Do the lockdown-imposed changes in a wastewater treatment plant catchment's socio-demographics impact longitudinal temporal trends in psychoactive pharmaceutical use?

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.

Out of pocket expenses: effect of fee-waivers on opioid prescribing and dispensing.

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.

Does a pharmacist-led medication use review improve medication adherence in polymedicated aged patients? Methodological choices matter!

RATIONALE, AIMS AND OBJECTIVES: The rise in chronic diseases urges for an identification of interventions that improve adherence. However, no golden standard exists for evaluating adherence in polymedicated patients. The objectives were to investigate the impact of a pharmacist-led medication use review (MUR) service on adherence implementation rates for chronic medication, and to evaluate the appropriateness of two adherence calculation approaches in this regard. METHOD: Before-after study (SIMENON study) including ambulatory, aged, polymedicated patients. Refill data were used to calculate the proportion of days covered (PDC) per medication before and after the MUR. Adherence was assessed for chronic, solid, oral medication using a prescription-based and interval-based approach, and the performance of both approaches was compared. RESULTS: Adherence was evaluated for 1483 medications from 316 patients. The median baseline PDC per medication was 0.95 (prescription-based method) and 0.91 (interval-based approach). Pearson correlation between both approaches was 0.616 (P < .0001). The prescription-based approach found less medication below the adherence threshold of 0.80 (319 medications; 21.5% vs 481 medications; 32.4%). Using the prescription-based approach, the proportion of non-adherent patients at baseline was 61.7% (195/316 patients), of which 54.9% (107/195 patients) was only non-adherent for one medication. Median PDC scores increased significantly from 0.95 to 0.99 and 0.91 to 0.99 with the prescription-based and interval-based approach respectively (both P < .0001). Only considering the 319 medications with baseline PDC scores <0.8 using the prescription-based approach, the median PDC scores significantly increased from 0.67 to 0.84 (P < .0001), with a median score improvement of 18.3%. CONCLUSIONS: Although baseline adherence was high in this population of polymedicated aged patients, both calculation methods showed the MUR significantly improved adherence. The prescription-based approach was considered the most appropriate method. Based on these findings and literature evidence, it is recommended to implement the MUR service in Belgium and target non-adherent patients for maximal effect.

Potential approaches for the pricing of cancer medicines across Europe to enhance the sustainability of healthcare systems and the implications.

Introduction: There are growing concerns among European health authorities regarding increasing prices for new cancer medicines, prices not necessarily linked to health gain and the implications for the sustainability of their healthcare systems.Areas covered: Narrative discussion principally among payers and their advisers regarding potential approaches to the pricing of new cancer medicines.Expert opinion: A number of potential pricing approaches are discussed including minimum effectiveness levels for new cancer medicines, managed entry agreements, multicriteria decision analyses (MCDAs), differential/tiered pricing, fair pricing models, amortization models as well as de-linkage models. We are likely to see a growth in alternative pricing deliberations in view of ongoing challenges. These include the considerable number of new oncology medicines in development including new gene therapies, new oncology medicines being launched with uncertainty regarding their value, and continued high prices coupled with the extent of confidential discounts for reimbursement. However, balanced against the need for new cancer medicines. This will lead to greater scrutiny over the prices of patent oncology medicines as more standard medicines lose their patent, calls for greater transparency as well as new models including amortization models. We will be monitoring these developments.