Ralph Brinks

The Prevalence and Incidence of Diabetes in Germany: An Analysis of Statutory Health Insurance Data on 65 Million Individuals From the Years 2009 and 2010

BACKGROUND The database of the German Institute of Medical Documentation and Information makes it possible for the first time to compute statistics on diabetes for all insurees of the statutory health insurance scheme in Germany. Data from this comprehensive source are less likely to be biased by differences in the membership structures of individual insurance carriers or by the underrepresentation of persons over age 80 that is seen in most population-based studies. METHODS International Classification of Diseases (ICD)-coded diagnosis data from the inpatient and outpatient sectors were used to define persons as having diabetes. Incidences were estimated from differences in prevalence from one year to the next and the expected mortality of persons with and without diabetes. RESULTS A diabetes diagnosis was present in 6.4 million out of a total of 65.6 million insurees in 2009 and in 6.7 million out of 64.9 million insures in 2010. The corresponding age and sex standardized prevalences of diabetes were 9.7% in 2009 and 9.9% in 2010, respectively. The number of persons with type 2 diabetes was 4.6 million in 2009 and 4.7 million in 2010. The prevalence and incidence of type 2 diabetes rose steeply from age 50 to age 80. Peak incidence was at age 85, with 24 newly diagnosed cases of diabetes per 1000 person-years. CONCLUSION On the basis of these data, we estimate that 5.8 million persons with type 2 diabetes are living in Germany today. The database used in this study is a valuable complement to population-based studies for monitoring the prevalence of diabetes, particularly in persons over age 80.

Low risk of renal flares and negative outcomes in women with lupus nephritis conceiving after switching from mycophenolate mofetil to azathioprine

OBJECTIVE MMF is teratogenic and needs to be replaced before pregnancy. This change may lead to flares. Our aim was to determine the risk of renal flares in women with LN who switched treatment from MMF to AZA before conception and to evaluate the outcome of their pregnancies. METHODS Medical records of women with LN counselled for pregnancy wish were reviewed. Women receiving treatment with either MMF or AZA (control group), with inactive lupus (SLEDAI ≤ 4) and quiescent LN (serum creatinine <1.5 mg/dl, inactive sediment and proteinuria <1 g/24 h for the preceding 6 months) were eligible for this study. RESULTS We identified 54 women [23 treated with MMF (group 1) and 31 treated with AZA (group 2)]. MMF dosage was tapered and subsequently transferred to AZA, which was maintained throughout pregnancy. Three (13%) patients (group 1) vs none (group 2) developed a renal flare 3-6 months after transitioning from MMF to AZA (P = 0.14) before pregnancy ensued. The only parameter with a significant difference in those with flare compared with those without was younger age (median 27 vs 30 years; P = 0.03). Risk for adverse outcome within 48 pregnancies (pre-eclampsia 9%, preterm delivery 20.5%) increased with every milligramme of prednisone dosage [odds ratio (OR) 2.03] and every single unit of SLEDAI score (OR 3.92). Renal flares occurred post-partum in two women. No patient developed worsening of renal function. CONCLUSION Replacing MMF with AZA in patients with quiescent LN for pregnancy planning rarely leads to renal flares. Pregnancy outcome was favourable.

On the convergence of derivatives of B-splines to derivatives of the Gaussian function

In 1992 Unser and colleagues proved that the sequence of normalized and scaled B-splines Bm tends to the Gaussian function as the order m increases, [1]. In this article the result of Unser et al. is extended to the derivatives of the B-splines. As a consequence, a certain sequence of wavelets defined by B-splines, tends to the famous Mexican hat wavelet. Another consequence can be observed in the continuous wavelet transform (CWT) of a function analyzed with different B-spline wavelets.

Renal Outcome in Patients with Lupus Nephritis Using a Steroid-free Regimen of Monthly Intravenous Cyclophosphamide: A Prospective Observational Study

Objective. Intravenous cyclophosphamide (IV CYC) in combination with high doses of corticosteroids is considered the “gold standard” of therapy for lupus nephritis (LN). However, the optimal dose of corticosteroids needed has not been defined. We evaluated the efficacy of a monotherapy with IV CYC in patients with a first episode of LN (duration ≤ 6 months). Methods. Forty patients with LN received IV CYC (12 pulses). Prednisone alone was administered and dose-adjusted to control extrarenal manifestations. Response after 24 months was defined as normalization of creatinine level, inactive urinary sediment, and proteinuria ≤ 0.2 g/day [complete response (CR)] or ≤ 0.5 g/day [partial response (PR)]. Results. CR was achieved in 25 (62.5%) and PR in 8 (20%) patients. Mean starting dose of prednisone was 23.9 ± 23.8 mg/day. In a posthoc analysis, we separately analyzed patients initially treated with prednisone doses ≥ 20 mg/day (Group A, n = 19) or < 20 mg/day (Group B, n = 21). CR was achieved in 52.6% (Group A) versus 71.4% (Group B; p = 0.37); and PR in 26.3% versus 14.3%, respectively (p = 0.58). During longterm followup (10.4 ± 3.1 yrs), 37.8% experienced a renal flare. Thirty patients (81%) still have normal renal function. Renal outcome was irrespective of initial prednisone doses (p = 0.46, Pearson chi-square test of independence). Conclusion. Our rates of CR and PR and longterm outcomes were comparable with rates after treatment with a combination of IV CYC with high doses of corticosteroids. These data warrant randomized controlled trials evaluating different doses of corticosteroids in LN.

Pregnancy outcome in patients with antiphospholipid syndrome after cerebral ischaemic events: an observational study

Among the most prominent features associated with antiphospholipid syndrome (APS) are cerebral ischaemic events (CVE). Pregnancy with APS increases the risk of thrombosis, including CVE. This study was undertaken to assess the risk of obstetric complications and recurrence of CVE during pregnancy in women with APS and previous CVE. We prospectively observed 23 pregnancies in 20 women (median age 31 years) with primary (n = 8) or secondary APS (n = 12). Eight patients had transient ischaemic attacks (TIA) and 12 had stroke before pregnancy. All patients received aspirin 100 mg daily in combination with low molecular weight heparin (LMWH) during their pregnancies. The live birth rate was 91.3% (n = 21). Obstetrical complications consisted mainly of preeclampsia (n = 8, 34.8%) and preterm delivery (n = 9, 42.9%). The risk for preeclampsia increased in patients who were positive for multiple antiphospholipid antibodies (aPL) (odds ratio (OR) 3.06 (95% confidence interval (CI) 1.01–9.32)) per positive aPL test (i.e anticardiolipin antibody, anti-ß2-glycoprotein I antibody, lupus anticoagulant) (p 0.049). Three patients experienced recurrent CVE in the context of pregnancy (one during pregnancy, two in the postpartum period). We found an increased, but not significant, risk of a new episode of cerebral ischaemia in patients with pregnancies complicated by preeclampsia (two out of the eight preeclampsia (p 0.15). Despite treatment, there is a significant risk for pregnancy complications in APS patients with previous CVE. Especially in the context of preeclampsia, anticoagulation should be given rigorously to prevent recurrence of CVE.

Projection of the burden of Type 2 diabetes mellitus in Germany: a demographic modelling approach to estimate the direct medical excess costs from 2010 to 2040

To model the future costs of Type 2 diabetes in Germany, taking into account demographic changes, disease dynamics and undiagnosed cases.

A new relation between prevalence and incidence of a chronic disease.

In 1991 Keiding published a relation between the age-specific prevalence and incidence of a chronic disease (in Age-specific incidence and prevalence: a statistical perspective. J. Roy. Stat. Soc. A, 154, 371–412). For special cases alternative formulations by differential equations were given recently in Brinks et al. (2013, Deriving age-specific incidence from prevalence with an ordinary differential equation. Statist. Med., 32, 2070–2078) and in Brinks & Landwehr (2014, Age- and time-dependent model of the prevalence of non-communicable diseases and application to dementia in Germany, Theor. Popul. Biol., 92, 62–68). From these works, we generalize formulations and discuss the advantages of the novel approach. As an implication, we obtain a new way of estimating the incidence rate of a chronic disease from prevalence data. This enables us to employ cross-sectional studies where otherwise expensive and lengthy follow-up studies are needed. This article illustrates and validates the novel method in a simulation study about dementia in Germany.

Prävalenz und Inzidenz von Diabetes mellitus in Deutschland

BACKGROUND The database of the German Institute of Medical Documentation and Information makes it possible for the first time to compute statistics on diabetes for all insurees of the statutory health insurance scheme in Germany. Data from this comprehensive source are less likely to be biased by differences in the membership structures of individual insurance carriers or by the underrepresentation of persons over age 80 that is seen in most population-based studies. METHODS International Classification of Diseases (ICD)-coded diagnosis data from the inpatient and outpatient sectors were used to define persons as having diabetes. Incidences were estimated from differences in prevalence from one year to the next and the expected mortality of persons with and without diabetes. RESULTS A diabetes diagnosis was present in 6.4 million out of a total of 65.6 million insurees in 2009 and in 6.7 million out of 64.9 million insures in 2010. The corresponding age and sex standardized prevalences of diabetes were 9.7% in 2009 and 9.9% in 2010, respectively. The number of persons with type 2 diabetes was 4.6 million in 2009 and 4.7 million in 2010. The prevalence and incidence of type 2 diabetes rose steeply from age 50 to age 80. Peak incidence was at age 85, with 24 newly diagnosed cases of diabetes per 1000 person-years. CONCLUSION On the basis of these data, we estimate that 5.8 million persons with type 2 diabetes are living in Germany today. The database used in this study is a valuable complement to population-based studies for monitoring the prevalence of diabetes, particularly in persons over age 80.

Age-specific prevalence of diagnosed systemic lupus erythematosus in Germany 2002 and projection to 2030.

Objective The objective of this report is to estimate the prevalence and future number of cases of systemic lupus erythematosus (SLE) in Germany. Methods Data from a representative sample of all insurants from the statutory health insurance in Germany comprising more than 2.3 million individuals have been screened for SLE diagnoses. The gender- and age-specific prevalence of SLE is calculated. The case definition is based on at least one recorded diagnosis of SLE during 2002. The stratum-specific prevalence is applied to the current and the future population of Germany in order to estimate and predict the number of people with SLE until 2030. Results The overall prevalence of diagnosed SLE in 2002 was 15.4 (95% CI: 13.1–17.9) and 55.4 (51.4, 59.8) per 100,000 in the male and female German population. This corresponds to an estimated 30,000 and 31,000 people with diagnosed SLE in 2002 and 2010, respectively. This number will slightly increase until 2020 and decrease thereafter. Conclusions Compared with health insurance data from France, the prevalence in our data is similar. Under the assumption that the gender- and age-specific prevalence of SLE in Germany will not change considerably, the number of cases in the next two decades will change only slightly.

Age- and time-dependent model of the prevalence of non-communicable diseases and application to dementia in Germany

We derive a partial differential equation (PDE) that models the age-specific prevalence of a disease as a function of the incidence, remission and mortality rates. The main focus is on non-communicable diseases (NCDs), although the PDE is not restricted to NCDs. As an application of the PDE, the number of persons with dementia in Germany until the year 2050 is estimated based on German incidence data and official population projections. Uncertainty is treated by different scenarios about life expectancy, number of migrants, prevalence of the disease in migrants, and scenarios about the future incidence, and mortality of demented persons. Life expectancy and incidence of dementia have the strongest impact on the future number of persons with dementia. In nearly all scenarios, our estimated case numbers exceed former estimates. Furthermore, we use an example to show that the PDE method yields more accurate results than a common alternative approach.