Basic characteristics and representativeness of the German Disease Analyzer database
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PURPOSE: The aim of this study was to evaluate the representativeness of diagnoses in the Disease Analyzer (DA) database for major chronic diseases (cancer, dementia, diabetes). MATERIALS AND METHODS: DA contains anonymized longitudinal data on drug prescriptions, diagnoses as well as medical and demographic data directly obtained from the computer system of a representative sample of practices throughout Germany. DA contains data from 2,498 practices with 7.8 million patients (2017). The distribution and sex-specific incidence of various cancer subsites among new cancer cases, the age- and sex-specific prevalence of dementia, and the prevalence of diabetes were assessed. National reference data were obtained from official sources. RESULTS: Mean age (43 years) and sex distribution (47% men) of primary care patients in DA were similar to the German population. Among incident cancer cases, there was good agreement between DA data and national data with respect to the various cancer subsites (e.g., breast cancer: DA 17%; reference: 15%). Furthermore, sex distribution was largely similar. The age distribution of prevalent dementia was similar to national reference data, both in men (80 - 84 years: DA: 26.8%; reference: 27.0%) and in women (80 - 84 years: DA: 24.6%; reference: 24.1%). Diabetes prevalence in the DA (10.7%) was higher than in claims data from physicians (9.8%) or patients from statutory health insurances (9.9%). CONCLUSION: There was a good agreement of the incidence or prevalence of major chronic diseases in the outpatient DA with German reference data. The higher diabetes prevalence in the DA is due to the increased number of outpatient visits of diabetes patients.
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Dispensing Patterns of Ranibizumab and Aflibercept for the Treatment of Neovascular Age-Related Macular Degeneration: A Retrospective Cohort Study in Australia.

INTRODUCTION: Anti-vascular endothelial growth factor therapy is the standard of care for neovascular age-related macular degeneration (nAMD). The dosage of two licensed agents, ranibizumab and aflibercept, was established through clinical trials; however, it is unclear if either agent is administered as recommended in routine clinical practice. Using pharmacy claims data, we investigated if the dispensing patterns of ranibizumab differ from those of aflibercept 6 and 12 months after treatment initiation. METHODS: Prescription data retrieved from the Australian IMS® AUS LRx database were used to identify nAMD patients with one or more claims for ranibizumab or aflibercept between December 1, 2012, and March 31, 2015, with follow-up of at least 6 months. The number of ranibizumab and aflibercept units dispensed was adjusted for baseline patient Medication-Based Disease Burden Index (MBDBI) scores. No difference in the number of ranibizumab versus aflibercept units dispensed was concluded if the 95% confidence interval (CI) limits of the adjusted mean difference between the study cohorts were 1.00 unit or less. RESULTS: Baseline patient MBDBI scores were similar for the ranibizumab (N = 1235) and aflibercept (N = 959) cohorts. The adjusted mean (standard deviation) number of units dispensed was 5.3 (1.3) versus 5.1 (1.4) at month 6 and 8.9 (2.2) versus 8.9 (2.3) at month 12. The 95% CI limits of the adjusted mean difference did not exceed 1.00 unit dispensed at either time point: 95% CI of 0.09 to 0.32 for an adjusted mean difference of 0.20 at month 6 and -0.23 to 0.30 for an adjusted mean difference of 0.04 at month 12. Mean (standard deviation) dispensing intervals were comparable for both cohorts: 35.3 (19.2) days versus 36.8 (20.0) days at month 6 (adjusted mean difference -1.59 days; 95% CI -2.51 to -0.67 days) and 41.2 (20.9) days versus 41.6 (20.4) days at month 12 (adjusted mean difference -0.40 days; 95% CI -1.70 to 0.91 days). CONCLUSIONS: Ranibizumab and aflibercept are dispensed in a similar manner by Australian pharmacies during the first year of treatment. FUNDING: Novartis Pharma AG.

A Retrospective Study of Ranibizumab Treatment Regimens for Neovascular Age-Related Macular Degeneration (nAMD) in Australia and the United Kingdom.

INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is the leading cause of vision loss among persons aged 65 years and older. Anti-vascular endothelial growth factor (anti-VEGF) treatment is the recommended standard of care. The current study compares the effectiveness of ranibizumab in routine clinical practice in two countries that generally apply two different treatment regimens, treat-and-extend (T&E) in Australia or pro re nata (PRN) in the UK. METHODS: This retrospective, comparative, non-randomised cohort study is based on patients' data from electronic medical record (EMR) databases in Australia and the UK. Treatment regimens were defined based on location, with Australia as a proxy for analysing T&E and UK as a proxy for analysing PRN. The study included patients with a diagnosis of nAMD who started treatment with ranibizumab between January 2009 and July 2014. A total of 647 eyes of 570 patients in Australia and 3187 eyes of 2755 patients in the UK with complete 12-months follow-up were analysed. RESULTS: Baseline patient characteristics were comparable between the two cohorts. After 1 year of treatment, T&E-treated eyes achieved higher mean (±SE) visual acuity (VA) gains (5.00 ± 0.54 letters [95% confidence interval (CI) 3.93-6.06]) than PRN-treated eyes [3.04 ± 0.24 letters (95% CI 2.57-3.51); difference in means 2.07 ± 0.69 (95% CI 0.73-3.41), p < 0.001]. Non-inferiority of T&E compared to PRN was concluded based on the change in mean visual acuity gains at 12 months. Over the 12-month follow-up, T&E-treated eyes received a higher mean [±standard deviation (SD)] number of injections (9.29 ± 2.43) than PRN-treated eyes (6.04 ± 2.19) (p < 0.0001). Australian patients had a lower mean (±SD) number of total clinic visits (10.29 ± 2.90) than UK patients (11.47 ± 2.93) (p < 0.0001). CONCLUSION: The higher injection frequency in the T&E cohort may account for the trend toward improved vision. FUNDING: Novartis Pharma AG, Basel, Switzerland.

The evolution of virulence when parasites cause host castration and gigantism.

It has been suggested that the harm parasites cause to their hosts is an unavoidable consequence of parasite reproduction with costs not only for the host but also for the parasite. Castrating parasites are thought to minimize their costs by reducing host fecundity, which may minimize the chances of killing both host and parasite prematurely. We conducted a series of experiments to understand the evolution of virulence of a castrating bacterium in the planktonic crustacean Daphnia magna. By manipulating food levels during the infection of D. magna with the bacterium Pasteuria ramosa, we showed that both antagonists are resource-limited and that a negative correlation between host and parasite reproduction exists, indicating resource competition among the antagonists. Pasteuria ramosa also induces enhanced growth of its hosts (gigantism), which we found to be negatively correlated with host fecundity but positively correlated with parasite reproduction. Because infected hosts never recovered from infections, we concluded that gigantism is beneficial only for the parasite. Hosts, however, have evolved counteradaptations. We showed that infected hosts have enhanced reproduction before castration. This shift to earlier reproduction increases overall host fecundity and compromises parasite reproduction. Finally, we showed that this resource conflict is subject to genetic variation among host and parasite genotypes within a population and is therefore likely to be an important force in the coevolution of virulence in this system. A verbal model is presented and suggests that the adaptive value of gigantism is to store host resources, which are liberated after parasitic castration for later use by the growing parasite. This hypothesis assumes that infections are long lasting, that is, that they have a high life expectancy.