Learning debiased graph representations from the OMOP common data model for synthetic data generation.

BACKGROUND: Generating synthetic patient data is crucial for medical research, but common approaches build up on black-box models which do not allow for expert verification or intervention. We propose a highly available method which enables synthetic data generation from real patient records in a privacy preserving and compliant fashion, is interpretable and allows for expert intervention. METHODS: Our approach ties together two established tools in medical informatics, namely OMOP as a data standard for electronic health records and Synthea as a data synthetization method. For this study, data pipelines were built which extract data from OMOP, convert them into time series format, learn temporal rules by 2 statistical algorithms (Markov chain, TARM) and 3 algorithms of causal discovery (DYNOTEARS, J-PCMCI+, LiNGAM) and map the outputs into Synthea graphs. The graphs are evaluated quantitatively by their individual and relative complexity and qualitatively by medical experts. RESULTS: The algorithms were found to learn qualitatively and quantitatively different graph representations. Whereas the Markov chain results in extremely large graphs, TARM, DYNOTEARS, and J-PCMCI+ were found to reduce the data dimension during learning. The MultiGroupDirect LiNGAM algorithm was found to not be applicable to the problem statement at hand. CONCLUSION: Only TARM and DYNOTEARS are practical algorithms for real-world data in this use case. As causal discovery is a method to debias purely statistical relationships, the gradient-based causal discovery algorithm DYNOTEARS was found to be most suitable.

A long-term cost-effectiveness analysis of cardiac resynchronisation therapy with or without defibrillator based on health claims data.

BACKGROUND: In Germany, CRT devices with defibrillator capability (CRT-D) have become the predominant treatment strategy for patients with heart failure and cardiac dyssynchrony. However, according to current guidelines, most patients would also be eligible for the less expensive CRT pacemaker (CRT-P). We conducted a cost-effectiveness analysis for CRT-P devices compared to CRT-D devices from a German payer's perspective. METHODS: Longitudinal health claims data from 3569 patients with de novo CRT implantation from 2014 to 2019 were used to parametrise a cohort Markov model. Model outcomes were costs and effectiveness measured in terms of life years. Transition probabilities were derived from multivariable parametric survival regression that controlled for baseline differences of CRT-D and CRT-P patients. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: The Markov model predicted a median survival of 84 months for CRT-P patients and 92 months for CRT-D patients. In the base case, CRT-P devices incurred incremental costs of € - 13,093 per patient and 0.30 incremental life years were lost. The ICER was € 43,965 saved per life year lost. In the probabilistic sensitivity analysis, uncertainty regarding the effectiveness was observed but not regarding costs. CONCLUSION: This modelling study illustrates the uncertainty of the higher effectiveness of CRT-D devices compared to CRT-P devices. Given the difference in incremental costs between CRT-P and CRT-D treatment, there would be significant potential cost savings to the healthcare system if CRT-D devices were restricted to patients likely to benefit from the additional defibrillator.

Device runtime and costs of cardiac resynchronization therapy pacemakers - a health claims data analysis.

Introduction: This study investigates the runtime and costs of biventricular defibrillators (CRT-D) and biventricular pacemakers (CRT-P). Accurate estimates of cardiac resynchronization therapy (CRT) device runtime across all manufactures are rare, especially for CRT-P. Methods: Health claims data of a large nationwide German health insurance was used to analyze CRT device runtime. We defined device runtime as the time between the date of implantation and the date of generator change or removal. The median costs for implantation, change, and removal of a CRT device were calculated accordingly. Results: In total, the data set comprises 17,826 patients. A total of 4,296 complete runtimes for CRT-D devices and 429 complete runtimes for CRT-P devices were observed. Median device runtime was 6.04 years for CRT-D devices and 8.16 years for CRT-P devices (log-rank test p<0.0001). The median cost of implantation for a CRT-D device was 14,270 EUR, and for a CRT-P device 9,349 EUR. Conclusions: Compared to CRT-P devices, CRT-D devices had a significantly shorter device runtime of about two years. Moreover, CRT-D devices were associated with higher cost. The study provides important findings that can be utilized by cost-effectiveness analyses.

Direct Costs of Healthcare for Children with Type 1 Diabetes Using a CGM System: A Health Economic Analysis of the VIDIKI Telemedicine Study in a German Setting.

AIMS: The Virtual Diabetes Outpatient Clinic for Children and Adolescents (VIDIKI) study was a 6-month quasi-randomized, multicentre study followed by an extension phase to evaluate the effects of monthly video consultations in addition to regular care. A health economic analysis was conducted to assess the direct costs. METHODS: The cost data of 240 study participants (1-16 years of age) with type 1 diabetes who were already using a continuous glucose monitoring system were collected in the first 6 months of the study. The intervention group (IG) received monthly video consultations plus regular care, and the waiting control group (WG) received only regular care. Cost data were collected for a comparable anonymized group of children from the participating health insurance companies during the 6-month period before the study started (aggregated data group [AG]). RESULTS: Cost data were analysed for the AG (N=840) 6 months before study initiation and those for the study participants (N=225/240). Hospital treatment was the highest cost category in the AG. There was a cost shift and cost increase in the IG and WG, whereby diabetes supplies were the highest cost category. The mean direct diabetes-associated 6-month costs were € 4,702 (IG) and € 4,936 (WG). CONCLUSION: The cost development within the cost collection period over two years possibly reflects the switch to higher-priced medical supplies. Video consultation as an add-on service resulted in a small but nonsignificant reduction in the overall costs.

Long-Term Effects of an Intensive Prevention Program After Acute Myocardial Infarction.

Effective long-term prevention after myocardial infarction (MI) is crucial to reduce recurrent events. In this study the effects of a 12-months intensive prevention program (IPP), based on repetitive contacts between non-physician "prevention assistants" and patients, were evaluated. Patients after MI were randomly assigned to the IPP versus usual care (UC). Effects of IPP on risk factor control, clinical events and costs were investigated after 24 months. In a substudy efficacy of short reinterventions after more than 24 months ("Prevention Boosts") was analyzed. IPP was associated with a significantly better risk factor control compared to UC after 24 months and a trend towards less serious clinical events (12.5% vs 20.9%, log-rank p = 0.06). Economic analyses revealed that already after 24 months cost savings due to event reduction outweighted the costs of the prevention program (costs per patient 1,070 € in IPP vs 1,170 € in UC). Short reinterventions ("Prevention Boosts") more than 24 months after MI further improved risk factor control, such as LDL cholesterol and blood pressure lowering. In conclusion, IPP was associated with numerous beneficial effects on risk factor control, clinical events and costs. The study thereby demonstrates the efficacy of preventive long-term concepts after MI, based on repetitive contacts between non-physician coworkers and patients.

Psychosocial and family-centered support among breast cancer patients with dependent children.

OBJECTIVE: To evaluate the psychosocial situation of breast cancer (BC) patients with dependent children, with regard to who used family-centered psychosocial support (PS) services, reasons against using it, as well as existing, unmet needs, and current PS need. METHODS: Data were collected via survey and patient files during an inpatient rehabilitation program for mothers with BC, who were accompanied by a child <12 years. Descriptive statistics and tests for statistical significance were used. RESULTS: Out of the total of 561 patients, 23.0% had used family-centered PS services before. Common reasons against it were enough support, no anticipated need and organizational issues. Patients stated a high number of unmet needs. The most urgent ones related to their children. About 59.3% of mothers stated a current PS need (PSN) and 33.3% a need for their children. Little social support and a worse maternal HRQOL, but not time since diagnosis, were related to a higher PSN in mothers and children (bivariate association). CONCLUSION: Among BC patients with dependent children, clinicians need to take the whole family and their support needs into account. They should know about the existing organizational barriers, which need to be overcome with the help of tailored offers. Patients with low HRQOL, little social support and single-mothers (with regard to children's PSN) need special attention as these can be indicators of high PSN.

Cardiac Resynchronisation Therapy in Patients with Moderate to Severe Heart Failure in Germany: A Cost-Utility Analysis of the Additional Defibrillator.

BACKGROUND: Cardiac resynchronisation therapy (CRT) is a well-established form of treatment for patients with heart failure and cardiac dyssynchrony. There are two different types of CRT devices: the biventricular pacemaker (CRT-P) and the biventricular defibrillator (CRT-D). The latter is more complex but also more expensive. For the majority of patients who are eligible for CRT, both devices are appropriate according to current guidelines. The purpose of this study was to conduct a cost-utility analysis for CRT-D compared to CRT-P from a German payer's perspective. METHODS: A cohort Markov-model was developed to assess average costs and quality-adjusted life-years (QALY) for CRT-D and CRT-P. The model consisted of six stages: one for the device implementation, one for the absorbing state death, and two stages ("Stable" and "Hospital") for either a CRT device or medical therapy. The time horizon was 20 years. Deterministic and probabilistic sensitivity analyses and scenario analyses were conducted. RESULTS: The incremental cost-effectiveness ratio (ICER) of CRT-D compared with CRT-P was €24,659 per additional QALY gained. In deterministic sensitivity analysis, the survival advantage of CRT-D to CRT-P was the most influential input parameter. In the probabilistic sensitivity analysis 96% of the simulated cases were more effective but also more costly. CONCLUSIONS: Therapy with CRT-D compared to CRT-P resulted in an additional gain of QALYs, but was more expensive. In addition, the ICER was subject to uncertainty, especially due to the uncertainty in the survival benefit. A randomised controlled trial and subgroup analyses would be desirable to further inform decision making.

[Legal Issues of Resource Allocation in the COVID-19 Pandemic - Between Utilitarianism and Life Value Indifference]. / Rechtsfragen der Ressourcenzuteilung in der COVID-19-Pandemie ­ Zwischen Utilitarismus und Lebenswertindifferenz.

The COVID-19 pandemic poses unprecedented challenges for the German health care system. What is already the case in some other countries, may occur in Germany in the near future also: Faced with limited ICU resources, doctors will be forced to decide which patients to treat and which to let die. This paper examines the legal implications of such decisions. It takes up arguments from the general discussion on prioritization in medicine. A constitutional hurdle for the application of utilitarian criteria (in particular patients' age or social role) comes from the principle that every human life is of equal value and must not be traded off against others ("life value indifference"). However, the limits that the Grundgesetz (German Basic Law) sets for state actions do not apply directly to doctors. According to the Musterberufsordnung (professional code of conduct), doctors act based on their conscience and the requirements of medical ethics and humanity. The implications of this normative standard for the prioritizing in an exceptional situation as the COVID 19 pandemic have not been sufficiently clarified. This uncertainty leads to emotional and moral burdens for doctors. The authors conclude that the German law grants a limited freedom of choice that allows physicians to apply utilitarian criteria in addition to purely medical decision algorithms.

Survival of malignant mesothelioma and other rare thoracic cancers in Germany and the United States: A population-based study.

Evidence on survival of malignant mesothelioma (MM) and other rare thoracic cancers is limited due to the rarity of these cancer sites. Here, we provide a comprehensive overview of MM incidence and survival after MM and other rare thoracic cancers in Germany and the United States (US). Incidence was estimated from a German National Cancer Database and from the Surveillance, Epidemiology and End Results (SEER) 18 database for 2000-2014. Patients diagnosed in 1997-2013 with malignant epithelial tumors of the trachea (Etra), epithelial tumors of the thymus (Ethy) and MM were extracted from a German cancer survival database and from the SEER 13 database. Period analysis was employed to compute 5-year relative survival (RS). During 2000-2014, an annual average of 0.9 and 0.6 MM cases per 100,000 person-years was diagnosed in Germany and the US. Rates decreased in Germany and in the US. Patients with Ethy had highest 5-year RS with US patients surviving longer (69.1% compared to 63.7%, p = 0.02). Survival after Etra was comparable in both countries (Germany 33.6%, US 34.4%, p = 0.07). Survival in MM patients was poor overall (Germany 11.8%, US 12.1%, p < 0.01). Survival improvements were only observed in MM patients in Germany (10.8% [2002-2007] vs. 13.0% [2008-2013], p < 0.01). The lack of progress in survival for Etra and Ethy patients underlines the need of novel preventive, therapeutic and diagnostic approaches. MM incidence significantly decreased in Germany and in the US. Further monitoring of MM incidence is warranted given that a peak in incidence is expected in 2020-2030 in Western countries.

Socioeconomic Inequalities in Total and Site-Specific Cancer Incidence in Germany: A Population-Based Registry Study.

Most chronic diseases follow a socioeconomic gradient with higher rates in lower socioeconomic groups. A growing body of research, however, reveals cancer to be a disease group with very diverse socioeconomic patterning, even demonstrating reverse socioeconomic gradients for certain cancers. To investigate this matter at the German national level for the first time, this study examined socioeconomic inequalities in cancer incidence in Germany, both for all cancers combined as well as for common site-specific cancers. Population-based data on primary cancers newly diagnosed in 2010-2013 was obtained from the German Centre for Cancer Registry Data. Socioeconomic position was assessed at the district level using the German Index of Socioeconomic Deprivation, which is a composite index of area-based socioeconomic indicators. Absolute and relative socioeconomic inequalities in total and site-specific cancer incidence were analyzed using multilevel Poisson regression models with the logarithm of the number of residents as an offset. Among men, socioeconomic inequalities in cancer incidence with higher rates in more deprived districts were found for all cancers combined and various site-specific cancers, most pronounced for cancers of the lung, oral and upper respiratory tract, stomach, kidney, and bladder. Among women, higher rates in more deprived districts were evident for kidney, bladder, stomach, cervical, and liver cancer as well as for lymphoid/hematopoietic neoplasms, but no inequalities were evident for all cancers combined. Reverse gradients with higher rates in less deprived districts were found for malignant melanoma and thyroid cancer in both sexes, and in women additionally for female breast and ovarian cancer. Whereas in men the vast majority of all incident cancers occurred at cancer sites showing higher incidence rates in more deprived districts and cancers with a reverse socioeconomic gradient were in a clear minority, the situation was more balanced for women. This is the first national study from Germany examining socioeconomic inequalities in total and site-specific cancer incidence. The findings demonstrate that the socioeconomic patterning of cancer is diverse and follows different directions depending on the cancer site. The area-based cancer inequalities found suggest potentials for population-based cancer prevention and can help develop local strategies for cancer prevention and control.

Association between risk factors and detection of cutaneous melanoma in the setting of a population-based skin cancer screening.

Early detection is considered to improve the prognosis of cutaneous melanoma. The value of population-based screening for melanoma, however, is still controversial. The aim of this study was to evaluate the predictive power of established risk factors in the setting of a population-based screening and to provide empirical evidence for potential risk stratifications. We reanalyzed data (including age, sex, risk factors, and screening results) of 354 635 participants in the Skin Cancer Research to provide Evidence for Effectiveness of Screening in Northern Germany (SCREEN)project conducted in the German state of Schleswig-Holstein (2003-2004). In multivariable analysis, atypical nevi [odds ratio (OR): 17.4; 95% confidence interval (CI): 14.4-20.1], personal history of melanoma (OR: 5.3; 95% CI: 3.6-7.6), and multiple (≥40) common nevi (OR: 1.3; 95% CI: 1.1-1.6) were associated with an increased risk of melanoma detection. Family history and congenital nevi were not significantly associated with melanoma detection in the SCREEN. The effects of several risk-adapted screening strategies were evaluated. Hypothesizing a screening of individuals aged more than or equal to 35 years, irrespective of risk factors (age approach), the number needed to screen is 559 (95% CI: 514-612), whereas a screening of adults (aged ≥20) with at least one risk factor (risk approach) leads to a number needed to screen of 178 (95% CI: 163-196). Converted into one screen-detected melanoma, the number of missed melanomas is 0.15 (95% CI: 0.12-0.18) with the age approach and 0.22 (95% CI: 0.19-0.26) with the risk approach. The results indicate that focusing on individuals at high risk for melanoma may improve the cost-effectiveness and the benefit-to-harm balance of melanoma screening programs.

[Non-pharmaceutical therapy of candidates for geriatric rehabilitation: Non-pharmaceutical therapy prescribed by SHI-accredited doctors after application for outpatient geriatric rehabilitative care]. / Heilmittelversorgung geriatrischer Rehabilitationskandidaten in Schleswig-Holstein: Vertragsärztlich verordnete Heilmitteltherapie nach Beantragung ambulanter geriatrischer rehabilitativer Versorgung.

BACKGROUND: The rejection of an application for ambulant geriatric rehabilitation (AGRV) is usually justified by the argument that non-pharmaceutical therapy prescribed by doctors accredited by social housing institutions (SHI) would suffice. The reality in healthcare during the 6 months following an application is unknown. METHODS: In this study 203 patients who had made an application for AGRV in the second half of 2010 in Flensburg, Lübeck or Ratzeburg were interviewed by telephone. RESULTS: The survey revealed that 25.7% of the applications for AGRV had been rejected. The majority of these patients received no ambulant non-pharmaceutical therapy (e.g. physical therapy, physiotherapy, occupational therapy, speech therapy or psychological therapy), less than 20% received more than 12 therapy sessions and in most cases exclusively physiotherapy. The 141 successful AGRV applicants received additional ambulant therapies of a similar magnitude. CONCLUSION: The difference between the intensified interdisciplinary therapy offered in the AGRV and additionally and the offer to rejected applicants is substantial.

Quality of life in partners of patients with localised prostate cancer.

PURPOSE: The diagnosis of prostate cancer and the following treatment does not only affect the patient, but also his partner. Partners often suffer even more severely from psychological distress than the patients themselves. This analysis aims to describe the quality of life (QoL) after the cancer diagnosis over time and to identify the effects of possible predictors of partners' quality of life in a German study population. DATA AND METHODS: Patients with localised prostate cancer and their partners were recruited from a prospective multicenter study in Germany, the Prostate Cancer, Sexuality, and Partnership (ProCaSP) Study. At five observation times during the follow-up period of 2 years after diagnosis, QoL (EORTC QLQ-C30) and personal, social, and cancer-related health factors as well as adaptation and coping factors of 293 couples were observed and analysed with mixed effects analysis. RESULTS: The men's prostate cancer diagnosis had a small, but significant impact on their partner's QoL. However, QoL of partners was most affected by the partners' own physical health and psychological condition, time, and their relationship quality. CONCLUSION: The finding that average QoL increased again 3 months after diagnosis and later should give partners faith and hope for the future. The identified most important predictors of partners' QoL are potentially susceptible to intervention, and further research on target groups in special need of support and on adequate interventions is needed.

Economical data and advanced prostate carcinoma: do we need new guidelines for decision making?

Based on epidemiological data of incidence, estimated prevalence of advanced prostate carcinoma in Germany, and the cost of androgen deprivation of different regimens were determined in a study model. We analyzed data, published by the Tumor Registry of Munich, which indicate that from 3,838 patients with carcinomas of the prostate, 38% has been treated exclusively with hormone suppression therapy, 14% of patients had undergone a combined radiation therapy and hormone suppression therapy and 9% underwent combined surgical therapy and hormone suppression therapy. The mean survival time of patients treated with medical therapy alone, for patients treated with combined radiation therapy and medical therapy were 60, 24, and 120 months, respectively. The cost for orchiectomy was estimated as $1,072, and for LH-RH therapy as $224/month. We estimated an incidence of 17,700 (per year) and a prevalence of 115,000 patients with advanced prostate cancer for Germany. Provided all patients received LH-RH treatment a total cost of $308,000,000/year would arise. Provided, all patients underwent surgery a total cost of $19,000.000/year would arise. If all patients received LH-RH agonists, the treatment would amount to $16,944 per patient, independently of the prognostic group; and for surgery $1,072 per patient would arise. Limited health care budgets mandate critical determination and evaluation of costs to provide a component for the complex decision making process. However, they must be complimented by validated data of quality of life, which can than be a basis for new guidelines of decision making.