Stability of individual dementia diagnoses in routine care: Implications for epidemiological studies

PURPOSE: Epidemiological and health care research frequently rely on diagnoses from routine care, but the intra-individual stability of diagnoses of Alzheimer's disease (AD), vascular dementia (VD) or other forms of dementia (oD) in patients over time is understudied. More data on the diagnostic stability is needed to appraise epidemiological findings from such studies. METHODS: Using health claims data of the years 2004–2016 from the German Pharmacoepidemiological Research Database, 160 273 patients aged ≥50 with incident dementia were identified and followed for 4 years. According to the incident ICD-10 codes patients were assigned to the categories AD, VD or oD. Changes between categories during follow-up were calculated. RESULTS: Overall, 18.8% had incident AD (VD: 21.5%, oD: 59.7%). Fifteen thousand eight hundred forty-two patients had only one dementia diagnosis during 4 years (AD: 7.4%, VD: 12.4%, oD: 9.8%). Among those with more than one diagnosis, the incident diagnosis matched the last diagnosis in 65.1% (AD), 53.9% (VD) and 73.8% (oD) of patients. Changes in the diagnostic category were higher in patients with AD (mean: 5.1) than in patients with VD (3.6) or oD (3.3). Patients with stable AD diagnoses during the observation period were younger (median: 76 vs. 79 years) and had less inpatient treatment days (median: 14 days) than patients with changes from an AD diagnosis to another category or from another category to AD (27 days). CONCLUSIONS: While health claims data are feasible for estimating the incidence of dementia in general, the substantial number of changes in dementia diagnoses during the course of the disease warrant caution on the interpretation of epidemiological data on specific dementia types

Use of combined oral contraceptives and risk of venous thromboembolism in young women: a nested case–control analysis using German claims data

OBJECTIVE: To compare the risk of venous thromboembolism (VTE) among young women for nine combined oral contraceptives (COCs), including progestogens with an as yet unclear risk of VTE such as chlormadinone and nomegestrol, using COCs containing levonorgestrel with low ethinylestradiol (<50 μg) as a reference. DESIGN: Case–control study nested in a cohort of new users of COCs. SETTING: German claims data. POPULATION: A total of 1166 cases of VTE matched to 11 660 controls nested in a cohort of 677 331 girls and young women aged 10–19 years with one or more COCs dispensed between 2005 and 2017 after a 1-year period without any COCs. METHODS: Confounder-adjusted odds ratios (aORs) of VTE associated with current use of the respective COCs were calculated using conditional logistic regression. MAIN OUTCOME MEASURES: Venous thromboembolism (VTE), defined as a diagnosis of pulmonary embolism or deep vein thrombosis. RESULTS: Compared with levonorgestrel with low ethinylestradiol (<50 μg), the risk of VTE was increased two-fold for COCs containing dienogest (aOR 2.23, 95% CI 1.77–2.80), cyproterone (aOR 2.15, 95% CI 1.43–3.25), chlormadinone (aOR 2.06, 95% CI 1.58–2.68), desogestrel (aOR 1.93, 95% CI 1.44–2.61) and drospirenone (aOR 1.89, 95% CI 1.41–2.55), and increased five-fold for gestodene (aOR 5.05, 95% CI 1.23–20.74). For norgestimate and nomegestrol, the point estimates suggest a two-fold increased risk (aOR 1.90, 95% CI 0.62–5.81) and 40% increased risk (aOR 1.41, 95% CI 0.52–3.81), respectively. CONCLUSIONS: Our study confirms that levonorgestrel with low ethinylestradiol (<50 μg) is the COC associated with the lowest risk of VTE and suggests that for chlormadinone the risk of VTE is two times higher, and thus in the same range as for desogestrel and drospirenone

Potential of Health Insurance Claims Data to Predict Fractures in Older Adults: A Prospective Cohort Study

PURPOSE: In older adults, fractures are associated with mortality, disability, loss of independence and high costs. Knowledge on their predictors can help to identify persons at high risk who may benefit from measures to prevent fractures. We aimed to assess the potential of German claims data to predict fractures in older adults. PATIENTS AND METHODS: Using the German Pharmacoepidemiological Research Database (short GePaRD; claims data from ~20% of the German population), we included persons aged ≥ 65 years with at least one year of continuous insurance coverage and no fractures prior to January 1, 2017 (baseline). We randomly divided the study population into a training (80%) and a test sample (20%) and used logistic regression and random forest models to predict the risk of fractures within one year after baseline based on different combinations of potential predictors. RESULTS: Among 2,997,872 persons (56% female), the incidence per 10,000 person years of any fracture in women increased from 133 in age group 65– 74 years (men: 71) to 583 in age group 85+ (men: 332). The maximum predictive performance as measured by the area under the curve (AUC) across models was 0.63 in men and 0.60 in women and was achieved by combining information on drugs and morbidities. AUCs were lowest in age group 85+. CONCLUSION: Our study showed that the performance of models using German claims data to predict the risk of fractures in older adults is moderate. Given that the models used data readily available to health insurance providers in Germany, it may still be worthwhile to explore the cost–benefit ratio of interventions aiming to reduce the risk of fractures based on such prediction models in certain risk groups

Anticholinergic burden: First comprehensive analysis using claims data shows large variation by age and sex

PURPOSE: The cumulative effect of medication inhibiting acetylcholine activity—also known as anticholinergic burden (AB)—can lead to functional and cognitive decline, falls, and death. Given that studies on the population prevalence of AB are rare, we aimed to describe it in a large and unselected population sample. METHODS: Using the German Pharmacoepidemiological Research Database (GePaRD) with claims data from ~20% of the German population we analyzed outpatient drug dispensations in 2016. Based on the Anticholinergic Cognitive Burden (ACB) scale, we classified persons into four categories and determined the cumulative AB as continuous variable. RESULTS: Among 16,470,946 persons (54% female), the prevalence of clinically relevant AB (ACB≥3) was 10% (women) and 7% (men). Below age 40 it was highest in persons ≤18 years (6% both sexes). At older ages (50–59 vs. 90–99 years), prevalence of ACB≥3 increased from 7% to 26% (men) and from 10% to 32% (women). Medication classes contributing to the cumulative AB differed by age: antihistamines, antibiotics, glucocorticoids (≤19 years), antidepressants (20–49 years), antidepressants, cardiovascular medication, antidiabetics (50–64 years), and additionally medication for urinary incontinence/overactive bladder (≥65 years). Medication dispensed by general physicians contributed most to the cumulative AB. CONCLUSION: Although a clinically relevant AB is particularly common in older persons, prevalence in younger age groups was up to 7%. Given the risks associated with AB in older persons, targeted interventions at the prescriber level are needed. Furthermore, risks associated with AB in younger persons should be explored

Screening colonoscopy similarly prevented distal and proximal colorectal cancer: A prospective study among 55–69-year-olds

OBJECTIVES: We aimed to evaluate the effectiveness of screening colonoscopy in reducing incidence of distal vs. proximal colorectal cancer (CRC) in persons aged 55–69 years. STUDY DESIGN AND SETTING: Using observational data from a German claims database (German Pharmacoepidemiological Research Database), we emulated a target trial with two arms: Colonoscopy screening vs. no-screening at baseline. Adjusted cumulative incidence of total, distal, and proximal CRC over 11 years of follow-up was estimated in 55–69-year-olds at an average CRC risk and without colonoscopy, polypectomy, or fecal occult blood test before baseline. RESULTS: Overall, 307,158 persons were included (screening arm: 198,389 and control arm: 117,399). The adjusted 11-year risk of any CRC was 1.62% in the screening group and 2.38% in the no-screening group resulting in a relative risk of 0.68 (95% CI: 0.63–0.73). The relative risk was 0.67 for distal CRC (95% CI: 0.62–0.73) and 0.70 (95% CI: 0.63–0.79) for proximal CRC. The cumulative incidence curves of the groups crossed after 6.7 (distal CRC) and 5.0 years (proximal CRC). CONCLUSION: Our results suggest that colonoscopy is effective in preventing distal and proximal CRC. Unlike previous studies not using a target trial approach, we found no relevant difference in the effectiveness by location

Quality of life in bariatric patients up to twelve years after surgery – Results from a nationwide retrospective cohort study

BACKGROUND: Bariatric interventions (BI, including surgical interventions) are effective in patients with massive obesity, i.e., a body mass index (BMI) > 40, and their number has steadily increased during the past decade. Yet, the stability of improvements in quality of life (QoL) in post-interventional patients is understudied and restricted to studies with small samples and short follow-ups. METHODS: Patients with BI between 2004 and 2018 were identified in a health claims database and invited to fill in a survey, comprising sociodemographic and lifestyle information and psychometric scales. QoL was assessed with the Bariatric QoL (BQL) scale with lower scores denoting worse QoL. BMI and excess weight loss (EWL) were calculated for the time soon after intervention (EWL-T1) and when filling the survey (EWL-T2). RESULTS: The majority of n = 2151 patients were female (80.7 %), had a mean age of 54.5 years and a mean BMI of 34.8. The mean EWL-T1 was 79 % (EWL-T2: 64.6 %). The mean BQL score was 47.6 and decreased with BMI (18.5–24.9: 52.6 vs. >40: 38.7), EWL-T2 (>66 %: 51.3 vs. <65 %: 42.1) and years since intervention (3–4: 48.2 vs >8: 45.1, each p < .001). For EWL-T1, the association between higher EWLs and higher BQL scores was stronger in females than in males (p < .005); for EWL at T2, both sexes did not differ in this regard (p = .848). Among normal-weight persons, males scored significantly lower on the BQL than females (44.9 vs. 54.9). CONCLUSIONS: Post-interventional QoL improvements diminish over time and depend on the weight loss, with significant differences between men and women

Effectiveness of Mammography Screening on Breast Cancer Mortality – A Study Protocol for Emulation of Target Trials Using German Health Claims Data

BACKGROUND: The efficacy of mammography screening in reducing breast cancer mortality has been demonstrated in randomized trials. However, treatment options - and hence prognosis – for advanced tumor stages as well as mammography techniques have considerably improved since completion of these trials. Consequently, the effectiveness of mammography screening under current conditions is unclear and controversial. The German mammography screening program (MSP), an organized population-based screening program, was gradually introduced between 2005 and 2008 and achieved nation-wide coverage in 2009. OBJECTIVE: We describe in detail a study protocol for investigating the effectiveness of the German MSP in reducing breast cancer mortality in women aged 50 to 69 years based on health claims data. Specifically, the proposed study aims at estimating per-protocol effects of several screening strategies on cumulative breast cancer mortality. The first analysis will be conducted once 10-year follow-up data are available. METHODS AND ANALYSIS: We will use claims data from five statutory health insurance providers in Germany, covering approximately 37.6 million individuals. To estimate the effectiveness of the MSP, hypothetical target trials will be emulated across time, an approach that has been demonstrated to minimize design-related biases. Specifically, the primary contrast will be in terms of the cumulative breast cancer mortality comparing the screening strategies of “never screen” versus “regular screening as intended by the MSP”. ETHICS AND DISSEMINATION: In Germany, the utilization of data from health insurances for scientific research is regulated by the Code of Social Law. All involved health insurance providers as well as the responsible authorities approved the use of the health claims data for this study. The Ethics Committee of the University of Bremen determined that studies based on claims data are exempt from institutional review. The findings of the proposed study will be published in peer-reviewed journals

Drug utilization analysis of osteoporosis medications in seven European electronic health databases

SUMMARY: We studied the characteristics of patients prescribed osteoporosis medication and patterns of use in European databases. Patients were mostly female, older, had hypertension. There was suboptimal persistence particularly for oral medications. Our findings would be useful to healthcare providers to focus their resources on improving persistence to specific osteoporosis treatments. PURPOSE: To characterise the patients prescribed osteoporosis therapy and describe the drug utilization patterns. METHODS: We investigated the treatment patterns of bisphosphonates, denosumab, teriparatide, and selective estrogen receptor modulators (SERMs) in seven European databases in the United Kingdom, Italy, the Netherlands, Denmark, Spain, and Germany. In this cohort study, we included adults aged ≥ 18 years, with ≥ 1 year of registration in the respective databases, who were new users of the osteoporosis medications. The study period was between 01 January 2018 to 31 January 2022. RESULTS: Overall, patients were most commonly initiated on alendronate. Persistence decreased over time across all medications and databases, ranging from 52–73% at 6 months to 29–53% at 12 months for alendronate. For other oral bisphosphonates, the proportion of persistent users was 50–66% at 6 months and decreased to 30–44% at 12 months. For SERMs, the proportion of persistent users at 6 months was 40–73% and decreased to 25–59% at 12 months. For parenteral treatment groups, the proportions of persistence with denosumab were 50–85% (6 month), 30–63% (12 month) and with teriparatide 40–75% (6 month) decreasing to 21–54% (12 month). Switching occurred most frequently in the alendronate group (2.8–5.8%) and in the teriparatide group (7.1–14%). Switching typically occurred in the first 6 months and decreased over time. Patients in the alendronate group most often switched to other oral or intravenous bisphosphonates and denosumab. CONCLUSION: Our results show suboptimal persistence to medications that varied across different databases and treatment switching was relatively rare