Population-Based Cohort Study of Anti-Infective Medication Use before and after the Onset of Type 1 Diabetes in Children and Adolescents

Abstract

A population-based cohort study was conducted in the Dutch PHARMO database to investigate prevalence and patterns of antiinfective medication use in children and adolescents with type 1 diabetes (T1D) before and after the onset of this disease. All patients <19 years with at least 2 insulin prescriptions (1999 to 2009) were identified (T1D cohort) and compared with an age-and sex-matched (ratio: 1 up to 4) diabetes-free reference group. The prevalence and average number of anti-infective use was studied from (up to) 8 years before until a maximum of 4 years after the onset of T1D. A total of 925 patients with T1D and 3,591 children and adolescents in the reference cohort (51% boys, mean age of 10.1 [standard deviation, 4.5] years) were included. The overall prevalence of anti-infective use (62.6 compared to 52.6%, P < 0.001) and average number of prescriptions (2.71 compared to 1.42 per child, P < 0.001) in the T1D cohort were significantly higher than those in the reference cohort after the onset of diabetes. This pattern was consistent across sex and age categories and already observed in the year before the onset of type 1 diabetes. Patients in the T1D cohort received more antibacterials (49.8 compared to 40%, P < 0.001), antimycotics (4.0 compared to 1.3%, P < 0.001), antivirals (2.5 compared to 0.4%, P < 0.001), and second-line antibiotics, such as aminoglycosides, quinolones, and third-generation cephalosporins and carbapenems. Our findings that elevated anti-infective use in the T1D cohort exists in the period before the onset of type 1 diabetes and the consumption of more second-line anti-infective compounds in this time period warrant further research.

Chronic comorbidities in children with type 1 diabetes: a population-based cohort study

“…The main strengths of our study are the population-based cohort design without many exclusion criteria, reasonable sample size, longitudinal data collection and a limited probability of information bias and recall bias 10 12. Using insulin as a proxy for T1D is another strength for this study since the treatment of hyperglycaemia is the only indication and it has been validated as a proxy for identifying cases of T1D 2.…”

“…We used the validated population-based Dutch PHARMO Record Linkage System (RLS) (http://www.pharmo.nl) which covers the whole country and includes high-quality and complete information linked on a patient level of, among other data, patient demographics and drug dispensing records from community pharmacies of more than four million inhabitants of the Netherlands (approximately 24% of the Dutch population) together with hospital discharge records 10 11. The drug dispensing records consist of data on the dispensed drug, the type of prescriber, the dispensing date, the amount dispensed and the written dose instructions.…”

“…Patients (<19 years old) with incident T1D were selected based on having a history of hospital admission for T1D (ICD-9 code 250) and/or at least two insulin dispensings (ATC A10A) between January 1999 and December 2009 (T1D cohort) 10 12. Either the date of first insulin dispensing or the date of first hospital admission for T1D was selected as the index date (cohort entry date), whichever came first.…”

“…To be sure that patients were really newly diagnosed with T1D, patients should be present in the database at least 1 year prior to the index date (except for children with a diagnosis of T1D before 1 year of age). Patients in the T1D cohort who used glucagon in the year prior to the cohort entry date, ever use of oral glucose-lowering medications (ATC A10B), or had history of cystic fibrosis were excluded 10 12. For each patient in the T1D cohort up to four children without any dispensing for glucose-lowering medications or diabetes hospitalisation during the study period and with the same sex, age and follow-up time were randomly sampled from the database (reference cohort).…”

Increasing trends in the incidence and prevalence rates of type 1 diabetes among children and adolescents in the Netherlands

“…We used insulin as a proxy to identify cases of type 1 diabetes . According to the Dutch law patients who are treated with insulin only need 1 insulin prescription at the start of treatment, but not for follow‐up dispensings .…”