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Simple Summary: Cancer registration has a long tradition in Germany. In 2013, new legislation obliged all German states to implement additional clinical cancer registration, including standardised documentation of all therapies, recurrences and further follow-up. The overall aim was to use cancer registry data to measure and improve the quality of cancer care. Now, 10 years later, the status of the extended cancer registration will be presented. In 2019, more than 500,000 new cancer cases were reported to the federal cancer registries. Age-standardised incidence has decreased slightly over the last decade. The five-year relative survival rate for all cancers was 67% for women and 63% for men. Therapy data show that an evidence-based assessment of quality of cancer care, including provider-based benchmarking, is feasible. Feedback of such results directly to healthcare providers should further improve cancer care. In conclusion, the introduction of population-based clinical cancer registration in Germany can be considered a success. Introduction: In 2013, a new federal law obligated all German federal states to collect additional clinical data in population-based cancer registries as an active tool for monitoring and improving the quality of cancer care, increasing transparency and promoting health research. Now, 10 years later, the current status of the expanded cancer registration is presented, including current figures on cancer in Germany. Methods: Reporting of cancer is mandatory for physicians, and about 5 to 10 reports from different healthcare providers are expected for each case. A uniform national dataset of about 130 items is used, and reports are usually sent electronically to the registry. We used the most recent data available from cancer registries up to the year of diagnosis in 2019. We calculated incidence rates and 5-year relative survival (5YRS) for common cancers. Data on clinical outcomes and benchmarking based on quality indicators (QIs) from guidelines were provided by the Cancer Registry Schleswig-Holstein (CR SH). Results: All federal state cancer registries met most of the previously defined national eligibility criteria. Approximately 505,000 cancer cases were registered in 2019, with breast, prostate, colorectal and lung cancer being the most common cancers. The age-standardised cancer incidence has slightly decreased during the last decade. and spatial heterogeneity can be observed within Germany. 5YRS for all cancers was 67% and 63% for women and men, respectively. Therapy data for rectal cancer in 2019–2021 from the CR SH are shown as an example: 69% of the registered patients underwent surgery, mostly with curative intent (84%) and tumour-free resection (91%). Radiotherapy was given to 33% of the patients, and chemotherapy was given to 40%. Three selected QIs showed differences between involved healthcare providers. Discussion: The implementation of population-based clinical cancer registration can be considered a success. Comprehensive recording of diagnosis, treatment and disease progression and the use of registry data for quality assurance, benchmarking and feedback have been implemented. [ABSTRACT FROM AUTHOR]

Cutaneous squamous cell carcinoma (cSCC) incidences are increasing but scarcely available separated. We analysed incidence rates of cSCC over three decades with an extrapolation to 2040. Cancer registries from the Netherlands, Scotland and two federal states of Germany (Saarland/Schleswig-Holstein) were sourced for separate cSCC incidence data. Incidence and mortality trends between 1989/90 and 2020 were assessed using Joinpoint regression models. Modified age-period-cohort models were applied to predict incidence rates up to 2044. Rates were age-standardised using the new European standard population (2013). Age-standardised incidence rates (ASIR, per 100,000 persons per year) increased in all populations. The annual percent increase ranged between 2.4% and 5.7%. The highest increase occurred in the age groups ≥60 years, especially in men aged ≥80 years, with a three to 5-fold increase. Extrapolations up to 2044 showed an unrestrained increase in incidence rates in all countries investigated. Age-standardised mortality rates (ASMR) showed slight increases between 1.4 and 3.2% per year in Saarland and Schleswig-Holstein for both sexes and for men in Scotland. For the Netherlands, ASMRs remained stable for women but declined for men. There was a continuous increase of cSCC incidence over three decades with no tendency for levelling-off, especially in the older populations as males ≥80 years. Extrapolations point to a further increasing number of cSCC up to 2044, especially among ≥60 years. This will have a significant impact on the current and future burden on dermatologic health care which will be faced with major challenges. • Age standardised incidence rates separated of cutaneous squamous cell carcinoma from four European registries were analysed. • An annual increase between +2.4% and +5.7% was observed over three decades. • Highest increases occurred in ages ≥60, especially in men ≥80. • Age-standardised mortality rates are rising in Germany and Scotland. • In extrapolations until 2044, an increase up to 5-fold in ages ≥60 is expected. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and purpose: Some groups of cardiovascular drugs (beta‐blocking drugs, Ca antagonists, antiarrhythmics) are listed as potentially worsening myasthenia. An empirical basis for alternative recommendations for antihypertensive and antiarrhythmic therapy in myasthenia patients has not yet been provided. Methods: From the World Health Organization pharmacovigilance database, we retrieved total and myasthenia‐related counts of adverse drug reactions for various groups of drugs used in cardiovascular disease and drugs with related mechanism of action used in other indications. We calculated the reporting odds ratio as a measure of a disproportional fraction of myasthenia‐related events among all events. A 95% confidence interval of reporting odds ratio (ROR) >1 was taken as an indication for a higher risk. Because our approach involves a considerable number of tests, this situation is referred to as a signal that requires additional confirmation. Results: A signal for an increased risk was noted for tizanidine, for alpha‐blocking drugs, for beta‐blocking drugs, and for Ca antagonists. ROR indicated a lower‐than‐average risk for salbutamol, angiotensin receptor antagonists, oral anticoagulants, thrombocytic function inhibitors, and heparins. Conclusions: Angiotensin receptor antagonists, angiotensin‐converting enzyme inhibitors, and diuretics seem to be safe in antihypertensive therapy. Surprisingly, and yet requiring confirmation by case reports, alpha receptor–blocking drugs seem to carry a risk of myasthenia worsening. Amiodarone seems to be a safe alternative in antiarrhythmic therapy in patients with myasthenia. [ABSTRACT FROM AUTHOR]

Background and purpose: Many drugs can worsen myasthenia symptoms. The clinician usually relies on cautionary lists compiled according to case reports. We intended to provide a quantitative basis for a risk comparison within the groups of antiepileptic, antidepressant, neuroleptic, and sedative drugs. Methods: We extracted adverse drug reaction (ADR) counts (total and myasthenia related) for drugs from these groups and calculated the reporting odds ratio (ROR) within the drug groups from the World Health Organization pharmacovigilance database. For a given drug, the ROR was increased above 1 if the proportion of myasthenia‐related ADRs for this drug was larger than the same proportion for the rest of drugs in that same group. If the 95% confidence interval of ROR was >1, this was taken as a signal for a higher risk of the given drug as compared to the average of the respective group. Results: Gabapentin, sertraline, citalopram, lithium, and amisulpride had a signal for the ROR to be increased above 1 within their respective groups. Bupropion, desvenlafaxine, duloxetine, escitalopram, and paroxetine had ROR values <1. For all other drugs, 1 was within the ROR confidence interval. Conclusions: For gabapentin and lithium, the analysis of RORs confirmed case reports and cautionary lists. For a number of antidepressant drugs associated with a higher‐than‐average risk, no case reports exist substantiating our results. For these drugs, special attention should be paid to this risk. The remarkable difference between citalopram and escitalopram could prompt experimental work to confirm differential influence of the two preparations on neuromuscular transmission. [ABSTRACT FROM AUTHOR]

Are there differences in the cardiometabolic health of ICSI-conceived adolescents compared with a control group, taking parental risk factors into account? ICSI-conceived adolescents (n = 272), their mothers (n = 273) and naturally conceived control adolescents (n = 273) and their mothers (n = 273) provided a blood test and answered a health-related questionnaire. The adolescents also attended a physical examination. ICSI-conceived males showed significantly higher mean weight (72.6 ± 15.1 versus 67.7 ± 12.6 kg, P = 0.005), body mass index (BMI) (22.2 ± 3.7 versus 21.0 ± 3.2 kg/m2, P = 0.007) and waist circumference (79.1 ± 11.6 versus 74.5 ± 8.7 cm, P < 0.001). The mean values for weight and BMI were also significantly higher in the ICSI parents. In the ICSI-conceived females significant differences in high-density lipoprotein cholesterol (1.5 ± 0.3 versus 1.6 ± 0.3 mmol/l, P = 0.033) and triglyceride values (1.1 ± 0.5 versus 1.0 ± 0.4 mmol/l, P = 0.013) were observed. ICSI mothers also had significantly higher triglycerides (P = 0.002), higher glutamate pyruvate transaminase/alanine aminotransferase (P < 0.001) and higher alkaline phosphatase values (P < 0.001). Increased values for weight were found in the male and differences in lipid parameters in the female ICSI-conceived adolescents, which were reflected in the values of their parents. Adjustment for parental risk factors generally attenuated the differences between the ICSI and the control groups, but did not completely remove them. Whether these observed differences are clinically relevant for the future health of the participants requires further study. To increase knowledge in this area, future studies should also include parental data. [ABSTRACT FROM AUTHOR]

Simple Summary: The incidence of keratinocyte skin cancer has rapidly been increasing over the last five decades in fair skinned populations throughout the world. About 20% account for squamous cell carcinoma (SCC), and mainly the elderly are affected. Although the mortality rate is low, keratinocyte skin cancer is associated with a high morbidity, especially if multiple tumors occur, and pose a problem for the healthcare system. Here, we present the epidemiology of keratinocyte skin cancer, with a focus on SCC in Queensland, Australia; the United States and the north of Europe, and give an outlook to further challenges. Keratinocyte skin cancer, consisting of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), is by far the most common cancer in white-skinned populations, with rapid increases over the last 50 years. While the age-standardized incidence rates increase worldwide, the age-standardized mortality rates are variable. The incidence rates of keratinocyte skin cancer are much higher compared to those of melanoma, and are largely attributed to the raising exposure to ultraviolet (UV) radiation, the most important causal risk factor for skin cancer. Whereas the development of BCC is mainly due to intense UV exposure during childhood and adolescence, the development of SCC is related to chronic, cumulative UV exposure over decades. Although mortality rates are relatively low, SCC is an increasing problem for healthcare services, significantly causing morbidity, especially in older age groups. This review reports on the epidemiology of keratinocyte skin cancer, with a focus on SCC, in Australia, the United States, and the north of Europe, with an outlook on further challenges health systems will be confronted with in the next 20 years. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Constituting 25-30 % of all head and neck cancer cases, laryngeal carcinoma is the most prevalent entity. Major risk factors of laryngeal cancer are smoking and excessive alcohol consumption. This study presents the recent developments in the incidence of laryngeal cancer from 1998 to 2011 in Germany. Laryngeal carcinoma was identified using International Statistical Classification of Diseases and Related Health Problems (ICD10) from German population-based cancer registries. The incidence was provided by the Robert Koch Institute, and the mortality data were derived from German death statistics for further evaluation. Both descriptive and analytical analyses were conducted. From 1998 to 2011, a total of 14,847 laryngeal carcinoma cases were reported, in 13,195 men and 1652 women. Glottic carcinoma represented the main entity, constituting 69 % of male cases and 50 % of female cases. For men, a decline in incidence was observed starting in 2006. The incidence rate for women remained stable for the period of observation. The incidence of laryngeal cancer resembles the development of smoking behaviour in Germany. To maintain the positive trend of the male population and to reduce the incidence in women, it is crucial to continue and to improve the prevention of smoking campaigns in Germany. [ABSTRACT FROM AUTHOR]

Purpose The aim of this cross-sectional health care study (use of bisphosphonates in primary tumors of the mammae, EBisMa) is to determine how often bisphosphonate medication is used in patients with non-metastatic primary breast cancer treatment, but who do not suffer from osteoporosis. Furthermore, we describe patients' characteristics and the most frequently used type of bisphosphonate in adjuvant therapy. Materials and Methods The study population included primary breast cancer patients of four breast centers in northern Germany. Data on bisphosphonate therapy were collected by use of patient questionnaires; clinical data were extracted from the registers. Patients with and without prescribed bisphosphonate adjuvant treatment were tested for statistically significant differences regarding their characteristics. Results Four hundred seventy-four of 663 contacted patients participated in the study. Thirty-nine out of 474 patients (9.6%) were on adjuvant bisphosphonate therapy. Zoledronic acid was the most frequently reported bisphosphonate used for prevention of bone metastases. Compared to patients who did not report bisphosphonate medication, women who did report bisphosphonate therapy had a significantly higher advanced tumor stage (p < 0.001). Both the T2-T4 stage and N+ stage remained significant predictors in multivariate-adjusted regression models. Conclusion Bisphosphonates are rarely used in the adjuvant treatment of primary breast cancer. Patients with advanced tumor stage were more likely to use bisphosphonates in the adjuvant treatment of primary breast cancer. Further research is needed to identify patients who may benefit most from adjuvant bisphosphonate treatment. [ABSTRACT FROM AUTHOR]

BACKGROUND: From July 1, 2003 to June 30, 2004, a population-based skin cancer screening project was conducted in Schleswig-Holstein, Germany. In total, 360,288 individuals aged ≥20 years were screened by means of a whole-body examination. In this report, the authors compare trends in melanoma mortality in Schleswig-Holstein with those in all adjacent regions, none of which had population-based skin cancer screening. METHODS: Trends in melanoma mortality rates for Schleswig-Holstein and the adjacent regions (Denmark and the German federal states of Mecklenburg-Vorpommern, Hamburg, and Lower Saxony) and in Germany excluding Schleswig-Holstein were compared. Log-linear regression was used to assess mortality trends. RESULTS: In Schleswig-Holstein during the pre skin cancer screening period (1998-1999), the age-standardized melanoma mortality rate (World standard population) was 1.9 per 100,000 for men and 1.4 per 100,000 for women. Melanoma mortality declined by 47% to 1.0 per 100,000 men and by 49% to 0.7 per 100,000 women by 2008/2009. The annual percentage change in the most recent 10-year period (2000-2009) was −7.5% (95% confidence interval, −14.0, −0.5) for men and −7.1% (95% confidence interval, −10.5, −2.9) for women. In each of the 4 adjacent regions and in the rest of Germany, mortality rates were stable, and the decline in Schleswig-Holstein was significantly different from the changes observed in all of the other areas studied. CONCLUSIONS: The current data represent strong evidence, but not absolute proof, that the skin cancer screening program produced a reduction in melanoma mortality in Schleswig-Holstein. Cancer 2012. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Scientists, physicians, and the general public legitimately expect scholarly publications to give true answers to study questions raised. We investigated whether findings from studies published in journals with higher Journal Impact Factors (JIFs) are closer to truth than findings from studies in less-cited journals via a meta-epidemiological approach. Methods: We screened intervention reviews from the Cochrane Database of Systematic Reviews (CDSR) and sought well-appraised meta-analyses. We used the individual RCT study estimates' relative deviation from the pooled effect estimate as a proxy for the deviation of the study results from the truth. The effect of the JIF on the relative deviation was estimated with linear regression and with local polynomial regression, both with adjustment for the relative size of studies. Several sensitivity analyses for various sub-group analyses and for alternative impact metrics were conducted. Results: In 2459 results from 446 meta-analyses, results with a higher JIF were on average closer to "truth" than the results with a lower JIF. The relative deviation decreased on average by −0.023 per JIF (95% CI −0.32 to −0.21). A decrease was consistently found in all sensitivity analyses. Conclusions: Our results indicate that study results published in higher-impact journals are on average closer to truth. However, the JIF is only one weak and impractical indicator among many that determine a studies' accuracy. [ABSTRACT FROM AUTHOR]

Abstract: Background: Currently, only 7 out of 16 Federal States of Germany provide testicular cancer incidence rates with an estimated completeness of at least 90% which complicates the regional comparison of incidence rates. The aim of this study was to provide a novel approach to estimate the testicular cancer incidence in Germany by using nationwide hospitalization data. Methods: We used the nationwide hospitalization data (DRG statistics) of the years 2005–2006 including 16,6 million hospitalizations among men. We identified incident testicular cancer cases by the combination of a diagnosis of testicular cancer and an orchiectomy during the same hospitalization and estimated the age-specific and age-standardized (World Standard Population) incidence of testicular cancer across Federal States. We also analyzed available cancer registry data from 2005 to 2006. Results: A total of 8544 hospitalizations indicated incident testicular cancer cases in 2005–2006. The nationwide crude incidence rate of testicular cancer was 10,6 per 100.000 person-years. The ratio of the number of registered cases (cancer registry) to the estimated number of cases based on the hospitalization statistics ranged between 79% and 100%. There was only little variation of the age-standardized DRG-based incidence estimates across Federal States (range: 8,2–10,6 per 100.000 person-years). Discussion: We provided testicular cancer incidence estimates for each of the 16 Federal States of Germany based on hospitalization data for the first time. The low within-population incidence variability in Germany and high between-population incidence variability in Europe may indicate that ecologic factors play a causal role in the European variation of testicular cancer. [Copyright &y& Elsevier]

Objective: To assess the neurodevelopmental health of children born after intracytoplasmatic sperm injection (ICSI). Design: Prospective controlled blinded study. Setting: Tertiary care center. Patient(s): A total of 276 term-born singletons conceived by ICSI and 273 matched spontaneously conceived (SC) singletons at the age of 5.5 years. Main Outcome Measure(s): Neuromotor development assessed by a detailed neurologic examination, including the standardized motor test MOT 4–6, and emotional/behavioral development and intelligence assessed with the Kaufman-Assessment Battery for Children. Result(s): There were no significant differences between ICSI children and control children regarding the neurologic examination, motor skills, emotional/behavioral development, and intelligence. Conclusion(s): The ICSI children born at term develop normally, similar to SC children. [Copyright &y& Elsevier]

Objective: To study the health of children born after ICSI and of spontaneously conceived control children at the age of 4–6 years. Design: Prospective, controlled, blinded study. Setting: Tertiary-care center. Patient(s): Two hundred seventy-six term-born singletons conceived by ICSI and 273 matched spontaneously conceived singletons at the age of 5.5 years. Intervention(s): Detailed physical examination, interview of the parents, and collection of data from each child''s examination booklet. Main Outcome Measure(s): Biometrical data; current health status; acute, chronic and childhood illnesses; hospitalizations; and surgeries. Result(s): Detailed physical examination did not reveal any relevant differences between ICSI and spontaneously conceived children. There were no relevant differences regarding the incidence of childhood illnesses, acute or chronic illnesses, accidents, and surgeries up to the age of 5.5 years. However, a history of undescended testicles was found significantly more often in boys born after ICSI (5.4% vs. 0.7%), with the consequence that they had significantly more urogenital surgery (19.2% vs. 8.9%). Significantly more ICSI children had been hospitalized (37.6% vs. 27.2%), although we did not find any specific reason for the increased hospitalization rate. Conclusion(s): Other than an increased risk of undescended testicles and therefore an increase in urogenital surgeries in ICSI boys, the physical health of ICSI children was comparable to that of spontaneously conceived children at the age of 5.5 years. [Copyright &y& Elsevier]

In the TeleGuard trial, 1500 patients with established coronary artery disease (CAD) were recruited and randomized to control or intervention groups. Patients in the intervention group were equipped with a 12-lead event recorder and could contact a call centre and transmit an ECG whenever they wished. In a 12-month study, the composite endpoint (all-cause mortality, myocardial infarction, re-hospitalization or re-vascularization) was seen in 40% of the intervention patients and in 38% of the control patients. In both groups, approximately 40% were re-hospitalized. In total, 73 patients experienced re-vascularization, 75 showed an infarction and 33 died. Equipping CAD patients with a 12-lead ECG device and providing a telemedicine centre with 24-hour availability did not decrease risk for the composite endpoint (re-hospitalization, re-vascularization, (subsequent) myocardial infarction and/or death). It is likely that the clinical pathway used in the telemedicine centre led to an increased hospital admission rate in the intervention group. [ABSTRACT FROM AUTHOR]

Patients with established coronary artery disease (CAD) were recruited in 11 hospitals and randomized to an intervention (telemedicine system; n = 752) or a control group (usual medical care; n = 748). On the day before discharge, patients in the intervention group were equipped with a 12-lead event recorder and trained to use the device. Whenever they had symptoms, they could contact the call centre, transmit an ECG (without redialling) and consult a physician. During a 12-month study, 171 patients (23%) in the intervention group contacted the call centre, a total of 269 times. The main reasons for calling were chest pain and radiating pain. Pathological changes were seen in 24% of the transmitted ECGs. Only 23% of the calls were made in the first hour after onset of symptoms and a further 12% in the subsequent hour, suggesting that patients should be encouraged to use ECG transmission at an earlier stage. At follow-up, 157 patients (21%) had had at least one recurrent cardiac event (myocardial infarction, cardiac hospital stay, re-vascularization). The proportion was significantly higher in telemedicine users (35%) than in non-users (17%), P < 0.001. Regardless of utilization, the majority of the intervention patients considered that the telemedicine system was helpful (users = 93%, non-users = 89%; P = 0.095). [ABSTRACT FROM AUTHOR]

A 12-lead electrocardiogram (ECG) recorded in patients with acute coronary syndrome (ACS) was transmitted to a call centre via telephone (tele-ECG). In 120 patients (mean age 64 years) referred to hospitals because of ACS, a standard 12-lead ECG and a tele-ECG recorded at the same time were compared by two cardiologists and one internist independently and blindly. Conduction times exhibited very good agreement between standard and tele-ECG with reliability coefficients (R) of 0.91, 0.86 and 0.89 for the PQ-, QRS- and QT interval, respectively. Rhythm analysis was correct in 99% of the cases. Negative T waves, ST-segment elevation and depression were detected with very high agreement in the tele-ECG exhibiting kappa (κ) coefficients between 0.75 and 0.96. The correct ECG diagnosis of ST-elevation myocardial infarction (STEMI) was possible with excellent agreement between standard and tele-ECG, showing κ coefficients of 0.96, 0.99 and 0.99, respectively, for three investigators. The 12-lead tele-ECG recorder proved accurate for the detection of acute STEMI. [ABSTRACT FROM AUTHOR]

We compared a 12-lead electrocardiogram (ECG) recorded by the patient and transmitted to a cardiology call centre via telephone (tele-ECG) with a standard 12-lead ECG recorded from the same patient at the same time. In 158 patients, tele-ECGs were compared with standard ECGs by two cardiologists and one internist, independently and blindly. In 14 patients peripheral electrodes were displaced, and in 12 patients there were baseline artefacts. These technical errors were corrected by telephone communication in all but two individuals. One patient could not use the tele-ECG device because of disability. Hence, in 155 of 158 patients (98%), the quality of the tele-ECG was adequate for diagnosis. Reliability coefficients (R) for PQ, QRS and QT intervals between tele- and standard ECG were high, with R values of 0.73, 0.75 and 0.79, depending on the physician. Negative T-waves could be detected with very good agreement in the tele-ECG as compared with the standard ECG (kappa values of 0.97, 0.95 and 0.94). The agreement between tele- and standard ECG concerning alterations of the ST segment was very good (kappa =0.99 for all investigators). Residual signs of myocardial infarction could be detected by tele-ECG, with very good agreement for anterior as well as for posterior localizations (kappa =0.99 and 1.00). The tele-ECG technique seems a promising approach to reducing pre- and in-hospital time delays to the initiation of thrombolytic therapy. [ABSTRACT FROM AUTHOR]

Objective: To determine pregnancy course and major malformation rate after intracytoplasmic sperm injection (ICSI).Design: Prospective, controlled, multicenter, nationwide German cohort study.Setting: Tertiary infertility centers in Germany.Patient(s): Three thousand three hundred seventy-two children and fetuses and 8,016 children and fetuses after the 16th week of gestation in pregnancies after ICSI and natural conception, respectively.Intervention(s): Standardized prospective follow-up.Main outcome measure(s): Major malformation rate.Result(s): The major malformation rate was 8.7% (295/3,372) for the ICSI cohort and 6.1% (488/8,016) for the population-based control cohort (relative risk, 1.44 [1.25–1.65]). After adjustment for risk factors, the risk declined (adjusted odds ratio, 1.24 [95% CI, 1.02–1.50]). Regarding singletons, there was a significant difference for birth weight and gestational age, with a higher number of preterm and low birth weight children in pregnancies achieved after ICSI.Conclusion(s): Children who are born after intracytoplasmic sperm injection have an increased risk of a major congenital malformation compared with those born after spontaneous conception. This risk is mainly due to paternal and maternal risk factors, which are more prevalent in couples who use ICSI for reproduction. An infertility-linked risk is highly probable for the observed findings. A technique-related risk, however, cannot be ruled out. [Copyright &y& Elsevier]

Presents a study which examined conflicting data on malformation rate in children born after intracytoplasmic sperm injection (ICSI). Treatment of severe male factor infertility using ICSI; Materials and methods used; Examination procedure and data assessment during child examination; Results of the study.

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. [ABSTRACT FROM AUTHOR]

In a prospective, controlled, blinded follow-up study of children born after intracytoplasmic sperm injection (ICSI), blinded examiners correctly intuited the mode of conception (ICSI versus spontaneous) in three out of four children, which must be considered when interpreting outcome data for children born after assisted reproduction. [ABSTRACT FROM AUTHOR]

Simple Summary: An important component in the study of survival in breast cancer patients is how the tumor is detected. This involves examining whether and to what extent survival differs when the tumor is detected, for example, by screening or by symptoms. In such an analysis, it is important to note that survival times are influenced by several biases. One important factor is the bias due to the so-called lead time, i.e., the time by which the diagnosis has been brought forward by screening. Therefore, survival may appear to be longer even if earlier diagnosis did not affect disease progression. We examine whether there is a remaining survival difference after correction for bias that could be attributable to the mode of detection, for example, because of higher quality of care. These results can then be used to further improve the survival of breast cancer patients. (1) Background: Screen-detected breast cancer patients tend to have better survival than patients diagnosed with symptomatic cancer. The main driver of improved survival in screen-detected cancer is detection at earlier stage. An important bias is introduced by lead time, i.e., the time span by which the diagnosis has been advanced by screening. We examine whether there is a remaining survival difference that could be attributable to mode of detection, for example, because of higher quality of care. (2) Methods: Women with a breast cancer (BC) diagnosis in 2000–2022 were included from a population-based cancer registry from Schleswig-Holstein, Germany, which also registers the mode of cancer detection. Mammography screening was available from 2005 onwards. We compared the survival for BC detected by screening with symptomatic BC detection using Kaplan–Meier, unadjusted Cox regressions, and Cox regressions adjusted for age, grading, and UICC stage. Correction for lead time bias was carried out by assuming an exponential distribution of the period during which the tumor is asymptomatic but screen-detectable (sojourn time). We used a common estimate and two recently published estimates of sojourn times. (3) Results: The analysis included 32,169 women. Survival for symptomatic BC was lower than for screen-detected BC (hazard ratio (HR): 0.23, 95% confidence interval (CI): 0.21–0.25). Adjustment for prognostic factors and lead time bias with the commonly used sojourn time resulted in an HR of 0.84 (CI: 0.75–0.94). Using different sojourn times resulted in an HR of 0.73 to 0.90. (4) Conclusions: Survival for symptomatic BC was only one quarter of screen-detected tumors, which is obviously biased. After adjustment for lead-time bias and prognostic variables, including UICC stage, survival was 27% to 10% better for screen-detected BC, which might be attributed to BC screening. Although this result fits quite well with published results for other countries with BC screening, further sources for residual confounding (e.g., self-selection) cannot be ruled out. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. European Commission. [ABSTRACT FROM AUTHOR]

Simple Summary: The use of synthetic patient data can help address patient privacy concerns and the general availability of clinical data. It can overcome the challenges associated with obtaining real patient data for use in medical research, healthcare analytics, and clinical decision support. We propose an approach to provide synthetic patient data for laryngeal cancer, a relatively rare but complex disease. We adapted an existing synthesis technology to produce realistic prevalence and age distributions in the generated patient datasets. We verified the methodology and validated the results using real patient data from a German cancer registry. Background: Obtaining large amounts of real patient data involves great efforts and expenses, and processing this data is fraught with data protection concerns. Consequently, data sharing might not always be possible, particularly when large, open science datasets are needed, as for AI development. For such purposes, the generation of realistic synthetic data may be the solution. Our project aimed to generate realistic cancer data with the use case of laryngeal cancer. Methods: We used the open-source software Synthea and programmed an additional module for development, treatment and follow-up for laryngeal cancer by using external, real-world (RW) evidence from guidelines and cancer registries from Germany. To generate an incidence-based cohort view, we randomly drew laryngeal cancer cases from the simulated population and deceased persons, stratified by the real-world age and sex distributions at diagnosis. Results: A module with age- and stage-specific treatment and prognosis for laryngeal cancer was successfully implemented. The synthesized population reflects RW prevalence well, extracting a cohort of 50,000 laryngeal cancer patients. Descriptive data on stage-specific and 5-year overall survival were in accordance with published data. Conclusions: We developed a large cohort of realistic synthetic laryngeal cancer cases with Synthea. Such data can be shared and published open source without data protection issues. [ABSTRACT FROM AUTHOR]

Purpose: Elderly cancer patients are less likely to be treated in accordance with evidence-based guideline recommendations. This study examines patient-related factors associated with deviations from guideline recommendations. Methods: Using medical documentation and cancer registry data, we investigated the treatment courses of female breast cancer patients aged 50 and older in Germany regarding compliance with German guidelines. Participants completed a questionnaire querying factors hypothesized to be associated with guideline adherence. We conducted univariate analyses to explore the data and select variables for multivariate logistic regression to estimate adjusted odds ratios. Results: Of 1150 participants, 206 (17.9%) were treated in deviation from guideline recommendations. Patients 70 years and older were more likely to be treated deviating from guideline recommendations than patients 50–69 years old (OR: 2.07; 95% CI: 1.52–2.80). Patients aged 50–69 years who reported that quality of life guided their treatment decision were more likely to be treated in deviation from guideline recommendations (AOR: 2.08; 95% CI: 1.11–3.92) than the elderly. In older patients, higher age was associated with an increased chance of receiving guideline-discordant care (AOR: 1.06; 95% CI: 1.01–1.11), as was depression diagnosed prior to cancer (AOR: 1.84; 95% CI: 1.00–3.40). Conclusion: Reasons for deviations from guideline recommendations in breast cancer patients differ by age. In decision-making concerning elderly patients, particular attention should be paid to those with pre-existing depressive disorders. Adequately addressing their needs and concerns could prevent inappropriate deviations from guideline recommendations. [ABSTRACT FROM AUTHOR]

Background: Approximately 27% of female breast cancer patients are diagnosed before the age of 55, a group often comprising mothers with young children. Maternal psychosocial well-being significantly impacts these children's psychosocial well-being. This study assesses the well-being of children with mothers who have early-onset breast cancer. Methods: We examined the eldest child (up to 15 years old) of women with nonmetastatic breast cancer (<55 years old, mean age: 40) enrolled in the mother–child rehab program 'get well together'. Using maternal reports on children's well-being (the Strengths and Difficulties Questionnaire; SDQ), we describe the prevalence of abnormally high SDQ scores and identify protective and risk factors via linear regression. Results: The mean SDQ scores of 496 children (4–15 years old, mean age: 8) fell below the thresholds, indicating psychosocial deficits. However, most SDQ scores deviated negatively from the general population, especially for emotional problems, with one in ten children displaying high and one in five displaying very high deficits. Female sex, more siblings, a positive family environment and maternal psychosocial well-being were protective factors for children's psychosocial well-being. Conclusions: Children of mothers with breast cancer may benefit from improved maternal well-being and family support. Further research is needed to identify appropriate interventions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Simple Summary: This study reports updates on colon and rectum cancer survival differences in the German–Danish border region and investigates the effects of tumor stage at diagnosis and first-line treatment on cancer survival. Based on cancer registry data from 2004 to 2016, we estimated the risk of dying from all causes after a colon or rectum cancer diagnosis while also controlling for stage and treatment. We observed that colon and rectum cancer survival improved in the entire German–Danish border region, but much more in the Danish regions. At first, colon and rectal cancer survival was higher on the German side of the border, but the Danish regions caught up. In the end, colon cancer survival was similar across the border and rectal cancer survival was better in Denmark. Stage and treatment could not explain the observed survival differences. Health care reforms and early detection strategies may also contribute to the regional differences. The aim of this study was (i) to update the reporting of colorectal cancer survival differences over time in the German–Danish border region (Schleswig-Holstein, Southern Denmark, and Zealand) and (ii) to assess the extent to which it can be explained by stage and primary treatment. Incident invasive colorectal cancer cases diagnosed from 2004 to 2016 with a follow-up of vital status through 31 December 2017 were extracted from cancer registries. Analyses were conducted by anatomical subsite and for four consecutive periods. Kaplan–Meier curves and log-rank tests were computed. Cox regression models using data from Schleswig-Holstein from 2004 to 2007 as the reference category were run while controlling for age, sex, stage, and treatment. The cox regression models showed decreasing hazard ratios of death for all three regions over time for both anatomical subsites. The improvement was stronger in the Danish regions, and adjustment for age, sex, stage, and treatment attenuated the results only slightly. In 2014–2016, colon cancer survival was similar across regions, while rectal cancer survival was significantly superior in the Danish regions. Regional survival differences can only partially be explained by differing stage distribution and treatment and may be linked additionally to healthcare system reforms and screening efforts. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer may lead to a reduced quality of life. Certain aspects such as sleep disorders and pain may be a problem not only in the short but also in the long term. Only recently have thresholds for quality of life scores indicating a need for supportive care been published. We asked 853 women with young children and with a breast cancer diagnosis before the age of 40 years about their quality of life, using a questionnaire called EORTC QLQ-C30. More than half of the women with breast cancer reported a reduced quality of life requiring supportive care. This was true 1 year and several years after diagnosis. Physicians, nurses, and other persons working in healthcare should (1) be aware of this and (2) talk to breast cancer survivors about supportive care options. A known cut-off problem hampers the interpretation of quality of life (QOL) scores. The purpose of this study was to apply a novel approach for the EORTC QLQ-C30 instrument to identify the proportion of breast cancer (BC) patients in need of supportive care. Changes in QOL during the COVID-19 pandemic were evaluated, as well as changes over time (after treatment termination and up to 4 years later). Data were obtained from a cohort study on young adult BC patients with minor children participating in a mother–child rehab program. Cross-sectional QOL data were collected from 2015 to 2021 (baseline). Follow-up data were available for up to 4 years after diagnosis for a subgroup. The baseline cohort included 853 women (mean age 35 years). More than 50% had a need for supportive care. In the subgroup with follow-up, this proportion remained at a high level up to several years after diagnosis. During the COVID-19 pandemic, changes regarding the proportion with this need were not as high as expected—with the exception of changes on the QLQ-C30 scale 'role functioning' (+15%). Even several years after diagnosis, every second BC patient with minor children had a need for supportive care, which is much higher than previously found. Healthcare staff should be aware of this potential need and should address this issue. [ABSTRACT FROM AUTHOR]

Inferior vena cava (IVC) diameter can be used to approximate right atrial pressure in patients admitted for acute decompensated heart failure (ADHF). Recent studies linked IVC dilation to an increased risk of early re-admission and short-term mortality. Moreover, renal insufficiency (RI) is an established risk factor for mortality in ADHF and is associated with congestion. We hypothesized that the IVC diameter is a marker of all-cause mortality but its prognostic impact may be influenced by kidney function. We analyzed data of 1101 patients admitted for ADHF with available echocardiography of the IVC by chart review and death registry linkage. Patients were dichotomized according to a cut-off value of 21 mm. Cox proportional hazards model was used to identify mortality predictors. A dilated IVC was detected in 474 (43.1%) patients. Overall, 400 (36.3%) patients died within 3 years. All-cause mortality was significantly higher in patients with dilated IVC [hazard ratio 1.45 (confidence interval 1.21-1.74); p < 0.001]. However, a dilated IVC was only associated with all-cause mortality in patients with RI function [hazard ratio 1.60 (confidence interval 1.26-2.03); p < 0.001] but not in patients with a preserved kidney function [hazard ratio 1.04 (confidence interval 0.72-1.50); P = 0.84]. IVC diameter was identified as an independent predictor for all-cause mortality in a Cox proportional hazards model with a significant interaction between IVC diameter and baseline kidney function. In conclusion, IVC dilation is a marker of high mortality risk in patients admitted for ADHF. However, this observation was confined to patients with RI. [ABSTRACT FROM AUTHOR]

Medical students and doctors have to be particularly stress-resilient, as both medical education and practice are considered very stressful. Specific stressors can lead to increased risks of developing, for example, depression, anxiety and burnout. Relaxation techniques have proven to be effective for the prevention of these outcomes in student populations. However, only a very few medical students practice relaxation techniques regularly early on in their studies. Furthermore, it is unclear which students make use of stress-management offers and hence whether vulnerable students are generally reachable. Therefore, the aim of our study was to explore predictors of participating in a voluntary stress management course for sophomore medical students. One cohort of freshmen at a German medical school was surveyed at the end of the freshman year [t1] and at the end of the sophomore year [t2]. In addition to sociodemographic information, we captured perceived study stress, self-rated general health and mental health and dimensions of study-related behaviour and experience as potential predictors of participation at t1. During the sophomore year, we offered the participants a progressive muscle relaxation (PMR) beginners’ course. At t2, we registered participation status. We used binary logistic regression analyses in order to assess correlations between potential predictors and participation. About one third of the whole class took part in the course. The main reason for non-participation was “no time”. Being female and higher levels of anxiety were the strongest predictors of course participation. Career ambition (the higher, the less likely to participate) and emotional distancing (the higher, the more likely to participate) were further significant predictors. Future interventions should be attractive to both male and female medical students. Ideally, for every hour of stress management teaching, the curriculum should be cut by at least the same amount of time. [ABSTRACT FROM AUTHOR]

Objective The main purpose of skin cancer screening is melanoma mortality reduction. Before the implementation of nationwide German skin cancer screening, the pilot project SCREEN was conducted in Schleswig-Holstein in 2003–2004. We aimed to determine whether the pilot project had achieved a mortality reduction. Methods Using an incidence-based approach (patients with both melanoma diagnosis and death in 2003–2008), we compared the observed melanoma mortality of the SCREEN cohort to the melanoma mortality expected without screening in the general population of Saarland. Results The age- and sex-standardized melanoma mortality ratio (SMR) for 5.5 years of follow-up was 0.59 (95% confidence interval, 0.40–0.83). Conclusion Our results indicate reduced mortality in the SCREEN cohort. Several potential biases cannot be excluded, but most of them tend to inflate the SMR. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims With the exception of the coronavirus pandemic, video consultations have not been a part of the standard care for children with diabetes in Germany. The "Virtual Diabetes Outpatient Clinic for Children and Adolescents 2.0" (VIDIKI 2.0) study investigated the effect of monthly and supplementary video consultations on standard care over one year. The qualitative substudy investigated the experiences of families with a child newly diagnosed with type 1 diabetes mellitus (T1DM) who received at least four weekly supplementary video consultations. Methods Guideline-based qualitative interviews were conducted with seven families with children under the age of eight and T1DM onset shortly before study entry. The answers were analyzed using a qualitative content analysis approach, particularly inductive category formation. Results Families of patients with T1DM onset have questions, almost daily, concerning various aspects of insulin therapy. The offer of high-frequency video consultations can reduce the number of trips to the diabetes team, facilitate the organization of daily life and increase the sense of security. Conclusion Video consultations as a supplementary offer of health care, especially after diabetes onset, were considered very helpful by the affected families. High-frequency video consultations may provide a tool to overcome existing deficiencies in specialized diabetes care. [ABSTRACT FROM AUTHOR]

Background. Shiga toxin-producing, enteroaggregative Escherichia coli was responsible for the 2011 outbreak of haemolytic uraemic syndrome (HUS). The present single-centre, observational study describes the 1-year course of the disease with an emphasis on kidney function. Outcome data after 1 year are associated with treatment and patient characteristics at onset of HUS. Methods. Patients were treated according to a standardized approach of supportive care, including a limited number of plasmapheresis. On top of this treatment, patients with severe HUS (n = 35) received eculizumab, a humanized anti-C5 monoclonal antibody inhibiting terminal complement activation. The per-protocol decision--to start or omit an extended therapy with eculizumab accompanied by azithromycin--separated the patients into two groups and marked Day 0 of the prospective study. Standardized visits assessed the patients' well-being, kidney function, neurological symptoms, haematological changes and blood pressure. Results. Fifty-six patients were regularly seen during the followup. All patients had survived without end-stage renal disease. Young(er) age alleviated restoring kidney function after acute kidney injury even in severe HUS. After 1 year, kidney function was affected with proteinuria [26.7%; 95% confidence interval (CI) 13.8-39.6], increased serum creatinine (4.4%, CI 0.0-10.4), increased cystatin C (46.7%, CI 32.1-61.3) and reduced (<90 mL/ min) estimated glomerular filtration rate (46.7%, CI 32.1-61.3). Nine of the 36 patients without previous hypertension developed de novo hypertension (25%, CI 10.9-39.1). All these patients had severe HUS. Conclusions. Although shiga toxin-producing Escherichia coli (STEC)-HUS induced by O104:H4 was a life-threatening acute disease, follow-up showed a good recovery of organ function in all patients. Whereas kidney function recovered even after longer duration of dialysis, chronic hypertension developed after severe HUS with neurological symptoms and could not be prevented by the extended therapy. [ABSTRACT FROM AUTHOR]

We used the comprehensive definition of AYA (age 15 to 39 years) to update 5-year relative survival (RS) estimates for AYAs in Europe and across countries and to evaluate improvements in survival over time. We used data from EUROCARE-6. We analysed 700,000 AYAs with cancer diagnosed in 2000–2013 (follow-up to 2014). We focused the analyses on the 12 most common cancers in AYA. We used period analysis to estimate 5-year RS in Europe and 5-year RS differences in 29 countries (2010–2014 period estimate) and over time (2004–06 vs. 2010–14 period estimates). 5-year RS for all AYA tumours was 84%, ranging from 70% to 90% for most of the 12 tumours analysed. The exceptions were acute lymphoblastic leukaemia, acute myeloid leukaemia, and central nervous system tumours, presenting survival of 59%, 61%, and 62%, respectively. Differences in survival were observed among European countries for all cancers, except thyroid cancers and ovarian germ-cell tumours. Survival improved over time for most cancers in the 15- to 39-year-old age group, but for fewer cancers in adolescents and 20- to 29-year-olds. This is the most comprehensive study to report the survival of 12 cancers in AYAs in 29 European countries. We showed variability in survival among countries most likely due to differences in stage at diagnosis, access to treatment, and lack of referral to expert centres. Survival has improved especially for haematological cancers. Further efforts are needed to improve survival for other cancers as well, especially in adolescents. • Tumours of adolescents and young adults can be treated effectively. • Application of paediatric protocols to AYAs with ALL improves outcomes. • We highlighted survival differences between European countries for most AYA tumours. • Survival improved over time for most cancers in the 15- to 39-year-old age group. • Survival improved over time for fewer cancers in those aged 15 to 29. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Our study addresses at the benefit of surveillance of probably benign lesions, detected outside mammographic screening, during a 3-year period. Methods: 28,588 women (mean age 57 ± 12 years) were examined. Two independent radiologists read the mammogram as well as the supplemented ultrasound (in case of breast density ACR type 3 and 4). In the case of discordance a third expert considered whether further examination was indicated or not. Results: 3,266 diagnostic procedures ended with BI-RADS 3 result and 2,512 (76.9 %) women underwent a follow-up examination. 295 (11.7 %) of them received assessment examination (imaging and/or biopsy) and 37 (12.5 %) (none of them palpable) ended with BI-RADS 6. This equals a tumor detection rate of 14.7/1,000. The ratio in situ:invasive was 7:10 (1:1.43) and the mean size was 11.1 ± 4.51 mm. In the total cohort, 536 carcinomas ended with BI-RADS 6 of them 17 % were in situ and 83 % were invasive breast cancers (ratio in situ:invasive 1:4.99), mean size was 13.8 ± 6.3 mm. The cancer detection ratio in these cases was 18.7/1,000. Conclusions: The amount of detected tumors at follow-up of women with preceding BI-RADS 3 equates the associated potential of malignancy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Malignant gonadal (GGCT) and extragonal germ cell tumors [GCT (EGCT)] are thought to originate from primordial germ cells. In contrast to well reported population-based data of GGCTs in males, analyses of GGCTs in females and EGCTs in both sexes remain limited. Methods: In a pooling project of nine population-based cancer registries in Germany for the years 1998- 2008, 16,883 malignant GCTs and their topographical sites were identified using ICD-O morphology and topography for persons aged 15 years and older. We estimated age-specific and age-standardized incidence rates. Results: Among males, the incidence of testicular GCTs increased over time. In contrast, there was no increase in the incidence of EGCTs. Among females, rates of ovarian GCTs were stable, while rates of EGCTs declined over time. The most frequent extragonadal sites were mediastinum among males and placenta among females. Conclusions: Our results underline different incidence trends and distinct age-specific incidence patterns of malignant GGCTs and EGCTs, as reported recently by several population-based registries. The differences suggest that GGCT and EGCT may have different etiologies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Increasing incidence rates of cutaneous melanoma (CM) observed during the last five decades in white populations are largely attributed to increased exposure to solar ultraviolet radiation (UVR), often expressed as population attributable fraction (PAF). Thus, many CMs could be prevented by reducing UVR exposure. The aim of this study was to estimate the PAF of CM attributable to UVR exposure and demographic changes in Denmark and Saarland/Germany for the period 1943 to 2036. CM incidence data (ICD-10, C43) for Denmark (1943–2016) and the German Federal State of Saarland (1972–2016) were retrieved from the NORDCAN database and from the Saarland Cancer Registry. The number of CMs attributable to UVR exposure was calculated by comparing contemporary or predicted CM incidence rates with CM rates in Denmark during the years 1943–1946. In Denmark, the proportion of CM cases attributable to UVR exposure increased from around 20% in 1947–1951 to 96% in 2012–2016; in the Federal State of Saarland, it increased from 50% in 1972–1976 to 90% in 2012–2016. Until 2032–2036, the PAF is expected to rise in Denmark to 97% and in the Saarland to 92%. The demographic influence, on the other hand, is rather small. More than 90% of all CM in Germany and Denmark are attributable to UVR exposure, and in principle, preventable. These findings underline the need for primary prevention strategies, aiming to increase the awareness of melanoma and its risk factors and to promote behavioural changes that decrease sun exposure. • Long-term estimates of UVR-related CM burden in Denmark and Germany from 1943 to 2036. • In 2012–2016, over 90% of CM cases in Denmark and Germany were attributable to UVR. • Increasing UVR-related CM burden is to be expected if risk behaviour does not change. • Primary prevention focusing on reducing UVR exposure is crucial for CM control. [ABSTRACT FROM AUTHOR]