Implementation of pharmacogenetic testing in medication reviews in a hospital setting.

AIM: To investigate whether it is feasible to perform pharmacogenetic testing and implement the test results as part of medication reviews during hospitalization of multimorbid patients. METHODS: Patients with ≥2 chronic conditions and ≥5 regular drugs with at least one potential gene-drug interaction (GDI) were included from one geriatric and one cardiology ward for pharmacogenetic testing. After inclusion by the study pharmacist, blood samples were collected and shipped to the laboratory for analysis. For patients still hospitalized at the time when the pharmacogenetic test results were available, the information was used in medication reviews. Recommendations from the pharmacist on actionable GDIs were communicated to the hospital physicians, who subsequently decided on potential immediate changes or forwarded suggestions in referrals to general practitioners. RESULTS: The pharmacogenetic test results were available for medication review in 18 of the 46 patients (39.1%), where median length of hospital stay was 4.7 days (1.6-18.3). The pharmacist recommended medication changes for 21 of 49 detected GDIs (42.9%). The hospital physicians accepted 19 (90.5%) of the recommendations. The most commonly detected GDIs involved metoprolol (CYP2D6 genotype), clopidogrel (CYP2C19 genotype) and atorvastatin (CYP3A4/5 and SLCOB1B1 genotype). CONCLUSIONS: The study shows that implementation of pharmacogenetic testing for medication review of hospitalized patients has the potential to improve drug treatment before being transferred to primary care. However, the logistics workflow needs to be further optimized, as test results were available during hospitalization for less than half of the patients included in the study.

Adjusting the dose in paediatric care: dispersing four different aspirin tablets and taking a proportion.

OBJECTIVES: When caring for children in a hospital setting, tablets are often manipulated at the ward to obtain the right dose. One example is manipulation of tablets containing the slightly water-soluble substance aspirin, used in paediatric care as an antiplatelet agent. The evidence base, however, for choosing certain tablet formulations and manipulation methods over others for extraction of proportions is lacking. The aim of this study was to investigate the effect of tablet formulation and manipulation technique on the dose accuracy and precision attained when dispersing different commercially available aspirin tablets and extracting a small proportion suitable for children. METHODS: The manipulation methods investigated simulated those observed in the paediatric clinic. Four tablet formulations-one chewable, one conventional and two dispersible-were dispersed in 10 mL water in a medicine measure. On (1) passive dispersion, (2) mixing by stirring with the syringe, or (3) stirring and pumping the dispersion in and out of the syringe, respectively, proportions (1 mL or 2 mL) were extracted and the doses recovered were determined using a validated UHPLC (ultra high-pressure liquid chromatography) method. RESULTS: Fractions from the four different dispersed aspirin tablet formulations varied from 99% to 3% of that intended with the lowest degree of mixing, and from 96% to 34% of that intended with the highest degree of mixing. Only the dispersible tablets gave average doses within 20% of the intended dose. CONCLUSIONS: Fraction extraction from dispersed aspirin tablets only gave doses within 20% of intended for the dispersible tablets, and then only for some of the manipulation methods: 'passive dispersion' for the 75 mg dispersible tablet and 'stirring and pumping' for the 300 mg dispersible tablet. The tablets not intended for dispersion gave unsatisfactory results, outside 20%, regardless of manipulation method. The findings underline the importance of considering both tablet formulation and dose extraction technique when manipulations are required.

Comparing Two Methods of Tablet Manipulation to Adjust the Warfarin Dose in Paediatric Care.

Tablets containing prescribed doses are not always available, and this is of particular importance in paediatric care where suitable age-appropriate formulations are generally lacking. To obtain a child-adjusted dose, tablets are manipulated in several ways; e.g., they may be dispersed in water before a fraction is extracted, or they may be split before the resulting fragment is dispersed. In this study, the accuracy attained through these manipulation methods was investigated for two generic tablets containing the anticoagulant warfarin. Tablets were dispersed in water (10 mL) before a fraction (10%) was withdrawn, alternatively tablets were split in half or quarter fragments before the fragments were dispersed in water. To investigate the contribution of variability from the different steps in the manipulation processes, the amount of warfarin recovered from the various dispersions was determined, as was the accuracy of the splitting. A validated UHPLC-method was used for quantitative determination of warfarin. Splitting of the tablets could result in deviation >30% from the ideal, theoretical weight. The amount of drug substance extracted as a fraction from the dispersed tablets deviated no more than 10% from the intended amount. To obtain the most accurate child-adjusted fraction dose of warfarin, the tablets investigated in this study should be dispersed and the desired proportion extracted. Practices that involve splitting tablets are likely to increase the variation, and should be avoided.

Adjusting the dose in paediatric care by dispersing fragments of four different aspirin tablets.

AIM: Tablets can be manipulated in several ways to obtain a fraction as the dose-a practice frequently seen in paediatric care due to lack of suitable formulations. Splitting tablets prior to fragment dispersion in a small volume of liquid is one such method. The objective of this study was to investigate the accuracy and precision of this method. METHODS: Four different types of aspirin tablets (two dispersible, one conventional and one chewing) were split with a tablet splitter into half and quarter fragments. The fragments were dispersed in a medicine measure or an oral syringe. The amount recovered was determined by UHPLC analysis. RESULTS: The largest quarter fragments ranged from 26.7% to 31.5% of the full tablet weight. Dispersing the fragment in an oral syringe, the amount recovered was greater than 90.8% of the fragment manipulated for all four tablet types, when rinsing was performed. Dispersing the fragment in a medicine measure, the amounts recovered spanned from 32.9% for the conventional tablets to 98.7% for one of the dispersible tablets. CONCLUSION: Dispersion of half or quarter tablets directly in an oral syringe, but not a medicine measure, could give satisfactory recovery from fragments of all the investigated aspirin tablets.

Limited effect of structured medication report as the only intervention at discharge from hospital.

OBJECTIVE: To investigate whether a structured medication report at discharge from the hospital could reduce the number of medication discrepancies in primary care. METHOD: The study was performed as an open, randomised controlled study including patients transferred from one hospital in Norway to nursing home or home care. Both groups received epicrisis on discharge. In addition, the intervention group received a structured medication report. After discharge, the medication list in primary care service was compared with the list at discharge and medication discrepancies identified. In addition, these medication lists were retrospectively compared with the lists prior to admission to the hospital and at admission to hospital. A questionnaire on time spent and quality of the medication information was filled in by nurses in primary care. RESULTS: Medication discrepancies were found for 72% (26) of the patients in the intervention group and 76% (42) in the control group (P=0.918). Most common was drugs omitted or committed to the medication lists in primary care service. Typically, the committed drugs in primary care were omitted drugs after admission to the hospital. Nurses used significantly less time (66%) obtaining medication information in the intervention group (P=0.041). CONCLUSIONS: Structured medication report as the only intervention did not reduce the medication discrepancies after discharge from hospital. There is a need for reconciliation at admission to ensure the quality of the medication report. Structured medication report resulted in the nurses spending less time on collecting medication information in primary care service.

Interventional study to improve adherence to phosphate binder treatment in dialysis patients.

BACKGROUND: Adherence to phosphate binder treatment is important to prevent high serum phosphate level in chronic dialysis patients. We therefore wanted to investigate patient knowledge, beliefs about and adherence to phosphate binders among these patients and assess whether one-to-one pharmacist-led education and counselling enhance adherence and lead to changes in serum phosphate levels. METHODS: A descriptive, interventional, single arm, pre-post study was performed at a hospital in Norway, including chronic dialysis patients aged 18 years or more using phosphate binders. The primary end-point was change in the proportion of patients with serum phosphate below 1.80 mmol/L and the secondary end-points included change in the patient's knowledge, beliefs and adherence after the intervention measured by completion of questionnaires 'Patient Knowledge', Medication Adherence Report Scale (MARS- 5) and Beliefs about Medicines Questionnaire (BMQ). Data was collected both prior to and after one-to-one pharmacist-led education and counselling about their phosphate binders. Other medicines used by the patient was also registered. RESULTS: A total of 69 patients were enrolled in the study. After intervention, the probability of serum phosphate being below the target threshold 1.80 mmol/L (5.58 mg/dL) increased, although no significant change in mean serum phosphate levels was seen. On the other hand, the knowledge regarding phosphate binder treatment and the patients' beliefs about the necessity of the treatment increased, while the concerns decreased (BMQ). This effect did not lead to increase in self-reported adherence measured by MARS-5. However the scores were high before the intervention. CONCLUSIONS: Short term one-to-one individualized pharmacist-led education and counselling about phosphate binders increased the probability of serum phosphate concentrations being below the target threshold level 1.80 mmol/L (5.58 mg/dL), although not statistically significant. However, it did not decrease the mean serum phosphate level or increase the patients' self-reported adherence. The patients increased their knowledge about the phosphate binder and their understanding of adherence, and were less concerned about the side effects of the medication. TRIAL REGISTRATION: ISRCTN52852596 , registered 11 April 2019. The trial was registered retrospectively.

Off-label and unlicensed medicines to hospitalised children in Norway.

OBJECTIVES: The aim of this study was to investigate the use of off-label (OL) and unlicensed (UL) medicines to hospitalised children in Norway, to add to the current knowledge on use of medicines in this vulnerable patient group. METHODS: The study was performed as a cross-sectional prospective study. Medication was classified as on- or off-label based on the comparison with the SmPC regarding age, indication, dosage, route of administration and handling of the product. UL products were classified as imported or pharmacy produced. KEY FINDINGS: More than 90% of children receiving medicines in our study were given OL or UL medicines. More patients received OL (83%) than UL (59%). Route of administration was the most frequently observed OL category. The vast majority of the OL prescriptions were for 'off-patent' products. One-third of products prescribed were UL. CONCLUSIONS: The study confirms that medicines to children in hospital to a significant degree are being used outside or without authorisation, in spite of recent paediatric regulatory initiatives. More data are still needed on efficacy and safety of medicines used in children, data to be incorporated in the SmPC. In addition, suitable formulations are needed to ensure optimal dosing and adherence without risky manipulations.

Manipulating tablets and capsules given to hospitalised children in Norway is common practice.

AIM: This study provided an overview of manipulating oral medicines given to hospitalised children and evaluated this practice in two hospitals. It focused on the type of manipulation and the dosage forms that were manipulated. METHOD: This was a cross-sectional, prospective study, carried out on the paediatric wards at two Norwegian hospitals for four weeks in 2013. A medicine was said to have been manipulated if it was not administered as described in the Norwegian summary of product characteristics. RESULTS: This study showed that 17% of the 3070 administrations of oral medicines to the hospitalised children involved manipulation. Tablets, including modified release preparations, were the most frequently manipulated medicines. In approximately half of these cases, only a segment of the unit dose was administered. No manipulation of oral liquids was seen. The bioavailability of as much as 44% of the most frequent given substances may be sensitive to such manipulations due to limited aqueous solubility. Various routines for splitting and handling the unit doses were observed. CONCLUSION: Manipulation of oral medication was regularly performed on paediatric wards. There is an urgent need for age-appropriate medicines, documented and standardised processes for manipulating medicines and staff training on the consequences of manipulation.

Evaluation of different formulation studies on air-filled polymeric microcapsules by multivariate analysis.

Air-filled polymeric microcapsules have been prepared by freeze-drying of emulsions containing the wall-forming polymer in the organic phase of oil in water emulsions. Echogenic air-filled microcapsules were prepared from emulsions containing either (-)-camphene, cyclohexane or cyclooctane as the solvent in the organic phase. Formulation studies have been performed to improve the yield and acoustic quality of the microcapsule suspensions. The yield was measured as particle concentration or efficacy, i.e. normalised attenuation at 3.5 MHz, related to the amount of polymer used. No overall conclusion could be made for all the variables when visually comparing the results from the different investigations. Multivariate analyses (PCA and PLS) were therefore necessary to be able to reveal any relevant systematic information from all the investigations. Different parameters describing the formulation, the production process and parameters describing the characterisation of the intermediates and the final product were set as independent X-variables. Three to four percent (w/v) of polymer was found to be the appropriate concentration of wall forming polymer. Including PEG 3000 resulted in improved freeze-dried product and suspension. Quenching of the emulsions by freezing in dry ice/methanol prior to freeze-drying was not necessary. Process parameters for homogenising and freeze-drying should be optimised with regard to the single systems, due to the different physico-chemical properties of the different solvents, especially melting point and vapour pressure.