Penicillin V versus amoxicillin for pneumonia in children-a Swedish nationwide emulated target trial.

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.

Parental socioeconomic status and asthma in children: Using a population-based cohort and family design.

BACKGROUND: The observed association between the parental socioeconomic status (SES, measured as education/income) and asthma or wheezing in offspring may be explained by confounding of unmeasured factors (shared genes and family environment). We aimed to study the association between parental SES and asthma/wheeze using cousin comparison. METHOD: Data were collected on individuals born in Sweden 2001-2013. Parental SES (education and income) was gathered from Statistics Sweden. Asthma/wheeze was identified using national health registers. The association between parental SES at birth and incident asthma/wheeze was estimated using Cox regression also comparing differently exposed cousins. The association between parental SES at 5 years and current asthma was estimated using logistic regression. RESULTS: Included were 955,371 individuals. Mothers with compulsory school only (lowest education group) compared with those with further education (highest education group) was associated with incident asthma/wheeze below 1 year of age HRadj = 1.45 (1.38-1.52) and over 1 year of age HRadj = 1.17 (1.13-1.20). The corresponding estimates for the lowest income group were HRadj = 1.61 (1.54-1.69) and HRadj = 0.94 (0.92-0.97), respectively. In maternal cousin comparisons, the associations for asthma/wheeze over 1 year of age was HRadj = 1.21 (1.05-1.40) for compulsory school only and HRadj = 0.94 (0.84-1.07) for the lowest income group. The ORadj for current asthma at 5 years was 1.05 (1.00-1.11) for mother's compulsory school only and 0.98 (0.94-1.02) for mother's lowest income group. Results for estimates were similar for father's SES. CONCLUSION: We confirm an association between low parental SES (measured as education) and asthma/wheeze. Cousin comparison suggests that this association is not wholly due to confounding of unknown familial factors, therefore supporting a causal relationship. The relationship between parental income and asthma/wheeze is less clear. This study is important for understanding risk factors for asthma/wheeze and for future prevention strategies. Further research is warranted to investigate the possible mechanisms for association between parental education and asthma/wheeze.

Early-Life Adversity Due to Bereavement and Inflammatory Diseases in the Next Generation: A Population Study in Transgenerational Stress Exposure.

Emerging evidence suggests that trauma experienced in childhood has negative transgenerational implications for offspring mental and physical health. We aimed to investigate whether early-life adversity experienced as bereavement is associated with chronic inflammatory health in offspring. The study population included 3 generations of Swedish families with a base population of 453,516 children (generation 3) born in 2001-2012. Exposure was defined as the middle generation's (generation 2) experiencing bereavement in childhood due to the death of a parent (generation 1). Outcomes in generation 3 included 2 diagnoses of inflammatory diseases, including asthma, allergic diseases, eczema, and autoimmune diseases. Survival analysis was used to identify causal pathways, including investigation of mediation by generation 2 mood disorders and socioeconomic status (SES). We found that early-life bereavement experienced by women was associated with early-onset offspring asthma (hazard ratio = 1.15, 95% confidence interval: 1.08, 1.23); mediation analysis revealed that 28%-33% of the association may be mediated by SES and 9%-20% by mood disorders. Early-life bereavement experienced by men was associated with autoimmune diseases in offspring (hazard ratio = 1.31, 95% confidence interval: 1.06, 1.62), with no evidence of mediation. In conclusion, adversity experienced early in life may contribute to an increased risk of inflammatory diseases which is partly mediated by mood disorders and SES.

Asthma and all-cause mortality in children and young adults: a population-based study.

BACKGROUND: Studies suggest an increased all-cause mortality among adults with asthma. We aimed to study the relationship between asthma in children and young adults and all-cause mortality, and investigate differences in mortality rate by also having a life-limiting condition (LLC) or by parental socioeconomic status (SES). METHODS: Included in this register-based study are 2 775 430 individuals born in Sweden between January 1986 and December 2012. We identified asthma cases using the National Patient Register (NPR) and the Prescribed Drug Register. Those with LLC were identified using the NPR. Parental SES at birth (income and education) was retrieved from Statistics Sweden. We estimated the association between asthma and all-cause mortality using a Cox proportional hazards regression model. Effect modification by LLC or parental SES was studied using interaction terms in the adjusted model. RESULTS: The adjusted hazard rate (adjHR) for all-cause mortality in asthma cases versus non-asthma cases was 1.46 (95% CI 1.33 to 1.62). The highest increased rate appeared to be for those aged 5-15 years. In persons with asthma and without LLC, the adjHR remained increased at 1.33 (95% CI 1.18 to 1.50), but differed (p=0.002) from those with asthma and LLC, with an adjHR of 1.87 (95% CI 1.57 to 2.22). Parental SES did not alter the association (income, p=0.55; education, p=0.83). CONCLUSION: This study shows that asthma is associated with an increased mortality in children and young adults regardless of LLC or parental SES. Further research is warranted to investigate the possible mechanisms for this association.

Update on the current methods for the diagnosis and treatment of severe childhood asthma.

The level of asthma control is the key outcome towards which asthma management is evaluated. The majority of children with asthma can obtain adequate control of symptoms through avoidance of triggering factors and/or with the help of low to moderate doses of current available medications. However, there is still a group of children with poor symptom control despite intensive treatment. The current review will provide an overview of a standardized approach to characterize this heterogeneous group of severely sick children. Factors that attenuate the effect of the prescribed treatment and make asthma difficult to treat are discussed. In addition, the usefulness of current methods of assessing asthma severity, pulmonary function, allergy and airway inflammation is also described. Finally, an overview of therapeutic options for children with severe asthma is provided.