Evaluation of the telemedical health care network "SAFE BIRTH" for pregnant women at risk, premature and sick newborns and their families: study protocol of a cluster-randomized controlled stepped-wedge trial.

BACKGROUND: The Perinatal Center of the University Hospital Carl Gustav Carus Dresden has initiated the telemedical healthcare network "SAFE BIRTH" to coordinate and improve specialized care in non-metropolitan regions for pregnant women and newborns. The network incorporates five intervention bundles (IB): (1) Multi-professional, inter-disciplinary prenatal care plan; (2) Neonatal resuscitation; (3) Neonatal antibiotic stewardship; (4) Inter-facility transfer of premature and sick newborns; (5) Psycho-social support for parents. We evaluate if the network improves care close to home for pregnant women, premature and sick newborns. METHODS: To evaluate the complex healthcare intervention "SAFE BIRTH" we will conduct a cluster-randomized controlled stepped-wedge trial in five prenatal medical outpatient offices and eight non-metropolitan hospitals in Saxony, Germany. The offices and hospitals will be randomly allocated to five respectively eight sequential steps over a 30-month period to implement the telemedical IB. We define one specific primary process outcome for each IB (for instance IB#1: "Proportion of patients with inclusion criterion IB#1 who have a prenatal care plan and psychosocial counseling within one week"). We estimated a separate multilevel logistic regression model for each primary process outcome using the intervention status as a regressor (control or intervention group). Across all IB, a total of 1,541 and 1,417 pregnant women or newborns need to be included in the intervention and control group, respectively, for a power above 80% for small to medium intervention effects for all five hypothesis tests. Additionally, we will assess job satisfaction and sense of safety of health professionals caring for newborns (questionnaire survey) and we will assess families' satisfaction, resilience, quality of life and depressive, anxiety and stress symptoms (questionnaire surveys). We will also evaluate the cost-effectiveness of "SAFE BIRTH" (statutory health insurance routine data, process data) and barriers to its implementation (semi-structured interviews). We use multilevel regression models adjusting for relevant confounders (e.g. socioeconomic status, age, place of residence), as well as descriptive analyses and qualitative content analyses. DISCUSSION: If the telemedical healthcare network "SAFE BIRTH" proves to be effective and cost-efficient, strategies for its translation into routine care should be developed. TRIAL REGISTRATION: German clinical trials register. DRKS-ID: DRKS00031482.

Effectiveness of IT-supported patient recruitment: study protocol for an interrupted time series study at ten German university hospitals.

BACKGROUND: As part of the German Medical Informatics Initiative, the MIRACUM project establishes data integration centers across ten German university hospitals. The embedded MIRACUM Use Case "Alerting in Care - IT Support for Patient Recruitment", aims to support the recruitment into clinical trials by automatically querying the repositories for patients satisfying eligibility criteria and presenting them as screening candidates. The objective of this study is to investigate whether the developed recruitment tool has a positive effect on study recruitment within a multi-center environment by increasing the number of participants. Its secondary objective is the measurement of organizational burden and user satisfaction of the provided IT solution. METHODS: The study uses an Interrupted Time Series Design with a duration of 15 months. All trials start in the control phase of randomized length with regular recruitment and change to the intervention phase with additional IT support. The intervention consists of the application of a recruitment-support system which uses patient data collected in general care for screening according to specific criteria. The inclusion and exclusion criteria of all selected trials are translated into a machine-readable format using the OHDSI ATLAS tool. All patient data from the data integration centers is regularly checked against these criteria. The primary outcome is the number of participants recruited per trial and week standardized by the targeted number of participants per week and the expected recruitment duration of the specific trial. Secondary outcomes are usability, usefulness, and efficacy of the recruitment support. Sample size calculation based on simple parallel group assumption can demonstrate an effect size of d=0.57 on a significance level of 5% and a power of 80% with a total number of 100 trials (10 per site). Data describing the included trials and the recruitment process is collected at each site. The primary analysis will be conducted using linear mixed models with the actual recruitment number per week and trial standardized by the expected recruitment number per week and trial as the dependent variable. DISCUSSION: The application of an IT-supported recruitment solution developed in the MIRACUM consortium leads to an increased number of recruited participants in studies at German university hospitals. It supports employees engaged in the recruitment of trial participants and is easy to integrate in their daily work.

Evaluation of Eligibility Criteria Relevance for the Purpose of IT-Supported Trial Recruitment: Descriptive Quantitative Analysis.

BACKGROUND: Clinical trials (CTs) are crucial for medical research; however, they frequently fall short of the requisite number of participants who meet all eligibility criteria (EC). A clinical trial recruitment support system (CTRSS) is developed to help identify potential participants by performing a search on a specific data pool. The accuracy of the search results is directly related to the quality of the data used for comparison. Data accessibility can present challenges, making it crucial to identify the necessary data for a CTRSS to query. Prior research has examined the data elements frequently used in CT EC but has not evaluated which criteria are actually used to search for participants. Although all EC must be met to enroll a person in a CT, not all criteria have the same importance when searching for potential participants in an existing data pool, such as an electronic health record, because some of the criteria are only relevant at the time of enrollment. OBJECTIVE: In this study, we investigated which groups of data elements are relevant in practice for finding suitable participants and whether there are typical elements that are not relevant and can therefore be omitted. METHODS: We asked trial experts and CTRSS developers to first categorize the EC of their CTs according to data element groups and then to classify them into 1 of 3 categories: necessary, complementary, and irrelevant. In addition, the experts assessed whether a criterion was documented (on paper or digitally) or whether it was information known only to the treating physicians or patients. RESULTS: We reviewed 82 CTs with 1132 unique EC. Of these 1132 EC, 350 (30.9%) were considered necessary, 224 (19.8%) complementary, and 341 (30.1%) total irrelevant. To identify the most relevant data elements, we introduced the data element relevance index (DERI). This describes the percentage of studies in which the corresponding data element occurs and is also classified as necessary or supplementary. We found that the query of "diagnosis" was relevant for finding participants in 79 (96.3%) of the CTs. This group was followed by "date of birth/age" with a DERI of 85.4% (n=70) and "procedure" with a DERI of 35.4% (n=29). CONCLUSIONS: The distribution of data element groups in CTs has been heterogeneously described in previous works. Therefore, we recommend identifying the percentage of CTs in which data element groups can be found as a more reliable way to determine the relevance of EC. Only necessary and complementary criteria should be included in this DERI.

[Interdisciplinary care path and potential IT support for people with rare diseases in Germany]. / Interdisziplinärer Versorgungspfad und mögliche IT-Unterstützung für Menschen mit Seltenen Erkrankungen in Deutschland.

INTRODUCTION: Due to the high variability and, at the same time, rare occurrence of rare diseases, the diagnosis of these patients (approx. 4 million people in Germany) can turn into an odyssey. The large time interval between the appearance of symptoms and the final diagnosis of the rare disease leads to a delay in the appropriate treatment. The often long period of uncertainty about the cause of symptoms as well as non-specific or even wrong therapies can have negative effects on both the course of disease and the patients' quality of life. For a better understanding of the current care situation and IT landscape, the interdisciplinary care pathway for people with rare diseases will be modelled and the possible uses of IT applications identified that have the potential to improve diagnosis, treatment and therapy of rare diseases. METHODS: In order to achieve these goals, an initial care pathway was modelled on the basis of process descriptions which are commonly used in the literature, discussed in detail, and agreed upon in a first workshop with six experts from outpatient and inpatient care as well as employees of Centers for Rare Diseases. In a second workshop, ten experts analyzed the resulting care pathway with regard to the possible use of IT applications, and the identification was agreed upon. The experts included those involved in the process, in particular physicians, patients / patient representatives, health care researchers, and experts in hospital IT, IT security, and data protection. RESULTS: The two workshops resulted in process models including the specification of possible uses for IT applications. The most important steps in the care pathway for people with rare diseases in Germany include: neonatal screening, seeking medical advice, outpatient care by general practitioners, outpatient care by specialists, care by specialist outpatient clinic, care by clinic, care by a Center for Rare Diseases: case review and case conference and treatment and therapy. The discussion of the possible uses of IT applications resulted in a focus on registers (e. g. with regard to experts, treatment and therapy options) as well as on digital tools, such as "digital findings and findings platform" and "digital referral with referral tracking". DISCUSSION: Our results show that the care pathway is very heterogeneous and complex. Thus, the sub-processes show different variants with many branches and repetitions. They also illustrate that the care for people with rare diseases requires a high level of interdisciplinary collaboration; diagnosis as well as treatment and therapy often take place across sectors and in cooperation between different medical health care institutions and professions. When analyzing the current IT landscape, it becomes clear that IT applications can be used at many process steps in the care for people with rare diseases and have a high potential. Therefore, they must be used to inform decisions about the adequate diagnosis and treatment as well as communication about the clinical pictures and the patient's case between practitioners and medical care sectors. CONCLUSION: The interdisciplinary collaboration highlights the need for cooperation between the various parties involved in the process, which requires the identification and implementation of interfaces between the stakeholders and their systems. However, it is not enough to include the view of the processes; the data perspective is also required. Creating interoperability also enables the use of IT applications. The basis for this is the results obtained.

Generating Enriched Synthetic German Hospital Claims Data - A Use Case Driven Approach.

Clinical data and above all individual patient data are highly sensitive. All the more it is important to protect these critical information while analyzing and exploring their specifics for further research. However, in order to enable students and other researchers to develop decision support systems and to use modern data analysis methods such as intelligent pattern recognition, the provision of clinical data is essential. In order to allow this while completely protecting the privacy of a patient, we present a mixed approach to generate semantically and clinically realistic data: (1) We use available synthetic data, extract information on patient visits and diagnoses and adapt them to the encoding systems of German claims data; (2) based on a statistical analysis of real German hospital data, we identify distributions of procedures, laboratory data and other measurements and transfer them to the synthetic patient's visits and diagnoses in a semi-automated way. This enabled us to provide students a data set that is as semantically and clinically realistic as possible to apply patient-level prediction algorithms within the development of clinical decision support systems without putting patient data at any risk.

Formal Modelling of FHIR Based, Medical Data Exchange Using Algebraic Petri Nets.

Enabling interoperability is a challenging task in medical data exchange and is often addressed by the use of versatile communication standards like HL7 FHIR. Although daily routine and scientific experiences show its suitability, the use comes with major risks regarding safety and security of data. To overcome these problems, we present an approach to enable a formal verification of medical communication use cases. We identified the Neonatal Screening as a practical example in which two process participants (physician and screening laboratory) are involved. We analyzed the FHIR specification as well as identified necessary resources in that context and formally modeled them as algebraic specifications. By that, we were able to represent the participants' behavior and data flow with help of Algebraic Petri Nets. This strategy allows to formally verify the correctness of a system by specified requirements regarding data safety and data security.

Development of left ventricular longitudinal speckle tracking echocardiography in very low birth weight infants with and without bronchopulmonary dysplasia during the neonatal period.

OBJECTIVES: In preterm infants, postnatal myocardial adaptation may be complicated by bronchopulmonary dysplasia (BPD). We aimed to describe the development of left ventricular function by serial 2D, Doppler, and speckle tracking echocardiography (2D-STE) in infants with and without BPD during the neonatal period and compare these to anthropometric and conventional hemodynamic parameters. STUDY DESIGN: Prospective echocardiography on day of life (DOL) 1, 7, 14, and 28 in 119 preterm infants <1500 g birth weight of whom 36 developed BPD (need for oxygen supplementation at 36 weeks gestational age). Non-BPD and BPD infants differed significantly in median (IQR) gestational age (25.5(24-26.5) weeks vs. 29(27-30) weeks, p<0.001) and birth weight (661(552-871) g vs. 1100(890-1290) g, p<0.001). RESULTS: The intra- and inter-observer variability of the 2D-STE parameters measured did not depend on time of measurement, although there were significant differences in the reproducibility of the parameters. Low intra- and inter-observer variability was seen for longitudinal systolic strain and strain rate mid septum with a median CV (coefficient of variation) of <4.6%. Much higher CVs (>10%) were seen for the apical segment. While anthropometric parameters show rapid development during the first 4 weeks of life, the speckle tracking parameters did not differ statistically significantly during the neonatal period. Infants with and without BPD differed significantly (p<0.001) in the development of anthropometric parameters, conventional hemodynamic parameters except for heart rate, and 2D-STE parameters: global longitudinal systolic strain rate (GLSSR) and longitudinal systolic strain for the mid left wall (LSSR). The largest differences were seen at DOL 1 and 7 in GLSSR (p<0.001) and in LSSR (p<0.01). CONCLUSIONS: Reproducible 2D-STE measurements are possible in preterm infants <1500 g. Cardiac deformation reveals early (DOL 1 and 7) ventricular changes (GLSSR and LSSR) in very low birth weight infants who develop BPD.

Tissue Doppler-derived strain and strain rate during the first 28 days of life in very low birth weight infants.

BACKGROUND: Preterm infants may have cardiac stress related to patent ductus arteriosus (PDA) or bronchopulmonary dysplasia (BPD). In this study, we examined the development of cardiac function in preterm infants by measuring tissue Doppler-derived peak systolic strain (PSS) and strain rate (PSSR) in the first 28 days of life. METHODS: Peak systolic strain and strain rate were measured in series in the free wall of the right (RV) and left (LV) ventricles on days 1, 7, 14, and 28 of life in 119 preterm infants <1500 g birth weight along with weight, heart rate, and presence of hemodynamically significant (hs) PDA or BPD. Both were assigned retrospectively. HsPDA was defined as a PDA requiring intervention whereas BPD was determined based on an infant's need for supplemental oxygen at 36 weeks of gestational age. RESULTS: Peak systolic strain and strain rate of the RV rose significantly during the first 28 days of life (P < 0.01). Infants who developed BPD had significantly lower RV free wall PSS on days 14 and 28 (P < 0.01 and <0.05). HsPDA resulted in a significantly lower PSS in the LV free wall as of day 14 (P < 0.01). After PDA intervention (day 28), LV PSS remained significantly lower (P < 0.05), but showed a tendency to increase (P = 0.18). CONCLUSIONS: Peak systolic strain determined in preterm infants appears to reflect increased afterload (decreased RV PSS in BPD infants) and increased preload (decreased LV PSS in hsPDA infants). The merits of such measurements as a basis for making clinical decisions still need to be explored.

Reproducibility and optimization of analysis parameters of tissue Doppler-derived strain and strain rate measurements for very low birth weight infants.

AIMS: To assess the effects of region of interest (ROI) size and strain length (SL) on the quality of analysis and to determine the feasibility and reproducibility of tissue Doppler-derived cardiac strain (S) and strain rate (SR) measurements for preterm infants <1500 g birth weight. METHODS AND RESULTS: The beat-to-beat variation (BBV) for different combinations of ROI width (RW), ROI length (RL), and SL was determined from 60 good quality images of left and right free walls and the interventricular septum. We examined the impact of RW, RL, and SL on BBV and estimated inter- and intra-operator variability. BBV was smallest for RW = 2 mm. Raising SL (even at the cost of RL) led to a decrease in BBV. Several combinations provided a low BBV without significant difference. Coefficients of variation for intra- and inter-operator variability ranged from 15.1% to 65.2%. Both were lower for systolic than for diastolic values. CONCLUSION: Tissue Doppler imaging-derived S and SR measurements are feasible in very low birth weight infants. Reproducibility is comparable to older infants for systolic S and SR. For optimal analysis quality, SL and RW should be high while RL should be small (though inside segment size). Best results were obtained with RW = 2 mm, RL = 1 mm, and SL = 6 mm.

Left ventricular longitudinal strain and strain rate measured by 2-D speckle tracking echocardiography in neonates during whole-body hypothermia.

The purpose of the study was to assess changes in cardiac performance in newborn infants with hypoxic-ischemic encephalopathy during therapeutic hypothermia and rewarming with two-dimensional speckle tracking echocardiography. For eight asphyxiated neonates (median birth weight (range): 3038 (2725-3253) g; umbilical artery pH: 6.9 (6.8-7.18) undergoing whole-body hypothermia (33-34°C), left ventricular longitudinal strain and strain rate, as well as heart rate, cardiac output and left ventricular fractional shortening, were determined at four points in time: the start (T1) and end of hypothermia (T2), immediately after rewarming (T3) and the age of 5 to 7 d (T4). Mean (standard deviation) heart rate increased from 93 (12) beats/min at T1 to 133 (12) beats/min at T4 (p < 0.001). Cardiac output was low during hypothermia (T1: 207 [43] mL/kg/min, T2: 240 [70] mL/kg/min) and increased significantly (p < 0.001) afterward (T3: 329 [70] mL/kg/min, T4: 388 [78] mL/kg/min). Left ventricular fractional shortening remained unchanged. Left ventricular global longitudinal peak systolic strain did not differ significantly between hypothermia and rewarming, whereas the systolic strain rate increased from -1.1 (0.3) s(-1) at T1 to -1.8 (0.26) s(-1) at T4 (p = 0.001). Hypothermia affects peak systolic strain rate, heart rate and cardiac output, with complete recovery after rewarming, whereas peak systolic strain and fractional shortening remain stable.