ObjectivesTo investigate the impact of disease activity, the course of the disease, its treatment over time, comorbidities and traditional risk factors on survival.MethodsData of the German biologics register RABBIT were used. Cox regression was applied to investigate the impact of time-varying covariates (disease activity as measured by the DAS28, functional capacity, treatment with glucocorticoids, biologic or synthetic disease modifying antirheumatic drugs (DMARDs)) on mortality after adjustment for age, sex, comorbid conditions and smoking.ResultsDuring 31 378 patient-years of follow-up, 463 of 8908 patients died (standardised mortality ratio: 1.49 (95% CI 1.36 to 1.63)). Patients with persistent, highly active disease (mean DAS28  > 5.1) had a significantly higher mortality risk (adjusted HR (HRadj)=2.43; (95% CI 1.64 to 3.61)) than patients with persistently low disease activity (mean DAS28 < 3.2). Poor function and treatment with glucocorticoids > 5 mg/d was significantly associated with an increased mortality, independent of disease activity. Significantly lower mortality was observed in patients treated with tumour necrosis factor α (TNFα) inhibitors (HRadj=0.64 (95% CI 0.50 to 0.81), rituximab (HRadj=0.57 (95% CI 0.39 to 0.84), or other biologics (HRadj=0.64 (95% CI 0.42 to 0.99), compared to those receiving methotrexate. To account for treatment termination in patients at risk, an HRadj for patients ever exposed to TNFα inhibitors or rituximab was calculated. This resulted in an HRadj of 0.77 (95% CI 0.60 to 0.97).ConclusionsPatients with long-standing high disease activity are at substantially increased risk of mortality. Effective control of disease activity decreases mortality. TNFα inhibitors and rituximab seem to be superior to conventional DMARDs in reducing this risk.

Objectives We would assess the possible impact of a range of physical and psychosocial working conditions on early exit from paid employment (i.e., before retirement age) in a representative employee population in Germany. Methods We analysed a cohort from the German Study on Mental Health at Work (S-MGA) with a baseline of 2351 employees in 2011/12, sampled randomly from the register of integrated employment biographies (IEB) at the Institute for Employment Research (IAB). Follow-up ended mid-2015. Early Exit comprised episodes of either pensioning, long-term sickness absence or unemployment ≥ 18 months. Total follow-up years were 8.422. Working conditions were partly assessed by the Copenhagen Psychosocial Questionnaire (COPSOQ). Through Cox regressions, associations of baseline working conditions with time to event of exit were estimated—adjusting for baseline age, gender, poverty, fixed-term contract and socioeconomic position. Results In multiple regressions, awkward body postures (HR = 1.24; 95% CI = 1.07–1.44), heavy lifting (1.17; 1.00–1.37) and high work pace (1.41; 1.16–1.72) were associated with exit. The estimated attributable fraction of exit for being exposed to less than optimal work environment was 25%. Regarding specific exit routes, repetitive movements (1.25; 1.03–1.53) increased the risk for the long-term sickness absence; work pace (1.86; 1.22–2.86) and role clarity (0.55; 0.31–1.00) were associated to unemployment; and control over working time (0.72; 0.56–0.95) decreased the risk of the early retirement. Conclusions Work environment seems to be important for subsequent early exit from work. Physical and psychosocial demands seem to be associated to exit to a stronger extent than resources at work.

ObjectivesThe aim of this study is to investigate the effects of occupational exposure to respirable quartz (RQ) on first acute myocardial infarction (AMI). RQ causes pulmonary diseases like silicosis and has also been linked to cardiovascular diseases. Inflammation is hypothesised as the underlying pathway.MethodsWe performed a 1:3 matched case–control study nested in a cohort of male uranium miners. We included cases (identified from hospital records and validated according to WHO criteria) who had suffered their first AMI while still employed and <65 years of age. Controls were matched by date of birth and Wismut recruitment era. RQ exposure was derived from a job-exposure matrix. We performed a conditional logistic regression adjusted for smoking, metabolic syndrome and baseline erythrocyte sedimentation rate. Subgroups by date of birth and Wismut recruitment era were analysed to minimise the impact of pre-exposures.ResultsThe study base comprised 292 matched sets. The cumulative exposure ranged from 0 to 38.9 mg/m3-years RQ. The adjusted OR of the highest RQ tertile (>14.62 mg/m3-years) was 1.27 (95% CI 0.82 to 1.98). However, for miners born after 1928 and hired in the earliest recruitment era (1946–1954), a significantly elevated risk was seen in the highest RQ tertile (OR=6.47 [95% CI 1.33 to 31.5]; 50 matched sets).ConclusionsAn impact of quartz dust on first AMI was observed only in a small subgroup that had virtually no pre-exposure to RQ. Further studies on the basis of complete occupational history are required to substantiate this finding.

Zusammenfassung Hintergrund Die Sichelzellkrankheit (SCD, ICD-10:D57) ist eine autosomal rezessiv vererbte Hämoglobinkrankheit mit globaler Public-Health-Relevanz. In Deutschland kommen pro Jahr 70–150 Kinder mit SCD zur Welt (1–2 je 10 000 Neugeborene). Die Früherkennung im asymptomatischen ersten Vierteljahr wäre leitliniengerecht und sekundärpräventiv bedeutsam. Ziel der Studie Das Ziel dieser Arbeit ist 1) die Ermittlung der Prävalenz von SCD in Routinedaten von AOK-versicherten Neugeborenen, 2) die Messung des Alters bei der Erstdiagnose D57, 3) die Zählung charakteristischer Krankenhausdiagnosen. Methode Analysiert wurden ambulante und stationäre Routinedaten von 204 AOK-versicherten Kindern. Dies sind alle, die 2009–2010 geboren sind, mindestens einen Tag im Geburtsjahr AOK-versichert waren und innerhalb von 6 Kalenderjahren jemals einen Code D57 erhielten. Die Anzahl Neugeborener in der AOK 2009–2010 (Nennerpopulation) ist bekannt. SCD-Fälle (Zähler) gelten als validiert, wenn D57 (außer D57.3) in mindestens 2 Quartalen (Q) codiert wurde. Es wird die Prävalenzproportion mit Bootstrap-Konfidenzintervall (CI) berechnet. Pro Fall wird quartalsgenau ausgelesen, wann D57 erstmals auftaucht. Der Standardized Incidence Ratio (SIR) wird berechnet für Krankenhausfälle vom Monat 13 bis Monat 61 im Vergleich zur Bevölkerung gleichen Geschlechts und Alters (1 bis unter 5 Jahre). Die Auswertung erfolgt mit SPSS 22 und Excel. Ergebnis Nach interner Validierung resultierten 78 Fälle von SCD. Die Prävalenz beträgt 1,96 (95% CI 1,53–2,41) pro 10 000 Neugeborene. Regionale Schwerpunkte zeigten sich in Berlin, Bremen, Hamburg (zusammengefasst) sowie in Nordrhein-Westfalen. Die Erstnennung von D57 erfolgte nur bei 15,4% der Fälle früh, d. h. in Q1–2. Der Median liegt in Q7. In 78 Fällen ereigneten sich 266 Krankenhausfälle mit einem SIR=6,8, d. h. die Hospitalisierungsrate ist 6,8fach höher als die der Bevölkerung. Unter den Entlassungsdiagnosen fanden sich gefürchtete Outcomes wie Pneumonie, Sepsis und Milzerkrankungen. Schlussfolgerung SCD in Deutschland lässt sich mit Routinedaten der größten gesetzlichen Krankenkasse plausibel darstellen. Derzeit wird die Krankheit zu selten frühzeitig erkannt. Die Zeit bis zur Erkennung ließe sich entscheidend verkürzen durch Aufnahme von SCD in das Neugeborenenscreening. Bis eine solche Lösung erreicht ist, sollten Eltern mit Migrationshintergrund und Fachleute ihre Aufmerksamkeit für SCD erhöhen.

BackgroundObservational data so far suggest that biologic disease modifying antirheumatic drugs (bDMARDs) can be safely used in patients with rheumatoid arthritis (RA) until conception/awareness of pregnancy. However, little is known about the course of the disease during pregnancy in women who stopped bDMARDs in the first trimester, how to treat high disease activity (e.g. glucocorticoid use) and the influence of treatments on the birth outcome.ObjectivesTo study the outcomes of pregnancies and the courses of disease activity in RA patients under different treatment regimens.MethodsWe analysed pregnancies and their outcomes that were reported to the German biologics register RABBIT until end of 2014, stratified by treatment at the time of conception. In a subgroup of patients with pregnancies reported between 2001 and 2011, data of the regular RABBIT study visits were complemented by telephone interviews with particular focus on the course of pregnancy as well as disease activity and treatment during pregnancy. Descriptive statistics were applied to study associations between pregnancy outcomes and exposure to bDMARDs, glucocorticoid use as well as the course of self-reported disease activity.ResultsIn 1,715 female RA patients ≤45 years, 95 pregnancies in 78 patients were reported. At time of conception 51 pregnancies were exposed to bDMARDs (26x etanercept, 10x adalimumab, 4x tocilizumab, 4x certolizumab pegol, 3x rituximab, 2x abatacept, 1x infliximab, and 1x golimumab). Out of 44 women unexposed to bDMARDs at time of conception, 9 were biologic naive and 35 had received their last infusion or injection at least 4 weeks (rituximab 6 months) before conception (10x etanercept, 9x adalimumab, 2x tocilizumab, 1x infliximab, 13x rituximab).The rates of spontaneous abortions were similar across treatment regimens and in the range of the rates of the general population (∼ 15-20%). Induced abortions were reported in 4 out of 95 pregnancies (one due to trisomia 21 with cardiac defect).More than one third of patients (37%) exposed to bDMARDs at conception also required bDMARDs and/or ≥10 mg/d glucocorticoids later in pregnancy. All preterm births occurred in patients with ≥10 mg/d glucocorticoids.Table: Pregnancy outcomes in the cohort and the interviewed subgroup (the latter with course of disease and treatment during pregnancy). LI = last infusion/injection before conception, ADA = adalimumab, RTX = rituximabConclusionsWithin this limited sample of pregnancies we confirmed previous reports and found no increased risk of malformations or other harmful consequences in patients exposed to biologic treatment around the time of conception.AcknowledgementsThe German Biologics Register RABBIT is supported by a joint, unconditional grant from AbbVie, Bristol-Myers Squibb, MSD Sharp&Dohme, Pfizer, Roche, and UCB.Disclosure of InterestNone declared