The influence of the SARS-CoV-2 lockdown on patients with inflammatory rheumatic diseases on their adherence to immunomodulatory medication: a cross sectional study over 3 months in Germany.

OBJECTIVES: To evaluate the influence of the SARS-CoV-2 pandemic on the adherence of patients with inflammatory rheumatic diseases (IRD) to their immunomodulatory medication during the three-month lockdown in Germany. METHODS: From 16th March until 15th June 2020, IRD patients from private practices and rheumatology departments were asked to answer a questionnaire addressing their behaviour with respect to their immunomodulating therapy. Eight private practices and nine rheumatology departments that included rheumatology primary care centres and university hospitals participated. A total of 4252 questionnaires were collected and evaluated. RESULTS: The majority of patients (54%) were diagnosed with RA, followed by psoriatic arthritis (14%), ankylosing spondylitis (10%), connective tissue diseases (12%) and vasculitides (6%). Most of the patients (84%) reported to continue their immunomodulatory therapy. Termination of therapy was reported by only 3% of the patients. The results were independent from the type of IRD, the respective immunomodulatory therapy and by whom the patients were treated (private practices vs rheumatology departments). Younger patients (<60 years) reported just as often as older patients to discontinue their therapy. CONCLUSION: The data show that most of the patients continued their therapy in spite of the pandemic. A significant change in behaviour with regard to their immunomodulatory therapy was not observed during the three months of observation. The results support the idea that the immediate release of recommendations of the German Society of Rheumatology were well received, supporting the well-established physician-patient relationship in times of a crisis.

[Paths to academic rheumatology]. / Weg in die akademische Rheumatologie.

BACKGROUND: The development of rheumatology into one of the most progressive medical disciplines is mainly based on the enormous scientific knowledge gained in recent decades. Physician scientists have played a substantial role in this development. With respect to the ongoing challenges, physician scientists will be urgently needed in the future. Therefore, young physicians need to be attracted to scientific research in rheumatology. OBJECTIVE: This article describes possible paths into academic rheumatology, highlights facilitators and barriers to a scientific career and discusses ideas for the recruitment of young scientists for rheumatology based on the existing literature. RESULTS AND DISCUSSION: It is without doubt that young scientists are urgently needed in rheumatology; however, the number of young physician scientists seems to be declining. The paths to academic rheumatology are manifold and variable but setting the course early on during medical school by science-oriented teaching, research internships and doctoral theses, appears to be advantageous. Favorable factors for the decision to pursue an academic career in rheumatology are enjoyment in research, recognition of research rotations for rheumatology training and improved career opportunities. The greatest barriers are considered to be the exemption from clinical duties as well as lack of experience with scientific methods and acquisition of research funding. Therefore, it is important to make potential scientists enthusiastic about the research underlying modern rheumatology and to encourage research during medical school in order to attract young people to academic rheumatology.

Mission statement from rheumatologists in the German Society of Rheumatology (DGRh e. V.) : We live rheumatology.

Systemic disease demands systemic thinkers. In this mission statement we define rheumatology, describe the role of the German Society of Rheumatology and the rheumatologist's spirit to their discipline. Rheumatologists are dedicated to improving the quality of life of their acute, chronic, and rehabilitative patients on the basis of up to date evidence and strong physician-patient relations. We think, act and interact systemically, scientifically, consistently, transparently, reliably, inclusively, innovatively and enthusiastically.

Birth weight for gestational age and the risk of infertility: a Danish cohort study.

STUDY QUESTION: Is birth weight for gestational age associated with infertility in adulthood among men and women? SUMMARY ANSWER: Being born small for gestational age (SGA) was associated with infertility in adulthood among men. WHAT IS KNOWN ALREADY: Fetal growth restriction may affect fertility, but results from previous studies have been inconsistent. STUDY DESIGN, SIZE, DURATION: In this population-based cohort study, we used data from a Danish birth cohort, including 5594 men and 5342 women born between 1984 and 1987. Information on infertility was obtained from Danish health registers during the period from the participants' 18th birthday and up until 31 December 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were men and women born in two Danish municipalities, Aalborg and Odense. Information on birth weight and gestational age was obtained from birth records, and information on infertility diagnoses and fertility treatment was retrieved from the Danish National Patient Registry (NPR) and the Danish In Vitro Fertilisation (IVF) registry. Information on potential maternal confounders was obtained from questionnaires during pregnancy and was included in adjusted analyses. Logistic regression analysis was used to estimate crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for infertility according to birth weight for gestational age. MAIN RESULTS AND THE ROLE OF CHANCE: Men born SGA had a 55% higher risk of being diagnosed with or treated for infertility compared to men born appropriate for gestational age (AGA) (adjusted OR = 1.55, 95% CI: 1.09-2.21). The association attenuated after exclusion of men born with hypospadias or cryptorchidism (OR = 1.37, 95% CI: 0.93-2.01). No association was found between women's birth weight for gestational age and risk of infertility (adjusted OR = 1.00, 95% CI: 0.73-1.37). LIMITATIONS, REASONS FOR CAUTION: Estimation of gestational age is associated with some uncertainty and might have caused non-differential misclassification. The study design implicitly assumed similar distribution of reproductive and health-seeking behaviour across the groups that were compared. WIDER IMPLICATIONS OF THE FINDINGS: Men born SGA had a higher risk of infertility. Genital malformations may account for part of the observed association, but this must be explored further. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by Health, Aarhus University. No competing interests are declared. TRIAL REGISTRATION NUMBER: N/A.

[SARS-CoV-2 & rheumatic disease : Consequences of the SARS-CoV-2 pandemic for patients with inflammatory rheumatic diseases. A comparison of the recommendations for action of rheumatological societies and risk assessment of different antirheumatic treatments]. / SARS-CoV-2 & Rheuma : Konsequenzen der SARS-CoV-2-Pandemie für Patienten mit entzündlich rheumatischen Erkrankungen. Ein Vergleich der Handlungsempfehlungen rheumatologischer Fachgesellschaften und Risikobewertung verschiedener antirheumatischer Therapien.

The recommendations of the German Society of Rheumatology (DGRh) update, which update and expand the guidance on the management of patients with inflammatory rheumatic diseases in view of SARS-CoV­2 created at the beginning of the COVID-19 pandemic, correspond in many points with the recommendations for action of the American (ACR) and European (EULAR) societies, but also differ in some points. Therefore, this article discusses the core recommendations of the DGRh update on the prevention of SARS-CoV-2/COVID-19, the risk assessment for inflammatory rheumatic diseases and the use of antirheumatic treatments in the context and in comparison to the ACR and EULAR recommendations, and provides an overview of the risk assessment of individual antirheumatic drugs.

[Mission statement from rheumatologists in the German Society of Rheumatology (DGRh e. V.) : We live rheumatology. German version]. / Leitbild der Rheumatologinnen und Rheumatologen in der Deutschen Gesellschaft für Rheumatologie e. V. (DGRh e. V.) : Wir sind die Rheumatologie.

Systemic disease demands systemic thinkers. In this mission statement we define rheumatology, describe the role of the German Society of Rheumatology and the rheumatologist's spirit to their discipline. Rheumatologists are dedicated to improving the quality of life of their acute, chronic, and rehabilitative patients on the basis of up to date evidence and strong physician-patient relations. We think, act and interact systemically, scientifically, consistently, transparently, reliably, inclusively, innovatively and enthusiastically.

[Current guidance of the German Society of Rheumatology for the care of patients with rheumatic diseases during the SARS-CoV-2/Covid 19 pandemic]. / Aktuelle Handlungsempfehlungen der Deutschen Gesellschaft für Rheumatologie für die Betreuung von Patienten mit rheumatischen Erkrankungen während der SARS-CoV­2/Covid 19-Pandemie.

In the current SARS-CoV-2 pandemic there are many questions regarding the safe treatment of patients with inflammatory rheumatic diseases. Many of these questions cannot yet be answered on an evidence-based basis and this does not make patient care easy. The German Society for Rheumatology (DGRh) hopes that these initial recommendations will provide support for specific issues in the care of patients with inflammatory rheumatic diseases in view of the current threat posed by SARS-CoV-2. In order to take advantage of the dynamic worldwide gain in knowledge for our patients, the recommendations will be updated regularly. The updated versions of the recommendations are deposited on the homepage of the DGRh.

[Hypereosinophilic syndrome and other rheumatic diseases with hypereosinophilia]. / Hypereosinophiles Syndrom und weitere rheumatische Erkrankungen mit Hypereosinophilie.

Among the eosinophilic diseases treated by rheumatologists other than eosinophilic granulomatosis with polyangiitis, there are further organ-related and systemic diseases with hypereosinophilia. Only the exact differential diagnostic demarcation of the diseases enables a pathogenetic oriented treatment. This article focuses on the hypereosinophilic syndromes. The potential differential diagnoses of Ig(immunoglobulin)G4-related disease, eosinophilic fasciitis and drug-induced vasculitis as well as eosinophilia-myalgia syndrome and toxic oil syndrome as historic drug-induced inflammatory rheumatic diseases are described and the clinical manifestations and treatment are summarized.

Autoantibodies, complement and type I interferon as biomarkers for personalized medicine in SLE.

Systemic lupus erythematosus (SLE) can be a mysterious disease, presenting with extremely divergent clinical phenotypes. Already, biomarkers are very helpful tools for diagnosis, assessment and monitoring of disease activity, differential diagnosis of clinical manifestations, prediction of the disease course and stratified therapy, and they hold the key to personalized medicine in SLE. We summarize the clinical information that can only be supplied by autoantibodies, complement components and interferon biomarkers in this diverse disease.

Prenatal exposure to environmental chemical contaminants and asthma and eczema in school-age children.

BACKGROUND: Emerging evidence suggests that prenatal or early-life exposures to environmental contaminants may contribute to an increased risk of asthma and allergies in children. We aimed to the explore associations of prenatal exposures to a large set of environmental chemical contaminants with asthma and eczema in school-age children. METHODS: We studied 1024 mother-child pairs from Greenland and Ukraine from the INUENDO birth cohort. Data were collected by means of an interview-based questionnaire when the children were 5-9 years of age. Questions from the ISAAC study were used to define asthma, eczema, and wheeze. We applied principal components analysis (PCA) to sixteen contaminants in maternal serum sampled during pregnancy, including perfluoroalkyl substances (PFASs), metabolites of diethylhexyl (DEHP) and diisononyl (DiNP) phthalates, PCB-153, and p,p'-DDE. Scores of five principal components (PCs) explaining 70% of the variance were included in multiple logistic regression models. RESULTS: In a meta-analysis that included both populations, the PC2 score, reflecting exposure to DiNP, was negatively associated with current eczema (OR 0.71, 95% CI 0.52-0.96). Other associations were not consistent between the two populations. In Ukrainian children, the PC3 score (DEHP) was positively associated with current wheeze (adjusted OR 1.56, 95% CI 1.03-2.37), whereas the PC5 score, dominated by perfluorooctanoic acid (PFOA), was inversely associated with current wheeze (OR 0.64, 0.41-0.99). In Greenlandic children, a negative association of PC4 (organochlorines) with ever eczema (OR 0.78, 0.61-0.99) was found. CONCLUSIONS: We found limited evidence to support a link between prenatal exposure to environmental chemical contaminants and childhood asthma and eczema.

[Biologics therapy for systemic lupus erythematosus. Current situation]. / Biologikatherapie beim systemischen Lupus erythematodes. Aktueller Stand.

BACKGROUND: Improved understanding of the immunopathogenesis of systemic lupus erythematosus (SLE) has paved the way for new specific immune interventions for this inflammatory disease similar to those for rheumatoid arthritis and spondylarthritides. METHODS: New biologics were developed on this basis or are in the process of clinical development and open up new therapy options for patients. In this context belimumab is of particular importance. As an innovative biologic the monoclonal antibody against the cytokine BAFF/BLyS (belimumab) has been approved for the treatment of serologically active SLE. A number of other biologics against other cytokines are in the clinical development phase and appear to be promising for further improvement of the current therapeutic possibilities in SLE. This article addresses the current aspects of immune interventions with biologics for SLE and the specific challenges of this disease.

[Adult onset Still's disease with small vessel vasculitis]. / Adulter Morbus Still mit Kleingefäßvaskulitis.

This article presents a particularly severe case of adult onset Still's disease aggravated by small vessel vasculitis. A satisfactory therapy was concluded 1.5 years after onset of the disease. The small vessel vasculitis was difficult to treat: methotrexate (MTX), cyclophosphamide and rituximab were not sufficiently effective. Tocilizumab in combination with intravenous immunoglobulin (IVIG) induced remission and maintenance therapy was carried out with tocilizumab.

Body mass index in young school-age children in relation to organochlorine compounds in early life: a prospective study.

OBJECTIVE: To investigate the association between maternal pregnancy and estimated postnatal serum concentrations of the organochlorines 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) and body mass index (BMI) z-scores in 5- to 9-year-old children. METHODS: Maternal sera from the INUENDO birth cohort (2002-2004) comprising mother-child pairs (N=1109) from Greenland, Warsaw (Poland), and Kharkiv (Ukraine) were analysed for CB-153 and p,p'-DDE, using gas chromatography-mass-spectrometry, and were grouped into tertiles for statistical analyses. A toxicokinetic model was used to estimate the first 12 months cumulative exposure to the compounds. Associations between these compounds and child age- and sex-specific BMI z-scores were calculated at follow-up (2010-2012), using multiple linear regression analysis. RESULTS: No clear associations between pregnancy CB-153 and p,p'-DDE and child BMI were observed (the pooled differences in BMI z-score (95% confidence interval) comparing 3rd tertile to 1st tertile were -0.07 (-0.32 to 0.18) and -0.10 (-0.30 to 0.10) kg m(-2), respectively). For postnatal CB-153 and p,p'-DDE and BMI, the overall differences in BMI z-score comparing 3rd tertile to 1st tertile were 0.12 (-0.15 to 0.39) and -0.03 (-0.20 to 0.27) kg m(-2), respectively. CONCLUSIONS: This follow-up study of Greenlandic, Polish and Ukrainian populations showed no clear association between pregnancy and postnatal exposure to p,p'-DDE and CB-153 and BMI at the age of 5-9 years.

Moderate alcohol intake and menstrual cycle characteristics.

STUDY QUESTION: Does moderate alcohol intake affect menstrual cycle characteristics among women in the Danish population? SUMMARY ANSWER: Levels of alcohol exposure as seen in this study do not substantially affect the menstrual cycle. WHAT IS KNOWN ALREADY: Animal studies indicate alcohol-induced disruptions of the reproductive system, but previous epidemiological studies addressing the possible association between alcohol intake and the menstrual cycle are sparse. STUDY DESIGN, SIZE, DURATION: A cross-sectional study with retrospectively collected data including 82 146 pregnant Danish women in the Danish National Birth Cohort (DNBC) enrolled during the years 1996-2002. PARTICIPANTS/MATERIALS, SETTING, METHODS: Information on weekly alcohol consumption and menstrual cycle characteristics before pregnancy was obtained through a computer-assisted telephone interview in pregnancy Week 12-16. The associations between weekly alcohol consumption and menstrual cycle irregularity (≥7 days difference between cycles) and length (short cycle: ≤24 days, long cycle: ≥32 days) were analysed using logistic regression with weekly alcohol intake categorized into abstainers (0 drinks per week), low (0.5-2.0 drinks per week), moderate (2.5-14.0 drinks per week) and high (14.0-86.5 drinks per week). Estimates are given as adjusted odds ratios with 95% confidence intervals. MAIN RESULTS AND THE ROLE OF CHANCE: The overall participation rate was 60% of the women invited. We found that a high weekly alcohol consumption was not associated with menstrual cycle disturbances. We observed higher odds of irregular and short cycles among abstainers when compared with women with a low weekly alcohol consumption, but found no trend of more cycle disturbances with higher alcohol consumption. LIMITATIONS, REASONS FOR CAUTION: Possible limitations in our study include a risk of selection bias due to the moderate participation rate and the use of retrospective information on alcohol exposure and menstrual cycle characteristics before getting pregnant. The higher odds of irregular and short cycles among abstainers may reflect other health problems in these women rather than an actual effect of alcohol on the menstrual cycle. WIDER IMPLICATIONS OF THE FINDINGS: The generalizability of the study results is restricted to women who manage to conceive and women who do not use oral contraceptives within 2 months before getting pregnant. This study suggests that the menstrual cycle is not substantially affected by higher alcohol consumption among the participating women. STUDY FUNDING/COMPETING INTEREST(S): Supported by a scholarship from Aarhus University Research Foundation. The Danish National Research Foundation has established the Danish Epidemiology Science Centre that initiated and created the DNBC. The cohort is furthermore a result of a major grant from this Foundation. Additional support for the DNBC is obtained from the Pharmacy Foundation, the Egmont Foundation, the March of Dimes Birth Defects Foundation, the Augustinus Foundation and the Health Foundation. No conflict of interest declared.

Menstrual cycle characteristics in fertile women from Greenland, Poland and Ukraine exposed to perfluorinated chemicals: a cross-sectional study.

STUDY QUESTION: Does perfluorooctane sulfonate (PFOS) and perfluorooctanate (PFOA) exposure disrupt the menstrual cyclicity? SUMMARY ANSWER: The female reproductive system may be sensitive to PFOA exposure, with longer menstrual cycle length at higher exposure. WHAT IS KNOWN ALREADY: PFOS and PFOA are persistent man-made chemicals. Experimental animal studies suggest they are reproductive toxicants but epidemiological findings are inconsistent. STUDY DESIGN, SIZE, DURATION: A cross-sectional study including 1623 pregnant women from the INUENDO cohort enrolled during antenatal care visits between June 2002 and May 2004 in Greenland, Poland and Ukraine. PARTICIPANTS/MATERIALS, SETTING, METHODS: Information on menstrual cycle characteristics was obtained by questionnaires together with a blood sample from each pregnant woman. Serum concentrations of PFOS and PFOA were measured by liquid chromatography tandem mass spectrometry. Multiple imputations were performed to account for missing data. The association between PFOS/PFOA and menstrual cycle length (short cycle: ≤24 days, long cycle: ≥32 days) and irregularities (≥7 days in difference between cycles) was analyzed using logistic regression with tertiles of exposure. Estimates are given as adjusted odds ratios (ORs) with 95% confidence intervals (CIs). MAIN RESULTS AND THE ROLE OF CHANCE: Higher exposure levels of PFOA were associated with longer menstrual cycles in pooled estimates of all three countries. Compared with women in the lowest exposure tertile, the adjusted OR of long cycles was 1.8 (95% CI: 1.0; 3.3) among women in the highest tertile of PFOA exposure. No significant associations were observed between PFOS exposure and menstrual cycle characteristics. However, we observed a tendency toward more irregular cycles with higher exposure to PFOS [OR 1.7 (95% CI: 0.8; 3.5)]. The overall response rate was 45.3% with considerable variation between countries (91.3% in Greenland, 69.1% in Poland and 26.3% in Ukraine). LIMITATIONS, REASONS FOR CAUTION: Possible limitations in our study include varying participation rates across countries; a selected study group overrepresenting the most fertile part of the population; retrospective information on menstrual cycle characteristics; the determination of cut-points for all three outcome variables; and lacking information on some determinants of menstrual cycle characteristics, such as stress, physical activity, chronic diseases and gynecological disorders, thus confounding cannot be excluded. WIDER IMPLICATIONS OF THE FINDINGS: The generalizability of the study results is restricted to fertile women who manage to conceive and women who do not use oral contraceptives when getting pregnant or within 2 months before getting pregnant. To our knowledge only one previous epidemiological study has addressed the possible association between perfluorinated chemical exposure and menstrual disturbances. Though pointing toward different disturbances in cyclicity, both studies suggest that exposure to PFOA may affect the female reproductive function. This study contributes to the limited knowledge on effects of exposure to PFOA and PFOS on female reproductive function and suggests that the female reproductive system may be affected by environmental exposure to PFOA. STUDY FUNDING/COMPETING INTEREST(S): Supported by a scholarship from Aarhus University Research Foundation. The collection of questionnaire data and blood samples was part of the INUENDO project supported by The European Commission (Contract no. QLK4-CT-2001-00 202), www.inuendo.dk. The Ukrainian part of the study was possible by a grant from INTAS (project 012 2205). Determination of PFOA and PFOS in serum was part of the CLEAR study (www.inuendo.dk/clear) supported by the European Commission's 7th Framework Program (FP7-ENV-2008-1-226217). No conflict of interest declared.