Influence of allopurinol on thiopurine associated toxicity: A retrospective population-based cohort study.

AIMS: Thiopurines are important for treating inflammatory bowel disease, but are often discontinued due to adverse effects. Concomitant use of allopurinol might lower the risk of these unwanted effects, but large studies in the general population are lacking. The aims of this study were to evaluate rates of hepatotoxicity, myelotoxicity, pancreas toxicity and therapy persistence in adult thiopurine users with or without allopurinol. METHODS: A retrospective population-based cohort study was conducted within current thiopurine users (Clinical Practice Research Datalink). Among these patients, co-use of allopurinol was compared to non-use. Hazard ratios (HRs) for hepatotoxicity, myelotoxicity and pancreatitis were derived using time-dependent Cox proportional hazards models, and were adjusted for potential confounders. Persistence of thiopurine use was evaluated using Log-rank statistics. RESULTS: Patients using thiopurines (n = 37 360) were identified of which 1077 were concomitantly taking allopurinol. A 58% decreased risk of hepatotoxicity was observed in those concomitantly taking allopurinol (HR 0.42; 95% CI 0.30-0.60; NNT 46). Rate of myelotoxicity (HR 0.96; 95% CI 0.89-1.03) was not influenced. Risk of pancreatitis was increased (HR 3.00; 95% CI 1.01-8.93; NNH 337), but was only seen in those with active gout (suggesting confounding by indication). Finally, allopurinol co-users were able to maintain thiopurine therapy over twice as long as those not on allopurinol (3.9 years vs. 1.8 years, P < 0.0001). CONCLUSION: In thiopurine users, allopurinol is associated with a 58% reduced risk of hepatotoxicity. In addition, thiopurine persistence was prolonged by 2.1 years in allopurinol users. These data support the use of allopurinol in individuals requiring thiopurine therapy.

A semi-mechanistic model based on glutathione depletion to describe intra-individual reduction in busulfan clearance.

AIM: To develop a semi-mechanistic model, based on glutathione depletion and predict a previously identified intra-individual reduction in busulfan clearance to aid in more precise dosing. METHODS: Busulfan concentration data, measured as part of regular care for allogeneic hematopoietic cell transplantation (HCT) patients, were used to develop a semi-mechanistic model and compare it to a previously developed empirical model. The latter included an empirically estimated time effect, where the semi-mechanistic model included theoretical glutathione depletion. As older age has been related to lower glutathione levels, this was tested as a covariate in the semi-mechanistic model. Lastly, a therapeutic drug monitoring (TDM) simulation was performed comparing the two models in target attainment. RESULTS: In both models, a similar clearance decrease of 7% (range -82% to 44%), with a proportionality to busulfan metabolism, was found. After 40 years of age, the time effect increased with 4% per year of age (0.6-8%, P = 0.009), causing the effect to increase more than a 2-fold over the observed age-range (0-73 years). Compared to the empirical model, the final semi-mechanistic model increased target attainment from 74% to 76%, mainly through better predictions for adult patients. CONCLUSION: These results suggest that the time-dependent decrease in busulfan clearance may be related to gluthathione depletion. This effect increased with older age (>40 years) and was proportional to busulfan metabolism. The newly constructed semi-mechanistic model could be used to further improve TDM-guided exposure target attainment of busulfan in patients undergoing HCT.

What does it cost to redispense unused medications in the pharmacy? A micro-costing study.

BACKGROUND: Redispensing unused medications that have been returned to outpatient pharmacies by patients may reduce waste and healthcare costs. However, little is known regarding the extra costs associated with this process, nor the price level of medications for which this is economically beneficial. The objective of this study was to assess costs associated with redispensing unused medications in the pharmacy and the price level at which redispensing becomes cost-beneficial. METHODS: A micro-costing study was conducted in four Dutch outpatient pharmacies for medications requiring room-temperature storage and requiring refrigeration. First, the pharmacy's necessary additional process steps and resources for redispensing were identified. Second, time required for each process step was simulated. Third, required resources were quantified by calculating labour, purchasing and overhead costs. Lastly, a model with different scenarios was constructed to calculate the price of a medication package at which redispensing becomes cost-beneficial. RESULTS: Three main additional process steps for redispensing were identified: (1) pack medications with product quality indicators before dispensing, (2) assess quality of medications returned to the pharmacy (temperature storage, package integrity, expiry date) and (3a) restock medications fulfilling quality criteria or (3b) dispose of medications not fulfilling criteria. Total time required for all steps up to restock one medication package was on average 5.3 (SD ±0.3) and 6.8 (SD ±0.3) minutes for medications stored at room-temperature and under refrigeration, respectively, and associated costs were €5.54 and €7.61. Similar outcomes were found if a medication package would ultimately be disposed of. The price level primarily depended upon the proportion of dispensed packages returned unused to the pharmacy and fulfilling the quality criteria: if 5% is returned, of which 60% fulfils quality criteria, the price level was €101 per package for medications requiring room-temperature storage and €215 per package for those requiring refrigeration. However, if 10% is returned, of which 60% fulfils the quality criteria, the price level decreases to €53 and €109, respectively (arbitrary proportions). CONCLUSIONS: Redispensing unused medications in the pharmacy is at least cost-beneficial if applied to expensive medications.

Associations Between Personality Traits and Adherence to Antidepressants Assessed Through Self-Report, Electronic Monitoring, and Pharmacy Dispensing Data: A Pilot Study.

Treatment with antidepressants is often compromised by substantial nonadherence. To understand nonadherence, specific medication-related behaviors and beliefs have been studied, but less is known about broader and temporally stable personality "traits." Furthermore, adherence has often been assessed by a single method. Hence, we investigated associations between the Big Five personality traits and adherence assessed by self-report, electronic drug use monitoring, and dispensing data. Using the Big Five Inventory, we assessed the personality traits "openness," "conscientiousness," "extraversion," "agreeableness," and "neuroticism" of patients treated with antidepressants who were invited through community pharmacies. Self-reported adherence was assessed with the Medication Adherence Rating Scale (score >24), electronic monitoring with medication event monitoring system (MEMS) devices (therapy days missed ≤ 10% and < 4 consecutive days missed), and dispensing data (medication possession ratio ≥ 80%). One hundred four women and 33 men participated (mean age, 51; standard deviation, 14). Paroxetine was most frequently prescribed (N = 53, 38%). Logistic regression analysis revealed that of the personality traits, the third and fourth quartiles of "conscientiousness" were associated with better self-reported adherence (odds ratio, 3.63; 95% confidence interval, 1.34-9.86 and odds ratio, 2.97; 95% confidence interval, 1.09-8.08; P ≤ 0.05). No relationships were found between personality traits and adherence assessed through electronic drug use monitoring or dispensing data. We therefore conclude that adherence to antidepressant therapy seems to be largely unrelated to personality traits.

Risk of Hospitalization for Hypoglycemia in Older Patients with Diabetes Using Antipsychotic Drugs.

OBJECTIVE: Antipsychotics may disrupt metabolic regulation in patients with diabetes mellitus. The risk of hypoglycemia in older users of antipsychotics with diabetes is largely unknown. Therefore, we investigated the association between the use of antipsychotic drugs and hypoglycemia requiring hospital admission in older patients with diabetes. METHODS: In a nested case-control study using community pharmacy records linked to hospital admission data in the Netherlands (1998-2008), a cohort of 68,314 patients at least 65 years with diabetes was studied. Cases were patients from the study cohort with a first hospital admission for hypoglycemia; up to five comparison subjects were selected for each case. Exposure to antipsychotic drugs was the primary determinant of interest. Logistic regression analysis was performed to estimate the strength of the association between antipsychotic drug use and hypoglycemia, taking into account potential confounders. RESULTS: Eight hundred fifteen patients were admitted to hospital for hypoglycemia. Current use of antipsychotic drugs was associated with an increased risk of hypoglycemia compared with non-use (adjusted OR: 2.26; 95% CI: 1.45-3.52; Wald χ(2) = 13.08, df = 1, p ≤0.001), especially in the first 30 days of treatment (adjusted OR: 7.65; 95% CI: 2.50-23.41; Wald χ(2) = 12.72, df = 1, p ≤0.001) and with higher doses (adjusted OR: 8.20; 95% CI: 3.09-21.75; Wald χ(2) = 17.90, df = 1, p ≤0.001). CONCLUSION: Use of antipsychotic drugs by older patients with diabetes mellitus was associated with an increased risk of hospitalization for hypoglycemia. Our findings suggest that glucose levels should be monitored closely after initiation of antipsychotic drugs.

Variability between nursing homes in prevalence of antipsychotic use in patients with dementia.

BACKGROUND: Antipsychotic drugs (APD) are widely prescribed for people with dementia residing in long term care facilities (LTCFs). Concern has been expressed that such prescribing is largely inappropriate. The objective of this study is to examine if differences in facility-level prevalence of APD use in a sample of LTCFs for patients with dementia can be explained by patient and facility-related characteristics. METHODS: A point prevalence study was conducted using data from the VU University Resident Assessment Instrument (VURAI) database from nursing homes and residential care facilities in the Netherlands. Patients were selected who had a diagnosis of dementia. LTCF and patient characteristics were extracted from the VURAI; facility-level resident satisfaction surveys were provided by the National Institute for Public Health. RESULTS: In total, 20 LTCFs providing care for 1,090 patients with dementia were investigated. Overall, 31% of patients used an APD. In facilities with a high prevalence of APD use behavioral symptoms were present in 62% of their patients. In facilities with medium APD use behavioral problems remained frequent (57%), and in facilities with low prevalence of APD use 54% of the patients had behavioral symptoms. Facilities with a high prevalence of APD use were often large, situated in urban communities, and scored below average on staffing, personal care, and recreational activities. CONCLUSIONS: There was considerable variation between the participating LTCFs in the prevalence of APD use. Variability was related to LTCF characteristics and patient satisfaction. This indicates potential inappropriate prescribing because of differences in institutional prescribing culture.

The association between CYP2D6 genotype and switching antipsychotic medication to clozapine.

PURPOSE: Genetic variation in the cytochrome P450 2D6 (CYP2D6) enzyme is responsible for interindividual differences in the metabolism of many antipsychotic drugs, but the clinical relevance of polymorphisms in CYP2D6 for response to antipsychotic treatment is relatively unknown. In the Netherlands, clozapine is prescribed only when patients are non-responsive to or intolerant of at least two different antipsychotics. The aim of our study was to determine the association of the CYP2D6 genotype with switching to clozapine, which served as a surrogate outcome marker for treatment response to antipsychotics. METHODS: CYP2D6 genotype was assessed in patients who had been switched to clozapine and compared with antipsychotic users whose treatment regimen included no more than two different antipsychotic drugs and no clozapine. We also performed the analysis in patients who only used CYP2D6-dependent antipsychotics. RESULTS: A total of 528 patients were included in the study (222 cases, 306 controls). No statistically significant differences were found in the distribution of the polymorphisms among the case and control groups, both in all patients and in only those patients using CYP2D6-dependent antipsychotics. However, a trend was observed, suggesting an inverse association between CYP2D6 genotype and the switch to clozapine. (9.5 vs. 5.1 % poor metabolisers and 1.3 vs. 2.6 % ultrarapid metabolisers in cases vs. controls, respectively). CONCLUSIONS: Although the results of our study suggest that the CYP2D6 phenotype is not a major determining factor for patients to be switched to clozapine treatment, larger studies are warranted with a focus on the clinical consequences of the CYP2D6 ultrarapid metaboliser and poor metaboliser phenotypes.

DosEmi study protocol: a phase IV, multicentre, open-label, crossover study to evaluate non-inferiority of pharmacokinetic-guided reduced dosing compared with conventional dosing of emicizumab in people with haemophilia A.

INTRODUCTION: Emicizumab effectively prevents bleeding in people with haemophilia A (PwHA), but is a burden for national healthcare budgets and consequently may limit access. According to the drug label, dosing of emicizumab is based on body weight with fixed intervals of 7, 14 or 28 days, which leads to mean plasma concentrations of 55 µg/mL (SD 15 µg/mL). However, a moderate variability of concentrations and a minimal effective concentration of 30 µg/mL have been suggested in studies. Therefore, a dose of emicizumab that targets a trough concentration of 30 µg/mL is hypothesised to be equally effective as conventional dosing in the prevention of bleeding. METHODS AND ANALYSIS: We designed a phase IV, multicentre, open-label, crossover study to evaluate non-inferiority of bleed control of ≥6 months on conventional dosing in comparison to ≥6 months on dose intervention. This dose intervention consists of reducing the dose of emicizumab to target a trough concentrations of 30 µg/mL using individual pharmacokinetic (PK) parameters. Ninety-five PwHA aged >1 years who received conventional dosing of emicizumab for ≥12 months with good bleeding control during the last 6 months will be recruited from all Dutch haemophilia treatment centres. The study is powered to detect a clinically relevant decrease (risk difference) of 15% in the proportion of patients without treated bleeds during follow-up. Secondary endpoints are spontaneous joint or muscle bleeds, and annualised treated bleeding rates (using negative binomial regression). Cost-effectivity between conventional dosing and individualised PK-guided dosing of emicizumab will be compared. ETHICS AND DISSEMINATION: The DosEmi study was approved by the Medical Ethics Review Committee NedMec of the University Medical Center of Utrecht, The Netherlands. Study results will be communicated through publications in international scientific journals and presentations at (inter)national conferences. TRIAL REGISTRATION NUMBER: EUCTR2021-004039-10-NL at https://trialsearch.who.int. PROTOCOL VERSION: V.4.1 on 28 October 2022 (DosEmi protocol_V4.1; NL81112.041.22).

Preventable hospital admissions related to medication (HARM): cost analysis of the HARM study.

OBJECTIVE: Adverse drug events (ADEs) can cause serious harm to patients and can lead to hospitalization or even death. ADEs are a burden not only to patients and their relatives, but also to society and have the potential to involve high costs. To provide more information on the economic burden of preventable adverse drug events of outpatients, we performed a cost study on the data collected in the Hospital Admissions Related to Medication (HARM) study. In this study we examined the frequency, preventability, and risk factors for hospital admissions related to medication. METHODS: The average costs for a preventable medication-related hospital admission were calculated by summing the direct medical costs and the production losses of all the preventable admissions, taking into account the different types of hospitals (academic and general) and the age of the admitted patients. RESULTS: The average medical costs for one preventable medication-related hospital admission were €5461. The average production loss costs for one admission were €1712 for a person younger than 65 years of age. Combining the medical costs and the costs of production losses resulted in average costs of €6009 for one, potentially preventable, medication-related hospital admission for all ages. CONCLUSIONS: The costs of potentially preventable hospital admissions related to medication are considerable. Therefore, patient safety interventions to prevent ADEs and hospital admissions may be cost-effective or even cost saving.

The effect of the COACH program (Continuity Of Appropriate pharmacotherapy, patient Counselling and information transfer in Healthcare) on readmission rates in a multicultural population of internal medicine patients.

BACKGROUND: Medication errors occur frequently at points of transition in care. The key problems causing these medication errors are: incomplete and inappropriate medication reconciliation at hospital discharge (partly arising from inadequate medication reconciliation at admission), insufficient patient information (especially within a multicultural patient population) and insufficient communication to the next health care provider. Whether interventions aimed at the combination of these aspects indeed result in less discontinuity and associated harm is uncertain. Therefore the main objective of this study is to determine the effect of the COACH program (Continuity Of Appropriate pharmacotherapy, patient Counselling and information transfer in Healthcare) on readmission rates in patients discharged from the internal medicine department. METHODS/DESIGN: An experimental study is performed at the internal medicine ward of a general teaching hospital in Amsterdam, which serves a multicultural population. In this study the effects of the COACH program is compared with usual care using a pre-post study design. All patients being admitted with at least one prescribed drug intended for chronic use are included in the study unless they meet one of the following exclusion criteria: no informed consent, no medication intended for chronic use prescribed at discharge, death, transfer to another ward or hospital, discharge within 24 hours or out of office hours, discharge to a nursing home and no possibility to counsel the patient.The intervention consists of medication reconciliation, patient counselling and communication between the hospital and primary care healthcare providers.The following outcomes are measured: the primary outcome readmissions within six months after discharge and the secondary outcomes number of interventions, adherence, patient's attitude towards medicines, patient's satisfaction with medication information, costs, quality of life and finally satisfaction of general practitioners and community pharmacists.Interrupted time series analysis is used for data-analysis of the primary outcome. Descriptive statistics is performed for the secondary outcomes. An economic evaluation is performed according to the intention-to-treat principle. DISCUSSION: This study will be able to evaluate the clinical and cost impact of a comprehensive program on continuity of care and associated patient safety. TRIAL REGISTRATION: Dutch trial register: NTR1519.

Patients' perceptions and illness severity at start of antidepressant treatment in general practice.

OBJECTIVES: Patients' perceptions are important to consider when trying to understand why patients often do not follow prescriptions for antidepressant treatment. This study aimed to investigate the influence of patients' perceptions and illness severity at the start on antidepressant-medication-taking behaviour. METHODS: Eighteen community pharmacies in the Netherlands participated in this 6-month follow-up study. One hundred and ten patients presenting a first antidepressant prescription, prescribed by a general practitioner (GP), were included. A questionnaire was completed at inclusion, after 6 and 26 weeks. KEY FINDINGS: Of all 110 patients, eight (7.3%) did not initiate drug taking, 32 (29.1%) discontinued use, six (5.5%) switched to different antidepressant medication, and 64 (58.2%) continued on the same antidepressant during follow-up. Compared to continuers, non-initiators had lower belief scores for impact of illness (P = 0.044), perceived norm GP (P < 0.001), intention to take medication (P < 0.001), and attitude towards medication (P = 0.004). Furthermore, non-initiators were less severely depressed (P = 0.024). Discontinuers and continuers did not differ in illness severity at inclusion. However, discontinuers more often reported a non-specific reason for use, such as fatigue and sleeping problems (P = 0.014). Compared to continuers, switchers had higher illness severity scores at inclusion (depression, P = 0.041; anxiety, P = 0.050). During follow-up depression and anxiety severity improved for all treatment groups and reached the same level of severity at 6 months. CONCLUSIONS: Patients' illness and treatment perceptions and illness severity influence their decisions about antidepressant drug taking. Patients' care could be improved by eliciting patients' beliefs about illness and treatment and assessing illness severity before prescribing.

Unexpected lower prevalence of depression in patients with diabetes: selection bias in a waiting room population.

BACKGROUND: We initially studied the association between diabetes and depression in general practice attendees. Subsequently, we investigated whether our findings were influenced by selection bias. METHODS: Unexpectedly, the prevalence of depression was lower in diabetes patients (4%) than in subjects without diabetes (14%). To explore the possibility of selection bias, we first described the selection process from the general population to our study population and provided prevalence data of diabetes and depression in the different populations based on literature and our data. Second, we performed a sensitivity analysis and described possible reasons for selection. Third, we studied the association between other chronic diseases and depression. RESULTS: These analyses suggested that the lower prevalence of depression in diabetes patients was due to selection bias. Visiting the general practitioner for a control visit seemed to play a role in this selection process. CONCLUSIONS: This study illustrated the potential for selection bias in a waiting room population. The degree of bias depended on the exposure under study.

HTR2C gene polymorphisms and the metabolic syndrome in patients with schizophrenia: a replication study.

In a previous study, we found an association between 5-hydroxytryptamine (serotonin) receptor 2C (HTR2C) polymorphisms and the occurrence of the metabolic syndrome in patients using antipsychotics. In the current study, we set out to replicate our findings in another sample of patients and to explore in a pooled analysis of both samples the influence of the effect of individual antipsychotics. Data for this cross-sectional study came from 2 different samples, the original sample (n = 112) and the replication sample (n = 164). Primary end point was the prevalence of the metabolic syndrome as classified by a modified version of the National Cholesterol Education Program's Adult Treatment Panel III. Primary determinants were polymorphisms in the promoter region of the HTR2C gene [HTR2C:c.1-142948(GT)n, rs3813929 (-759 C/T), and rs518147 (-697 G/C)] and an intragenic polymorphism (rs1414334:C>G). The variants of HTR2C:c.1-142948(GT)n (odds ratio [OR], 1.69; 95% confidence interval [CI], 0.75-3.81) and rs1414334 (OR, 2.35; 95% CI, 0.96-5.77) were not significantly associated with the metabolic syndrome in the replication sample but did show significance in the pooled analysis (OR, 2.09; 95% CI, 1.12-3.91; and OR, 2.35; 95% CI, 1.19-4.62, respectively). The variant rs1414334 C allele was specifically associated with the metabolic syndrome in patients using clozapine (OR, 9.20; 95% CI, 1.95-43.45) or risperidone (OR, 5.35; 95% CI, 1.26-22.83). This study extends previous findings to a larger sample of patients and implicates specific antipsychotic drugs. The increased risk for the metabolic syndrome is particularly strong in carriers of the rs1414334 C allele using clozapine or risperidone.

Polymorphisms of the LEP- and LEPR gene and obesity in patients using antipsychotic medication.

Weight gain is one of the most serious adverse effects of atypical antipsychotic agents. Genetic factors influence the risk of an individual to gain weight. The objective of our study was to determine whether the LEPR Q223R polymorphism and the LEP promoter 2548G/A polymorphism are associated with obesity in a group of male and female patients using atypical antipsychotic drugs. A cross-sectional study design was used. The study population consisted of 200 patients aged between 18 and 65 years, diagnosed with a psychotic disorder, all of whom had been using an atypical antipsychotic for at least 3 months. The primary outcome measure was the presence of obesity. Determinants were the LEPR Q223R (rs1137101) polymorphism and the LEP promoter 2548G/A single nucleotide polymorphism ([SNP] rs7799039). Of the 200 included patients, 61 (31%) were obese. In females, the LEPR 223QR (adjusted odds ratio, 0.11; 95% confidence interval [CI], 0.02-0.54) and LEPR 223RR (adjusted odds ratio, 0.07; 95% CI, 0.01-0.63) genotypes were associated with a lower risk of obesity. In males, this association was not found. In females, the average body weight was 13.6 kg more (95% CI, 1.11-26.1) in the LEPR 223QQ group compared with the LEPR 223RR group. No significant association was found between the LEP promoter 2548G/A polymorphism and obesity. Taken together, the results of our study show that the LEPR Q223R polymorphism may be associated with obesity in women with a psychotic disorder treated with atypical antipsychotic drugs and stress the importance of stratification for gender when investigating the role of variations of the LEP- and LEPR genes on the metabolic side effects of antipsychotic medications.

Association between lithium serum level, mood state, and patient-reported adverse drug reactions during long-term lithium treatment: a naturalistic follow-up study.

OBJECTIVES: To assess the association between mood state and the prevalence and the severity of lithium adverse drug reactions (ADRs). METHODS: A 26-year follow-up study was conducted among patients > or =18 years treated at the outpatient lithium clinic of the University Medical Center Groningen, The Netherlands, between November 1973 and December 2000. At each monthly scheduled visit, patients were questioned by a research nurse in a standardized manner about the presence and the severity of nine specific ADRs that frequently occur as a consequence of lithium treatment and that can be identified by the patients themselves. In addition, lithium serum level was measured and mood state was rated at each visit. RESULTS: A total of 186 patients participated and the median duration of follow-up was 5.7 years (interquartile range 2.2-11.8 years). We observed an increased prevalence and severity of ADRs with increased lithium serum level (p < 0.05), also when adjusting for mood state. The prevalence and the severity of ADRs increased with decreasing mood state into the depressive range and decreased with mood state increasing into the manic range (p < 0.05), also when adjusting for lithium serum level. Taking into account the intraindividual dependency of the data resulted in a statistically significant (p < 0.001) association between, respectively, lithium serum level, mood state, and the prevalence and severity of ADRs. CONCLUSIONS: Both physicians and researchers need to be aware that lithium serum level and mood state are independently associated with patient reporting and severity scoring of ADRs, which may complicate objective assessment of ADRs.

Frequency and nature of drug-drug interactions in a Dutch university hospital.

AIM: Drug-drug interactions (DDIs) may lead to often preventable adverse drug events and health damage. Especially within hospitals, this might be an important factor, as patients are severely ill and multiple medications may be prescribed simultaneously. The objective of this study was to measure the frequency and nature of DDI alerts in a Dutch university hospital. METHODS: All patients hospitalized in the University Medical Centre Utrecht in 2006 who were prescribed at least one medication were included. The frequency of DDIs was calculated as: (i) the percentage of patients experiencing at least one DDI, and (ii) the percentage of prescriptions generating a DDI alert. Based on the national professional guideline, DDIs were classified into categories of potential clinical outcome, management advice, clinical relevance (A-F) and available evidence (0-4). RESULTS: Of the 21 277 admissions included, 5909 (27.8%) encountered at least one DDI. Overall, the prescribing physician received a DDI alert in 9.6% of all prescriptions. The most frequently occurring potential clinical consequence of the DDIs was an increased risk of side-effects such as increased bleeding risk (22.0%), hypotension (14.9%), nephrotoxicity (12.6%) and electrolyte disturbances (10.5%). Almost half (48.6%) of the DDIs could be managed by monitoring laboratory values. CONCLUSIONS: Computerized DDI alerts may be a useful tool to prevent adverse drug events within hospitals, but they may also result in 'alert fatigue'. The specificity of alerts could significantly improve by the use of more sophisticated clinical decision support systems taking into account, for example, laboratory values.

Evaluation of available treatment guidelines for the management of lithium intoxication.

Intoxications with lithium carry considerable risk for long-term morbidity and even mortality. Consequently, any patient suspected of lithium intoxication requires immediate and appropriate care. The objectives of this study were to assess the completeness and the applicability of generally available treatment guidelines for the management of patients with a lithium intoxication and, hence, to provide general recommendations for improvement of existing treatment guidelines. Nineteen treatment guidelines originating from 7 different countries were gathered by searching the Internet, online databases, and textbooks and by contacting different poison information centers and university medical centers. A list of items was composed from the retrieved treatment guidelines and a further literature search. Most relevant items were present in the various guidelines. However, in some guidelines, essential information was missing or potentially hazardous information was provided. Clarity, presentation, and applicability of the guidelines, as assessed using parts of the Appraisal of Guidelines Research and Evaluation instrument, were relatively poor. Regular updates of treatment guidelines should be performed to incorporate new essential information. To improve applicability of guidelines, unambiguous key recommendations, alternative treatments, and special care requirements should be provided and authors are recommended to test treatment guidelines using a panel of less experienced caregivers in a hypothetical case scenario.

Patients' perceptions of information received at the start of selective serotonin-reuptake inhibitor treatment: implications for community pharmacy.

BACKGROUND: Pharmacists are increasingly acknowledging their responsibility to inform and counsel patients. However, it is unclear how these tasks are implemented and whether patients' needs are being fulfilled. OBJECTIVE: To examine patients' perceptions of information received at the start of selective serotonin-reuptake inhibitor (SSRI) treatment, aiming to identify (1) information needs and (2) the potential role of the community pharmacist as information provider. METHODS: A qualitative descriptive study comprising semi-structured telephone interviews was carried out with patients who had recently started a new course of SSRI treatment. Patients were recruited through 6 Dutch community pharmacies. The interviews were guided by the following topics: type of information obtained, unmet information needs, preferred information provider, and the role of the pharmacist. RESULTS: Forty-one patients took part in an interview. Information needs varied widely among patients; overall, patients felt that they would benefit from information tailored to their needs. Many patients required more concrete and practical information on adverse effects and delayed onset of action than was provided. In addition, an explanation of the term dependency in the context of SSRI use and a discussion of the necessity for use and believed harms of long-term treatment were important to patients. Regardless of patients' needs, the role of the pharmacist was generally perceived as limited, and patients identified several pharmacy-related barriers to improved communication, including the timing of information (mainly restricted to first-time dispensing), lack of time and privacy, lack of empathy and a protocol-driven way of providing information, and inexperience of pharmacy technicians. CONCLUSIONS: Patients starting treatment with antidepressants may benefit from information tailored to their personal needs. Along with the prescribing physician, community pharmacists could have an important role in informing and counseling patients.

Documentation quality in community pharmacy: completeness of electronic patient records after patients' first visits.

BACKGROUND: When patients visit a community pharmacy for the first time, the creation of an electronic patient record (EPR) with relevant and up-to-date data is a prerequisite for adequate medication surveillance and patient counseling. OBJECTIVE: To investigate the level of completeness of documentation in the EPR after a patient's first visit to a Dutch community pharmacy. METHODS: In each participating pharmacy, newly enlisted (<3 mo) patients to whom at least one medication had been dispensed were enrolled in this survey. For each patient who could be interviewed, pharmacy master students used a structured questionnaire to gather relevant, mandatory patient data (ie, basic characteristics, current drugs used, diseases, intolerabilities, specific conditions) and nonmandatory patient data (eg, diagnostic and monitoring data, personal experiences and habits, drug use problems) from the patient's EPR and from a structured telephone interview with the patient. Data retrieved from the patient's EPR were compared with data provided by the patient during the telephone interview. RESULTS: Of 403 selected patients, 154 (38.2%) could be interviewed by telephone. Poor documentation of telephone numbers in the EPR was the main reason for nonresponse (134/249). Interviewers found that 67.7% of prescription drugs, 0% of over-the-counter drugs, 19.6% of diseases, 3.7% of intolerabilities, and none of the specific conditions reported by patients had been documented in the EPR. Nonmandatory data (personal experiences and habits, drug use problems) reported during the patient interview had not been documented in the EPR. CONCLUSIONS: The EPR after a patient's first visit to the community pharmacy is often incomplete. For new patients, the pharmacist should more proactively and systematically gather patient information, and all relevant information should be recorded, preferably in coded form, in the pharmacy information system to allow more adequate clinical risk management.

Effect of medication reconciliation with and without patient counseling on the number of pharmaceutical interventions among patients discharged from the hospital.

BACKGROUND: Hospital admissions are a risk factor for the occurrence of unintended medication discrepancies between drugs used before admission and after discharge. To diminish such discrepancies and improve quality of care, medication reconciliation has been developed. The exact contribution of patient counseling to the medication reconciliation process is unknown, especially not when compared with community pharmacy medication records, which are considered reliable in the Netherlands. OBJECTIVE: To examine the effect of medication reconciliation with and without patient counseling among patients at the time of hospital discharge on the number and type of interventions aimed at preventing drug-related problems. METHODS: A prospective observational study in a general teaching hospital was performed. Patients discharged from the pulmonology department were included. A pharmacy team assessed the interventions with and without patient counseling on discharge medications for each patient. RESULTS: Two hundred sixty-two patients were included. Medication reconciliation without patient counseling was responsible for at least one intervention in 87% of patients (mean 2.7 interventions/patient). After patient counseling, at least one intervention (mean 5.3 interventions/patient) was performed in 97% of patients. After patient counseling, discharge prescriptions were frequently adjusted due to discrepancies in use or need of drug therapy. Most interventions led to the start of medication due to omission and dose changes due to incorrect dosages being prescribed. Patients also addressed their problems/concerns with use of the drug, which were discussed before discharge. CONCLUSIONS: Significantly more interventions were identified after patient counseling. Therefore, patient information is essential in medication reconciliation.