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BACKGROUND Benzodiazepine receptor agonists (BZRAs) are commonly prescribed in older adults despite an unfavorable risk-benefit ratio. Hospitalizations may provide a unique opportunity to initiate BZRA cessation, yet little is known about cessation during and after hospitalization. We aimed to measure the prevalence of BZRA use before hospitalization and the rate of cessation 6 months later, and to identify factors associated with these outcomes. METHODS We conducted a secondary analysis of a cluster randomized controlled trial (OPtimising thERapy to prevent Avoidable hospital admissions in the Multimorbid elderly [OPERAM]), comparing usual care and in-hospital pharmacotherapy optimization in adults aged 70 years or over with multimorbidity and polypharmacy in four European countries. BZRA cessation was defined as taking one or more BZRA before hospitalization and not taking any BZRA at the 6-month follow-up. Multivariable logistic regression was performed to identify factors associated with BZRA use before hospitalization and with cessation at 6 months. RESULTS Among 1601 participants with complete 6-month follow-up data, 378 (23.6%) were BZRA users before hospitalization. Female sex (odds ratio [OR] 1.52 [95% confidence interval 1.18-1.96]), a higher reported level of depression/anxiety (OR up to 2.45 [1.54-3.89]), a higher number of daily drugs (OR 1.08 [1.05-1.12]), use of an antidepressant (OR 1.74 [1.31-2.31]) or an antiepileptic (OR 1.46 [1.02-2.07]), and trial site were associated with BZRA use. Diabetes mellitus (OR 0.60 [0.44-0.80]) was associated with a lower probability of BZRA use. BZRA cessation occurred in 86 BZRA users (22.8%). Antidepressant use (OR 1.74 [1.06-2.86]) and a history of falling in the previous 12 months (OR 1.75 [1.10-2.78]) were associated with higher BZRA cessation, and chronic obstructive pulmonary disease (COPD) (OR 0.45 [0.20-0.91]) with lower BZRA cessation. CONCLUSION BZRA prevalence was high among included multimorbid older adults, and BZRA cessation occurred in almost a quarter of them within 6 months after hospitalization. Targeted BZRA deprescribing programs could further enhance cessation. Specific attention is needed for females, central nervous system-acting co-medication, and COPD co-morbidity. REGISTRATION ClinicalTrials.gov identifier: NCT02986425. December 8, 2016.

Background as a result of the high prevalence of polypharmacy in nursing homes (NHs), nursing home residents (NHRs) are exposed to numerous drug–drug interactions (DDIs) that can lead to adverse drug effects, and increased morbidity and mortality. Objectives to evaluate (i) the prevalence of DDIs among NHRs and its evolution over time, and (ii) factors associated with a favourable evolution. Design posthoc analysis of the COME-ON study, a cluster-randomised controlled trial aiming at reducing potentially inappropriate prescriptions in NHs, through the implementation of a complex intervention. Setting and subjects 901 NHRs from 54 Belgian NHs. Methods DDIs were identified using a validated list of 66 potentially clinically relevant DDIs in older adults. We defined a favourable evolution at 15 months as the resolution of at least one DDI present at baseline, without the introduction of any new DDI. Factors associated with a favourable evolution were analysed using multivariable logistic regression. Results at baseline, 475 NHRs (52.7%) were exposed to at least 1 DDI and 225 NHRs (25.0%) to more than one DDI. Most common DDI was ‘Concomitant use of at least three central nervous system active drugs’. At 15 months, we observed a 6.3% absolute decrease in DDI prevalence in intervention group, and a 1.0% absolute increase in control group. The intervention, older age and private NH ownership were significantly associated with a favourable DDI evolution. Conclusion a high prevalence of DDI in Belgian NHs was observed, but the COME-ON intervention was associated with a favourable evolution over time.

The revised Patients' Attitudes Towards Deprescribing (rPATD) questionnaire explores older adults' views on deprescribing in general. Those views may differ, however, when the target is a specific drug such as benzodiazepine receptor agonists (BZRA). This study aimed to adapt the 22-item French rPATD questionnaire to create a BZRA-specific instrument and to assess the psychometric properties of this new tool. The adaptation of the questionnaire comprised 3 steps: 1) item transformation during group discussions with 8 healthcare providers and 8 BZRA users (aged ≥65 years), 2) pre-test of the questionnaire with 12 other older adults to ensure items understanding, 3) evaluation of the psychometric properties of the new questionnaire with 221 older BZRA users recruited in Belgium, France, and Switzerland. Construct validity was assessed using exploratory factor analysis (EFA), internal consistency with Cronbach's alpha, and test-retest reliability with intraclass correlation coefficient (ICC). After the pre-test, the questionnaire had 24 items (19 adapted from the French rPATD, 3 removed, and 5 added). The EFA, however, found that several items performed poorly. Eleven items were consequently removed, based on statistical performance and clinical relevance. Three factors were extracted from the EFA performed on the 11 retained items and were named "Concerns about stopping BZRA", "BZRA inappropriateness", and "Dependence on BZRA". The questionnaire also includes two global questions about willingness to reduce BZRA dosage and willingness to discontinue BZRA. All factors showed acceptable internal consistency (0.68 ≤ Cronbach's alpha ≤0.74). Two factors showed acceptable test-retest reliability. The "Concerns about stopping BZRA" factor was found to vary over time (ICC [95%CI]: 0.35[-0.02; 0.64]). We developed and validated a 13-item questionnaire to evaluate the attitudes of older people towards BZRA deprescribing. Despite some limitations, this questionnaire appears to be a useful tool for facilitating shared decision-making on BZRA deprescribing.

In this chapter, we aim to present and discuss the activities performed by pharmacists at individual patient level for optimising drug therapy and the role of pharmacists in training other healthcare professionals (HCPs) towards medicines optimisation in older people. Then, we describe the different models of care and their levels of implementation in the ambulatory, acute and long-term care settings. The case of pharmacist prescribing is also addressed. There has been a strong evolution over the last decades in the role played by pharmacists in optimising drug therapy for older people, either as individual HCPs or as part of multidisciplinary teams. This role now goes far beyond medication supply and checking drug interactions, for example. In parallel, educational programs to train pharmacists in patient-centred care and geriatric pharmacotherapy have been developed, and pharmacists are now better equipped to take on their expanding roles as part of multidisciplinary teams.

OBJECTIVES: Clonidine is an alpha-2 adrenoreceptor agonist and is frequently combined with opioids (ie, morphine hydrochloride (HCl)) for the management of chronic pain. In palliative care, the administration of clonidine and morphine HCl is recommended in case of tolerance effect. This study aimed to evaluate the physical and chemical stability of this admixture at high and low concentrations in 14 and 48 mL polypropylene syringes.METHODS: The stability of a low concentration admixture of clonidine (Catapressan 0.15 mg/mL, Boehringer Ingelheim, Germany) and morphine (morphine HCl 40 mg/mL, Sterop, Belgium) at 0.003 and 0.417 mg/mL, respectively, was evaluated by using five polypropylene syringes of 48 mL. The high concentration admixture consisted of 0.032 mg/mL clonidine and 4.286 mg/mL morphine HCl and was evaluated by using five polypropylene syringes of 14 mL. All syringes were stored for 30 days at 5°C±3°C. Periodic samples were visually and microscopically examined to observe any particle appearance or colour change. pH and absorbance at three wavelengths (350, 410 and 550 nm) were monitored. The concentrations were measured by ultra-high performance liquid chromatography-photodiode array detection.RESULTS: During the 30 days, there was no change in colour or appearance of opacity, turbidity or precipitation, and pH remained stable. The low and high concentration admixtures were considered chemically stable since the lower limit of the 90% CI remained superior to 90% of the initial concentration. Concentration measurements showed that the degradation rate was less than 1% over 10 days for each component in both admixtures.CONCLUSIONS: The admixture of clonidine and morphine HCl at low and high concentrations in polypropylene syringes appeared to be physically and chemically stable throughout the study period of 30 days at 5°C±3°C. In conclusion, the admixture can be prepared in advance under aseptic conditions by a centralised intravenous additive service in the pharmacy department.

Background : In a retrospective study in 4 Belgian hospitals, we showed that the use of linezolid (LZD) was larger and the rate of adverse drug reactions (ADRs) higher (especially anemia and thrombocytopenia) than described in the summary of product characteristics (1). Associated risk factors for ADRs were long treatment duration, renal impairment at the treatment initiation, and presence of comorbidities (evaluated by the Charlson index (2)). Moreover, literature suggests that trough levels (Cmin) > 9 mg/L increase the risk of hematological toxicity (HT) [...].

BACKGROUND: Despite recommendations to deprescribe chronic benzodiazepine receptor agonists (BZRA) among older adults, the prevalence of their use in Belgian nursing homes (NHs) remains above 50%. The use of a behavioral science approach, starting with the evaluation of barriers and enablers for BZRA deprescribing, has the potential to decrease BZRA prescribing. OBJECTIVES: To identify barriers and enablers for BZRA deprescribing perceived by the different stakeholders involved in nursing home care in Belgium. METHODS: In a purposive sample of 6 NHs, we conducted face-to-face interviews with general practitioners (GPs), and focus groups with other healthcare providers (HCPs), including nurses, pharmacists, occupational therapists, physical therapists, and with NH residents and relatives. All interviews with HCPs were analyzed through deductive thematic analysis, using the theoretical domains framework (TDF) as the coding framework. Residents' and relatives' interviews were analyzed using an inductive thematic approach. RESULTS: We interviewed 13 GPs, 35 other HCPs, 22 nursing home residents, and 5 relatives. Overall, 9 TDF domains were identified as most relevant among HCPs interviewed: Skills, Beliefs about capabilities, Goals, Memory attention and decision processes, Environmental context and resources, Social influences, Knowledge, Social/professional role and identity, and Beliefs about consequences. Five additional themes emerged from residents' and relatives' interviews: knowledge on medications used, communication with NH staff and GPs, perceived efficacy and necessity of BZRA, influence of the environment, and reluctance towards BZRA deprescribing. Some domains and themes differ between stakeholders (e.g., knowledge), while others match between groups (e.g., environmental aspects). CONCLUSION: BZRA deprescribing is influenced by knowledge and skills gaps, automatic BZRA refilling, competing priorities, social challenges, environmental factors and poor nursing home residents involvement. Targeting these barriers will be a key step for implementation of BZRA deprescribing. ispartof: Explor Res Clin Soc Pharm vol:9 issue:March 2023 pages:100258- ispartof: location:United States status: Published online

Background Diabetes overtreatment is a frequent and severe issue in multimorbid older patients with type 2 diabetes (T2D). Objective This study aimed at assessing the association between diabetes overtreatment and 1-year functional decline, hospitalisation and mortality in older inpatients with multimorbidity and polypharmacy. Methods Ancillary study of the European multicentre OPERAM project on multimorbid patients aged ≥70 years with T2D and glucose-lowering treatment (GLT). Diabetes overtreatment was defined according to the 2019 Endocrine Society guideline using HbA1c target range individualised according to the patient’s overall health status and the use of GLT with a high risk of hypoglycaemia. Multivariable regressions were used to assess the association between diabetes overtreatment and the three outcomes. Results Among the 490 patients with T2D on GLT (median age: 78 years; 38% female), 168 (34.3%) had diabetes overtreatment. In patients with diabetes overtreatment as compared with those not overtreated, there was no difference in functional decline (29.3% vs 38.0%, P = 0.088) nor hospitalisation rates (107.3 vs 125.8/100 p-y, P = 0.115) but there was a higher mortality rate (32.8 vs 21.4/100 p-y, P = 0.033). In multivariable analyses, diabetes overtreatment was not associated with functional decline nor hospitalisation (hazard ratio, HR [95%CI]: 0.80 [0.63; 1.02]) but was associated with a higher mortality rate (HR [95%CI]: 1.64 [1.06; 2.52]). Conclusions Diabetes overtreatment was associated with a higher mortality rate but not with hospitalisation or functional decline. Interventional studies should be undertaken to test the effect of de-intensifying GLT on clinical outcomes in overtreated patients.

Introduction: Multimorbidity and polypharmacy are risk factors for drug-related hospital admissions (DRAs) in the ageing population. DRAs caused by medication errors (MEs) are considered potentially preventable. The STOPP/START criteria were developed to detect potential MEs in older people. Objective: The aim of this study was to assess the detectability of MEs with a STOPP/START-based in-hospital medication review in older people with polypharmacy and multimorbidity prior to a potentially preventable DRA. Methods: Hospitalised older patients (n = 963) with polypharmacy and multimorbidity from the intervention arm of the OPERAM trial received a STOPP/START-based in-hospital medication review by a pharmacotherapy team. Readmissions within 1 year after the in-hospital medication review were adjudicated for drug-relatedness. A retrospective assessment was performed to determine whether MEs identified at the first DRA were detectable during the in-hospital medication review. Results: In total, 84 of 963 OPERAM intervention patients (8.7%) were readmitted with a potentially preventable DRA, of which 72 patients (n = 77 MEs) were eligible for analysis. About half (48%, n = 37/77) of the MEs were not present during the in-hospital medication review and therefore were not detectable at that time. The pharmacotherapy team recommended a change in medication regimen in 50% (n = 20/40) of present MEs, which corresponds to 26% (n = 20/77) of the total identified MEs at readmission. However, these recommendations were not implemented. Conclusion: MEs identified at readmission were not addressed by a prior single in-hospital medication review because either these MEs occurred after the medication review (~50%), or no recommendation was given during the medication review (~25%), or the recommendation was not implemented (~25%). Future research should focus on optimisation of the timing and frequency of medication review and the implementation of proposed medication recommendations. Registration: ClinicalTrials.gov identifier: NCT02986425. December 8, 2016. Funding: European Union HORIZON 2020, Swiss State Secretariat for Education, Research and Innovation (SERI), Swiss National Science Foundation (SNSF) Graphical abstract: [Figure not available: see fulltext.].

BackgroundA patient-centred approach to medicines optimisation is considered essential. The OPtimising thERapy to prevent Avoidable hospital admissions in Multimorbid older people (OPERAM) trial evaluated the effectiveness of medication review with shared decision-making (SDM) in older people with multimorbidity. Beyond evaluating the clinical effectiveness, exploring the patient experience facilitates a better understanding of contextual factors and mechanisms affecting medication review effectiveness.ObjectiveTo explore experiences of hospital-initiated medication changes in older people with multimorbidity.MethodsWe conducted a multicentre mixed-methods study, embedded in the OPERAM trial, combining semi-structured interviews and the Beliefs about Medicines Questionnaire (BMQ) with a purposive sample of 48 patients (70–94 years) from four European countries. Interviews were analysed using the Framework approach. Trial implementation data on SDM were collected and the 9-item SDM questionnaire was conducted with 17 clinicians.ResultsPatients generally displayed positive attitudes towards medication review, yet emphasised the importance of long-term, trusting relationships such as with their general practitioners for medication review. Many patients reported a lack of information and communication about medication changes and predominantly experienced paternalistic decision-making. Patients’ beliefs that ‘doctors know best’, ‘blind trust’, having limited opportunities for questions, use of jargon terms by clinicians, ‘feeling too ill’, dismissive clinicians, etc highlight the powerlessness some patients felt during hospitalisation, all representing barriers to SDM. Conversely, involvement of companions, health literacy, empathetic and trusting patient-doctor relationships, facilitated SDM. Paradoxical to patients’ experiential accounts, clinicians reported high levels of SDM. The BMQ showed that most patients had high necessity and low concern beliefs about medicines. Beliefs about medicines, experiencing benefits or harms from medication changes, illness perception, trust and balancing advice between different healthcare professionals all affected acceptance of medication changes.ConclusionTo meet patients’ needs, future medicines optimisation interventions should enhance information exchange, better prepare patients and clinicians for partnership in care and foster collaborative medication reviews across care settings.

BackgroundMany strategies aimed at deprescribing benzodiazepine receptor agonists (BZRA) in older adults have already been evaluated with various success rates. There is so far no consensus on which strategy components increase deprescribing the most. Yet, despite an unfavourable benefit-to-risk ratio, BZRA use among older adults remains high. We systematically reviewed barriers and enablers for BZRA deprescribing in older adults.MethodsTwo reviewers independently screened records identified from five electronic databases—Medline, Embase, PsycINFO, CINAHL and the Cochrane library—and published before October 2020. They searched for grey literature using Google Scholar. Qualitative and quantitative records reporting data on the attitudes of older adults, caregivers and healthcare providers towards BZRA deprescribing were included. Populations at the end of life or with specific psychiatric illness, except for dementia, were excluded. The two reviewers independently assessed the quality of the included studies using the mixed-methods appraisal tool. Barriers and enablers were identified and then coded into domains of the theoretical domains framework (TDF) using a combination of deductive and inductive qualitative analysis. The most relevant TDF domains for BZRA deprescribing were then identified.ResultsTwenty-three studies were included 13 quantitative, 8 qualitative and 2 mixed-method studies. The points of view of older adults, general practitioners and nurses were reported in 19, 9 and 3 records, respectively. We identified barriers and enablers in the majority of TDF domains and in two additional themes: “patient characteristics” and “BZRA prescribing patterns”. Overall, the most relevant TDF domains were “beliefs about capabilities”, “beliefs about consequences”, “environmental context and resources”, “intention”, “goals”, “social influences”, “memory, attention and decision processes”. Perceived barriers and enablers within domains differed across settings and across stakeholders.ConclusionThe relevant TDF domains we identified can now be linked to behavioural change techniques to help in the design of future strategies and health policies. Future studies should also assess barriers and enablers perceived by under-evaluated stakeholders (such as pharmacists, psychiatrists and health care professionals in the hospital setting).Trial registrationThis work was registered on PROSPERO under the title “Barriers and enablers to benzodiazepine receptor agonists deprescribing”. Registration number:CRD42020213035

Gemcitabine is an analogue of cytidine arabinoside, used alone or in combination chemotherapy to treat various type of cancer. The dose-banding of gemcitabine provides the opportunity to anticipate the preparation of this anticancer drug on condition of carrying out stability studies. The aim of this study is to develop and validate a stability-indicating ultra-high-performance Liquid Chromatography (UHPLC) method for measuring the concentration of gemcitabine and to evaluate its stability at standardised rounded doses in polyolefin bags. The UHPLC with photodiode array (PDA) detector method was developed and validated (linearity, precision, accuracy, limits of detection and quantification, robustness and degradation test). Thirty polyolefin bags of gemcitabine (1600 mg/292 ml (n = 10), 1800 mg/297 ml (n = 10) and 2000 mg/303 ml (n = 10)) were prepared under aseptic conditions and stored at 5 ± 3 °C and 23 ± 2 °C for 49 days. Physical stability tests were periodically performed: visual and microscopic inspection and optical densities. The chemical stability was evaluated through pH monitoring and chromatographic assays. The results confirm the stability of Gemcitabine at selected standardised rounded doses of 1600 mg, 1800 mg and 2000 mg in NaCl 0.9% polyolefin bags for at least 49 days at 5 ± 3 °C and 23 ± 2 °C, allowing in-advance preparation.

Management of chemotherapies is a strategic issue for european healthcare. Dose-banding enables to reduce waiting time of patients in day care units and drug wastage. The aim of this study was to assess the stability of 5-Fluorouracile (5-FU) at standardised rounded doses of 4 and 5 g in MyFuser® portable infusion pump for in-advance preparation. Ten MyFuser® (4 and 5 gr 5-FU added to NaCl 0.9%) were prepared under aseptic conditions and stored at room temperature (23 ± 2 °C) for 28 days then at 30 °C for three days. Physical stability tests were periodically performed: visual and microscopic inspection, pH measurements and optical densities. The concentration of solutions was measured by High Performance Liquid Chromatography/UV detector. Results confirm the stability of 5-FU at selected SRD of 4 g and 5 g with NaCl 0.9% in MyFuser® for at least 28 days at room temperature and three days at 30 °C, allowing in-advance preparation.

BACKGROUND Identifying patients at high risk of drug-related hospital admission (DRA) may help to efficiently target preventive interventions. We developed a score to predict DRAs in older patients with multimorbidity and polypharmacy. METHODS We used participants from the multicenter European OPERAM trial ("Optimising PharmacothERapy in the Mutlimorbid Elderly"). We assessed the association between easily identifiable predictors and 1-year DRAs by univariable logistic regression. Variables with p-value3 points had a 40.4% predicted and 38.9% observed risk of DRA. The scaled Brier score was 0.05. Calibration showed an adequate match between predicted and observed proportions. CONCLUSION Comorbidities related to drug metabolism, specific medications, non-elective admission, and a history of hospitalization, were associated with a higher risk of DRA. Awareness of these associations and the score we developed may help identify patients most likely to benefit from preventive interventions.

Key summary points Aim This review aimed to identify, describe and discuss different interventions targeting medication use optimization in nursing homes and to identify research gaps. Finding Prescription of the whole medication regimen or of specific medication classes was the most studied aspect. Medication review and multidisciplinary approaches appeared to be effective strategies in reducing appropriate use, but further large-scale randomized trials are needed. Messages Efforts to optimize medication use among nursing home residents are still needed and should focus on less evaluated intervention components, specific medication classes and medication use aspects not related to prescribing., Purpose Polypharmacy, medication errors and adverse drug events are frequent among nursing home residents. Errors can occur at any step of the medication use process. We aimed to review interventions aiming at optimization of any step of medication use in nursing homes. Methods We narratively reviewed quantitative as well as qualitative studies, observational and experimental studies that described interventions, their effects as well as barriers and enablers to implementation. We prioritized recent studies with relevant findings for the European setting. Results Many interventions led to improvements in medication use. However, because of outcome heterogeneity, comparison between interventions was difficult. Prescribing was the most studied aspect of medication use. At the micro-level, medication review, multidisciplinary work, and more recently, patient-centered care components dominated. At the macro-level, guidelines and legislation, mainly for specific medication classes (e.g., antipsychotics) were employed. Utilization of technology also helped improve medication administration. Several barriers and enablers were reported, at individual, organizational, and system levels. Conclusion Overall, existing interventions are effective in optimizing medication use. However there is a need for further European well-designed and large-scale evaluations of under-researched intervention components (e.g., health information technology, patient-centered approaches), specific medication classes (e.g., antithrombotic agents), and interventions targeting medication use aspects other than prescribing (e.g., monitoring). Further development and uptake of core outcome sets is required. Finally, qualitative studies on barriers and enablers for intervention implementation would enable theory-driven intervention design.

The physico-chemical stability of an injectable preparation (IV) is conditioned by different parameters. A collaboration between the pharmacy, the chemistry laboratory and the statisticians of the scientific support unit was established in 1996, in order to carry out long-term chemical stability studies of commonly used IVs and to be able to take charge of their preparation in pharmacy. In 24 years of activity, the Drug Stability Research Group (DSRG) tested 39 IV at different concentration and temperature of storage. The DSRG has organized an annual symposium since 2015. The theme of the 2019 edition was devoted to the robotization of injectable reconstitution operations, focused on their impact on the workplace and the existing equipment.

Background Chemotherapy doses are usually prescribed on the basis of body surface area but dose banding is emerging as an efficient alternative. Dose banding presents the possibility of in-advance preparation in a Centralized Intravenous Admixture Service. Aim of the study To evaluate the long-term stability of 5-fluorouracil at banded doses (700 mg and 800 mg) in polyolefin bags. Materials and methods Ten polyolefin bags were prepared under aseptic conditions and stored at 23 ± 2°C for 24 days. Five of them were composed of 14 mL 5-fluorocuracil (700 g) in 100 mL 0.9% sodium chloride solution and the five other of 16 mL 5-fluorouracil (800 mg) in 100 mL 0.9% sodium chloride solution. At defined times, physical stability parameters were assessed: optical densities, pH measurements, visual and microscopical inspections. Solutions concentrations were measured using high-performance liquid chromatography coupled with a photodiode array detector. Results No change was observed on pH and optical density measurements during the study period. Visual and microscopical inspections remained free of colour change, precipitate, microagregate or crystal. The concentrations of 5-Fluorouracil in 800 mg bags remained stable for 24 days while the concentration in 700 mg bags showed a stability of at least 17 days. Conclusion Five-fluorouracil at banded doses of 700 and 800 mg in polyolefin bags is physicochemically stable for at least 17 days at 23 ± 2°C. These results support the possibility of in advance centralised preparation.

Objectives: We identified factors associated with healthcare costs and health-related quality of life (HRQoL) of multimorbid older adults with polypharmacy. Methods: Using data from the OPERAM (OPtimising thERapy to prevent Avoidable hospital admissions in the Multimorbid older people) trial, we described the magnitude and composition of healthcare costs, and time trends of HRQoL, during 1-year after an acute-care hospitalization. We performed a cluster analysis to identify groups with different cost and HRQoL trends. Using multilevel models, we also identified factors associated with costs and HRQoL. Results: Two months after hospitalization monthly mean costs peaked (CHF 7′124) and HRQoL was highest (0.67). They both decreased thereafter. Age, falls, and comorbidities were associated with higher 1-year costs. Being female and housebound were negatively associated with HRQoL, while moderate alcohol consumption had a positive association. Being independent in daily activities was associated with lower costs and higher HRQoL. Conclusion: Although only some identified potential influences on costs and HRQoL are modifiable, our observations support the importance of prevention before health deterioration in older people with multimorbid illness and associated polypharmacy.

No abstract available

BACKGROUND AND AIM Clonidine is frequently combined to opioids for the management of chronic pain. The aim of this study was to evaluate the physical stability of this combination at high and low concentrations in polypropylene syringes at 5±3°C and at 22±3°C. METHODS Five syringes with low concentration of clonidine (0.003 mg/mL) and morphine hydrochloride (0.417 mg/mL) and five syringes with high concentration of clonidine (0.032 mg/mL)and morphine hydrochloride (4.286 mg/mL) were evaluated. The turbidity, the pH and the crystal formation were controlled after the production and until 72h post-production. RESULTS No changes in color or appearance of opacity or turbidity were observed. Spectrophotometric measurements (at 350, 410 and 550 nm) and pH were not affected. The microscopic analysis did not detect any aggregate or crystal formation. DISCUSSION AND CONCLUSION The mixture of clonidine and morphine hydrochloride at low and high concentrations is physically stable for at least 72 hours post-production at 5±3°C and at 22±3°C. These results paved the way for a subsequent chemical stability study.

Background identifying drug-related hospital admissions (DRAs) in older people is difficult. A standardised chart review procedure has recently been developed. It includes an adjudication team (physician and pharmacist) screening using 26 triggers and then performing causality assessment to determine whether an adverse drug event (ADE) occurred (secondary to an adverse drug reaction, overuse, misuse or underuse) and whether the ADE contributed to hospital admission (DRA). Objective to assess the performance of those triggers in detecting DRA. Design retrospective study using data from the OPERAM (OPtimising thERapy to prevent Avoidable hospital admissions in Multimorbid older people) trial. Settings four European medical centres. Subjects multimorbid (≥ 3 chronic medical conditions) older (≥ 70 years) inpatients with polypharmacy (≥ 5 chronic medications) were enrolled in the OPERAM trial (N = 2,008) and followed for 12 months. We included patients with ≥1 adjudicated hospitalisation during the follow-up. Methods the positive predictive value (PPV; number of DRAs identified by trigger/number of triggers) was calculated for each trigger and for the tool as a whole. Results of 1,235 hospitalisations adjudicated for 832 patients, 716 (58%) had at least one trigger; an ADE was identified in 673 (54%) and 518 (42%) were adjudicated as DRAs. The overall PPV of the trigger tool for detecting DRAs was 0.66 [0.62–0.69]. Conclusions this tool performs well for identifying DRAs in older people. Based on our results, a revised version of the tool was proposed but will require external validation before it can be incorporated into research and clinical practice.

Death rattle, which could often be associated with a pulmonary fluid overload, occurs in 25% to 90% of dying patients. The co-administration of scopolamine (anticholinergic drug)and bumetanide (loop diuretic) could be considered in order to avoid unnecessary fluid overload at end-stage of life. The objective of this study was to investigate the physical and chemical stabilities of the admixture bumetanide and scopolamine in order to prepare them in advance by a centralized intravenous additive service in-hospital pharmacy. The stability of the lowest (LOW)concentration was evaluated on five polypropylene syringes containing the admixture bumetanide (Burinex, 2 mg/4 mL) and scopolamine (0.25 mg/mL) at 41.67 µg/mL and 5.21 µg/mL. The highest (HIGH) concentration with 125 µg/mL of bumetanide and 31.25 µg/mL of sc opolamine was evaluated on five polypropylene syringes. Ali syringes were stored for 18 days at 5°C ± 3°C. Periodic samples were visually and microscopically examined to observe any particle appearance or color change.The pH and absorbance at 3 wavelengths (350 nm, 410 nm, and 550 nm) were monitored. The concentrations were measured by ultra-high-performance liquid chromatography-photodiode array detection, using a newly developed method.During the 18 days of test, there was no change in color or appearance of opacity, turbidity, or precipitation, and the pH remained stable. Mean concentrations of bumetanide and scopolamine at LOW and HIGH concentrations after 18 days remained statistically unchanged. The lower limits of the 95% confidence intervals of molecules at LOW and HIGH concentrations remained higher than a 90% threshold of concentration thus considering the mixture chemically stable. Degradation rates of bumetanide and scopolamine content at LOW and HIGH concentration should not exceed a maximum of 0.70% every 10 days. This study was the first one to show that the admixture of bumetanide and scopolamine is physically and chemically stable at two concentrations used in a palliative-care unit. This combination available in ready-to-use polypropylene syringes presents numerous advantages for patient's comfort and safety.

Purpose Successful deprescribing requires understanding the attitudes of older adults and caregivers towards this process. This study aimed to capture these attitudes in four French-speaking countries, and to investigate associated factors. Methods A multicenter cross-sectional study was conducted by administrating the French version of the revised Patients’ Attitudes Towards Deprescribing (rPATD) questionnaire in Belgium, Canada, France and Switzerland. Community-dwelling or nursing home older adults ≥ 65 years taking ≥ 1 prescribed medications, and caregivers of older adults with similar characteristics were included. Multivariate logistic regressions were carried out to examine factors associated with willingness to deprescribe. Results A total of 367 older adults (79.3 ± 8.7 years, 63% community-dwelling, 54% ≥5 medications) and 255 unrelated caregivers (64.4 ± 12.6 years) of care recipients (83.4 ± 7.9 years, 52% community-dwelling, 69% ≥5 medications) answered the questionnaire. Among them, 87.5% older adults and 75.6% caregivers would be willing to stop medications if the physician said it was possible. Reluctance to stop a medication taken for a long time was expressed by 46% of both older adults and caregivers. A low score for the factor “concerns about stopping” [older adults: aOR: 0.21; 95%CI: 0.07–0.59], and a high score for the factor “involvement” [older adults: aOR: 2.66; 95%CI: 1.01–7.07; caregivers: aOR: 11.28; 95%CI: 1.48–85.91] were associated with willingness to deprescribe. Conclusions A significant proportion of older adults and caregivers of French speaking countries are open to deprescribing. Despite this apparent willingness, deprescribing conversations in clinical practice remains marginal, emphasizing the importance of optimizing the integration of existing tools such as rPATD.

Background Benzodiazepine receptor agonist (BZRA) use is highly prevalent in hospitalised older people although these drugs are associated with numerous and serious adverse events. Deprescribing can reduce risks associated with chronic BZRA use. The aim of this study was to measure the prevalence of, and factors associated with, BZRA deprescribing in acute geriatric units. Methods During a one-year period, this multicentre retrospective study included patients aged ≥70 years, hospitalised in acute geriatric units, and using ≥1 BZRA on admission. BZRA deprescribing at discharge was defined as: ≥25% decrease in lorazepam-equivalent admission dose; discontinuation of all BZRAs; or cessation of a rescue prescription at discharge. BZRA cessation was defined as discontinuation of all BZRAs at discharge. We identified social, medical, geriatric and medication factors associated with BZRA deprescribing using logistic regression. Results In total, 561 patients were included (mean age: 85.3±5.9 years, 70% of women). BZRA deprescribing occurred in 240 (42.8%), including 85 with BZRA cessation (15.2%). Deprescribing occurred more frequently in patients with a BZRA-related adverse event on admission or during hospital stay (odds ratio (OR) 4.5; 95% confidence interval [2.6; 7.9]), with an antidepressant (1.6 [1.1; 2.4]) and a higher lorazepam-equivalent dosage on admission (OR 1.2 [1; 1.4]), and less frequently in patients with antipsychotic drug (OR 0.5 [0.3; 0.8]). BZRA cessation was more likely in patients with a BZRA-related adverse event (OR 2.2 [1.2; 4.3]) and a lower lorazepam-equivalent dosage on admission (OR 0.5 [0.3; 0.6]). Conclusions During hospitalisation in the acute geriatric units of our hospital, BZRA deprescribing occurred in 42.8% of the patients. Identification of an BZRA-related adverse event by the treating physician appears to be a major factor: this reactive deprescribing accounted for 74% of cases in our study. Further prospective studies are needed to measure long-term persistence of in-hospital deprescribing and encourage proactive management.

Most patients present for catheter ablation of atrial fibrillation (CAAF) with residual or full effect of vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs). In daily practice, it has been observed that the activated clotting time (ACT) was actually poorly sensitive to the effect of DOACs and that patients on DOACs required more unfractionated heparin (UFH) to achieve the ACT target of 300 s during the procedure, leading some authors to worry about potential overdosing. Conversely, we hypothesize that these higher doses of UFH are necessary to achieve adequate hemostasis during CAAF regardless of the residual effect of DOACs. During CAAF, thrombosis is promoted mainly by the presence of thrombogenic sheaths and catheters in the bloodstream. Preclinical data suggest that only high doses of DOACs are able to mitigate catheter-induced thrombin generation, whereas low dose UFH already do so. In addition, the effect of UFH seems to be lower in patients on DOACs, compared to patients on VKAs, explaining part of the differences observed in heparin requirements. Clinical studies could not identify increased bleeding risk in patients on DOACs compared to those on VKAs despite similar efficacy during CAAF procedures. Moreover, targeting a lower ACT was associated with an increased periprocedural thrombotic risk for both DOAC and VKA patients. Therefore, the low sensitivity of the ACT to the residual effect of DOACs should not be a major concern in its use in the interventional cardiology laboratory.

BACKGROUND: Older patients are regularly exposed to multiple medication changes during a hospital stay and are more likely to experience problems understanding these changes. Medication counselling is often proposed as an important component of seamless care to ensure appropriate medication use after hospital discharge. OBJECTIVES: The purpose of this systematic review was to describe the components of medication counselling in older patients (aged ≥ 65 years) prior to hospital discharge and to review the effectiveness of such counselling on reported clinical outcomes. METHODS: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology (PROSPERO CRD42019116036), a systematic search of MEDLINE, EMBASE and CINAHL was conducted. The QualSyst Assessment Tool was used to assess bias. The impact of medication counselling on different outcomes was described and stratified by intervention content. RESULTS: Twenty-nine studies were included. Fifteen different components of medication counselling were identified. Discussing the dose and dosage of patients' medications (19/29; 65.5%), providing a paper-based medication list (19/29; 65.5%) and explaining the indications of the prescribed medications (17/29; 58.6%) were the most frequently encountered components during the counselling session. Twelve different clinical outcomes were investigated in the 29 studies. A positive effect of medication counselling on medication adherence and medication knowledge was found more frequently, compared to its impact on hard outcomes such as hospital readmissions and mortality. Yet, evidence remains inconclusive regarding clinical benefit, owing to study design heterogeneity and different intervention components. Statistically significant results were more frequently observed when counselling was provided as part of a comprehensive intervention before discharge. CONCLUSIONS: Substantial heterogeneity between the included studies was found for the components of medication counselling and the reported outcomes. Study findings suggest that medication counselling should be part of multifaceted interventions, but the evidence concerning clinical outcomes remains inconclusive.

Introduction: Estimation of residual apixaban plasma concentrations may be requested in the management of emergencies. This study aims at assessing the performance of specific anti-Xa assays calibrated with apixaban on real-life samples with low apixaban plasma concentrations (®-Liquid Anti-Xa assay (STA ® LAX) and the low and normal procedures of the Biophen ®Direct Factor Xa Inhibitors (DiXaI) assay was tested on 134 blood samples, collected from patients on apixaban, wherefrom 74 patients received LMWH after apixaban cessation. The results were compared with the liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) measurements. Results: The Biophen ®DiXaI, Biophen ®DiXaI LOW, and STA ®LAX showed very good correlation with LC-MS/MS measurements in patients without LMWH administration (Spearman r.95,.99, and.98, respectively). Their limits of quantitation were defined at 48, 24, and 12 ng/mL, respectively. The Bland-Altman test measured mean bias (SD) at 5.6 (13.1), −2.5 (5.0), and −0.8 (6.1) ng/ml, respectively. The Spearman r of the Biophen ®DiXaI decreased to 0.64 in presence of low apixaban concentrations. The Spearman r of the Biophen ®DiXaI LOW and STA ®LAX decreased to 0.39 and 0.26, respectively, in presence of LMWH. Conclusions: The accuracy of the low methodologies (Biophen ®DiXaI LOW and STA ®LAX) is slightly improved for low apixaban plasma concentrations, compared with the normal procedure of Biophen ®DiXaI. The interference of LMWH on the low methodologies is measurable, however, less important than the previously reported interference of LMWH on rivaroxaban calibrated specific anti-Xa assays.

BackgroundInappropriate polypharmacy has been linked with adverse outcomes in older, multimorbid adults. OPERAM is a European cluster-randomized trial aimed at testing the effect of a structured pharmacotherapy optimization intervention on preventable drug-related hospital admissions in multimorbid adults with polypharmacy aged 70 years or older. Clinical results of the trial showed a pattern of reduced drug-related hospital admissions, but without statistical significance. In this study we assessed the cost-effectiveness of the pharmacotherapy optimisation intervention.MethodsWe performed a pre-planned within-trial cost-effectiveness analysis (CEA) of the OPERAM intervention, from a healthcare system perspective. All data were collected within the trial apart from unit costs. QALYs were computed by applying the crosswalk German valuation algorithm to EQ-5D-5L-based quality of life data. Considering the clustered structure of the data and between-country heterogeneity, we applied Generalized Structural Equation Models (GSEMs) on a multiple imputed sample to estimate costs and QALYs. We also performed analyses by country and subgroup analyses by patient and morbidity characteristics.ResultsTrial-wide, the intervention was numerically dominant, with a potential cost-saving of CHF 3’588 (95% confidence interval (CI): -7’716; 540) and gain of 0.025 QALYs (CI: -0.002; 0.052) per patient. Robustness analyses confirmed the validity of the GSEM model. Subgroup analyses suggested stronger effects in people at higher risk.ConclusionWe observed a pattern towards dominance, potentially resulting from an accumulation of multiple small positive intervention effects. Our methodological approaches may inform other CEAs of multi-country, cluster-randomized trials facing presence of missing values and heterogeneity between centres/countries.

Background: The revised Patients’ Attitudes Towards Deprescribing (rPATD) questionnaire allows capture of the beliefs and attitudes of older adults and caregivers towards deprescribing. Objectives: To translate and validate the rPATD questionnaire into French. Methods: The French rPATD was translated using forward-backward translation. Psychometric properties were evaluated in both older adults ≥65 years living in the community or in institutions and who were taking at least one chronic medication and in caregivers of older adults with similar characteristics. Participants were recruited in four French-speaking countries (Belgium, Canada, France and Switzerland). Face and content validity were assessed during the translation process. Construct validity (exploratory factor analysis (EFA)) and internal consistency (Cronbach's alpha) were investigated in questionnaires without missing data. Test-retest reliability was evaluated using intra-class correlation coefficient (ICC) in a sample of participants. Results: In total, 320 questionnaires from older adults and 215 questionnaires from caregivers were included to evaluate construct validity and internal consistency. EFA extracted four factors in the older adults' and caregivers' versions of the questionnaire consistent with the English rPATD. The extracted factors related to the perceived burden of medication taking, the beliefs in appropriateness of medications, concerns about stopping medications and the level of involvement in making decisions and of knowledge of medications. Internal consistency was satisfactory for three factors for both versions (Cronbach's alpha >0.70), with lower internal consistency in the concerns about stopping factor. Test-retest reliability was overall good for all factors in the caregivers' version (ICC > 0.75) while for the older adults' version, moderate (ICC range: 0.75–0.50) to good ICC values were found. Conclusions: The French rPATD presents globally good psychometric properties and can be used to explore attitudes towards deprescribing in French-speaking older adults and caregivers. Refereed/Peer-reviewed

Objective To examine the effect of optimising drug treatment on drug related hospital admissions in older adults with multimorbidity and polypharmacy admitted to hospital. Design Cluster randomised controlled trial. Setting 110 clusters of inpatient wards within university based hospitals in four European countries (Switzerland, Netherlands, Belgium, and Republic of Ireland) defined by attending hospital doctors. Participants 2008 older adults (≥70 years) with multimorbidity (≥3 chronic conditions) and polypharmacy (≥5 drugs used long term). Intervention Clinical staff clusters were randomised to usual care or a structured pharmacotherapy optimisation intervention performed at the individual level jointly by a doctor and a pharmacist, with the support of a clinical decision software system deploying the screening tool of older person’s prescriptions and screening tool to alert to the right treatment (STOPP/START) criteria to identify potentially inappropriate prescribing. Main outcome measure Primary outcome was first drug related hospital admission within 12 months. Results 2008 older adults (median nine drugs) were randomised and enrolled in 54 intervention clusters (963 participants) and 56 control clusters (1045 participants) receiving usual care. In the intervention arm, 86.1% of participants (n=789) had inappropriate prescribing, with a mean of 2.75 (SD 2.24) STOPP/START recommendations for each participant. 62.2% (n=491) had ≥1 recommendation successfully implemented at two months, predominantly discontinuation of potentially inappropriate drugs. In the intervention group, 211 participants (21.9%) experienced a first drug related hospital admission compared with 234 (22.4%) in the control group. In the intention-to-treat analysis censored for death as competing event (n=375, 18.7%), the hazard ratio for first drug related hospital admission was 0.95 (95% confidence interval 0.77 to 1.17). In the per protocol analysis, the hazard ratio for a drug related hospital admission was 0.91 (0.69 to 1.19). The hazard ratio for first fall was 0.96 (0.79 to 1.15; 237 v 263 first falls) and for death was 0.90 (0.71 to 1.13; 172 v 203 deaths). Conclusions Inappropriate prescribing was common in older adults with multimorbidity and polypharmacy admitted to hospital and was reduced through an intervention to optimise pharmacotherapy, but without effect on drug related hospital admissions. Additional efforts are needed to identify pharmacotherapy optimisation interventions that reduce inappropriate prescribing and improve patient outcomes. Trial registration ClinicalTrials.gov NCT02986425 .

Purpose The concomitant use of direct oral anticoagulants (DOAC) and strong P-glycoprotein (P-gp) and cytochrome P450 3A4 (CYP3A4) inducers may lead to reduced DOAC levels and therapeutic failure. This study aimed to describe DOAC concentrations in patients receiving strong P-gp and CYP3A4 inducers, in relation to individual risk factors for high or low DOAC levels. Methods We retrospectively identified hospitalized patients simultaneously receiving a DOAC and carbamazepine, phenobarbital, phenytoin, or rifampicin between 2016 and 2021. Among them, patients who underwent DOAC measurement at steady state were included. DOAC peak or trough levels were compared with on-therapy ranges observed in pivotal trials. Individual risk factors for high or low DOAC levels were identified. Results We included 17 patients (median age 75 years), mainly receiving apixaban and carbamazepine. For 5 patients (29%), DOAC trough or peak level was below the expected range. Among the remaining 12 patients, 8 had at least one measurement in the lower quartile of the range. The median number of risk factors for drug accumulation was 0 (range 0-1) in patients with ≥1 measurement below the range and 2 (range 0-3) in other patients. DOAC measurement led to treatment adjustments in 9 patients (DOAC dose increase or switch). Conclusion Our data suggest a significant risk of reduced DOAC levels in patients taking strong P-gp and CYP3A4 inducers, especially those without risk factors for drug accumulation. DOAC measurement could help manage this relevant drug–drug interaction.

Automated compounding systems appeared on the market during these last 15 years as an alternative for manual compounding of intravenous (IVD) drugs. A literature review was conducted on reconstitution of IVD. The following methods were identified: manual, semi- automatic and automatic. A classification was carried out in three categories: automatic syringes, peristaltic pumps, and compounding doses robots. The number of compounding robots is increasing. A table describes the different features of each device. The ampuls cannot be supported by these robots. Large doses vials improve the time of reconstitution compared to current dosage vials. Advantages of automated preparation are: higher consistency of process and products, higher accuracy of products, Integrated digitized processing, precise, complete documentation, reduced effort and wrist injuries, reduced personnel requirement, increased worker satisfaction. Disadvantages of automated preparation are: risk of failure/down time, dependency on power supply, software (updates), high investment costs/high maintenance costs, specialized personnel with additional training, decreased worker satisfaction (early adopter), complexity when products are switched or added, potential for new errors. This review allows the potential user to know the current availability on the market.

Background: Thrombin generation testing has been used to provide information on the coagulation phenotype of patients. The most used technique is the calibrated automated thrombogram (CAT) but it suffers from a lack of standardization, preventing its implementation in routine. The ST Genesia is a new analyzer designed to assess thrombin generation based on the same principle as the CAT. Unlike the CAT system, the ST Genesia is a benchtop, fully automated analyzer, able to perform the analyses individually and not by batch, with strict control of variables such as temperature and volumes, ensuring, theoretically, maximal reproducibility. Objectives: This study aimed at assessing the performance of the STG-DrugScreen application on the ST Genesia analyzer. We also aimed at exploring stability of plasma samples after freezing and defining a reference normal range. Results: Results demonstrated the excellent interexperiment precision of the ST Genesia and confirmed that the use of a reference plasma helps reducing the inter-experiments variability. Stability revealed that plasma samples are stable for at least 11 months at −70°C or lower, except for those containing low molecular weight heparins which have to be tested within 6 months. Freezing had no effect on the majority of thrombin generation parameters except on time to peak. Conclusions: Our results suggest an easy implementation of thrombin generation with the use of ST Genesia in the routine laboratory. This will facilitate the design of multicentric studies and enable the establishment of reliable and evidence-based thresholds, which may improve the management of patients treated with anticoagulants.

Background and Objective: Infusion containing lorazepam is used by geriatric department to limit anxiety disorders in the elderly. Currently, these infusions are prepared according to demand by the nursing staff, but the preparation in advance in a centralized service could improve quality of preparation and time management. The aim of this study was to investigate the long-term stability of this infusion in polypropylene syringes stored at 5 ± 3°C. Then, results obtained were compared with stability data of lorazepam in syringes stored at room temperature, glass bottles at 5 ± 3°C, and glass bottles at room temperature. Method: Eight syringes and 6 bottles of infusion were prepared by diluting 1 mL lorazepam 4 mg in 23 mL of NaCl 0.9% under aseptic conditions. Five syringes and 3 bottles were stored at 5 ± 3°C and 3 syringes and 3 bottles were stored at room temperature for 30 days. During the storage period, particle appearance or color change were periodically checked by visual and microscope inspection. Turbidity was assessed by measurements of optical density (OD) at 3 wavelengths (350 nm, 410 nm, 550 nm). The stability of pH was also evaluated. The lorazepam concentrations were measured at each time point by high-performance liquid chromatography with ultraviolet detector at 220 nm. Results: Solutions were physically unstable in syringes at 5 ± 3°C after 4 days: crystals and a drop of OD at 350 nm were observed. However, pH was stable. After 2 days, solutions were considered as chemically unstable because a loss of lorazepam concentration higher than 10% was noticed: the lower 1-sided confidence limit at 95% was below 90% of the initial concentration. To assess temperature and polypropylene influence, results were compared with those obtained for syringes at room temperature and bottles at 5 ± 3°C and room temperature. Precipitation, drop of OD at 350 nm, and chemical instability were observed in all conditions. Conclusion: Solutions of lorazepam were unstable after 2 days in syringes at 5 ± 3°C. Preparation in advance appears, therefore, not possible for the clinical use. Storage conditions (temperature and form) do not improve the stability.

Objectives We aimed to establish an explicit list of potentially clinically significant drug-drug interactions (DDIs) in people aged ≥65 years. Design A preliminary list of potentially clinically significant DDIs was compiled, based on 154 DDIs identified from literature review. Subsequently, a 2-round online Delphi survey was undertaken with a multidisciplinary expert panel. A consensus meeting and a final round were conducted to validate the final DDI list and the scope of information provided. Setting and Participants Twenty nine experts, including geriatricians and clinical pharmacists from 8 European countries. Measures For each DDI, in the first 2 rounds, experts were asked to score the severity of potential harm on a 5-point Likert-type scale. DDIs were directly included on the final list if the median score was 4 (major) or 5 (catastrophic). DDIs with a median score of 3 (moderate) were discussed at a consensus meeting and included if ≥75% of participants voted for inclusion in the final round. Results Consensus was achieved on 66 potentially clinically significant DDIs (28 had a median score of 4/5 and 48 of 3 in the Delphi survey). Most concerned cardiovascular, antithrombotic, and central nervous system drugs. The final list includes information on the mechanism of interaction, harm, and management. Treatment modification is recommended for three-quarters of DDIs. Conclusion and Implications We validated a list of potentially clinically significant DDIs in older people, which can be used in clinical practice and education to support identification and management of DDIs or to assess prevalence in epidemiologic and intervention studies. pre-print 896 KB

Hospital staff are a priority target group in the European COVID-19 vaccination strategy. Measuring the extent of COVID-19 vaccination hesitancy and understanding the reasons behind it are essential to be able to tailor effective communication campaigns. Using the Health Belief Model (HBM) as a theoretical framework, a survey was conducted among staff members of a Belgian three-site hospital center between 6 and 20 January 2021. Multivariable logistic ordinal regression was performed to assess determinants of the attitude towards COVID-19 vaccination. Reasons for and against COVID-19 vaccination and the need for information were explored among hesitant staff members. Among the respondents (N = 1132), 58% and 4.9% said that they would certainly and certainly not get vaccinated, respectively, 37.1% were hesitant, with different degrees of certainty. A positive attitude towards COVID-19 vaccination was associated with being older, being a physician, being vaccinated against seasonal flu, and with several HBM factors (including perceived benefits and cues to actions). Among hesitant staff, concerns about potential side effects and the impression that the vaccine was developed too quickly were the main reasons against COVID-19 vaccination. The key factors in the decision process were data on vaccine efficacy and safety, and knowing that vaccination went well in others. These data are helpful to further tailor the communication campaign and ensure sufficient vaccination coverage among hospital staff.

Direct oral anticoagulants (DOACs) are increasingly prescribed in older patients with non-valvular atrial fibrillation (NVAF). They provide higher convenience than vitamin K antagonists (VKA), with an improved efficacy and a reduced risk of intracranial bleeding. Dose reduction criteria are clearly established for each DOAC, depending on renal function, weight, age or concomitant medications. However, many observational studies have reported that DOACs were frequently prescribed at an off-label dose, especially in older patients. It is therefore possible that some patients do not receive the full benefit of their anticoagulant treatment. [...]

Background Patients undergoing chemotherapeutic treatment are currently treated by a concomittent infusion of alizapride and ondansetron. To optimise the procedure and to ensure patients’ safety, the admixture could be prepared in advance by the Centralized Intravenous Additive Service (CIVAS) provided that the stability of the mixture has been proven beforhand to reduce nausea and vomiting. Aim of the study: to evaluate the long-term stability of an admixture of alizapride 0.926 mg/l and ondansetron 0.074 mg/ml in 0.9% sodium chloride polyolefin bags stored at 5 ± 3°C. Material and methods Five polyolefin bags containing 100 ml sodium chloride 0.9% added with 4 ml alizapride (100 mg) and 4 ml ondansetron (8 mg) were prepared in aseptic conditions and stored at 5 ± 3°C for 56 days. Periodically, physical stability tests were performed including: pH measurements, optical density measurements at 350, 410 and 550 nm to track turbidity appearance, visual and microscopical inspections to detect colour changes, precipitation, microaggregates or crystals. The concentrations of the solutions were measured by High Performance Liquid Chromatography coupled with an UV detector. Results There was no change in pH and optical densities during the study period. Visual and microscopical inspections didn’t show any change of colour neither precipitation, microaggregate or crystal. The alizapride and ondansetron concentrations remained stable over the study. Conclusion The admixture of alizapride and ondansetron in 0.9% sodium chloride solution polyolefin bags is physicochemically stable up to 56 days at 5 ± 3°C. These results support the possibility of preparing the solutions in advance by a CIVAS.

All dosage forms prepared in hospital pharmacies should be labelled with an appropriate shelf-life. This shelf-life should be validated taking chemical, physical and microbiological data into consideration. This guidance focuses on parenteral aseptically prepared products, as they are high-risk preparations. The risk is exacerbated by a requirement for longer shelf lives for reasons of economy and efficiency. The scope of this guidance includes individual patient preparations, preparations prepared in series (same type of preparation being repeatedly prepared) and batch preparations prepared from the same initial bulk admixture.

BACKGROUND/OBJECTIVES: To describe the use and deprescribing of benzodiazepine receptor agonists (BZRAs) among nursing home residents (NHRs), to evaluate appropriateness of use and to identify factors associated with BZRA use and deprescribing. DESIGN: Posthoc analysis of the Collaborative Approach to Optimize Medication Use for Older People in Nursing Homes (COME-ON) study, a cluster controlled trial that evaluated the impact of a complex intervention on potentially inappropriate prescriptions (PIPs) in nursing homes (NHs). SETTING: A total of 54 NHs in Belgium. PARTICIPANTS: A total of 797 NHRs included in the study who had complete medical, clinical, and medication information at baseline and at the end of the study (month 15). MEASUREMENTS: Data were recorded by participating healthcare professionals. Reasons why BZRA use was considered as PIPs were assessed using the 2019 American Geriatrics Society Beers Criteria® and the Screening Tool of Older Persons' Prescriptions (STOPP) criteria, version 2. Deprescribing included complete cessation or decreased daily dose. We identified factors at the NHR, prescriber, and NH levels associated with BZRA use and BZRA deprescribing using multivariable binary and multinomial logistic regression, respectively. RESULTS: At baseline, 418 (52.4%) NHRs were taking a BZRA. The use of BZRA for longer than 4 weeks, with two or more other central nervous system active drugs, and in patients with delirium, cognitive impairment, falls, or fractures was found in more than 67% of BZRA users. Eight NHR-related variables and two prescriber-related variables were associated with regular BZRA use. Deprescribing occurred in 28.1% of BZRA users (32.9% in the intervention group and 22.1% in the control group). In addition to four other factors, dementia (odds ratio [OR] = 2.35; 95% confidence interval [CI] = [1.45-3.83]) and intervention group (OR = 1.74; 95% CI = 1.07-2.87) were associated with deprescribing. CONCLUSION: Use of BZRAs was highly prevalent, and reasons to consider it as PIP were frequent. Deprescribing occurred in one-fourth of NHRs, which is encouraging. Future interventions should focus on specific aspects of PIPs (ie, indication, duration, drug-drug and drug-disease interactions) as well as on nondementia patients. ispartof: JOURNAL OF THE AMERICAN GERIATRICS SOCIETY vol:68 issue:12 pages:2768-2777 ispartof: location:United States status: published

Background Serious adverse drug reactions have been associated with the underuse or the misuse of oral anticoagulant therapy. We systematically reviewed the impact of computerized clinical decision support systems (CDSS) on the prescribing of oral anticoagulants and we described CDSS features associated with success or failure. Methods We searched Medline, Embase, CENTRAL, CINHAL, and PsycINFO for studies that compared CDSS for the initiation or monitoring of oral anticoagulants with routine care. Two reviewers performed study selection, data collection, and risk-of-bias assessment. Disagreements were resolved with a third reviewer. Potentially important CDSS features, identified from previous literature, were evaluated. Results Sixteen studies were included in our qualitative synthesis. Most trials were performed in primary care (n = 7) or hospitals (n = 6) and included atrial fibrillation (AF) patients (n = 9). Recommendations mainly focused on anticoagulation underuse (n = 11) and warfarin-drug interactions (n = 5). Most CDSS were integrated in electronic records or prescribing and provided support automatically at the time and location of decision-making. Significant improvements in practitioner performance were found in 9 out of 16 studies, while clinical outcomes were poorly reported. CDSS features seemed slightly more common in studies that demonstrated improvement. Conclusions CDSS might positively impact the use of oral anticoagulants in AF patients at high risk of stroke. The scope of CDSS should now evolve to assist prescribers in selecting the most appropriate and tailored medication. Efforts should nevertheless be made to improve the relevance of notifications and to address implementation outcomes.

Cette étude offre un aperçu de la pratique actuelle de l'administration des vaccins dans les États voisins ou comparables à la Belgique. Nous avons décrit un panorama hétérogène de systèmes de santé qui gèrent l'administration du vaccin de différentes manières. La littérature sur le thème du transfert des tâches vers l'administration de vaccins sans médecin suggère qu'il y a des pistes à explorer en termes de possibilités de communication et d'accessibilité pour les patients. Les informations que nous avons recueillies indiquent qu'il existe de nombreuses possibilités d'apprentissage trans-frontaliers dans ce domaine

Background Critically ill patients are at high risk of iatrogenic withdrawal syndrome (IWS), due to exposure to high doses or prolonged periods of opioids and benzodiazepines. Purpose To examine pharmacological management strategies designed to prevent and/or treat IWS from opioids and/or benzodiazepines in critically ill neonates, children and adults. Methods We included non-randomised studies of interventions (NRSI) and randomised controlled trials (RCTs), reporting on interventions to prevent or manage IWS in critically ill neonatal, paediatric and adult patients. Database searching included: PubMed, CINAHL, Embase, Cochrane databases, TRIP, CMA Infobase and NICE evidence. Additional grey literature was examined. Study selection and data extraction were performed in duplicate. Data collected included: population, definition of opioid, benzodiazepine or mixed IWS, its assessment and management (drug or strategy, route of administration, dosage and titration), previous drug exposures and outcomes measures. Methodological quality assessment was performed by two independent reviewers using the Cochrane risk of bias tool for RCTs and the ROBINS-I tool for NRSI. A qualitative synthesis of the results is provided. For the subset of studies evaluating multifaceted protocolised care, we meta-analysed results for 4 outcomes and examined the quality of evidence using GRADE post hoc. Results Thirteen studies were eligible, including 10 NRSI and 3 RCTs; 11 of these included neonatal and paediatric patients exclusively. Eight studies evaluated multifaceted protocolised interventions, while 5 evaluated individual components of IWS management (e.g. clonidine or methadone at varying dosages, routes of administration and duration of tapering). IWS was measured using an appropriate tool in 6 studies. Ten studies reported upon occurrence of IWS, showing significant reductions (n = 4) or no differences (n = 6). Interventions failed to impact duration of mechanical ventilation, ICU length of stay, and adverse effects. Impact on opioid and/or benzodiazepine total doses and duration showed no differences in 4 studies, while 3 showed opioid and benzodiazepine cumulative doses were significantly reduced by 20–35% and 32–66%, and treatment durations by 1.5–11 and 19 days, respectively. Variable effects on intervention drug exposures were found. Weaning durations were reduced by 6–12 days (n = 4) for opioids and/or methadone and by 13 days (n = 1) for benzodiazepines. In contrast, two studies using interventions centred on transition to enteral routes or longer tapering durations found significant increases in intervention drug exposures. Interventions had overall non-significant effects on additional drug requirements (except for one study). Included studies were at high risk of bias, relating to selection, detection and reporting bias. Conclusion Interventions for IWS management fail to impact duration of mechanical ventilation or ICU length of stay, while effect on occurrence of IWS and drug exposures is inconsistent. Heterogeneity in the interventions used and methodological issues, including inappropriate and/or subjective identification of IWS and bias due to study design, limited the conclusions. Electronic supplementary material The online version of this article (10.1007/s40265-020-01338-4) contains supplementary material, which is available to authorized users.

Background and objective Infusion containing paracetamol, alizapride, ketorolac and tramadol is used after a general anaesthesia in order to limit pain, fever and nausea. Currently, these infusions are prepared according to demand in the anaesthesia unit, but the preparation in advance could improve quality of preparation and time management. The aim of this study was to investigate the long-term stability of this infusion in glass bottles at 5°C ± 3 °C. Method Five bottles of infusion were stored at 5°C ± 3 °C for 60 days. A visual and microscope inspection were performed periodically to observe any particle appearance or colour change. pH and absorbance at three wavelengths were measured. The concentrations were measured by ultra-high performance liquid chromatography – diode array detection. Results Multiple verifications were performed during the first 35 days and no crystal, impurity or colour change were observed. At the next time point (42nd day), crystals were visible to the naked eye. pH and absorbance at 350 nm and 550 nm were stable. A slight increase in the absorbance at 410 nm was observed during the study, suggesting that a degradation product could be formed and absorb at this wavelength. The infusion was considered chemically stable while the lower one-sided prediction limit at 95% remains superior to 90% of the initial concentration. Concentration measurements demonstrated that ketorolac and alizapride remained stable in the infusion for 35 days. The stability of tramadol was 28 days. However, degradation of paracetamol was much faster given that concentration has fallen below 90% of the initial concentration after 7 days. Conclusion Infusion of paracetamol, alizapride, ketorolac and tramadol remains stable for 7 days in glass bottles at 5°C ± 3 °C and could be prepared in advance with these storage conditions.

BACKGROUND AND OBJECTIVE: Medication errors in nursing homes are highly prevalent and occur in different stages of the medicines pathway. The application of the SEIPS (System Engineering Initiative for Patient Safety) model facilitates the identification of work system factors that contribute to errors. Therefore, the aim of our research was to investigate in-depth the medicines pathway in nursing homes by using the SEIPS model and to develop a set of key activities and aggregated key interventions to be used as a basis for quality-improvement strategies. METHODS: A variety of qualitative methods, including observations, semi-structured interviews, the development of a flowchart, an expert meeting and a working symposium, were used to identify processes and work system components. Key interventions and activities were developed in three rounds (one development and two validation rounds) across the different research methods to fine-tune the defined key interventions and activities. RESULTS: Our analysis revealed a large variety of tasks as well as persons elements, aspects related to technology and tools, organisational factors and environmental elements that all interact and influence the medicines pathway. The large number of tasks could be linked to eight overarching processes: prescribing, purchase and ordering, delivery, storage, preparation, administration, monitoring and (re-)admission. After three rounds (one development and two validation rounds), a final set of 137 key activities and 27 aggregated key interventions, concretising the eight processes, was obtained. CONCLUSION: The in-depth analysis of processes within the medicines pathway in nursing homes resulted in a set of key activities and aggregated key interventions which may serve as a basis for the nursing home sector and policy makers to enhance a safe and efficient medicines pathway. ispartof: RESEARCH IN SOCIAL & ADMINISTRATIVE PHARMACY vol:16 issue:3 pages:360-376 ispartof: location:United States status: published

Nous avons déjà analysé à plusieurs reprises dans Minerva la place de l’aspirine en prévention cardiovasculaire primaire (1-6). Ces 3 analyses les plus récentes font état d’un manque d’arguments (balance bénéfice-risque non favorable) pour accorder une place à l’aspirine en prévention primaire. Ces analyses se basaient sur 2 méta-analyses récentes (6,7). Une autre étude réalisée en Nouvelle-Zélande a cherché à déterminer quels patients resteraient malgré tout bénéficiaires de l’aspirine en prévention primaire (c'est-à-dire les patients à haut risque cardiovasculaire et faible risque de saignements) (8). Le risque d’hémorragie intracrânienne (HI) est le plus redouté avec l’aspirine. Les nouvelles données disponibles (trois larges études randomisées contrôlées (9-11)), le manque de consistance des données sur le risque d’HI ainsi que le manque de détails sur les sous-types de saignements les plus fréquents ont mené à la réalisation d’une revue systématique et méta-analyse.

Background Efficient testing to identify poor quality artemisinin-based combination therapy (ACT) is important to optimize efforts to control and eliminate malaria. Healthcare professionals interact with both ACT and malaria patients they treat and hence could observe, first-hand, suspect poor quality artemisinin-based combinations linked to poor malaria treatment outcomes and the factors associated with inappropriate use or treatment failure. Methods A cross-sectional study of 685 HCP perspectives about the efficacy of ACT between June and July 2018 at selected health facilities in Uganda. Medicine samples were obtained from the seven regions of Uganda and tested for quality using the Germany Pharma Health Fund™ minilabs. Results The average age of the 685 respondents was 30 (SD = 7.4) years. There was an almost equal distribution between male and female respondents (51:49), respectively. Seventy percent (n = 480) were diploma holders and the nurses contributed to half (49%, n = 334) of the study population. Sixty-one percent of the HCPs reported having ever encountered ACT failures while treating uncomplicated malaria. Nineteen percent of HCPs thought that dihydroartemisinin/piperaquine gave the most satisfactory patient treatment outcomes, while 80% HCPs thought that artemether/lumefantrine gave the least satisfactory patient treatment outcomes, possibly due to dosing schedule and pill burden. Healthcare professionals from the Central region (OR = 3.0, CI 0.3–1.0; P = 0.0001), Eastern region (OR = 5.4, CI 2.9–9.8; P = 0.0001) and Northern region (OR = 5.3, CI 2.9–9.9; P = 0.0001) had a higher chance of encountering ACT failure in 4 weeks prior to the survey as compared to those from the western region. Healthcare professionals from private health facilities also had higher chances of encountering ACT failures in past 4 weeks as compared to those from public health facilities (OR = 2.7, CI 1.7–3.9; P = 0.0001). All 192 samples passed the quality screening tests. The random sample of 10% of all samples randomly obtained by the laboratory staff also passed the chemical content analysis and dissolution tests. Conclusion ACT medicines are widely available over-the-counter to the public and it is very difficult to report and monitor a decrease in efficacy or treatment failure. The perspectives of HCPs on treatment failure or lack of efficacy may potentially guide optimization efforts of sampling methodologies for the quality survey of ACT medicines.

OBJECTIF : La dénutrition est un problème majeur dans la prise en charge du patient. Le dépistage nutritionnel, prérequis essentiel, est souvent insuffisamment réalisé pour diverses raisons : manque de temps, de ressources humaines… Une étude prospective observationnelle monocentrique a été menée durant neuf semaines afin de valider l’hypothèse qu’il était possible de faire participer le patient en lui demandant de fournir seul les informations nécessaires à l’établissement d’un diagnostic nutritionnel dans les 48 heures de son admission. MÉTHODE : Le patient complétait à l’admission un document reprenant les données nutritionnelles nécessaires à l’établissement du diagnostic nutritionnel. Ensuite, le même questionnaire était réalisé par le diététicien de l’équipe investigatrice qui établissait le diagnostic nutritionnel à la fois sur base des éléments transmis par le patient (diagnostic patient) et sur base de ses données (diagnostic diététicien). La corrélation entre ces deux diagnostics a été analysée par le kappa de Cohen et le kappa quadratique. RÉSULTATS : Le document fut complété par 281 patients ; 167 furent confrontés à celui réalisé par le diététicien. Sur base des questionnaires patients, un diagnostic fut possible pour 158 des 167 questionnaires. Le kappa de Cohen et le kappa quadratique étaient respectivement de 0,74 et 0,84. En ce qui concerne le délai du dépistage, 162 de ces 167 patients ont remis leur questionnaire dans les 48 heures de l’admission. CONCLUSION : Ce travail valide l’hypothèse de faire du patient l’acteur principal d’un dépistage nutritionnel de qualité et disponible dans les 48 heures de l’admission. [When the nutritionnal screening is entrusted to the patient: A prospective observational study in a belgian university hospital] OBJECTIVES : Undernutrition is a major problem when you have to take in charge a patient. Nutritional screening, essential prerequisite, is insufficiently done for various reasons: lack of time, lack of human resources… A prospective observational monocentric study has been conducted during nine weeks to validate the hypothesis that it was possible to empower the patient by asking him/her to provide the information needed to establish a nutritional diagnosis within 48 hours of admission. METHOD : On admission, the patient completed a document containing the nutritional data needed to establish the nutritional diagnosis. Then, the same survey was conducted by the dietician of the investigative team who made the nutritional diagnosis based on both the elements shared by the patient (patient's diagnosis) and the ones of his own data (dietician's diagnosis). The correlation between these two diagnosis has been analyzed by Cohen's kappa and the quadratic kappa. RESULTS : 281 patients filled in the document; 167 documents were compared to the one made by the dietician. Based on the patients’ forms, a diagnosis was possible for 158 out of 167 questionnaires. The Cohen's kappa and quadratic kappa were respectively of 0,74 and 0,84. As far as the timing of the screening is concerned, 162 of these 167 patients submitted their questionnaires within 48 hours of the admission. CONCLUSION : This study validates the hypothesis of making the patient the main actor of a qualitative nutritional screening and available within 48 hours of admission.