A cost-benefit analysis of hospital-wide medication reviews: a period prevalence study.

Background For specific medical specialties it has been shown that clinical pharmacists can have a beneficial effect on the reduction of drug-related problems by performing medication reviews. However, little is known on the cost-benefit ratio of hospital-wide implementation of medication reviews. Aim To investigate the effect of conducting hospital-wide medication reviews on the detection and resolution of drug-related problems, and to calculate the cost-benefit ratio of the intervention. Method In this observational prospective period prevalence study, medication reviews were conducted during five consecutive working days in a Dutch university hospital. Patients admitted for more than 24 h were included. The cost-benefit ratio of conducting the medication reviews was calculated by dividing the total costs by the total savings. Results In 622 medication reviews, 709 potential drug-related problems (1.1 per patient) were detected. The most common advice was to stop medication (38.6%). Patients with a potentially drug-related problem were significantly older, had a higher median number of prescriptions, and the median number of days from admission to the time of medication reviews was longer. Conducting medication reviews showed a positive cost-benefit ratio of 9.7. Conclusions Hospital-wide medication reviews by clinical pharmacists have a positive cost-benefit ratio and contribute to the detection and the resolution of drug related problems (DRPs), mainly by reducing overtreatment.

Physicians' acceptance of pharmacists' interventions in daily hospital practice.

Background The physicians' acceptance rate of pharmacists' interventions to improve pharmacotherapy can vary depending on the setting. The acceptance rate of interventions proposed by pharmacists located in the hospital pharmacy over the telephone and factors associated with acceptance are largely unknown. Objective To determine the physicians' acceptance rate of pharmacists' interventions proposed over the telephone in daily hospital practice and to identify factors associated with acceptance. Setting A retrospective case-control study was performed concerning adult patients admitted to a university hospital in the Netherlands. Method Pharmacists' interventions, based on alerts for drug-drug interactions and drug dosing in patients with renal impairment, recorded between January 2012 and June 2013 that were communicated over the telephone were included. Factors associated with physicians' acceptance were identified with the use of a mixed-effects logistic model. Main outcome measure The primary outcome was the proportion of accepted interventions. Results A total of 841 interventions were included. Physicians accepted 599 interventions, resulting in an acceptance rate of 71.2%. The mixed-effects logistic model showed that acceptance was significantly associated with the number of prescribed drugs (16 to ≤ 20 drugs ORadj 1.88; 95% CI 1.05-3.35, > 20 drugs ORadj 2.90; 95% CI 1.41-5.96, compared to ≤ 10 drugs) and the severity of the drug-related problem (problem without potential harm ORadj 6.36; 95% CI 1.89-21.38; problem with potential harm OR 6.78; 95% CI 2.09-21.99, compared to clinically irrelevant problems), and inversely associated with continuation of pre-admission treatment (ORadj 0.55; 95% CI 0.35-0.87). Conclusion Over the study period, the majority of pharmacists' interventions proposed over the telephone were accepted by physicians. The probability for acceptance increased for patients with an increasing number of medication orders, for clinically relevant problems and for problems related to treatment initiated during admission.

No Superiority of Tacrolimus Suppositories vs Beclomethasone Suppositories in a Randomized Trial of Patients With Refractory Ulcerative Proctitis.

BACKGROUND & AIMS: Ulcerative proctitis (UP) refractory to 5-aminosalicylic acid (5-ASA) suppositories is a challenge to treat, often requiring step up to immunomodulator or biological therapy. Topical tacrolimus is effective and safe in patients with refractory UP. However, it is not clear how tacrolimus suppositories fit into in the treatment algorithm of UP. METHODS: We performed a randomized controlled, double-blind study at 8 hospitals in the Netherlands and Belgium from 2014 through 2017. Eighty-five patients with refractory UP (65% women) were randomly assigned to groups given once daily tacrolimus suppositories (2 mg; n = 43) or beclomethasone (3 mg; n = 42) for 4 weeks. The primary outcome was clinical response (decrease in Mayo score of 3 or more). Secondary outcomes included clinical remission, endoscopic response and remission, adverse events and quality of life. Outcomes were compared using Fisher's exact test and Mann-Whitney U test. RESULTS: Proportions of patients with clinical responses were 63% in the tacrolimus group and 59% in the beclomethasone group (P = .812); proportions of patients in clinical remission were 46% and 38%, respectively (P = .638). Proportions of patients with an endoscopic response were 68% and 60% in the tacrolimus group and in the beclomethasone group (P = .636); proportions in endoscopic remission rates were 30% and 13%, respectively (P = .092) Median increases in the inflammatory bowel disease questionnaire score were 18.0 in the tacrolimus group and 20.5 in the beclomethasone group (P = .395). Adverse event rates did not differ significantly between groups. CONCLUSIONS: In a 4-week randomized controlled trial, tacrolimus and beclomethasone suppositories induce comparable clinical and endoscopic responses in patients with UP refractory to 5-ASA. There were no significant differences in adverse events rates. Tacrolimus and beclomethasone suppositories are therefore each safe and effective treatment options for 5-ASA refractory disease. EUDRACT 2013-001259-11; Netherlands Trial Register NL4205/NTR4416.

Medication review using a Systematic Tool to Reduce Inappropriate Prescribing (STRIP) in adults with an intellectual disability: A pilot study.

A Systematic Tool to Reduce Inappropriate Prescribing (STRIP), which includes the Screening Tool to Alert doctors to Right Treatment (START) and the Screening Tool of Older Peoples' Prescriptions (STOPP), has recently been developed in the Netherlands for older patients with polypharmacy in the general population. Active involvement of the patient is part of this systematic multidisciplinary medication review. Although annual review of pharmacotherapy is recommended for people with an intellectual disability (ID), a specific tool for this population is not yet available. Besides, active involvement can be compromised by ID. Therefore, the objective of this observational pilot study was to evaluate the process of medication review using STRIP in adults with an ID living in a centralized or dependent setting and the identification of drug-related problems using this tool. The study was performed in three residential care organizations for ID. In each organization nine clients with polypharmacy were selected by an investigator (a physician in training to become a specialized physician for individuals with an ID) for a review using STRIP. Clients as well as their legal representatives (usually a family member) and professional caregivers were invited to participate. Reviews were performed by an investigator together with a pharmacist. First, to evaluate the process time-investments of the investigator and the pharmacist were described. Besides, the proportion of reviews in which a client and/or his legal representative participated was calculated as well as the proportion of professional caregivers that participated. Second, to evaluate the identification of drug-related problems using STRIP, the proportion of clients with at least one drug-related problem was calculated. Mean time investment was 130minutes for the investigator and 90minutes for the pharmacist. The client and/or a legal representatives were present during 25 of 27 reviews (93%). All 27 professional caregivers (100%) were involved. For every client included at least one drug-related problem was identified. In total 127 drug-related problems were detected, mainly potentially inappropriate or unnecessary drugs. After six months, 15.7% of the interventions were actually implemented. Medication review using STRIP seems feasible in adults with an ID and identifies drug-related problems. However, in this pilot study the implementation rate of suggested interventions was low. To improve the implementation rate, the treating physician should be involved in the review process. Besides, specific adaptations to STRIP to address drug-related problems specific for this population are required.

Identification of drug-related problems by a clinical pharmacist in addition to computerized alerts.

BACKGROUND: Both clinical pharmacists and computerized physician order entry systems with clinical decision support (CPOE/CDSS) can reduce drug-related problems (DRPs). However, the contribution of a clinical pharmacist in addition to CPOE/CDSS has not been established in a prospective study. OBJECTIVE: To determine which DRPs can be identified by a clinical pharmacist in a setting with routine use of CPOE/CDSS. SETTING: Two surgical and two neurological wards in St. Elisabeth hospital, a 600-bed teaching hospital in the Netherlands. METHODS: In this observational prospective follow-up study a clinical pharmacist reviewed the pharmacotherapy of patients admitted to surgical and neurological wards to identify DRPs (i.e. medication errors and adverse drug events) and discussed the relevance of identified problems and interventions to resolve these with the responsible physician. Acceptance of the proposed interventions and the presence of alerts in CPOE/CDSS were assessed. Primary outcome was the proportion of DRPs identified by the clinical pharmacist that also triggered a CPOE/CDSS alert. Differences between the DRPs that generated an alert and those that did not were expressed as relative risks or analyzed with Chi square statistics or Mann-Whitney U tests. MAIN OUTCOME MEASURE: The proportion of drug-related problems identified by the clinical pharmacist that also generated an alert in the CPOE/CDSS. RESULTS: During 1206 medication reviews, 442 potential DRPs were identified; 286 (65 %) DRPs were considered relevant and 247 (56 %) of the proposed interventions were accepted. A CPOE/CDSS alert was generated for 35 (8 %) of the DRPs the clinical pharmacist identified. The only difference between problems that triggered an alert and those that did not was the class of the DRP (indication 23 vs. 36 %, effectiveness 23 vs. 13 %, safety 23 vs. 10 % and pharmaceutical care issues 31 vs. 42 %, p = 0.02). CPOE/CDSS triggered 623 additional alerts that were handled during routine pharmacy service. CONCLUSIONS: As most DRPs identified by a clinical pharmacist were not detected in daily clinical practice by CPOE/CDSS, a clinical pharmacist contributes to reducing DRPs. The sensitivity of CPOE/CDSS to detect certain classes of problems should be optimized.

Prescription errors in older individuals with an intellectual disability: prevalence and risk factors in the Healthy Ageing and Intellectual Disability Study.

Prescribing pharmacotherapy for older individuals with an intellectual disability (ID) is a complex process, possibly leading to an increased risk of prescription errors. The objectives of this study were (1) to determine the prevalence of older individuals with an intellectual disability with at least one prescription error and (2) to identify potential risk factors for these prescription errors (age, gender, body mass index (BMI), frailty index, level of intellectual disability and living situation). The study population consisted of 600 older (≥ 50 years) individuals with an ID using one or more drugs who were randomly selected from the study cohort of the Healthy Ageing and Intellectual Disability (HA-ID) Study. The medication used at the time of measurement was screened for errors by a hospital pharmacist/clinical pharmacologist and a Master's student pharmacy using consensus methodology. Participants with one or more prescription errors were compared to participants without prescription errors by multivariate logistic regression to identify potential risk factors. The prevalence of individuals with one or more prescription errors was 47.5% (285 of 600 individuals; 95% confidence interval (CI) 43-52%). Relevant errors, defined as errors that actually do require a change of pharmacotherapy, were identified in 26.8% of the individuals (161 of 600 individuals; 95% CI 23-30%). Higher age (adjusted odds ratio (OR adj) 1.03; 95% CI 1.01-1.06), less severe intellectual disability (moderate: OR adj 0.48; 95% CI 0.31-0.74 and severe: OR adj 0.56; 95% CI 0.32-0.98), higher BMI (OR adj 1.04; 95% CI 1.01-1.08), higher frailty index (0.39-0.54: OR adj 2.4; 95% CI 1.21-4.77 and ≥ 0.55: OR adj 3.4; 95% CI 1.03-11.02), polypharmacy (OR adj 8.06; 95% CI 5.59-11.62) and use of medicines acting on the central nervous system (OR adj 3.34; 95% CI 2.35-4.73) were independently associated with the occurrence of prescription errors. Interventions targeted to high risk patients should be designed and implemented to improve pharmacotherapy in older individuals with an intellectual disability.

Preventable and non-preventable adverse drug events in hospitalized patients: a prospective chart review in the Netherlands.

BACKGROUND: Medication safety research and clinical pharmacy practice today is primarily focused on managing preventable adverse drug events (pADEs). Determinants of both pADEs and non-preventable adverse drug reactions (ADRs) have been identified. However, relatively little is known on the overlap between these determinants and the balance of preventable and non-preventable harm inpatients experience in modern computerized hospitals. OBJECTIVE: The aim of this study was to analyse the prevalence of pADEs and non-preventable ADRs as well as the determinants, including multimorbidity, of these ADEs, i.e. both pADEs and ADRs. METHODS: Adverse events experienced by patients admitted to two Dutch hospitals with functioning computerized physician order entry (CPOE) systems were prospectively identified through chart review. Adverse events were divided into pADEs (i.e. as a result of a medication error) and non-preventable ADRs. In both cases, a causal relationship between adverse events and patients' drugs was established using the simplified Yale algorithm. Study data were collected anytime between April 2006 and May 2008 over a 5-month period at each hospital ward included in the study, beginning from 8 weeks after CPOE was implemented at the ward. RESULTS: pADEs and non-preventable ADRs were experienced by 349 (58%) patients, of whom 307 (88%) had non-preventable ADRs. Multimorbidity (adjusted odds ratio [OR(adj)] 1.90; 95% CI 1.44, 2.50; OR(adj) 1.28; 95% CI 1.14, 1.45, respectively), length of stay (OR(adj) 1.13; 95% CI 1.06, 1.21; OR(adj) 1.11; 95% CI 1.07, 1.16, respectively), admission to the geriatric ward (OR(adj) 7.78; 95% CI 2.15, 28.13; OR(adj) 3.82; 95% CI 1.73, 8.45, respectively) and number of medication orders (OR(adj) 1.25; 95% CI 1.16, 1.35; OR(adj) 1.13; 95% CI 1.06, 1.21, respectively) were statistically significantly associated with pADEs and ADRs. Admission to the gastroenterology/rheumatology ward (OR(adj) 0.22; 95% CI 0.06, 0.77; OR(adj) 0.40; 95% CI 0.24, 0.65, respectively) was inversely related to both pADEs and ADRs. Other determinants for ADRs only were female sex (OR(adj) 1.77; 95% CI 1.12, 2.80) and use of drugs affecting the nervous system (OR(adj) 1.83; 95% CI 1.09, 3.07). Age was a significant determinant for pADEs only (OR(adj) 1.07; 95% CI 1.03, 1.11). CONCLUSIONS: In this study more than half of the patients admitted to the hospitals are harmed by drugs, of which most are non-serious, non-preventable ADRs (after the introduction of CPOE). Determinants of both pADEs and ADRs overlap to a large extent. Our results imply the need for signalling early potential adverse events that occur during the normal use of drugs in multimorbid patients or those in geriatric wards. Subsequent therapeutic interventions may improve the well-being of hospitalized patients to a greater extent than focusing on errors in the medication process only.

Comparison of potential risk factors for medication errors with and without patient harm.

PURPOSE: To compare determinants for medication errors leading to patient harm with determinants for medication errors without patient harm. METHODS: A two-way case-control design was used to identify determinants for medication errors without harm (substudy 1) and determinants for medication errors causing harm (substudy 2). Data of patients admitted to five internal medicine wards of two Dutch hospitals during 5 months were collected prospectively by chart review. Medication errors were detected and classified by two pharmacists. Consensus between five pharmacists was reached on the causal relationship between medication errors and patient harm. Data analysis was performed by multivariate logistic regression. RESULTS: We included 7286 medication orders, of which 3315 without errors (controls), and 5622 medication errors without harm (cases substudy 1) and 102 medication errors causing harm (cases substudy 2) were identified. Hospital, ward and the therapeutic class anti-infectives were associated with both medication errors without harm (hospital odds ratio (OR) 1.40; 95% confidence interval (CI) 1.21-1.63), TweeSteden hospital (TSh) geriatrics OR 2.03; 95% CI 1.73-2.38, TSh general internal medicine OR 1.44; 95% CI 1.23-1.69 and anti-infectives OR 1.28; 95% CI 1.06-1.56) and medication errors with harm (hospital OR 4.91; 95% CI 3.02-7.79, TSh geriatrics OR 5.76; 95% CI 2.52-13.15, TSh general internal medicine OR 6.51; 95% CI 2.82-15.02 and anti-infectives OR 4.20; 95% CI 2.24-7.90). CONCLUSIONS: This study shows that organisational determinants (hospital, ward) are comparable for medication errors with and without harm. For conclusions on patient- and medication-related determinants studies with larger sample sizes are needed.

Computerized physician order entry (CPOE) system: expectations and experiences of users.

OBJECTIVES: To explore physicians' and nurses' expectations before and experiences after the implementation of a computerized physician order entry (CPOE) system in order to give suggestions for future optimization of the system as well as the implementation process. METHOD: On four internal medicine wards of two Dutch hospitals, 18 physicians and 42 nurses were interviewed to measure expectations and experiences with the CPOE system. Using semi-structured questionnaires, expectations and experiences of physicians and nurses with the CPOE system were measured with statements on a 5-point Likert scale (1 = completely disagree, 5 = completely agree). The percentage respondents agreeing (score of 4 or 5) was calculated. Chi-squared tests were used to compare the expectations versus experiences of physicians and nurses and to assess the differences between physicians and nurses. RESULTS: In general, both physicians and nurses were positive about CPOE before and after the implementation of this system. Physicians and nurses did not differ in their views towards CPOE except for the overview of patients' medication use that was not clear according to the nurses. Both professions were satisfied with the implementation process. CPOE could be improved especially with respect to technical aspects (including the medication overview) and decision support on drug-drug interactions. CONCLUSION: Overall we conclude that physicians and nurses are positive about CPOE and the process of its implementation and do accept these systems. However, these systems should be further improved to fit into clinical practice.

The influence that electronic prescribing has on medication errors and preventable adverse drug events: an interrupted time-series study.

OBJECTIVE: This study evaluated the effect of a Computerized Physician Order Entry system with basic Clinical Decision Support (CPOE/CDSS) on the incidence of medication errors (MEs) and preventable adverse drug events (pADEs). DESIGN: Interrupted time-series design. MEASUREMENTS: The primary outcome measurements comprised the percentage of medication orders with one or more MEs and the percentage of patients with one or more pADEs. RESULTS: Pre-implementation, the mean percentage of medication orders containing at least one ME was 55%, whereas this became 17% post-implementation. The introduction of CPOE/CDSS has led to a significant immediate absolute reduction of 40.3% (95% CI: -45.13%; -35.48%) in medication orders with one or more errors. Pre-implementation, the mean percentage of admitted patients experiencing at least one pADE was 15.5%, as opposed to 7.3% post-implementation. However, this decrease could not be attributed to the introduction of CPOE/CDSS: taking into consideration the interrupted time-series design, the immediate change was not significant (-0.42%, 95% CI: -15.52%; 14.68%) because of the observed underlying negative trend during the pre-CPOE period of -4.04% [95% CI: -7.70%; -0.38%] per month. CONCLUSIONS: This study has shown that CPOE/CDSS reduces the incidence of medication errors. However, a direct effect on actual patient harm (pADEs) was not demonstrated.

Reliability of the assessment of preventable adverse drug events in daily clinical practice.

PURPOSE: To determine the reliability of the assessment of preventable adverse drug events (ADEs) in daily practice and to explore the impact of the assessors' professional background and the case characteristics on reliability. METHODS: We used a combination of the simplified Yale algorithm and the National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) scheme to assess on the one hand the causal relationship between medication errors (MEs) and adverse events in hospitalised patients and on the other hand the severity of the clinical consequence of MEs. Five pharmacists and five physicians applied this algorithm to 30 potential MEs. After individual assessment, the pharmacists reached consensus and so did the physicians. Outcome was both MEs' severity (ordinal scale, NCC MERP categories A-I) and the occurrence of preventable harm (binary outcome, NCC MERP categories A-D vs. E-I). Kappa statistics was used to assess agreement. RESULTS: The overall agreement on MEs' severity was fair for the pharmacists (kappa = 0.34) as well as for the physicians (kappa = 0.25). Overall agreement for the 10 raters was fair (kappa = 0.25) as well as the agreement between both consensus outcomes (kappa = 0.30). Agreement on the occurrence of preventable harm was higher, ranging from kappa = 0.36 for the physicians through kappa = 0.49 for the pharmacists. Overall agreement for the 10 raters was fair (kappa = 0.36). The agreement between both consensus outcomes was moderate (kappa = 0.47). None of the included case characteristics had a significant impact on agreement. CONCLUSIONS: Individual assessment of preventable ADEs in real patients is difficult, possibly because of the difficult assessment of contextual information. Best approach seems to be a consensus method including both pharmacists and physicians.