Complete cancer prevalence in Europe in 2020 by disease duration and country (EUROCARE-6): a population-based study.

BACKGROUND: Cancer survivors-people living with and beyond cancer-are a growing population with different health needs depending on prognosis and time since diagnosis. Despite being increasingly necessary, complete information on cancer prevalence is not systematically available in all European countries. We aimed to fill this gap by analysing population-based cancer registry data from the EUROCARE-6 study. METHODS: In this population-based study, using incidence and follow-up data up to Jan 1, 2013, from 61 cancer registries, complete and limited-duration prevalence by cancer type, sex, and age were estimated for 29 European countries and the 27 countries in the EU (EU27; represented by 22 member states that contributed registry data) using the completeness index method. We focused on 32 malignant cancers defined according to the third edition of the International Classification of Diseases for Oncology, and only the first primary tumour was considered when estimating the prevalence. Prevalence measures are expressed in terms of absolute number of prevalent cases, crude prevalence proportion (reported as percentage or cases per 100 000 resident people), and age-standardised prevalence proportion based on the European Standard Population 2013. We made projections of cancer prevalence proportions up to Jan 1, 2020, using linear regression. FINDINGS: In 2020, 23 711 thousand (95% CI 23 565-23 857) people (5·0% of the population) were estimated to be alive after a cancer diagnosis in Europe, and 22 347 thousand (95% CI 22 210-22 483) in EU27. Cancer survivors were more frequently female (12 818 thousand [95% CI 12 720-12 917]) than male (10 892 thousand [10 785-11 000]). The five leading tumours in female survivors were breast cancer, colorectal cancer, corpus uterine cancer, skin melanoma, and thyroid cancer (crude prevalence proportion from 2270 [95%CI 2248-2292] per 100 000 to 301 [297-305] per 100 000). Prostate cancer, colorectal cancer, urinary bladder cancer, skin melanoma, and kidney cancer were the most common tumours in male survivors (from 1714 [95% CI 1686-1741] per 100 000 to 255 [249-260] per 100 000). The differences in prevalence between countries were large (from 2 to 10 times depending on cancer type), in line with the demographic structure, incidence, and survival patterns. Between 2010 and 2020, the number of prevalent cases increased by 3·5% per year (41% overall), partly due to an ageing population. In 2020, 14 850 thousand (95% CI 14 681-15 018) people were estimated to be alive more than 5 years after diagnosis and 9099 thousand (8909-9288) people were estimated to be alive more than 10 years after diagnosis, representing an increasing proportion of the cancer survivor population. INTERPRETATION: Our findings are useful at the country level in Europe to support evidence-based policies to improve the quality of life, care, and rehabilitation of patients with cancer throughout the disease pathway. Future work includes estimating time to cure by stage at diagnosis in prevalent cases. FUNDING: European Commission.

Differences in survival and recurrence of colorectal cancer by stage across population-based European registries.

Recurrence after colorectal cancer resection is rarely documented in the general population while a key clinical determinant for patient survival. We identified 8785 patients with colorectal cancer diagnosed between 2010 and 2013 and clinically followed up to 2020 in 15 cancer registries from seven European countries (Bulgaria, Switzerland, Germany, Estonia, France, Italy, and Spain). We estimated world age-standardized net survival using a flexible cumulative excess hazard model. Recurrence rates were calculated for patients with initially resected stage I, II, or III cancer in six countries, using the actuarial survival method. The proportion of nonmetastatic resected colorectal cancers varied from 58.6% to 78.5% according to countries. The overall 5-year net survival by country ranged between 60.8% and 74.5%. The absolute difference between the 5-year survival extremes was 12.8 points for stage II (Bulgaria vs Switzerland), 19.7 points for stage III (Bulgaria vs. Switzerland) and 14.8 points for Stage IV and unresected cases (Bulgaria vs. Switzerland or France). Five-year cumulative rate of recurrence among resected patients with stage I-III was 17.7%. As compared to the mean of the whole cohort, the risk of developing a recurrence did not differ between countries except a lower risk in Italy for both stage I/II and stage III cancers and a higher risk in Spain for stage III. Survival after colorectal cancer differed across the concerned European countries while there were slight differences in recurrence rates. Population-based collection of cancer recurrence information is crucial to enhance efforts for evidence-based management of colorectal cancer follow up.

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.

Estimates of protection levels against SARS-CoV-2 infection and severe COVID-19 in Germany before the 2022/2023 winter season: the IMMUNEBRIDGE project.

PURPOSE: Despite the need to generate valid and reliable estimates of protection levels against SARS-CoV-2 infection and severe course of COVID-19 for the German population in summer 2022, there was a lack of systematically collected population-based data allowing for the assessment of the protection level in real time. METHODS: In the IMMUNEBRIDGE project, we harmonised data and biosamples for nine population-/hospital-based studies (total number of participants n = 33,637) to provide estimates for protection levels against SARS-CoV-2 infection and severe COVID-19 between June and November 2022. Based on evidence synthesis, we formed a combined endpoint of protection levels based on the number of self-reported infections/vaccinations in combination with nucleocapsid/spike antibody responses ("confirmed exposures"). Four confirmed exposures represented the highest protection level, and no exposure represented the lowest. RESULTS: Most participants were seropositive against the spike antigen; 37% of the participants ≥ 79 years had less than four confirmed exposures (highest level of protection) and 5% less than three. In the subgroup of participants with comorbidities, 46-56% had less than four confirmed exposures. We found major heterogeneity across federal states, with 4-28% of participants having less than three confirmed exposures. CONCLUSION: Using serological analyses, literature synthesis and infection dynamics during the survey period, we observed moderate to high levels of protection against severe COVID-19, whereas the protection against SARS-CoV-2 infection was low across all age groups. We found relevant protection gaps in the oldest age group and amongst individuals with comorbidities, indicating a need for additional protective measures in these groups.

[Social pediatric care situation and needs during the COVID-19 pandemic from 2020 to 2022. What is needed now?] / Sozialpädiatrische Versorgungssituation und -bedarfe in Zeiten der COVID-19-Pandemie 2020 bis 2022. Was wird jetzt gebraucht?

BACKGROUND: Children and adolescents with social pediatric care needs represent a group with special challenges. The aim of this qualitative study was to describe social pediatric care during the pandemic from the perspective of experts. From this, conclusions were to be drawn for any social pediatric care needs that may have arisen. METHODS: Between May and November 2022, 25 experts from the field of social pediatrics were interviewed using guided interviews on the following topics: deviations in care, utilization behavior of families, individual burdens and resources, and sustainable needs. The interviews were analyzed by two research assistants. RESULTS: Overall, the social pediatric care offer was temporarily clearly limited. While families who were already well connected before the pandemic could be adequately cared for with the help of telephone/video contacts, an unreported number of at-risk groups, were described, for example, those with low competence to act, who did not make use of services or did so with delays. It was observed that there was a need for care for newly developed mental disorders and regression in therapy due to limited opportunities for support, as well as a need to catch up on missed opportunities for early support in the case of developmental disorders. DISCUSSION: To meet the needs that have arisen, underserved families should be identified and cared for promptly, taking individual characteristics into account. To this end, for example, more outreach services should be established that reach affected families unbureaucratically.

Temporal trends in age- and stage-specific incidence of colorectal adenocarcinomas in Germany.

BACKGROUND: A national colorectal cancer (CRC) screening programme was launched in 2002 in Germany. A comprehensive evaluation of the programme effectiveness using real-world data is still lacking. In addition, there are regional reports on increasing colorectal cancer incidence in younger populations. Therefore, we aimed to describe and compare the overall, age- and stage-specific incidence trends for colorectal, colon and rectal cancer. METHODS: We used data from seven population-based cancer registries in Germany. We report absolute and relative changes in incidence rates between the early screening phase (2003-2005) and the most recent time period available (2015-2017), as well as annual percent changes. We analysed incidences according to tumour site (colorectum, colon, and rectum) and to six age groups (young adults: 15-34, 35-39, 40-49, screening-entitled/older adults: 50-54, 55-69 and 70 + years old). RESULTS: In our sample of 271,011 colorectal adenocarcinomas, about two-thirds were located in the colon and 95% of them occurred in the age group 50+ (50-54: 5%, 55-69: 32.8%, 70+: 57.2%). For the time period 2003-2005 the age-specific incidence rates of individuals in the age group 55-69 were about 76/100,00 for colon and 54/100,000 for rectal cancer (age group 70 + colon: 179/100,000; rectum: 84/100,000). The incidence rates in young adults were less than 13% of that of individuals in the age group 55-69 (< 5% of individuals aged 70+; <33% of individuals aged 50-54). Over time, incidence decreased in individuals at the age of 55+, for all subsites considered as well as for early and late stage cancers (with few exceptions), while incidence of young adult CRC (both early and late stage) increased steepest in the youngest age groups. For late stage rectal cancer, a shift was observed in all age groups from UICC stage IV to stage III being the most frequent stage. CONCLUSIONS: Six years after the introduction of the national colonoscopy screening program, late stage CRC incidence began to decline substantially in the screening-eligible age groups (55-69, 70+). It is likely that this decline and the increase in early stage CRC observed in younger age groups can be attributed to the program. Long lasting public awareness campaigns for CRC screening might have led to opportunistic screening in younger adults. Whether these benefits outweigh the possible harm of screening in younger age groups remains unclear.

Physicians' perspectives on family caregivers' roles in elderly cancer patients' therapies: a qualitative, interview-based study.

PURPOSE: Clinical communication and facilitating informed and sound medical decisions become challenging as patients age and suffer from age-associated impairments. Family caregivers are perceived as essential actors in addressing these challenges. Here, we explore physicians' perspectives on family caregivers' roles and their involvement in consultations and therapy decision-making situations of elderly cancer patients. METHODS: We examined 38 semi-structured interviews with physicians from different specialities (oncologists, non-oncology specialists, and general practitioners) in Germany who treated elderly cancer patients. Data were analyzed using reflexive thematic analysis. RESULTS: We identified five general and distinct perspectives on the involvement of family caregivers in the therapy process. Family caregivers are seen as (1) translators of medical information; (2) providers of support for the patient; (3) providers of information about the patient; (4) stakeholders with relevant points of view regarding the treatment decision; or (5) individuals who have a disruptive influence on the consultation. The interviewed physicians rarely involved family caregivers closely in consultations. CONCLUSIONS: Although physicians frequently attribute supportive roles to family caregivers, they rarely include them in consultations. Previous studies have found that a triadic setting is often better suited to agreeing upon a patient-centered and needs-based treatment decision for older cancer patients. We infer that physicians too rarely recognize the potential importance of family caregivers. Educators should further integrate family caregiver involvement and its implications in general medical education and professional training.

Use of novel artificial intelligence computer-assisted detection (AI-CAD) for screening mammography: an analysis of 17,884 consecutive two-view full-field digital mammography screening exams.

BACKGROUND: Novel artificial intelligence computer-assisted detection (AI-CAD) systems based on deep learning (DL) promise to support screen reading. PURPOSE: To test a DL-AI-CAD system compared to human reading on consecutive screening mammograms. MATERIAL AND METHODS: In this retrospective study, 17,884 consecutive anonymized screening mammograms, double-read from January to November 2018, were processed by the DL-AI-CAD system. AI-CAD reading was considered positive if the AI-CAD case scores exceeded 30 (range = 1-100) and the lesion was correctly marked. Likewise, human reading (R1 or R2, respectively) was considered positive if the lesion was correctly identified and called. Receiver operating characteristic (ROC) analysis was performed and accuracy data were calculated. Ground truth for benign lesions: absence of malignancy after cancer registry matching (2022); for malignancy: histopathologic proof; evaluation was patient-based. RESULTS: In total, 114 screen-detected and 17 interval cancers (ICA) occurred. ROC analysis of screen-detected cancers yielded an AUC of 89% for AI-CAD. Sensitivity/specificity was 81.7%/80.2% for AI-CAD; 77.1%/91.7% for R1; 78.6/91.6% for R2. Combining each human reading with AI-CAD was as sensitive as human double-reading (all approximately 88%), but less specific (approximately 75%) compared to human double-reading (approximately 87%). These AI-CAD combinations required consensus readings for twice as many cases as the human combination. Four of 17 ICA exceeded a case score of 30; two of four CAD correctly marked the quadrant of the subsequent ICA. CONCLUSION: Including ICA cases, this AI-CAD achieved comparable sensitivity to human reading at lower specificity. Combining human reading and AI-CAD allows increasing sensitivity compared to single-reading.

The Role of Urine and Washing Cytology in Primary Transurethral Resection of Bladder Tumours.

INTRODUCTION: Urine cytology (UC) is a recommended tool for the diagnosis of urothelial malignancies. Thus far, no specific recommendations regarding the role of washing cytology (WC) have been included in the guidelines. The goal of our study was to analyse the relationship between the histology of transurethrally (transurethral resection of the bladder [TURBT]) resected bladder tumours (BCa) and intraoperative UC or WC findings. MATERIALS AND METHODS: Five hundred consecutive primary TURBT cases conducted between November 2010 and 2015 at our department of the University Hospital Luebeck were retrospectively analysed. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of UC and WC were evaluated to detect BCa. Multivariate logistic regression models were fit to further examine associations between patient- and tumour-related factors and a bladder UC or WC positive for BCa. RESULTS: UC was performed in 297 patients, WC in 294 patients, and both in 261 patients. Sensitivity was 50.7% in UC, 58.1% in WC, and 62.1% for both tests combined. Specificity was 97.8% for UC, 98.0% for WC, and 96.4% for the combined tests. PPV was 98.0% for UC, 98.1% for WC, and 97.2% for combined tests. NPV was 47.8% for UC, 54.5% for WC, and 55.9% for the combined tests. The multivariate analyses revealed no association between positive UC or WC results and subsequent radical cystectomy (UC OR 1.35, 95% CI: 0.3-5.7; WC OR 2.0, 95% CI: 0.4-11.4). Neither UC nor WC was significantly correlated with local recurrence. CONCLUSIONS: Cytologic testing is an important diagnostic tool in BCa detection, showing acceptable sensitivity of around 60% and excellent specificity of over 90%. UC and WC present similar sensitivity. Our results advocate, however, against cytologic testing during primary TURBT, especially with regard to the lack of value in assessing the risk of recurrence. The clinical benefit of taking both types of samples at once is minimal. Furthermore, intraoperative WC collection does not reliably predict subsequent cystectomies.

Survival of patients undergoing cardiac resynchronization therapy with or without defibrillator: the RESET-CRT project.

AIMS: Cardiac resynchronization therapy (CRT) is an established treatment for heart failure. There is contradictory evidence whether defibrillator capability improves prognosis in patients receiving CRT. We compared the survival of patients undergoing de novo implantation of a CRT with defibrillator (CRT-D) option and CRT with pacemaker (CRT-P) in a large health claims database. METHODS AND RESULTS: Using health claims data of a major German statutory health insurance, we analysed patients with de novo CRT implantation from 2014 to 2019 without indication for defibrillator implantation for secondary prevention of sudden cardiac death. We performed age-adjusted Cox proportional hazard regression and entropy balancing to calculate weights to control for baseline imbalances. The analysis comprised 847 CRT-P and 2722 CRT-D patients. Overall, 714 deaths were recorded during a median follow-up of 2.35 years. A higher cumulative incidence of all-cause death was observed in the initial unadjusted Kaplan-Meier time-to-event analysis [hazard ratio (HR): 1.63, 95% confidence interval (CI): 1.38-1.92]. After adjustment for age, HR was 1.13 (95% CI: 0.95-1.35) and after entropy balancing 0.99 (95% CI: 0.81-1.20). No survival differences were found in different age groups. The results were robust in sensitivity analyses. CONCLUSION: In a large health claims database of CRT implantations performed in a contemporary setting, CRT-P treatment was not associated with inferior survival compared with CRT-D. Age differences accounted for the greatest part of the survival difference that was observed in the initial unadjusted analysis.

Association of early-stage incidence and mortality in malignant melanoma - a population-based ecological study.

BACKGROUND: Germany-wide skin cancer screening was introduced in 2008 to reduce skin cancer mortality and morbidity. However, the effectiveness of the program is still unclear. We explore the relationship between early-stage melanoma incidence and melanoma mortality in subsequent years, using early-stage melanoma incidence as surrogate for screening participation and early detection. PATIENTS AND METHODS: Data on melanoma incidence for 2005-2016 and melanoma mortality for 2005-2018 were obtained for 244 German counties. We investigated the correlation between several measures of incidence and mortality with correlation analyses and linear regressions. RESULTS: Melanoma incidence of early stages (in situ and T1) rose by 69% between pre-screening (2005-2007) and screening period (2008-2010). In contrast, there was no temporal trend in mortality over time. Correlation coefficients between incidence and mortality variables ranged between -0.14 and 0.10 (not significant). Linear regression indicated that mortality 6 years after screening introduction decreases with increasing change in early-stage incidence (b = -0.0029, 95% confidence interval [-0.0066, 0.0007]). CONCLUSIONS: The estimated population-based effects of skin cancer screening on melanoma mortality were minimal and not significant. A potential effectiveness cannot be demonstrated.

Evaluation of skin cancer screening in Germany - Spatiotemporal associations between skin cancer screening and skin cancer mortality based on ambulatory claims data.

BACKGROUND: There are regional differences in skin cancer screening uptake in Germany. So far, it is unclear whether a high uptake of screening services leads to a reduction in mortality. This article presents study results on the investigation of spatiotemporal associations between skin cancer screening and mortality. The methods used are discussed regarding their suitability. MATERIAL AND METHODS: The basis is ambulatory claims data on the utilization of early skin cancer detection as well as data on skin cancer mortality from the cause-of-death statistics of the years 2011-2015 at county level in Germany. In addition to a descriptive evaluation, spatiotemporal cluster analyses and regression models were used to investigate the relationship between the uptake of early detection and mortality. In addition to age, adjustments were also made for other selected socio-economic and socio-graphical variables. RESULTS: The descriptive results show striking spatial patterns of skin cancer screening and mortality. Cluster analyses identified regions with significantly higher and lower cases of early detection and skin cancer mortality. The spatiotemporal regression analyses show no clear association. Only early detection by a dermatologist, adjusted for age, shows an association with mortality. CONCLUSIONS: No clear association between early skin cancer detection and mortality can be derived from the results. However, the study design used with a spatiotemporal cluster and regression analysis has shown that these methods allow in-depth statements about the relationship between early skin cancer detection and mortality.

Evaluation of early skin cancer detection in Germany with cancer registry data - challenges, solutions and current trends.

BACKGROUND AND AIMS: The evidence for the benefit of the skin cancer screening introduced in Germany in 2008 is weak. We investigate to what extent data from the German epidemiological cancer registries are suitable to contribute to the evaluation of skin cancer screening and report these evaluation results. MATERIAL AND METHODS: Skin cancer-related cancer registry data from 1999-2019 were described in terms of completeness and comprehensiveness. Regional pools with data of different validity were defined, missing data were multiply imputed where appropriate, and temporal trends were analyzed. In addition, data from the cause of death statistics were used. RESULTS: Reliable estimates of completeness are only available for malignant melanoma (ICD-10: C43). Based on a regional data pool covering approximately 21% of the German population, melanoma-related incidence can be validly described since 2005. Sufficient information for multiple imputation is available for T-stage and localization. The trend analyses show incidence changes that can be expected in the short term in the temporal context of the introduction of early detection, which changes into a long-lasting high incidence. The rate of advanced stages does not decrease significantly. From 2014 onwards, the melanoma mortality rate, which had been rising until then, decreases. CONCLUSIONS: Adequately selected and processed cancer registry data are suitable for population-based evaluation of skin cancer screening. An explanation of the persistently high incidence level is not possible based on the cancer registry data. Overdiagnosis or an increase in the background incidence can be considered. The benefit of skin cancer screening remains open.

Evaluation of skin cancer screening in Germany - participation, tumor detection and interval tumors based on SHI data.

BACKGROUND AND GOALS: The rising incidence of skin cancer in Germany has increased the need for secondary prevention measures. For this purpose, a statutory skin cancer screening for insured persons aged 35 and older was introduced on 1 June 2008. The aim of this work package in the Innovation Fund project "Perspectives of a multimodal evaluation of early skin cancer detection" (Pertimo) was to test an evaluation of skin cancer screening using secondary data. PATIENTS AND METHODS: The data basis was statutory insured persons of the DAK Health from the age of 35 who were insured as of 31 December 2010 and were followed up until the end of 2015. The rates of participation, skin tumors detected in skin cancer screening (tumor detections), and interval tumors that occurred within two years after a finding-free skin cancer screening were calculated. RESULTS: The biennial skin cancer screening take-up rate in 2014 and 2015 was 33.6% for women and 32.6% for men. Of those screened, 4.2% had a skin cancer finding (tumor detection) in the course of skin cancer screening. Of all incident skin cancer diagnoses (2012-2015), 50.1% were detected in skin cancer screening. In 1.5% of the insured persons with skin cancer screening without findings, an incidental skin tumor was diagnosed in the following two years (interval tumor). CONCLUSIONS: The data from the statutory health insurance mapped the skin cancer screening occurrence in Germany and highlighted the importance of dermatologists in the screening process. The analysis provided important new insights.

Chinese never smokers with adenocarcinoma of the lung are younger and have fewer lymph node metastases than smokers.

BACKGROUND: Lung cancers arising in never smokers have been suggested to be substantially different from lung cancers in smokers at an epidemiological, genetic and molecular level. Focusing on non-small cell lung cancer (NSCLC), we characterized lung cancer patients in China looking for demographic and clinical differences between the smoking and never-smoking subgroups. METHODS: In total, 891 patients with NSCLC, including 841 with adenocarcinoma and 50 with squamous cell carcinoma, were recruited in this study. Association of smoking status with demographic and clinical features of NSCLC was determined, and risk factors for lymph node metastasis and TNM stage were evaluated using Multivariate logistic regression analysis. RESULTS: In patients with adenocarcinoma, never smokers showed a younger age at diagnosis (54.2 ± 12.7vs. 59.3 ± 9.4, padjusted<0.001), a lower risk for lymph node metastasis than smokers (7,6% vs. 19.5%, padjusted<0.001) and less severe disease as indicated by lower percentages of patients with TNM stage of III or IV (5.5% vs. 14.7%, padjusted<0.001 ). By contrast, these associations were not observed in 50 patients with squamous cell carcinoma. Multivariate logistic regression analysis showed that smoking status was a risk factor for lymph node metastasis (OR = 2.70, 95% CI: 1.39-5.31, p = 0.004) but not for TNM stage (OR = 1.18, 95% CI: 0.09-14.43, p = 0.896) in adenocarcinoma. CONCLUSION: This study demonstrates that lung adenocarcinoma in never smokers significantly differ from those in smokers regarding both age at diagnosis and risk of lymph node metastasis, supporting the notion that they are distinct entries with different etiology and pathogenesis.

A critical appraisal of safety data on dydrogesterone for the support of early pregnancy: a scoping review and meta-analysis.

No data support the suggestion that first-trimester dydrogesterone use increases the risk of fetal abnormalities; however, two low-quality retrospective studies (one retracted by the journal) have suggested such a link. A scoping review and meta-analysis were carried out to address this discrepancy. The literature was reviewed but it was not possible to identify any evidence of a plausible mechanism for potential causality between dydrogesterone and fetal abnormalities. To investigate whether any evidence existed, a preliminary meta-analysis was undertaken of clinical studies published since 2005 on first-trimester dydrogesterone use with assessment of fetal abnormalities. A fixed effects model was used to determine pooled odds ratios with 95% confidence intervals (95% CI). From 83 articles identified, six randomized controlled trials were included. Pooled risk ratios (RR) for maternal dydrogesterone use and fetal abnormalities gave a RR approaching 1 (RR 0.96; 95% CI 0.57, 1.62), confirming previous conclusions of no causal association between fetal abnormalities and first-trimester dydrogesterone use. Physicians, scientists and journal reviewers should exercise due diligence to prevent promulgation of retracted data. We are confident in using dydrogesterone, if indicated, in the treatment of threatened or recurrent miscarriage, and believe that its favourable safety profile should extend to its appropriate use in assisted reproductive technologies.

Impact of COVID-19 crisis on medical care of patients with metastasized uro-oncologic disease under systemic cancer therapy: a multicenter study in German university hospitals.

PURPOSE: To date, over 4.2 million Germans and over 235 million people worldwide have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Uro-oncology (UO) patients are particularly vulnerable but in urgent need of life-saving systemic treatments. Our multicentric study examined the impact of the COVID-19 crisis on the medical care of UO patients in German university hospitals receiving ongoing systemic anti-cancer treatment and to detect the delay of medical care, defined as deferred medical treatment or deviation of the pre-defined follow-up assessment. METHODS: Data of 162 UO patients with metastatic disease undergoing systemic cancer treatment at five university hospitals in Germany were included in our analyses. The focus of interest was any delay or change in treatment between February 2020 and May 2020 (first wave of the COVID-19 crisis in Germany). Statistical analysis of contingency tables were performed using Pearson's chi-squared and Fisher's exact tests, respectively. Effect size was determined using Cramér's V (V). RESULTS: Twenty-four of the 162 patients (14.8%) experienced a delay in systemic treatment of more than 2 weeks. Most of these received immuno-oncologic (IO) treatments (13/24, 54.2%, p = 0.746). Blood tests were delayed or canceled significantly more often in IO patients but with a small effect size (21.1%, p = 0.042, V = 0.230). Treatment of patients with renal cell carcinoma (12/73, 16.4%) and urothelial carcinoma (7/32, 21.9%) was affected the most. CONCLUSIONS: Our data show that the COVID-19 pandemic impacted the medical care of UO patients, but deferment remained modest. There was a tendency towards delays in IO and ADT treatments in particular.

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.

Protocol of the Luebeck longitudinal investigation of SARS-CoV-2 infection (ELISA) study - a prospective population-based cohort study.

BACKGROUND: Considering the insufficiently controlled spread of new SARS-CoV-2 variants, partially low vaccination rates, and increased risk of a post-COVID syndrome, well-functioning, targeted intervention measures at local and national levels are urgently needed to contain the SARS-CoV-2 pandemic. Surveillance concepts (cross-sectional, cohorts, clusters) need to be carefully selected to monitor and assess incidence and prevalence at the population level. A critical methodological gap for identifying specific risks/dynamics for SARS-Cov-2 transmission and post-COVID-19-syndrome includes repetitive testing for past or present infection of a defined cohort with simultaneous assessment of symptoms, behavior, risk, and protective factors, as well as quality of life. METHODS: The ELISA-Study is a longitudinal, prospective surveillance study with a cohort approach launched in Luebeck in April 2020. The first part comprised regular PCR testing, antibody measurements, and a recurrent App-based questionnaire for a population-based cohort of 3000 inhabitants of Luebeck. The follow-up study protocol includes self-testing for antibodies and PCR testing for a subset of the participants, focusing on studying immunity after vaccination and/or infection and post-COVID-19 symptoms. DISCUSSION: The ELISA cohort and our follow-up study protocol will enable us to study the effects of a sharp increase of SARS-CoV-2 infections on seroprevalence of Anti-SARS-CoV-2 antibodies, post-COVID-19-symptoms, and possible medical, occupational, and behavioral risk factors. We will be able to monitor the pandemic continuously and discover potential sequelae of an infection long-term. Further examinations can be readily set up on an ad-hoc basis in the future. Our study protocol can be adapted to other regions and settings and is transferable to other infectious diseases. TRIAL REGISTRATION: DRKS.de, German Clinical Trials Register (DRKS), Identifier: DRKS00023418 , Registered on 28 October 2020.

[Linkage of claims data with data from epidemiological cancer registries: possibilities and limitations in the German federal states]. / Verknüpfung von Abrechnungsdaten gesetzlicher Krankenkassen mit Daten epidemiologischer Krebsregister: länderspezifische Möglichkeiten und Limitationen.

BACKGROUND: In recent years, there has been an increasing demand for the reuse of research data in accordance with the so-called FAIR principles. This would allow researchers to conduct projects on a broader data basis and to investigate new research questions by linking different data sources. OBJECTIVES: We explored if nationwide linking of claims data from statutory health insurances (SHI) with data from population-based cancer registries can be used to obtain additional information on cancer that is missing in claims data and to assess the validity of SHI tumour diagnoses. This paper focuses on describing the specific requirements of German federal states for such data linkage. MATERIALS AND METHODS: The Pharmacoepidemiological Research Database GePaRD at the Leibniz Institute for Prevention Research and Epidemiology - BIPS and six cancer registries were used as data sources. The logistically complex direct linkage was compared with a less complex indirect linkage. For this purpose, permission had to be obtained for GePaRD and for each cancer registry from the respective responsible authority. RESULTS: Regarding the linkage of cancer registry data with GePaRD, the cancer registries showed profound differences in the modalities for data provision, ranging from a complete rejection to an uncomplicated implementation of linkage procedures. DISCUSSION: In Germany, a consistent legal framework is needed to adequately enable the reuse and record linkage of personal health data for research purposes according to the FAIR principles. The new law on the consolidation of cancer registry data could provide a remedy regarding the linkage of cancer registry data with other data sources.