The German National Pandemic Cohort Network (NAPKON): rationale, study design and baseline characteristics.

The German government initiated the Network University Medicine (NUM) in early 2020 to improve national research activities on the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. To this end, 36 German Academic Medical Centers started to collaborate on 13 projects, with the largest being the National Pandemic Cohort Network (NAPKON). The NAPKON's goal is creating the most comprehensive Coronavirus Disease 2019 (COVID-19) cohort in Germany. Within NAPKON, adult and pediatric patients are observed in three complementary cohort platforms (Cross-Sectoral, High-Resolution and Population-Based) from the initial infection until up to three years of follow-up. Study procedures comprise comprehensive clinical and imaging diagnostics, quality-of-life assessment, patient-reported outcomes and biosampling. The three cohort platforms build on four infrastructure core units (Interaction, Biosampling, Epidemiology, and Integration) and collaborations with NUM projects. Key components of the data capture, regulatory, and data privacy are based on the German Centre for Cardiovascular Research. By April 01, 2022, 34 university and 40 non-university hospitals have enrolled 5298 patients with local data quality reviews performed on 4727 (89%). 47% were female, the median age was 52 (IQR 36-62-) and 50 pediatric cases were included. 44% of patients were hospitalized, 15% admitted to an intensive care unit, and 12% of patients deceased while enrolled. 8845 visits with biosampling in 4349 patients were conducted by April 03, 2022. In this overview article, we summarize NAPKON's design, relevant milestones including first study population characteristics, and outline the potential of NAPKON for German and international research activities.Trial registration https://clinicaltrials.gov/ct2/show/NCT04768998 . https://clinicaltrials.gov/ct2/show/NCT04747366 . https://clinicaltrials.gov/ct2/show/NCT04679584.

Risk of postmenopausal hormone therapy and patient history factors for the survival rate in women with endometrial carcinoma.

PURPOSE: Postmenopausal hormone therapy (HT) is known to affect the development of hormone-dependent endometrial carcinoma (type I EC). Several studies on breast and ovarian carcinoma have shown that HT influences the molecular profile and prognostic behavior of these tumors. This study aimed to investigate the influence of prior HT and other risk factors on the prognosis in a cohort of patients with invasive endometrial carcinoma (EC). METHODS: Among 525 patients diagnosed with EC between 1987 and 2010, 426 postmenopausal patients were identified. Information regarding HT was available in 287 of these patients, 78 of whom had a history of HT and 209 of whom did not. Both overall survival (OS) and progression-free survival (PFS) were analyzed. In addition to OS and PFS, risk factors such as age at diagnosis, postmenopausal HT, body mass index (BMI), diabetes mellitus, tumor stage, EC type (I or II), and recurrences were analyzed. RESULTS: Relative to HT alone, women with EC and a history of HT had a longer survival than those with no HT. However, the Cox proportional hazards model showed that it was not HT itself, but rather other characteristics in the HT group that were causally associated with longer survival. CONCLUSIONS: Age (the older, the worse) and tumor stage (the higher, the worse) were significant influences on overall survival. Patients with HT also had lower BMIs, less diabetes, more type I EC, and fewer recurrences in comparison with the non-HT group. With regard to the PFS, it made no difference whether the patient was receiving HT.

[Quality of Life and Satisfaction During the Diabetes Prevention Program GLICEMIA: a Cluster-Randomized, Controlled Trial]. / Lebensqualität und Zufriedenheit während der Teilnahme am Diabetes-Präventionsprogramm GLICEMIA: eine cluster-randomisierte, kontrollierte Studie.

OBJECTIVES: We aimed to assess the health-related quality of life as well as participant satisfaction during the pharmacy-based diabetes prevention program GLICEMIA. METHODS: GLICEMIA comprises 3 individual counseling sessions and 5 group-based lectures addressing a lifestyle modification. In a cluster-randomized controlled trial, GLICEMIA was compared with reduced standard information in the control group. After 12 months, the groups were compared regarding the diabetes risk score FINDRISC, health-related quality of life with the 12-item Short Form health survey (SF-12) and participant satisfaction. RESULTS: In total, the data of 1,087 participants were analyzed. During GLICEMIA, 38.9% reduced their FINDRISC whereas 20.9% reached this goal in the control group. Moreover, the physical quality of life improved significantly in the intervention group compared with the control group (adjusted effect size: 2.39 points, 95% CI 1.43-3.34). Participants of GLICEMIA who reduced their diabetes risk had enhanced mental and physical quality of life after one year. This was not observed in the control group. The overall benefit and satisfaction were rated very high in the intervention group. CONCLUSION: Participation in GLICEMIA results in a significant reduction of the diabetes risk according to the FINDRISC, as well as an improved physical and mental quality of life. The high satisfaction of the participants reflects the overall benefit. Nationwide implementation of the program is recommended.

Association between breast cancer risk factors and molecular type in postmenopausal patients with hormone receptor-positive early breast cancer.

PURPOSE: Evidence shows that genetic and non-genetic risk factors for breast cancer (BC) differ relative to the molecular subtype. This analysis aimed to investigate associations between epidemiological risk factors and immunohistochemical subtypes in a cohort of postmenopausal, hormone receptor-positive BC patients. METHODS: The prospective, single-arm, multicenter phase IV PreFace study (Evaluation of Predictive Factors Regarding the Effectivity of Aromatase Inhibitor Therapy) included 3529 postmenopausal patients with hormone receptor-positive early BC. Data on their epidemiological risk factors were obtained from patients' diaries and their medical histories. Data on estrogen receptor, progesterone receptor, and HER2 receptor status were obtained from pathology reports. Patients with incomplete information were excluded. Data were analyzed using conditional inference regression analysis, analysis of variance, and the chi-squared test. RESULTS: In a cohort of 3392 patients, the strongest association with the molecular subtypes of BC was found for hormone replacement therapy (HRT) before diagnosis of early BC. The analysis showed that patients who took HRT at diagnosis had luminal A-like BC more often (83.7%) than those who had never taken HRT or had stopped taking it (75.5%). Luminal B-like BC and HER2-positive BC were diagnosed more often in women who had never taken HRT or had stopped taking it (13.3% and 11.2%, respectively) than in women who were taking HRT at diagnosis of BC (8.3% and 8.0%, respectively). CONCLUSIONS: This analysis shows an association between HRT and the distribution of molecular subtypes of BC. However, no associations between other factors (e.g., age at diagnosis, body mass index, smoking status, age at menopause, number of deliveries, age at first delivery, breastfeeding history, or family history) were noted.

Outcomes of dialysis patients with critical limb ischemia after revascularization compared with patients with normal renal function.

OBJECTIVE: An analysis was conducted of intermediate outcomes and possible influencing factors in patients with end-stage renal disease (ESRD) and critical limb ischemia after lower limb revascularization compared with patients with regular renal function (non-ESRD). METHODS: Data collection was performed by inquiry of the German multicenter registry of First-Line Treatments in Patients with Critical Limb Ischemia (CRITISCH); 102 ESRD patients and 674 non-ESRD patients were included. Four different therapy modalities were analysed: bypass surgery, endovascular therapy (EVT), femoral artery endarterectomy, and no vascular intervention (conservative treatment or primary major amputation). Predefined end points were amputation-free survival (AFS), death, major amputation, and reintervention. Cox regression models were built to analyze independent risk factors for outcome parameters. RESULTS: ESRD patients showed inferior results at 2 years in the rate of AFS (ESRD, 35.4%; non-ESRD, 67.2%; P < .001). Similarly, death rate (ESRD, 55.0%; non-ESRD, 20.7%; P < .001) and major amputation rate (ESRD, 24.5%; non-ESRD, 15.8%; P = .029) were significantly elevated for ESRD patients. The choice of therapeutic approach in ESRD did not influence the incidence of the investigated end points (death or major amputation: EVT, 56.9% vs bypass, 76.9% [P = .225]; death: EVT, 46.2% vs bypass, 61.5% [P = .372]; amputation: EVT, 15.4% vs bypass, 15.4% [P = 1.000]; reintervention: EVT, 32.3% vs bypass, 15.4% [P = .324]). Cox regression analysis indicated that dialysis patients carry a twofold increased hazard of death or major amputation (hazard ratio, 2.27; 95% confidence interval, 1.67-3.10; P < .001), and open surgical treatment (all patients combined) was associated with reduced risk of death compared with EVT (hazard ratio, 0.58; 95% confidence interval, 0.37-0.91; P = .017). Comorbidities were not found to have a noticeable impact on AFS, survival, reintervention, or major amputation. CONCLUSIONS: Two-year AFS, overall survival, and freedom from major amputation were decreased in ESRD patients compared with non-ESRD patients with critical limb ischemia. Cardiovascular comorbidities were without significant impact on outcome parameters, whereas choice of treatment modality within the ESRD group did not influence AFS. Decision-making in ESRD as to choice of therapeutic approach in dialysis patients should notably account for the individual's lesion characteristics and vascular disease; surgical revascularization and EVT may be used as complementary options.

Prediction of pathological complete response and prognosis in patients with neoadjuvant treatment for triple-negative breast cancer.

BACKGROUND: It has been reported that pathological complete response is an important surrogate marker for disease-free survival and overall survival in patients with triple-negative breast cancer. This study investigates predictors of the response to neoadjuvant platinum-based or anthracycline-based treatment, and of the prognosis, in patients with triple-negative breast cancer. METHODS: A total of 121 patients with triple-negative breast cancer received neoadjuvant treatment with either platinum or anthracycline between 2008 and 2013. Pathological complete response was assessed relative to different treatments using logistic regression models with age, clinical tumor stage, grading, and Ki-67 as predictors and interaction terms, to obtain adjusted and subgroup-specific results. The impact of the pathological complete response rate on disease-free survival and overall survival was also analyzed. RESULTS: The pathological complete response rate was higher after platinum/taxane treatment compared with anthracycline/taxane (50.0% vs. 41.8%), but this was not significant in the adjusted analysis (OR 1.44; 95% CI, 0.68 to 3.09). A high histological grade (G3) was a predictor for higher pathological complete response in platinum-based therapy (OR 2.27; 95% CI, 1.00 to 5.30). The effect of neoadjuvant chemotherapy on pathological complete response was significantly different for G1-2 vs. G3 (Pinteraction = 0.013), and additional subgroup-specific differences were noted. Pathological complete response was a predictor for improved disease-free survival and overall survival in both treatment groups, with and without platinum chemotherapy. CONCLUSIONS: This retrospective study of patients with triple-negative breast cancer adds to the evidence that the treatment effect of platinum may be greatest particularly in G3 tumors. In addition, the effect of pathological complete response on the prognosis does not depend on the treatment used.

[Knowledge and information sources of parents of 3­ to 6­year-old children concerning skin cancer risk factors]. / Kenntnisse und Wissensquellen zu Hautkrebs-Risikofaktoren bei Eltern von 3­ bis 6­jährigen Kindern.

BACKGROUND: The dissemination of knowledge on risk factors and preventive strategies is a core element of skin cancer prevention. However, little is known about the information channels utilised by the population for this purpose. OBJECTIVES: Descriptive analysis of information sources used by parents of 3­ to 6­year-old children as a particularly relevant target group and analysis of association patterns between socio-demographic factors, types of information sources and acquired knowledge. MATERIALS AND METHODS: A cross-sectional study was performed using a self-administered questionnaire with an online option between October 2011 and February 2012 with 3129 families who had at least one child visiting a kindergarten in the county of Erlangen-Höchstadt, the city of Erlangen or the city of Ansbach (Bavaria, Germany), with an 87.5% response rate on the level of kindergartens and 56.5% on the level of observational units (families). RESULTS: There were few structural differences between study regions. The internet was used by only 13.3% of participants. A positive association was found between the use of multiple information sources and relevant knowledge and, partly, protective behaviour. A negative association was identified between the use of the internet and knowledge. In contrast, the use of print media or audio-visual or personal channels of information was positively associated with knowledge. CONCLUSIONS: Preventive efforts should be increased that target parts of the population with lower formal education. The internet does not seem to play an important role and may even adversely affect knowledge, possibly due to unvalidated and misleading information.

Incremental value of serum neurofilament light chain and glial fibrillary acidic protein as blood-based biomarkers for predicting functional outcome in severe acute ischemic stroke.

INTRODUCTION: Blood-based biomarkers may improve prediction of functional outcome in patients with acute ischemic stroke. The role of neurofilament light chain (NfL) and glial fibrillary acidic (GFAP) as potential biomarkers especially in severe stroke patients is unknown. PATIENTS AND METHODS: Prospective, monocenter, cohort study including consecutive patients with severe ischemic stroke in the anterior circulation on admission (NIHSS score ⩾ 6 points or indication for mechanical thrombectomy). Outcome was assessed 3 months after the index stroke by the modified Rankin Scale (mRS). Serum biomarkers levels of NfL and GFAP were determined by ultrasensitive ELISA. Univariate and multivariate logistic regression models were performed to determine the association of biomarker levels and functional disability. Discrimination, calibration, and overall performance were analyzed in different models via AUROC, calibration plots (with Emax and Eavg), Brier-score and R2 using variables, identified as important covariates for functional outcome in previous studies. RESULTS: Between 06/2020 and 08/2021, 213 patients were included [47% female, mean age 76 (SD ± 12) years, median NIHSS score 13 (interquartile range, IQR 9; 17)]. Biomarker serum levels were measured at a median of 1 [IQR, 1; 2] day after admission. Compared to patients with mRS 0-2 at 3 months, patients with mRS 3-6 had higher serum levels of NfL (median: 136 pg/ml vs 41 pg/ml; p < 0.0001) and GFAP (700 ng/ml vs 9.6 ng/ml; p < 0.0001). Both biomarkers were significantly associated with functional outcome [adjusted logistic regression, odds ratio (95% CI) for NfL: 2.63 (1.62; 4.56), GFAP: 2.16 (1.58; 3.09)]. In all models the addition of serum NfL led to a significant improvement in the AUROC, as did the addition of serum GFAP. Calibration plots showed high agreement between the predicted and observed outcomes and after addition of the two blood-based biomarkers there was an improvement of the overall performance. CONCLUSION: Prediction of functional outcome after severe acute ischemic stroke was improved by the blood-based biomarkers serum NfL and GFAP, measured in the acute phase of stroke. These findings have to be replicated in independent external cohorts.Study registration: DRKS00022064.

Salt-Intake-Related Behavior Varies between Sexes and Is Strongly Associated with Daily Salt Consumption in Obese Patients at High Risk for MASLD.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) imposes a significant burden on Westernized regions. The Western diet, high in salt intake, significantly contributes to disease development. However, there are a lack of data on salt literacy and salt intake among MASLD patients in Germany. Our study aims to analyze daily salt intake and salt-intake-related behavior in MASLD patients. METHODS: 234 MASLD patients were prospectively included. Daily salt intake and salt-intake-related behavior were assessed via a food frequency questionnaire (FFQ-DEGS) and a salt questionnaire (SINU). Statistical analyses were performed using SPSS. RESULTS: Mean daily salt intake was higher in men than in women (7.3 ± 5 g/d vs. 5.3 ± 4 g/d; p < 0.001). There was significant agreement between increased daily salt intake (>6 g/d) and the behavioral salt index (SI) (p < 0.001). Men exhibited higher SI scores compared to women, indicating lower awareness of salt in everyday life. Multivariate analysis identified specific salt-intake-related behaviors impacting daily salt consumption. CONCLUSIONS: Our study reveals a strong link between daily salt intake and salt-intake-related behavior, highlighting sex-specific differences in an MASLD cohort. To enhance patient care in high-cardiovascular-risk populations, specific behavioral approaches may be considered, including salt awareness, to improve adherence to lifestyle changes, particularly in male patients.

In-Hospital ECG Findings, Changes in Medical Management, and Cardiovascular Outcomes in Patients With Acute Stroke or Transient Ischemic Attack.

Background In patients with acute ischemic stroke, little is known regarding the frequency of abnormal ECG findings other than atrial fibrillation and their association with cardiovascular outcomes. We aim to analyze the frequency and type of abnormal ECG findings, subsequent changes in medical treatment, and their association with cardiovascular outcomes in patients with acute ischemic stroke. Methods and Results In the investigator-initiated multicenter MonDAFIS (impact of standardized monitoring for detection of atrial fibrillation in ischemic stroke) study, 3465 patients with acute ischemic stroke or transient ischemic attack and without known atrial fibrillation were randomized 1:1 to receive Holter-ECG for up to 7 days in-hospital with systematic evaluation in a core cardiology laboratory (intervention group) or standard diagnostic care (control group). Outcomes included predefined abnormal ECG findings (eg, pauses, atrial fibrillation, brady-/tachycardias), medical management in the intervention group, and combined vascular end point (recurrent stroke, myocardial infarction, major bleeds, or all-cause death) and mortality at 24 months in both randomization groups. Predefined abnormal ECG findings were detected in 326 of 1693 (19.3%) patients in the intervention group. Twenty of these 326 patients (6.1%) received a pacemaker, and 62 of 326 (19.0%) patients had newly initiated or discontinued ß-blocker medication. Discontinuation of ß-blockers was associated with a higher death rate in the control group than in the intervention group during 24 months after enrollment (adjusted hazard ratio, 11.0 [95% CI, 2.4-50.4]; P=0.025 for interaction). Conclusions Systematic in-hospital Holter ECG reveals abnormal findings in 1 of 5 patients with acute stroke, and mortality was lower at 24 months in patients with systematic ECG recording in the hospital. Further studies are needed to determine the potential impact of medical management of abnormal ECG findings. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02204267.

Off-label-dosing of non-vitamin K-dependent oral antagonists in AF patients before and after stroke: results of the prospective multicenter Berlin Atrial Fibrillation Registry.

AIMS: We aimed to analyze prevalence and predictors of NOAC off-label under-dosing in AF patients before and after the index stroke. METHODS: The post hoc analysis included 1080 patients of the investigator-initiated, multicenter prospective Berlin Atrial Fibrillation Registry, designed to analyze medical stroke prevention in AF patients after acute ischemic stroke. RESULTS: At stroke onset, an off-label daily dose was prescribed in 61 (25.5%) of 239 NOAC patients with known AF and CHA2DS2-VASc score ≥ 1, of which 52 (21.8%) patients were under-dosed. Under-dosing was associated with age ≥ 80 years in patients on rivaroxaban [OR 2.90, 95% CI 1.05-7.9, P = 0.04; n = 29] or apixaban [OR 3.24, 95% CI 1.04-10.1, P = 0.04; n = 22]. At hospital discharge after the index stroke, NOAC off-label dose on admission was continued in 30 (49.2%) of 61 patients. Overall, 79 (13.7%) of 708 patients prescribed a NOAC at hospital discharge received an off-label dose, of whom 75 (10.6%) patients were under-dosed. Rivaroxaban under-dosing at discharge was associated with age ≥ 80 years [OR 3.49, 95% CI 1.24-9.84, P = 0.02; n = 19]; apixaban under-dosing with body weight ≤ 60 kg [OR 0.06, 95% CI 0.01-0.47, P < 0.01; n = 56], CHA2DS2-VASc score [OR per point 1.47, 95% CI 1.08-2.00, P = 0.01], and HAS-BLED score [OR per point 1.91, 95% CI 1.28-2.84, P < 0.01]. CONCLUSION: At stroke onset, off-label dosing was present in one out of four, and under-dosing in one out of five NOAC patients. Under-dosing of rivaroxaban or apixaban was related to old age. In-hospital treatment after stroke reduced off-label NOAC dosing, but one out of ten NOAC patients was under-dosed at discharge. CLINICAL TRIAL REGISTRATION: NCT02306824.

Systematic monitoring for detection of atrial fibrillation in patients with acute ischaemic stroke (MonDAFIS): a randomised, open-label, multicentre study.

BACKGROUND: Systematic electrocardiogram (ECG) monitoring improves detection of covert atrial fibrillation in stroke survivors but the effect on secondary prevention is unknown. We aimed to assess the effect of systematic ECG monitoring of patients in hospital on the rate of oral anticoagulant use after 12 months. METHODS: In this investigator-initiated, randomised, open-label, parallel-group multicentre study with masked endpoint adjudication, we recruited patients aged at least 18 years with acute ischaemic stroke or transient ischaemic attack without known atrial fibrillation in 38 certified stroke units in Germany. Patients were randomly assigned (1:1) to usual diagnostic procedures for atrial fibrillation detection (control group) or additional Holter-ECG recording for up to 7 days in hospital (intervention group). Patients were stratified by centre using a random permuted block design. The primary outcome was the proportion of patients on oral anticoagulants at 12 months after the index event in the intention-to-treat population. Secondary outcomes included the number of patients with newly diagnosed atrial fibrillation in hospital and the composite of recurrent stroke, major bleeding, myocardial infarction, or death after 6 months, 12 months, and 24 months. This trial was registered with ClinicalTrials.gov, NCT02204267, and is completed and closed for participants. FINDINGS: Between Dec 9, 2014, and Sept 11, 2017, 3465 patients were randomly assigned, 1735 (50·1%) to the intervention group and 1730 (49·9%) to the control group. Oral anticoagulation status was available in 2920 (84·3%) patients at 12 months (1484 [50·8%] in the intervention group and 1436 [49·2%] in the control group). For the primary outcome, at 12 months, 203 (13·7%) of 1484 patients in the intervention group versus 169 (11·8%) of 1436 in the control group were on oral anticoagulants (odds ratio [OR] 1·2 [95% CI 0·9-1·5]; p=0·13). Atrial fibrillation was newly detected in patients in hospital in 97 (5·8%) of 1714 in the intervention group versus 68 (4·0%) of 1717 in the control group (hazard ratio [HR] 1·4 [95% CI 1·0-2·0]; p=0·024). The composite of cardiovascular outcomes and death did not differ between patients randomly assigned to the intervention group versus the control group at 24 months (232 [13·5%] of 1714 vs 249 [14·5%] of 1717; HR 0·9 [0·8-1·1]; p=0·43). Skin reactions due to study ECG electrodes were reported in 56 (3·3%) patients in the intervention group. All-cause death occured in 73 (4·3%) patients in the intervention group and in 103 (6·0%) patients in the control group (OR 0·7 [0·5-0·9]). INTERPRETATION: Systematic core centrally reviewed ECG monitoring is feasible and increases the detection rate of atrial fibrillation in unselected patients hospitalised with acute ischaemic stroke or transient ischaemic attack, if added to usual diagnostic care in certified German stroke units. However, we found no effect of systematic ECG monitoring on the rate of oral anticoagulant use after 12 months and further efforts are needed to improve secondary stroke prevention. FUNDING: Bayer Vital. TRANSLATION: For the German translation of the abstract see Supplementary Materials section.

Differentiation of malignant liver tumors by software-based perfusion quantification with dynamic contrast-enhanced ultrasound (DCEUS).

BACKGROUNDEnhancement patterns on contrast-enhanced ultrasound (CEUS) help to distinguish different liver tumors. OBJECTIVE: Assessing the diagnostic value of dynamic contrast-enhanced ultrasound (DCEUS) for the discrimination of different malignant liver lesions. METHODS: 148 malignant focal liver lesions were assessed prospectively with DCEUS (hepatocellular carcinoma = HCC; cholangiocellular carcinoma = CCC; pancreatic adenocarcinoma = PCA; breast cancer = BC; colorectal cancer = CRC; melanoma = MM). Focal-nodular-hyperplasias (FNH) served as a reference for benign lesions. DCEUS-clips were recorded continuously over three minutes. DCEUS-values were compared between the tumor entities. For better inter-individual comparability, perfusion kinetics were analyzed considering the perfusion characteristics of the surrounding liver parenchyma (Relative Signal Intensity = RSI: lesion-liver tissue/liver tissue) at different points in time. RESULTS: Absolute signal intensity in FNH showed a tendency towards higher values compared with malignant liver lesions [Peak Enhancement(a.u.): FNH 7111.4; HCC 549.9; CCC -6654.3; PCA -7307.9; BC -4562.4; CRC -10672.9; MM -3034.1]. Washout was significantly less in FNH versus PCA and CRC, and more pronounced and earlier in PCA and CRC versus HCC [RSI 30 seconds after PE-lesion(%): FNH +52; PCA -65; CRC -76; HCC -26]. Rise Time, Fall Time and mean-Transit-Time did not differ significantly. CONCLUSIONS: DCEUS-values reflect significant differences between malignant liver lesions, especially at peak enhancement and during the washout phases.

Shedding Light on the Shade: How Nurseries Protect Their Children from Ultraviolet Radiation.

Minimizing exposure to ultraviolet radiation (UVR) is strongly recommended as the most important primary prevention measure regarding skin cancer. The responsibility for adequate sun protection of young children lies with their parents and external caregivers. Since a high proportion of 3- to 6-year-old children in Germany attend nurseries, the practice of sun protection in this setting was assessed. A survey was conducted in 246 nurseries in southern Germany during spring and summer of 2014 and 2015. Shade coverage in the outdoor area of the nursery was assessed by study team members and UVR protective behavior of staff was assessed by an interview with the directors. On average, 52% of the entire outdoor area and 65% of the children's outdoor play area were covered by shade, with a significant difference between nurseries of different sizes, pointing to a better shade coverage in larger nurseries. The daily outdoor stay was not regularly scheduled before or after peak sun intensity hours around noon to avoid intense UVR exposure. General sun protection rules were present in the majority of the nurseries and addressed predominantly wearing sunhats and applying sunscreen. Our findings show that current sun protection recommendations for children are only partially met in nurseries and indicate a lower level of sun protection in small institutions. Especially, avoidance of excessive exposure to UVR around noon and the importance of shade provision over play structures needs to be emphasized in future information campaigns.

Association between month of birth and melanoma risk: fact or fiction?

Background: Evidence on the effect of ultraviolet radiation (UVR) exposure in infancy on melanoma risk in later life is scarce. Three recent studies suggest that people born in spring carry a higher melanoma risk. Our study aimed at verifying whether such a seasonal pattern of melanoma risk actually exists. Methods: Data from the population-based Cancer Registry Bavaria (CRB) on the birth months of 28 374 incident melanoma cases between 2002 and 2012 were analysed and compared with data from the Bavarian State Office for Statistics and Data Processing on the birth month distribution in the Bavarian population. Crude and adjusted analyses using negative binomial regression models were performed in the total study group and supplemented by several subgroup analyses. Results: In the crude analysis, the birth months March-May were over-represented among melanoma cases. Negative binomial regression models adjusted only for sex and birth year revealed a seasonal association between melanoma risk and birth month with 13-21% higher relative incidence rates for March, April and May compared with the reference December. However, after additionally adjusting for the birth month distribution of the Bavarian population, these risk estimates decreased markedly and no association with the birth month was observed any more. Similar results emerged in all subgroup analyses. Conclusions: Our large registry-based study provides no evidence that people born in spring carry a higher risk for developing melanoma in later life and thus lends no support to the hypothesis of higher UVR susceptibility during the first months of life.

Monitoring of naevus density at age 6: Is it both feasible and meaningful?

BACKGROUND: Instruments for the evaluation of campaigns targeting the reduction of UV exposure in the population, and thus skin cancer risk, are needed. OBJECTIVE: To examine the "childhood monitoring of naevus density" approach suggested some 10 years ago in a routine setting of mandatory pre-school examinations. METHODS: Data were collected between 1999 and 2005 in Göttingen, Wolfenbüttel, Northeim, Salzgitter, and Erlangen. Besides basic data, freckling, iris and hair colour, and "Fitzpatrick skin type" as well as counts of melanocytic naevi were documented. Negative binomial regression analysis quantified the association between naevus counts and above factors, and year and site of examination, respectively. RESULTS: Of 12,809 children examined at five different sites over a period of 6 years, 11,345 were eligible for the analysis. While differences between sites were marked and significant, only a very minute, albeit significant, decrease in risk was found between the reference group (Göttingen 1999/2000) and the last year examined in Göttingen (2005). CONCLUSIONS: Significant between-site variation in the analysis adjusted for constitutional factors points to problems with standardization; thus, a broad application of this instrument does not seem to be advisable.

The Effect of Exposure to Ultraviolet Radiation in Infancy on Melanoma Risk.

Evidence on the effect of ultraviolet radiation (UVR) exposure in infancy on melanoma risk in later life is scarce. Three recent studies suffering from methodological shortcomings suggested that people born in spring carry a higher melanoma risk. Data from the Bavarian population-based cancer registry on 28374 incident melanoma cases between 2002 and 2012 were analyzed to reexamine this finding. Crude and adjusted analyses - using negative binomial regression models - were performed addressing the relationship. In the crude analysis, the birth months March - May were significantly overrepresented among melanoma cases. However, after additionally adjusting for the birth month distribution of the Bavarian population, the ostensible seasonal effect disappeared. Similar results emerged in all subgroup analyses. Our large registry-based study provides no evidence that people born in spring carry a higher risk for developing melanoma in later life and thus lends no support to the hypothesis of higher UVR-susceptibility during the first months of life.

Effects of the lifestyle intervention program GLICEMIA in people at risk for type 2 diabetes: a cluster-randomized controlled trial.

OBJECTIVE: The aim of this study was to assess the efficacy of a 12-month prevention program conducted in 42 community pharmacies in reducing the risk for diabetes. RESEARCH DESIGN AND METHODS: In a cluster-randomized controlled trial in 1,092 participants, mean change in the risk for diabetes (indicated by the Finnish Diabetes Risk Score [FINDRISC]) between intervention and control groups was calculated. In the intervention program GLICEMIA, three appointments with individual counseling and five educational group sessions were combined, whereas in the control group, only information about the participants' health was obtained in three assessments. RESULTS: After adjusting for cluster structure and differences in baseline characteristics, improvement in FINDRISC in the intervention group was 0.74 points (95% CI 0.42-1.04) above the control group. CONCLUSIONS: The GLICEMIA program shows the feasibility of a pharmacy-based intervention and leads to a significant modest reduction in diabetes risk score but does not reduce the rate of diabetes progression over 1 year.