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INTRODUCTION: Older adults face a higher risk of vancomycin-related toxicity given their (patho)-physiological changes, making early management of supratherapeutic exposure crucial. Yet, data on vancomycin exposure in older adults is scarce. This study aims to compare vancomycin concentrations between older and younger patients, emphasizing supratherapeutic concentrations and the effect of patient characteristics. METHODS: This observational retrospective study was conducted in the University Hospital of Leuven (EC Research S65213). We analyzed early (first) vancomycin concentrations between older (≥ 75 years) and younger patients. Multivariable analyses were conducted to evaluate the association between baseline patient characteristics with supratherapeutic exposure (logistic regression), and dose-normalized concentrations (linear regression). RESULTS: We included 449 patients aged ≥ 75 years (median 80) and 1609 aged < 75 years (median 61). In univariable analysis, the first-measured vancomycin concentrations were significantly higher in older adults (p < 0.001), who more frequently reached supratherapeutic concentrations (30.7% versus 21%; p < 0.001). In multivariable analysis, factors associated with supratherapeutic concentrations were decreased the estimated glomerular filtration rate calculated by using the Chronic Kidney Disease Epidemiology Collaboration equation (eGFRCKD-EPI) [odds ratio (OR) of 0.98, confidence interval (CI) 0.97-0.98]. Supratherapeutic concentrations had inverse association with giving lower loading dose (OR of 0.59, CI 0.39-0.90), and lower maintenance dose (OR of 0.45, CI 0.26-0.77). Factors that predicted increased dose-normalized concentrations included decreased eGFRCKD-EPI (coefficient of -0.05, CI -0.06 to -0.04), lower body weight (coefficient of -0.04, CI -0.05 to -0.03), increased blood urea nitrogen (coefficient of 0.02, CI 0.01-0.03), and delayed time to therapeutic drug monitoring (TDM) sampling (coefficient of 0.08, CI 0.06-0.09). CONCLUSIONS: The absence of age as a significant factor in the multivariable analysis suggests that eGFRCKD-EPI mediated the relationship between age and vancomycin exposure. Older adults may benefit more from vancomycin TDM.
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OBJECTIVES: Chronic antipsychotic use among nursing home (NH) residents carries risks with uncertain benefits. Despite guidelines recommending restricted use, these agents remain widely prescribed. This study investigates chronic antipsychotic use in Belgian NHs. DESIGN: We examined the evolution of chronic antipsychotic use, associated NH resident profiles, impact of NH admissions, and variation among Belgian NHs in a retrospective dynamic cohort study between 2017 and 2022. SETTING AND PARTICIPANTS: Antipsychotic dispensation rates were extracted for members of the Independent Health Insurance Funds in NHs. Prescription trends and resident profiles were evaluated for around 15,000 residents yearly (n = 14,733-15,451) from 2017 to 2022 and variation was assessed among 59 NHs. The impact of NH admission was analyzed for 9647 admissions between 2020 and 2022, and variation was evaluated among 22 NHs. METHODS: For 22 antipsychotics identified at the ATC3 level, chronic use was defined as ≥80 defined daily doses (DDD) and/or ≥16 weekly dispensations per year. We analyzed changes in the 4 most frequently used antipsychotics (haloperidol, olanzapine, quetiapine, risperidone) on NH admission, with chronic use defined as ≥80 minimal prescribed doses (MPD) annually. RESULTS: The prevalence of chronic antipsychotic use among NH residents decreased from 24% in 2017 to 22.5% in 2022 (P = .002). Factors associated with higher antipsychotic use included younger age, greater dependency, and lower socioeconomic status. Upon NH admission, 30% (n = 818 of 2723) of residents discontinued treatment, while in 33% (n = 949 of 2854) treatment was initiated, predominantly with quetiapine or risperidone. This led to a small but significant increase of 1.4% after admission (P < .001). Defining chronic use as ≥80 MPD annually appeared to be more sensitive in measuring chronic antipsychotic use. CONCLUSIONS AND IMPLICATIONS: Chronic antipsychotic use remains widespread in Belgian NHs, with care transition as an important decision point. Further research should explore effects of safer (de)prescribing strategies on patient well-being.
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INTRODUCTION: The pharmacy profession faces a lack of evidence pertaining to pharmaceutical care in oncology, both in terms of its effectiveness and its integration into clinical practice. While Europe-based pharmacists are active in many therapeutic areas, their role in cancer care is less defined. Conversely, the complexity of oncology, increasing cancer cases, and evolving therapies highlight the potential for pharmacists in this field. Their limited involvement in Europe may be attributed to inadequate undergraduate training and research. PERSPECTIVE: Collaborative care shows potential in oncology, but still needs more trial evidence. Here, we can learn from pharmaceutical care in cardiology, where more research has been conducted. The limited role of pharmacists in oncology may be due to a lack of focus on oncology research and insufficient education. IMPLICATIONS: Addressing the teaching gap requires improving oncology education in pharmacy programs, at both undergraduate and postgraduate levels. Current postgraduate courses and US PharmD programs could serve as models. Equipping pharmacy students with fundamental oncology knowledge is a vital first step, for further meaningful research and practice. Formal education could bridge the gap between evidence and practice in these fields.
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Educação em Farmácia , Oncologia , Farmacêuticos , Humanos , Educação em Farmácia/métodos , Educação em Farmácia/tendências , Educação em Farmácia/normas , Oncologia/educação , Papel Profissional , Ensino/normas , Ensino/estatística & dados numéricos , Europa (Continente) , Currículo/tendências , Currículo/normasRESUMO
BACKGROUND: Polypharmacy is a growing concern, impacting patient safety and healthcare costs. Monitoring its prevalence and temporal trends is essential for effective healthcare management. AIM: This study aimed to determine prevalence and trends of polypharmacy and excessive polypharmacy in Belgium. METHOD: Utilizing a federal claims database, medication data were analyzed from 2012 to 2021. Polypharmacy (≥ 5 medications) and excessive polypharmacy (≥ 10 medications) were evaluated, with prevalence calculated per 1000 inhabitants, and reported per year, age group and region. Linear regression estimated the impact of age and year on polypharmacy prevalence. RESULTS: In 2021, polypharmacy and excessive polypharmacy were reported in 135/1000 and 31/1000 Belgians respectively. Prevalence of both increased steadily from 2012 to 2021, with excessive polypharmacy rising more prominently. Among adults aged ≥ 65 years, prevalence rates were higher, with polypharmacy at 434/1000 and excessive polypharmacy at 106/1000. Regional variations were observed, with prevalence highest in the Walloons region. Patient age and year (2012-2021) were associated with both polypharmacy and excessive polypharmacy (p < 0.001). CONCLUSION: We observed increases in polypharmacy and excessive polypharmacy over a decade in Belgium, particularly among older adults. Efforts to monitor, manage, and optimize medication use are imperative to ensure safe and effective healthcare delivery.
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Bases de Dados Factuais , Polimedicação , Humanos , Idoso , Bélgica/epidemiologia , Estudos Retrospectivos , Prevalência , Pessoa de Meia-Idade , Masculino , Feminino , Adulto , Idoso de 80 Anos ou mais , Adolescente , Adulto Jovem , Criança , Pré-Escolar , Lactente , Fatores EtáriosRESUMO
BACKGROUND: Atrial fibrillation occurs in nearly half of geriatric inpatients and is a major cause of morbidity and mortality. Suboptimal anticoagulation use is an important concern in this population. This study aimed to evaluate the appropriateness of antithrombotic therapies in this patient cohort. METHODS: A retrospective analysis was conducted on the geriatric wards of a teaching hospital in Belgium, on a background of clinical pharmacy services. The first 90 atrial fibrillation patients from 2020 to 2022 were included if they received an oral anticoagulant. We assessed utilisation and appropriateness of antithrombotics at discharge, examined reasons for guideline deviations, and explored factors associated with underdosing. Temporal associations for appropriateness and type of anticoagulant (vitamin K antagonist (VKA) vs direct oral anticoagulant (DOAC)) were assessed. RESULTS: The mean age of patients was 86.5 (±5.3) years and the median CHA2DS2-VASc score was 5 (interquartile range (IQR) 4-6). At discharge, 256 (94.8%) patients used a DOAC; nine (3.3%) used a VKA; one (0.4%) a DOAC-antiplatelet combination, and in four patients (1.5%) all antithrombotics were discontinued. The majority (64.4%) of patients received reduced DOAC doses with apixaban prescribed in 40.7%. In 39 (14.4%) patients, antithrombotic use was considered inappropriate, mostly without a rationale (23/39). Year 2022 (odds ratio (OR) 0.104; 95% confidence interval (CI), 0.012-0.878) was the sole determinant for underdosing. No significant differences were found with respect to appropriateness (p=0.533) or anticoagulant class (p=0.479) over time. CONCLUSION: Most geriatric inpatients received a justified reduced DOAC dose. A significant proportion was managed inappropriately with underdosing (= unjustified reduced dose) being most common. Frequently no rationale was provided for deviating from trial-tested doses.
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Special populations, like geriatric patients, experience altered paracetamol pharmacokinetics (PK), complicating pain management. More PK research is essential to optimize paracetamol (acetaminophen) dosing. Yet, the reference method ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) is not readily available. Therefore, we aimed to evaluate the agreement between UPLC-MS/MS and the more accessible colorimetric Roche acetaminophen (ACETA) assay in quantifying paracetamol plasma concentrations, to facilitate PK studies and therapeutic drug monitoring for pain management. Patient data and plasma samples were obtained from a prospective study including geriatric patients admitted to the geriatric wards. ACETA and UPLC-MS/MS assays were performed in two separate laboratories. Bland-Altman plot and Passing-Bablok regression were used to assess agreement. Accuracy was evaluated using the McNemar test for a threshold value of 10 mg/L. Population PK modeling was employed to bridge PK data obtained from both methods (NONMEM 7.5). A total of 242 plasma sample pairs were available from 40 geriatric patients (age range, 80-95 years). Paracetamol plasma concentrations from ACETA (median 9.8 [interquartile range 6.1-14.4] mg/L) and UPLC-MS/MS (9.5 [6.2-14.8] mg/L) did not differ significantly (P > 0.05). No significant proportional nor additive bias was observed between both assay methods. The classification accuracy (at threshold 10 mg/L) was 85% (P = 0.414). The conversion factor between ACETA and UPLC-MS/MS was estimated at 1.06 (relative standard error 5%), yet with a 13.4% (relative standard error 23%) interindividual variability. ACETA assay showed no systematic bias in comparison with the UPLC-MS/MS assay in determining paracetamol exposure in geriatric blood samples despite the imprecision.
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Acetaminofen , Colorimetria , Humanos , Idoso , Idoso de 80 Anos ou mais , Cromatografia Líquida/métodos , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Estudos ProspectivosAssuntos
Fragilidade , Neoplasias , Trombose , Humanos , Idoso , Fragilidade/tratamento farmacológico , Idoso Fragilizado , Trombose/tratamento farmacológico , Trombose/etiologia , Anticoagulantes/uso terapêutico , Interações Medicamentosas , Neoplasias/complicações , Neoplasias/tratamento farmacológicoRESUMO
BACKGROUND: Hypertension is highly prevalent and remains one of the most frequent and preventable causes of cardiovascular morbidity and mortality. Yet, suboptimal blood pressure control is common. Hypertension clinics might play an important role in improving target attainment, by targeting drug therapy adherence, improving guideline compliance and by involving pharmacists. OBJECTIVES: We aimed to characterize patient drug therapy adherence, prescriber guideline compliance and pharmacist interventions at the hypertension clinic. METHODS: A prospective observational study was performed at the hypertension clinic of a large, academic hospital. Adult Dutch-speaking patients were eligible for inclusion. Following data were collected: patient demographics, medication use, patient adherence to prescribed antihypertensive drug therapies according to the BAASIS tool and prescriber compliance to the 2018 European Society of Cardiology (ESC) hypertension guidelines. RESULTS: A cohort of 108 patients was included with 51.9% male and aged 65 (IQR: 52-75) years. In total, 104 patients took at least 1 antihypertensive drug and 46 patients (44.2%) were classified as non-adherent with regard to their antihypertensive treatment; 82 patients (78.8%) had suboptimal blood pressure control. Compliance with the ESC guidelines was 66.3% prior to the consultation at the clinic and significantly increased to 77.9% thereafter (p = 0.0015). The clinical pharmacist performed a medication review for 27 patients with a total of 44 recommendations and an acceptance rate of 59.1%. CONCLUSION: A visit to the multidisciplinary hypertension clinic improved prescriber guideline compliance and the use of single pill combinations. Involvement of a clinical pharmacist could be beneficial to further improve patient drug therapy adherence and guideline compliance.
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Anti-Hipertensivos , Hipertensão , Adulto , Humanos , Masculino , Feminino , Anti-Hipertensivos/efeitos adversos , Fidelidade a Diretrizes , Estudos Prospectivos , Adesão à Medicação , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológicoRESUMO
BACKGROUND: Polypharmacy and inappropriate medication use are associated with unplanned hospital admissions. Targeted interventions might reduce the hospitalization risk. Yet, it remains unclear which patient profiles derive the largest benefit from such interventions. OBJECTIVE: The aim of this study was to determine independent risk factors, among which polypharmacy, for unplanned hospital admissions in a cohort of community dwelling adults. METHODS: A retrospective study was performed using a large general practice registry and an insurance database in Flanders, Belgium. Community dwelling adults aged 40 years or older with data for 2013-2015 were included. The index date was the last general practitioner contact in 2014. Determinants were collected during the preceding year. Unplanned hospital admissions were determined during the year after the index date. Univariable logistic regression models were fitted on each risk factor for an unplanned hospital admission as the primary outcome. Two multivariable models were derived. RESULTS: In total, 40411 patients were included and 2126 (5.26%) experienced an unplanned hospital admission. Mean age was 58.3 (±12.3) years. The two models identified the following determinants for an unplanned hospital admission: excessive polypharmacy, older age, male sex, number of comorbidities, atrial fibrillation, chronic obstructive pulmonary disease or stroke, low hemoglobin, use of hypnotics, antipsychotics, antidepressants or antiepileptics and prior hospital and general practitioner visits. Prior hospital visits was the largest determinant. CONCLUSIONS: In our study we identified and confirmed the presence of known determinants for unplanned hospital admissions in community dwelling adults, most of which align with a geriatric phenotype. Our findings can inform the allocation of interventions aiming to reduce unplanned hospital admissions.
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Hospitalização , Vida Independente , Humanos , Masculino , Adulto , Idoso , Pessoa de Meia-Idade , Estudos de Coortes , Estudos Retrospectivos , HospitaisRESUMO
BACKGROUND: Chronic use of hypnotic agents is prevalent in older adults, who as a result are at increased risk for certain adverse events, such as day-time drowsiness and falls. Multiple strategies to discontinue hypnotics have been tested in geriatric patients, but evidence remains scarce. Hence, we aimed to investigate a multicomponent intervention to reduce hypnotic drug use in geriatric inpatients. METHODS: A before-after study was performed on the acute geriatric wards of a teaching hospital. The before group (= control group) received usual care, while intervention patients (= intervention group) were exposed to a pharmacist-led deprescribing intervention, comprising education of health care personnel, access to standardized discontinuation regimens, patient education and support of transitional care. The primary outcome was hypnotic drug discontinuation at one month after discharge. Secondary outcomes among others were sleep quality and hypnotic use at one and two weeks after enrolment and at discharge. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) upon inclusion, two weeks after enrolment and one month after discharge. Determinants for the primary outcome were identified using regression analysis. RESULTS: A total of 173 patients were enrolled, with 70.5% of patients taking benzodiazepines. Average age was 85 years (interquartile range 81-88.5) and 28.3% were male. A higher discontinuation rate at one month after discharge was observed in favour of the intervention (37.7% vs. 21.9%, p = 0.02281). No difference in sleep quality was found between both groups (p = 0.719). The average sleep quality was 8.74 (95% confidence interval (CI): 7.98-9.49) and 8.57 (95% CI: 7.75-9.39) in the control and intervention groups respectively. Determinants for discontinuation at one month were: the intervention (odds ratio (OR) 2.36, 95% CI: 1.14-4.99), fall on admission (OR 2.05; 95% CI: 0.95-4.43), use of a z-drug (OR 0.54, 95% CI: 0.23-1.22), PSQI score on admission (OR 1.08, 95% CI: 0.97-1.19) and discontinuation prior to discharge (OR 4.71, 95% CI: 2.26-10.17). CONCLUSIONS: A pharmacist-led intervention in geriatric inpatients was associated with a reduction of hypnotic drug use one month after discharge, without any loss in sleep quality. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05521971 (retrospectively registered on 29th of August 2022).
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Alta do Paciente , Farmacêuticos , Humanos , Masculino , Idoso , Idoso de 80 Anos ou mais , Feminino , Pacientes Internados , Assistência ao Convalescente , Estudos Controlados Antes e Depois , Hipnóticos e Sedativos/efeitos adversosRESUMO
Heart failure is a prevalent syndrome among older adults, with a major impact on morbidity and mortality. Higher age is correlated with underuse of guideline-directed medical therapies which, in turn, has been linked to worse clinical outcomes. Importantly, most evidence so far has been collected in adults who were younger, less multi-morbid and polymedicated compared with those who are commonly treated in daily clinical practice. Hence, we aimed to assess and describe the evidence base for pharmacotherapy in older adults with heart failure with a reduced ejection. First, a narrative review was undertaken using Medline, from inception to January 2023. Four foundational therapies were selected based on the latest European Society of Cardiology clinical practice guideline: angiotensin-converting enzyme inhibitors/angiotensin receptor neprilysin inhibitors, beta blockers, mineralocorticoid receptor antagonists and sodium-glucose cotransporter-2 inhibitors. Post hoc analyses from landmark heart failure drug trials were searched and included if they contained data on the impact of age on efficacy, safety and/or timeliness of therapies in the management of heart failure with a reduced ejection fraction. Second, a proposal was developed to support and promote the use of evidence-based heart failure pharmacotherapy in complex, older adults. In total, 11 articles were selected: 4 meta-analyses, 6 post hoc analyses and 1 review paper. No attenuation of efficacy for any of the foundational agents was found in older adults. Regarding safety, dedicated analyses showed that beta blockers, mineraloid receptor antagonists, sacubitril-valsartan, dapagliflozin and empagliflozin retained their overall benefit-risk profile regardless of age. Time to benefit was short and occurred generally within 1 month. Consensus was achieved on a five-step proposal to manage complex medication regimens in older adults suffering from heart failure. In conclusion, older adults suffering from heart failure with a reduced ejection fraction should not be denied treatment based on their age.
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Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Idoso , Humanos , Antagonistas Adrenérgicos beta/efeitos adversos , Antagonistas de Receptores de Angiotensina/efeitos adversos , Combinação de Medicamentos , Insuficiência Cardíaca/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Volume Sistólico , Tetrazóis/farmacologia , Tetrazóis/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Heart failure (HF) is an important health problem and guidelines recommend multidisciplinary management. The pharmacist is an important member of the multidisciplinary heart failure team, both in the hospital and community setting. This study aims to explore the perceptions of community pharmacists on their role in HF care. METHODS: We conducted a qualitative study based on face-to-face semi-structured interviews with 13 Belgian community pharmacists between September 2020 and December 2020. We used the Qualitative Analysis Guide of Leuven (QUAGOL) method as guidance for data analysis until data saturation was reached. We structured interview content into a thematic matrix. RESULTS: We identified two major themes: heart failure management and multidisciplinary management. Pharmacists feel responsible for the pharmacological and non-pharmacological management of heart failure, citing easy access and pharmacological expertise as important assets. Diagnostic uncertainty, lack of knowledge and time, disease complexity and difficulties in communication with patients and informal care providers are barriers to optimal management. General practitioners are the most important partners in multidisciplinary community heart failure management, although pharmacists perceive a lack of appreciation and cooperation and deplore communication difficulties. They feel intrinsically motivated to provide extended pharmaceutical care in HF but cite the lack of financial viability and information sharing structures as important barriers. CONCLUSION: The importance of pharmacist involvement in multidisciplinary heart failure teams is undisputed by Belgian pharmacists, who cite easy access and pharmacological expertise as important assets. They point out several barriers impeding evidence-based pharmacist care for outpatients with heart failure: diagnostic uncertainty and disease complexity, lack of multidisciplinary information technology and insufficient resources. We recommend that future policy should focus on improved medical data exchanges between primary and secondary care electronic health records as well as the reinforcement of interprofessional relationships between locally affiliated pharmacists and general practitioners.
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Insuficiência Cardíaca , Farmácia , Humanos , Farmacêuticos , Insuficiência Cardíaca/tratamento farmacológico , Comunicação , Análise de DadosRESUMO
Drug-drug interactions (DDIs) are common in cancer management and complicate the choice of anticoagulation in cancer-associated thrombosis. Cancer confers an increased risk of thrombotic events. Also, more bleeding events are observed in those who receive anticoagulation compared to those without cancer. In the treatment of cancer-associated thrombosis, direct oral anticoagulants (DOACs) have been found to be at least as effective as low-molecular weight heparins, which became the standard of care after several trials demonstrated superiority over vitamin K antagonists. Non-inferiority compared to low-molecular weight heparins has been shown for rivaroxaban, edoxaban and apixaban with a signal of fewer recurrent thrombotic events, albeit with an increase in bleeding events. Yet, potentially major pharmacokinetic drug-drug interactions have been identified as a reason to withhold DOACs and to rather choose an alternative. Practical guidance on what constitutes a major pharmacokinetic interaction and/or how to deal with these interactions in clinical practice is limited. Hence, here we have provided a framework to allow clinicians to better deal with pharmacokinetic drug-drug interactions between DOACs and cancer therapies in the management of cancer-associated thrombosis. In this review we have discussed the current literature, how the pharmacokinetic profile links to the label information on DDI, and have provided a practical proposal, applied to a clinical case.
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Neoplasias , Trombose , Tromboembolia Venosa , Humanos , Anticoagulantes , Rivaroxabana/uso terapêutico , Rivaroxabana/farmacocinética , Trombose/etiologia , Trombose/induzido quimicamente , Hemorragia/induzido quimicamente , Heparina de Baixo Peso Molecular/uso terapêutico , Interações Medicamentosas , Administração Oral , Tromboembolia Venosa/induzido quimicamente , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neoplasias/induzido quimicamenteRESUMO
Older adults, the fastest growing population, represent almost 50% of all users of direct oral anticoagulants (DOACs). Unfortunately, we have very little relevant pharmacological and clinical data on DOACs, especially in older adults with geriatric profiles. This is highly relevant as pharmacokinetics and pharmacodynamics (PK/PD) often differ substantially in this population. Hence, we need to obtain a better understanding of the PK/PD of DOACs in older adults, to ensure appropriate treatment. This review summarises the current insights into PK/PD of DOACs in older adults. A search was undertaken up to October 2022 to identify PK/PD studies of apixaban, dabigatran, edoxaban, and rivaroxaban, that included older adults aged ≥ 75 years. This review identified 44 articles. Older age alone did not influence exposure of edoxaban, rivaroxaban and dabigatran, while apixaban peak concentrations were 40% higher in older adults than in young volunteers. Nevertheless, high interindividual variability in DOAC exposure in older adults was noted, which can be explained by distinctive older patient characteristics, such as kidney function, changes in body composition (especially reduced muscle mass), and co-medication with P-gp inhibitors, which is in line with the current dosing reduction criteria of apixaban, edoxaban, and rivaroxaban. Dabigatran had the largest interindividual variability among all DOACs since its dose adjustment criterion is only age, and thus it is not a preferable option. Additionally, DOAC exposure, which fell outside of on-therapy ranges, was significantly related to stroke and bleeding events. No definite thresholds linked to these outcomes in older adults have been established.