Non-patient-related SARS-CoV-2 exposure from colleagues and household members poses the highest infection risk for hospital employees in a German university hospital: follow-up of the prospective Co-HCW seroprevalence study.

PURPOSE: The Co-HCW study is a prospective, longitudinal, single-center observational study that aims to assess the SARS-CoV-2 seroprevalence and infection status in staff members of Jena University Hospital (JUH) in Jena, Germany. METHODS: This follow-up study covers the observation period from 19th May 2020 to 22nd June 2021. At each of the three voluntary study visits, participants filled out a questionnaire regarding their SARS-CoV-2 exposure and provided serum samples to detect specific SARS-CoV-2 antibodies. Participants who were tested positive for antibodies against nucleocapsid and/or spike protein without previous vaccination and/or reported a positive SARS-CoV-2 PCR test were regarded to have been infected with SARS-CoV-2. Multivariable logistic regression modeling was applied to identify potential risk factors for infected compared to non-infected participants. RESULTS: Out of 660 participants that were included during the first study visit, 406 participants (61.5%) were eligible for the final analysis as their COVID-19 risk area (high-risk n = 76; intermediate-risk n = 198; low-risk n = 132) did not change during the study. Forty-four participants [10.8%, 95% confidence interval (95%CI) 8.0-14.3%] had evidence of a current or past SARS-CoV-2 infection detected by serology (n = 40) and/or PCR (n = 28). No association between SARS-CoV-2 infection and the COVID-19 risk group according to working place was detected. However, exposure to a SARS-CoV-2 positive household member [adjusted OR (AOR) 4.46, 95% CI 2.06-9.65] or colleague (AOR 2.30, 95%CI 1.10-4.79) was found to significantly increase the risk of a SARS-CoV-2 infection. CONCLUSION: Our results demonstrate that non-patient-related SARS-CoV-2 exposure posed the highest infection risk for hospital staff members of JUH.

Short-term Pasteurization of Breast Milk to Prevent Postnatal Cytomegalovirus Transmission in Very Preterm Infants.

BACKGROUND: Postnatally acquired cytomegalovirus (pCMV) infection through breast milk (BM) may cause severe illness and even death, yet BM is advantageous for preterm infants. Therefore, effective methods to prevent CMV transmission are needed. METHODS: To assess the effectiveness of short-term pasteurization (62°C for 5 seconds) in preventing CMV transmission via BM in preterm infants. Design: Prospective interventional bicentric cohort study with infant enrollment between 6/2010 and 1/2012. A cohort from the Tuebingen neonatal intensive care unit (NICU) from 1995-1998 served as historical controls. Differences in CMV transmission were compared with reference to the cumulative time at risk for CMV transmission. Setting: Two German level-3 NICUs. Eighty-seven preterm infants of 69 CMV immunoglobulin G-positive mothers with birth weight <1500 g or gestational age <32 weeks and 83 historical controls were included. Intervention: BM samples were short-term pasteurized from postnatal day 4 to discharge. Primary endpoint: CMV status at discharge, evaluated by polymerase chain reaction and short-term microculture from urine. RESULTS: Two of 87 (2.3%) study infants had a pCMV transmission. This compared to 17 of 83 (20.5%) controls. Total time under risk for infection was 9.6 years vs 10.0 years in controls, yielding an incidence of 0.21/year (95% confidence interval [CI], 0.03 to 0.75/year) vs 1.70/year (95% CI, 0.99 to 2.72/year), respectively. The risk ratio controls vs study infants was 8.3 (95% CI, 2.4 to 52.4) according to Cox proportional hazard model (P = .0003). CONCLUSIONS: Short-term pasteurization significantly reduces the incidence of pCMV infection through BM in the NICU. CLINICAL TRIALS REGISTRATION: NCT01178905.

A Nosocomial Foodborne Outbreak of a VIM Carbapenemase-Expressing Citrobacter freundii.

Background: A foodborne outbreak of VIM carbapenemase-expressing Citrobacter freundii (CPC) occurred between February 2016 and June 2016 at a major university hospital in Germany. Methods: An explosive increase in CPC isolated from rectal swabs of patients during weekly routine screening led to the declaration of an outbreak. A hospital-wide prevalence screening was initiated as well as screening of all patients on admission and before transfer to another ward, canteen staff, patient rooms, medical and kitchen inventory, and food. Swabs were streaked out on selective plates. All CPC isolates were analyzed using mass spectrometry, and selected isolates were analyzed using whole-genome sequencing. Results: A total of 76 were identified; most were unrelated cases in different wards. The CPC was isolated from retained samples of prepared vegetable salads and puddings and from a mixing machine used to prepare these foods only after an overnight culture. The immediate ban on serving potential source food resulted in a sharp decline and finally disappearance of novel cases. Repeated testing of presliced vegetables showed a high degree of contamination with C. freundii without a carbapenemase, indicating a possible source. Conclusions: An explosive increase in carbapenemase-expressing Enterobacteriaceae contamination may have been caused by a foodborne source, and presliced vegetables should be taken into account as a putative pathogen repository. These findings underline the importance of appropriate cooling, transport, reheating, and distribution of meals and indicate that probing of nonorganic surfaces is limited by low sensitivity, which may be increased by additional overnight cultivation in appropriate media.

Cost-effectiveness of the long-term use of temozolomide for treating newly diagnosed glioblastoma in Germany.

Concomitant radiochemotherapy followed by six cycles of temozolomide (= short term) is considered as standard therapy for adults with newly diagnosed glioblastoma. In contrast, open-end administration of temozolomide until progression (= long-term) is proposed by some authors as a viable alternative. We aimed to determine the cost-effectiveness of long-term temozolomide therapy for patients newly diagnosed with glioblastoma compared to standard therapy. A Markov model was constructed to compare medical costs and clinical outcomes for both therapy types over a time horizon of 60 months. Transition probabilities for standard therapy were calculated from randomized controlled trial data by Stupp et al. The data for long-term temozolomide therapy was collected by matching a cohort treated in the Department of Neurosurgery at Jena University Hospital. Health utilities were obtained from a previous cost utility study. The cost perspective was based on health insurance. The base case analysis showed a median overall survival of 17.1 months and a median progression-free survival of 7.4 months for patients in the long-term temozolomide therapy arm. The cost-effectiveness analysis using all base case parameters in a time-dependent Markov model resulted in an incremental effectiveness of 0.022 quality-adjusted life-years (QALYs). The incremental cost-effectiveness ratio (ICER) was €351,909/QALY. Sensitivity analyses showed that parameters with the most influence on ICER were the health state utility of progression in both therapy arms. Although open-ended temozolomide therapy is very expensive, the ICER of this therapy is comparable to that of the standard temozolomide therapy for patients newly diagnosed with glioblastoma.

Manual Compression versus Vascular Closing Device for Closing Access Puncture Site in Femoral Left-Heart Catheterization and Percutaneous Coronary Interventions: A Retrospective Cross-Sectional Comparison of Costs and Effects in Inpatient Care.

OBJECTIVES: To compare complication rates, length of hospital stay, and resulting costs between the use of manual compression and a vascular closing device (VCD) in both diagnostic and interventional catheterization in a German university hospital setting. METHODS: A stratified analysis according to risk profiles was used to compare the risk of complications in a retrospective cross-sectional single-center study. Differences in costs and length of hospital stay were calculated using the recycled predictions method, based on regression coefficients from generalized linear models with gamma distribution. All models were adjusted for propensity score and possible confounders, such as age, sex, and comorbidities. The analysis was performed separately for diagnostic and interventional catheterization. RESULTS: The unadjusted relative risk (RR) of complications was not significantly different in diagnostic catheterization when a VCD was used (RR = 0.70; 95% confidence interval [CI] 0.22-2.16) but significantly lower in interventional catheterization (RR = 0.44; 95% CI 0.21-0.93). Costs were on average €275 lower in the diagnostic group (95% CI -€478.0 to -€64.9; P = 0.006) and around €373 lower in the interventional group (95% CI -€630.0 to -€104.2; P = 0.014) when a VCD was used. The adjusted estimated average length of stay did not differ significantly between the use of a VCD and manual compression in both types of catheterization. CONCLUSIONS: In interventional catheterization, VCDs significantly reduced unadjusted complication rates, as well as costs. A significant reduction in costs also supports their usage in diagnostic catheterization on a larger scale.

Prospective single-center study of health-related quality of life after COVID-19 in ICU and non-ICU patients.

Long-term sequelae in hospitalized Coronavirus Disease 2019 (COVID-19) patients may result in limited quality of life. The current study aimed to determine health-related quality of life (HRQoL) after COVID-19 hospitalization in non-intensive care unit (ICU) and ICU patients. This is a single-center study at the University Hospital of Wuerzburg, Germany. Patients eligible were hospitalized with COVID-19 between March 2020 and December 2020. Patients were interviewed 3 and 12 months after hospital discharge. Questionnaires included the European Quality of Life 5 Dimensions 5 Level (EQ-5D-5L), patient health questionnaire-9 (PHQ-9), the generalized anxiety disorder 7 scale (GAD-7), FACIT fatigue scale, perceived stress scale (PSS-10) and posttraumatic symptom scale 10 (PTSS-10). 85 patients were included in the study. The EQ5D-5L-Index significantly differed between non-ICU (0.78 ± 0.33 and 0.84 ± 0.23) and ICU (0.71 ± 0.27; 0.74 ± 0.2) patients after 3- and 12-months. Of non-ICU 87% and 80% of ICU survivors lived at home without support after 12 months. One-third of ICU and half of the non-ICU patients returned to work. A higher percentage of ICU patients was limited in their activities of daily living compared to non-ICU patients. Depression and fatigue were present in one fifth of the ICU patients. Stress levels remained high with only 24% of non-ICU and 3% of ICU patients (p = 0.0186) having low perceived stress. Posttraumatic symptoms were present in 5% of non-ICU and 10% of ICU patients. HRQoL is limited in COVID-19 ICU patients 3- and 12-months post COVID-19 hospitalization, with significantly less improvement at 12-months compared to non-ICU patients. Mental disorders were common highlighting the complexity of post-COVID-19 symptoms as well as the necessity to educate patients and primary care providers about monitoring mental well-being post COVID-19.

New shift models for doctors in a large German University Neurosurgery Department: how they comply with the European Working Time Directive 3 years after implementation.

BACKGROUND: Due to the European Working Time Directive (EWTD) and a new collective agreement for doctors working at University hospitals in 2006 new shift models had to be designed in the Department of Neurosurgery of the University Hospital Tübingen, Germany. The aim of the study was to show the fit of the models regarding the average weekly working time limits (aWTL), the daily maximum of 10-h working time (10-h dWT), and the staff expenditures 3 years after implementation. METHODS: The new shift model was implemented in 2008, and hence planning and documentation were done electronically. Adherence to the work schedules was measured, and aWTL adherence rates were compared. The relative number of 10-h dWT violations in 2009 and 2010 was analysed. Staff costs relative to performance before and after implementation were calculated and tested using analysis of variance (ANOVA). Four other departments without alteration of shift models served as a control group in cost trend analysis. RESULTS: In 2010 all doctors in the Department of Neurosurgery were able to stay within the limit of 54 h/week; one doctor without opt-out exceeded the 48 h/week limit (50.1 h/week). The median per capita rate of 10-h dWT violations in 2009 was 20.3 % of all eligible working days and further declined to 10.7 % in 2010 (p < 0.001). Staff costs per case-weight point did not change significantly (2007: 339.88€, 2009: 307.99€, 2010: 322.54€; p = 0.22) in neurosurgery or in the control group (2007: 633.72€, 2009: 637.06€, 2010: 690.30€; p = 0.67). CONCLUSIONS: After implementation of the new shift model, current monitoring and properly matching modifications led to long-term stability in complying with the EWTD regulations without increasing costs for staff expenditures.

Prospective surveillance study in a 1,400-bed university hospital: COVID-19 exposure at home was the main risk factor for SARS-CoV-2 point seroprevalence among hospital staff.

The Co-HCW study is a prospective cohort study among hospital staff, including healthcare workers (HCWs) and administration staff, at the Jena University Hospital (JUH), Germany. The objectives of this study were to assess SARS-CoV-2 IgG seroprevalence, individual exposure risk factors and compliance of HCWs to wear personal protective equipment (PPE). After the first nosocomial COVID-19 outbreak at JUH, mandatory masking was implemented on 20th March 2020. We evaluated point seroprevalence using two IgG detecting immunoassays and issued a questionnaire to assess COVID-19 exposure, clinical symptoms and compliance to wear PPE. Antibody retesting was offered to participants with a divergent result of both immunoassays 5-10 weeks after the first test. Between 19th May and 19th June 2020, we analysed 660 participants [out of 3,228; 20.4%]. Among them, 212 participants (32.1%) had received a previous COVID-19 test. Four of them (1.9%) reported a positive test result. After recruitment, 18 participants (2.7%) had SARS-CoV-2 antibodies in at least one immunoassay. Overall, 21 participants (3.2%) had any evidence of a past or current SARS-CoV-2 infection. Among them, 13 (61.9%) were not aware of direct COVID-19 exposure and 9 (42.9%) did not report any clinical symptoms. COVID-19 exposure at home (adjusted OR (aOR) with 95% CI: 47.82 (5.49, 416.62)) was associated with SARS-CoV-2 seroprevalence. We observed no evidence for an association between seroprevalence and exposure at work (aOR 0.48 (0.13, 1.70)) or with COVID-19 risk area according to the working place (aOR for intermediate-risk vs. high-risk: 1.97 (0.42, 9.22), aOR for low-risk versus high-risk: 2.10 (0.40, 11.06); p = .655). Reported compliance of HCWs to wear PPE differed (p < .001) between working in high-risk (98.3%) and in intermediate-risk areas (69.8%). In conclusion, compared to administration staff, we observed no additional risk to acquire SARS-CoV-2 infections by patient care, probably due to high compliance to wear PPE.

New short-term heat inactivation method of cytomegalovirus (CMV) in breast milk: impact on CMV inactivation, CMV antibodies and enzyme activities.

OBJECTIVES: Breast milk (BM) is the primary source of cytomegalovirus (CMV) transmission to premature infants with potentially harmful consequences. We therefore wanted to evaluate temperature and duration of short-term BM pasteurisation with respect to CMV inactivation, effect on CMV-IgG antibodies and BM enzyme activities. METHODS: 116 artificially CMV-spiked BM and 15 wild-type virus-infected samples were subjected for 5 s to different temperatures (55°C-72°C). CMV-IE-1 expression in fibroblast nuclei was assessed using the milk whey fraction in short-term microculture. BM lipase and alkaline phosphatase (AP) activities and CMV binding using CMV-recomLine immunoblotting and neutralising antibodies using epithelial target cells were analysed before and after heating. RESULTS: A minimum of 5 s above 60°C was necessary for CMV inactivation in both CMV-AD-169 spiked and wild-type infected BM. Lipase was very heat sensitive (activities of 54% at 55°C, 5% at 60°C and 2% at 65°C). AP showed activities of 77%, 88% and 10%, respectively. CMV-p150 IgG antibodies were mostly preserved at 62°C for 5 s. CONCLUSION: Our results show that short-term pasteurisation of BM at 62°C for 5 s might be efficient for CMV inactivation and reduces loss of enzyme activities, as well as CMV binding, and functional CMV antibodies.

[Structuring of inpatient case management to improve quality and cost-effectiveness of inpatient healthcare providers from a university hospital's point of view]. / Strukturierung des stationären Fallmanagements für die Verbesserung von Qualität und Wirtschaftlichkeit stationärer Gesundheitsdienstleister aus Sicht eines Universitätsklinikums.

OBJECTIVE: In hospitals, case management (CM) on hospital wards is essential for maintaining a high level of quality and efficiency of care. The present study examined how CM at the Point of Care (POC) can be optimized and which potentials exist. METHODS: The potentials for optimization of typical case management processes performed on hospital wards were analyzed using a structured interview guide. For this purpose, a field study was performed in 24 German hospital departments of tertiary care. Structured interviews were conducted with homogeneous focus groups. The results were evaluated using an extended Balanced Score Card approach and discussed afterwards with the focus groups. RESULTS: Above all, the process quality and safety of case management as well as ensuring the relevant documentation at the POC appears to offer significant potential for optimization. An essential approach to eventually realize the potential for optimization is the reduction of fragmentation of the micro-processes associated with the case management duties on inpatient wards. This homogenization of these activities ideally requires a new and interdisciplinary acting profession, the clinical case managers. CONCLUSION: The homogenization of the case management activities on hospital wards by clinical case managers has the potential and possibilities to relieve both medical and nursing staff of these activities, while improving the quality and efficiency of care for patients, staff and cross-sectoral healthcare provider at the same time.

Economic burden of surgical site infections in patients undergoing cardiac surgery†.

OBJECTIVES: This study aimed to determine the additional costs and length of stay (LOS) due to surgical site infections (SSIs) after coronary artery bypass grafting (CABG) at Jena University Hospital. METHODS: The data of 999 consecutive patients who underwent CABG from January 2013 to December 2014 were collected. We extracted the number, type and duration of antimicrobial therapy and V.A.C.® therapy (negative pressure wound therapy) treatments and calculated the additional SSI-related costs based on the hospital's perspective. We also evaluated the prolongation of LOS using a multistate model and calculated the costs due to the additional LOS. RESULTS: In total, 983 patients were included in our analysis, and 126 patients with SSIs following CABG were identified during the study period; 124 patients with SSIs (98.4%) were discharged alive. The mean cost of antimicrobial therapy to treat the SSIs was €818 [95% confidence interval (CI) 392-1245], and the mean cost of V.A.C. therapy was €1179 (95% CI 748-1610) per infected patient. The mean additional LOS due to SSIs (±standard error) was estimated to be 9.3 ± 2.6 days. The cost per SSI-infected patient attributable to the additional LOS was €9444 (95% CI 4242-14 645). CONCLUSIONS: SSIs following CABG are associated with an additional LOS and a significant economic burden depending on the classification of SSI. A very important component of the additional cost is the prolongation of LOS. Therefore, it is essential to shorten the hospital stay due to SSIs as far as possible.

Estimating extra length of stay due to healthcare-associated infections before and after implementation of a hospital-wide infection control program.

INTRODUCTION: Healthcare-associated infections (HAIs) are a major health concern and have substantial effects on morbidity and mortality and increase healthcare costs. We investigated the effect of a hospital-wide program for the prevention of HAIs on additional length of stay (LOS). METHODS: We analyzed data from a prospective, single-center, quasi-experimental study with two surveillance periods before and after implementation of an infection prevention intervention program. HAI diagnosis was made according to surveillance definition criteria established by the US Centers for Disease Control and Prevention. A multistate model was used to estimate additional LOS for patients with HAI in both surveillance periods. RESULTS: During the first and second periods, 1,568 and 2,336 HAIs were identified among 26,943 and 35,211 patients, respectively. For HAI patients exclusively treated in a general ward, additional LOS was 8.4 (95% confidence interval, CI: 6.8-10.0) days in the first period and 9.6 (95% CI: 8.3-11.0) days in the second period (p = 0.26). For HAI patients treated in both an intensive care unit (ICU) and a general ward, additional LOS was 8.1 (95% CI: 6.3-9.9) days in the first period to 7.3 (95% CI: 6.1-8.5) days in the second period (p = 0.47). CONCLUSIONS: Healthcare-associated infections prolong LOS. A hospital-wide infection control program did not alter the prolongation of LOS.

Do perceived working conditions and patient safety culture correlate with objective workload and patient outcomes: A cross-sectional explorative study from a German university hospital.

BACKGROUND: Workload and demands on hospital staff have been growing over recent years. To ensure patient and occupational safety, hospitals increasingly survey staff about perceived working conditions and safety culture. At the same time, routine data are used to manage resources and performance. This study aims to understand the relation between survey-derived measures of how staff perceive their work-related stress and strain and patient safety on the one hand, and routine data measures of workload and quality of care (patient safety) on the other. METHODS: We administered a written questionnaire to all physicians and nurses in the inpatient units at a German university hospital. The questionnaire was an amalgam of the Copenhagen Psychosocial Questionnaire (COPSOQ), the Copenhagen Burnout Inventory (CBI) scale to assess patient-related burnout of and portions of the Hospital Survey on Patient Safety Culture (HSPSC). Indicators from administrative data used to assess workload and patient-related work-strain were: amount of overtime worked, work intensity recording of nurses, cost weight, occupancy rate and DRG-related length of stay. Quality of care was assessed using readmission rates and disease-related length of stay. Univariate associations were tested with Pearson correlations. RESULTS: Response rate were 37% (224) for physicians and 39% (351) for nurses. Physicians' overtime correlated strongly with perceived quantitative demands (.706, 95% CI: 0.634 to 0.766), emotional demands (.765; 95% CI: 0.705 to 0.814), and perceived role conflicts (.655, 95% CI: 0.573 to 0.724). Nurses' work-intensity measures were associated with decreasing physician job satisfaction and with less favorable perceptions of the appropriateness of staffing (-.527, 95% CI:-0.856 to 0.107). Both professional groups showed medium to strong associations between the morbidity measure (cost weight) and role conflicts; between occupancy rates and role clarity (-.482, 95% CI: -0.782 to -0.02) and predictability of work (-.62, 95% CI: -0.848 to -0.199); and between length of stay and internal team functioning (-.555, 95% CI: -0.818 to -0.101). Higher readmission rates were associated with lower perceived patient safety (-.476, 95% CI: -0.779 to 0.006), inadequate staffing (-.702, 95% CI: -0.884 to -0.334), and worse team functioning (-.520, 95% CI: -0.801 to -0.052). Shorter disease-related length of stay was associated with better teamwork within units (-.555, 95% CI: -0.818 to -0.101) and a lower risk of physician burnout (-.588, 95% CI: -0.846 to -0.108). CONCLUSION: Perceptions of hospital personnel regarding sub-optimal workplace safety and teamwork issues correlated with worse patient outcome measures. Furthermore, objective measures of overtime work as well as objective measures of workload correlated clearly with subjective work-related stress and strain. This suggests that objective workload measures (such as overtime worked) could be used to indirectly monitor job-related psychosocial strain on employees and, thus, improve not only staff wellbeing but also patient outcomes. On the other hand, listening to their personnel could help hospitals to improve patient (and employee) safety.

[Medicine and Economy: Measures for a Science Based, Patient-Centred and Resource Conscious Care. The Association of Scientific Medical Societies' (AWMF) Strategy Paper]. / Medizin und Ökonomie: Maßnahmen für eine wissenschaftlich begründete, patientenzentrierte und ressourcenbewusste Versorgung. Ein Strategiepapier der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF).

The AWMF and its medical societies perceive an increasing dominance of economic targets in the hospital health care sector, leading to impairment of patient care. While resource use in health care should be appropriate, efficient and fairly allocated, "economization" creates a burdensome situation for physicians, nurses and other health care professionals.The AMWF and the medical societies studied causes and developed measures for a scientific, patient-centred and resource-conscious medical care. Disincentives due to the remuneration system, number and equipment of hospitals resp. specialist departments and their basic funding need to be overcome. Proposed actions relate to the patient-doctor-level, the management level of hospitals and the level of planning and financing hospitals including compensation of hospital care. To place patients and their health in the forefront again, joint efforts of all stakeholders in health care are needed.

Cytomegalovirus transmission to preterm infants during lactation.

Breastfeeding has a major impact on HCMV epidemiology. The incidence of postnatal HCMV reactivation during lactation equals the maternal seroprevalence. Infectious virus, viral DNA and RNA can be isolated easily from cell and fat-free milk whey. Early onset of viral DNAlactia and virolactia as well as high viral load in milk whey are maternal risk factors for virus transmission. The dynamics of HCMV reactivation can be described by unimodal kinetics with interindividual variation. Virus reactivation during lactation is a self-limiting local process in the absence of systemic HCMV infection. Preterm infants below 1000g birthweight and a gestational age below 30 weeks may be at high risk of acquiring a symptomatic HCMV infection. Several recent studies described low transmission rates and mostly asymptomatically infected neonates using frozen milk. Despite different freeze-storing procedures, HCMV transmissions occurred, and severe HCMV infections were observed. Few data exist on the long-term outcome of postnatally acquired HCMV infection via breast milk. To substantiate the international debate on the use of native or inactivated milk for feeding of preterm infants, additional data are necessary for better identification of mother-infant-pairs at risk for viral transmission and symptomatic infection early after birth.

Smart Medical Information Technology for Healthcare (SMITH).

INTRODUCTION: This article is part of the Focus Theme of Methods of Information in Medicine on the German Medical Informatics Initiative. "Smart Medical Information Technology for Healthcare (SMITH)" is one of four consortia funded by the German Medical Informatics Initiative (MI-I) to create an alliance of universities, university hospitals, research institutions and IT companies. SMITH's goals are to establish Data Integration Centers (DICs) at each SMITH partner hospital and to implement use cases which demonstrate the usefulness of the approach. OBJECTIVES: To give insight into architectural design issues underlying SMITH data integration and to introduce the use cases to be implemented. GOVERNANCE AND POLICIES: SMITH implements a federated approach as well for its governance structure as for its information system architecture. SMITH has designed a generic concept for its data integration centers. They share identical services and functionalities to take best advantage of the interoperability architectures and of the data use and access process planned. The DICs provide access to the local hospitals' Electronic Medical Records (EMR). This is based on data trustee and privacy management services. DIC staff will curate and amend EMR data in the Health Data Storage. METHODOLOGY AND ARCHITECTURAL FRAMEWORK: To share medical and research data, SMITH's information system is based on communication and storage standards. We use the Reference Model of the Open Archival Information System and will consistently implement profiles of Integrating the Health Care Enterprise (IHE) and Health Level Seven (HL7) standards. Standard terminologies will be applied. The SMITH Market Place will be used for devising agreements on data access and distribution. 3LGM2 for enterprise architecture modeling supports a consistent development process.The DIC reference architecture determines the services, applications and the standardsbased communication links needed for efficiently supporting the ingesting, data nourishing, trustee, privacy management and data transfer tasks of the SMITH DICs. The reference architecture is adopted at the local sites. Data sharing services and the market place enable interoperability. USE CASES: The methodological use case "Phenotype Pipeline" (PheP) constructs algorithms for annotations and analyses of patient-related phenotypes according to classification rules or statistical models based on structured data. Unstructured textual data will be subject to natural language processing to permit integration into the phenotyping algorithms. The clinical use case "Algorithmic Surveillance of ICU Patients" (ASIC) focusses on patients in Intensive Care Units (ICU) with the acute respiratory distress syndrome (ARDS). A model-based decision-support system will give advice for mechanical ventilation. The clinical use case HELP develops a "hospital-wide electronic medical record-based computerized decision support system to improve outcomes of patients with blood-stream infections" (HELP). ASIC and HELP use the PheP. The clinical benefit of the use cases ASIC and HELP will be demonstrated in a change of care clinical trial based on a step wedge design. DISCUSSION: SMITH's strength is the modular, reusable IT architecture based on interoperability standards, the integration of the hospitals' information management departments and the public-private partnership. The project aims at sustainability beyond the first 4-year funding period.

Breast milk and cytomegalovirus infection in preterm infants.

The incidence of postnatal human cytomegalovirus (HCMV) reactivation during lactation equals the maternal seroprevalence. Infectious virus, viral DNA and RNA can be isolated from cells and fat free milk whey. Early onset of viral DNAlactia and virolactia as well as high viral load in milk whey are maternal risk factors for virus transmission. Preterm infants below 1000 g birthweight and a gestational age below 30 weeks may be at high risk of acquiring a symptomatic HCMV infection. Several recent studies using frozen milk for feeding describe low transmission rates and mostly asymptomatically infected neonates. However despite different freeze-storing procedures HCMV transmission occurred and severe HCMV infections were observed. Only few data exist on the long-term outcome of postnatally acquired HCMV infection via breast milk. Additional long-term outcome studies are needed. The newly developed short-term pasteurisation may be a reliable alternative to freezing and Holder pasteurisation, since important milk constituents are conserved.

Characterization of human breast milk leukocytes and their potential role in cytomegalovirus transmission to newborns.

BACKGROUND: Breast milk is the primary source of cytomegalovirus (CMV) transmission to newborns and premature infants. The role of cell-free milk whey in virus transmission is well understood, yet the knowledge about the role of milk cells in this process is scarce. OBJECTIVE: To preliminarily characterize different breast milk cell types during various stages of lactation to evaluate their potential role in the transmission of CMV. MATERIALS AND METHODS: Breast milk cells of 18 lactating and 3 CMV-seropositive mothers of preterm infants were isolated and characterized for expression of myeloid markers by flow cytometry. In parallel, cytospin preparations were stained with α-naphthyl acetate esterase to identify milk macrophages and describe the dynamic changes of the macrophage-granulocyte population during lactation. The influence of different time points of lactation was analyzed by FACS analysis of double-stained (CD15/CD66b) milk cells. To characterize CMV target cells in breast milk, we enriched CD14+ cells by MACS (Miltenyi) and monitored cell fractions using CMV IEEx4 nested PCR and pp67 CMV RNA by NASBA. RESULTS: Virolactia, viral DNAlactia, and viral pp67 late mRNA could be detected in breast milk cells only in defined time periods. Granulocytes and macrophages demonstrated an inverse dynamic with neutrophils predominating in the early stages (<30 days postpartum) and macrophages in later stages (>60 days postpartum) of lactation. Enrichment of CD14-positive cells resulted in viral DNA and pp67 late mRNA detection. CONCLUSIONS: Granulocytes and monocytes/macrophages are the predominating cell populations in breast milk with changing frequencies during early lactation. These results demonstrate that CD14-positive breast milk cells seem to be one of the target cells for CMV in breast milk.