Search

Wastewater-based epidemiology (WBE) includes the analysis of human metabolic biomarkers of xenobiotics in influent wastewater. WBE complements existing drug utilization approaches and provides objective, spatio-temporal information on the consumption of pharmaceuticals in the general population. This approach was applied to 24-h composite influent wastewater samples from Leuven, Belgium. Daily samples were analysed from September 2019 to December 2019 (n = 76), and on three days of the week (Monday, Wednesday, Saturday) from January 2020 to April 2022 (n = 367). Sample analysis consisted of 96-well solid-phase extraction and liquid chromatography coupled to tandem mass spectrometry. Measured concentrations of 21 biomarkers for antidepressant and opioid use were converted to population-normalized mass loads (PNML) by considering the flow rate and catchment population. To capture population movements, mobile phone data was used. Amitriptyline, hydroxy-bupropion, norcitalopram, citalopram, normirtazapine, trazodone, O-desmethylvenlafaxine, codeine, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), methadone, morphine, O-desmethyltramadol, and tramadol were included in the temporal assessment since concentrations were above the lower limit of quantification. The PNML of most biomarkers increased (with 3-119 %) throughout the sampling period. The population disruption during the COVID-19 pandemic led to a major change in the socio-demographics of the catchment area, resulting in temporal differences in the PNML of the different biomarkers. As such, higher PNML were observed during the different lockdown phases, which were characterized by the outflow of university students and a decreasing commuting in and out the catchment area. The effects of the fluctuating socio-demographics of the catchment population were further evidenced by the different week-weekend pattern of PNMLs over the course of the sampling campaign. Mean parent/metabolite ratios (i.e., citalopram/norcitalopram, tramadol/O-desmethyltramadol, venlafaxine/O-desmethylvenlafaxine, and methadone/EDDP) remained relatively stable throughout the entire sampling campaign (RSD% below 25 % for all ratios, except for methadone/EDDP) and therefore were not affected by this population change., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Pharmaceutical reimbursement policies should aim for satisfactory health care at reasonable prices and assure treatment adherence while avoiding wasteful pharmaceutical spending. In Belgium, the maximum billing system, also called "Maximum Amount Fixed" system (MAF), ensures that out-of-pocket payments beyond a ceiling are fully reimbursed to guarantee pharmaceutical treatment in vulnerable population groups (e.g. low-income people and chronic patients). Starting from 2015, a policy change occurred and these expenses were waived during the same calendar year once this ceiling was reached instead of reimbursing these expenses in the next fiscal year. Each subsequent fiscal year, out-of-pocket payments were reintroduced in January., Methods: Longitudinal dispensing trends, from early 2013 to mid-2020, for 13 prevalent reimbursed opioids were investigated., Results: For MAF patients, significant seasonal increases in opioid dispensing reoccurred towards the end of the year. This pattern was absent for non-MAF patients and was only observed after the 2015 policy change. Periodic changes in out-of-pocket expenses, a characteristic of the reimbursement policy in Belgium, clearly influences opioid availability in an already at-risk group., Conclusions: Out-of-pocket reimbursement policies should be urgently re-evaluated to minimize unnecessary opioid exposure, while preserving the affordability of pain treatment for vulnerable patients., Competing Interests: Declarations of Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The long-term use of benzodiazepine receptor agonists (BZRAs) is associated with multiple side effects, such as increased sedation, hangover or an elevated risk of dependency and abuse. Unfortunately, the long-term use of BZRAs is reaching worrying intake rates, and therefore, the need for action is high. It was demonstrated already that the overall willingness of patients for deprescription increased when a slow dose reduction scheme with the possibility for dose increase, if needed, is employed. The current study aims to develop a flexible dosing platform of zolpidem hemitartrate (ZHT) to facilitate such withdrawal therapy. As this is the first report on the extrusion and 3D printing of ZHT, its thermal behaviour and sensitivity towards photolytic degradation was characterised. It was shown that ZHT possesses multiple polymorphs and was especially prone to oxidative photolysis. Next, a variety of immediate release polymers (Eudragit EPO, Kollidon VA64, Kollidon 12PF and Soluplus) were blended and extruded with Polyox WSR N10 to investigate their feedability and printability by mechanical and rheological analysis. The addition of PEO was shown to enable printing of these brittle pharmaceutical polymers, although the processing temperature was deemed critical to avoid surface defects on the resulting filaments. An EPO(70)PEO(30) system was selected based on its suitable mechanical properties and low hygroscopicity favoring ZHT stability. The matrix was blended with 1% or 10% API. The effect of certain printing parameters (caplet size, nozzle diameter, % overlap) on dissolution behaviour and caplet weight/dimensions/quality was assessed. A flexible dosing platform capable of delivering <1 mg and up to 10 mg of ZHT was created. Either caplet modification (incorporation of channels) or disintegrant addition (Primojel, Explotab, Ac-Di-Sol, Primellose and Polyplasdone-XL) failed to achieve an immediate release profile. This study provides the first report of a 3D-printed flexible dosing platform containing ZHT to aid in withdrawal therapy.

Background: Pharmacovigilance legislation was introduced back in 2012 with new concepts such as the inverted black triangles and risk minimisation activities. Healthcare professionals need to familiarize themselves with these new notions in order to comply with their obligations such as risk mitigation and reporting of adverse drug reactions., Objective: To measure the magnitude and relevance of these new concepts and the impact on everyday dispensing in Belgian community pharmacies., Methods: An inventory database was constructed containing all relevant pharmacovigilance information at product level, and this data was made available within the pharmacy dispensing software. Furthermore, for a typical community pharmacy, the number of concerned products and the number of dispensed products with supplementary pharmacovigilance responsibilities was determined., Results: The number of available and dispensed medicines with black triangle or additional risk minimisation activities has increased significantly since July 2014. During July 2017, each pharmacy dispensed around 120 packs with risk minimisation obligations and around 70 with a black triangle, clearly illustrating the relevance of having all information at hand., Conclusions: With relevant safety information available at the point of dispensing, pharmacists can now focus on complying with their pharmacovigilance responsibilities., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: This study aimed to compare determinants of professional development between different countries to identify barriers and facilitators of development towards clinical pharmacy services and stimulate discussion of under-used potential and opportunities., Materials: The study was conceived as a survey. The questionnaire was administered to a group of experts., Methods: The survey was conducted as a cross-sectional study with descriptive and correlation analysis. A questionnaire was developed and adjusted to the study focus, covering aspects on general regulations for community pharmacies, professional education, implementation of clinical pharmacy services, and research in patient care. Results were compared for analyses., Results: A total of twelve countries were included in this survey. Pharmacy studies took between 4 and 6 years plus residency in most countries. Curricula remained drug-oriented only in Austria, Bosnia-Herzegovina, and Germany; these three countries had the least pharmacotherapy content in their curricula. Canada, the USA, and Australia have established clinical pharmacy services in almost all fields of practice. Most other countries have implemented at least some clinical services, with the exception of Bosnia-Herzegovina, Germany, and Kosovo. The correlation coefficient between education, research, and implementation was 0.91., Conclusion: The results of the survey show that clinical pharmacy services are established to very different extents among the participating countries. The strong correlation suggests that achieving a successful transition in professional practice needs to address several aspects of education and research to reach progress. The collected data might help to identify potential areas of improvement to foster implementation of clinical pharmacy services.
.

Background: In October 2013, a New Medicines Service (NMS) was introduced in community pharmacies in Belgium to support asthma patients who are novice users of inhaler devices with corticosteroids. The protocol-based intervention used the Asthma Control Test (ACT) and the Medication Adherence Report Scale (MARS) to assess asthma control and medication adherence. The NMS is the first initiative that puts advanced pharmaceutical care into practice in Belgium. The present study evaluated the degree to which the NMS program is delivered as intended, drawing on the concept of implementation fidelity (IF)., Methods: The main dimensions of IF and potential moderating and facilitating factors for the implementation of NMS in community pharmacies were evaluated using telephone interviews with pharmacists (n = 497), semi-structured interviews with patients eligible for NMS (n = 30), focus groups among general practitioners (n = 72) and lung specialists (n = 5), and a work system analysis in community pharmacies (n = 19)., Results: The uptake of NMS in Belgian community pharmacies remains low. In addition to practical barriers, pharmacists found it difficult to identify new asthmatic patients when they were not informed about the diagnosis. A lack of commitment from physicians, patients and pharmacists was noted in the early start-up phase of the program. Many pharmacists did not see how NMS differed from existing pharmaceutical care. Physicians considered this service as part of their own tasks and discouraged ACT for asthma follow-up in the community pharmacy., Conclusions: The introduction of the NMS program was not sufficiently embedded in the Belgian health care organization, causing low uptake and resistance to its implementation by pharmacists, patients, and other health care professionals. To increase the uptake of this type of service and its possible extension to other patient groups, more collaboration among the different health care professionals during design and implementation is necessary, as well as systematic data collection to monitor the quality of the service, better training of pharmacists, and more information for patients and physicians., (Copyright © 2016 Elsevier Inc. All rights reserved.)

A systematic quality control of compounded medicines, and an associated guidance of community pharmacists, was identified as a complementary opportunity to improve and guarantee the quality of compounded medicines. Before implementing this on a national scale, a pilot project was organized. Fifty pharmacies prepared the same formula and had it checked regarding labelling, preparation reports and analytical parameters. This proof of concept demonstrated that the organisation of quality control of compounded medicines by the professional body itself is feasible. Such audits fit well in de quality assurance systems in place in community pharmacy, where any corrective measures are properly documented and implemented. This form of self-regulation has a preventive character for detecting defects and contributes to improving the quality of the preparations and thus to the patient safety.

Introduction: Counseling of patients filling a first prescription is an essentiaL aspect of pharmaceutical care. The use of a protocol summarizing all relevant counseling aspects can be a useful tool to standardize pharmaceutical care and to promote impLementation., Aim: (1) To develop a protocol for counseling of patients starting with oral hypoglycaemic agents (OHA), and (2) to investigate current provision of counseling for these patients in Belgian community pharmacies., Method: Based on literature, a consensus meeting with community pharmacists and consultation with physicians, we developed a protocol for counseling patients starting OHA. Additionally, an observational study of current provision of counseling for patients starting OHA was performed in 90 community pharmacies., Results: All pharmacists reported to provide the most important item of our protocol, i.e. dose and timing of OHA intake. All other protocol items were provided by a smaller proportion of pharmacists: indication (by 64.4% of pharmacists), mechanism of action (30.0%), what to do if a dose is missed (3.3%), side effects (34.4%), hypoglycaemia (24.4%) and Lifestyle advice (68.9%). About 45% of pharmacists reported to give written drug information to patients starting OHA. Reduction of the administrative workload was most frequently mentioned as measure to spend more time on patient counseling. The majority of pharmacists considered our protocol as feasible and appLicabLe in daily pharmacy practice., Conclusion: This study found that current counseLing practices for patients starting OHA can be improved. Our protocol could be a useful and feasible tool to facilitate implementation of first prescription counseling.

Aims: To explore drug related problems a community pharmacist encounters when a patient is discharged from hospital. The study also investigates which information from the hospital reaches the community pharmacy., Methods: A validated survey was presented, by community pharmacists, to patients or their family after hospital discharge, between the 1st of December 2007 and the 29th of February 2008. The survey contained questions on 4 items: patient characteristics--discharge medication--information received from the hospital--drug related problems and pharmacists interventions. Analyses were done with SPSS 16.0., Main Results: 82 community pharmacists participated. 261 patients were included. Only 25% of the patients collected their medication from the pharmacy themselves. On discharge, patients on average received two additional drugs, compared to the pre-hospital situation. 69% received a medication chart, but less than half of them brought this chart along when visiting the pharmacy. Only 9% got computer-generated prescriptions from the hospital and < 3% received a letter of referral addressed to their pharmacist. In 33% of the cases the pharmacists noticed one or more problems concerning the medication prescribed after hospital discharge. The chance to detect a problem increased significantly when the chart was brought to the pharmacy (p=0.033). In case of observed problems, the community pharmacist succeeded to reach the treating specialist by phone in less than one third of those cases., Conclusion: The results foster the discussion on the need for a better seamless care and the role clinical and community pharmacists could play in this care model.

CEC was used to develop a method for the enantiomeric excess determination of levetiracetam, an antiepileptic drug. Different types of calibration curve were evaluated for use in the range between 0.01 and 1 mg/mL when aniracetam was used as an internal standard. The method gave comparable results when only the areas of the impurity were used in the calibration curve. The predicted detection and quantification limits from the S/N were 1.1 and 3.6 microg/mL, respectively. However, experimental results showed that LOD and LOQ were underestimated. Repeatability of injection was demonstrated by the RSD values obtained for retention time, resolution, ratios of the areas impurity/internal standard, and areas of impurity and internal standard individually, which were below or equal to 9.30%. The between-days variability experiments indicated that it is better to make a calibration curve daily. The finally selected calibration curves were used to test the accuracy of the developed method on bulk samples and Keppra tablets containing 250 mg levetiracetam. Both selected calibration curves performed similarly. The one using the internal standard information gave overall recoveries between 88 and 118%, while the one using areas gave results between 84 and 118%.

A CE method for metacycline (MTC) determination was investigated in an inter-laboratory experiment. Many problems were encountered in this study, most of which were related to the transfer of the method to different CE equipment. The reported problems could be classified into different categories: problems related to the precision, to the parameters in the protocol, and to the MTC peak shape. As the peak shape problem was partially responsible for the poor precision, a new CE method was developed in order to obtain a good MTC peak shape on all equipment. The precision of this new method for MTC determination was examined in an intermediate precision study, where the influence of the factors "time" and "equipment" was investigated. Although the new method could be transferred to different instruments, the precision remained poor mainly due to the contributions of the between-replicate and the between-injection variances.

Patients' demands for automatic blood pressure monitors have increased steadily over the last few years. The offer in the Belgian community pharmacies has risen accordingly. For approximately 40 automatic devices op the Belgian market, an overview is given stating their most important aspects, with emphasis on clinical validation.

Medicines and food supplements based on the dry extract of the leaves of Ginkgo biloba L. were evaluated by determination of the content of total flavonoids, rutin and terpene lactones by means of liquid chromatography. All examined medicines complied with the fixed requirements whereas all food supplements deviated from 1 or more of the criteria. It could also be demonstrated that some products contained extracts to which rutin was added.

Piracetam preparations formulated as capsules, tablets and granules were evaluated with different tests including in vitro dissolution and assay with previously validated methods according to the guideline of the European network of official medicines control laboratories (OMCLs). All examined products complied with the requirements as described here and in the European Pharmacopoeia except for the dissolution test where 3 products did not meet the USP acceptance criteria applied on the established specification.

Ranitidine preparations formulated as tablets and granules were evaluated with different tests including in vitro dissolution and assay. Previously the analytical methods of these tests were validated according to the guidelines of the European network of Official Medicines Control Laboratories (OMCLs). All examined products complied to the requirements as described in the European, the British and the US Pharmacopoeia and consequently they can be considered as pharmaceutically equivalent.

Ribozymes are sequences of catalytic RNA that are being evaluated as possible antisense therapeutics. This paper describes how capillary electrophoresis (CE) could be used to measure the catalytic rate of a synthetic hammerhead ribozyme in cleaving its substrate. This substrate was a synthetic full-RNA 17-mer, whereas the ribozyme was made up of a mixture of 37 2'-OH and 2'-OCH3 RNA nucleotides. After experimental conditions to exclude ribonuclease contamination were successfully met, different CE modes were tried out to separate the ribozyme from its substrate. Only the combination of chemical and thermal denaturation was adequate to disrupt strong secondary structures and to inhibit comigration of the two molecules. Cleavage kinetics were measured by continuous injection from the reaction vial into a polymer-filled capillary, and by determination of the area of the shrinking substrate peak. Compared to the well-established slab gel electrophoresis, CE is at least one order of magnitude faster, may be completely automated, allows easier and more precise quantitation of results, and, due to the small scale and self-contained nature of the apparatus, reduces health risks from dangerous chemicals. Unfortunately, UV detection in a 100-microm internal diameter capillary lacked the sensitivity to perform assays in the nanomolar range, which was necessary for a full Michaelis-Menten analysis., (Copyright 1999 Academic Press.)

A capillary electrophoresis system that integrated an enzymatic reaction and capillary polymer sieving electrophoresis was used to check the enzymatic stability of oligonucleotides. Phosphodiesterase I was employed to assess the susceptibility to 3'-exonucleolytic breakdown of some unmodified and modified oligonucleotides. Before degradation, the purity of the synthetic oligodeoxynucleotides was checked by capillary electrophoresis with a replaceable hydroxyethyl cellulose polymer solution. Enzymatic breakdown was achieved inside the capillary by merging substrate and enzyme zones based on their difference in electrophoretic mobility. After reaction, oligonucleotide fragments were swept to the detector, where they were individually detected and the remaining substrate was quantified. The results from the in-capillary degradation were compared to an off-line incubation and separation.

The possibility of determining the Michaelis constant of the irreversible deamination of adenosine to inosine by adenosine deaminase, using capillary electrophoresis, was investigated. This paper describes the use of electrophoretically mediated microanalysis (EMMA) as the technique for carrying out the assay. Initial reaction velocities of the enzymatic reaction were estimated from the peak area of inosine, and the Michaelis constant was calculated according to the Lineweaver-Burk equation. The result (Km = 5.3 x 10(-5) M +/- 8 x 10(-6) M) was consistent with previously reported values. Using the present method, a total amount of as few as 1.2 fmole of enzyme and 9.2 ng of substrate were injected in the capillary for the construction of a Michaelis Menten curve (seven concentrations of substrate, each concentration analyzed in triplicate), which is far smaller than the quantities required in conventional methods.