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The COVID-19 pandemic affected daily life significantly and had massive consequences for healthcare systems with tremendous regional differences. This retrospective study aimed to investigate whether the pandemic and resulting societal changes impacted the diagnosis of pediatric malignancies in a distinct region. Pediatric cancer cases in Bavaria (2016-2021) and SARS-CoV-2 proceedings during the peak phase of the pandemic (2020-2021) were retrospectively analyzed. All new diagnoses of pediatric malignancies reported from cancer centers in Bavaria were included. Clinical data from pre-pandemic years was compared to diagnoses made during the pandemic. Official SARS-CoV-2 reports were received from the Bavarian Health and Food Safety Authority and data on regional pandemic measures were obtained from the Healthcare Data Platform. With this design, a comprehensive analysis of the pandemic proceedings was performed. We found significantly decreased incidence-rate ratios for pediatric cancer diagnosis during the early spring peak of SARS-CoV-2 as it was observed in May during the pandemic, followed by non-significantly increased metastatic cancer diagnosis two months later. Additionally, the time-to-diagnosis of pediatric malignancies was significantly prolonged during the pandemic, and outpatient contacts were significantly reduced, although the availability of consultations remained the same. From our findings, we may hypothesize that there have been effects on pediatric cancer diagnosis during the COVID-19 pandemic at vulnerable times. Interpretation of changes remains speculative with potential causes from behavior patterns, such as hesitation, concerns, and potential societal changes during phases of public restrictions, rather than overwhelmed medical capacities. Nevertheless, specific awareness is needed to protect this patient population during potential future pandemics.

Introduction: The Medical Service of the Federal Employment Agency is responsible for socio-medical assessments of clients whose ability to work in the labor market is in question. Data about the Medical Service, its structure, and its performance were previously only available within the Federal Employment Agency., Methods: In October 2023, data from the Medical Service containing information on the employee structure, clients, and orders were extracted from three data systems, processed, and analyzed., Results: The number of full-time equivalents (FTEs) in the Medical Service decreased significantly from 2016 (n = 859.1 FTEs) to 2021 (n = 799.0 FTEs). This holds true for the professional groups of physicians, specialist assistants, medical assistants, and externally contracted physicians. The number of female employee FTEs rose significantly during this period from 85.6% (2016) to 87.0% (2021). The part-time ratio also increased significantly from 41.4% (2016) to 50.6% (2021). The number of assignments to the Medical Service was stable in 2017-2019 at around 630,000 but showed a reduction in 2020 (n = 518,538) and 2021 (n = 545,289); in particular, the number of assessments with client contact decreased significantly from 2019 (n = 166,980) to 2020 (n = 52,484). Most of the assignments came from the field of job placement (n = 349,346)., Discussion: The size of the Medical Service was in line with the total number of orders, which can certainly be seen as COVID-19-related in 2020 and 2021 and is likely due to the overall shortage of skilled personnel. The proportion of women and part-time employees increased significantly, with a nationwide part-time trend emerging not only among women. In order to enable all clients who may be unable to perform in the labor market to receive a quick assessment, it is necessary that the number of employees in the Medical Service does not decrease in the future., (© 2024. Springer-Verlag GmbH Deutschland, ein Teil von Springer Nature.)

Introduction: During the COVID-19 pandemic, single parents and their children were particularly exposed to stress due to the containment measures and to limited resources. We analyzed differences in the social and health situation of children and adolescents in one-parent households and two-parent households at the end of the pandemic., Methods: The analysis is based on data from the KIDA study, in which parents of 3‑ to 15-year-old children as well as 16- to 17-year-old adolescents were surveyed in 2022/2023 (telephone: n = 6992; online: n = 2896). Prevalences stratified by family type were calculated for the indicators psychosocial stress, social support, health, and health behavior. Poisson regressions were adjusted for gender, age, level of education, and household income., Results: Children and adolescents from one-parent households are more likely to be burdened by financial restrictions, family conflicts, and poor living conditions and receive less school support than peers from two-parent households. They are more likely to have impairments in health as well as increased healthcare needs, and they use psychosocial services more frequently. Furthermore, they are less likely to be active in sports clubs, but they take part in sporting activities at schools as often as minors from two-parent households. The differences are also evident when controlling for income and education., Discussion: Children and adolescents from one-parent households can be reached well through exercise programs in a school setting. Low-threshold offers in daycare centers, schools, and the community should therefore be further expanded. Furthermore, interventions are needed to improve the socioeconomic situation of single parents and their children., (© 2024. The Author(s).)

Background: Partial or total avoidance of weight-bearing by a lower limb is regularly needed after trauma and surgery. There are approximately 200 such cases per 100 000 persons per year. Forearm crutches have mainly been used in Germany until now to keep these patients mobile. For those who lack the strength or co - ordination needed to use crutches, a wheelchair may become necessary, or they might find themselves forced to continue weightbearing on the affected limb, with possible impending adverse consequences and complications., Methods: The supplementary use of a new type of orthopedic scooter by patients who must avoid weight-bearing by a lower limb, wholly or in part, was studied in a multicenter randomized controlled trial involving 88 subjects. The endpoints were improvement in quality of life (EQ5D, SF36) and improved abilities in everyday life (retrospective registration: DRKS00032980)., Results: Patients who used orthopedic knee scooters (KS) reported a better overall state of health more frequently than those who used forearm crutches (UC) (SF-36 score: 67 [KS group], 95% CI [61; 73]; 59 [UC group], [53; 64]). They also reported less anxiety and depressed mood, greater mobility, and more independence than the patients who used crutches. In addition, they more frequently reported being able to transport themselves 4 x 500 meters in less than 20 minutes (n 30 [KS], 63.8% [48.5; 77.3]; n 6 [UC], 14.6% [5.6, 29.2])., Conclusion: The supplementary use of an orthopedic knee scooter can improve these patients' mobility and independence and prolong the distance over which they can transport themselves. For many patients, this form of treatment may well shorten the time of their total or partial inability to work and thus lower the socioeconomic costs of lower limb injuries and surgery.

Development of Janus-kinase (JAK) inhibitors has revolutionized the therapeutic landscape for patients with myeloproliferative neoplasia (MPN). Following approval of the first JAK1/2-inhibitor Ruxolitinib, symptoms of this inflammatory disease, characterized by splenomegaly, release of inflammatory cytokines and appearance of thrombosis, could be effectively reduced for the first time. However, JAK-inhibitor treatment is limited in several aspects: 1) duration of response: 3 years after initiation of therapy more than 50% of patients have discontinued JAK-inhibitor treatment due to lack of efficacy or resistance; 2) reduction of disease burden: while effective in reducing inflammation and constitutional symptoms, JAK-inhibitors fail to reduce the malignant clone in the majority of patients and therefore lack long-term efficacy. Early clinical trials for patients with myelofibrosis (MF) have tried to address these issues for patients with suboptimal response to Ruxolitinib therapy while combination therapies with Fedratinib are rare. Recent reports provided first evidence on how the JAK2-V617F mutated myeloid cells may influence T-cell responses. JAK2-V617F promoted the synthesis of PD-L1 in MPN cells leading to limited anti-neoplastic T-cell responses, metabolic changes in T-cells and eventually JAK2-V617F-driven immune-escape of MPN cells. These findings may facilitate the use of immunotherapeutic approaches for JAK-mutated clones. Immune checkpoints refer to a variety of inhibitory pathways that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. The FRACTION study is a single arm, open label Phase II trial investigating the combination of Fedratinib with the PD-1 inhibitor Nivolumab in patients with myelofibrosis and suboptimal or lack of response to JAK-inhibitor therapy. Over a 12 months period the trial assesses longer term outcomes, particularly the effects on clinical outcomes, such as induction of clinical remissions, quality of life and improvement of anemia. No prospective clinical trial data exist for combinations of JAK- and immune-checkpoint-inhibitors in the planned MF study population and this study will provide new findings that may contribute to advancing the treatment landscape for MF patients with suboptimal responses and limited alternatives., (© 2024. The Author(s).)

Background: Several legacy and emerging per- and polyfluoroalkyl substances (PFAS) have been regulated around the world. There is growing concern over the proliferation of alternative PFAS, as well as PFAS precursors. Biomonitoring data for PFAS are critical for assessing exposure and human health risk., Methods: We collected serum samples from 289 adult female participants in a 2018-2021 follow-up study of the Maternal-Infant Research on Environmental Chemicals (MIREC) Canadian pregnancy cohort. Samples were analyzed for 40 PFAS using ultra-performance liquid chromatography-tandem mass spectrometry. For those compounds with > 50% detection, as well as the sum of these compounds, we describe serum concentrations and patterns of exposure according to sociodemographic and obstetrical history characteristics., Results: 17 out of 40 PFAS were detected in > 50% of samples with 7 of these detected in > 97% of samples. Median [95th percentile] concentrations (µg/L) were highest for PFOS (1.62 [4.56]), PFOA (0.69 [1.52]), PFNA (0.38 [0.81]), and PFHxS (0.33 [0.92]). Geometric mean concentrations of PFOA and PFHxS were approximately 2-fold lower among those with more children (≥ 3 vs. 1), greater number of children breastfed (≥ 3 vs. ≤ 1), longer lifetime duration of breastfeeding (> 4 years vs. ≤ 9 months), and shorter time since last pregnancy (≤ 4 years vs. > 8 years). We observed similar patterns for PFOS, PFHpS, and the sum of 17 PFAS, though the differences between groups were smaller. Concentrations of PFOA were higher among "White" participants, while concentrations of N-MeFOSE, N-EtFOSE, 7:3 FTCA, and 4:2 FTS were slightly higher among participants reporting a race or ethnicity other than "White". Concentrations of legacy, alternative, and precursor PFAS were generally similar across levels of age, education, household income, body mass index, and menopausal status., Conclusions: We report the first Canadian biomonitoring data for several alternative and precursor PFAS. Our findings suggest that exposure to PFAS, including several emerging alternatives, may be widespread. Our results are consistent with previous studies showing that pregnancy and breastfeeding are excretion pathways for PFAS., (© 2024. Crown.)

Background: Active transport- for example walking and bicycling to travel from place to place- may improve physical fitness and health and mitigate climate change if it replaces motorised transport. The aim of this study is to analyse the active transport behaviour of adults living in Germany, to investigate differences among population groups and to determine whether climate protection is a frequent motive for this behaviour., Methods: This study uses self-reported data of 4,971 adults who participated in a national health survey (German Health Update 2021), which was conducted as a telephone survey from July to December 2021. Associations between active transport behaviour and corresponding motives with sociodemographic and health-related variables were analysed using logistic regression models., Results: Of the adult population, 83% use active transport at least once a week. The frequency and duration of walking per week are significantly higher than those for bicycling (walking 214 min/week; bicycling 57 min/week). Those with a lower education level are less likely to practise active transport than those with a higher education level. Furthermore, women are less likely to use a bicycle for transport than men. Among those practising active transport, the most frequently mentioned motive is "is good for health" (84%) followed by "to be physically active" (74%) and "is good for the climate/environment" (68%). Women and frequent bicyclists (at least 4 days/week) mention climate protection as a motive more often than men and those bicycling occasionally., Conclusions: The improvement of active transport, especially among people with lower education and women (for bicycling), may benefit from better insights into motives and barriers. Climate protection is an important motivator for practising active transport within the adult population living in Germany and should therefore have greater emphasis in behavioural change programmes., (© 2024. The Author(s).)

Background: Approximately one in three survivors of critical illness suffers from intensive-care-unit-acquired weakness, which increases mortality and impairs quality of life. By counteracting immobilization, a known risk factor, active mobilization may mitigate its negative effects on patients. In this single-center trial, the effect of robotic-assisted early mobilization in the intensive care unit (ICU) on patients' outcomes was investigated., Methods: We enrolled 16 adults scheduled for lung transplantation to receive 20 min of robotic-assisted mobilization and verticalization twice daily during their first week in the ICU (intervention group: IG). A control group (CG) of 13 conventionally mobilized patients after lung transplantation was recruited retrospectively. Outcome measures included the duration of mechanical ventilation, length of ICU stay, muscle parameters evaluated by ultrasound, and quality of life after three months., Results: During the first week in the ICU, the intervention group received a median of 6 (interquartile range 3-8) robotic-assisted sessions of early mobilization and verticalization. There were no statistically significant differences in the duration of mechanical ventilation (IG: median 126 vs. CG: 78 h), length of ICU stay, muscle parameters evaluated by ultrasound, and quality of life after three months between the IG and CG., Conclusion: In this study, robotic-assisted mobilization was successfully implemented in the ICU setting. No significant differences in patients' outcomes were observed between conventional and robotic-assisted mobilization. However, randomized and larger studies are necessary to validate the adequacy of robotic mobilization in other cohorts., Trial Registration: This single-center interventional trial was registered in clinicaltrials.gov as NCT05071248 on 27/08/2021., (© 2024. The Author(s).)

Background : Among the risk factors for nonunion are unchangeable patient factors such as the type of injury and comorbidities, and factors that can be influenced by the surgeon such as fracture treatment and the postoperative course. While there are numerous studies analyzing unchangeable factors, there is poor evidence for factors that can be affected by the physician. This raises the need to fill the existing knowledge gaps and lay the foundations for future prevention and in-depth treatment strategies. Therefore, the goal of this study was to illuminate knowledge about nonunion in general and uncover the possible reasons for their development; Methods : This was a retrospective analysis of 327 patients from 2015 to 2020 from a level I trauma center in Germany. Information about patient characteristics, comorbidities, alcohol and nicotine abuse, fracture classification, type of osteosynthesis, etc., was collected. Matched pair analysis was performed, and statistical testing performed specifically for atrophic long-bone nonunion; Results : The type of osteosynthesis significantly affected the development of nonunion, with plate osteosynthesis being a predictor for nonunion. The use of wire cerclage did not affect the development of nonunion, nor did the use of NSAIDs, smoking, alcohol, osteoporosis and BMI; Conclusion : Knowledge about predictors for nonunion and strategies to avoid them can benefit the medical care of patients, possibly preventing the development of nonunion.

Background: Early mobilization is only carried out to a limited extent in the intensive care unit. To address this issue, the robotic assistance system VEMOTION® was developed to facilitate (early) mobilization measures more easily. This paper describes the first integration of robotic assistance systems in acute clinical intensive care units., Objective: Feasibility test of robotic assistance in early mobilization of intensive care patients in routine clinical practice., Setting: Two intensive care units guided by anesthesiology at a German university hospital., Participants: Patients who underwent elective surgery with postoperative treatment in the intensive care unit and had an estimated ventilation time over 48 h., Methods: Participants underwent robot-assisted mobilization, scheduled for twenty-minute sessions twice a day, ten times or one week, conducted by nursing staff under actual operational conditions on the units. No randomization or blinding took place. We assessed data regarding feasible cutoff points (in brackets): the possibility of enrollment (x ≥ 50 %), duration (pre- and post-setup (x ≤ 25 min), therapy duration (x = 20 min), and intervention-related parameters (number of mobilizing professionals (x ≤ 2), intensity of training, events that led to adverse events, errors or discontinuation). Mobilizing professionals rated each mobilization regarding their physical stress (x ≤ 3) and feasibility (x ≥ 4) on a 7 Point Likert Scale. An estimated sample size of at least twenty patients was calculated. We analyzed the data descriptively., Results: Within 6 months, we screened thirty-two patients for enrollment. 23 patients were included in the study and 16 underwent mobilization using robotic assistance, 7 dropped out (enrollment eligibility = 69 %). On average, 1.9 nurses were involved per therapy unit. Participants received 5.6 robot-assisted mobilizations in mean. Pre- and post-setup had a mean duration of 18 min, therapy a mean of 21 min. The robot-assisted mobilization was started after a median of 18 h after admission to the intensive care unit. We documented two adverse events (pain), twelve errors in handling, and seven unexpected events that led to interruptions or discontinuation. No serious adverse events occurred. The mobilizing nurses rated their physical stress as low (mean 2.0 ± 1.3) and the intervention as feasible (mean 5.3 ± 1.6)., Conclusions: Robot-assisted mobilization was feasible, but specific safety measures should be implemented to prevent errors. Robotic-assisted mobilization requires process adjustments and consideration of unit staffing levels, as the intervention does not save staff resources or time., Registration: clinicaltrials.org TRN: NCT05071248; Date: 2021/10/08; URL https://clinicaltrials.gov/ct2/show/NCT05071248., Tweetable Abstract: Robot-assisted early mobilization in intensive care patients is feasible and no adverse event occurred., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests. The company that manufactures the VEMOTION® system is part of the overall study consortium. However, it was not part of the clinical study or the analysis team., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Prior animal and epidemiological studies suggest that per- and polyfluoroalkyl substances (PFAS) exposure may be associated with reduced birth weight. However, results from prior studies evaluated a relatively small set of PFAS., Objectives: Determine associations of gestational PFAS concentrations in maternal serum samples banked for 60 years with birth outcomes., Methods: We used data from 97 pregnant women from Boston and Providence that enrolled in the Collaborative Perinatal Project (CPP) study (1960-1966). We quantified concentrations of 27 PFAS in maternal serum in pregnancy and measured infant weight, height and ponderal index at birth. Covariate-adjusted associations between 11 PFAS concentrations (>75% detection limits) and birth outcomes were estimated using linear regression methods., Results: Median concentrations of PFOA, PFNA, PFHxS, and PFOS were 6.189, 0.330, 14.432, and 38.170 ng/mL, respectively. We found that elevated PFAS concentrations during pregnancy were significantly associated with lower birth weight and ponderal index at birth, but no significant associations were found with birth length. Specifically, infants born to women with PFAS concentrations ≥ median levels had significantly lower birth weight (PFOS: β = -0.323, P = 0.006; PFHxS: β = -0.292, P = 0.015; PFOA: β = -0.233, P = 0.03; PFHpS: β = -0.239, P = 0.023; PFNA: β = -0.239, P = 0.017). Similarly, women with PFAS concentrations ≥ median levels had significantly lower ponderal index (PFHxS: β = -0.168, P = 0.020; PFHxA: β = -0.148, P = 0.018)., Conclusions: Using data from this US-based cohort study, we found that 1) maternal PFAS levels from the 1960s exceeded values in contemporaneous populations and 2) that gestational concentrations of certain PFAS were associated with lower birth weight and infant ponderal index. Additional studies with larger sample size are needed to further examine the associations of gestational exposure to individual PFAS and their mixtures with adverse birth outcomes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Dr. Braun was compensated for serving as an expert witness on behalf of plaintiffs in litigation related to PFAS-contaminated drinking water., (Copyright © 2023. Published by Elsevier Inc.)

Age-standardized cancer incidence has decreased over the last years for many cancer sites in developed countries. Whether these trends led to narrowing or widening socioeconomic inequalities in cancer incidence is unknown. Using cancer registry data covering 48 million inhabitants in Germany, the ecological association between age-standardized total and site specific (colorectal, lung, prostate and breast) cancer incidence in 2007 to 2018 and a deprivation index on district level (aggregated to quintiles) was investigated. Incidence in the most and least deprived districts were compared using Poisson models. Average annual percentage changes (AAPCs) and differences in AAPCs between deprivation quintiles were assessed using Joinpoint regression analyses. Age-standardized incidence decreased strongly between 2007 and 2018 for total cancer and all cancer sites (except female lung cancer), irrespective of the level of deprivation. However, differences in the magnitude of trends across deprivation quintiles resulted in increasing inequalities over time for total cancer, colorectal and lung cancer. For total cancer, the incidence rate ratio between the most and least deprived quintile increased from 1.07 (95% confidence interval: 1.01-1.12) to 1.23 (1.12-1.32) in men and from 1.07 (1.01-1.13) to 1.20 (1.14-1.26) in women. Largest inequalities were observed for lung cancer with 82% (men) and 88% (women) higher incidence in the most vs the least deprived regions in 2018. The observed increase in inequalities in cancer incidence is in alignment with trends in inequalities in risk factor prevalence and partly utilization of screening. Intervention programs targeted at socioeconomically deprived and urban regions are highly needed., (© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

The approved dose of bosutinib in chronic phase CML is 400 mg QD in first-line and 500 mg QD in later-line treatment. However, given that gastrointestinal (GI) toxicity typically occurs early after treatment initiation, physicians often tend to start therapy with lower doses although this has never been tested systematically in prospective trials in the Western world. The Bosutinib Dose Optimization (BODO) Study, a multicenter phase II study, investigated the tolerability and efficacy of a step-in dosing concept of bosutinib (starting at 300 mg QD) in chronic phase CML patients in 2 nd or 3 rd line who were intolerant and/or refractory to previous TKI treatment. Of 57 patients included until premature closure of the study due to slow recruitment, 34 (60%) reached the targeted dose level of 500 mg QD following the 2-weekly step-in dosing regimen. While the dosing-in concept failed to reduce GI toxicity (grade II-IV, primary study endpoint) to < 40% (overall rate of 60%; 95% CI: 45-74%), bosutinib treatment (mean dosage: 403 mg/day) showed remarkable efficacy with a cumulative major molecular remission (MMR) rate of 79% (95% CI: 66 to 88%) at month 24. Of thirty patients refractory to previous therapy and not in MMR at baseline, 19 (64%) achieved an MMR during treatment. GI toxicity did not significantly impact on patient-reported outcomes (PRO) and led to treatment discontinuation in only one patient. Overall, the results of our trial support the efficacy and safety of bosutinib after failure of second-generation TKI pre-treatment. Trial registration: NCT02577926., (© 2023. The Author(s).)

Background: It is well known that there are gender differences in the health behaviour and physical and mental health of children. The COVID-19 pandemic influenced the health and lifestyles of children and adolescents by changing their living conditions. The present work investigates whether gender differences in selected health indicators are evident more than two years after the onset of the pandemic., Methods: In the study Kindergesundheit in Deutschland aktuell (KIDA) (German Children's Health Update), cross-sectional telephone surveys were conducted with parents of 3- to 15-year-olds (n=3,478). Parental information on the general and mental health of the child, on increased need for health care and mental health services, as well as on physical activity and utilisation of sports activities were queried in standardised manner. Gender differences were assessed using Chi 2 tests., Results: A total of 91% of the girls and 92% of the boys had their general health assessed as being (very) good by their parents (difference not significant, n.s.). An increased need for care and support was indicated for 10.6% of the 3- to 15-year-olds (girls: 9%, boys: 12%, n.s.). Boys met the physical activity recommendations of the WHO significantly more often (60%) than girls (54%). Good to excellent mental health was reported for 93% of both boys and girls. When changes during the pandemic were reported, no differences were found in the responses for girls compared to boys., Conclusions: Gender differences were found for individual parameters and age groups. These differences must be assessed in the context of other social determinants of health, and need to be considered when planning preventive measures., Competing Interests: Conflicts of interest The authors declared no conflicts of interest., (© Robert Koch Institute. All rights reserved unless explicitly granted.)

Introduction: High consumption of red and processed meat increases the risk of several chronic diseases. Many people, especially in high-income countries, eat more meat than recommended by nutritional and health agencies. Meat production also has negative impacts on the environment and contributes to climate change. Therefore, climate protection, besides health or animal welfare, could motivate individuals to eat less meat. Willingness to reduce meat consumption and motives to do so are not yet fully understood., Methods and Analysis: Based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) extended guidelines, a scoping review of peer-reviewed original studies will be conducted to address three questions: What is the evidence regarding (1) the willingness of individuals to reduce meat consumption to mitigate climate change, (2) the awareness of individuals about the link between their meat consumption and the potential to mitigate climate change and (3) individuals having reduced meat consumption for the reason of climate protection? We will search the databases Medline (via PubMed), Scopus, Embase, Greenfile (via Ebsco) and PsynDex/CurrentContent/Agris (via Livivo) using a systematic search string. Studies from 2015 onwards, published in English, German, Danish or Dutch, will be included. We will include observational studies, qualitative studies, intervention studies (if they include surveys) and reviews. Data will be summarised in a narrative synthesis, comprising methods, population characteristics, meat type under study, indicators measured and limitations. Key findings will be grouped according to the research questions. This scoping review will help clarify the role of climate protection in individual reduction of meat consumption and identify research gaps in this field., Ethics and Dissemination: Formal ethical approval is not required, as primary data will not be collected in this study. Findings of this scoping review will be presented at scientific conferences and published in a peer-reviewed journal., Trial Registration Number: https://doi.org/10.17605/OSF.IO/MWB85., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Incomplete data due to nonparticipation and noncompliance with the study protocol can bias the results of studies. We investigated how a nationwide accelerometer sample of adolescents and young adults is affected by such incomplete data., Methods: We analyzed cross-sectional data from 6465 participants (11-31 y old) who participated in a national health survey in Germany (KiGGS Wave 2; 2014-2017). The data included information about the participation in the measurement of physical activity using accelerometers, compliance with the wear-time protocol, and sociodemographic and health-related variables. Multivariable regression analyses were conducted to detect factors associated with incomplete data., Results: Of the total sample, 78.0% participated in the accelerometer part of the study, and 83.5% of the participants with data available complied with the wear-time protocol. In 11- to 17-year-olds, the likelihood of having incomplete accelerometer data was higher in boys, older adolescents, adolescents with a lower sociodemographic status, adolescents with overweight, adolescents not participating in organized sport, adolescents not speaking only German at home, current smokers, and adolescents having a higher soft drink consumption. In 18- to 31-year-olds, the likelihood of having incomplete accelerometer data was higher in men, adults with a lower educational level, adults not speaking only German at home, and adults who smoke., Conclusions: Our results suggest that accelerometer samples are biased such that participants with more beneficial health behaviors provide complete accelerometer data more often. This knowledge should be used to design effective recruitment strategies and should be considered when interpreting results of accelerometer studies.

Methylparaben (MP) and propylparaben (PP) are commonly used as food, cosmetic, and drug preservatives. These parabens are detected in the majority of US women and children, bind and activate estrogen receptors (ER), and stimulate mammary tumor cell growth and invasion in vitro. Hemizygous B6.FVB-Tg (MMTV-PyVT)634Mul/LellJ female mice (n = 20/treatment) were exposed to MP or PP at levels within the US Food and Drug Administration's "human acceptable daily intake." These paraben-exposed mice had increased mammary tumor volume compared with control mice (P < 0.001) and a 28% and 91% increase in the number of pulmonary metastases per week compared with the control mice, respectively (P < 0.0001). MP and PP caused differential expression of 288 and 412 mammary tumor genes, respectively (false discovery rate < 0.05), a subset of which has been associated with human breast cancer metastasis. Molecular docking and luciferase reporter studies affirmed that MP and PP bound and activated human ER, and RNA-sequencing revealed increased ER expression in mammary tumors among paraben-exposed mice. However, ER signaling was not enriched in mammary tumors. Instead, both parabens strongly impaired tumor RNA metabolism (eg, ribosome, spliceosome), as evident from enriched KEGG pathway analysis of differential mammary tumor gene expression common to both paraben treatments (MP, P < 0.001; PP, P < 0.01). Indeed, mammary tumors from PP-exposed mice had an increased retention of introns (P < 0.05). Our data suggest that parabens cause substantial mammary cancer metastasis in mice as a function of their increasing alkyl chain length and highlight the emerging role of aberrant spliceosome activity in breast cancer metastasis., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Physical activity is a significant health promotion behaviour. COVID-19 pandemic mitigation measures, such as reducing social contact, closing sports facilities and working from home offices, may make it more difficult to engage in regular physical activity., Methods: The data collected between July and October 2021 from the nationally representative study German Health Update (GEDA 2021) were used. The activity behaviour is described by the change in the amount of sports activity as well as the amount of physical active transport (walking/cycling) since the beginning of the COVID-19 pandemic. The sample comprises 2,985 participants aged 18 and older., Results: A quarter of the population reduced their sports activity compared to before the COVID-19 pandemic, while 12% increased their sports activity and 38% reported no change. In terms of physical active transport, it shows that 15% reduced the amount, 17% increased it and 55% maintained it. Compared to younger adults, older adults were more likely to maintain their activity behaviour rather than reduce or increase it., Conclusion: Even before the pandemic, physical inactivity was common among the population. The high proportion of adults who reduced their sports activity during the pandemic underlines the need for effective measures to promote physical activity., Competing Interests: Conflicts of interest The authors declared no conflicts of interest., (© Robert Koch Institute. All rights reserved unless explicitly granted.)

Background: Sedentary behaviour is increasingly perceived as a risk factor for the development of diseases and for increased mortality. In particular, increased time spent sitting in combination with low physical activity seems to have negative health consequences., Methods: In the nationwide cross-sectional study German Health Update (GEDA 2019/2020-EHIS), the indicator 'sitting' was captured by the self-report of the participants., Results: For at least eight hours a day, 16.7% of women and 22.3% of men sit: Men more often than women, younger persons more often than older persons and the proportion increases significantly from the low to the high education group. Similarly, about one fifth of adults in Germany sit for at least four hours a day and do not engage in physical activity in their leisure time., Conclusion: The results indicate that preventive measures are needed to reduce time spent sitting and increase physical activity., Competing Interests: Conflicts of interest The authors declared no conflicts of interest., (© Robert Koch Institute. All rights reserved unless explicitly granted.)

Background: The rising number of people using methamphetamine leads to an increasing need for treatment options for this patient group. Evidence-based research on the efficacy of treatment programs for methamphetamine users is limited. Due to specific characteristics of methamphetamine users, the question arises whether established treatment methods for individuals using other substances can be effective for the treatment of methamphetamine dependence as well. We hypothesize that there are significant differences between the two groups that may affect the effectiveness of treatment and worsen the prognosis of treatment outcomes for methamphetamine users compared to consumers of other substances., Aim: To investigate potential differences in cognitive functioning and psychopathology between methamphetamine users and other substance users and possible correlations with treatment outcomes., Methods: A total of 110 subjects were recruited for an observational, longitudinal study from a German inpatient addiction treatment center: 55 patients with methamphetamine dependence and 55 patients with dependence of other substances ("OS group"). Both groups were examined at beginning (baseline) and end of treatment (after 6 mo) with regard to treatment retention, craving, cognitive functioning, psychosocial resources, personality traits, depression, and other psychiatric symptoms. Instruments used were Raven's IQ test, Mannheimer craving scale, cognitrone cognitive test battery, NEO personality factors inventory, Hamilton depression scale, Becks depression inventory, and a symptom checklist. The statistical methods used were χ 2 -test, t -test and multiple mixed ANOVAs., Results: A total drop-out rate of 40% (methamphetamine-group: 36.4%; OS-group: 43.6%) was observed without significant differences between groups. At baseline, methamphetamine-group subjects significantly differed from OS-group individuals in terms of a lower intelligence quotient, fewer years of education, slower working speed, and decreased working accuracy, as well as less cannabinoid and cocaine use. Methamphetamine-group subjects further showed a significantly lower score of conscientiousness, depressive, and psychiatric symptoms than subjects from the OS-group. In both groups, a reduction of craving and depressive symptoms and an improvement of working speed and working accuracy was noted after treatment., Conclusion: There are differences between methamphetamine users and users of other drugs, but not with regard to the effectiveness of treatment in this inpatient setting. There are differences in cognitive function and psychopathology between methamphetamine and other drugs users. The existing treatment options seem to be an effective approach in treating methamphetamine dependence., Competing Interests: Conflict-of-interest statement: All authors declare no conflict of interests for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Previous evidence has suggested that physically inactive individuals and extensive media users are at high risk for experiencing depressive symptoms. We examined personality traits and perceived social support as potential moderators of this association. Personality and perceived social support were included as two of the most frequently considered variables when determining predispositioning factors for media use phenomena also discussed in relation to physical activity., Methods: We analysed cross-sectional data from 1402 adults (18-31 years old) who participated in a national health survey in Germany (KiGGS, Study on the health of children and adolescents in Germany, wave 2). The data included one-week accelerometer assessments as objective indicators of physical activity, self-reported media use, depressive symptoms, perceived social support and Big 5 personality traits. An elastic net regression model was fit with depressive symptoms as outcome. Ten-fold cross-validation was implemented., Results: Amongst the main effects, we found that high media use was positively correlated with depressive symptoms, whereas physical activity was not correlated. Looking at support and individual differences as moderators, revealed that PC use was more strongly correlated with depressive symptoms in cases of low levels of perceived social support. Positive associations of social media use with depressive symptoms were more pronounced, whereas negative associations of moderate to vigorous physical activity with depressive symptoms were less pronounced in extraverts than they were in introverts., Conclusions: Results highlight the importance of considering individual factors for deriving more valid recommendations on protective health behaviours., (© 2022. The Author(s).)

Background: Pharmacological neuroenhancement (PN) is a common healthcare problem at least among students. PN seems to be associated with stressful situations. There is a lack of data about personal characteristics, comorbidities, and coping strategies regarding stress and factors of resilience in students and medical staff. Methods: A web-based survey about the non-medical use of PN drugs with a focus on neuroenhancement was developed and distributed among medical students throughout Germany; the questionnaire was open in April and May of 2020. The survey contained questions about the use of well-known PN drugs, frequency, special purposes, reasons for the use, psychiatric disorders, use of psychotropic drugs apart from PN purposes, and factors of resilience using the brief resilience scale. Results: Data of 1,159 students of medicine were analyzed. The most frequently used substances for PN were coffee (78.8% lifetime prevalence rate), energy drinks (45.7%), caffeine tablets (24.3%), methylphenidate (5.2%), illicit amphetamines (2.0%), and cocaine (1.7%). 98.4% suspected that PN drug use could lead to addiction. PN drug use specifically for PN was significantly associated with the use of (a) any psychotropic drug (other than neuroenhancers), (b) any psychiatric disorder, and (c) higher values of feeling pressure to perform in professional/students' life and in private life as well as (d) the subjective feeling of pressure to perform to be burdening and (e) harmful to one's own health. PN drug use in general was significantly associated with being less resilient. The use of illicit PN drugs, over the counter drugs and prescription drugs was associated with being less resilient. Conclusion: This study indicates that PN with legal and illegal drugs is a widespread phenomenon among German medical students. Users seem to be more often burdened by psychiatric disorders, especially addictive disorders, the perception of stress, pressure to perform and low levels of resilience. These aspects should be considered in further investigation of PN drug use., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jebrini, Manz, Koller, Krause, Soyka and Franke.)

Background: Maps of the temporal evolution of the regional distribution of a health-related measure enable public health-relevant assessments of health outcomes., Objectives: The paper introduces the concept of standardized case fatality rate (sCFR). It describes the ratio of the regional variation in mortality to the regional variation in the documented infection process. The regional sCFR values are presented in maps and the time-varying regional heterogeneity observed in them is interpreted., Materials and Methods: The regional sCFR is the quotient of the regional standardized mortality and case rate. It is estimated using a bivariate model. The sCFR values presented in maps are based on SARS-CoV‑2 reporting data from Bavaria since the beginning of April 2020 until the end of March 2021. Four quarters (Q2/20, Q3/20, Q4/20, and Q1/21) are considered., Results: In the quarters considered, the naïve CFR values in Bavaria are 5.0%, 0.5%, 2.5%, and 2.8%. In Q2/20, regional sCFR values are irregularly distributed across the state. This heterogeneity weakens in the second wave of the epidemic. In Q1/21, only isolated regions with elevated sCFR (> 1.25) appear in southern Bavaria. Clusters of regions with sCFR > 1.25 form in northern Bavaria, with Oberallgäu being the region with the lowest sCFR (0.39, 95% credibility interval: 0.25-0.55)., Conclusions: In Bavaria, heterogeneous regional SARS-CoV-2-specific sCFR values are shown to change over time. They estimate the relative risk of dying from or with COVID-19 as a documented case. Strong small-scale variability in sCFR suggests a preference for regional over higher-level measures to manage the incidence of infection., (© 2021. The Author(s).)

Objective: Stapes surgery is considered an effective treatment in otosclerosis, but controversy remains regarding predictors of surgical outcome., Study Design: Retrospective cohort study., Setting: Tertiary referral center., Patients: One hundred sixty three cases of stapes surgery between 2012 and 2019 were reviewed., Main Outcome Measures: Primary outcome measures were relative hearing improvement (relHI), defined as preoperative minus postoperative air conduction divided by preoperative air-bone gap (ABG), as well as relative ABG closure (relABGc), defined as preoperative ABG minus postoperative ABG divided by preoperative ABG. Univariate and multivariate linear regression analyses were performed to determine independent predictors for these outcomes., Results: Higher preoperative bone conduction (BC) and primary surgery (compared with revision) were independently associated with increased relHI (p = 0.001 and p = 0.004, respectively). Lower preoperative BC, higher preoperative ABG, primary surgery, and age were independently associated with increased relABGc (p = 0.0030, p < 0.001, p = 0.0214, and p = 0.0099, respectively). Sex did not predict surgical outcome. In patients with less than 20 dB preoperative ABG, likelihood of negative relABGc was increased (compared with 20-30 dB or >30 dB preoperative ABG, p = 0.0292, Fisher's exact test). This tendency was not significant for relHI (p = 0.074)., Conclusions: Our findings demonstrate that calculating HI and ABGc in relation to preoperative ABG can reliably predict outcomes of stapes surgery. Both primary and revision stapes surgery are effective treatment options, but relative improvement is higher in primary cases. Preoperative BC, preoperative ABG, and age predict surgical outcomes as well. Otosclerosis patients with low preoperative ABG, especially less than 20 dB, should be counseled and selected cautiously regarding stapes surgery., Competing Interests: Conflict of interest and financial disclosure: Any financial or personal relationships with other people or organizations, that could inappropriately influence (bias) the work, are disclosed by all authors. The authors declare that they have no conflict of interest. The authors received no financial support for the research, authorship, and/or publication of this article., (Copyright © 2021, Otology & Neurotology, Inc.)

Introduction: Pharmacological neuroenhancement (PN) is a topic of increasing importance and prevalence among students. However, there is a lack of differentiating PN substances, according to their psychoactive effects. In particular, there is a lack of data about PN by caffeinated drinks, even if coffee is a common and broadly used Neuroenhancer because of its cognitively enhancing effects regarding wakefulness, alertness and concentration. Materials and Methods: A web-survey was developed for German students and alumni about the non-medical use of caffeine for PN contained questions about coffee, caffeinated drinks and energy drinks, caffeine pills and methylxanthine tea regarding frequency and further contextual factors. Results: Six hundred and eighty-three participants completed the survey. Nearly all participants knew about PN (97.7%). 88.1% admitted using some over-the-counter substances. For PN purposes, coffee was used by 72.9% followed by energy drinks (68.2%) and cola drinks (62.4%). Methylxanthine containing tea was used for PN purposes, too (black tea 52.3%, green tea 51.7%). 1.8% admitted using illegal substances or prescription drugs, too. Discussion: Using legal methylxanthine containing drinks for PN seems to be extremely common with coffee and energy drinks being the preferred substances, while illegal and prescription drugs are only minimally used. Further studies should investigate the awareness of methylxanthine containing drinks as well as its character to be a flavoring drink or a neuroenhancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Franke, Koller, Krause, Proebstl, Kamp, Pogarell, Jebrini, Manz, Chrobok and Soyka.)

Background: As children show a more complex but less structured movement behavior than adults, assessment of their many spontaneous and impulsive movements is a challenge for physical activity (PA) assessment. Since neither questionnaires nor accelerometers enable optimal detection of all facets of PA, a multimodal, combined approach of self-reported and device-based methods is recommended. Based on the number of days on which the participants reached the physical activity (PA) values given in the WHO guideline, this study examines 1) the difference between self-reported and device-based, measured PA and 2) whether PA differences between age and gender groups obtained by two methods are comparable., Methods: Participants aged 6-17 years were randomly chosen and data were collected representatively at 167 sample points throughout Germany within the Motorik-Modul Study. PA of n = 2694 participants (52.3% female) was measured using the ActiGraph accelerometer (ACC) and a physical activity questionnaire (PAQ). The sample was divided into three age groups (6-10 yrs. n = 788, 11-13 yrs. n = 823, 14-17 yrs. n = 1083). Numbers of days per week with at least 60 min moderate to vigorous PA (MVPA) were analyzed for both methods., Results: Only every 25th respondent (4%) reaches the WHO standard of 60 min MVPA every day if measured with ACC. Self-reported PA was slightly higher (9%) (mean PAQ  = 3.82 days; mean ACC  = 2.34 days; F method  = 915.85; p = <.001; f Cohen  = .64). The differences between the methods are significantly smaller in younger children than in the older age groups (F age  = 264.2, p < .001; f Cohen  = .48). The older the subjects are, the lower is the proportion of those who meet the WHO guideline on each day, with girls meeting the guideline less frequently than boys in all age groups., Conclusion: Children and adolescents living in Germany show a very low adherence to the WHO guideline on PA. While younger children are much more active with their free play, especially children over 10 years of age and especially girls should be the target of programs to increase PA.

Background: Diagnostic delay and neurologic deterioration are still a problem for the treatment of rapidly progressing CNS lymphoma (CNSL); there is an unmet need for a diagnostic test with a high diagnostic yield and limited risk, minimizing the time to the initiation of effective treatment. Methods: In this prospective monocentric study, we analyzed the utility of CXCL13 and CXCL9 as diagnostic, therapeutic and prognostic biomarkers for CNSL. Cerebrospinal fluid (CSF) from 155 consecutive patients admitted with brain lesions of various origins was collected. Levels of CXCL13 and CXCL9 were analyzed by ELISA. Additionally, CSF was analyzed during CNSL disease course (relapse, remission, progress) in 17 patients. Results: CXCL13 and CXCL9 CSF levels were significantly increased in patients with CNSL compared to control patients with lesions of other origin. Using logistic regression and a minimal- p -value approach, a cut-off value of 80 pg/ml for CXCL13 shows high sensitivity (90.7%) and specificity (90.1%) for the diagnosis of active CNSL. CXCL9 at a cut-off value of 84 pg/ml is less sensitive (61.5%) and specific (87.1%). Both cytokines correlate with the clinical course and response to therapy. Conclusions: Our results confirm the excellent diagnostic potential of CXCL13 and introduce CXCL9 as a novel albeit less powerful marker for PCNSL., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Masouris, Manz, Pfirrmann, Dreyling, Angele, Straube, Langer, Huber, Koedel and Von Baumgarten.)

Background: Physical activity (PA) has beneficial effects on health and health-related quality of life (HRQoL), which is a protective factor of illness and mortality. The purpose of this examination was to investigate if self-reported and device-based measures of PA were related to HRQoL in adolescents., Methods: Participants (N = 1565; 54.3% female; M age  = 14.37 years, SD age  = 1.99) were recruited from 167 sample points across Germany. Adolescents self-reported their PA, supplemented by a 1-week examination of device-based PA using accelerometry. Additionally, they completed the multidimensional KIDSCREEN-27 to assess HRQoL., Results: Results showed that self-reported PA was correlated with overall HRQoL, Physical Well-Being, Psychological Well-Being, Social Support & Peers, and School Environment, whereas device-based PA was only correlated with Physical as well as Psychological Well-Being. Further, self-reported PA significantly predicted all facets of HRQoL except for Autonomy and Parent Relations, whereas device-based PA solely heightened the amount of explained variance in the Physical Well-Being subscale., Conclusions: Findings demonstrate the importance of self-reported PA as it is related to almost all facets of HRQoL. Both measures of PA are not congruent in their relationship with HRQoL and thus implications have to be carefully considered. Future studies should investigate the direct effect of PA on HRQoL and health in a longitudinal approach to account for the causality of effects.

Aim of Study: This study aims to provide population-based reference values for heart rate-based indicators of cardiorespiratory fitness for adults with physical activity readiness aged 18 to 64 years living in Germany., Methods: Based on data on 2,826 individuals who participated in a submaximal cycle ergometer exercise test as part of the German National Health Interview and Examination Survey for Adults (DEGS1) between 2008 and 2011, we calculated the following indicators: physical working capacity at 150 and 130 beats/min and at 75% of estimated maximum heart rate (PWC150, PWC130 and PWC75%) as well as heart rate-based estimated maximum oxygen uptake (VO 2 max). We used the LMS method by Cole & Green 1992 to calculate reference values., Results: 25 th , 50 th and 75 th percentiles of PWC150 were 1.5, 1.77 and 2.08 watts/kg among men and 1.18, 1.44 and 1.69 among women. 25 th , 50 th and 75 th percentiles of PWC130 were 1.16, 1.41 and 1.68 watts/kg among men and 0.81, 1.05 and 1.29 among women. Age-dependent median PWC75% values among men and women were 1.87 - age in years× 0.01 and 1.31 - (age in years/100) 2 × 0.98, respectively, and VO 2 max among men is 41.7 - age× 0.15., Conclusions: The references values presented can be used for individual rating of cardiorespiratory fitness among adults living in Germany. Furthermore, they can serve as a basis for regular monitoring purposes., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenskonflikt besteht., (Thieme. All rights reserved.)

The COVID-19 pandemic poses new challenges to both individuals and societies that impact health behaviour in many ways. This narrative review brings together initial findings for smoking, alcohol use, nutrition, physical activity and obesity. Smoking and obesity are potential direct risk factors for a severe course of COVID-19, and alcohol abuse, physical inactivity and an unbalanced diet can be indirect risk factors. The constraints of public life to contain the COVID-19 pandemic reduced the opportunities for physical activity and sports, although the initial results on physical activity during this period for Germany do not reflect this assumption. While a part of the population reports making healthier diet choices than before the pandemic, others do not. For smoking and risky alcohol use, data at an aggregate level for the general population do not indicate any behaviour changes. However, different trends appear to be emerging for different population groups pointing to the fact that social inequalities in pandemic-related changes to health behaviour must be assumed. Should further studies confirm these results, this would indicate a need for pandemic-specific prevention measures. Furthermore, specifically during the pandemic, prevention and health promotion measures directed at changes to health behaviour should continue to be implemented and adapted to the restrictions due to the pandemic. Equity in health should be promoted in particular., Competing Interests: Conflicts of interest The authors declared no conflicts of interest., (© Robert Koch Institute. All rights reserved unless explicitly granted.)

This study investigates the effects of two different residential treatments and of treatment drop-out in a German methamphetamine (MA) dependent sample. 108 subjects from two addiction treatment concepts were recruited at treatment begin and followed-up at 12 (T2) and 18 (T3) months after treatment. Based on follow-up samples (n = 38 at T2, n = 25 at T3), 77.1% at T2 and 68.0% at T3 were MA abstinent. Classifying everyone, who did not participate at follow-ups as having had a relapse, showed MA-abstinence rates of 25.0% (at T2) and 15.7% (at T3). There was no difference in MA-use between treatment conditions nor between treatment completers and drop-outs. Having injected any substance predicted MA-use at T2 (p = .03). The median time of relapse was 1.5 days after hospital release. Depression scores at T2 predicted MA-use at T3 (p = .02). T2 participants that dropped out of treatment had higher craving scores at T2, than T2 subjects who completed treatment (p = .03). The results show positive effects of current inpatient treatment programs without differences between different concepts. More research is needed to clarify the impact of treatment drop-out. Attention should be paid to a successful transition from residential to outpatient services and to a reduction of study attrition., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Behavioural interventions may increase social inequalities in health. This study aimed to project the equity impact of physical activity interventions that have differential effectiveness across education groups on the long-term health inequalities by education and gender among older adults in Germany., Methods: We created six intervention scenarios targeting the elderly population: Scenarios #1-#4 applied realistic intervention effects that varied by education (low, medium high). Under scenario #5, all older adults adapted the physical activity pattern of those with a high education. Under scenario #6, all increased their physical activity level to the recommended 300 min weekly. The number of incident ischemic heart disease, stroke and diabetes cases as well as deaths from all causes under each of these six intervention scenarios was simulated for males and females over a 10-year projection period using the DYNAMO-HIA tool. Results were compared against a reference-scenario with unchanged physical activity., Results: Under scenarios #1-#4, approximately 3589-5829 incident disease cases and 6248-10,320 deaths could be avoided among males over a 10-year projection period, as well as 4381-7163 disease cases and 6914-12,605 deaths among females. The highest reduction for males would be achieved under scenario #4, under which the intervention is most effective for those with a high education level. Scenario #4 realizes 2.7 and 2.4% of the prevented disease cases and deaths observed under scenario #6, while increasing inequalities between education groups. In females, the highest reduction would be achieved under scenario #3, under which the intervention is most effective amongst those with low levels of education. This scenario realizes 2.7 and 2.9% of the prevented disease cases and deaths under scenario #6, while decreasing inequalities between education groups. Under scenario #5, approximately 31,687 incident disease cases and 59,068 deaths could be prevented among males over a 10-year projection period, as well as 59,173 incident disease cases and 121,689 deaths among females. This translates to 14.4 and 22.2% of the prevented diseases cases among males and females under scenario #6, and 13.7 and 27.7% of the prevented deaths under scenario #6., Conclusions: This study shows how the overall population health impact varies depending on how the intervention-induced physical activity change differs across education groups. For decision-makers, both the assessment of health impacts overall as well as within a population is relevant as interventions with the greatest population health gain might be accompanied by an unintended increase in health inequalities.

Background: Currently, no nationwide objective physical activity data exists for children and adolescents living in Germany. The German Health Interview and Examination Survey for Children and Adolescents (KiGGS) and the Motorik-Modul study (MoMo) is a national cohort study that has incorporated accelerometers in its most recent data collection wave (wave 2, since 2014). This wave 2 marks the first nationwide collection of objective data on the physical activity of children and adolescents living in Germany., Objective: The purpose of this protocol is to describe the methods used in the KiGGS and MoMo study to capture the intensity, frequency, and duration of physical activity with accelerometers., Methods: Participants (N=11,003, aged 6 to 31 years) were instructed to wear an ActiGraph GT3X+ or wGT3X-BT accelerometer laterally on the right hip. Accelerometers were worn on consecutive days during waking hours, including at least 4 valid weekdays and 1 weekend day (wear time >8 hours) in the evaluation. A nonwear time protocol was also implemented., Results: Data collection was completed by October 2017. Data harmonization took place in 2018. The first accelerometer results from this wave were published in 2019, and detailed analyses are ready to be submitted in 2020., Conclusions: This study protocol provides an overview of technical details and basic choices when using accelerometers in large-scale epidemiological studies. At the same time, the restrictions imposed by the specified filters and the evaluation routines must be taken into account., International Registered Report Identifier (irrid): DERR1-10.2196/14370., (©Alexander Burchartz, Kristin Manz, Bastian Anedda, Claudia Niessner, Doris Oriwol, Steffen CE Schmidt, Alexander Woll. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 14.07.2020.)

Purpose: The German Maintenance Study (GERMAIN) was designed to evaluate the impact of lenalidomide maintenance after induction therapy with bortezomib, melphalan and prednisolone (VMP) in transplant-ineligible newly diagnosed multiple myeloma (MM) patients., Methods: Due to poor accrual and high dropout rate, only 85 patients (planned 286) entered the trial and 40 (planned 200) were randomized to lenalidomide maintenance (n = 19) vs. observation (n = 21)., Results: The primary endpoint, improved progression-free survival, was not met (p = 0.3572). After a median follow-up of 12.9 months, median progression-free survival in the lenalidomide arm was 14.4 months and 11.4 months with placebo. The hazard ratio 0.621 (95% confidence interval: [0.224, 1.725]) was about the same as expected (0.625). However, with only 40 patients randomized, the actual power to detect a difference was 11%. Of patients receiving at least one dose of induction, 54% were frail according to a modified International Myeloma Working Group frailty score. Discontinuations were high during induction (47%), and affected mainly frail patients (54%). Despite a higher rate of adverse events in the lenalidomide arm (p = 0.0061), only 2 patients discontinued lenalidomide due to toxicity., Conclusion: A frailty assessment with appropriate dose modification for induction therapy should be mandatory for all elderly non-transplant-eligible myeloma patients.

Cardiorespiratory fitness (CRF) is an established predictor of adverse health outcomes. The aim of this study is to investigate potential behavioral, interpersonal and socioeconomic correlates of CRF among men and women living in Germany using data from a population-based nationwide cross-sectional study. 1,439 men and 1,486 women aged 18-64 participated in the German Health Interview and Examination Survey (2008-2011) and completed a standardized sub-maximal cycle ergometer test. Maximal oxygen consumption ([Formula: see text]) in ml·min -1 ·kg -1 was estimated. Mean values of VO 2 max for various anthropometric, behavioral, interpersonal, and sociodemographic variables were estimated. Linear regression analyses using multiple imputations technique for missing values was performed to analyze the influence of potential correlates on CRF. Women with high alcohol consumption had higher [Formula: see text], (β = 2.20; 95% CI 0.98 to 3.42) than women with low alcohol consumption and women with high occupational status had higher [Formula: see text] (β = 1.83; 95% CI 0.21 to 3.44) in comparison to women with low occupational status. Among men, high fruit intake (β = 1.52; 95% CI 0.63 to 2.40), compared to low or medium fruit intake and performing at least 2.5 hours of total PA per week (β = 2.19; 95% CI 1.11 to 3.28), compared to less than 2.5 hours was associated with higher [Formula: see text]. Among both men and women, lower body mass index, lower waist circumference and higher levels of physical exercise were considerably associated with higher [Formula: see text]. Among women, those in higher age groups showed a considerably lower level of [Formula: see text] compared with those aged 18-24. Furthermore, mean estimated [Formula: see text] was higher among men (36.5; 95% CI 36.0 to 37.0) than among women (30.3; 95% CI 29.8 to 30.7). Despite the cross-sectional nature of the current study, we conclude that several behavioral, anthropometric, and sociodemographic factors are associated with CRF in the general adult population in Germany. These results can provide evidence to tailor prevention measures according to the needs of specific subgroups.

Introduction: Risky alcohol consumption (RAC) and heavy episodic drinking (HED) by parents can have negative effects on their children. At present, little is known about these forms of alcohol consumption among parents in Germany. The aim of this analysis is to estimate the percentage of parents living in Germany who practise RAC and HED and to study associations between these consumption patterns and sociodemographic factors., Material and Methods: The data basis comprises the data of the nationwide studies "Gesundheit in Deutschland aktuell" (GEDA) of 2009, 2010, and 2012. The data were collected by means of computer-assisted telephone interviews (CATI). Our analysis included all participants living in a household with at least one child of their own under 18 years of age ( n  = 16,224). Information on RAC and HED was collected using the AUDIT-C screening instrument. Logistic regression models were used to study the relationship between parental alcohol consumption and sociodemographic variables., Results: 18.4% of the mothers and 29.6% of the fathers exhibited RAC; 8.4% of the mothers and 21.0% of the fathers practised HED. After mutual adjustment, RAC showed a significant association with the level of education, income (only mothers), employment status (only mothers), migration background, relationship status (only mothers), and the age of the youngest child. HED showed a significant association with income (only mothers), the age of the youngest child (only mothers), and the level of education (only fathers)., Conclusions: The presented analysis emphasizes the relevance of preventive measures to reduce parental alcohol consumption. In addition to universal interventions, risk group-specific measures (e.g., for parents with high income) are needed to reduce parental alcohol consumption and thus support a healthy development of children., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 Gianni Varnaccia et al.)

This study aimed at estimating the prevalence in adults of complying with the aerobic physical activity (PA) recommendation through transportation-related walking and cycling. Furthermore, potential determinants of transportation-related PA recommendation compliance were investigated. 10,872 men and 13,144 women aged 18 years or older participated in the cross-sectional 'German Health Update 2014/15 - EHIS' in Germany. Transportation-related walking and cycling were assessed using the European Health Interview Survey-Physical Activity Questionnaire. Three outcome indicators were constructed: walking, cycling, and total active transportation (≥600 metabolic equivalent, MET-min/week). Associations were analyzed using multilevel regression analysis. Forty-two percent of men and 39% of women achieved ≥600 MET-min/week with total active transportation. The corresponding percentages for walking were 27% and 28% and for cycling 17% and 13%, respectively. Higher population density, older age, lower income, higher work-related and leisure-time PA, not being obese, and better self-perceived health were positively associated with transportation-related walking and cycling and total active transportation among both men and women. The promotion of walking and cycling among inactive people has great potential to increase PA in the general adult population and to comply with PA recommendations. Several correlates of active transportation were identified which should be considered when planning public health policies and interventions.

A continuously rising consumption of methamphetamine (MA) has been suggested to be associated with increasing cognitive dysfunction. The objective of this study was to investigate associations between cognitive functions and gender, drug using patterns and treatment-attending profiles of recently abstinent MA users over the course of six months abstinence. Data were collected from 108 participants in two inpatient rehabilitation centers. The mean duration of MA use was 11.5 years. Interviews and cognitive tests (cognitrone, Stroop, TMT, nback) were performed right after the withdrawal and again after approx. six months of abstinence. Comparisons and explorative analyses between the groups (gender, primary MA/ multidrug users, early dropouts/ completers) regarding cognitive variables were performed. At baseline a significant decline in general neuropsychological functioning and attention/concentration after ongoing years of consumption were found. After a period of six months abstinence, cognitive performances remained stable or improved significantly for cognitrone percentile and cognitive flexibility. Normal cognitive functions were measured in former MA users after acute withdrawal which remained stable and partly improved in those patients who refrained from substance abuse over six months. Continued long-term MA intake was the only identified indicator of poorer cognitive performance. These results point towards a regain of cognitive performance in patients abstinent from MA., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Regular physical activity and good motor performance are the basis for healthy physical development in childhood and are considered a protective factor for various health risks. However, children and adolescents in Germany are not physically active enough because sedentary activities have increased. One consequence is the decline in motor capacity, the totality of structures and functions that are responsible for the performance of motor actions.In the second follow-up survey of the study on the health of children and adolescents in Germany (KiGGS Wave 2, 2014-2017), the motor performance (LF) of 4‑ to 10-year-old children was examined with three motor tests: one-leg stand (EIN), stand and reach (RB), and jumping sideways (SHH). The purpose of this paper is to present the results of the tests and to compare them with data from the KiGGS baseline survey (2003-2006). It also analyzes how motor performance differs in terms of different characteristics such as sociodemographic factors, obesity, and physical activity.Compared to the KiGGS baseline survey, the 4‑ to 10-year-olds' motor performance in KiGGS Wave 2 has slightly improved in EIN, but RB and SHH are stagnating at low level. The test results indicate that middle and high social status, club sport activity, and "no overweight" are associated with above-average motor performance.Health policy, sports organizations, schools, and kindergartens should work together more closely so that all children have the same chance of good motor performance.

Background: There is an increasing demand of evidence-based treatment options for methamphetamine users, but research in this field is limited. This study therefore evaluates the efficacy of two residential treatment programs for methamphetamine users., Method: A total of 108 patients with a history of methamphetamine abuse from two inpatient rehabilitation centers were studied for psychiatric symptoms, craving, psychosocial resources, and cognitive functioning at the start and end of therapy. Patients from one center ("amphetamine type stimulant group") received conventional group therapy plus an additional 10 h of group therapy focusing on stimulant use. Patients from the other center ("treatment as usual") received conventional group therapy only. Predictors of drop-out were estimated., Results: A drop-out rate of 40.7% was observed without a significant difference between both centers. Patients remained significantly longer in treatment as usual compared to amphetamine type stimulant treatment. Irrespective of treatment program, craving and psychiatric symptoms significantly decreased while psychosocial resources, processing speed, and cognitive flexibility improved over time. Other cognitive measures yielded mixed results. History of injection drug use was a significant predictor for treatment drop-out., Conclusions: Existing treatments are effective in reducing craving and psychiatric symptoms. Additional stimulant specific groups do not appear to influence treatment completion and secondary outcome measures. Institutions should therefore offer treatment for methamphetamine users, even if they do not provide a therapy content focusing on methamphetamine. History of injection drug use should receive attention in treatment to prevent drop-out. Changes in cognitive functioning need to be further explored., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Stimulant drugs can cause persistent changes in the brain. Imaging studies show that these changes are most apparent in dopamine transporter (DAT) or receptor availability within the striatum., Methods: This work focuses on influences of stimulant use on dopaminergic function assessed using nuclear-medicine imaging (PET/SPECT). Included are 39 studies on 655 cocaine, amphetamine, methamphetamine or nicotine users, as well as 690 healthy controls. Metaanalyses were conducted separately for D2/D3 receptors and dopamine transporters of the entire striatum, its subregions caudate and putamen respectively., Results: Meta-analyses results regarding nicotine did not show significant effects between smokers and nonsmokers. In cocaine users there was a significant decrease in dopamine receptor availability in all regions. The striatal DAT availability was significantly increased in cocaine users. Methamphetamine users showed a significantly decreased dopamine receptor and transporter density in all regions. Significant results also indicate a lower transporter availability in all regions. Amphetamine users showed reduced DAT availability in the striatum, as well as in the sub regions., Conclusion: This meta-analysis provides evidence that there are ongoing changes in the dopaminergic system associated with the use of stimulants. Especially the results of cocaine, methamphetamine and amphetamine use mainly showed a downregulation. In addition, this meta-analysis is the first to include nicotine. This subset of studies showed evidence for a decreased receptor and DAT availability but no significant results were found in the metaanalyses., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

A balanced diet and sufficient physical activity are essential for the healthy growth of children and adolescents and for obesity prevention. Data from the second wave of the population-based German Health Interview and Examination Survey for Children and Adolescents (KiGGS Wave 2; 2014-2017) were used to analyse the association between food intake and physical activity among 6- to 17-year-old children and adolescents ( n = 9842). Physical exercise (PE) and recommended daily physical activity (RDPA) were assessed with self-administered questionnaires and food intake by a semi-quantitative food frequency questionnaire. Multivariable logistic regression was used to analyse the association between food group intake (dependent variable) and level of PE or RDPA. High levels of physical activity (PE or RDPA) were associated with higher consumption of juice, water, milk, dairy products, fruits, and vegetables among both boys and girls, and among boys with a higher intake of bread, potatoes/pasta/rice, meat, and cereals. Higher PE levels were also less likely to be associated with a high soft drink intake. High levels of RDPA were associated with high intake of energy-dense foods among boys, which was not observed for PE. This study indicates that school-aged children and adolescents with higher levels of physical activity consume more beneficial foods and beverages compared to those with lower physical activity levels.

Objectives: To develop a road map towards a harmonized pan-European surveillance system for children and adolescents., Methods: Representatives of five European surveillance systems and the German Health Interview and Examination Survey for Children and Adolescents contributed to the road map through a structured workshop in 2016., Results: A conceptual framework for this road map was developed with seven action points (APs) guiding the successive cross-country harmonization. First, key indicators of health behaviour and their determinants in children and adolescents will be identified (AP1, 2); short screening instruments will be developed and implemented to assess and monitor key indicators (AP3, 4). In parallel, optional supplementary modules could be implemented to provide objective data (AP5). This would allow mutual calibration and improvement of existing instruments before their progressive replacement by more comparable measurement tools (AP6). The establishment of a competence platform is envisaged for guiding the harmonization process (AP7)., Conclusions: This approach builds on existing systems, provides comparable key health indicators across European regions, helps to assess temporal trends and-once in place-will facilitate health reporting and monitoring of national and international health targets.

Background: Temperature distributions resulting from hyperthermia treatment of patients with high-risk soft-tissue sarcoma (STS) were quantitatively evaluated and globally compared with thermal simulations performed by a treatment planning system. The aim was to test whether the treatment planning system was able to predict correct temperature distributions., Methods: Five patients underwent computed tomography (CT) fluoroscopy-guided placement of tumor catheters used for the interstitial temperature measurements. For the simulations, five 3 D patient models were reconstructed by segmenting the patient CT datasets into different tissues. The measured and simulated data were evaluated by calculating the temperature change ( Δ T ), T90, T50, T20, T mean , T min and T max , as well as the 90th percentile thermal dose (CEM43T90). In order to measure the agreement between both methods quantitatively, the Bland-Altman analysis was applied., Results: The absolute difference between measured and simulated temperatures were found to be 2°, 6°, 1°, 4°, 5° and 4 °C on average for T min , T max , T90, T50, T20 and T mean , respectively. Furthermore, the thermal simulations exhibited relatively higher thermal dose compared to those that were measured. Finally, the results of the Bland-Altman analysis showed that the mean difference between both methods was above 2 °C which is considered to be clinically unacceptable., Conclusion: Given the current practical limitations on resolution of calculation grid, tissue properties, and perfusion information, the software SigmaHyperPlan™ is incapable to produce thermal simulations with sufficient correlation to typically heterogeneous tissue temperatures to be useful for clinical treatment planning.

Objectives: The utility of cerebrospinal fluid (CSF) CXCL13 for diagnosis of acute Lyme neuroborreliosis (LNB) has been debated and the test is not yet routinely performed. This study's aim was to evaluate its overall diagnostic accuracy through meta-analysis., Methods: Electronic searches in PubMed MEDLINE and Web of Science were performed to identify relevant articles published before January 2018. A summary receiver operating characteristic curve and an optimal cut-off were estimated modelling multiple cut-offs. Publication bias was evaluated using a funnel plot and the associated regression test., Results: A total of 18 studies involving 618 individuals with acute LNB and 2326 individuals with other neurological disorders meeting the eligibility criteria were identified. The pooled sensitivity for CSF CXCL13 was 89% (95% CI 85%-93%) and the pooled specificity was 96% (95% CI 92%-98%), using the identified optimal cut-off value of 162 pg/mL. There was marked heterogeneity between studies, caused by differences in the designs of the study populations and age distribution. The optimal cut-off in the seven studies with a cross-sectional design was 91 pg/mL (sensitivity 96%, 95% CI 92%-98%; specificity 94%, 95% CI 86%-97%) and in the 11 case-control studies it was 164 pg/mL (sensitivity 85%, 95% CI 78%-91%; specificity 95%, 95% CI 90%-98%). CSF CXCL13 values above the optimal cut-off level (determined in this meta-analysis) were also detectable in some other central nervous system disorders, namely neurosyphilis and central nervous system lymphoma., Conclusions: Our meta-analysis shows that CSF CXCL13 has the potential to become a useful adjunct in the diagnosis of acute LNB., (Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objectives: To investigate individual, interpersonal and environmental baseline factors predicting regular aerobic physical activity (PA) participation among older adults in Germany at follow-up 12 years later., Design: Population-based cohort study., Setting: Cluster-randomised general population sample selected based on population registry address information from 130 nationally distributed sample points collected from 1997 to 1999 and re-evaluated 12 years later from 2008 to 2011., Participants: 1184 adults, aged 65 years or older at follow-up with complete data at baseline and follow-up, were included in the final study sample., Outcome Measure: Regular 'aerobic PA ≥1 day/week' assessed based on self-reported information., Results: At follow-up, 53.2% of the participants engaged in aerobic PA ≥1 day/week. Participants aged 50 to 60 years at baseline were more likely to engage in aerobic PA ≥1 day/week than participants aged 61 to 78 years; OR 1.88, 95% CI 1.46 to 2.40. Participants with middle and high socioeconomic status (SES) were more likely to engage in aerobic PA ≥1 day/week than participants with low SES; OR middle SES 2.08, 1.33 to 3.25; high SES 3.44, 2.11 to 5.60. Participants with high social support were more likely to engage in aerobic PA ≥1 day/week at follow-up than participants with low social support; OR 1.98, 1.26 to 3.12. Furthermore, participants who engaged in leisure time PA at least once per week at baseline were more likely to engage in aerobic PA ≥1 day/week at follow-up than those who engaged less than once per week; OR 1.95, 1.46 to 2.60., Conclusions: Several influencing factors assessed at baseline predicted regular aerobic PA participation 12 years later. These factors should be considered when planning interventions to prevent physical inactivity in older adults. There is great potential to increase aerobic PA participation in older adults in Germany, in particular among those with low SES and low social support., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Introduction: Tyrosine kinase inhibitors (TKIs) can safely be discontinued in chronic myeloid leukemia (CML) patients with sustained deep molecular response. ABCG2 (breast cancer resistance protein), OCT1 (organic cation transporter 1), and ABCB1 (multidrug resistance protein 1) gene products are known to play a crucial role in acquired pharmacogenetic TKI resistance. Their influence on treatment-free remission (TFR) has not yet been investigated., Materials and Methods: RNA was isolated on the last day of TKI intake from peripheral blood leukocytes of 132 chronic phase CML patients who discontinued TKI treatment within the European Stop Tyrosine Kinase Inhibitor Study trial. Plasmid standards were designed including subgenic inserts of OCT1, ABCG2, and ABCB1 together with GUSB as reference gene. For expression analyses, quantitative real-time polymerase chain reaction was used. Multiple Cox regression analysis was performed. In addition, gene expression cutoffs for patient risk stratification were investigated., Results: The TFR rate of 132 patients, 12 months after TKI discontinuation, was 54% (95% confidence interval [CI], 46%-62%). ABCG2 expression (‰) was retained as the only significant variable (P = .02; hazard ratio, 1.04; 95% CI, 1.01-1.07) in multiple Cox regression analysis. Only for the ABCG2 efflux transporter, a significant cutoff was found (P = .04). Patients with an ABCG2/GUSB transcript level >4.5‰ (n = 93) showed a 12-month TFR rate of 47% (95% CI, 37%-57%), whereas patients with low ABCG2 expression (≤4.5‰; n = 39) had a 12-month TFR rate of 72% (95% CI, 55%-82%)., Conclusion: In this study, we investigated the effect of pharmacogenetics in the context of a CML treatment discontinuation trial. The transcript levels of the efflux transporter ABCG2 predicted TFR after TKI discontinuation., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Geographic information systems (GISs) are computer-based systems with which geographical data can be recorded, stored, managed, analyzed, visualized and provided. In recent years, they have become an integral part of public health research. They offer a broad range of analysis tools, which enable innovative solutions for health-related research questions. An analysis of nationwide studies that applied geographic information systems underlines the potential this instrument bears for health monitoring in Germany. Geographic information systems provide up-to-date mapping and visualization options to be used for national health monitoring at the Robert Koch Institute (RKI). Furthermore, objective information on the residential environment as an influencing factor on population health and on health behavior can be gathered and linked to RKI survey data at different geographic scales. Besides using physical information, such as climate, vegetation or land use, as well as information on the built environment, the instrument can link socioeconomic and sociodemographic data as well as information on health care and environmental stress to the survey data and integrate them into concepts for analyses. Therefore, geographic information systems expand the potential of the RKI to present nationwide, representative and meaningful health-monitoring results. In doing so, data protection regulations must always be followed. To conclude, the development of a national spatial data infrastructure and the identification of important data sources can prospectively improve access to high quality data sets that are relevant for the health monitoring.

Consuming harmful amounts of alcohol is considered a contributing factor in over 200 diseases. Women who drink over 10 g and men who drink more than 20 g of pure alcohol daily are already consuming risky amounts. According to GEDA 2014/2015-EHIS data, 13.8% of women and 18.2% of men consume risky amounts of alcohol at least weekly. The consumption of potentially dangerous levels of alcohol is most widespread in the 45-64 age group. Across all age groups, the prevalence of risky alcohol consumption patterns is higher among highly educated women compared to women with a lower level of education. For men, this pattern only appears in those aged 65 and over. Preventive measures including social and environmental interventions and responsible drinking campaigns should contribute to further reducing risky alcohol consumption among the population., Competing Interests: Conflicts of interest The authors declared no conflicts of interest., (© Robert Koch Institute. All rights reserved unless explicitly granted.)