Publications by authors named "Lorenz Van der Linden"

32 Publications

Development and validation of a Screening Tool to Evaluate and Warrant Anticoagulation Treatment prior to Discharge in inpatients with Atrial Fibrillation (STEWARD-AF).

Int J Med Inform 2021 Aug 17;154:104555. Epub 2021 Aug 17.

Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium; Pharmacy Department, University Hospitals Leuven, Leuven, Belgium. Electronic address:

Objective: Anticoagulation is highly effective for stroke prevention in atrial fibrillation (AF), reducing the risk by about 64%. Despite overwhelming evidence in support of anticoagulation, up to 40% of AF patients remain untreated. We aimed to develop and validate STEWARD-AF: a Screening Tool to Evaluate and Warrant Anticoagulation Treatment prior to Discharge in Atrial Fibrillation.

Materials And Methods: STEWARD-AF was developed by integrating information extracted from the electronic health record (EHR). A stepwise decision process was applied, based on AF diagnosis, estimated CHADS-VASc-score and anticoagulant use. A priority score was assigned accordingly, ranging from 0 (no risk) to 5 (highest risk of undertreatment). A cross-sectional study was performed to assess the accuracy of STEWARD-AF. Criterion and tool validity were ascertained by determining sensitivity and specificity, compared to a manual check of the EHR in an inpatient sample (n = 800). Consistency regarding the priority score was determined by estimating Cohen's kappa.

Results: A tool to screen for un(der)treated AF was developed and embedded into the EHR. Sensitivity and specificity for AF diagnosis were 98.4% and 87.6%, respectively. Overall sensitivity and specificity for identification of a CHADS-VASc-score ≥ 2 was 97.7% and 72.7%. Sensitivity and specificity to determine the presence of anticoagulant treatment was at least 87.8% and 97.1% There was good agreement for the priority score (κ 0.74 (unweighted); 0.66 (weighted)).

Conclusions: STEWARD-AF was able to identify untreated AF inpatients reliably and with a high sensitivity. Nearly no patients were missed. We will now implement this AF-screening tool in clinical practice to improve the use of anticoagulation and reduce the risk of stroke.
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http://dx.doi.org/10.1016/j.ijmedinf.2021.104555DOI Listing
August 2021

Pharmacokinetics of two oral paracetamol formulations in hospitalized octogenarians.

Br J Clin Pharmacol 2021 Aug 21. Epub 2021 Aug 21.

Pharmacy Department, University Hospitals Leuven, Leuven, Belgium.

Aim: It is currently unclear how paracetamol (acetaminophen) should be dosed in order to increase its efficacy while warranting safety in very old adults. The objective was to evaluate the pharmacokinetics of two oral paracetamol formulations and its metabolites in hospitalized octogenarians.

Methods: Geriatric inpatients aged 80 years and older received a 1000mg paracetamol tablet or granulate at 8AM, 2PM and 8PM. After at least four consecutive gifts, plasma samples were collected around the 8AM dose [trough,+0.5,+1,+2,+4,+5 and +6hours]. Plasma concentrations of paracetamol and its metabolites were determined and individual pharmacokinetic parameters were derived. The Edmonton Frail Scale was used to assess frailty. An analgesic plasma target was defined as an average plasma concentration (Cavg) of 10 mg/L.

Results: The mean (±SD) age was 86.78 (±4.20) years. The majority (N=26/36, 72%) received the tablet, 10 (28%) the granulate. Thirty patients (85%) were classified with moderate to severe frailty. Seven (21%) patients had a Cavg above 10 mg/L. The median [IQR] time to reach the peak concentration (T ) was 50.5 [31.50-92.50] and 42.50 [33.75-106.75] min for the tablet and granulate, respectively. The coefficient of variation was 95% for T and 30% for Cavg of paracetamol. A correlation of Cavg of paracetamol was observed with female sex and total serum bilirubin.

Conclusion: Large interindividual differences were found for pharmacokinetic parameters of oral paracetamol in frail inpatients after multiple dosing. Female sex and higher total serum bilirubin concentrations were associated with paracetamol exposure. No significant differences were observed between the tablet and granulate.
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http://dx.doi.org/10.1111/bcp.15049DOI Listing
August 2021

Venous Thromboembolism in Patients Discharged after COVID-19 Hospitalization.

Semin Thromb Hemost 2021 Jun 23;47(4):362-371. Epub 2021 Apr 23.

Department of Cardiovascular Diseases, University Hospitals Leuven, Leuven, Belgium.

Background:  Venous thromboembolism (VTE) is a frequent complication of COVID-19, so that the importance of adequate in-hospital thromboprophylaxis in patients hospitalized with COVID-19 is well established. However, the incidence of VTE after discharge and whether postdischarge thromboprophylaxis is beneficial and safe are unclear. In this prospective observational single-center study, we report the incidence of VTE 6 weeks after hospitalization and the use of postdischarge thromboprophylaxis.

Methods:  Patients hospitalized with confirmed COVID-19 were invited to a multidisciplinary follow-up clinic 6 weeks after discharge. D-dimer and C-reactive protein were measured, and all patients were screened for deep vein thrombosis with venous duplex-ultrasound. Additionally, selected high-risk patients received computed tomography pulmonary angiogram or ventilation-perfusion (V/Q) scan to screen for incidental pulmonary embolism.

Results:  Of 485 consecutive patients hospitalized from March through June 2020, 146 patients were analyzed, of which 39% had been admitted to the intensive care unit (ICU). Postdischarge thromboprophylaxis was prescribed in 28% of patients, but was used more frequently after ICU stay (61%) and in patients with higher maximal D-dimer and C-reactive protein levels during hospitalization. Six weeks after discharge, elevated D-dimer values were present in 32% of ward and 42% of ICU patients. Only one asymptomatic deep vein thrombosis (0.7%) and one symptomatic pulmonary embolism (0.7%) were diagnosed with systematic screening. No bleedings were reported.

Conclusion:  In patients who had been hospitalized with COVID-19, systematic screening for VTE 6 weeks after discharge revealed a low incidence of VTE. A strategy of selectively providing postdischarge thromboprophylaxis in high-risk patients seems safe and potentially effective.
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http://dx.doi.org/10.1055/s-0041-1727284DOI Listing
June 2021

Age is just a number: the concept of time to benefit in older adults.

Eur J Hosp Pharm 2021 Apr 16. Epub 2021 Apr 16.

Pharmacy Department, KU Leuven University Hospitals Leuven Gasthuisberg Campus, Leuven, Belgium.

A female nursing home resident aged >70 years was admitted to the geriatric ward with de novo dysphagia 6 days after being discharged from the stroke unit. Metformin and ezetimibe had been added to her treatment regimen which already consisted of clopidogrel, atorvastatin, denosumab, calcium and vitamin D. At the geriatric ward a multidisciplinary team involving clinical pharmacists reviewed all treatments and appraised the time to benefit, ascertaining whether there was sufficient time left to experience therapeutic benefits. As a result, metformin, ezetimibe, denosumab, calcium and vitamin D were discontinued. This case report illustrates that both mortality risk assessment and evaluation of the time to benefit should be part of any medication review in frail older adults. Conversely, with limited available data pertaining to the concept of time to benefit, we advocate a broader awareness among pharmacists and a systematic assessment in future clinical trials.
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http://dx.doi.org/10.1136/ejhpharm-2020-002561DOI Listing
April 2021

Itraconazole for COVID-19: preclinical studies and a proof-of-concept randomized clinical trial.

EBioMedicine 2021 Apr 19;66:103288. Epub 2021 Mar 19.

Department of Cardiovascular Sciences and Clinical Department of Laboratory Medicine, KU Leuven, Belgium.

Background: The antifungal drug itraconazole exerts in vitro activity against SARS-CoV-2 in Vero and human Caco-2 cells. Preclinical and clinical studies are required to investigate if itraconazole is effective for the treatment and/or prevention of COVID-19.

Methods: Due to the initial absence of preclinical models, the effect of itraconazole was explored in a clinical, proof-of-concept, open-label, single-center study, in which hospitalized COVID-19 patients were randomly assigned to standard of care with or without itraconazole. Primary outcome was the cumulative score of the clinical status until day 15 based on the 7-point ordinal scale of the World Health Organization. In parallel, itraconazole was evaluated in a newly established hamster model of acute SARS-CoV-2 infection and transmission, as soon as the model was validated.

Findings: In the hamster acute infection model, itraconazole did not reduce viral load in lungs, stools or ileum, despite adequate plasma and lung drug concentrations. In the transmission model, itraconazole failed to prevent viral transmission. The clinical trial was prematurely discontinued after evaluation of the preclinical studies and because an interim analysis showed no signal for a more favorable outcome with itraconazole: mean cumulative score of the clinical status 49 vs 47, ratio of geometric means 1.01 (95% CI 0.85 to 1.19) for itraconazole vs standard of care.

Interpretation: Despite in vitro activity, itraconazole was not effective in a preclinical COVID-19 hamster model. This prompted the premature termination of the proof-of-concept clinical study.

Funding: KU Leuven, Research Foundation - Flanders (FWO), Horizon 2020, Bill and Melinda Gates Foundation.
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http://dx.doi.org/10.1016/j.ebiom.2021.103288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979145PMC
April 2021

Optimizing pharmacotherapy on geriatric hospital units in Belgium - a national survey.

Acta Clin Belg 2020 Dec 21:1-8. Epub 2020 Dec 21.

Department of Geriatric Medicine, University Hospitals Leuven, Leuven, Belgium.

: Inappropriate prescribing remains highly prevalent on geriatric units. The aim of this investigation, initiated by the Belgian College for Geriatrics, was to evaluate the implementation of strategies to optimize pharmacotherapy on geriatric units in Belgium.: A literature search was performed to identify strategies to support the appropriate use of medications in very old inpatients. These strategies were subsequently validated based on Delphi consensus rounds and a national survey was developed. Experts were selected by the research team in collaboration with the Belgian College for Geriatrics. The survey was sent to the heads of the geriatric departments of all Belgian hospitals (n = 100).: After 3 months a response rate of 55% was achieved. Strategies that were implemented more frequently were the use of electronic prescribing (85%), performing a structured medication review (69%) and providing patient education (76%). In a minority (24%) of hospitals, a clinical pharmacist was directly involved in the multidisciplinary geriatric team. Implementation of clinical decisions support systems (CDSS) was reported by 36% of the hospitals. Educational strategies for healthcare professionals and strategies to optimize transitional care were variable.: Taking into account the current body of evidence, strategies that include transitional care components, CDSS or ward-based clinical pharmacy services should be further promoted on Belgian geriatric units.
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http://dx.doi.org/10.1080/17843286.2020.1864162DOI Listing
December 2020

Polypharmacy and excessive polypharmacy in community-dwelling middle aged and aged adults between 2011 and 2015.

Int J Clin Pract 2021 Apr 3;75(4):e13942. Epub 2021 Jan 3.

Pharmacy Department, University Hospitals Leuven, Leuven, Belgium.

Aims: We aimed to assess the prevalence, components and evolution of polypharmacy and to evaluate risk factors associated with polypharmacy.

Methods: A retrospective dynamic cohort study was performed, using a primary healthcare database comprising Flemish community-dwelling adults aged ≥40 years between 2011 and 2015. Polypharmacy and excessive polypharmacy were defined as the use of 5-9 or minimum 10 different medications during 1 year, respectively. Temporal changes were analysed using an autoregressive error model. Risk factors for polypharmacy were evaluated using logistic regression.

Results: In total, 68 426 patients were included in the analysis. The prevalence of polypharmacy was 29.5% and 16.1% for excessive polypharmacy in 2015. The age-standardised prevalence rate of patients using minimum five medications increased with 1.3% per year (95% confidence interval (CI): 0.1968-2.4279). The mean number of unplanned hospital admissions was 0.07 (standard deviation (SD) 0.33) for polypharmacy patients and 0.19 (SD 0.53) for excessive polypharmacy patients. Four risk factors were found to be significantly correlated with polypharmacy: age (odds ratio (OR) 1.015; 95% CI: 1.013-1.017), female gender (OR 1.161; 95% CI: 1.108-1.216), number of chronic diseases (OR 1.126; 95% CI: 1.114-1.139) and number of general practitioner contacts (OR 1.283; 95% CI: 1.274-1.292).

Conclusion: The prevalence of polypharmacy increased between 2011 and 2015. Polypharmacy and excessive polypharmacy patients appeared to differ based on our observations of characteristics, drug therapy and outcomes. Age, female gender, number of chronic diseases and number of general practitioner contacts were associated with polypharmacy.
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http://dx.doi.org/10.1111/ijcp.13942DOI Listing
April 2021

Preventing medication-related harm: Perfect is the enemy of the good.

Br J Clin Pharmacol 2021 07 2;87(7):3014-3015. Epub 2020 Dec 2.

Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.

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http://dx.doi.org/10.1111/bcp.14673DOI Listing
July 2021

Impact of Check of Medication Appropriateness (CMA) in optimizing analgesic prescribing: An interrupted time series analysis.

Eur J Pain 2021 03 11;25(3):704-713. Epub 2020 Dec 11.

Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.

Background: Pain therapy in inpatients is regularly suboptimal and might be improved by clinical pharmacy services. In our hospital, we have implemented a software-supported 'Check of Medication Appropriateness' (CMA), which is a centralized pharmacist-led service consisting of a clinical rule-based screening for potentially inappropriate prescriptions (PIPs), and a subsequent medication review by pharmacists. We aimed to investigate the impact of the CMA on pain-related prescribing.

Methods: A quasi-experimental study was performed in a large teaching hospital, using an interrupted time series design. Pre-implementation, patients were exposed to standard of care. Afterwards, a pain-focused CMA comprising 12 specific clinical rules pertaining to analgesic prescribing were implemented in the post-implementation period. A regression model was used to assess the impact of the intervention on the number of pain-related residual PIPs between both periods. The total number of recommendations and acceptance rate was recorded for the post-implementation period.

Results: At baseline, a median number of 13.1 (range: 9.5-15.8) residual PIPs per day was observed. After the CMA intervention, the number was reduced to 2.2 (range: 0-9.5) per day. Clinical rules showed an immediate relative reduction of 66% (p < .0001) in pain-related residual PIPs. A significant decreasing time trend was observed during the post-implementation period. Post-implementation, 1683 recommendations were given over 1 year with an acceptance rate of 74.3%.

Conclusions: We proved that the CMA approach reduced the number of pain-related residual PIPs. More pharmacist involvement and the use of clinical rules during hospital stay should be further promoted to optimize appropriate prescribing of analgesics.

Significance: Prescribing of analgesics should be improved in inpatients to optimize pain control and to reduce iatrogenic harm. The Check of Medication Appropriateness (CMA) approach, comprising a clinical rule-based screening for patients at risk and a targeted medication review by pharmacists, reduced the number of pain-related potentially inappropriate prescriptions in a highly significant and sustained manner. This study presents the opportunities of a centralized clinical pharmacy service to help clinicians to further improve analgesic prescribing.
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http://dx.doi.org/10.1002/ejp.1705DOI Listing
March 2021

Computerised prescribing support still needs a human touch.

Age Ageing 2020 Sep 30. Epub 2020 Sep 30.

Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.

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http://dx.doi.org/10.1093/ageing/afaa200DOI Listing
September 2020

Deprescribing in geriatric inpatients is associated with a lower readmission risk: a case control study.

Int J Clin Pharm 2020 Oct 17;42(5):1374-1378. Epub 2020 Aug 17.

Hospital Pharmacy Department, University Hospitals Leuven, Herestraat 49, Leuven, 3000, Belgium.

Background Polypharmacy is prevalent in older adults and has been associated with iatrogenic harm. Deprescribing has been promoted to reduce polypharmacy. It remains however unclear whether deprescribing during hospital stay can reduce the readmission risk. Objective We sought to determine whether deprescribing in geriatric inpatients was associated with a lower readmission risk at three months post-discharge. Method A case control study was performed, using data from a prospective, controlled study in geriatric inpatients. Deprescribing was defined as the percentage of discontinued preadmission medications and was assessed upon discharge. A logistic regression analysis was used to determine the odds ratio for deprescribing and the outcome of readmissions. An adjusted odds ratio was then estimated, taking into account age, sex, mortality, the number of preadmission medications and the Charlson Comorbidity Index. Results Data of 166 patients were analysed, of whom 61 had experienced at least one readmission. Adjusting for age, number of preadmission medications and mortality resulted in the most informative regression model, based on the lowest Akaike information criterion (adjusted odds ratio 0.981, 95% confidence interval 0.964 to 0.998). Conclusion Deprescribing in geriatric inpatients was associated with a reduced readmission risk at three months post-discharge.Trial registration S53664.
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http://dx.doi.org/10.1007/s11096-020-01091-4DOI Listing
October 2020

Medication Counselling in Older Patients Prior to Hospital Discharge: A Systematic Review.

Drugs Aging 2020 09;37(9):635-655

Department of Pharmacy, Ghent University Hospital, Ghent, Belgium.

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.
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http://dx.doi.org/10.1007/s40266-020-00780-zDOI Listing
September 2020

Clinical Pharmacy Services in Older Inpatients: An Evidence-Based Review.

Drugs Aging 2020 03;37(3):161-174

Pharmacy Department, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.

Background: Hospital admissions in older adults are frequently drug related and avoidable. Clinical pharmacy interventions during hospital stay might reduce drug-related harm and reduce hospital visits. Moreover, several recent positive clinical pharmacy investigations incorporated a transitional care component to further improve medication use after discharge. It is currently unclear what the strength of evidence is and what the exact components should be of such clinical pharmacy interventions in older adults.

Objective: An evidence-based review was performed to determine the status of the evidence and also to explore whether a clinical pharmacy intervention incorporating transitional care was associated with reduced hospital visits after discharge.

Methods: Prospective controlled investigations were included if they contained a clinical pharmacy intervention that was initiated before discharge in older inpatients. Relevant quasi-experimental and randomized controlled trials were searched in MEDLINE. First, an evidence-based review was performed, including a description of the study design, characteristics, and outcomes. Major components of successful clinical pharmacy interventions were described and potential implications for clinical practice and research were determined. Second, the Fisher's exact test was used to explore the association between transitional care and reduced hospital visits. Third, based on these findings, a medication review proposal was developed to improve medication use in older adults.

Results: Thirty-five studies were included, with 26 randomized controlled trials. Median patient follow-up after discharge was 90 days (interquartile range 37-180 days) and investigators enrolled a median of 210 (interquartile range 110-498) study participants. On average, patients were aged 77.5 years (interquartile range 73-82.2 years). Nine randomized controlled trials had sufficient power to detect a reduction in hospital visits after discharge; this was reduced in three randomized controlled trials. Post-discharge follow-up was not associated with reduced post-discharge hospital visits (20 randomized controlled trials: follow-up vs. no follow-up: 6/11 vs. 1/9, p = 0.070). There was a significant reduction in post-discharge hospital visits in patients aged 75 years or older (12 randomized controlled trials: follow-up vs. no follow-up: 5/7 vs. 0/5, p = 0.028). A medication review proposal was developed, consisting of six steps.

Conclusions: Three powered randomized controlled trials were identified that found a significant association between a pharmacist-led intervention in older adults and a reduction in post-discharge hospital visits. In clinical practice, an intervention consisting of medication reconciliation, review, counseling, and post-discharge follow-up should be provided to such high-risk inpatients. Regarding research priorities, large, multi-center randomized controlled trials should be performed to generate more evidence on the impact of clinical pharmacy interventions on the patient trajectory and economic outcomes.
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http://dx.doi.org/10.1007/s40266-019-00733-1DOI Listing
March 2020

Efficacy and safety of non-benzodiazepine and non-Z-drug hypnotic medication for insomnia in older people: a systematic literature review.

Eur J Clin Pharmacol 2020 Mar 14;76(3):363-381. Epub 2019 Dec 14.

Department of Geriatric Medicine, University Hospitals Leuven, Herestraat 49, Leuven, 3000, Belgium.

Purpose: Insomnia is highly prevalent in older persons and significantly impacts quality of life, functional abilities, and health status. It is frequently treated with benzodiazepines or Z-drugs. Due to adverse events, an increased use of alternative sedative medications has been observed in older adults. We aimed to study the efficacy and safety of alternative sedative medications for treating insomnia in older people, excluding benzodiazepines and Z-drugs.

Methods: We conducted a systematic search of MEDLINE (PubMed), EMBASE, and the Cochrane Central register of Controlled Trials databases. We included randomized controlled trials and prospective and retrospective quasi-experimental studies, conducted in patients older than 65 years, without psychiatric or neurological comorbidities.

Results: The systematic search yielded 9483 articles, of which 24 were included in this review, describing nine different sleep medications in total. No clear beneficial impact on sleep could be demonstrated in studies investigating the impact of melatonin (n = 10), paroxetine (n = 1), diphenhydramine (n = 1), tiagabine (n = 2), and valerian (n = 1). Ramelteon slightly improved sleep latency (n = 4), while doxepin was found to provide a sustained sleep improvement with a safety profile that was comparable to placebo (n = 3). Suvorexant showed an improved sleep maintenance with only mild side effects (n = 1). One study detected increased adverse effects of trazodone after 3 months but did not evaluate the effect on sleep.

Conclusions: The overall level of evidence was limited, making it difficult to draw robust conclusions. Preliminary evidence points towards suvorexant, doxepin, and possibly ramelteon as effective and safe pharmacological alternatives for treating insomnia in older adults.
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http://dx.doi.org/10.1007/s00228-019-02812-zDOI Listing
March 2020

Clinical Outcomes of Rate vs Rhythm Control for Atrial Fibrillation in Older People: A Systematic Review and Meta-Analysis.

Drugs Aging 2020 01;37(1):19-26

Geriatric Department, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.

Background And Objectives: Atrial fibrillation (AF) is highly prevalent in older adults and has been associated with increased morbidity and mortality. To reduce this AF-related morbidity in older adults, antiarrhythmic drugs (AADs) are regularly used for rhythm control, assuming that increasing time in sinus rhythm reduces AF-related morbidity. However, whether AADs can improve clinical outcomes in older adults remains unclear because of the increased risk for adverse drug events compared with rate control. The aim of this study was to determine the impact of rhythm control versus rate control on clinical outcomes in older adults with AF.

Design And Methods: We conducted a systematic review and meta-analysis targeting patients aged ≥65 years with AF and using drugs to control rate or rhythm. Articles that met the following criteria were included: enrolled older patients (sample mean ≥75 years) with AF, compared pharmacological rate versus rhythm control, and reported all-cause mortality, cardiovascular mortality, or ischemic stroke.

Results: Five observational studies were included. In total, 86,926 patients with AF with a mean age ranging from 75 to 92 years were studied. No differences were found between rhythm and rate control for all-cause mortality (odds ratio [OR] 1.11; 95% confidence interval [CI] 0.78-1.59; I = 79.6%; n = 28,526; four studies) and cardiovascular mortality (OR 1.09; 95% CI 0.81-1.47; I = 0%; n = 2292; two studies). Rhythm control resulted in fewer strokes (OR 0.86; 95% CI 0.80-0.93; I = 0%; n = 59,496), although this was mainly determined by one study.

Conclusion: All collected data were observational, which precluded making strong recommendations. Furthermore, all CIs were wide, increasing the uncertainty of the observed effects. As such, evidence was insufficient to recommend rhythm or rate control as the first-line therapy for AF in older adults. As AF is particularly prevalent in older people, more randomized controlled trials are needed in this population.
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http://dx.doi.org/10.1007/s40266-019-00722-4DOI Listing
January 2020

Factors associated with the number of clinical pharmacy recommendations: findings from an observational study in geriatric inpatients.

Acta Clin Belg 2021 Apr 23;76(2):119-126. Epub 2019 Oct 23.

Department of Geriatric Medicine, University Hospitals Leuven, Leuven, Belgium.

: Drug-related problems are prevalent in older inpatients and can be reduced by providing clinical pharmacy (CP) services. Details concerning implementation in clinical practice are frequently lacking. The aim was to describe the output of one such CP program and to identify factors associated with CP recommendations.: A CP program was installed at three acute geriatric wards in a teaching hospital. A convenience sample was collected, consisting of inpatients who received a CP consultation at discharge. Medical conditions, patient demographics, and drug use were evaluated retrospectively. Number and type of the CP recommendations were determined. A Poisson regression analysis was performed to determine factors associated with the number of CP recommendations.: A cohort of 524 patients, aged 85 (interquartile range (IQR): 82-89) years was included. On admission, 10.31 (standard deviation: 4.49) drugs were taken. Three (IQR: 2-4) CP recommendations were provided per patient, of which 70.2% targeted drug discontinuation. A model was derived, containing the following factors: number of drugs on admission (incidence rate ratio (IRR): 1.063; 95% confidence interval (CI): 1.052-1.074), number of previous contacts with the geriatric department (IRR: 0.869; 95%CI: 0.816-0.926), presence of left-ventricular dysfunction (IRR: 1.179, 95% CI: 1.023-1.360), the number of new drugs (IRR: 1.046; 95% CI: 1.021-1.071) and use of colecalciferol (IRR: 1.22; 95% CI: 1.088-1.367).: Five factors were associated with the number of CP recommendations at discharge. This could allow for further patient stratification to increase the efficiency of the CP program.
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http://dx.doi.org/10.1080/17843286.2019.1683128DOI Listing
April 2021

Physician's feedback on a clinical pharmacy program on geriatric wards.

Acta Clin Belg 2020 Oct 10;75(5):321-328. Epub 2019 Jun 10.

Pharmacy Department, University Hospitals Leuven , Leuven, Belgium.

Objectives: As clinical pharmacy (CP) services can improve drug use and clinical outcome in older inpatients, a dedicated CP program was installed at the geriatric wards of an academic hospital. The aim of this study was to evaluate and potentially improve the CP program, by obtaining physician's feedback.

Methods: An anonymous e-questionnaire was sent to all physicians who were active between October 2014 and March 2018 on the acute geriatric wards (80 beds) of the University Hospitals Leuven, Belgium. Thematic content analysis was applied. Six themes were defined: satisfaction with the service, time allocation of the clinical pharmacists, content and clinical relevance of pharmaceutical interventions, communication, time savings for the treating physician and future perspectives.

Results: A total of 45 physicians (59%) completed the e-questionnaire. All respondents were satisfied with the content of the provided pharmaceutical recommendations. A minority (44%) found that a 0.8 full-time equivalent clinical pharmacist presence was sufficient in terms of the expected workload. The provided CP interventions improved quality of care according to 38 (84%) physicians. Oral and written communication were considered necessary by 89% and 82% of physicians, respectively. On average, an estimated 30 minutes physician time (IQR: 15-60) per patient was saved as a result of the program. The majority (87%) preferred clinical pharmacist presence for discharge support in all geriatric patients.

Conclusion: Physician's satisfaction with the CP service was very high. CP services in geriatric inpatients were perceived to be clinically relevant as well as time-saving by the involved physicians.
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http://dx.doi.org/10.1080/17843286.2019.1629054DOI Listing
October 2020

External validation of a clinical pharmacy intervention in geriatric inpatients: a controlled study.

Int J Clin Pharm 2019 Aug 15;41(4):853-858. Epub 2019 May 15.

Department of Geriatric Medicine, University Hospitals Leuven, Louvain, Belgium.

Background Clinical pharmacist interventions have been shown to improve drug use in older adults. Study findings are seldom externally validated however. Objective First, to validate a minimized iteration of a previously tested intervention of clinical pharmacists in a non-academic setting with limited staffing resources. Second, to compare the potentially inappropriate medication (PIM) reduction to two previous controlled interventional studies. Methods A controlled study was performed at geriatric wards. The control group received usual care. The intervention group was exposed to a clinical pharmacist led medication review, based on the use of the RASP list, (the Rationalization of Home Medication by an Adjusted STOPP list in Older Patients). Drug use on admission and at discharge were evaluated, including the number of RASP-identified potentially inappropriate medications (PIMs). The PIM reduction was compared to two previous controlled study findings using a linear mixed model. Results Drug use declined during hospital stay, without differences between control (n = 29) and intervention group (n = 32). Antidepressants and hypnotic drugs were discontinued more frequently in IG patients. More PIMs were reduced in the intervention patients (control vs. intervention: 1.0 vs. 3.0, p < 0.001). Across three controlled studies, a robust reduction of 1.56 PIMs (95% confidence interval 1.10-2.02, p < 0.001) was observed in favor of the CP interventions. Conclusion The minimal CP intervention resulted in fewer RASP PIMs. No net reduction of drug use was observed, yet fewer antidepressants and hypnotic drugs were used. The RASP PIM reduction was comparable to previous investigations.
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http://dx.doi.org/10.1007/s11096-019-00846-yDOI Listing
August 2019

Medication review in older adults: Importance of time to benefit.

Am J Health Syst Pharm 2019 Feb;76(4):247-250

Department of Geriatric Medicine, University Hospitals Leuven, Leuven, Belgium.

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http://dx.doi.org/10.1093/ajhp/zxy038DOI Listing
February 2019

Medication review versus usual care to improve drug therapies in older inpatients not admitted to geriatric wards: a quasi-experimental study (RASP-IGCT).

BMC Geriatr 2018 07 3;18(1):155. Epub 2018 Jul 3.

Department of Geriatric Medicine, University Hospitals Leuven, Louvain, Belgium.

Background: Interdisciplinary geriatric consultation teams (IGCT) are regularly requested to provide comprehensive geriatric assessments in older inpatients. Our primary aim was to evaluate whether medication reviews increased the number of IGCT-provided drug-related recommendations. Secondary aims were to reduce the number of potentially inappropriate medications (PIMs), and to identify the acceptance rate of and determinants for the number of recommendations.

Methods: A before-after study was performed in older inpatients not admitted to acute geriatric wards. The before cohort received usual care (UC); the after cohort was subjected to the intervention (I), consisting of a systematic medication review, based on but not limited to the RASP (Rationalization of Home Medication by an Adjusted STOPP in Older Patients) list. The primary outcome measure was the number of IGCT-provided drug-related recommendations. Age, sex, Charlson Comorbidity Index, creatinine clearance and serum creatinine were ascertained upon enrolment. Following variables were determined on admission and at discharge: number of drugs and number as well as type of RASP-identified PIMs. Acceptance by ward-based physicians was also determined. Poisson regression was performed to identify determinants for the primary outcome measure.

Results: Fifty-nine participants were enrolled (n = 29; n = 30). The intervention increased the number of drug-related recommendations from a median of 0 (IQR: 0-1) to 8 (IQR: 6.75-10) (p < 0.001). The median number of accepted recommendations differed significantly as well (UC vs. I: 0.0 (0.0-0.5) vs. 3.0 (0.0-5.3); p < 0.001). In the intervention cohort, patients were discharged with fewer drugs compared to admission (UC vs. I: 108.5%, IQR: 100.0-135.8% vs. 92%, IQR: 80.5-103.5%; p = 0.002). More RASP PIMs were discontinued in the intervention cohort, with a mean difference of 1.49 RASP PIMs (95% confidence interval (CI): 0.70, 2.23; p < 0.001). Regression analysis identified two determinants: allocation to the intervention cohort with an incidence rate ratio (IRR) of 14.1 (95% CI: 8.30, 23.8) and the number of preadmission drugs with an IRR of 1.06 (95% CI: 1.03, 1.09).

Conclusions: A structured medication review as part of usual IGCT care may contribute to an increased detection of drug-related problems and help to further reduce polypharmacy in older inpatients, not admitted to acute geriatric care wards.

Trial Registration: NCT02165618 , retrospectively registered June 17, 2014.
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http://dx.doi.org/10.1186/s12877-018-0843-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029069PMC
July 2018

Enough Power to Build a Strong Case for Clinical Pharmacy Services?

JAMA Intern Med 2018 06;178(6):864

Geriatric Medicine, Department of Chronic Diseases, Ageing and Metabolism, University Hospitals Leuven, and KU Leuven, Belgium.

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http://dx.doi.org/10.1001/jamainternmed.2018.1706DOI Listing
June 2018

Clinical Pharmacy Services on Geriatric Care Wards: Catch 22 of Implementation and Research.

Drugs Aging 2018 05;35(5):375-377

Department of Geriatric Medicine, University Hospitals Leuven, Louvain, Belgium.

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http://dx.doi.org/10.1007/s40266-018-0547-1DOI Listing
May 2018

Predictors for unintentional medication reconciliation discrepancies in preadmission medication: a systematic review.

Eur J Clin Pharmacol 2017 Nov 25;73(11):1355-1377. Epub 2017 Jul 25.

Pharmacy Department, University Hospitals Leuven, Leuven, Belgium.

Purpose: Discrepancies in preadmission medication (PAM) are common and potentially harmful. Medication reconciliation is able to reduce the discrepancy rate, yet implementation is challenging. In order for reconciliation efforts to be more cost-effective, patients at high risk for reconciliation errors should be identified. The purpose of this systematic review is to identify predictors for unintentional discrepancies in PAM.

Methods: Medline and Embase were searched systematically until June 2017. Only studies concerning adult subjects were retained. Quantitative studies were included if predictors for unintentional discrepancies in the PAM had been determined on hospital admission. Variables were divided into patient-, medication-, and setting-related predictors based on a thematic analysis. Studies on identification of predictors for discrepancies and potentially harmful discrepancies were handled separately.

Results: Thirty-five studies were eligible, of which 5 studies focused on potentially harmful discrepancies. The following 16 significant variables were identified using multivariable prediction models: number of preadmission drugs, patient's age, availability of a drug list, patients' understanding of medication, usage of different outpatient pharmacies, number of high-risk drugs, discipline for which the patient is admitted, admitting physician's experience, number and type of consulted sources, patient's gender, type of care before admission, number of outpatient visits during the past year, class of medication, number of reimbursements, use of an electronic prescription system, and type of admission (elective vs emergency). The number of preadmission drugs was identified as a predictor in 20 studies. Potentially harmful discrepancies were ascertained in 5 studies with age found to have a predictive value in all 5 studies.

Conclusion: Multiple suitable predictors for PAM-related discrepancies were identified of which higher age and polypharmacy were reported most frequently.
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http://dx.doi.org/10.1007/s00228-017-2308-1DOI Listing
November 2017

Combined Use of the Rationalization of Home Medication by an Adjusted STOPP in Older Patients (RASP) List and a Pharmacist-Led Medication Review in Very Old Inpatients: Impact on Quality of Prescribing and Clinical Outcome.

Drugs Aging 2017 02;34(2):123-133

Department of Geriatric Medicine, University Hospitals Leuven, Louvain, Belgium.

Background: Polypharmacy and potentially inappropriate drugs have been associated with negative outcomes in older adults which might be reduced by pharmacist interventions.

Objectives: Our objective was to evaluate the effect of a pharmacist intervention, consisting of the application of the Rationalization of home medication by an Adjusted STOPP in older Patients (RASP) list and a pharmacist-led medication review on polypharmacy, the quality of prescribing, and clinical outcome in geriatric inpatients.

Methods: A monocentric, prospective controlled trial was undertaken at the geriatric wards of a large university hospital. Pharmacists applied the RASP list to the drugs reconciled on admission and additionally performed an expert-based medication review, upon which recommendations were provided to the treating physicians. The primary outcome was the composite endpoint of drug discontinuation and dose reduction of drugs taken on admission. Secondary outcomes included RASP-identified potentially inappropriate medications (PIMs), the number of Emergency Department (ED) visits and quality of life (QOL) registered up to 3 months after discharge.

Results: On average, patients (n = 172) took 10 drugs on admission and were 84.5 years (standard deviation 4.8) of age. More drugs were discontinued or reduced in dose in the intervention group {control vs.intervention:median (interquartile range [IQR]) 3 (2-5) vs. 5 (3-7); p < 0.001}. More PIMs were discontinued in the intervention group, leading to less PIM at discharge [control vs.intervention:median (IQR) 2 (1-3) vs. 0.5 (0-1); p < 0.001]. No signal of harm was seen, and a significant improvement of QOL and less ED visits without hospitalization were observed.

Conclusions: The combined intervention safely reduced drug use in very old inpatients and outperformed usual geriatric care. An increased QOL was seen, as well as a trend towards less ED visits. ClinicalTrials.gov Identifier: NCT01513265.
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February 2017

Exploring the relationship between fall risk-increasing drugs and fall-related fractures.

Int J Clin Pharm 2016 Apr 9;38(2):243-51. Epub 2016 Jan 9.

Clinical Pharmacology and Pharmacotherapy, University Hospitals Leuven, Herestraat 49, 3000, Louvain, Belgium.

Background: Hospital admissions due to fall-related fractures are a major problem in the aging population. Several risk factors have been identified, including drug use. Most studies often retrieved prescription-only drugs from national databases. These are associated with some limitations as they do not always reliably reproduce the complete patient's active drug list.

Objective: To evaluate the association between the number of FRIDs intake identified by a standardised medication reconciliation process and a fall-related fracture leading to a hospital admission in older adults.

Setting: The first cohort has been recruited from one traumatology ward of a tertiary teaching hospital in Belgium and the second cohort has been recruited from 11 community pharmacies in Belgium.

Method: A prospective study with two individually matched cohorts was performed. Adult patients (≥75 years) admitted with an injury due to a fall were included in the first cohort (faller group). The second cohort consisted of patients who did not suffer from a fall within the last 6 months (non-faller group). Matching was performed for age, gender, place of residence and use of a walking aid. In both groups, clinical pharmacists and undergraduate pharmacy students obtained the medication history, using a standardised approach. A list of drugs considered to increase the risk of falling was created. It included cardiovascular drugs and drugs acting on the nervous system. A linear mixed model was used to compare the number of fall risk-increasing drugs between fallers and non-fallers.

Main Outcome Measure: The number of fall risk-increasing drugs in a faller versus a non-faller group.

Results: Sixty-one patients were matched with 121 non-fallers. Patients received on average 3.1 ± 2.1 and 3.2 ± 1.8 fall risk-increasing drugs in the faller and in the non-faller group, respectively. The mean number of fall risk-increasing drugs was comparable in both groups (p = 0.844), even after adjusting for alcohol consumption, fear of falling, vision and foot problems (p = 0.721).

Conclusion: In a sample of hospitalised patients admitted for a fall-related injury, no significant difference in the number of fall risk-increasing drugs versus that of an outpatient group of non-fallers was found.
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April 2016
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