ABSTRACT
OBJECTIVES: Although most countries recommend amoxicillin for paediatric pneumonia, there is a long tradition of treatment with penicillin V (PcV) in Sweden, thus not empirically covering Haemophilus influenzae. There are, however, large regional differences in treatment practice. The aim was to compare clinical outcomes (treatment failure and severe complications), in children aged 1-59 months treated with PcV vs. amoxicillin for pneumonia. METHODS: This population-based emulated target trial included all children born in Sweden between 2001 and 2021, using national health, sociodemographic, and population registers. All pneumonia cases from hospitals and paediatric outpatient clinics in children aged 1-59 months treated as outpatients with PcV or amoxicillin between July 2005 and December 2021, were identified. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for treatment failure (newly dispensed antibiotic prescription or pneumonia-associated hospitalization day 1-14) and severe complications (lung complications, an invasive bacterial disease, admission to intensive care unit or death day 1-28) were calculated with logistic regression analysis. RESULTS: PcV was prescribed in 14 766 cases and amoxicillin in 10 566. Treatment failure occurred in 7.7% with PcV vs. 4.7% with amoxicillin, aOR 1.76 (95% CI: 1.54-2.00). Severe complications were rare, with no significant difference between PcV and amoxicillin (0.3% vs. 0.2%, aOR 0.96, 95% CI: 0.53-1.73). Sensitivity and interaction analyses showed consistent results. DISCUSSION: PcV treatment compared with amoxicillin, was associated with an increased risk for treatment failure but not for severe complications. The absolute risks for adverse outcomes were low in both groups suggesting a minor role of H. influenzae in paediatric pneumonia.
ABSTRACT
BACKGROUND: Little is known about shared origins between inflammatory bowel disease (IBD) and allergic diseases (asthma, allergic rhinitis, and eczema). We aimed to expand current knowledge on the etiological sources of comorbidities between these disorders using a range of genetically informed methods. METHODS: Within-individual and familial co-aggregation analysis was applied to 2â 873â 445 individuals born in Sweden from 1987 to 2014 and their first- and second-degree relatives. Quantitative genetic modeling was applied to 38â 723 twin pairs to decompose the genetic and environmental sources for comorbidity. Polygenic risk score analysis between IBD and allergic diseases was conducted in 48â 186 genotyped twins, and linkage disequilibrium score regression was applied using publicly available data to explore the genetic overlap. RESULTS: IBD was associated with asthma (adjusted odds ratio [aOR], 1.35; 95% confidence interval [CI], 1.30 to 1.40), allergic rhinitis (aOR, 1.27; 95% CI, 1.20 to 1.34), and eczema (aOR, 1.47; 95% CI, 1.38 to 1.56), with similar estimates for ulcerative colitis or Crohn's disease. The ORs for familial co-aggregation decreased with decreasing genetic relatedness. Quantitative genetic modeling revealed little evidence of common genetic factors between IBD and allergic diseases (eg, IBD and allergic rhinitis; genetic correlation raâ =â 0.06; 95% CI, -0.03 to 0.15) but did reveal some evidence of unique environmental factors between IBD and eczema (reâ =â 0.16; 95% CI, 0.00 to 0.32). Molecular genetic analyses were similarly null for IBD and allergic diseases, except for a slight association between Crohn's disease polygenic risk score and eczema (OR, 1.09; 95% CI, 1.06 to 1.12). CONCLUSIONS: We found little evidence to support a shared origin between IBD and any allergic disease but weak evidence for shared genetic and unique environmental components for IBD and eczema.
Comorbidities between inflammatory bowel disease (IBD) with asthma and allergic diseases have been documented, but shared origin remains unknown. Using multiple genetically informed approaches, we found little evidence of a shared origin explaining the comorbidities of IBD with asthma and allergic rhinitis but weak evidence for IBD and eczema.