A Tool for Specifying Data Quality Checks for Clinical Data Management Systems - A Technical Case Report.

INTRODUCTION: Prospective data collection in clinical trials is considered the gold standard of clinical research. Validating data entered in input fields in case report forms is unavoidable to maintain good data quality. Data quality checks include both the conformance of individual inputs to the specification of the data element, the detection of missing values, and the plausibility of the values entered. STATE-OF-THE-ART: Besides Libre-/OpenClinica there are many applications for capturing clinical data. While most of them have a commercial approach, free and open-source solutions lack intuitive operation. CONCEPT: Our ocRuleTool is made for the specific use case to write validation rules for Open-/LibreClinica, a clinical study management software for designing case report forms and managing medical data in clinical trials. It addresses parts of all three categories of data quality checks mentioned above. IMPLEMENTATION: The required rules and error messages are entered in the normative Excel specification and then converted to an XML document which can be uploaded to Open-/LibreClinica. The advantage of this intermediate step is a better readability as the complex XML elements are broken down into easy to fill out columns in Excel. The tool then generates the ready to use XML file by itself. LESSONS LEARNED: This approach saves time, is less error-prone and allows collaboration with clinicians on improving data quality. CONCLUSION: Our ocRuleTool has proven useful in over a dozen studies. We hope to increase the user base by releasing it to open source on GitHub.

Effect of Automated Telephone Infectious Disease Consultations to Nonacademic Hospitals on 30-Day Mortality Among Patients With Staphylococcus aureus Bacteremia: The SUPPORT Cluster Randomized Clinical Trial.

Importance: Staphylococcus aureus bacteremia (SAB) is a common and potentially severe infectious disease (ID). Retrospective studies and derived meta-analyses suggest that bedside infectious disease consultation (IDC) for SAB is associated with improved survival; however, such IDCs might not always be possible because of the lack of ID specialists, particularly at nonacademic hospitals. Objectives: To investigate whether unsolicited telephone IDCs (triggered by an automated blood stream infection reporting system) to nonacademic hospitals improved 30-day all-cause mortality in patients with SAB. Design, Setting, and Participants: This patient-blinded, multicenter, interventional, cluster randomized, controlled, crossover clinical trial was conducted in 21 rural, nonacademic hospitals in Thuringia, Germany. From July 1, 2016, to December 31, 2018, 1029 blood culture reports were assessed for eligibility. A total of 386 patients were enrolled, whereas 643 patients were not enrolled for the following reasons: death before enrollment (n = 59); palliative care (n = 41); recurrence of SAB (n = 9); discharge from the hospital before enrollment (n = 77); age younger than 18 years (n = 5); duplicate report from a single patient (n = 26); late report (n = 17); blood culture reported during the washout phase (n = 48); and no signed informed consent for other or unknown reasons (n = 361). Interventions: During the ID intervention phase, ID specialists from Jena University Hospital provided unsolicited telephone IDCs to physicians treating patients with SAB. During the control phase, patients were treated according to local standards. Crossover was performed after including 15 patients or, at the latest, 1 year after the first patient was included. Main Outcomes and Measures: Thirty-day all-cause mortality. Results: A total of 386 patients (median [IQR] age, 75 [63-82] years; 261 [67.6%] male) were included, with 177 randomized to the IDC group and 209 to the control group. The 30-day all-cause mortality rate did not differ between the IDC and control groups (relative risk reduction [RRR], 0.12; 95% CI, -2.17 to 0.76; P = .81). No evidence was found of a difference in secondary outcomes, including 90-day mortality (RRR, 0.17; 95% CI, -0.59 to 0.57; P = .62), 90-day recurrence (RRR, 0.10; 95% CI, -2.51 to 0.89; P = .89), and hospital readmission (RRR, 0.04; 95% CI, -0.63 to 0.48; P = .90). Exploratory evidence suggested that indicators of quality of care were potentially realized more often in the IDC group than in the control group (relative quality improvement, 0.16; 95% CI, 0.08-0.26; P = .01). Conclusions and Relevance: In this cluster randomized clinical trial, unsolicited telephone IDC, although potentially enhancing quality of care, did not improve 30-day all-cause mortality in patients with SAB. Trial Registration: drks.de Identifier: DRKS00010135.

The epidemiology of bloodstream infections and antimicrobial susceptibility patterns in Thuringia, Germany: a five-year prospective, state-wide surveillance study (AlertsNet).

BACKGROUND: Monitoring pathogens of bloodstream infections (BSI) and their antibiotic susceptibility is important to guide empiric antibiotic treatment strategies and prevention programs. This study assessed the epidemiology of BSI and antibiotic resistance patterns at the German Federal State of Thuringia longitudinally. METHODS: A surveillance network consisting of 26 hospitals was established to monitor BSIs from 01/2015 to 12/2019. All blood culture results, without restriction of age of patients, of the participating hospitals were reported by the respective microbiological laboratory. A single detection of obligate pathogens and a repeated detection of coagulase-negative staphylococci, Bacillus spp., Corynebacterium spp., Micrococcus spp. and Propionibacterium spp., within 96 h were regarded as a relevant positive blood culture. If one of the aforementioned non-obligate pathogens has been detected only once within 96 h, contamination has been assumed. Logistic regression models were applied to analyse the relationship between resistance, year of BSI and hospital size. Generalized estimating equations were used to address potential clustering. RESULTS: A total of 343,284 blood cultures (BC) of 82,527 patients were recorded. Overall, 2.8% (n = 9571) of all BCs were classified as contaminated. At least one relevant pathogen was identified in 13.2% (n = 45,346) of BCs. Escherichia coli (25.4%) was the most commonly detected pathogen, followed by Staphylococcus aureus (15.2%), Staphylococcus epidermidis (8.1%) and Klebsiella pneumoniae (4.6%). In S. aureus, we observed a decline of methicillin resistance (MRSA) from 10.4% in 2015 to 2.5% in 2019 (p < 0.001). The rate of vancomycin resistance in Enterococcus faecium (VRE) has increased from 16.7% in 2015 to 26.9% in 2019 (p < 0.001), with a peak in 2018 (42.5%). In addition, we observed an increase of Cefotaxime (3GC) resistance in E. coli from 10.7% in 2015 to 14.5% in 2019 (p = 0.007) whereas 3GC resistance in K. pneumoniae was stable (2015: 9.9%; 2019: 7.4%, p = 0.35). Carbapenem resistance was less than 1% for both pathogens. These patterns were robustly observed across sensitivity analyses. CONCLUSIONS: We observed evidence for a decline in MRSA, an increase in VRE and a very low rate of carbapenem resistance in gram-negative bacteria. 3GC resistance in E. coli increased constantly over time.

Hospital-wide ELectronic medical record evaluated computerised decision support system to improve outcomes of Patients with staphylococcal bloodstream infection (HELP): study protocol for a multicentre stepped-wedge cluster randomised trial.

INTRODUCTION: Staphylococci are the most commonly identified pathogens in bloodstream infections. Identification of Staphylococcus aureus in blood culture (SAB) requires a prompt and adequate clinical management. The detection of coagulase-negative staphylococci (CoNS), however, corresponds to contamination in about 75% of the cases. Nevertheless, antibiotic therapy is often initiated, which contributes to the risk of drug-related side effects. We developed a computerised clinical decision support system (HELP-CDSS) that assists physicians with an appropriate management of patients with Staphylococcus bacteraemia. The CDSS is evaluated using data of the Data Integration Centers (DIC) established at each clinic. DICs transform heterogeneous primary clinical data into an interoperable format, and the HELP-CDSS displays information according to current best evidence in bacteraemia treatment. The overall aim of the HELP-CDSS is a safe but more efficient allocation of infectious diseases specialists and an improved adherence to established guidelines in the treatment of SAB. METHODS AND ANALYSIS: The study is conducted at five German university hospitals and is designed as a stepped-wedge cluster randomised trial. Over the duration of 18 months, 135 wards will change from a control period to the intervention period in a randomised stepwise sequence. The coprimary outcomes are hospital mortality for all patients to establish safety, the 90-day disease reoccurrence-free survival for patients with SAB and the cumulative vancomycin use for patients with CoNS bacteraemia. We will use a closed, hierarchical testing procedure and generalised linear mixed modelling to test for non-inferiority of the CDSS regarding hospital mortality and 90-day disease reoccurrence-free survival and for superiority of the HELP-CDSS regarding cumulative vancomycin use. ETHICS AND DISSEMINATION: The study is approved by the ethics committee of Jena University Hospital and will start at each centre after local approval. Results will be published in a peer-reviewed journal and presented at scientific conferences. TRIAL REGISTRATION NUMBER: DRKS00014320.

Approaching Clinical Data Transformation from Disparate Healthcare IT Systems Through a Modular Framework.

Many healthcare IT systems in Germany are unable to interoperate with other systems through standardised data formats. Therefore it is difficult to store and retrieve data and to establish a systematic collection of data with provenance across systems and even healthcare institutions. We outline the concept for a Transformation Pipeline that can act as a processor for proprietary medical data formats from multiple sources. Through a modular construction, the pipeline relies on different data extraction and data enrichment modules as well as on interfaces to external definitions for interoperability standards. The developed solution is extendable and reusable, enabling data transformation independent from current format definitions and entailing the opportunity of collaboration with other research groups.

Extra length of stay and costs because of health care-associated infections at a German university hospital.

BACKGROUND: Health care-associated infections (HAIs) can be associated with increased health care costs. We examined extra length of hospital stay (LOS) and associated per diem costs attributable to HAIs in a large academic medical center. METHODS: Data for analysis were acquired in a preinterventional phase of a prospective cohort study (ALERTS) conducted over 12 months in 27 general and 4 intensive care units at Jena University Hospital. HAIs were identified among patients hospitalized for ≥48 hours with at least 1 risk factor for HAI and new antimicrobial therapy; the diagnosis was confirmed by U.S. Centers for Disease Control and Prevention criteria. Extra LOS was estimated by multistate modeling, and associated extra costs were based on average per diem costs for clinical units sampled. RESULTS: Of a total of 22,613 patients hospitalized for ≥48 hours, 893 (3.95%) experienced 1,212 episodes of HAI during 12 months. The associated mean extra LOS ± SEM in general units was 8.45 ± 0.80 days per case and 8.09 ± 0.91 days for patients treated in both general and intensive care units. Additional costs attributable to HAIs were €5,823-€11,840 ($7,453-$15,155) per infected patient. CONCLUSION: HAIs generated substantial extra costs by prolonging hospitalization. Potential clinical and financial savings may be realized by implementing effective infection prevention programs.

Bloodstream infections, antibiotic resistance and the practice of blood culture sampling in Germany: study design of a Thuringia-wide prospective population-based study (AlertsNet).

INTRODUCTION: Bloodstream infections are a major cause of death worldwide; blood culture (BC) sampling remains the most important tool for their diagnosis. Current data suggest that BC rates in German hospitals are considerably lower than recommended; this points to shortfalls in the application of microbiological analyses. Since early and appropriate BC diagnostics are associated with reduced case fatality rates and a shorter duration of antimicrobial therapy, a multicomponent study for the improvement of BC diagnostics was developed. METHODS AND ANALYSIS: An electronic BC registry established for the German Federal state of Thuringia is the structural basis of this study. The registry includes individual patient data (microbiological results and clinical data) and institutional information for all clinically relevant positive BCs at the participating centres. First, classic result quality indicators for bloodstream infections (eg, sepsis rates) will be studied using Poisson regression models (adjusted for institutional characteristics) in order to derive relative ranks for feedback to clinical institutions. Second, a target value will be established for the process indicator BC rate. On the basis of this target value, recommendations will be made for a given combination of institutional characteristics as a reference for future use in quality control. An interventional study aiming at the improvement of BC rates will be conducted thereafter. On the basis of the results of a survey in the participating institutions, a targeted educational intervention will be developed. The success of the educational intervention will be measured by changes in the process indicator and the result indicators over time using a pre-post design. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Ethics committee of the University Hospital Jena and from the Ethics committee of the State Chamber of Physicians of Thuringia. Findings of AlertsNet will be disseminated through public media releases and publications in peer-reviewed journals. TRIAL REGISTRATION NUMBER: DRKS00004825.

The Thuringian registry for bloodstream infections, antibiotic resistance and the practice of blood culture sampling--AlertsNet.

Evidence-based blood culture (BC) testing is of utmost importance for intensive care unit (ICU) patients suspected for sepsis. Knowledge of the aetiological agent and its susceptibility to anti-infective agents enables the clinician to initiate appropriate antimicrobial therapy and guides diagnostic procedures. This has been shown to reduce mortality, ICU stay and antibiotic overuse. Whereas microbiological laboratory practice has been highly standardised, shortfalls in pre-analytic procedures in the ICU have a significant effect on the diagnostic yield. Currently, surveillance data on BC practice lack hospital-, patient- and laboratory-based denominator data. Supporting information on differences in the clinical practice of BC testing, differences in the characteristics of the institution and the case-mix on specific wards, as well as differences in the availability of microbiological laboratories is demanded on a population basis. A population-based survey on BC practice has been established for the German Federal State of Thuringia connecting both hospitals and microbiological laboratories within an electronic registry for immediate enrolment of BC findings (AlertsNet; http://www.alertsnet.de). The registry includes microbiological results and clinical data as well as institutional variables (e.g. case severity indices) from all patients with clinically relevant positive BCs at the participating centres. The main objectives are to sustain and expand a population-based surveillance and warning system for the assessment of diagnosis, risk factors, treatment and outcomes of hospitalised patients and to improve outcomes of patients with bloodstream infections.

Serial measurement of Therapeutic Intervention Scoring System-28 (TISS-28) in a surgical intensive care unit.

PURPOSE: The aim of the study was to assess the use of the Therapeutic Intervention Scoring System-28 (TISS-28) in surgical intensive care unit (ICU) patients and the relationship of the score to the type of surgery, severity of illness, and outcome in these patients. MATERIALS AND METHODS: Prospectively collected data from all patients admitted to a postoperative ICU between March 1, 2004, and June 30, 2006, were analyzed retrospectively. RESULTS: A total of 6903 patients were admitted during the study period (63.5% male; mean age, 62.3 years) constituting 29 140 observation days. The mean Simplified Acute Physiology Score (SAPS) II, Sequential Organ Failure Assessment (SOFA), and TISS-28 scores on the day of ICU admission were 36.9 ± 18.2, 5.8 ± 3.9, and 43.2 ± 10.8, respectively. The highest admission TISS-28 was observed in patients who underwent cardiothoracic surgery (47.7 ± 10.1), the lowest in neurosurgical patients (40 ± 9.6), and both declined during the 2 weeks after ICU admission; however, in trauma patients and those admitted after gastrointestinal surgery, TISS scores increased gradually after the first 2 to 5 days in the ICU. The TISS-28 score was moderately correlated to SAPS II (R(2) = 0.42; P < .001) and SOFA score (R(2) = 0.48; P < .001) throughout the ICU stay and was consistently higher in nonsurvivors than in survivors during the first 2 weeks in the ICU. CONCLUSIONS: There are marked variations in TISS-28 scores according to the type of surgery. Therapeutic Intervention Scoring System-28 correlates with the severity of illness and outcome in these patients.

Prognostic value of serum myoglobin in patients after cardiac surgery.

PURPOSE: Serum myoglobin as a marker of myocardial damage and injury has been shown to be of prognostic value in patients with cardiovascular events. In this study, we analyzed the prognostic value of serum myoglobin in comparison to other parameters of muscle damage and renal function in patients after cardiac surgery. METHODS: We retrospectively analyzed data from 373 cardiac surgical patients (mean age, 66 +/- 10 years; range, 30-88 years) by using the highest levels of serum myoglobin, creatinine, and creatine phosphokinase (CK) within the first 24 h after admission to the Intensive Care Unit (ICU). Patients' severity of illness was assessed by the Acute Physiology and Chronic Health Evaluation (APACHE) II score. Predictive properties, in terms of ICU mortality and need for renal replacement therapy (RRT), were analyzed by receiver operating characteristics (ROC) statistics and described by the area under the curve (AUC). RESULTS: Serum myoglobin was significantly higher in nonsurvivors (n = 29) than in survivors (n = 344; median, 1449 vs 356 microg x l(-1); P < 0.001). With respect to ICU mortality, AUCs were 0.81 for myoglobin, 0.80 for creatinine, and 0.63 for CK. For comparison, an AUC of 0.82 was found for the APACHE II score. In terms of the need for RRT, AUCs were 0.87 for myoglobin, 0.92 for creatinine, and 0.60 for CK. For both endpoints, the AUCs of myoglobin and creatinine were significantly higher than that for CK. CONCLUSION: Serum myoglobin is associated with outcome in patients after cardiac surgery. Prediction of ICU mortality and need for RRT was comparable for myoglobin and creatinine, while both were significantly superior to CK.