Anja Viehmann

Long-term urban particulate air pollution, traffic noise, and arterial blood pressure.

Background: Recent studies have shown an association of short-term exposure to fine particulate matter (PM) with transient increases in blood pressure (BP), but it is unclear whether long-term exposure has an effect on arterial BP and hypertension. Objectives: We investigated the cross-sectional association of residential long-term PM exposure with arterial BP and hypertension, taking short-term variations of PM and long-term road traffic noise exposure into account. Methods: We used baseline data (2000–2003) on 4,291 participants, 45–75 years of age, from the Heinz Nixdorf Recall Study, a population-based prospective cohort in Germany. Urban background exposure to PM with aerodynamic diameter ≤ 2.5 μm (PM2.5) and ≤ 10 μm (PM10) was assessed with a dispersion and chemistry transport model. We used generalized additive models, adjusting for short-term PM, meteorology, traffic proximity, and individual risk factors. Results: An interquartile increase in PM2.5 (2.4 μg/m3) was associated with estimated increases in mean systolic and diastolic BP of 1.4 mmHg [95% confidence interval (CI): 0.5, 2.3] and 0.9 mmHg (95% CI: 0.4, 1.4), respectively. The observed relationship was independent of long-term exposure to road traffic noise and robust to the inclusion of many potential confounders. Residential proximity to high traffic and traffic noise exposure showed a tendency toward higher BP and an elevated prevalence of hypertension. Conclusions: We found an association of long-term exposure to PM with increased arterial BP in a population-based sample. This finding supports our hypothesis that long-term PM exposure may promote atherosclerosis, with air-pollution–induced increases in BP being one possible biological pathway.

Long-term residential exposure to urban air pollution, and repeated measures of systemic blood markers of inflammation and coagulation

Background In several studies, exposure to fine particulate matter (PM) has been associated with inflammation, with inconsistent results. We used repeated measurements to examine the association of long-term fine and ultrafine particle exposure with several blood markers of inflammation and coagulation. Methods We used baseline (2000–2003) and follow-up (2006–2008) data from the Heinz Nixdorf Recall Study, a German population-based prospective cohort of 4814 participants. A chemistry transport model was applied to model daily surface concentrations of PM air pollutants (PM10, PM2.5) and particle number on a grid of 1 km2. Applying mixed regression models, we analysed associations of long-term (mean of 365 days prior to blood draw) particle exposure at each participants residence with the level of high-sensitivity C reactive protein (hs-CRP), fibrinogen, platelet and white cell count (WCC), adjusting for short-term PM exposure (moving averages of 1–7 days), personal characteristics, season, ambient temperature (1–5 days), ozone and time trend. Results We analysed 6488 observations: 3275 participants with baseline data and 3213 with follow-up data. An increase of 2.4 µg/m3 in long-term PM2.5 was associated with an adjusted increase of 5.4% (95% CI 0.6% to 10.5%) in hs-CRP and of 2.3% (95% CI 1.4% to 3.3%) in the platelet count. Fibrinogen and WCC were not associated with long-term particle exposure. Conclusions In this population-based cohort, we found associations of long-term exposure to PM with markers of inflammation (hs-CRP) and coagulation (platelets). This finding supports the hypothesis that inflammatory processes might contribute to chronic effects of air pollution on cardiovascular disease.

Residential Road Traffic Noise and High Depressive Symptoms after Five Years of Follow-up: Results from the Heinz Nixdorf Recall Study

Background: Traffic noise affects a large number of people, particularly in urbanized areas. Noise causes stress and annoyance, but less is known about the relationship between noise and depression. Objective: We investigated the association of residential road traffic noise with depressive symptoms using 5-year follow-up data from a German population-based study. Methods: We analyzed data from 3,300 participants in the Heinz Nixdorf Recall study who were between 45 and 75 years old and were without depressive symptoms at baseline (2000–2003). Depressive symptoms were defined based on the Center for Epidemiologic Studies Depression scale (CES-D) 15-item questionnaire (total score ≥ 17) and antidepressant medication intake. Road traffic noise was modeled according to European Parliament/Council Directive 2002/49/EC. High noise exposure was defined as annual mean 24-hr noise levels > 55 A-weighted decibels [dB(A)]. Poisson regression with robust variance was used to estimate relative risks (RRs) a) adjusting for the potential confounders age, sex, socioeconomic status (SES), neighborhood-level SES, and traffic proximity; b) additionally adjusting for body mass index and smoking; and c) additionally adjusting for the potential confounders/intermediates comorbidities and insomnia. Results: Overall, 35.7% of the participants were exposed to high residential road traffic noise levels. At follow-up (mean = 5.1 years after baseline), 302 participants were classified as having high depressive symptoms, corresponding to an adjusted RR of 1.29 (95% CI: 1.03, 1.62; Model 1) for exposure to > 55 versus ≤ 55 dB(A). Adjustment for potential confounders/intermediates did not substantially alter the results. Associations were stronger among those who reported insomnia at baseline (RR = 1.62; 95% CI: 1.10, 2.59 vs. RR = 1.21; 95% CI: 0.94, 1.57) and appeared to be limited to those with ≤ 13 years of education (RR = 1.43; 95% CI: 1.10, 1.85 vs. 0.92; 95% CI: 0.56, 1.53 for > 13 years). Conclusion: Our results suggest that exposure to residential road traffic noise increases the risk of depressive symptoms. Citation: Orban E, McDonald K, Sutcliffe R, Hoffmann B, Fuks KB, Dragano N, Viehmann A, Erbel R, Jöckel KH, Pundt N, Moebus S. 2016. Residential road traffic noise and high depressive symptoms after five years of follow-up: results from the Heinz Nixdorf Recall Study. Environ Health Perspect 124:578–585; http://dx.doi.org/10.1289/ehp.1409400

Incidence of second cancers after radiotherapy and systemic chemotherapy in heritable retinoblastoma survivors: A report from the German reference center

Survivors of heritable retinoblastoma carry a high risk to develop second cancers. Eye‐preserving radiotherapy raises this risk, while the impact of chemotherapy remains less defined.

Insomnia and urban neighbourhood contexts – are associations modified by individual social characteristics and change of residence? Results from a population-based study using residential histories

BackgroundUntil now, insomnia has not been much of interest in epidemiological neighbourhood studies, although literature provides evidence enough for insomnia-related mechanisms being potentially dependent on neighbourhood contexts. Besides, studies have shown differences in sleep along individual social characteristics that might render residents more vulnerable to neighbourhood contextual exposures. Given the role of exposure duration and changes in the relationship between neighbourhoods and health, we studied associations of neighbourhood unemployment and months under residential turnover with insomnia by covering ten years of residential history of nearly 3,000 urban residents in the Ruhr Area, Germany.MethodsIndividual data were retrieved from the Heinz Nixdorf Recall Study, a population-based study of randomly chosen participants from adjacent cities, which contains self-rated insomnia symptoms and individual social characteristics. Participants’ residential addresses were retrospectively assessed using public registries. We built individually derived exposure measures informing about mean neighbourhood unemployment rates and months under high residential turnover. These measures were major predictors in multivariate logistic regressions modelling the association between social neighbourhood characteristics and insomnia in the whole sample and subgroups defined by low income, low education, social isolation, and change of residence. Traffic-related noise, age, gender, economic activity, and education were considered as covariates.ResultsNearly 12 per cent of the participants complained about insomnia. Associations of neighbourhood unemployment with insomnia were more consistent than those of residential turnover in the whole sample (adjusted OR 1.42, 95% CI 1.00-2.03 for neighbourhood unemployment and OR 1.33, 95% CI 0.78-2.25 for residential turnover in the highest exposure categories). In low-income and socially isolated participants, neighbourhood unemployment odds of reporting insomnia were particularly elevated (adjusted OR 2.90, 95% CI 1.39-6.02 and OR 3.32, 95% CI 1.11-9.96, respectively). Less educated participants displayed relatively high odds of reporting insomnia throughout all upper neighbourhood unemployment exposure categories. Change of residence weakened associations, whereas undisrupted exposure sharpened them by trend.ConclusionsOur findings hint at multiple stressors being effective in both the neighbourhood context and individual resident, possibly reflecting precarious life situations undermining residents’ sleep and health chances. Moreover, our results suggest a temporal dependency in the association between neighbourhood and insomnia.

Pediatric second primary malignancies after retinoblastoma treatment

Children with retinoblastoma carry a high risk to develop second primary malignancies in childhood and adolescence. This study characterizes the type of pediatric second primary malignancies after retinoblastoma treatment and investigates the impact of different treatment strategies and prognostic factors at presentation.

Sporadic unilateral retinoblastoma or first sign of bilateral disease

Background A small number of children with unilateral retinoblastoma later develop retinoblastoma in the contralateral eye (metachronous bilateral retinoblastoma). Methods We analysed the clinical and genetic characteristics of children with sporadic unilateral retinoblastoma to identify risk factors for the development of metachronous bilateral disease. Results Fifteen (3.1%) of 480 children with unilateral retinoblastoma later developed metachronous bilateral retinoblastoma (latency period >30 days). The maximum latency period was 2.3 years after initial diagnosis. Nine (22.5%) of 40 children with a RB1 mutation detectable in blood developed metachronous bilateral disease while all 155 children proved to be without a germline RB1 mutation remained unilaterally affected. Clinically, the risk of developing metachronous bilateral retinoblastoma was higher for age at diagnosis ≤0.5 years compared with >0.5 years (19.6% vs 1.2%), and for multifocal compared with unifocal unilateral retinoblastoma (17.1% vs 2.2%). Conclusions This study shows that an oncogenic RB1 mutation in the blood is a risk factor for metachronous bilateral retinoblastoma. Additional clinical risk factors for metachronous bilateral disease are diagnosis at young age (≤0.5 years) and multifocal unilateral retinoblastoma. Early genetic analysis may identify children at high risk of developing metachronous bilateral disease and may help to preserve vision using risk-adapted follow-up and early treatment.

How Eye-Preserving Therapy Affects Long-Term Overall Survival in Heritable Retinoblastoma Survivors

PURPOSE Intraocular retinoblastoma is curable, but survivors with a heritable predisposition are at high risk for second malignancies. Because second malignancies are associated with high mortality, prognostic factors for second malignancy influence long-term overall survival. This study investigates the impact of all types of eye-preserving therapies on long-term survival in the complete German cohort of patients with heritable retinoblastoma. PATIENTS AND METHODS Overall survival, disease staging using international scales, time period of diagnosis, and treatment type were analyzed in the 633 German children treated at the national reference center for heritable retinoblastoma. RESULTS The 5-year overall survival of children diagnosed in Germany with heritable retinoblastoma between 1940 and 2008 was 93.2% (95% CI, 91.2% to 95.1%), but long-term mortality was increased compared with patients with nonheritable disease. Overall survival correlated with tumor staging, and 92% of patients were diagnosed with a favorable tumor stage (International Retinoblastoma Staging System stage 0 or I). Despite a 5-year overall survival of 97.4% (95% CI, 96.0% to 98.8%) in patients with stage 0 or I, only 79.5% (95% CI, 74.2% to 84.8%) of these patients survived 40 years after diagnosis. Long-term overall survival was reduced in children treated with eye-preserving radiotherapy compared with enucleation alone, and adding chemotherapy aggravated this effect. CONCLUSION The benefits of preserving vision must be balanced with the impact of eye-preserving treatments on long-term survival in heritable retinoblastoma, and the genetic background of the patient influences choice of eye-preserving treatment. Germline RB1 genetic analysis is important to identify heritable retinoblastoma among unilateral retinoblastoma cases. Eye-preserving radiotherapy should be carefully considered in patients with germline RB1 mutations. Life-long oncologic follow-up is crucial for all retinoblastoma survivors, and less detrimental eye-preserving therapies must be developed.

Effectiveness of a web-based education program to improve vaccine storage conditions in primary care (Keep Cool): study protocol for a randomized controlled trial

BackgroundImmunization programs are among the most effective public health strategies worldwide. Adequate vaccine storage is a prerequisite to assure the vaccines’ effectiveness and safety. In a questionnaire survey among a random sample of German primary care physicians, we discovered vaccine storage deficits: 16 % of physicians had experience with cold chain breaches either as an error or near error, 49 % did not keep a temperature log, and 21 % did not use a separate refrigerator for vaccine storage. In a recent feasibility study of 21 practice refrigerators, we showed that these were outside the target range 10.2 % of the total time with some single refrigerators being outside the target range as much as 66.3 % of the time. These cooling-chain deficits are consistent with the international medical literature, yet an effective, easy to disseminate, practice-centered intervention to improve storage conditions is lacking.Methods/designThis randomized intervention trial will be conducted in a random sample of primary care practices. Based on continuous temperature recordings over 7 days, all practices with readings outside the target range for vaccine storage (+2 °C to +8 °C) will be randomly allocated to a web-based education program or a waiting list control group. The practice physicians and their teams constitute the target population. Participants will be educated about best practices in vaccine storage and will receive a manual including storage checklists and templates for temperature documentation. In all practices, temperatures of the vaccine refrigerators will be monitored continuously using a data logger with a glycol probe as a surrogate for vaccine vial temperature. The effectiveness of the web-based education program will be determined after 6 months in terms of the proportion of refrigerators with vaccine vial temperatures within the target range (+2 °C to +8 °C) during 7-day temperature logging. Secondary outcome parameters include temperature monitoring, no critically low temperatures (≤ -0.5 °C), compliance with storage recommendations, knowledge of good vaccine storage conditions, and assignment of personnel as vaccine storage manager and backup.DiscussionKeep Cool will develop and evaluate a web-based education program to improve vaccine storage conditions in primary care and thereby ensure immunization safety and effectiveness.Trial registrationDRKS00006561 (date of registration: 20 February 2015)

Hypertension management in primary care: study protocol for a cluster randomized controlled trial

BackgroundStudies worldwide show insufficient blood pressure control rates, and effective management of hypertension remains a challenge in general practice. Although structured forms of care improved blood pressure in randomized controlled trials, little is known about their effects under routine primary care. This cluster randomized trial (CRT) evaluates the effects of a modern interactive medical education series for general practitioners on hypertension management, including practice redesign strategies.Methods/DesignFor this CRT, 24 primary care academic teaching practices of the University of Duisburg-Essen, Germany, are randomized into two study arms. With the objective of improving hypertension control, general practitioners of the intervention group participate in a three-session medical education program on structured hypertension management. The program aims at changing physician awareness and practice design. Various practice tools are provided: for example, checklists on valid blood pressure readings, medication selection, detection of secondary hypertension, and patient education. General practitioners of both study groups include hypertensive patients with and without hypertension-related diseases such as angiographically proven coronary disease, and peripheral or cerebral vascular disease. Blood pressure is measured by 24-hour readings. Analyses will focus on differences in blood pressure control and changes of practice management between intervention and control group.DiscussionThe study will determine the effectiveness of our practice redesign intervention on hypertension control. The intervention addresses general practitioners and practice assistants, while aiming at benefits on the patient level. Therefore, the cluster design is used to evaluate the effects.Trial registrationDRKS00006315 (date of registration: 14 July 2014).