In detail

The use of medicines is a fundamental component of the care of older people, but inappropriate prescribing – in the form of over-, mis- or under-prescribing – is frequent. This causes substantial morbidity, impairs quality of life for patients and increases costs for the society. Measuring appropriateness of prescribing in older people is complex, and we develop methods for better measuring inappropriate prescribing and its adverse consequences. We then use these methods to describe the prevalence of inappropriate prescribing in various settings. By exploring the reasons underlying inappropriate use and the patient’s perspectives, we aim to identify important factors that need to be taken into account when designing approaches for optimization. Finally, we implement and evaluate the effect of approaches for optimization.

OPERAM

The OPERAM project is a European project (H2020, 2015-2020) led by University of Bern. The core part of the OPERAM project is a large-scale cluster RCT to evaluate the effect of a complex intervention on drug-related admissions and other clinical and patient-reported outcomes. The intervention comprises clinical decision support using an electronic system called STRIPA, and medication review performed by a geriatrician and a clinical pharmacist. Patient recruitement was completed in October 2018, and almost 400 patients were recruited from the Belgian site (Cliniques universitaires Saint-Luc). Patient follow-up was completed in October 2019. The final results will be published in 2021, and numerous substudies are ongoing.

As leaders of the work package on “clinical outcomes and patient perspective”, we have (a) developed a core outcome set (COS) for clinical trials of medication review in older patients with multi-morbidity and polypharmacy (b) developed a method to adjudicate drug-related admissions in older people (c) conducted a substudy about the patients’ experience of medication review. The results of the latter will be published in 2021.

In addition, we have participated in the Health Economics work package to identify health economic characteristics of interventions to improve pharmacotherapy in older multimorbid people. We have assessed resource use, cost implications and cost-effectiveness of the OPERAM randomized clinical trial intervention in the 4 countries in which data were collected (Switzerland, Ireland, Belgium, the Netherlands). A cost-effectiveness analysis was performed in 2020, and its methodological challenges was assessed.

Recently, we evaluated the performance of the trigger tool developed to detect DRAs using data from the 1235 hospitalizations adjudicated for 832 OPERAM patients. A revised trigger tool was then developed based positive predictive values of triggers, correlations between triggers, and on the analysis on non-triggered events.

COME-ON (nursing home setting)

The COME-ON (Collaborative approach to Optimise MEdication use for Older people in Nursing homes) study, led in collaboration with KULeuven (Prof V Foulon), was a multicentre cluster-controlled trial set up in Belgian nursing homes, with the aim to evaluate the effect of a complex, multifaceted intervention on the appropriateness of prescribing of medicines for older people in Belgian nursing homes. The results on the primary and secondary outcomes, as well as detailed data on the process evaluation have been published in 2019.

In 2020 we have continued to perform additional posthoc analyses on the Come-On database. In-depth evaluations of data on the use of benzodiazepine receptor agonists (BZRA) have been completed. We found that BZRA use and potentially inappropriate prescribing were highly prevalent. Deprescribing occurred in 28.1% of BZRA users at the end of the study. Being in the intervention group was associated with higher odds of deprescribing, as compared to the control group.

We have also evaluated appropriateness of prescribing in a subgroup of frail NHRs, using the STOPPFrail criteria. Among the 308 frail nursing home residents (NHRs), two third of them had ≥1 potentially inappropriate medication (PIM) at baseline. Although the prevalence of PIM remained high at 8 months follow-up (50%), a significant and encouraging decrease was observed over time after the implementation of the medication review process, except for some medication classes (i.e. calcium, multivitamins and antidiabetic agents).

Finally, an evaluation of the occurrence of potentially clinically relevant drug-drug interactions is ongoing.

We participated in a study led by the University of Limoges (Prof ML Laroche), whose aim is to validate a French version of the ‘revised Patients’s Attitudes Towards Deprescribing (rPATD)’ questionnaire. Results have been recently published.

In 2019, we have launched new research projects focusing on BZRA deprescribing in older people. Several aspects are addressed, including: current practices in benzodiazepine deprescribing in the inpatient, outpatient and nursing home settings; patient as well as healthcare professionals’ attitudes towards benzodiazepine deprescribing; and effect of an approach that includes patient participation and interprofessional collaboration.

In this context, as no validated tool exists specifically to evaluate older adluts’ attitude towards BZRA deprescribing, the rPATD questionnaire was adapted into a BZRA specific instrument ith the implication of healthcare professionals and older adults taking BZRA. Ongoing current work includes the assessment of the psychometric properties of this adapted questionnaire in a sample of 240 older adults taking a BZRA in the ambulatory setting or in nursing homes. The recruitment of patients is still ongoing, and is highly impacted by the COVID19 crisis.

When designing approaches to BZRA deprescribing, it is important to account for barriers and enablers to deprescribing. To that end, we are currently conducting (a) a systematic review of the barriers and enablers of BZRA deprescribing, and (b) a qualitative study with healthcare professionals and residents in the nursing home setting. For both studies, we use the Theoretical Domains Framework to categorize barriers and enablers.

This new research dimension is being developed by Séverine Henrard, who joined our research group in 2016.

Heterogeneity of type 2 diabetes in older patients: pathophysiology and therapeutic implications

The aim of the project is to assess the heterogeneity in older patients with type 2 diabetes, with the aim of improving the therapeutic management of the different profiles of patients.

This project, which started in 2017, is designed as a multidisciplinary translational investigation, gathering metabolic, bio-clinical and (pharmaco-)epidemiological approaches and is conducted in collaborations with clinicians from Saint-Luc University Hospital.

In 2020, we have conducted a retrospective study on older geriatric inpatients ≥75 years with type 2 diabetes and taking a glucose lowering therapy (GLT), and assessed the inappropriateness of GLT prescribing defined by the 2019 Endocrine Society guideline on diabetes treatment in older adults, and the one-year mortality rate. GLT overtreatment was present in 57.2% of these geriatric patients, undertreatment in 17.9%, and appropriate treatment in 24.8%. Poor health status (vs intermediate), as well as overtreatment (vs appropriate) were both associated with a significantly higher 1-year mortality rate, but not undertreatment. A special attention should be paid to individualisation of the HbA1c target goals in geriatric patients with diabetes, and to GLT de-intensification in those being over-treated.

Finally, we have conducted and are finalizing a systematic review of Clinical Practice Guidelines recommendations on the individualization of glycaemic management in older people with type 2 diabetes.

In 2020 we have continued some research word on the challenges associated with the appropriate use of Direct oral anticoagulants (DOACs) and vitamin-K antagonists (VKA).

We systematically reviewed the impact of computerized clinical decision support systems (CDSS) and described CDSS features associated with success or failure. We found that CDSS might positively impact the use of oral anticoagulants in AF patients at high risk of stroke. The scope of CDSS should however evolve to assist prescribers in selecting the most appropriate and tailored medication. Efforts should also be made to improve the relevance of notifications and to address implementation outcomes

In collaboration with FACM (see other section of this report), we perform pharmacokinetic studies in specific patients populations (haemodialysis patients) in order to propose optimized therapeutic doses, and pharmacoepidemiological studies to evaluate the off-label use of specific antibiotics.

Rational peri-operative use of antibiotics in Benin MUSTPIC

In 2016, we started an international collaboration with Université d'Abomey-Calavi to assess the impact of a multidisciplinary approach, including a clinical pharmacy intervention, to rationalize the use of antibiotics and promote hand hygiene in c-section practice and digestive surgery in Benin. This is the Multidisciplinary STrategy for Prevention and Infection Control (MUSTPIC) project.

In 2020, we identified the causative agents involved in surgical site infections (mainly S. aureus, 28.5%, in obstetrics, and E.coli, 38.4%, in gastrointestinal surgery) and the alarming rate of multidrug-resistant bacteria (90.8% of aerobic bacteria) in six public hospitals in Benin. In addition, we described the first detection of a plasmid-encoded New-Delhi metallo-beta-lactamase-1 (NDM-1) producing Acinetobacter baumannii isolated in Benin (to be published in 2021).

We observed healthcare workers from these 6 hospitals to describe hand hygiene actions in surgical care units. Overall, hand washing (72.1%) or alcohol rubbing (27.9%) was performed in 33.3% of hand hygiene opportunities. When hand hygiene was applied, technique and duration were not appropriate. Exploration of healthcare professionals’ perception of antibioprophylaxis and hand hygiene will continue in 2021.