Association of Tumor Necrosis Factor-α Inhibitors with Incident Dementia: Analysis Based on Population-Based Cohort Studies.

BACKGROUND AND OBJECTIVE: Preliminary evidence suggests a possible preventive effect of tumor necrosis factor-α inhibitors (TNFi) on incident dementia. The objective of the analysis was to investigate the association between TNFi and the risk of incident dementia in a population undergoing treatment for rheumatological disorders. METHODS: We followed patients aged ≥ 65 years with dementia and rheumatological conditions in two cohort studies, DANBIO (N = 21,538), a Danish clinical database, and AOK PLUS (N = 7112), a German health insurance database. We defined incident dementia using diagnostic codes and/or medication use and used Cox regression to compare the associations of TNFi with other rheumatological therapies on the risk of dementia. To ensure that the patients were receiving long-term medication, we included patients with rheumatic diseases and systemic therapies. RESULTS: We observed similar trends towards a lower risk of dementia associated with TNFi versus other anti-inflammatory agents in both cohorts (hazard ratios were 0.92 [95% confidence interval 0.76, 1.10] in DANBIO and 0.89 [95% confidence interval 0.63, 1.24] in AOK PLUS, respectively). CONCLUSIONS: Tumor necrosis factor-α inhibitors may decrease the risk of incident dementia although the association did not reach statistical significance in this analysis. Further research, ideally with randomization, is needed to gauge the potential of repurposing TNFi for dementia prevention and/or treatment.

Socioeconomic differences in the utilization of diagnostic imaging and non-pharmaceutical conservative therapies for spinal diseases.

BACKGROUND: A different utilization of health care services due to socioeconomic status on the same health plan contradicts the principle of equal treatment. We investigated the presence and magnitude of socioeconomic differences in utilization of diagnostic imaging and non-pharmaceutical conservative therapies for patients with spinal diseases. METHODS: The cohort study based on routine healthcare data from Germany with 11.7 million patient-years between 2012 and 2016 for patients with physician-confirmed spinal diseases (ICD-10: M40-M54), occupation and age 20 to 64 years. A Poisson model estimated the effects of the socioeconomic status (school education, professional education and occupational position) for the risk ratio of receiving diagnostic imaging (radiography, computed tomography, magnetic resonance imaging) and non-pharmaceutical conservative therapies (physical therapy including exercise therapy, manual therapy and massage, spinal manipulative therapy, acupuncture). RESULTS: Patients received diagnostic imaging in 26%, physical therapy in 32%, spinal manipulative therapy in 25%, and acupuncture in 4% of all patient-years. Similar to previous survey-based studies higher rates of utilization were associated with higher socioeconomic status. These differences were most pronounced for manual therapy, exercise therapy, and magnetic resonance imaging. CONCLUSIONS: The observed differences in health care utilization were highly related to socioeconomic status. Socioeconomic differences were higher for more expensive health services. Further research is necessary to identify barriers to equitable access to health services and to take appropriate action to decrease existing social disparities.

Acceptance of a digital therapy recommender system for psoriasis.

BACKGROUND: About 2% of the German population are affected by psoriasis. A growing number of cost-intensive systemic treatments are available. Surveys have shown high proportions of patients with moderate to severe psoriasis are not adequately treated despite a high disease burden. Digital therapy recommendation systems (TRS) may help implement guideline-based treatment. However, little is known about the acceptance of such clinical decision support systems (CDSSs). Therefore, the aim of the study was to access the acceptance of a prototypical TRS demonstrator. METHODS: Three scenarios (potential test patients with psoriasis but different sociodemographic and clinical characteristics, previous treatments, desire to have children, and multiple comorbidities) were designed in the demonstrator. The TRS demonstrator and test patients were presented to a random sample of 76 dermatologists attending a national dermatology conference in a cross-sectional face-to-face survey with case vignettes. The dermatologist were asked to rate the demonstrator by system usability scale (SUS), whether they would use it for certain patients populations and barriers of usage. Reasons for potential usage of the TRS demonstrator were tested via a Poisson regression with robust standard errors. RESULTS: Acceptance of the TRS was highest for patients eligible for systemic therapy (82%). 50% of participants accepted the system for patients with additional comorbidities and 43% for patients with special subtypes of psoriasis. Dermatologists in the outpatient sector or with many patients per week were less willing to use the TRS for patients with special psoriasis-subtypes. Dermatologists rated the demonstrator as acceptable with an mean SUS of 76.8. Participants whose SUS was 10 points above average were 27% more likely to use TRS for special psoriasis-subtypes. The main barrier in using the TRS was time demand (47.4%). Participants who perceived time as an obstacle were 22.3% less willing to use TRS with systemic therapy patients. 27.6% of physicians stated that they did not understand exactly how the recommendation was generated by the TRS, with no effect on the preparedness to use the system. CONCLUSION: The considerably high acceptance and the preparedness to use the psoriasis CDSS suggests that a TRS appears to be implementable in routine healthcare and may improve clinical care. Main barrier is the additional time demand posed on dermatologists in a busy clinical setting. Therefore, it will be a major challenge to identify a limited set of variables that still allows a valid recommendation with precise prediction of the patient-individual benefits and harms.

Validation of the qSOFA and CRB-65 in SARS-CoV-2-infected community-acquired pneumonia.

Rationale: Prognostic accuracy of the quick sequential organ failure assessment (qSOFA) and CRB-65 (confusion, respiratory rate, blood pressure and age (≥65 years)) risk scores have not been widely evaluated in patients with SARS-CoV-2-positive compared to SARS-CoV-2-negative community-acquired pneumonia (CAP). The aim of the present study was to validate the qSOFA(-65) and CRB-65 scores in a large cohort of SARS-CoV-2-positive and SARS-CoV-2-negative CAP patients. Methods: We included all cases with CAP hospitalised in 2020 from the German nationwide mandatory quality assurance programme and compared cases with SARS-CoV-2 infection to cases without. We excluded cases with unclear SARS-CoV-2 infection state, transferred to another hospital or on mechanical ventilation during admission. Predefined outcomes were hospital mortality and need for mechanical ventilation. Results: Among 68 594 SARS-CoV-2-positive patients, hospital mortality (22.7%) and mechanical ventilation (14.9%) were significantly higher when compared to 167 880 SARS-CoV-2-negative patients (15.7% and 9.2%, respectively). All CRB-65 and qSOFA criteria were associated with both outcomes, and age dominated mortality prediction in SARS-CoV-2 (risk ratio >9). Scores including the age criterion had higher area under the curve (AUCs) for mortality in SARS-CoV-2-positive patients (e.g. CRB-65 AUC 0.76) compared to SARS-CoV-2 negative patients (AUC 0.68), and negative predictive value was highest for qSOFA-65=0 (98.2%). Sensitivity for mechanical ventilation prediction was poor with all scores (AUCs 0.59-0.62), and negative predictive values were insufficient (qSOFA-65=0 missed 1490 out of 10 198 patients (∼15%) with mechanical ventilation). Results were similar when excluding frail and palliative patients. Conclusions: Hospital mortality and mechanical ventilation rates were higher in SARS-CoV-2-positive than SARS-CoV-2-negative CAP. For SARS-CoV-2-positive CAP, the CRB-65 and qSOFA-65 scores showed adequate prediction of mortality but not of mechanical ventilation.

Incident autoimmune diseases in association with SARS-CoV-2 infection: a matched cohort study.

OBJECTIVES: To investigate whether the risk of developing an incident autoimmune disease is increased in patients with prior COVID-19 disease compared to those without COVID-19, a large cohort study was conducted. METHOD: A cohort was selected from German routine health care data. Based on documented diagnoses, we identified individuals with polymerase chain reaction (PCR)-confirmed COVID-19 through December 31, 2020. Patients were matched 1:3 to control patients without COVID-19. Both groups were followed up until June 30, 2021. We used the four quarters preceding the index date until the end of follow-up to analyze the onset of autoimmune diseases during the post-acute period. Incidence rates (IR) per 1000 person-years were calculated for each outcome and patient group. Poisson models were deployed to estimate the incidence rate ratios (IRRs) of developing an autoimmune disease conditional on a preceding diagnosis of COVID-19. RESULTS: In total, 641,704 patients with COVID-19 were included. Comparing the incidence rates in the COVID-19 (IR=15.05, 95% CI: 14.69-15.42) and matched control groups (IR=10.55, 95% CI: 10.25-10.86), we found a 42.63% higher likelihood of acquiring autoimmunity for patients who had suffered from COVID-19. This estimate was similar for common autoimmune diseases, such as Hashimoto thyroiditis, rheumatoid arthritis, or Sjögren syndrome. The highest IRR was observed for autoimmune diseases of the vasculitis group. Patients with a more severe course of COVID-19 were at a greater risk for incident autoimmune disease. CONCLUSIONS: SARS-CoV-2 infection is associated with an increased risk of developing new-onset autoimmune diseases after the acute phase of infection. Key Points • In the 3 to 15 months after acute infection, patients who had suffered from COVID-19 had a 43% (95% CI: 37-48%) higher likelihood of developing a first-onset autoimmune disease, meaning an absolute increase in incidence of 4.50 per 1000 person-years over the control group. • COVID-19 showed the strongest association with vascular autoimmune diseases.

Development of a risk score to identify patients at high risk for a severe course of COVID-19.

Aim: We aimed to develop a risk score to calculate a person's individual risk for a severe COVID-19 course (POINTED score) to support prioritization of especially vulnerable patients for a (booster) vaccination. Subject and methods: This cohort study was based on German claims data and included 623,363 individuals with a COVID-19 diagnosis in 2020. The outcome was COVID-19 related treatment in an intensive care unit, mechanical ventilation, or death after a COVID-19 infection. Data were split into a training and a test sample. Poisson regression models with robust standard errors including 35 predefined risk factors were calculated. Coefficients were rescaled with a min-max normalization to derive numeric score values between 0 and 20 for each risk factor. The scores' discriminatory ability was evaluated by calculating the area under the curve (AUC). Results: Besides age, down syndrome and hematologic cancer with therapy, immunosuppressive therapy, and other neurological conditions were the risk factors with the highest risk for a severe COVID-19 course. The AUC of the POINTED score was 0.889, indicating very good predictive validity. Conclusion: The POINTED score is a valid tool to calculate a person's risk for a severe COVID-19 course. Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-023-01884-7.

[Recommendations for the Utilization of Claims Data During a Pandemic: Lessons Learned from the Project EgePan-Unimed of the Netzwerk Universitätsmedizin (NUM)]. / Potentiale von und Empfehlungen zur Nutzung von GKV Routinedaten in einer pandemischen Versorgungslage ­ Erfahrungen aus dem Projekt egePan-Unimed des Netzwerk Universitätsmedizin (NUM).

For appropriate response to the COVID-19 pandemic, and for obtaining answers to various relevant research questions, empirical data are required. Claims data of health insurances are a valid data source in such a situation. Within the project egePan-Unimed of the Netzwerk Universitätsmedizin (NUM) we investigated five COVID-19-related research questions using German claims data of statutory health insurances. We studied the prevalence and relevance of risk factors for a severe course of COVID-19, the background incidence of cerebral venous sinus thrombosis and myocarditis, the frequency and symptoms of post-COVID as well as the care of people with a psychiatric condition during the COVID-19 pandemic. Based on these cases, context-specific recommendations regarding the use of German claims data for future pandemics or other public health emergencies were derived, namely that the utilization of established and interdisciplinary project teams enables a timely project start and furthermore, meta-analytic methods are a valuable way to pool aggregated results of claims data analyses when data protection regulations do not allow a consolidation of data sets from different statutory health insurances. Under these circumstances, claims data are a readily available and valid data source of empirical evidence base necessary for public health measures during a pandemic.

Post-COVID-19-associated morbidity in children, adolescents, and adults: A matched cohort study including more than 157,000 individuals with COVID-19 in Germany.

BACKGROUND: Long-term health sequelae of the Coronavirus Disease 2019 (COVID-19) are a major public health concern. However, evidence on post-acute COVID-19 syndrome (post-COVID-19) is still limited, particularly for children and adolescents. Utilizing comprehensive healthcare data on approximately 46% of the German population, we investigated post-COVID-19-associated morbidity in children/adolescents and adults. METHODS AND FINDINGS: We used routine data from German statutory health insurance organizations covering the period between January 1, 2019 and December 31, 2020. The base population included all individuals insured for at least 1 day in 2020. Based on documented diagnoses, we identified individuals with polymerase chain reaction (PCR)-confirmed COVID-19 through June 30, 2020. A control cohort was assigned using 1:5 exact matching on age and sex, and propensity score matching on preexisting medical conditions. The date of COVID-19 diagnosis was used as index date for both cohorts, which were followed for incident morbidity outcomes documented in the second quarter after index date or later.Overall, 96 prespecified outcomes were aggregated into 13 diagnosis/symptom complexes and 3 domains (physical health, mental health, and physical/mental overlap domain). We used Poisson regression to estimate incidence rate ratios (IRRs) with 95% confidence intervals (95% CIs). The study population included 11,950 children/adolescents (48.1% female, 67.2% aged between 0 and 11 years) and 145,184 adults (60.2% female, 51.1% aged between 18 and 49 years). The mean follow-up time was 236 days (standard deviation (SD) = 44 days, range = 121 to 339 days) in children/adolescents and 254 days (SD = 36 days, range = 93 to 340 days) in adults. COVID-19 and control cohort were well balanced regarding covariates. The specific outcomes with the highest IRR and an incidence rate (IR) of at least 1/100 person-years in the COVID-19 cohort in children and adolescents were malaise/fatigue/exhaustion (IRR: 2.28, 95% CI: 1.71 to 3.06, p < 0.01, IR COVID-19: 12.58, IR Control: 5.51), cough (IRR: 1.74, 95% CI: 1.48 to 2.04, p < 0.01, IR COVID-19: 36.56, IR Control: 21.06), and throat/chest pain (IRR: 1.72, 95% CI: 1.39 to 2.12, p < 0.01, IR COVID-19: 20.01, IR Control: 11.66). In adults, these included disturbances of smell and taste (IRR: 6.69, 95% CI: 5.88 to 7.60, p < 0.01, IR COVID-19: 12.42, IR Control: 1.86), fever (IRR: 3.33, 95% CI: 3.01 to 3.68, p < 0.01, IR COVID-19: 11.53, IR Control: 3.46), and dyspnea (IRR: 2.88, 95% CI: 2.74 to 3.02, p < 0.01, IR COVID-19: 43.91, IR Control: 15.27). For all health outcomes combined, IRs per 1,000 person-years in the COVID-19 cohort were significantly higher than those in the control cohort in both children/adolescents (IRR: 1.30, 95% CI: 1.25 to 1.35, p < 0.01, IR COVID-19: 436.91, IR Control: 335.98) and adults (IRR: 1.33, 95% CI: 1.31 to 1.34, p < 0.01, IR COVID-19: 615.82, IR Control: 464.15). The relative magnitude of increased documented morbidity was similar for the physical, mental, and physical/mental overlap domain. In the COVID-19 cohort, IRs were significantly higher in all 13 diagnosis/symptom complexes in adults and in 10 diagnosis/symptom complexes in children/adolescents. IRR estimates were similar for age groups 0 to 11 and 12 to 17. IRs in children/adolescents were consistently lower than those in adults. Limitations of our study include potentially unmeasured confounding and detection bias. CONCLUSIONS: In this retrospective matched cohort study, we observed significant new onset morbidity in children, adolescents, and adults across 13 prespecified diagnosis/symptom complexes, following COVID-19 infection. These findings expand the existing available evidence on post-COVID-19 conditions in younger age groups and confirm previous findings in adults. TRIAL REGISTRATION: ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT05074953.

Indication for spinal surgery: associated factors and regional differences in Germany.

BACKGROUND: Rising surgery rates have raised questions about the indications for spinal surgery. The study investigated patient-level and regional factors associated with spinal surgery for patients with spinal diseases. METHODS: We undertook a cohort study based on routine healthcare data from Germany of 18.4 million patients within 60.9 million episodes of two patient-years before a possible spinal surgery in the time period 2008 to 2016. Using a Poisson model, the effects of a broad range of patient-related (sociodemographic, morbidity, social status), disease- and healthcare-related (physicians' specialty, conservative treatments) and regional variables were analyzed. RESULTS: There was substantial regional heterogeneity in the occurrence of spinal surgery which decreased by only one quarter when controlling for the various determinants assessed. Previous musculoskeletal and mental health disorders as well as physical therapy were associated with a lower probability of surgery in the fully-adjusted model. Prescriptions for pain medication and consultations of specialists were associated with a higher probability of surgery. However, the specific severity of the vertebral diseases could not be taken into account in the analysis. Furthermore, a substantial proportion of patients with surgery did not receive a consultation with an outpatient specialist (29.5%), preoperative diagnostics (37.0%) or physical therapy (48.3%) before hospital admission. CONCLUSION: This large study on spinal diseases in Germany highlights important patterns in medical care of spinal diseases and their association with the probability of spinal surgery. However, only a relatively small proportion of the regional heterogeneity in spinal surgery could be explained by the extensive consideration of confounders, which suggests the relevance of other unmeasured factors like physicians' preferences.

[Treatment practice of patients with Parkinson's disease in Saxony : A secondary data-based analysis of utilization in the observation period 2011-2019]. / Versorgungssituation von Parkinson-Patienten in Sachsen : Eine sekundärdatenbasierte Analyse der Inanspruchnahme im Beobachtungszeitraum 2011 bis 2019.

BACKGROUND: The consequences of demographic change are already noticeable in Saxony, the federal state with the highest average age in Germany and predominantly rural areas. In order to improve medical care for patients with Parkinson's disease (PwP), a status quo analysis of current care practice is required. OBJECTIVE: To what extent does the utilization of medical services by PwP differ a) between urban and rural areas in Saxony and b) between PwP with and without neurologist contact in the observation period from 2011 to 2019? MATERIAL AND METHODS: The cohort study was based on extensive routine data for Saxony from the health insurance company AOK PLUS from 2010 to 2019. A cohort of 15,744 PwP (n = 67,448 patient-years) was compared to a matched cohort (n = 674,480 patient-years; criteria: year of birth, gender, year of insurance, place of residence: urban/rural) without an ICD-10 coding of a movement disorder. RESULTS: Overall, there was a steady increase in the number of PwP in the dynamic cohort from 2011 (n = 6829) to 2019 (n = 8254). Urban-rural differences included a smaller proportion of patients being seen by a neurologist in rural areas. The PwP had a 3.5 to 4­fold higher risk of dying compared to those in the comparison cohort. Changes in drug therapy for Parkinson's disease (i.e., increases in COMT and MAO inhibitors) and in remedy delivery (i.e., increases in occupational therapy and speech therapy) over the observation period were primarily seen in PwP who were seen by a neurologist. DISCUSSION: The study identified increased morbidity and mortality in PwP who are suitable targets for innovative care concepts. The increasing number of patients and the described differences document the need for this. At the same time, changes in prescription practice show that innovative forms of treatment are being used by neurologists in outpatient care.

Impact of safety warnings for fluoroquinolones on prescribing behaviour. Results of a cohort study with outpatient routine data.

PURPOSE: The need for drug-related safety warnings is undisputed, but their impact on prescribing behaviour is not always clear. Safety warnings usually do not contain therapeutic alternatives. Based on German outpatient routine healthcare data, our cohort study investigated the impact of three warnings for fluoroquinolones on prescribing behaviour. METHODS: Structural breaks were estimated in a time-series analysis (2005-2014) of 184,134 first antibiotic prescriptions for patients (≥ 18 years) diagnosed with community-acquired pneumonia (CAP), acute bacterial sinusitis (ABS), or acute exacerbation of chronic bronchitis (AECB). Subsequently, risk factors for patients' before/after safety warnings presented as risk ratios (RR) were estimated by Poisson regression. RESULTS: Following the 2008 warning for moxifloxacin, the RR of being prescribed moxifloxacin was reduced by 56% (95% CI 0.41-0.47; p < 0.001) for CAP, by 65% (95% CI 0.32-0.39; p < 0.001) for ABS, by 57% (95% CI 0.41-0.45; p < 0.001) for AECB. After the 2012 warning for levofloxacin, the RR of being prescribed levofloxacin was reduced by 31% (95% CI 0.64-0.74; p < 0.001) for CAP, by 14% (95% CI 0.77-0.96; p = 0.007) for ABS, by 27% (95% CI 0.69-0.77; p < 0.001) for AECB. We noticed a prescription-switch to other antibiotics which was not in line with the national guideline recommendations. The warning for moxifloxacin 2009 had no impact on prescribing behaviour. CONCLUSION: This study observed an impact on prescribing behaviour in response to regulatory safety warnings for two out of three warnings. Information on therapeutic alternatives should be a part of any safety warning to encourage the intended changes in prescribing behaviour.

Depression and anxiety with exposure to ozone and particulate matter: An epidemiological claims data analysis.

BACKGROUND: Depression and anxiety have complex etiologies and are associated with a significant burden of disease. Although air pollution has been hypothesized as a possible risk factor of these disorders, the associations are still under-investigated. We aimed to analyze associations between long-term exposure to ambient ozone and particulate matter with diameter <10 µm (PM10) and diagnoses of depression and anxiety in a general population. METHODS: We utilized data from a large statutory health insurance company from Saxony, Germany. Information on outpatient clinical diagnoses of depression and anxiety was available for the years 2005-2014. We assigned ambient ozone and PM10 estimates to residential districts of 1.13 million individuals aged 16 and older. Depression and anxiety were defined as diagnoses counts. Associations with depression and anxiety were assessed using adjusted generalized estimating equations models. RESULTS: In the ten-year study period, the observed prevalences of depression and anxiety were 7.40% and 3.82%, respectively. In the two-pollutant model, 10 more days with a maximum 8-h average ozone concentration exceeding 120 µg/m³ resulted in a relative risk (RR) of 1.010 with 95% confidence interval (CI) (1.005, 1.014) for depression and an RR of 1.007 (95% CI (1.000, 1.014)) for anxiety. The effect estimates of PM10 for depression and anxiety were 1.180 (95% CI (1.160, 1.201)) and 1.176 (95% CI (1.148, 1.205)) per 10 µg/m³ increase in PM10 concentration, respectively. Age, sex, and access to healthcare of the individual were also associated with the diagnosis of the disorders. The associations were consistent across one- and two-pollutant models. CONCLUSIONS: Our findings indicate that increased levels of ambient ozone and PM10 may elevate the risk of a depression or anxiety diagnosis in the general population. However, given the lack of data on individual air pollutant exposure and socioeconomic status, our results should be interpreted with caution. Further well-designed epidemiological studies should replicate our findings.

The moderating role of allergy immunotherapy in asthma progression: Results of a population-based cohort study.

BACKGROUND: Allergic asthma causes substantial morbidity and constitutes a public health burden, which increases with asthma severity. There is evidence that allergy immunotherapy (AIT) prevents the progression of allergic rhinitis (AR) to asthma. However, evidence is missing on the potential of AIT to prevent progression from milder to more severe asthma. METHODS: This population-based cohort study utilized healthcare data (2005 to 2014) from a statutory health insurance in Germany. The severity of asthma was classified according to the treatment steps recommended by the global initiative for asthma (GINA). The effect of AIT on the transition between the GINA steps was analyzed using multivariable Cox regression models adjusted for age and sex. RESULTS: From the total cohort of 1,739,440 patients, 39,167 individuals aged 14 years or older were classified as having incident asthma during the observation period and were included in the study. From these, 4111 patients (10.5%) received AIT. AIT exposure was associated with a significantly decreased likelihood of asthma progression from GINA step 1 to GINA step 3 (HR 0.87; 95% CI 0.80-0.95) and GINA step 3 to GINA step 4 (HR 0.66; 95% CI 0.60-0.74). GINA medication for step 2 and step 5 was rarely prescribed. CONCLUSIONS: This observational study in a real-world setting indicates that patients with allergic asthma who receive AIT are less likely to experience progression of asthma severity than asthma patients not receiving AIT.

Impact of the 13-Valent Pneumococcal Conjugate Vaccine on the Incidence of All-cause Pneumonia in Adults Aged ≥60 Years: A Population-based, Retrospective Cohort Study.

In this population-based study evaluating the effectiveness of the 13-valent pneumococcal conjugate vaccine (2012-2016) to prevent all-cause pneumonia in adults ≥60 years of age, we found significant, 0.63% absolute risk and 11.9% relative risk reductions on the 3-year (2014-2016) cumulative incidences of all-cause pneumonia after vaccination.

Outdoor air pollution, greenspace, and incidence of ADHD: A semi-individual study.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a frequently occurring neurodevelopmental disorder, symptoms of which first appear in early childhood. Etiology of ADHD is not well understood. We investigated whether outdoor air pollution and greenspace affect ADHD incidence in children residing in Saxony. METHODS: 66,823 children, all beneficiaries of the statutory health insurance company AOK PLUS and born between 2000 and 2004, were followed until 2014. We considered any child with at least one ICD-10-GM F90 diagnosis by a child/adolescent psychiatrist, neuropaediatrician, or psychotherapist an ADHD case. Children's home addresses were known up to their four-digit postal code area. Population-weighted mean values of particulate matter with diameter of < 10 µm (PM10), nitrogen dioxide (NO2), and MODIS Normalized Difference Vegetation Index (NDVI) were calculated for 186 postal code areas. Associations with each exposure were assessed by two-level adjusted Poisson regression models. RESULTS: 2044 children (3.06%) were diagnosed with ADHD within the observation period. An increase of PM10 and NO2 by 10 µg/m3 raised the relative risk of ADHD by a factor of 1.97 [95% CI: 1.35-2.86] and 1.32 [1.10-1.58], respectively. A 0.1-unit increase in NDVI decreased the relative risk of ADHD by a factor of 0.82 [0.68-0.98]. Better access to child/adolescent psychiatrists was the most important confounder that increased ADHD risk across all models. CONCLUSION: Our results provide some evidence that air pollution might affect ADHD. Future studies with more detailed address information and better control for confounders, in particular socioeconomic status and parental psychopathology, should replicate the observed associations.