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Objective This retrospective cohort study analyzes risk factors for abnormal pre-pregnancy body mass index and abnormal gestational weight gain in twin pregnancies. Methods Data from 10 603/13 682 twin pregnancies were analyzed using uni- and multivariable logistic regression models to determine risk factors for abnormal body mass index and weight gain in pregnancy. Results Multiparity was associated with pre-existing obesity in twin pregnancies (aOR: 3.78, 95% CI: 2.71 – 5.27). Working in academic or leadership positions (aOR: 0.57, 95% CI: 0.45 – 0.72) and advanced maternal age (aOR: 0.96, 95% CI: 0.95 – 0.98) were negatively associated with maternal obesity. Advanced maternal age was associated with a lower risk for maternal underweight (aOR: 0.95, 95% CI: 0.92 – 0.99). Unexpectedly, advanced maternal age (aOR: 0.98, 95% CI: 0.96 – 0.99) and multiparity (aOR: 0.6, 95% CI: 0.41 – 0.88) were also associated with lower risks for high gestational weight gain. Pre-existing maternal underweight (aOR: 1.55, 95% CI: 1.07 – 2.24), overweight (aOR: 1.61, 95% CI: 1.39 – 1.86), obesity (aOR: 3.09, 95% CI: 2.62 – 3.65) and multiparity (aOR: 1.64, 95% CI: 1.23 – 2.18) were all associated with low weight gain. Women working as employees (aOR: 0.85, 95% CI: 0.73 – 0.98) or in academic or leadership positions were less likely to have a low gestational weight gain (aOR: 0.77, 95% CI: 0.64 – 0.93). Conclusion Risk factors for abnormal body mass index and gestational weight gain specified for twin pregnancies are relevant to identify pregnancies with increased risks for poor maternal or neonatal outcome and to improve their counselling. Only then, targeted interventional studies in twin pregnancies which are desperately needed can be performed.

Zusammenfassung Hintergrund Um die Schlaganfallversorgung zu optimieren, wurden in Deutschland in den letzten Jahren verschiedene qualitätsfördernde Maßnahmen (qfM) in regional unterschiedlichem Maß eingeführt. Ob sich diese Maßnahmen über die Jahre flächendeckend etabliert haben, ist unklar. Methode Für die strukturbezogenen Analysen der Schlaganfallversorgung in Deutschland wurden alle relevanten dokumentierten Schlaganfälle (ICD-10) aus den Qualitätsberichten (QB) deutscher Krankenhäuser und eine repräsentative Stichprobe von Krankenversicherungsdaten (AOK) im Zeitraum von 2006 (QB)/2007 (AOK) bis 2017 verwendet. Diese Informationen wurden u. a. durch Angaben zu zertifizierten Stroke Units der Deutschen Schlaganfall-Gesellschaft (DSG) und Daten zur Führung von regionalen Schlaganfall-Registern der Arbeitsgemeinschaft Deutschsprachiger Schlaganfall-Register (ADSR) ergänzt. Zur Verfolgung der Veränderungen des Versor-gungsgeschehens im deutschen Bundesgebiet wurden die Daten mit geografischen Daten (Bundesamt für Kartographie und Geodäsie) verknüpft. Es erfolgten univariate Analysen der Daten und eine Trend-Analyse der verschiedenen qfM im Jahresverlauf (Konkordanzkoeffizient nach Kendall). Ergebnisse Die QB Analysen zeigten einen Anstieg kodierter Schlaganfälle in Krankenhäusern mit qfM um 14–20%. In 2006 wurden 80% der Schlaganfälle (QB) in einem Krankenhaus mit min. einer qfM kodiert, in 2017 95%. Diese Entwicklungen spiegelten sich auch in den AOK-Routinedaten wider, wobei in 2007 89% und in 2017 97% der Patient:innen unter mindestens einer qfM behandelt wurden. Dabei waren in 2007 bei 55% der behandelnden Krankenhäuser qfM vorhanden, in 2017 bei 72%. Schlussfolgerung Patient:innen werden inzwischen signifikant häufiger in Krankenhäusern mit Spezialisierung auf die Schlaganfallversorgung behandelt. Auch die verschiedenen qfM haben sich im Laufe der Jahre im gesamten Bundesgebet verbreitet, jedoch existieren noch Versorgungslücken, die geschlossen werden sollten, damit in Zukunft alle Patient:innen qualitativ hochwertig behandelt werden können.

Zusammenfassung Einleitung Die Delegation ärztlicher Leistungen an rheumatologische Fachassistent:innen (RFA) hat sich in der Evaluation des Forschungsprojektes „StärkeR“ als sicher und effektiv erwiesen. Im Nachgang wurden die Erfahrungen der beteiligten RFA und der Rheumatolog:innen mit der Delegation im Rahmen eines Meinungsforschungsprojekts erfragt und diskutiert. Methoden Zum Ende des Projekts wurden die teilnehmenden RFA (mittleres Alter 45 Jahre, 100 % weiblich, durchschnittlich 11 Jahre Berufserfahrung) und Rheumatolog:innen (mittleres Alter 54 Jahre, 32 % weiblich, durchschnittlich 21 Jahre Berufserfahrung), über einen Online-Fragebogen (quantitative Analyse) befragt (21 Fragen an die Ärzt:innen und 44 Fragen an die RFA). Zusätzlich fanden für die RFA Fokusgruppensitzungen statt, die von einer Moderatorin und einer Protokollführerin geleitet wurden. Die Ergebnisse der Fokusgruppensitzungen (qualitative Analysen) wurden gemäß der strukturierten Methode nach Kuckartz ausgewertet. Ergebnisse An den Online-Befragungen beteiligten sich alle im Projekt involvierten 31 RFA und 25 Rheumatolog:innen. An den beiden Fokusgruppen nahmen 9 RFA teil. In den Online-Befragungen der RFA und Ärzt:innen ergaben sich überwiegend gute bis sehr gute Bewertungen hinsichtlich RFA-Schulung, Durchführung der Delegation in den Praxen und Ambulanzen, in der Rolle der RFA und der Bewertung des Delegationskonzeptes insgesamt. In den Fokusgruppendiskussionen wurden viele mögliche Einschränkungen hinsichtlich Akzeptanz und Umsetzung des Delegationskonzeptes genannt. Schlussfolgerungen Die Delegation ärztlicher Aufgaben an RFA ist ein mehrheitlich von beiden Seiten, der Rheumatolog:innen und der RFA, positiv eingeschätztes Konzept mit hoher Akzeptanz. Im Vergleich zwischen den einzelnen Praxen und Klinikambulanzen besteht hinsichtlich der Bereitschaft und der logistischen Möglichkeiten in der Umsetzung des Delegationskonzeptes noch eine deutliche Heterogenität.

Background In on-pump cardiac surgery, lungs are at high risk of periprocedural organ impairment because of atelectasis formation, ventilator-induced lung injury, and hyperinflammation due to the cardiopulmonary bypass which results in postoperative pulmonary complications in half of this patient population. The new ventilation mode flow-controlled ventilation (FCV) uniquely allows full control of ins- and expiratory airway flows. This approach reduces the mechanical power of invasive ventilation as a possible cause of ventilator-induced lung injury. The scope of FLOWVENTIN HEARTSURG is to compare perioperative individualized FCV with best clinical practice pressure-controlled ventilation (PVC) modes in patients with elective on-pump cardiac surgery procedures. We hypothesize that the postoperative inflammatory response can be reduced by the perioperative application of FCV compared to PCV. Methods FLOWVENTIN HEARTSURG is a single-center, randomized, parallel-group trial with two intervention arms: perioperative PCV modes (n = 70, PCV group) with an individualized positive end-expiratory pressure (PEEP) and a tidal volume of 6–8 ml/kg predicted bodyweight compared to perioperative FCV (n = 70, FCV group) with an individualized PEEP and driving pressure, resulting in a liberal tidal volume. As the primary study endpoint interleukin 8 plasma level is assessed 6 h after cardiopulmonary bypass as a surrogate biomarker of systemic and pulmonary inflammation. As secondary aims clinically relevant patient outcomes are analyzed, e.g., perioperative lung function regarding oxygenation indices, postoperative pulmonary and extra-pulmonary complications, SIRS-free days as well as ICU and total inpatient stays. As additional sub-studies with an exploratory approach perioperative right ventricular function parameters are assessed by echocardiography and perioperative lung aeration by electrical impedance tomography. Discussion Current paradigms regarding protective low tidal volume ventilation are consciously left in the FCV intervention group in order to reduce mechanical power as a determinant of ventilator-induced lung injury in this high-risk patient population and procedures. This approach will be compared in a randomized controlled trial with current best clinical practice PCV in FLOWVENTIN HEARTSURG. Trial registration German Clinical Trials Register DRKS00018956. Registered on 12 June 2020 (Version 1), last update on 22 August 2022 (Version 4).

The delegation of medical services to rheumatology assistants (RFA) has proven to be safe and effective in the evaluation of the research project "StaerkeR". Afterwards, the experiences of the participating RFAs and rheumatologists with delegation were surveyed and discussed within the framework of an opinion research project.At the end of the project, the participating RFAs and rheumatologists were surveyed via an online questionnaire (quantitative analysis) (21 questions for physicians and 44 questions for RFAs). In addition, focus group meetings were held for the RFAs, which were led by a moderator and a secretary. The results of the focus group sessions (qualitative analyses) were analyzed according to the structured method of Kuckartz.All 31 RFAs and 25 rheumatologists involved in the project participated in the online surveys and 9 RFAs took part in the 2 focus groups. In the online surveys, both the RFAs and the rheumatologists gave predominantly good to very good ratings with respect to RFA training, the implementation of delegation in the practices and outpatient clinics, the role of the RFAs and the overall evaluation of the delegation concept. In the focus group discussions, many possible limitations regarding acceptance and implementation of the delegation concept were mentioned.The delegation of medical tasks to RFAs is a concept that is positively assessed and highly accepted by both sides, the rheumatologists and the RFAs. In a comparison between the individual practices and hospital outpatient departments, there is still a clear heterogeneity with respect to the willingness and logistical possibilities in the implementation of the delegation concept.EINLEITUNG: Die Delegation ärztlicher Leistungen an rheumatologische Fachassistent:innen (RFA) hat sich in der Evaluation des Forschungsprojektes „StärkeR“ als sicher und effektiv erwiesen. Im Nachgang wurden die Erfahrungen der beteiligten RFA und der Rheumatolog:innen mit der Delegation im Rahmen eines Meinungsforschungsprojekts erfragt und diskutiert.Zum Ende des Projekts wurden die teilnehmenden RFA (mittleres Alter 45 Jahre, 100 % weiblich, durchschnittlich 11 Jahre Berufserfahrung) und Rheumatolog:innen (mittleres Alter 54 Jahre, 32 % weiblich, durchschnittlich 21 Jahre Berufserfahrung), über einen Online-Fragebogen (quantitative Analyse) befragt (21 Fragen an die Ärzt:innen und 44 Fragen an die RFA). Zusätzlich fanden für die RFA Fokusgruppensitzungen statt, die von einer Moderatorin und einer Protokollführerin geleitet wurden. Die Ergebnisse der Fokusgruppensitzungen (qualitative Analysen) wurden gemäß der strukturierten Methode nach Kuckartz ausgewertet.An den Online-Befragungen beteiligten sich alle im Projekt involvierten 31 RFA und 25 Rheumatolog:innen. An den beiden Fokusgruppen nahmen 9 RFA teil. In den Online-Befragungen der RFA und Ärzt:innen ergaben sich überwiegend gute bis sehr gute Bewertungen hinsichtlich RFA-Schulung, Durchführung der Delegation in den Praxen und Ambulanzen, in der Rolle der RFA und der Bewertung des Delegationskonzeptes insgesamt. In den Fokusgruppendiskussionen wurden viele mögliche Einschränkungen hinsichtlich Akzeptanz und Umsetzung des Delegationskonzeptes genannt.Die Delegation ärztlicher Aufgaben an RFA ist ein mehrheitlich von beiden Seiten, der Rheumatolog:innen und der RFA, positiv eingeschätztes Konzept mit hoher Akzeptanz. Im Vergleich zwischen den einzelnen Praxen und Klinikambulanzen besteht hinsichtlich der Bereitschaft und der logistischen Möglichkeiten in der Umsetzung des Delegationskonzeptes noch eine deutliche Heterogenität.

The role of educational facilities, including schools and universities, in the SARS-CoV-2 pandemic is heavily debated. Specifically, the risk of infection in student dormitories has not been studied. This cohort study monitored students living in dormitories in Bochum, Germany, throughout the winter term of 2020/2021. Over the course of four months, participants were tested repeatedly for SARS-CoV-2 infections using RT-PCR from gargle samples and serological testing. An online questionnaire identified individual risk factors. A total of 810 (46.5% female) students participated. Of these, 590 (72.8%) students participated in the final visit. The cross-sectional antibody prevalence was n = 23 (2.8%) in November 2020 and n = 29 (4.9%) in February 2021. Of 2513 gargle samples analyzed, 19 (0.8%) tested positive for SARS-CoV-2, corresponding to 14 (2.4%) infections detected within the study period. Gargle samples available of cases with confirmed present infection were always positive. The person-time incidence rate was 112.7 (95% CI: 54.11–207.2) per 100,000 person weeks. The standardized incidence ratio was 0.9 (95% CI 0.51–1.46, p = 0.69). In conclusion, students living in student dormitories do not appear to be major drivers of SARS-CoV-2 infections. RT-PCR from gargle samples is a patient-friendly and scalable surveillance tool for detection of SARS-CoV-2 infections.

Summary: Background: As evidence concerning the impact of socioeconomic factors on the risk of peripheral artery disease (PAD) is sparse, we assessed the association of education and area-level factors (population density, type of municipality and local unemployment rate) on the onset of PAD in older adults. Patients and methods: The analysis used data of the getABI study, a prospective cohort study with seven years of follow-up. Onset of PAD was determined by ankle brachial index (

To date, there have only been provisional recommendations about the appropriate gestational weight gain in twin pregnancies. This study aimed to contribute evidence to this gap of knowledge.Using a cohort of 10 603 twin pregnancies delivered between 2000 and 2015 in the state of Hessen, Germany, the individual and combined impact of maternal body mass index and gestational weight gain on maternal and neonatal outcomes was analyzed using uni- and multivariable logistic regression models. The analysis used newly defined population-based quartiles of gestational weight gain in women carrying twin pregnancies (Q1:419.4 g/week [low weight gain], Q2-Q3: 419.4-692.3 g/week [optimal weight gain], Q4:692.3 g/week [high weight gain]) and the World Health Organization body mass index classification.Pre-pregnancy body mass index ≥25 kg/mIn twin pregnancies, nonoptimal weekly maternal weight gain seems to be strongly associated with maternal and neonatal adverse outcomes. Since gestational weight gain is a modifiable risk factor, health care providers have the opportunity to counsel pregnant women with twins and target their care accordingly. Additional research to confirm the validity and generalizability of our findings in different populations is warranted.

Introduction Socio-economic and ethnic background have been discussed as possible risk factors for SARS-CoV-2 infections in children. Improved knowledge could lead to tailored prevention strategies and help improve infection control. Aim We aimed to identify risk factors for SARS-CoV-2 infections in children in the first and second wave of the pandemic. Methods We performed an observational population-based cohort study in children (6 months–18 years) scheduled for legally required preventive examination and their parents in a metropolitan region in Germany. Primary endpoint was the SARS-CoV-2 seroconversion rate during the study period. Risk factors assessed included age, pre-existing medical conditions, socio-economic factors and ethnicity. Results We included 2,124 children and their parents. Seroconversion rates among children in all age groups increased 3–4-fold from June 2020 to February 2021. Only 24 of 58 (41%) seropositive children reported symptoms. In 51% of infected children, at least one parent was also SARS-CoV-2-positive. Low level of parental education (OR = 3.13; 95% CI: 0.72–13.69) non-significantly increased the risk of infection. Of the total cohort, 38.5% had a migration background, 9% of Turkish and 5% of Middle Eastern origin, and had the highest risk for SARS-CoV-2 infections (OR = 6.24; 95% CI: 1.38–28.12 and OR = 6.44 (95% CI: 1.14–36.45) after adjustment for other risk factors. Conclusion In the second half of 2020, seroprevalence for SARS-CoV-2 in children increased especially in families with lower-socioeconomic status. Culture-sensitive approaches are essential to limit transmission and could serve as a blueprint for vaccination strategies.

Background and ObjectiveDiscontinuation of fingolimod ≥2 months before pregnancy is recommended to minimize potential teratogenicity. The magnitude of MS pregnancy relapse risk, particularly severe relapses, after fingolimod cessation is unclear, as is whether this risk is reduced by pregnancy or modifiable factors.MethodsPregnancies who stopped fingolimod treatment within 1 year before or during pregnancy were identified from the German MS and Pregnancy Registry. Data were collected through structured telephone-administered questionnaires and neurologists' notes. Severe relapses were defined as a ≥2.0 increase in Expanded Disability Status Scale (EDSS) or new or worsening relapse-related ambulatory impairment. Women who continued to meet this definition 1 year postpartum were classified as reaching the Severe Relapse Disability Composite Score (SRDCS). Multivariable models accounting for measures of disease severity and repeated events were used.ResultsOf the 213 pregnancies among 201 women (mean age at pregnancy onset 32 years) identified, 56.81% (n = 121) discontinued fingolimod after conception. Relapses during pregnancy (31.46%) and the postpartum year (44.60%) were common. Nine pregnancies had a severe relapse during pregnancy and additional 3 during the postpartum year. One year postpartum, 11 of these (6.32% of n = 174 with complete EDSS information) reached the SRDCS. Adjusted relapse rates during pregnancy were slightly higher compared with the year before pregnancy (relapse rate ratio = 1.24, 95% CI 0.91–1.68). Neither exclusive breastfeeding nor resuming fingolimod within 4 weeks of delivery were associated with a reduced risk of postpartum relapses. Most pregnancies relapsed during the first 3 months postpartum (n = 55/204, 26.96%).DiscussionRelapses during pregnancy after fingolimod cessation are common. Approximately 6% of women will retain clinically meaningful disability from these pregnancy-related, fingolimod cessation relapses 1 year postpartum. This information should be shared with women on fingolimod desiring pregnancy, and optimizing MS treatment with nonteratogenic approaches should be discussed.

Socioeconomic conditions and social attitudes are known to represent epidemiological determinants. Credible knowledge on socioeconomic driving factors of the COVID-19 epidemic is still incomplete. Based on a linear random effects regression, a predictive model is derived to estimate COVID-19 incidence in German rural districts from local socioeconomic factors and popularity of political parties in terms of their share of vote. Thereby, time series provided by Germany's public health institute (Robert Koch Institute) of weekly notified 7-day incidences per 100,000 inhabitants per district from the outset of the epidemic in 2020 up to December 1, 2021, have been used to construct the dependent variable. Local socioeconomic conditions including share of votes, retrieved from the Federal Statistical Office of Germany, have been used as potential risk factors. Popularity of the right-wing party Alternative for Germany (AfD) bears a considerable risk of increasing COVID-19 incidence both in terms of predicting the maximum incidences during three epidemic periods (alternatively, cumulative incidences over the periods are used to quantify the dependent variable) and in a time-continuous sense. Thus, districts with high AfD popularity rank on top in the time-average regarding COVID-19 incidence. The impact of the popularity of the Free Democrats (FDP) is markedly intermittent in the course of time showing two pronounced peaks in incidence but also occasional drops. A moderate risk emanates from popularities of the Green Party (GRÜNE) and the Christian Democratic Union (CDU/CSU) compared to the other parties with lowest risk level. Socioeconomic parameters like \emph{per capita} income, proportions of protection seekers and social benefit claimants, and educational level have negligible impact. To the contrary, incidence significantly increases with population density. In order to effectively combat the COVID-19 epidemic, public health policymakers are well advised to account for social attitudes and behavioural patterns reflected in local popularities of political parties, which are conceived as proper surrogates for these attitudes. Whilst causal relations between social attitudes and the presence of parties remain obscure, the political landscape in terms of share of votes constitutes at least viable predictive "markers" relevant for public health policy making.

To compare the impact of lifestyle interventions for overweight and obese pregnant women a systematic review and meta-analysis was conducted using pre-registration and audit of the interventions as selection criteria. PubMed, Web of Science and CENTRAL were searched for randomized controlled trials examining diet, exercise, combined interventions or associated behavioral therapy. Trials were selected if they reported one of the primary outcomes (gestational diabetes, hypertensive disorders, perinatal mortality, admission to neonatal intensive care unit). Results were established from the total group and separately from pre-registered or clinically audited studies. Out of 1304 titles, 28 randomized controlled trials were included. Among the primary outcomes only hypertensive disorders were significantly reduced by exercise in the total group: odds ratio 0.52 (95% confidence interval 0.28 to 0.96, four trials, 1324 participants). When behavioral therapy supported combined interventions, maternal weight gain, (Standardized Mean Difference -0.16 kilogram; 95% confidence interval -0.28 to -0.04, four trials, 2132 participants) and neonatal birthweight, (Standardized Mean Difference -0.4 gram; 95% confidence interval -0.62 to -0.18, five trials, 1058 participants), were significantly reduced within the total group and both specified meta-analyses. Higher frequencies of physical activity improved the results. Risk of bias, assessed with the Cochrane Tool, was low to moderate. Elements of behavioral therapy might better prevent adverse effects of maternal obesity when combined with lifestyle interventions. Unfortunately, high heterogeneity due to different intervention and population characteristics was a limiting factor. Future studies should also focus on increased intensities of physical activity.Das Ziel war, die Auswirkungen von Lebensstil-Interventionen auf übergewichtige und adipöse Schwangere zu vergleichen. Dazu wurde eine systematische Auswertung der Literatur mit spezifizierten Metaanalysen durchgeführt; Auswahlkriterien waren Registrierung vor Studiendurchführung und Prüfung von Interventionen.Die Datenbanken PubMed, Web of Science und CENTRAL wurden nach randomisierten kontrollierten Studien durchsucht, welche die Auswirkungen von Ernährung, körperlicher Betätigung, kombinierten Interventionen sowie damit assoziierten Verhaltenstherapien untersuchten. Studien wurden in die Auswertung aufgenommen, wenn sie Informationen über Primärergebnisse (Gestationsdiabetes, Hypertonie, perinatale Sterblichkeit, Aufnahme auf eine Intensivstation für Früh- und Neugeborene) enthielten. Die Ergebnisse wurden für die Gesamtgruppe sowie separat für im Vorfeld registrierte oder klinisch geprüfte Studien ermittelt.Aus insgesamt 1304 Publikationen wurden 28 randomisierte kontrollierte Studien ausgewählt und in die Auswertung aufgenommen. Bei den Primärergebnissen zeigte sich, dass in der Gesamtgruppe nur die Hypertonie durch mehr körperliche Betätigung signifikant reduziert werden konnte: Odds Ratio (OR) 0,52 (95%-Konfidenzintervall [KI] 0,28–0,96, 4 Studien, 1324 Teilnehmer). Wenn kombinierte Interventionen durch eine Verhaltenstherapie unterstützt wurden, kam es innerhalb der Gesamtgruppe sowie in den spezifizierten Metaanalysen zu einer deutlichen Reduzierung der mütterlichen Gewichtszunahme, (standardisierter Mittelwertdifferenz −0,16 Kg; 95%-KI −0,28 bis −0,04, 4 Studien, 2132 Teilnehmer) und des neonatalen Geburtsgewichts (standardisierter Mittelwertdifferenz −0,4 g; 95%-KI −0,62 bis −0,18, 5 Studien, 1058 Teilnehmer). Höhere Häufigkeiten bei der körperlichen Betätigung verbesserten die Ergebnisse. Das mit dem Cochrane-Tool bewertete Verzerrungspotenzial war gering bis mäßig.Elemente der Verhaltenstherapie können die negativen Auswirkungen einer mütterlichen Adipositas besser verhindern, wenn sie mit Lebensstil-Interventionen kombiniert werden. Leider war die hohe Heterogenität infolge der unterschiedlichen Interventionen und Bevölkerungscharakteristiken ein limitierender Faktor. Künftige Studien sollten ihr Augenmerk auch auf die Intensität der körperlichen Betätigung richten.

Background We evaluated Aβ misfolding in combination with Aβ42/40 ratio as a prognostic tool for future clinical progression to mild cognitive impairment (MCI) or dementia due to Alzheimer’s disease (AD) in individuals with subjective cognitive decline (SCD). Methods Baseline plasma samples (n = 203) from SCD subjects in the SCIENCe project and Amsterdam Dementia Cohort (age 61 ± 9 years; 57% male, mean follow-up time 2.7 years) were analyzed using immuno-infrared-sensor technology. Within 6 years of follow-up, 22 (11%) individuals progressed to MCI or dementia due to AD. Sensor readout values > 1646 cm− 1 reflected normal Aβ folding; readouts at ≤ 1646 cm− 1 reflected low and at − 1 high misfolding. We used Cox proportional hazard models to quantify Aβ misfolding as a prognostic biomarker for progression to MCI and dementia due to AD. The accuracy of the predicted development of MCI/AD was determined by time-dependent receiver operating characteristic (t-ROC) curve analyses that take individual follow-up and conversion times into account. Statistical models were adjusted for age, sex, and APOEε4 status. Additionally, plasma Aβ42/40 data measured by SIMOA were statistically analyzed and compared. Results All 22 patients who converted to MCI or AD-dementia within 6 years exhibited Aβ misfolding at baseline. Cox analyses revealed a hazard ratio (HR) of 19 (95% confidence interval [CI] 2.2–157.8) for future conversion of SCD subjects with high misfolding and of 11 (95% CI 1.0–110.1) for those with low misfolding. T-ROC curve analyses yielded an area under the curve (AUC) of 0.94 (95% CI 0.86–1.00; 6-year follow-up) for Aβ misfolding in an age, sex, and APOEε4 model. A similar model with plasma Aβ42/40 ratio yielded an AUC of 0.92 (95% CI, 0.82–1.00). The AUC increased to 0.99 (95% CI, 0.99–1.00) after inclusion of both Aβ misfolding and the Aβ42/40 ratio. Conclusions A panel of structure- and concentration-based plasma amyloid biomarkers may predict conversion to clinical MCI and dementia due to AD in cognitively unimpaired subjects. These plasma biomarkers provide a noninvasive and cost-effective alternative for screening early AD pathological changes. Follow-up studies and external validation in larger cohorts are in progress for further validation of our findings.

BACKGROUND There are still only a few therapeutic strategies to improve taste sensation, which is part of oral health and quality of life. OBJECTIVE Therefore, here we aimed to investigate gustatory functions of healthy subjects performing mechanical tongue cleaning (MTC), an easy-to-perform oral hygiene procedure, to demonstrate taste changes and to describe possible negative side effects. METHODS Prior to and 14 days following MTC with an Orabrush® , the following tests were conducted in 65 healthy participants including both non-smokers (n = 50, 76.9%) and smokers (n = 15, 23.1%): 'taste strips' test, the Winkel Tongue Coating Index (WTCI), and subjective self-assessment. RESULTS Among non-smokers, subjective self-assessments of gustatory function (P

Background older patients are less frequently treated in stroke units (SUs). Clinicians do not seem convinced that older patients benefit from specialised treatment in SU similarly to younger patients. Objective our study aimed to compare older patients’ long-term outcomes with and without SU treatment. Methods this study used routinely collected health data of 232,447 patients admitted to hospitals in Germany between 2007 and 2017 who were diagnosed with ischaemic stroke (ICD 10 I63). The sample included 29,885 patients aged ≥90 years. The outcomes analysed were 10-, 30- and 90-day, and 1-, 3- and 5-year mortality and the combinations of death or recurrence, inpatient treatment and increase in long-term care needs. Bivariate chi-square tests and multivariable logistic regression analyses were used, adjusting for the covariates age, sex, co-morbidity, long-term care needs before stroke and socioeconomic status of the patients’ region of origin. Results between 2007 and 2017, 57.1% of patients aged Conclusions even very old patients with stroke benefit from SU treatment in the short and long term. Therefore, SU treatment should be the norm even in older patients.

Abstract. Objective: To describe the impact of the COVID-19 pandemic-related restrictions (PR) in April and May 2020 on physical activity (PA), sedentary screen time (SST), and mental well-being (MWB) in German adolescents, and to analyze associations between these variables. Methods: The Münster District Government invited all secondary school students (aged 11–17) in the region to take part in the online survey that assessed PA, SST, and MWB. For data analysis, we calculated descriptive statistics and ran linear regression analysis. Results: 1,038 students (627 [60.4%] female; 14.18 [± 1.97] years) were included in the analysis. During the PR, a marked decline in overall PA ( p < .001) and a significant increase ( p < .001) in SST were observed. One-third of the students reported worrying more and being less satisfied with their lives since PR. A decrease in life satisfaction (ß = –.524, p < .001) as well as an increase in general worrying (ß = –.336, p = .015) were associated with a decrease in PA during PR. Conclusion: The results show that the restrictions led to a decrease in physical activity, which may have detrimental effects on the students’ mental and physical health.

Treatment specific survival curves are an important tool to illustrate the treatment effect in studies with time-to-event outcomes. In non-randomized studies, unadjusted estimates can lead to biased depictions due to confounding. Multiple methods to adjust survival curves for confounders exist. However, it is currently unclear which method is the most appropriate in which situation. Our goal is to compare forms of Inverse Probability of Treatment Weighting, the G-Formula, Propensity Score Matching, Empirical Likelihood Estimation and augmented estimators as well as their pseudo-values based counterparts in different scenarios with a focus on their bias and goodness-of-fit. We provide a short review of all methods and illustrate their usage by contrasting the survival of smokers and non-smokers, using data from the German Epidemiological Trial on Ankle-Brachial-Index. Subsequently, we compare the methods using a Monte-Carlo simulation. We consider scenarios in which correctly or incorrectly specified models for describing the treatment assignment and the time-to-event outcome are used with varying sample sizes. The bias and goodness-of-fit is determined by taking the entire survival curve into account. When used properly, all methods showed no systematic bias in medium to large samples. Cox regression based methods, however, showed systematic bias in small samples. The goodness-of-fit varied greatly between different methods and scenarios. Methods utilizing an outcome model were more efficient than other techniques, while augmented estimators using an additional treatment assignment model were unbiased when either model was correct with a goodness-of-fit comparable to other methods. These doubly-robust methods have important advantages in every considered scenario., 30 pages, 6 figures, revised version for "Statistics in Medicine", was presented at the International Biometric Conference 2022

Introduction Maternal obesity and excessive gestational weight gain (GWG) affect the outcomes of women and their offspring. Our aim was to evaluate population-based data from Germany. Material and Methods Data from 583 633/791 514 mother-child pairs obtained from the perinatal database in Hesse for the period from 2000 to 2015 were used after excluding incomplete or non-plausible datasets. Early-stage pregnancy maternal body mass index (BMI) and GWG were evaluated. Significant outcome changes were calculated using linear or logistic regression models. Results The mean maternal age increased from 29.9 to 31.28 years; GWG increased from 445.1 to 457.2 g/week (p Conclusions In just 15 years, pre-pregnancy BMI and GWG rates of women with singleton pregnancies have increased, and this increase has been accompanied by a significant rise in the rate of cesarean sections and a significant worsening of short-term maternal and neonatal outcomes. It is time to discuss the risks and the short-term and more worrying long-term consequences for mothers and their offspring and the future impact on our healthcare system.

Purpose While observational studies revealed inverse associations between serum vitamin D levels [25(OH)D] and depression, randomized controlled trials (RCT) in children and adolescents are lacking. This RCT examined the effect of an untreated vitamin D deficiency compared to an immediate vitamin D3 supplementation on depression scores in children and adolescents during standard day and in-patient psychiatric treatment. Methods Patients with vitamin D deficiency [25(OH)D ≤ 30 nmol/l] and at least mild depression [Beck Depression Inventory II (BDI-II) > 13] (n = 113) were 1:1 randomized into verum (VG; 2640 IU vitamin D3/d) or placebo group (PG) in a double-blind manner. During the intervention period of 28 days, both groups additionally received treatment as usual. BDI-II scores were assessed as primary outcome, DISYPS-II (Diagnostic System for Mental Disorders in Childhood and Adolescence, Self- and Parent Rating) and serum total 25(OH)D were secondary outcomes. Results At admission, 49.3% of the screened patients (n = 280) had vitamin D deficiency. Although the intervention led to a higher increase of 25(OH)D levels in the VG than in the PG (treatment difference: + 14 ng/ml; 95% CI 4.86–23.77; p = 0.003), the change in BDI-II scores did not differ (+ 1.3; 95% CI − 2.22 to 4.81; p = 0.466). In contrast, DISYPS parental ratings revealed pronounced improvements of depressive symptoms in the VG (− 0.68; 95% CI − 1.23 to − 0.13; p = 0.016). Conclusion Whereas this study failed to show a vitamin D supplementation effect on self-rated depression in adolescent in- or daycare patients, parents reported less depressive symptoms in VG at the end of our study. Future trials should consider clinician-rated depressive symptoms as primary outcome. Trial registration “German Clinical Trials Register” (https://www.drks.de), registration number: DRKS00009758

Introduction Studies on maternal weight, gestational weight gain and associated outcomes in twin pregnancies are scarce. Therefore, we analyzed these items in a large cohort. Methods Data from 10,603/13,725 total twin pregnancies from the perinatal database in Hessen, Germany between 2000 and 2015 were used after exclusion of incomplete or non-plausible data sets. The course of maternal and perinatal outcomes was evaluated by linear and logistic regression models. Results The rate of twin pregnancies increased from 1.5 to 1.9% (p p 2 increased from 11.9 to 16.9% with a mean of 24.4–25.4 kg/m2 (p p p Conclusion The global trend of the obesity epidemic is equally observed in German twin pregnancies. The increase of mean maternal weight and the calculated quartiles specific for twin pregnancies help to identify inadequate weight gain in twin gestations. Policy makers should be aware of future health risks specified for singleton and twin gestations.

Key Points Question Is early natalizumab cessation before or during the first trimester of pregnancy associated with multiple sclerosis relapse occurrence and relapse-related disability? Findings In this cohort study of 274 pregnancies, relapses during pregnancy and postpartum were common, with more than 10% of women retaining clinically meaningful disability from pregnancy-related natalizumab cessation relapses 1 year after delivery. Neither pregnancy itself, restarting natalizumab shortly after delivery, nor exclusive breastfeeding was associated with protection against these relapses. Meaning These findings suggest that women with multiple sclerosis need to be informed about the risks of early natalizumab cessation due to pregnancy or planned pregnancy, and treatment alternatives should be considered., This cohort study examines the associations between cessation of natalizumab therapy in women with multiple sclerosis before or during the first trimester of pregnancy with relapse occurrence and relapse-related disability., Importance The magnitude of risk of pregnancy-related multiple sclerosis relapses, particularly severe relapses, following natalizumab cessation is unclear, as is whether this risk is reduced by pregnancy or other modifiable factors. Objective To determine the association of early natalizumab withdrawal before or during pregnancy with risk of severe relapses and relapse-related disability. Design, Setting, and Participants This prospective cohort study used data from the German Multiple Sclerosis and Pregnancy Registry, which enrolled participants between November 2006 and February 2018. Data were collected through structured telephone-administered questionnaires and review of neurologists’ notes. Registry patients who stopped natalizumab treatment within the 2 years before or in the first trimester of pregnancy were included in this analysis. Data were analyzed between January and November 2021. Exposures Cessation of natalizumab before pregnancy or until the first trimester. Main Outcomes and Measures Severe and significant relapse-related disability was defined as at least a 2.0-point increase on the expanded disability status scale or new or worsening relapse-related ambulatory impairment. Multivariable models accounting for measures of disease severity and repeated events were used. Results The cohort comprised 255 women with 274 pregnancies (mean [SD] age at pregnancy onset, 31.25 [4.27] years) who stopped natalizumab before pregnancy (n = 85; median time before last menstrual period, 14.29 weeks [IQR, 3.14-42.43 weeks]) or in the first trimester (n = 189). During pregnancy and the postpartum year, relapses were reported in 183 pregnancies (66.78%), severe relapses in 44 pregnancies (16.05%), and potentially life-threatening relapses in 3 pregnancies (1.10%). One year post partum, significant relapse-related disability was accrued in 29 pregnancies (10.58%). Relapses during pregnancy (n = 109; 39.78%) and in the postpartum period (n = 135; 49.27%) were common. Pregnancy (as a time-dependent covariate) was not associated with a reduced relapse risk (adjusted HR, 0.90; 95% CI, 0.64-1.27). Neither exclusive breastfeeding (adjusted HR, 1.34; 95% CI, 0.86-2.10) nor restarting natalizumab within 4 weeks post partum (adjusted HR, 1.06; 95% CI, 0.48-2.36) were associated with a reduced risk of early postpartum relapses 6 months after delivery. However, the relapse rate ratio during 12 months post partum was lower (0.49; 95% CI, 0.28-0.86) when natalizumab was restarted in the first 4 weeks after birth. Conclusions and Relevance This cohort study’s finding suggest that 10% of women may retain clinically meaningful disability from pregnancy-related natalizumab cessation relapses 1 year post partum. This information should be shared with women on natalizumab who desire pregnancy to weigh the high risk of pregnancy-related relapses and disability to the partly uncertain risks of continuing natalizumab throughout pregnancy or switching to depleting agents before conception.

Objective: In active early rheumatoid arthritis (RA), glucocorticoids are often used for bridging, due to the delayed action of methotrexate. This study was undertaken to compare the effect of 3 bridging strategies, including high-dose and low-dose prednisolone, on radiographic and clinical outcomes. Methods: Adult RA patients from 1 rheumatology hospital and 23 rheumatology practices who presented with moderate/high disease activity were randomized (1:1:1) to receive 60 mg prednisolone (high-dose prednisolone [HDP]) or 10 mg prednisolone (low-dose prednisolone [LDP]) daily (tapered to 0 mg within 12 weeks) or placebo. The 12-week intervention period was followed by 40 weeks of therapy at the physicians' discretion. The primary outcome measure was radiographic change at 1 year measured using the total modified Sharp/van der Heijde score (SHS). Disease activity was assessed with the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR). Results: Of 395 randomized patients (HDP, n = 132; LDP, n = 131; placebo, n = 132), 375 (95%) remained in the modified intention-to-treat analysis. Mean ± SD changes in SHS scores in the 3 groups after 1 year were comparable: mean ± SD 1.0 ± 2.0 units in the HDP group, 1.1 ± 2.2 units in the LDP group, and 1.1 ± 1.5 units in the placebo group. The primary analysis showed no superiority of HDP compared to placebo (estimated difference of the mean change −0.04 [95% confidence interval (95% CI) −0.5, 0.4]). At week 12, the mean DAS28-ESR differed: −0.6 (95% CI −1.0, −0.2) for HDP versus placebo; –0.8 (95% CI −1.2, −0.5) for LDP versus placebo. At week 52, there was no significant difference in DAS28-ESR between the 3 groups (range 2.6–2.8). Serious adverse events occurred similarly often. Conclusion: Short-term glucocorticoid bridging therapy at a high dose showed no benefit with regard to progression of radiographic damage at 1 year.