Impact of dose adaptations following voriconazole therapeutic drug monitoring in pediatric patients.

Voriconazole is the mainstay of treatment for invasive aspergillosis in immunocompromised pediatric patients. Although Therapeutic Drug Monitoring (TDM) of voriconazole is recommended, it remains unknown if TDM-based dose adaptations result in target attainment. Patients <19 years from two pediatric hematologic-oncology wards were retrospectively identified based on unexplained high voriconazole trough concentrations (Cmin > 6 mg/l). Patient demographics, clinical characteristics, treatment, voriconazole dosing information, voriconazole Cmin before and after adjustment based on TDM were obtained. Twenty-one patients, median (range) age 7.0 (1.2-18.5) years, were identified in two centers. First Cmin (3.1 mg/l [0.1-13.5]) was obtained after 3 days (1-27) of treatment. The median of all Cmin (n = 485, median 11 per patient) was 2.16 mg/l (0.0 (undetectable)-28.0), with 24.1% of Cmin < 1 mg/l, 48.9% 1-4 mg/l, 9.3% 4-6 mg/l, and 17.7% > 6 mg/l. Intrapatient variability was large (94.1% for IV, 88.5% for PO). Dose increases at Cmin < 1 mg/l resulted in an increased Cmin in 76.4%, with 60% between 1 and 4 mg/l. Dose decreases at Cmin > 6 mg/l resulted in a decreased Cmin in 80%, with 51% between 1 and 4 mg/l. Overall, in 45% of the cases (33 out of 55 and 12 out of 45) therapeutic targets were attained after dose adjustment. Fifty-five percent of initial Cmin was outside the therapeutic target of 1-4 mg/l, with multiple dose adaptations required to achieve therapeutic concentrations. Only 60% and 51% of dose adaptations following sub- and supra-therapeutic Cmin, respectively, did result in target attainment. Intensive and continuous TDM of voriconazole is a prerequisite for ensuring adequate exposure in pediatric patients.

The effect of a medication reconciliation program in two intensive care units in the Netherlands: a prospective intervention study with a before and after design.

BACKGROUND: Medication errors occur frequently in the intensive care unit (ICU) and during care transitions. Chronic medication is often temporarily stopped at the ICU. Unfortunately, when the patient improves, the restart of this medication is easily forgotten. Moreover, temporal ICU medication is often unintentionally continued after ICU discharge. Medication reconciliation could be useful to prevent such errors. Therefore, the aim of this study was to determine the effect of medication reconciliation at the ICU. METHODS: This prospective 8-month study with a pre- and post-design was carried out in two ICU settings in the Netherlands. Patients were included when they used ≥ 1 chronic medicine and when the ICU stay exceeded 24 h. The intervention consisted of medication reconciliation by pharmacists at the moment of ICU admission and prior to ICU discharge. Medication transfer errors (MTEs) were collected and the severity of potential harm of these MTEs was measured, based on a potential adverse drug event score (pADE = 0; 0.01; 0.1; 0.4; 0.6). Primary outcome measures were the proportions of patients with ≥ 1 MTE at ICU admission and after discharge. Secondary outcome measures were the proportions of patients with a pADE score ≥ 0.01 due to these MTEs, the severity of the pADEs and the associated costs. Odds ratio and 95% confidence intervals were calculated, by using a multivariate logistic regression analysis. RESULTS: In the pre-intervention phase, 266 patients were included and 212 in the post-intervention phase. The proportion of patients with ≥ 1 MTE at ICU admission was reduced from 45.1 to 14.6% (ORadj 0.18 [95% CI 0.11-0.30]) and after discharge from 73.9 to 41.2% (ORadj 0.24 [95% CI 0.15-0.37]). The proportion of patients with a pADE ≥ 0.01 at ICU admission was reduced from 34.8 to 8.0% (ORadj 0.13 [95% CI 0.07-0.24]) and after discharge from 69.5 to 36.2% (ORadj 0.26 [95% CI 0.17-0.40]). The pADE reduction resulted in a potential net cost-benefit of € 103 per patient. CONCLUSIONS: Medication reconciliation by pharmacists at ICU transfers is an effective safety intervention, leading to a significant decrease in the number of MTE and a cost-effective reduction in potential harm. Trial registration Dutch trial register: NTR4159, 5 September 2013, retrospectively registered.

The effect of the TIM program (Transfer ICU Medication reconciliation) on medication transfer errors in two Dutch intensive care units: design of a prospective 8-month observational study with a before and after period.

BACKGROUND: The transfer of patients to and from the Intensive Care Unit (ICU) is prone to medication errors. The aim of the present study is to determine whether the number of medication errors at ICU admission and discharge and the associated potential harm and costs are reduced by using the Transfer ICU and Medication reconciliation (TIM) program. METHODS: This prospective 8-month observational study with a pre- and post-design will assess the effects of the TIM program compared with usual care in two Dutch hospitals. Patients will be included if they are using at least one drug before hospital admission and will stay in the ICU for at least 24 h. They are excluded if they are transferred to another hospital, admitted and discharged in the same weekend or unable to communicate in Dutch or English. In the TIM program, a clinical pharmacist reconciles patient's medication history within 24 h after ICU admission, resulting in a "best possible" medication history and presents it to the ICU doctor. At ICU discharge the clinical pharmacist reconciles the prescribed ICU medication and the medication history with the ICU doctor, resulting in an ICU discharge medication list with medication prescription recommendations for the general ward doctor. Primary outcome measures are the proportions of patients with one or more medication transfer errors 24 h after ICU admission and 24 h after ICU discharge. Secondary outcome measures are the proportion of patients with potential adverse drug events, the severity of potential adverse drug events and the associated costs. For the primary outcome relative risks and 95% confidence intervals will be calculated. DISCUSSION: Strengths of this study are the tailor-made design of the TIM program and two participating hospitals. This study also has some limitations: A potential selection bias since this program is not performed during the weekends, collecting of potential rather than actual adverse drug events and finally a relatively short study period. Nevertheless, the findings of this study will provide valuable information on a crucial safety intervention in the ICU. TRIAL REGISTRATION: Dutch trial register: NTR4159 , 5 September 2013.

Problems with medicine packages: experiences reported to a Dutch medicine reporting system.

BACKGROUND: Practical issues such as ease of use and packaging appear to cause significant problems in daily use of medicines, but there are only few published studies about these aspects of medicine use. OBJECTIVE: To assess the type of experiences related to practical aspects of medicine use reported to an Internet-based medicine reporting system (www.meldpuntmedicijnen.nl). METHODS: All reports submitted from May 2004 to December 2007 to an Internet-based medicine reporting system in the Netherlands related to practical aspects of drug use were analyzed. The experiences were grouped into the following categories: difficulty with opening the package, other difficulties with use, and problems with printed text on packages and the information leaflet. RESULTS: Of the 5175 individuals who submitted a report, 530 submitted 611 reports on practical aspects of medicine use. More than half of the reports concerned difficulties with the opening of packages, mostly about opening blister packages (46.2%). One third of the reports were related to other problems with use, mainly package size (13.0%) and preference for different packaging (8.5%). About 1 in 10 reports was related to the printing and information on packages, mostly about unclear and confusing text print on the primary package (5.7%). In all, 25.2% of the reporters informed their prescribing physician of the problem and 38.2% informed the pharmacist or pharmacy staff. CONCLUSIONS: Some medicine users experience considerable difficulties with the packaging of their drugs; one of the major issues is opening a blister package. Packaging of pharmaceuticals needs more attention; issues need to be addressed by the pharmaceutical manufacturers, registration authorities, and, most immediately, community pharmacists.