Cognitive processes in pharmacists' clinical decision-making.

BACKGROUND: Pharmacists' clinical decision-making is a core process in pharmaceutical care. However, the practical aspects and effective teaching methods of this process remain largely unexplored. OBJECTIVE: To examine the cognitive processes involved in pharmacists' perceptions of how they make clinical decisions in pharmacy practice. METHODS: Semi-structured, face-to-face interviews were conducted with pharmacists working in community, outpatient, and hospital care in the Netherlands between August and December 2021. Participants were explicitly asked for examples when asked how they make clinical decisions in practice and how they teach this to others. After transcribing audio-recorded interviews, an inductive thematic analysis was conducted to identify cognitive processes. A theoretical model of clinical decision-making was then used and adapted to structure the identified processes. RESULTS: In total, 21 cognitive processes were identified from interviews with 16 pharmacists working in community (n = 5), outpatient (n = 2), and hospital care (n = 9). These cognitive processes were organized into 8 steps of the adapted theoretical model, i.e. problem and demand for care consideration, information collection, clinical reasoning, clinical judgment, shared decision-making, implementation, outcomes evaluation, and reflection. Pharmacists struggled to articulate their clinical decision-making and went back-and-forth in their explanations of this process. All pharmacists emphasized the importance of identifying the problem and described how they collect information through reviewing, gathering, recalling, and investigating. Clinical reasoning entailed various cognitive processes, of which comprehending the problem in the patient's context was deemed challenging at times. Pharmacists seemed least active in evaluating patient outcomes and reflecting on these outcomes. CONCLUSIONS: Pharmacists use multiple cognitive processes when making clinical decisions in pharmacy practice, and their back-and-forth explanations emphasize its dynamic nature. This study adds to a greater understanding of how pharmacists make clinical decisions and to the development of a theoretical model that describes this process, which can be used in pharmacy practice and education.

Factors influencing pharmacists' clinical decision making in pharmacy practice.

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.

Application of routine electronic health record databases for pharmacogenetic research.

Inter-individual variability in drug responses is a common problem in pharmacotherapy. Several factors (non-genetic and genetic) influence drug responses in patients. When aiming to obtain an optimal benefit-risk ratio of medicines and with the emergence of genotyping technology, pharmacogenetic studies are important for providing recommendations on drug treatments. Advances in electronic healthcare information systems can contribute to increasing the quality and efficiency of such studies. This review describes the definition of pharmacogenetics, gene selection and study design for pharmacogenetic research. It also summarizes the potential of linking pharmacoepidemiology and pharmacogenetics (along with its strengths and limitations) and provides examples of pharmacogenetic studies utilizing electronic health record databases.

Discontinuation of anticoagulant care during admission to a psychiatric hospital.

PURPOSE: Continuation of coumarin therapy is important to prevent thromboembolic events. Continuation of medication, unrelated to the reason for hospital admission, may be at risk due to the patient's psychiatric status and the involvement of several physicians in patient care. METHODS: We performed a retrospective follow-up study of users of orally administered anticoagulants who were admitted to a psychiatric hospital. Information on patient characteristics, anticoagulant use, and International Normalized Ratio (INR) measurements was collected. Discontinuation of anticoagulant care was defined as no anticoagulant dispensing during the first 7 days of hospitalization and/or no INR measurement during hospitalization. Relative risks (RR) of discontinuation, overall and stratified by patient characteristics, was estimated using Cox regression analysis. RESULTS: Of 111 patients, 24.3 % had their anticoagulant care discontinued. For 17.1 %, no anticoagulant was dispensed during the first week, and 13.5 % had no INR measurement during hospitalization. CONCLUSIONS: Admission to a psychiatric hospital leads to discontinuation of anticoagulant care in 24.3 % of patients, with highest risk of discontinuation in patients admitted to nonpsychogeriatric wards. More research is needed to evaluate the clinical impact of this finding.

High versus standard clopidogrel loading in patients undergoing carotid artery stenting prior to cardiac surgery to assess the number of microemboli detected with transcranial Doppler: results of the randomized IMPACT trial.

AIM: The aim of this study was to compare the effects of 300 mg or 600 mg clopidogrel loading dose, prior to carotid artery stenting (CAS) on the number of transcranial Doppler (TCD)-detected microembolic signals (MES) and to investigate the relationship between the magnitude of platelet reactivity and MES. METHODS: In this prospective randomized, double-blind study, 35 consecutive asymptomatic patients (17.1% females), scheduled for CAS and cardiac surgery were included. The primary endpoint was the number of TCD-detected MES. The secondary endpoints were the absolute magnitude of on-treatment platelet reactivity and the adverse cerebral events. Negative binomial regression to find predictors for sum of single emboli, the student's t-test to assess the association between platelet function tests and randomized dose of 300 mg or 600 mg clopidogrel, and the R2 calculation for the assessment of the association between platelet function tests and embolic load, were used. RESULTS: No statistically significant difference in the number of TCD-detected MES, in the sum of all the single emboli or showers and platelet aggregation measurements between the two groups was observed (aggregometry: 21.7±18.3 versus 23±18%, P=0.8499 and 45.8±17.5 versus 46.5±14.5%, P=0.9003) (verifyNow P2Y12 assay: 231±93 PRU versus 222±86 PRU, P=0.7704). In one patient a transient ischemic attack occurred. CONCLUSION: A loading dose of 300 mg of clopidogrel in combination with aspirin is as effective as 600 mg of clopidogrel in achieving adequate platelet inhibition and preventing periprocedural events in asymptomatic patients undergoing CAS prior to cardiac surgery.

Maintenance of anesthesia in morbidly obese patients using propofol with continuous BIS-monitoring: a comparison of propofol-remifentanil and propofol-epidural anesthesia.

PURPOSE: Aim of this study was to evaluate maintenance of anesthesia using propofol with continuous Bispectral Index (BIS)-monitoring in morbidly obese patients receiving propofol-remifentanil and propofol-epidural anesthesia. METHODS: In the first group in ten morbidly obese patients receiving remifentanil analgesia, a propofol infusion was started at 10 mg/kg/hr and modified by aiming at BIS values between 40-60 together with predefined hemodynamic parameters. In the second group, the propofol dose resulting from the first group was prospectively evaluated in a matched cohort of six morbidly obese patients receiving propofol-epidural analgesia aiming for the same BIS and hemodynamic parameters. In both groups, propofol concentration and infusion rates, BIS and hemodynamic values were collected. RESULTS: In the propofol-remifentanil group (Body Mass Index (BMI) 39-60 kg/m2), the mean propofol infusion rate that corresponded to the predefined BIS and hemodynamic parameters was 4.8 mg/kg/hr (SD 1.5). On this basis, a maintenance dose of 5 mg/kg/hr was started in the propofol-epidural group (BMI 38-58 kg/m2). In this second group, the mean propofol infusion rate that corresponded to predefined BIS and hemodynamic parameters was 5.0 mg/kg/hr (SD 0.6). Between the two groups, there was no difference in the propofol concentration-BIS relation. CONCLUSION: Using both BIS and hemodynamic parameters as an endpoint, a maintenance dose of propofol of 4-6 mg/kg/hr is proposed for maintenance of anesthesia in morbidly obese patients undergoing bariatric surgery either in combination with remifentanil or epidural analgesia. There was no difference in propofol concentration-BIS relation in morbidly obese patients receiving propofol-remifentanil or propofol-epidural anesthesia.

Combined influence of proton-pump inhibitors, calcium-channel blockers and CYP2C19*2 on on-treatment platelet reactivity and on the occurrence of atherothrombotic events after percutaneous coronary intervention.

BACKGROUND: The carriage of CYP2C19*2 and the use of proton-pump inhibitors (PPIs) and calcium-channel blockers (CCBs) has been associated with the diminished efficacy of clopidogrel. However, previous studies have only assessed the isolated impact of these risk factors for clopidogrel poor response. OBJECTIVES: The aim of the present study was to investigate the impact of the combined presence of three risk factors for clopidogrel poor response, that is, the use of CCBs, PPIs and the carriage of CYP2C19*2, on on-treatment platelet reactivity and the occurrence of atherothrombotic events in 725 patients on dual antiplatelet therapy undergoing elective coronary stenting. METHODS: In a prospective, follow-up study, on-treatment platelet reactivity was quantified using ADP-induced light transmittance aggregometry (LTA) and the VerifyNow P2Y12 assay. The clinical study endpoint was the composite of all-cause mortality, myocardial infarction, stent thrombosis and stroke at 1 year after stenting. RESULTS: Patients with either one or more than one risk factor exhibited increased platelet reactivity (mean relative increase one risk factor: 11% and > 1 risk factor: 22%, respectively). Sixty-four events occurred during follow-up (8.8% of the study population). Patients with one risk factor for clopidogrel poor response did not have an increased risk of the composite endpoint. However, patients using both CCBs and PPIs and carriers of CYP2C19*2 who used CCBs had a statistically significant increased risk of the composite endpoint [hazard ratio(HR)(adj) 2.2 95% CI, 1.0-5.3, P = 0.044 and HR(adj) 3.3 95% CI, 1.1-9.8, P = 0.032, respectively]. CONCLUSIONS: The presence of more than one of the three investigated risk factors for clopidogrel poor response is associated with an increased risk of adverse cardiovascular events within 1 year after elective coronary stenting.

Pharmacogenetics: from bench to byte--an update of guidelines.

Currently, there are very few guidelines linking the results of pharmacogenetic tests to specific therapeutic recommendations. Therefore, the Royal Dutch Association for the Advancement of Pharmacy established the Pharmacogenetics Working Group with the objective of developing pharmacogenetics-based therapeutic (dose) recommendations. After systematic review of the literature, recommendations were developed for 53 drugs associated with genes coding for CYP2D6, CYP2C19, CYP2C9, thiopurine-S-methyltransferase (TPMT), dihydropyrimidine dehydrogenase (DPD), vitamin K epoxide reductase (VKORC1), uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1), HLA-B44, HLA-B*5701, CYP3A5, and factor V Leiden (FVL).

Pharmacogenetics: from bench to byte.

Despite initial enthusiasm, the use of pharmacogenetics has remained limited to investigation in only a few clinical fields such as oncology and psychiatry. The main reason is the paucity of scientific evidence to show that pharmacogenetic testing leads to improved clinical outcomes. Moreover, for most pharmacogenetic tests (such as tests for genetic variants of cytochrome P450 enzymes) a detailed knowledge of pharmacology is a prerequisite for application in clinical practice, and both physicians and pharmacists might find it difficult to interpret the clinical value of pharmacogenetic test results. Guidelines that link the result of a pharmacogenetic test to therapeutic recommendations might help to overcome these problems, but such guidelines are only sparsely available. In 2001, an early step was taken to develop such guidelines for the therapeutic use of antidepressants, and these included CYP2D6-related dose recommendations drawn from pharmacokinetic study data. However, the use of such recommendations in routine clinical practice remains difficult, because they are currently outside the ambit of the clinical environment and are not accessible during the decision-making process by physicians and pharmacists, namely the prescription and dispensing of drugs.

[Prolonged diminished effect of coumarin derivatives after use of rifampicin]. / Langdurig verminderd effect van cumarinederivaten na gebruik van rifampicine.

A 73-year-old woman with endocarditis was treated with flucloxacillin and rifampicin. She already used the anticoagulant acenocoumarol because of a recent heart valve replacement. After starting rifampicin therapy the sensitivity for the acenocoumarol was reduced. The international normalised ratio (INR) did not exceed 2.0, while values of 2.5-3.5 were required. Increase of the daily dose of acenocoumarol with a factor 6 compared to the dose which resulted in a therapeutic INR before hospitalisation, proved insufficient to obtain a therapeutic INR during long-term rifampicin therapy. 21 days after rifampicin discontinuation the INR finally responded to high coumarin dosages. The breakdown of coumarins in the liver is increased by rifampicin due to induction of several isoenzymes of the cytochrome P450-system. This case illustrates that sensitivity to coumarins can be decreased profoundly even after discontinuation of rifampicin therapy. INR should be monitored closely not only at the start and discontinuation of rifampicin therapy, but also during the weeks after discontinuation of rifampicin treatment.

Inhibition of platelet function by abciximab or high-dose tirofiban in patients with STEMI undergoing primary PCI: a randomised trial.

BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI, few data exist on the magnitude of platelet activation, aggregation and dosing of glycoprotein (GP) IIb/IIIa receptor inhibitors. METHODS: Sixty STEMI patients were randomised to abciximab, to high-dose tirofiban or to no additional GP IIb/IIIa inhibitor treatment. Platelet activation (P-selectin expression) was measured using flow cytometry and the level of inhibition of platelet aggregation was assessed using the Plateletworks assay. Additionally, the PFA-100 with the collagen/adenosine-diphosphate cartridge (CADP) was used to compare the levels of platelet inhibition. All measurements were performed at baseline (T(0)), immediately after (T(1)), 30 minutes (T(2)), 60 minutes (T(3)) and 120 minutes (T(4)) after primary PCI. RESULTS: The level of platelet activation in both GP IIb/IIIa receptor inhibitor treated groups was significantly lower compared with the control group at all time points after primary PCI (p=0.04). Also the administration of the currently recommended dose of abciximab resulted in significantly lower levels of inhibition of aggregation compared with high-dose tirofiban (p<0.0001). In addition, the CADP closure times were significantly prolonged in both GP IIb/IIIa inhibitor treated groups compared with the control group at time points T(1) (p=0.006) and T(4) (p<0.0001). CONCLUSION: The administration of high-dose tirofiban resulted in a significantly higher inhibition of platelet aggregation compared with the currently recommended dose of abciximab. Large clinical trials are needed to assess whether this laboratory superiority of high-dose tirofiban translates into higher clinical efficacy. (Neth Heart J 2007;15:375-81.).

Angiotensin-converting enzyme inhibitor use and pneumonia risk in a general population.

The aim of the present study was to assess whether the use of angiotensin-converting enzyme (ACE) inhibitors is associated with a decreased risk of hospitalisation for community-acquired pneumonia (CAP) in a general, essentially white population. Data were obtained from the Dutch PHARMO Record Linkage System. Cases were defined as patients with a first hospital admission for CAP. For each case, up to four population controls were matched by age and sex. The study population comprised 1,108 patients with a first hospital admission for CAP and 3,817 matched controls. After adjusting for several confounders, ACE inhibitor use was not associated with a decreased incidence of pneumonia (adjusted odds ratio (OR) 1.12; 95% confidence interval (CI) 0.88-1.43). Additionally, no significant association was observed in patients with diabetes, respiratory diseases, heart failure, or patients with both of the last two conditions. Furthermore, adjustment of treatment effects on pneumonia risk using stratification on balancing score also showed no significant association between ACE inhibitor use and pneumonia risk within the different strata (overall adjusted OR 1.09; 95% CI 0.87-1.36). In contrast with previous findings in Asian populations, the current authors were not able to confirm the beneficial effect of angiotensin-converting enzyme inhibitors on pneumonia risk in a general, essentially white population.

Clopidogrel resistance: fact and fiction.

The antiplatelet agent clopidogrel in combination with aspirin has been shown to reduce thrombotic events in patients with acute coronary syndromes and/or who are undergoing percutaneous coronary intervention. However, a large interindividual response variability to clopidogrel has been described. The reported rates of inadequate clopidogrel response vary considerably depending on the definition and methodologies used to measure the inhibition of platelet function. Recently, several (small) studies have demonstrated the clinical relevance of an inadequate response to clopidogrel. Moreover, several factors have been associated with a high interindividual variability in response to clopidogrel. These are: dosing, impaired intestinal absorption, cytochrome P450 3A4 and 3A5 activity, drug-drug interactions, polymorphisms of the receptors involved in the process of arterial thrombosis and hemostasis, and the method of measurement of platelet function. Future research for the evaluation of clopidogrel resistance should be based on the assessment of selective P2Y12 receptor inhibition (e.g., the vasodilator-stimulated phosphoprotein-assay or the measurement of stabilization of platelet aggregates) with quick and simple tests. Only then can we reveal the true prevalence and impact of clopidogrel resistance.

Absorption kinetics and pharmacodynamics of two oral dosage forms of flecainide in patients with an episode of paroxysmal atrial fibrillation.

OBJECTIVES: The objectives were to study the absorption kinetics and pharmacodynamics of two oral formulations of flecainide in patients with atrial fibrillation (AF) and to assess the relationship between pharmacokinetic parameters and the efficacy in restoring sinus rhythm. METHODS: The data of 54 patients included in a randomised, open, parallel-group study were used. Patients received an oral solution containing 300 mg flecainide and 20 mg cisapride or three tablets each containing 100 mg flecainide. The pharmacokinetic profile of flecainide was fitted using a one-compartment model with lag-time and first-order absorption. RESULTS: The tablets gave a maximum concentration (C (max\ fit)) of 0.43+/-0.14 mg/l at 2.37+/-1.20 h. The oral solution resulted in a much faster peak concentration at 1.05+/-0.71 h (P<0.0001). The C (max\ fit) of the oral solution of 0.60+/-0.17 mg/l was higher (P=0.0002) than that of the tablets, and interindividual variabilities of C (max\ fit) were 28% and 33%, respectively. The absorption rate constant (ka) of the oral solution was twofold larger (P<0.0001). A higher ka (P=0.04) and a duration of AF less than 24 h (P=0.006) increased the probability of cardioversion. If atrial fibrillation lasted less than 24 h, only ka (P=0.016) was obtained as a significant variable in multivariate analysis. The linear models of QRS interval changes versus flecainide concentrations of both formulations had similar slopes with similar interindividual variabilities. CONCLUSIONS: The probability of cardioversion after an oral loading dose of flecainide in patients with AF is dependent on ka. Rapid loading of the effect compartment, i.e. the atria, appears to be critical to reach cardioversion. Higher flecainide serum concentrations and a more rapid absorption does not increase interindividual variability of pharmacokinetics and pharmacodynamics, which is important when safety is considered.

Buccal transport of flecainide and sotalol: effect of a bile salt and ionization state.

Patients with infrequent attacks of supraventricular arrhythmia may benefit from self administration of antiarrhythmic drugs on an 'as required' basis. The oral cavity is easily accessible and the potential for rapid absorption exists. The effects of ionization state and sodium glycocholate on the ex vivo transport of sotalol and flecainide across porcine buccal mucosa were studied. The permeated amounts at 3 h (Q) and fluxes (J) of sotalol in an aqueous solution at pH 7.4 and 9.0 were similar. At pH 7.4, in contrast to pH 9.0, the addition of 1.0% (w/v) sodium glycocholate decreased Q and J four and five fold. Flecainide base in propylene glycol resulted in a nine and 12 fold higher Q and J as compared with an aqueous solution of flecainide acetate at pH 5.8. The presence of sodium glycocholate reduced the transport rate of the flecainide base. However, Q and J were increased 110 and 75 fold by adding 1.0% (w/v) sodium glycocholate to a solution of flecainide acetate at pH 5.8. Sodium glycocholate seems to be an effective penetration enhancer for the buccal absorption of the more polar ionized form of flecainide in an aqueous solution. Sodium glycocholate does not seem to improve the transport of sotalol.