious and should be avoided.CONCLUSIONS: We have succeeded in demonstrating the feasibility of formal methods for improving medical protocols.

In preterm infants receiving supplemental oxygen, manual control of the inspired oxygen fraction is often time-consuming and inappropriate. We developed a system for automatic oxygen control and hypothesized that this system is more effective than routine manual oxygen control in maintaining target arterial oxygen saturation levels. We performed a randomized controlled crossover clinical trial in 12 preterm infants receiving nasal continuous positive airway pressure and supplemental oxygen. Periods with automatic and routine manual oxygen control were compared with periods of optimal control by a fully dedicated person. The median (range) percentage of time with arterial oxygen saturation levels within target range (87-96%) was 81.7% (39.0-99.8) for routine manual oxygen control, 91.0% (41.4-99.3) for optimal control, and 90.5% (59.0-99.4) for automatic control (ANOVA: p = 0.01). Pairwise post hoc comparisons revealed a statistically significant difference between automatic and routine manual oxygen control (Dunnett's test: p = 0.02). The frequency of manual oxygen adjustments was lowest in automatic control (Friedman's test: p < 0.001). Automatic oxygen control may optimize oxygen administration to preterm infants receiving nasal continuous positive airway pressure and reduce nursing time spent with oxygen control.

Objectives: Many groups are developing computer-interpretable clinical guidelines (CIGs) for use during clinical encounters. CIGs use “Task-Network Models” for representation but differ in their approaches to addressing particular modeling challenges. We have studied similarities and differences between CIGs in order to identify issues that must be resolved before a consensus on a set of common components can be developed. Design: We compared six models: Asbru, EON, GLIF, GUIDE, PRODIGY, and PRO form a. Collaborators from groups that created these models represented, in their own formalisms, portions of two guidelines: the American College of Physicians–American Society of Internal Medicine's guideline for managing chronic cough and the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Measurements: We compared the models according to eight components that capture the structure of CIGs. The components enable modelers to encode guidelines as plans that organize decision and action tasks in networks. They also enable the encoded guidelines to be linked with patient data—a key requirement for enabling patient-specific decision support. Results: We found consensus on many components, including plan organization, expression language, conceptual medical record model, medical concept model, and data abstractions. Differences were most apparent in underlying decision models, goal representation, use of scenarios, and structured medical actions. Conclusion: We identified guideline components that the CIG community could adopt as standards. Some of the participants are pursuing standardization of these components under the auspices of HL7.

Traditionally, diagnosis and treatment have been seen as two distinct tasks. Consequently, most approaches to computer supported health care focus on one of the two—mostly on diagnosis or rather on the interpretation of measurements which is much better understood and formalised. However, in practice diagnosis and treatment overlap and influence each other in many ways. Combinations range from repeatedly going through the diagnosis-treatment loop over a period of time to permanent monitoring of the patients’ health condition as it is done in intensive care units. In this article we describe how to model these combinations using the clinical protocol-representation language asbru . It implements treatment steps in a hierarchy of skeletal, time-oriented plans. Diagnosis can either be described in a declarative way in the conditions, under which treatment steps are taken or it can be modelled explicitly as plans of their own right. We demonstrate our approach using examples taken from the American Association of Paediatricians’ guideline for the treatment of hyperbilirubinemia in the new-born.

This paper describes our approach for fostering and facilitating communication among patients and caregivers in the context of shared decision making, i.e., when decisions must be taken not only on the basis of scientific evidence but also of the patient’s preferences and context. This happens because clinical practice guidelines cannot provide recommendations for every possible situation, and cannot foresee every change in a patient’s context, which might imply the deviation from a previously acknowledged recommendation. Within the EU-funded project MobiGuide (www.mobiguide-project.eu), supporting remote patient management, we propose decision theory as a methodological framework for a tool that, during face to face encounters, is used to tailor pre-defined, generic decision models to the individual patient, by involving the patient himself in the customization of the model parameters. Although this approach is not appropriate for all patients, it leads, in well-chosen cases, to a more informed choice, with potentially better treatment compliance.

As shown in numerous studies, a significant part of published clinical guidelines is tainted with different types of semantical errors that interfere with their practical application. The adaptation of generic guidelines, necessitated by circumstances such as resource limitations within the applying organization or unexpected events arising in the course of patient care, further promotes the introduction of defects. Still, most current approaches for the automation of clinical guidelines are lacking mechanisms, which check the overall correctness of their output. In the domain of software engineering in general and in the domain of knowledge-based systems (KBS) in particular, a common strategy to examine a system for potential defects consists in its verification. The focus of this work is to present an approach, which helps to ensure the semantical correctness of clinical guidelines in a three-step process. We use a particular guideline specification language called Asbru to demonstrate our verification mechanism. A scenario-based evaluation of our method is provided based on a guideline for the artificial ventilation of newborn infants. The described approach is kept sufficiently general in order to allow its application to several other guideline representation formats.

Background Patients with type 2 diabetes are likely to have comorbid conditions which represent a high burden for patients and a challenge for primary care physicians. The aim of this cross-sectional survey was to assess the impact of additional comorbidities on quality of life within a large sample of patients with type 2 diabetes in primary care. Methods A cross-sectional survey within a large sample (3.546) of patients with type 2 diabetes in primary care was conducted. Quality of life (QoL) was assessed by means of the Medical Outcome Study Short Form (SF-36), self reported presence of comorbid conditions was assessed and groups with single comorbidities were selected. QoL subscales of these groups were compared to diabetes patients with no comorbidities. Group comparisons were made by ANCOVA adjusting for sociodemographic covariates and the presence of depressive disorder. Results Of 3546 questionnaires, 1532 were returned, thereof 1399 could be analysed. The mean number of comorbid conditions was 2.1. 235 patients declared to have only hypertension as comorbid condition, 97 patients declared to have osteoarthritis only. Patients suffering from diabetes and hypertension reached similar scores like diabetic patients with no comorbidities. Patients with diabetes and osteoarthritis reached remarkable lower scores in all subscales. Compared to patients with diabetes alone these differences were statistically significant in the subscales representing pain and physical impairment. Conclusion The impact of osteoarthritis as an often disabling and painful condition on QoL in patients with type 2 diabetes is higher than the impact of hypertension as common but often asymptomatic comorbidity. Individual care of patients with chronic conditions should aim at both improving QoL and controlling risk factors for severe complications.