Child and Parental Executive Functioning in Type 1 Diabetes: Their Unique and Interactive Role Toward Treatment Adherence and Glycemic Control

Objective. Managing type 1 diabetes (T1D) requires the ability to make complex and critical decisions regarding treatment, to execute complex tasks accurately, and to make adjustments when problems arise. This requires effective neuropsychological competences of patients and their families, especially in the domain of executive functioning (EF): the ability to self-monitor, plan, solve problems, and set priorities. Previous research focused mainly on child EF, neglecting the impact of parental EF. This study included both mothers and fathers and examined associations between child and parental EF and treatment adherence to T1D in a broad age range of patients. Methods. Parents of 270 patients (6-18 years) with T1D (mean age 12.7yrs; 52.6% female) were included. Mothers (N= 232) and fathers (N=168) completed questionnaires on child and parental EF and on treatment adherence. Analyses examined the associations linking child and parental EF to treatment adherence and glycemic control (and potential moderation effects in these associations) using hierarchical linear regression. Results. Child EF problems were negatively associated with treatment adherence. As an indication of moderation, this effect was stronger in older children. Better treatment adherence and glycemic control were reported when both child and parent showed less EF problems. Effects were more pronounced in mothers than in fathers. Conclusions. This study demonstrated a significant interplay between child and parental EF in the association with treatment adherence and glycemic control. Researchers and clinicians should remain attentive toward the role of neuropsychological concepts such as EF. Implementation in clinical practice seems meaningful.status: publishe

Child and parental executive functioning in type 1 diabetes : their unique and interactive role toward treatment adherence and glycemic control

Objective: Managing type 1 diabetes (T1D) requires the ability to make complex and critical decisions regarding treatment, to execute complex tasks accurately, and to make adjustments when problems arise. This requires effective neuropsychological competences of patients and their families, especially in the domain of executive functioning (EF): the ability to self-monitor, plan, solve problems, and set priorities. Previous research focused mainly on child EF, neglecting the impact of parental EF. This study included both mothers and fathers and examined associations between child and parental EF and treatment adherence to T1D in a broad age range of patients. Methods: Parents of 270 patients (6-18years) with T1D (mean age 12.7years; 52.6% female) were included. Mothers (N=232) and fathers (N=168) completed questionnaires on child and parental EF and on treatment adherence. Analyses examined the associations linking child and parental EF to treatment adherence and glycemic control (and potential moderation effects in these associations) using hierarchical linear regression. Results: Child EF problems were negatively associated with treatment adherence. As an indication of moderation, this effect was stronger in older children. Better treatment adherence and glycemic control were reported when both child and parent showed less EF problems. Effects were more pronounced in mothers than in fathers. Conclusions: This study demonstrated a significant interplay between child and parental EF in the association with treatment adherence and glycemic control. Researchers and clinicians should remain attentive toward the role of neuropsychological concepts such as EF. Implementation in clinical practice seems meaningful

A 12-gene pharmacogenetic panel to prevent adverse drug reactions: an open-label, multicentre, controlled, cluster-randomised crossover implementation study

© 2023Background: The benefit of pharmacogenetic testing before starting drug therapy has been well documented for several single gene–drug combinations. However, the clinical utility of a pre-emptive genotyping strategy using a pharmacogenetic panel has not been rigorously assessed. Methods: We conducted an open-label, multicentre, controlled, cluster-randomised, crossover implementation study of a 12-gene pharmacogenetic panel in 18 hospitals, nine community health centres, and 28 community pharmacies in seven European countries (Austria, Greece, Italy, the Netherlands, Slovenia, Spain, and the UK). Patients aged 18 years or older receiving a first prescription for a drug clinically recommended in the guidelines of the Dutch Pharmacogenetics Working Group (ie, the index drug) as part of routine care were eligible for inclusion. Exclusion criteria included previous genetic testing for a gene relevant to the index drug, a planned duration of treatment of less than 7 consecutive days, and severe renal or liver insufficiency. All patients gave written informed consent before taking part in the study. Participants were genotyped for 50 germline variants in 12 genes, and those with an actionable variant (ie, a drug–gene interaction test result for which the Dutch Pharmacogenetics Working Group [DPWG] recommended a change to standard-of-care drug treatment) were treated according to DPWG recommendations. Patients in the control group received standard treatment. To prepare clinicians for pre-emptive pharmacogenetic testing, local teams were educated during a site-initiation visit and online educational material was made available. The primary outcome was the occurrence of clinically relevant adverse drug reactions within the 12-week follow-up period. Analyses were irrespective of patient adherence to the DPWG guidelines. The primary analysis was done using a gatekeeping analysis, in which outcomes in people with an actionable drug–gene interaction in the study group versus the control group were compared, and only if the difference was statistically significant was an analysis done that included all of the patients in the study. Outcomes were compared between the study and control groups, both for patients with an actionable drug–gene interaction test result (ie, a result for which the DPWG recommended a change to standard-of-care drug treatment) and for all patients who received at least one dose of index drug. The safety analysis included all participants who received at least one dose of a study drug. This study is registered with ClinicalTrials.gov, NCT03093818 and is closed to new participants. Findings: Between March 7, 2017, and June 30, 2020, 41 696 patients were assessed for eligibility and 6944 (51·4 % female, 48·6% male; 97·7% self-reported European, Mediterranean, or Middle Eastern ethnicity) were enrolled and assigned to receive genotype-guided drug treatment (n=3342) or standard care (n=3602). 99 patients (52 [1·6%] of the study group and 47 [1·3%] of the control group) withdrew consent after group assignment. 652 participants (367 [11·0%] in the study group and 285 [7·9%] in the control group) were lost to follow-up. In patients with an actionable test result for the index drug (n=1558), a clinically relevant adverse drug reaction occurred in 152 (21·0%) of 725 patients in the study group and 231 (27·7%) of 833 patients in the control group (odds ratio [OR] 0·70 [95% CI 0·54–0·91]; p=0·0075), whereas for all patients, the incidence was 628 (21·5%) of 2923 patients in the study group and 934 (28·6%) of 3270 patients in the control group (OR 0·70 [95% CI 0·61–0·79]; p <0·0001). Interpretation: Genotype-guided treatment using a 12-gene pharmacogenetic panel significantly reduced the incidence of clinically relevant adverse drug reactions and was feasible across diverse European health-care system organisations and settings. Large-scale implementation could help to make drug therapy increasingly safe. Funding: European Union Horizon 2020