Jurjen van der Schans

Association of atopic diseases and attention-deficit/hyperactivity disorder : A systematic review and meta-analyses

HighlightsAsthma, eczema, and rhinitis, are independently associated with ADHD in childhood.Children with atopy have 30% to 50% higher odds of developing ADHD later in life.Insight into the underlying working mechanism could improve care for both diseases. ABSTRACT Over the last decades, the hypothesis has been raised that an atopic response could lead to the development of attention‐deficit/hyperactivity disorder (ADHD). This study systematically reviews the observational cross‐sectional and longitudinal studies that assessed the association between atopic disorders including asthma, atopic eczema, allergic rhinitis, and ADHD in children and adolescents. For longitudinal studies, a weighted Mantel‐Haenszel odds ratio of these associations was estimated. The majority of cross‐sectional and longitudinal studies reported a statistically significant positive association. The meta‐analysis of longitudinal studies revealed an overall weighted odds ratio for asthma of 1.34 (95% confidence interval [CI] 1.24–1.44), 1.32 (95% CI 1.20–1.45) for atopic eczema, and 1.52 (95% CI 1.43‐1.63) for allergic rhinitis. Heterogeneity of study data was low (I2: 0%, p = 0.46 and p = 0.64, respectively) for both studies examining asthma and eczema but substantial for rhinitis studies (I2: 82%, p = 0.004). This current systematic review provides strong evidence that ADHD is associated with atopic diseases and that individuals have a 30% to 50% greater chance of developing ADHD compared to controls.

Cost-Effectiveness of Extended-Release Methylphenidate in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder Sub-Optimally Treated with Immediate Release Methylphenidate

Background Attention-Deficit/Hyperactivity Disorder (ADHD) is a common psychiatric disorder in children and adolescents. Immediate-release methylphenidate (IR-MPH) is the medical treatment of first choice. The necessity to use several IR-MPH tablets per day and associated potential social stigma at school often leads to reduced compliance, sub-optimal treatment, and therefore economic loss. Replacement of IR-MPH with a single-dose extended release (ER-MPH) formulation may improve drug response and economic efficiency. Objective To evaluate the cost-effectiveness from a societal perspective of a switch from IR-MPH to ER-MPH in patients who are sub-optimally treated. Methods A daily Markov-cycle model covering a time-span of 10 years was developed including four different health states: (1) optimal response, (2) sub-optimal response, (3) discontinued treatment, and (4) natural remission. ER-MPH options included methylphenidate osmotic release oral system (MPH-OROS) and Equasym XL/Medikinet CR. Both direct costs and indirect costs were included in the analysis, and effects were expressed as quality-adjusted life years (QALYs). Univariate, multivariate as well as probabilistic sensitivity analysis were conducted and the main outcomes were incremental cost-effectiveness ratios. Results Switching sub-optimally treated patients from IR-MPH to MPH-OROS or Equasym XL/Medikinet CR led to per-patient cost-savings of €4200 and €5400, respectively, over a 10-year treatment span. Sensitivity analysis with plausible variations of input parameters resulted in cost-savings in the vast majority of estimations. Conclusions This study lends economic support to switching patients with ADHD with suboptimal response to short-acting IR-MPH to long-acting ER-MPH regimens.

Association between medication prescription for atopic diseases and attention-deficit/hyperactivity disorder.

BACKGROUND Data on the association between atopic diseases and attention-deficit/hyperactivity disorder (ADHD) have been inconclusive. OBJECTIVE To assess whether children with drug-treated ADHD are more likely to receive treatment for asthma, allergic rhinitis, or eczema before the start of ADHD medication use compared with controls and to examine the effect of parents receiving medication for ADHD and atopic diseases on ADHD medication use in their offspring. METHODS We conducted a retrospective nested case-control study among children (6-12 years of age) using the Groningen University prescription database. Cases were defined as children with at least 2 prescriptions of methylphenidate within 12 months. For each case, 4 controls were matched on age, sex, and regional area code. Parental prescription data were linked to cases and controls to assess the influence of parents receiving medication for ADHD and atopic diseases on ADHD medication use in their offspring. RESULTS We identified 4257 cases and 17,028 matched controls. Drug treatment for asthma, allergic rhinitis, and eczema was more common in cases than controls (adjusted odds ratios [aORs], 1.4 [95% confidence interval (CI), 1.3-1.6], 1.4 [95% CI, 1.1-1.8], and 1.3 [95% CI, 1.1-1.5], respectively). Medication for allergic rhinitis and asthma among parents was associated with ADHD treatment in their children (aORs, 1.3 [95% CI, 1.1-1.5] and 1.2 [95% CI, 1.1-1.3], respectively). CONCLUSION This study provides further evidence to support the hypothesis that atopic diseases are associated with ADHD. The parental-offspring association suggests a possible genetic and/or environmental component.

Pharmacy-based predictors of non-persistence with and non-adherence to statin treatment among patients on oral diabetes medication in the Netherlands

Abstract Aims: To evaluate statin non-persistence and non-adherence as discrete processes in diabetes patients, and identify pharmacy-based predictors of these processes in the first year after statin initiation. Methods: We conducted a retrospective cohort study of statin initiators using a pharmacy database. Persistence and adherence were measured in the first, second and third year. Non-persistence was defined as a gap >180 days. Non-adherence was calculated in persistent patients and defined as a medication possession ratio <80%. Cox regression hazard ratios (HRs) and logistic regression odds ratios (ORs) were assessed for sociodemographic and medication-related factors as possible predictors. Results: Of 12,741 initiators, 20.0% were non-persistent in the first year, while 9.0% and 7.5% were non-persistent in the second and third years. Non-adherence in persistent patients increased from 13.4% in the first to 15.6% and 18.1% in the second and third years. Predictors of non-persistence were female gender (HR: 1.10; 95% CI: 1.01–1.19), older age (HR: 1.52; 95% CI: 1.31–1.75), primary prevention (HR: 1.10; 95% CI: 1.00–1.20), initiating on low dose (HR: 1.44; 95% CI: 1.07–1.94) or standard dose (HR: 1.56; 95% CI: 1.16–2.10), and no cardiovascular co-medication (HR: 1.19; 95% CI: 1.07–1.33), while patients with four or more other medications were more likely to be persistent. Age <50 years (OR: 1.47; 95% CI: 1.22–1.77), low socioeconomic status (OR: 1.27; 95% CI: 1.12–1.45) and primary prevention (OR: 1.21; 95% CI: 1.07–1.38) were predictors of non-adherence, while females were more likely to be adherent (OR: 0.87; 95% CI: 0.77–0.98). Conclusion: Non-persistence was the foremost problem in the first year after statin initiation, while non-adherence in persistent patients increased in the second and third years. Pharmacy-based predictors of statin non-persistence were different from predictors of non-adherence among persistent patients.

Association Between Attention-Deficit/Hyperactivity Disorder and Asthma Among Adults: A Case-Control Study.

1. Morrison W, Derrington SF. Stories and the longitudinal patient relationship: what can clinical ethics consultants learn from palliative care? J Clin Ethics. 2012;23(3):224-230. 2. Maung AA, Toevs CC, Kayser JB, Kaplan LJ. Conflict management teams in the intensive care unit: a concise definitive review. J Trauma Acute Care Surg. 2015;79(2):314-320. 3. Carter BS, Wocial LD. Ethics and palliative care: which consultant and when? Am J Hosp Palliat Care. 2012;29(2):146-150. 4. Aulisio MP, Chaitin E, Arnold RM. Ethics and palliative care consultation in the intensive care unit. Crit Care Clin. 2004;20(3): 505-523. x-xi.

Concordance assessment of self-reported medication use in the Netherlands three-generation Lifelines Cohort Study with the pharmacy database IADB.nl: The PharmLines Initiative. Clinical Epidemiology 2018:2010;1-9

Background While self-reported data are commonly used as a source of medication use for pharmaco-epidemiological studies, such information is prone to forms of bias. Several previous studies showed that various factors like age, type of drug and data collection method may influence accuracy. We aimed to assess the concordance of the self-reported medication use that was documented at entry to the Lifelines Cohort Study, a three-generation follow-up study in the Netherlands that started in 2006 and included over 167,000 participants. Materials and methods As part of the PharmLines Initiative, we collected medication data from the Lifelines participants encoded according to the Anatomical Therapeutic Chemical (ATC) coding scheme and linked the data via Statistics Netherlands to the widely used and representative pharmacy prescription database of the University of Groningen, IADB.nl. Analyses were conducted at second level of ATC coding for all recorded medications as well as a top list of most used medications at drug-specific fifth level. Cohen’s kappa statistics were used to measure the concordance for all participants according to sex and age. Results The level of concordance between the two data sources largely differed according to the therapeutic class. Medication used for the cardiovascular system and diabetes, thyroid therapy, bisphosphonates and anti-thrombotic drugs showed a very good agreement (κ>0.75). Medication as needed or prone to stigmatization bias showed a moderate agreement (κ=0.41–0.60), whereas medications used for short periods of time showed a fair agreement (κ=0.0–0.4). Concordance was similar for males and females, but younger adults tended to have lower concordance rates than older adults. Conclusion The self-reported method was valid for capturing prevalent chronic medication use at one moment in time, but invalid for medication used for short periods of time. There is no effect of sex on the agreement, and more studies are needed on the influence of age. Future pharmaco-epidemiological studies should preferably combine the two data sources to achieve the highest accuracy of drug exposure rates.

Predictors of non-adherence to and non-persistence with statin therapy among patients on oral diabetes medication in the netherlands: A retrospective inception cohort study

Background: To minimise post-marketing uncertainties for products with a Conditional Marketing Authorisation (CMA) in Europe, specific obligations (e.g. interventional and observational studies) are imposed as a condition to the marketing authorisation (MA). A yearly follow-up of these requirements and assessment of study results is conducted during annual renewal (AR). Objectives: To characterise changes in descriptions and due dates of obligations over time, and identify drug and obligation-related factors associated with these changes. Methods: We performed a retrospective cohort study of obligations imposed on the CMA of products licensed (excluding vaccines) since 2006 with at least one year follow-up or one AR (until 31/12/ 16). Changes in wording or due date of obligations were identified by comparing the MAs of products at granting, AR(s) and conversion of the CMA. Unconditional logistic regression was performed to calculate odds ratios (OR) and 95% confidence intervals (CI) for the association between factors extracted from documentation of the European Medicines Agency and post-marketing changes in completed obligations. Results: For 26 CMA products 79 obligations were requested (median: 2, interquartile range [IQR]: 1-3.75) with a median follow-up of 2 ARs (IQR: 1-3). Of these, 67 were imposed at time of MA and 12 during AR (6 products). In total, 31 changes were observed in 25 obligations (32% of all obligations). Changes concerned a change (delay) of due date (n = 19, 61%), description (n = 4, 13%) or both (n = 8, 26%). Six drug-related factors for changes in 61 completed obligations were identified: prospective use of CMA (OR 0.2, 95% CI 0.06-0.8), CHMP agreement on MA (majority vs. consensus; OR 3.9, 95% CI 1.2-12.4), indication (oncology vs. infectious disease; OR 3.9, 95% CI 1.1-14.0), duration of MA procedure (> 1 vs. ≤ 1 year, including clock stop time; OR 3.4, 95% CI 1.03-11.1), biologicals vs. small molecules (OR 3.3, 95% CI 1.03-10.6) and argumentation for unmet medical need (no satisfactory treatment available vs. major therapeutic advantage; OR 0.2, 95% CI 0.03- 0.8). No obligation-related risk factors were identified. Conclusions: In almost one-third of obligations imposed as a condition to a CMA, at least one change in initial wording or planning was identified. We found six factors associated with risk of change that can inform strategies for better prospective planning of post-marketing studies to reduce uncertainties.

Association of attention-deficit/hyperactivity disorder and atopic diseases : a case-control study

Healthy Living: The European Congress of Epidemiology, 2015 Esther Bols • Luc Smits • Matty Weijenberg Springer Science+Business Media Dordrecht 2015