Institute for Biometrics and Epidemiology

Düsseldorf, Germany

Institute for Biometrics and Epidemiology

Düsseldorf, Germany
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PubMed | Institute for Biometrics and Epidemiology, Childrens and Youth Hospital Auf der Bult, University of Ulm, axaris software & systeme GmbH and 2 more.
Type: | Journal: Journal of clinical epidemiology | Year: 2016

Complex longitudinal sampling and the observational structure of patient registers in health services research are associated with methodological challenges regarding data management and statistical evaluation. We exemplify common pitfalls and want to stimulate discussions on the design, development, and deployment of future longitudinal patient registers and register-based studies.For illustrative purposes, we employ data from the prospective, observational, German DIabetes Versorgungs-Evaluation (DIVE) register. One aim was to explore predictors for the initiation of a basal insulin supported therapy in patients with type 2 diabetes initially prescribed to glucose-lowering drugs alone.Major challenges are missing mortality information, time-dependent outcomes, delayed study entries, different follow-up times, and competing events. We show that time-to-event methodology is a valuable tool for improved statistical evaluation of register data and should be preferred to simple case-control approaches.Patient registers provide rich data sources for health services research. Analyses are accompanied with the trade-off between data availability, clinical plausibility, and statistical feasibility. Cox proportional hazards model allows for the evaluation of the outcome-specific hazards, but prediction of outcome probabilities is compromised by missing mortality information.


Kostev K.,IMS Health | Rathmann W.,Institute for Biometrics and Epidemiology
Journal of Diabetes Science and Technology | Year: 2017

Background: The aim was to compare the prescribed and calculated daily insulin dosages based on prescription data in type 2 diabetes patients in a general practice database. Methods: A total of 17 782 type 2 diabetes patients (age: 70.0 ± 11.5 years; 52% males; 16% diabetologist care) with ≥2 insulin prescriptions from 834 practices were analyzed (Disease Analyser: 01/2011-12/2015). Prescribed daily dosage (PDD) (physician documentation) and calculated daily dose (CDD) (pack size × strength × volume / days between 2 prescriptions) were calculated for short-acting, long-acting, and premixed insulins. PDD and CDD were compared using paired t-tests. Linear regression models assessed the associations of insulin dosage difference (CDD-PDD) with age, sex, diabetologist care, private health insurance, obesity, HbA1c, hypertension, hyperlipidemia, macro- and microvascular complications. Results: Mean [SD] CDDs were higher than PDDs for short-acting (52 [28] vs 48 [26] units/day), long-acting (30 [20] vs 24 [15] units/day), and premixed (46 [26] vs 40 [21] units/day) insulins (all P <.05). In regression models, age (per year) was associated with higher CDD-PDD differences (+0.11, +0.04, +0.10; P <.01) for short-, long-acting, and premixed insulins, respectively. Diabetologist care was related to lower differences (-2.92, -1.02, -3.65; all P <.05). HbA1c was associated with higher differences in long-acting and premixed insulins, but was related to a lower difference in short-acting insulins (all P <.05). Conclusions: CDD in primary care database studies substantially overestimate the PDD (8-25%). Age, diabetologist care, and glycemic control were related to CDD-PDD differences. Priming and safety shots with pens, dosing errors, or the accumulation of insulin reserves by patients may be underlying reasons. © Diabetes Technology Society.


Beyer P.,Protestant Hospital | Heidtmann B.,Catholic Childrens Hospital Wilhelmstift | Rosenbauer J.,Institute for Biometrics and Epidemiology | Holl R.W.,University of Ulm
Pediatric Diabetes | Year: 2012

Objective: Initiation of continuous subcutaneous insulin therapy (CSII) requires an appropriate basal rate profile. Different approaches exist; however, there is a lack of evidence-based recommendations, especially in young children. Study design: In this large multicenter survey, 5941 CSII patients from the German/Austrian prospective documentation system (DPV) were analyzed. Patients were divided into four age groups: <6 yr (n = 837), 6 to <12 yr (n = 1739), 12 to <18 yr (n = 2985) and 18 to <25 yr (n = 380). Basal insulin requirement and diurnal distribution were evaluated based on the most recent documentation for each patient. Results: Basal insulin requirement differed significantly between the four age groups (<6: 0.25 ± 0.12; 6 to <12: 0.33 ± 0.12; 12 to <18: 0.43 ± 0.15; 18 to <25: 0.35 ± 0.13 U/kg; p < 0.001). Circadian insulin profiles were markedly different between the younger and older age groups. In addition to age, longer diabetes duration, female gender, higher HbA1c and lower body mass index standard deviation score (BMI-SDS) were related to higher basal insulin requirement per kilogram of body weight. Conclusions: Age of the patient is the primary factor that influences both total daily requirement and circadian distribution of basal insulin in CSII. Experience from a large database may therefore facilitate the initiation of pump therapy in pediatric patients. © 2011 John Wiley & Sons A/S.


Heidemann C.,Robert Koch Institute | Niemann H.,Robert Koch Institute | Paprott R.,Robert Koch Institute | Du Y.,Robert Koch Institute | And 2 more authors.
Diabetic Medicine | Year: 2014

Aims: To investigate whether an indicator of overall traffic intensity is related to the risk of Type 2 diabetes in a nationwide cohort. Methods: The study population comprised 3604 adults aged 18-79 years and without diabetes from the German National Health Interview and Examination Survey (GNHIES98, 1997-1999) who participated again in a follow-up survey (DEGS1, 2008-2011). The association between the participants' reported traffic intensity at their residential address and Type 2 diabetes incidence was examined using logistic regression models. Results: During a mean of 12.1 years of follow-up, 252 of the participants included in the study developed Type 2 diabetes. Compared with people living in traffic-calmed areas, odds ratios were 1.15 (95% CI 0.80-1.67) for people living on moderately busy side streets, 1.11 (95% CI 0.69-1.80) for people living on considerably busy side streets, 1.41 (95% CI 0.96-2.08) for people living on heavily busy roads, and 1.97 (95% CI 1.07-3.64) for people living on extremely busy roads, after adjusting for age, sex, active and passive smoking, type of heating, education, BMI, waist circumference, sport activity and parental diabetes history. Conclusions: The twofold higher risk of Type 2 diabetes observed for people exposed to intense traffic in this nationwide cohort extends the limited evidence from previous selected populations. Although the underlying traffic-related components and their biological mechanisms still need to be unravelled, traffic exposure control should be considered in public health strategies to reduce the global burden of diabetes. © 2014 The Authors.


Szendroedi J.,Institute for Clinical Diabetology | Szendroedi J.,Heinrich Heine University Düsseldorf | Kaul K.,Institute for Clinical Diabetology | Kloock L.,Institute for Clinical Diabetology | And 16 more authors.
Diabetes Care | Year: 2014

OBJECTIVE Muscle insulin resistance has been implicated in the development of steatosis and dyslipidemia by changing the partitioning of postprandial substrate fluxes. Also, insulin resistance may be due to reduced mitochondrial function. We examined the association between mitochondrial activity, insulin sensitivity, and steatosis in a larger human population. RESEARCH DESIGN AND METHODS We analyzed muscle mitochondrial activity from ATP synthase flux (fATP) and ectopic lipids by multinuclei magnetic resonance spectroscopy from 113 volunteers with and without diabetes. Insulin sensitivity was assessed from M values using euglycemic-hyperinsulinemic clamps and/or from oral glucose insulin sensitivity(OGIS) using oral glucose tolerance tests. RESULTS Muscle fATP correlated negatively with hepatic lipid content and HbA1c. After model adjustment for study effects and other confounders, fATP showed a strong negative correlation with hepatic lipid content and a positive correlation with insulin sensitivity and fasting C-peptide. The negative correlation of muscle fATPwith age, HbA1c, and plasma free fatty acids was weakened after adjustment. Body mass, muscle lipid contents, plasma lipoproteins, and triglycerides did not associate with fATP. CONCLUSIONS The association of impaired muscle mitochondrial activity with hepatic steatosis supports the concept of a close link between altered muscle and liver energy metabolism as early abnormalities promoting insulin resistance. © 2014 by the American Diabetes Association.


Czabanka M.,Charité - Medical University of Berlin | Pena-Tapia P.,University of Heidelberg | Schubert G.A.,University of Heidelberg | Heppner F.L.,Institute for Neuropathology | And 4 more authors.
Cerebrovascular Diseases | Year: 2011

Background: Moyamoya disease (MMD) is graded based on digital subtraction angiography (DSA) with limited clinical applications. The aim was to identify clinically relevant parameters that may be used to develop a novel MMD grading system. Methods: In 40 MMD patients bilateral revascularization surgery was performed. Clinical data including DSA, MRI and regional cerebral blood flow studies were assessed. χ 2 test corrected for dependency of measurements at the same subject and analysis of receiver operating characteristics were used to identify key parameters. Grading system included: DSA (stenosis/occlusion = 1 point; stenosis/occlusion + intracranial compensation = 2 points; stenosis/occlusion + intracranial compensation + extra-intracranial compensation = 3 points), MRI (no sign of ischemia = 0 points; signs of ischemia = 1 point) and cerebrovascular reserve capacity (CVRC > -5% = 0 points; CVRC < -5% = 2 points). MMD grade I referred to 1-2 points, grade II to 3-4 and grade III to 5-6 points. Results: DSA, MRI and CVRC were dependent factors associated with the occurrence of clinical symptoms. Receiver operating characteristics analysis indentified the grading system as superior to each single parameter in predicting clinical symptoms. Fourteen hemispheres were graded as mild (grade I), 35 as moderate (grade II) and 31 as severe (grade III); 21% of grade I, 63% of grade II and 93% of grade III hemispheres were clinically symptomatic. Conclusions: The proposed grading system allows to stratify for clinical symptomatology in MMD patients. Future studies will have to investigate its value for assessing clinical symptoms and treatment risks. © 2011 S. Karger AG, Basel.


Kostev K.,IMS Health | Rockel T.,IMS Health | Rosenbauer J.,Institute for Biometrics and Epidemiology | Rathmann W.,Institute for Biometrics and Epidemiology
Primary Care Diabetes | Year: 2014

Background Previous studies have shown that only a small number of pediatric and young adult patients discontinue pump therapy, but risk factors for discontinuation are unclear.Objective To identify characteristics of pediatric and young adult patients with pump therapy which are associated with discontinuation of treatment. Subjects and methods Retrospective cohort study using a representative nationwide database (LRx; IMS Health) in Germany covering >80% of all prescriptions to members of statutory health insurances in 2008-2011. All patients (age group <25 years) with new prescriptions of insulin pumps were identified (2009-2010) and were followed for 12 months.Results Overall, 2452 new pump users were identified, of whom 177 (7.2%) switched to other forms of insulin therapy within 12 months. In multivariate logistic regression, younger age (<6 years; reference 18 to <25 years: Odds ratio, OR, 95% CI: 0.36; 0.17-0.74) and use of teflon needles (reference steel needles: OR, 95% CI: 0.59; 0.41-0.83) were related to a lower odds of pump discontinuation. A non-significant trend was found for male sex (OR, 95% CI: 0.75; 0.52-1.08). Prescriptions of thyroid therapeutics (ATC H03A: OR, 95% CI: 1.79; 1.23-2.61) and antiepileptics (N03: OR, 95% CI: 3.14; 1.49-6.59) were significantly associated with discontinuation of pump therapy.Conclusions About 93% of pediatric and young adult patients maintained insulin pump therapy within 12 months. Age <6 years, male sex and teflon needle use were associated with a lower risk of discontinuation. Thyroid therapy (indicating autoimmunity) and antiepileptic drug prescriptions were associated with a higher likelihood for discontinuation of insulin pump treatment. © 2014 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.


Kowall B.,Institute for Biometrics and Epidemiology | Rathmann W.,Institute for Biometrics and Epidemiology | Kostev K.,IMS Health
Diabetes Care | Year: 2015

OBJECTIVE : Several meta-analyses of observational studies suggested that metformin use reduces cancer risk in type 2 diabetes. However, this result was not confirmed by the few available randomized controlled trials (RCTs), and many observational studies onmetformin and cancer were potentially afflicted with time-related bias. We aimed to avoid this bias when comparing cancer incidence in users of sulfonylurea, insulin, and other diabetes medications, respectively, with cancer incidence in metformin users.RESEARCH DESIGN AND METHODS : In a retrospective observational study, we used the German Disease Analyzer database with patient data from general practices throughout Germany. The study sample included 22,556 patients diagnosed with type 2 diabetes. During the median follow-up time of 4.8 years, 1,446 (6.4%) patients developed any cancer. In Cox regression analyses with either monotherapies or first diabetes medications as drug exposure, users of sulfonylurea (or insulin or other antidiabetes medications) were compared with metformin users.RESULTS : In multivariable adjusted models, hazard ratios were 1.09 (95% CI 0.87-1.36) for sulfonylurea monotherapy, 1.14 (95% CI 0.85-1.55) for insulin monotherapy, and 0.94 (95% CI 0.67-1.33) for other diabetes medications compared with metformin monotherapy. Results were similar for comparison of first diabetes medications.CONCLUSIONS : In a retrospective database analysis, taking into account potential time-related biases, no reduced cancer risk was found in metformin users. To clarify the association between diabetes medication and cancer risk, further well-designed observational studies and RCTs are needed. © 2015 by the American Diabetes Association.


PubMed | IMS Health, Institute for Biometrics and Epidemiology and Sanofi S.A.
Type: Journal Article | Journal: Primary care diabetes | Year: 2016

To identify patient-related characteristics and other impact factors predicting early discontinuation of basal insulin therapy in type 2 diabetes in primary care.A total of 4837 patients who started basal insulin therapy (glargine: n=3175; NPH: n=1662) in 1072 general and internal medicine practices throughout Germany were retrospectively analyzed (Disease Analyser Database: 01/2008-03/2014). Early discontinuation was defined as switching back to oral antidiabetic drugs (OAD) therapy within 90 days after first basal insulin prescription (index date, ID). Patient records were assessed 365 days prior and post ID. Logistic regression models were used to adjust for age, sex, diabetes duration, diabetologist care, disease management program participation, HbA1c, and comorbidity.Within 3 months after ID, 202 (6.8%) of glargine patients switched back to OAD (NPH: 130 (8.5%); p<0.05). In multivariable logistic regression, predictors of early basal insulin discontinuation were 1 documented hypoglycemia before ID (adjusted Odds ratio; 95% CI: 2.20; 1.27-3.82), diagnosed depression (1.31; 1.01-1.70) and referrals to specialists within 90 days after ID (2.06; 1.61-2.63). Diabetologist care (0.57; 0.36-0.89) and glargine treatment (vs. NPH: 0.78; 0.61-0.98) were related to a lower odds of having early insulin discontinuation.Less than 10% of type 2 diabetes patients switched back to oral antidiabetic drugs within 90 days after start of basal insulin therapy. In particular, patients with baseline depression and frequent or severe hypoglycemia have a higher likelihood for early discontinuation of basal insulin, whereas use of insulin glargine and diabetologist care are related to an increased chance of continuous insulin treatment.


PubMed | Hannover Medical School, University of Ulm and Institute for Biometrics and Epidemiology
Type: | Journal: Pediatric diabetes | Year: 2017

To evaluate the impact of self-reported chronic-generic and condition-specific quality of life (QoL) on glycemic control among adolescents and emerging adults with long-duration type 1 diabetes (T1D) in a longitudinal design.The database used was a nationwide cohort study of patients with 10 years T1D duration at baseline in Germany. The baseline questionnaire survey was conducted in 2009-2010, the follow-up survey in 2012-2013; additional clinical data of routine care procedures were linked. QoL was assessed by the DISABKIDS chronic generic module (DCGM-12) and diabetes module (DM) with treatment and impact scales. Regression analyses were conducted for the outcome hemoglobin A1c (HbA1c) at follow up with baseline DISABKIDS scores as predictors and sociodemographic and health-related covariates.At baseline, the included 560 patients had a mean age of 15.9 (SD 2.3) years, a diabetes duration of 13.0 (2.0) years, and an HbA1c of 67 (14.2) mmol/mol. Mean follow-up time was 3.0 (0.6) years. Univariate analyses indicated associations between baseline QoL scores and HbA1c at follow-up ([DCGM-12] = -0.174 (SE 0.038), [DM treatment] = -0.100 (0.022), [DM impact] = -0.177 (0.030), p < .001). The associations remained significant after adjustment for sociodemographic and illness-related factors, but dissolved (p > .60) when additionally adjusting for baseline HbA1c. In patients with poor baseline HbA1c (>75 mmol/mol), significant associations were observed between DCGM-12 and DM impact scores and follow-up HbA1c ([DCGM-12] = -0.144 (0.062), p = .021; [DM impact] = -0.139 (0.048), p = .004).QoL was inversely associated with HbA1c after 3 years in the course of T1D only in patients poorly controlled at baseline.

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