Non-adherence to inhaled corticosteroids and the risk of asthma exacerbations in children

Erwin C Vasbinder,1 Svetlana V Belitser,2 Patrick C Souverein,2 Liset van Dijk,3 Arnold G Vulto,1 Patricia MLA van den Bemt1 1Erasmus University Medical Center, Department of Hospital Pharmacy, Rotterdam, 2Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3NIVEL, Utrecht, the Netherlands Background: Non-adherence to inhaled corticosteroids (ICSs) is a major risk factor for poor asthma control in children. However, little is known about the effect of adherence to ICS on the incidence of asthma exacerbations. The objective of this study was to examine the effect of poor adherence to ICS on the risk of exacerbations in children with asthma. Methods: In this nested case–control study using data from the Dutch PHARMO Record Linkage System, children aged 5–12 years who had an asthma exacerbation needing oral corticosteroids or hospital admission were matched to patients without exacerbations. Refill adherence was calculated as medication possession ratio from ICS-dispensing records. Data were analyzed using a multivariable multiplicative intensity regression model. Results: A total of 646 children were included, of whom 36 had one or more asthma exacerbations. The medication possession ratio was 67.9% (standard deviation [SD] 30.2%) in children with an exacerbation versus 54.2% (SD 35.6%) in the control group. In children using long-acting beta-agonist, good adherence to ICS was associated with a higher risk of asthma exacerbations: relative risk 4.34 (95% confidence interval: 1.20–15.64). Conclusion: In children with persistent asthma needing long-acting beta-agonist, good adherence to ICS was associated with an increased risk of asthma exacerbations. Possible explanations include better motivation for adherence to ICS in children with more severe asthma, and reduced susceptibility to the consequences of non-adherence to ICS due to overprescription of ICS to children who are in clinical remission. Further study into the background of the complex interaction between asthma and medication adherence is needed. Keywords: asthma exacerbation, children, database, inhaled corticosteroids, refill adherence pharmacoepidemiology, observational study, the Netherlands&nbsp

Preventing hospital admissions by reviewing medication (PHARM) in primary care: an open controlled study in an elderly population

What is known and objective Limited and conflicting evidence exists on the effect of a multicomponent pharmaceutical care intervention (i.e. medication review, involving collaboration between general practitioners (GPs), pharmacists and patients) on medication-related hospitalizations, survival, adverse drug events (ADEs) and quality of life. We aimed to investigate the effect of a multicomponent pharmaceutical care intervention on these outcomes. Methods An open controlled multicentre study was conducted within primary care settings. Patients with a high risk on medication-related hospitalizations based on old age, use of five or more medicines, non-adherence and type of medication used were included. The intervention consisted of a patient interview, a review of the pharmacotherapy and the execution and follow-up evaluation of a pharmaceutical care plan. The patient's own pharmacist and GP carried out the intervention. The control group Results and discussion 364 intervention and 310 control patients were included. Less medication-related hospital admissions were found in the intervention group (n=6; 1.6%) than in the control group (n=10; 3.2%) but the overall effect was not statistically significant (hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.12-1.59). The secondary outcomes were not statistically significantly different either. The study was underpowered, which may explain the negative results. A post hoc analysis What is new and conclusion A multicomponent pharmaceutical care intervention does not prevent medication-related hospital admissions. Whether this is true for such interventions in general is unknown, because the PHARM study was underpowered. The intervention may significantly reduce medication-related hospitalizations in patients with five or more comorbidities, but this is only based on a post hoc analysis and thus needs confirmation in large controlled trials

Determinants of DNA yield and purity collected with buccal cell samples

Buccal cells are an important source of DNA in epidemiological studies, but little is known about factors that influence amount and purity of DNA. We assessed these factors in a self-administered buccal cell collection procedure, obtained with three cotton swabs. In 2,451 patients DNA yield and in 1,033 patients DNA purity was assessed. Total DNA yield ranged from 0.08 to 1078.0 mu g (median 54.3 mu g; mean 82.2 mu g +/- A SD 92.6). The median UV 260:280 ratio, was 1.95. Samples from men yielded significantly more DNA (median 58.7 mu g) than those from women (median 44.2 mu g). Diuretic drug users had significantly lower purity (median 1.92) compared to other antihypertensive drug users (1.95). One technician obtained significantly lower DNA yields. Older age was associated with lower DNA purity. In conclusion, DNA yield from buccal swabs was higher in men and DNA purity was associated with age and the use of diuretics

Double-adjustment in propensity score matching analysis: choosing a threshold for considering residual imbalance

Double-adjustment can be used to remove confounding if imbalance exists after propensity score (PS) matching. However, it is not always possible to include all covariates in adjustment. We aimed to find the optimal imbalance threshold for entering covariates into regression.We conducted a series of Monte Carlo simulations on virtual populations of 5,000 subjects. We performed PS 1:1 nearest-neighbor matching on each sample. We calculated standardized mean differences across groups to detect any remaining imbalance in the matched samples. We examined 25 thresholds (from 0.01 to 0.25, stepwise 0.01) for considering residual imbalance. The treatment effect was estimated using logistic regression that contained only those covariates considered to be unbalanced by these thresholds.We showed that regression adjustment could dramatically remove residual confounding bias when it included all of the covariates with a standardized difference greater than 0.10. The additional benefit was negligible when we also adjusted for covariates with less imbalance. We found that the mean squared error of the estimates was minimized under the same conditions.If covariate balance is not achieved, we recommend reiterating PS modeling until standardized differences below 0.10 are achieved on most covariates. In case of remaining imbalance, a double adjustment might be worth considering