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Background:Adherence to antihypertensive drugs (AHDs) is crucial for controlling blood pressure (BP). We aimed to determine the effectiveness of measuring AHD concentrations using a dried blood spot (DBS) sampling method to identify nonadherence, combined with personalized feedback, in reducing resistant hypertension.Methods:We conducted a multicenter, randomized, controlled trial (RHYME-RCT, ICTRP NTR6914) in patients with established resistant hypertension. Patients were randomized to receive either an intervention with standard of care (SoC) or SoC alone. SoC consisted of BP measurement and DBS sampling at baseline, 3 months (t3), 6 months (t6), and 12 months (t12); AHD concentrations were measured but not reported in this arm. In the intervention arm, results on AHD concentrations were discussed during a personalized feedback conversation at baseline and t3. Study endpoints included the proportion of patients with RH and AHD adherence at t12.Results:Forty-nine patients were randomized to receive the intervention+SoC, and 51 were randomized to receive SoC alone. The proportion of adherent patients improved from 70.0 to 92.5% in the intervention+SoC arm (P = 0.008, n = 40) and remained the same in the SoC arm (71.4%, n = 42). The difference in adherence between the arms was statistically significant (P = 0.014). The prevalence of resistant hypertension decreased to 75.0% in the intervention+SoC arm (P < 0.001, n = 40) and 59.5% in the SoC arm (P < 0.001, n = 42) at t12; the difference between the arms was statistically nonsignificant (P = 0.14).Conclusion:Personalized feedback conversations based on DBS-derived AHD concentrations improved AHD adherence but did not reduce the prevalence of RH.

BACKGROUND: Pharmacists' clinical decision-making is considered a core process of pharmaceutical care in pharmacy practice, but little is known about the factors influencing this process.OBJECTIVE: To identify factors influencing clinical decision-making among pharmacists working in pharmacy practice.METHODS: Semi-structured interviews were conducted with pharmacists working in primary, secondary, and tertiary care settings in the Netherlands between August and December 2021. A thematic analysis was conducted using an inductive approach. The emerged themes were categorized into the Capability-Opportunity-Motivation-Behaviour (COM-B) model domains.RESULTS: In total, 16 pharmacists working in primary care (n = 7), secondary care (n = 4) or tertiary care (n = 5) were interviewed. Factors influencing pharmacists' capability to make clinical decisions are a broad theoretical knowledge base, clinical experience, and skills, including contextualizing data, clinical reasoning, and clinical judgment. The pharmacy setting, data availability, rules and regulations, intra- and interprofessional collaboration, education, patient perspectives, and time are mentioned as factors influencing their opportunity. Factors influencing pharmacists' motivation are confidence, curiosity, critical thinking, and responsibility.CONCLUSIONS: The reported factors covered all domains of the COM-B model, implying that clinical decision-making is influenced by a combination of pharmacists' capability, opportunity, and motivation. Addressing these different factors in pharmacy practice and education may improve pharmacists' clinical decision-making, thereby improving patient outcomes.

The case report describes a case of a severe dapsone (more than 200 tablets dapsone 100 mg) and mild methotrexate intoxication (10 tablets methotrexate 10 mg) as an attempt to commit suicide, resulting in severe cyanosis with elevation in methemoglobin concentration, treated with methylene blue, ascorbic acid, folinic acid, multidose activated charcoal and hemodialysis. Measurements of blood gases, dapsone and methotrexate levels were performed. Furthermore a hepatitis, pulmonary artery thrombus and a strange taste sensation were diagnosed, probably related to dapsone. The patient recovered and was discharged from hospital after five days. Acute intoxication from excessive dapsone intake is uncommon and clear treatment guidelines are lacking. We here report the treatment modalities as a result of a dapsone intoxication, including the effects on the overall condition of the patient.

Purpose: Hypertension significantly contributes to cardiovascular diseases and premature deaths. Effective treatment is crucial to reduce cardiovascular risks, but poor adherence to antihypertensive drugs is a major issue. Numerous studies attempted to investigate interventions for identifying non-adherence, but often failed to address the issue effectively. The RHYME-RCT trial sought to bridge this gap by measuring non-adherence by determining antihypertensive drug concentrations in blood through a dried blood spot (DBS) method in patients with resistant hypertension. This measurement was followed by personalized feedback to improve adherence. During the course of this trial several challenges emerged, including selection bias, the gatekeeper role of physicians, the Hawthorne effect and the role of randomization.Aim: This communication aims to inform fellow researchers and clinicians of challenges that can arise when conducting clinical trials to improve adherence and offer insights for refining study designs to avoid these issues in forthcoming adherence studies.

BACKGROUND: Adherence to antihypertensive drugs (AHDs) is important for adequate blood pressure control. Not taking these drugs as prescribed is one of the main underlying causes for resistant hypertension (RH), which in turn leads to an increased risk of cardiovascular events, stroke and kidney damage. Therefore, correct identification of patients that are non-adherent to AHDs is crucial to improve clinical outcome. For this goal, therapeutic drug monitoring is the most reliable method. The primary objective of this trial is to investigate whether monitoring of drug concentrations with a dried blood spot (DBS) sampling method combined with personalised feedback leads to a decrease in prevalence of RH after 12 months due to an increase in adherence. Secondary objectives include the difference over time in the number of required AHDs as well as the defined daily dose (DDD). Lastly, the cost-utility of SoC versus the intervention in RH is determined.METHODS: This is a multi-centre single-blinded randomised controlled trial (RHYME-RCT). First, at an eligibility visit, DBS sampling, to monitor drug concentrations in blood, and a 24-h ambulatory blood pressure measurement (24-h ABPM) are performed simultaneously. Patients with a daytime systolic blood pressure (SBP) > 135 and/or diastolic blood pressure (DBP) > 85 mmHg are randomised to SoC or intervention + SoC. The intervention is performed by the treating physician and includes information on drug concentrations and a comprehensive personalised feedback conversation with the use of a communication tool. The follow-up period is one year with visits at 3, 6 and 12 months randomisation and includes 24-h ABPM and DBS sampling.DISCUSSION: This will be the first trial that focusses specifically on patients with RH without taking into account suspicion of non-adherence and it combines monitoring of AHD concentrations to identify non-adherence to AHDs with a comprehensive feedback to improve non-adheren

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Effective pharmacologic treatments for psychiatric disorders are available, but their effect is limited due to patients’ genetic heterogeneity and low compliance-related to frequent adverse events. Only one third of patients respond to treatment and experience remission. Pharmacogenetics is a relatively young field which focusses on genetic analyses in the context of the metabolism and outcome of drug treatment. These genetic factors can, among other things, lead to differences in the activity of enzymes that metabolize drugs. Recently, a clinical guideline was authorized by the Dutch Clinical Psychiatric Association (NVvP) on the clinical use of pharmacogenetics in psychiatry. The main goal was to provide guidance, based on current evidence, on how to best use genotyping in clinical psychiatric practice. A systematic literature search was performed, and available publications were assessed using the GRADE methodology. General recommendations for psychiatric clinical practice were provided, and specific recommendations per medication were made available. This clinical guideline for caregivers prescribing psychotropic drugs is the product of a broad collaboration of professionals from different disciplines, making use of the information available at the Dutch Pharmacogenetics Working Group (DPWG) and the Clinical Pharmacogenetics Implementation Consortium (CPIC) so far. We summarize the relevant literature and all recommendations in this article. General recommendations are provided and also detailed recommendations per medication. In summary we advise to consider genotyping, when there are side effects or inefficacy for CYP2C19 and CYP2D6. When genotype information is available use this to select the right drug in the right dose for the right patient.

BACKGROUND: Minimally invasive sampling methods are important to facilitate therapeutic drug monitoring and pharmacokinetic research in children with behavioral problems. This study assessed the feasibility and pain of dried blood spot (DBS) sampling in this population. METHODS: Repeated DBS sampling was performed in children with autism spectrum disorder (ASD) and severe behavioral problems using antipsychotic drugs, aged between 6 and 18 years. The child, guardian, and DBS performer assessed pain using the numeric rating scale (NRS-11) or 5-face Faces Pain Scale. The influence of age, sex, and the fingerprick performer on the child's pain intensity was analyzed using linear mixed models. RESULTS: Overall, 247 fingerpricks were performed in 70 children. Seven children refused all DBS sampling. The median (interquartile range) NRS-11 pain scores were 2 (3) rated by children, 3 (2.5) by guardians, and 2 (2) by fingerprick performers. The child's age and sex, and fingerprick performer had no significant influence on pain intensity. CONCLUSIONS: DBS sampling could be performed in most children with ASD and severe behavioral problems. However, 1 in 5 children refused one or more DBS fingerpricks owing to distress. Most expressed minimal pain (NRS < 4). Repeated sampling with DBS is feasible in children with ASD and severe behavioral problems.