Publications by authors named "Hans Wouters"

41 Publications

Association between sedentary time and cognitive function: A focus on different domains of sedentary behavior.

Prev Med 2021 Jul 16:106731. Epub 2021 Jul 16.

Radboud Institute for Health Sciences, Department of Physiology, Radboud university medical center, Nijmegen, the Netherlands; Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, United Kingdom. Electronic address:

Studies which examined the association between sedentary behavior (SB) and cognitive function have presented equivocal findings. Mentally active/inactive sedentary domains may relate differently to cognitive function. We examined associations between SB and cognitive function, specifically focusing on different domains. Participants were recruited from the Nijmegen Exercise Study 2018 in the Netherlands. SB (hours/day) was measured with the Sedentary Behavior Questionnaire. Cognitive function was assessed with a validated computer self-test (COST-A), and a z-score calculated for global cognitive function. Multivariate linear regression assessed associations between tertiles of sedentary time and cognitive function. Cognition tests were available from 2821 participants, complete data from 2237 participants (43% female), with a median age of 61 [IQR 52-67] and a mean sedentary time of 8.3 ± 3.2 h/day. In fully adjusted models, cognitive function was significantly better in participants with the highest total sedentary time (0.07 [95% CI 0.02-0.12], P = 0.01), work-related sedentary time (0.13 [95% CI 0.07-0.19], P < 0.001), and non-occupational computer time (0.07 [95% CI 0.02-0.12], P = 0.01), compared to the least sedentary. Leisure sedentary time and time spent sedentary in the domains TV, reading or creative time showed no association with cognitive function in final models (all P > 0.05). We found a strong, independent positive association between total SB and cognitive function in a heterogenous population. This relation was not consistent across different domains, with especially work- and computer-related SB being positively associated with cognitive function. This highlights the importance of assessing the various sedentary domains in understanding the relation between sedentary time and cognitive function.
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http://dx.doi.org/10.1016/j.ypmed.2021.106731DOI Listing
July 2021

Developing a clinical prediction rule for repeated consultations with functional somatic symptoms in primary care: a cohort study.

BMJ Open 2021 01 8;11(1):e040730. Epub 2021 Jan 8.

Department of General Practice and Elderly Care Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Objectives: Patients who present in primary care with chronic functional somatic symptoms (FSS) have reduced quality of life and increased health care costs. Recognising these early is a challenge. The aim is to develop and internally validate a clinical prediction rule for repeated consultations with FSS.

Design And Setting: Records from the longitudinal population-based ('Lifelines') cohort study were linked to electronic health records from general practitioners (GPs).

Participants: We included patients consulting a GP with FSS within 1 year after baseline assessment in the Lifelines cohort.

Outcome Measures: The outcome is repeated consultations with FSS, defined as ≥3 extra consultations for FSS within 1 year after the first consultation. Multivariable logistic regression, with bootstrapping for internal validation, was used to develop a risk prediction model from 14 literature-based predictors. Model discrimination, calibration and diagnostic accuracy were assessed.

Results: 18 810 participants were identified by database linkage, of whom 2650 consulted a GP with FSS and 297 (11%) had ≥3 extra consultations. In the final multivariable model, older age, female sex, lack of healthy activity, presence of generalised anxiety disorder and higher number of GP consultations in the last year predicted repeated consultations. Discrimination after internal validation was 0.64 with a calibration slope of 0.95. The positive predictive value of patients with high scores on the model was 0.37 (0.29-0.47).

Conclusions: Several theoretically suggested predisposing and precipitating predictors, including neuroticism and stressful life events, surprisingly failed to contribute to our final model. Moreover, this model mostly included general predictors of increased risk of repeated consultations among patients with FSS. The model discrimination and positive predictive values were insufficient and preclude clinical implementation.
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http://dx.doi.org/10.1136/bmjopen-2020-040730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799137PMC
January 2021

Drug Burden Index and Cognitive and Physical Function in Aged Care Residents: A Longitudinal Study.

J Am Med Dir Assoc 2020 08;21(8):1086-1092.e1

Department of PharmacoTherapy, PharmacoEpidemiology & PharmacoEconomics, University of Groningen, Groningen Research Institute of Pharmacy, Groningen, the Netherlands.

Objectives: Anticholinergic/antimuscarinic and sedative medications (eg, benzodiazepines) have been found to be associated with poorer cognitive and physical function and mobility impairment in older age. However, previous studies were mostly conducted among community-dwelling older individuals and had often a cross-sectional design. Accordingly, our aim was to examine longitudinal associations between cumulative exposure to anticholinergic and sedative medications and cognitive and physical function among residents from aged care homes.

Design: Longitudinal study.

Setting And Participants: A total of 4624 residents of Dutch aged care homes of whom data were collected between June 2005 and April 2014.

Methods: Outcome measures were collected with the Long-Term Care Facilities assessment from the international Residential Assessment Instrument (interRAI-LTCF) and included the Cognitive Performance Scale, the Activities of Daily Living (ADL) Hierarchy scale, a timed 4-meter walk test, distance walked, hours of physical activity, and days being outside. Cumulative exposure to anticholinergic and sedative medications was calculated with the Drug Burden Index (DBI), a linear additive pharmacological dose-response model. Associations were examined with linear mixed models to take the potential dependence of observations into account (ie, data were collected at repeated assessment occasions of residents who were clustered in aged care homes). Analyses were adjusted for sex, age, dementia, comorbidity (neurological, psychiatric, cardiovascular, oncological, and pulmonary), fractures, depressive symptoms, and medications excluded from the DBI.

Results: We observed significant longitudinal associations between a higher DBI and poorer ADLs, fewer hours of physical activity, and fewer days being outside. We found no significant longitudinal association between a higher DBI and poorer cognitive function.

Conclusions And Implications: Over time, cumulative exposure to anticholinergic and sedative medications is associated with poorer physical but not cognitive function in aged care residents. Careful monitoring of aged care residents with high cumulative anticholinergic and sedative medication exposure is needed.
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http://dx.doi.org/10.1016/j.jamda.2020.05.037DOI Listing
August 2020

Factors associated with workarounds in barcode-assisted medication administration in hospitals.

J Clin Nurs 2020 Jul 28;29(13-14):2239-2250. Epub 2020 Feb 28.

Department Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen, The Netherlands.

Aims And Objectives: To identify that workarounds (defined as "informal temporary practices for handling exceptions to normal procedures or workflow") by nurses using information technology potentially compromise medication safety. Therefore, we aimed to identify potential risk factors associated with workarounds performed by nurses in Barcode-assisted Medication Administration in hospitals.

Background: Medication errors occur during the prescribing, distribution and administration of medication. Errors could harm patients and be a tragedy for both nurses and medical doctors involved. Interventions to prevent errors have been developed, including those based on information technology. To cope with shortcomings in information technology-based interventions as Barcode-assisted Medication Administration, nurses perform workarounds. Identification of workarounds in information technology is essential to implement better-designed software and processes which fit the nurse workflow.

Design: We used the data from our previous prospective observational study, performed in four general hospitals in the Netherlands using Barcode techniques, to administer medication to inpatients.

Methods: Data were collected from 2014-2016. The disguised observation was used to gather information on potential risk factors and workarounds. The outcome was a medication administration with one or more workarounds. Logistic mixed models were used to determine the association between potential risk factors and workarounds. The STROBE checklist was used for reporting our data.

Results: We included 5,793 medication administrations among 1,230 patients given by 272 nurses. In 3,633 (62.7%) of the administrations, one or more workarounds were observed. In the multivariate analysis, factors significantly associated with workarounds were the medication round at 02 p.m.-06 p.m. (adjusted odds ratio [OR]: 1.60, 95% CI: 1.05-2.45) and 06 p.m.-10 p.m. (adjusted OR: 3.60, 95% CI: 2.11-6.14) versus the morning shift 06 a.m.-10 a.m., the workdays Monday (adjusted OR: 2.59, 95% CI: 1.51-4.44), Wednesday (adjusted OR: 1.92, 95% CI: 1.2-3.07) and Saturday (adjusted OR: 2.24, 95% CI: 1.31-3.84) versus Sunday, the route of medication, nonoral (adjusted OR: 1.28, 95% CI: 1.05-1.57) versus the oral route of drug administration, the Anatomic Therapeutic Chemical classification-coded medication "other" (consisting of the irregularly used Anatomic Therapeutic Chemical classes [D, G, H, L, P, V, Y, Z]) (adjusted OR: 1.49, 95% CI: 1.05-2.11) versus Anatomic Therapeutic Chemical class A (alimentary tract and metabolism), and the patient-nurse ratio ≥6-1 (adjusted OR: 5.61, 95% CI: 2.9-10.83) versus ≤5-1.

Conclusions: We identified several potential risk factors associated with workarounds performed by nurses that could be used to target future improvement efforts in Barcode-assisted Medication Administration.

Relevance To Clinical Practice: Nurses administering medication in hospitals using Barcode-assisted Medication Administration frequently perform workarounds, which may compromise medication safety. In particular, nurse workload and the patient-nurse ratio could be the focus for improvement measures as these are the most clearly modifiable factors identified in this study.
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http://dx.doi.org/10.1111/jocn.15217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328795PMC
July 2020

Barriers and Facilitators of Conducting Medication Reviews in Nursing Home Residents: A Qualitative Study.

Front Pharmacol 2019 18;10:1026. Epub 2019 Sep 18.

Department of PharmacoTherapy, Epidemiology & Economics (PTEE), Faculty of Science and Engineering, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, Netherlands.

Inappropriate medication prescribing is a recognized clinical problem in nursing home residents of whom many have polypharmacy. However, results about the effectiveness of medication reviews targeted at improving prescribing and deprescribing have been equivocal. We therefore examined barriers and facilitators of conducting medication reviews. We purposively sampled medication reviews to capture salient barriers and facilitators of conducting medication reviews both in nursing home care units for dementia and disabling conditions. We held semi-structured interviews about consecutive steps of medication reviews. Interviews were transcribed verbatim and analyzed with the "method of constant comparison." Six nursing home residents/relatives of nursing home residents, 8 elder care physicians, 5 pharmacists, and 10 nurses took part in the semi-structured interviews. We observed four overarching themes of barriers and facilitators: "realizing fidelity of the patient perspective (theme 1)," "level of comprehensiveness of medication reviews (theme 2)," "inclinations of healthcare providers (theme 3)," and "inter-professional collaboration and alliances (theme 4)." Theme 1 "realizing fidelity of the patient perspective" referred to the observation that assessing the patient perspective was a delicate balance between the value and the impediments of a proper assessment of the patient perspective. Theme 2 "level of comprehensiveness of medication reviews" reflected the struggle of practitioners to find an optimum between medication reviews being both comprehensive and feasible. Theme 3 "inclinations of healthcare providers" concerned setting intervention targets that were complementary to the practices of physicians and keeping the pharmacist blind to the patient perspective as a countermeasure to physicians' inclinations. Finally, theme 4 "inter-professional collaboration and alliances" highlighted mutual support and inter-professional collaboration to strengthen healthcare practitioners' contributions. These themes of barriers and facilitators emphasize the need to improve meta-communication during the medication review process. This pertains to the need for healthcare providers to appraise the fidelity of the patient perspective in a dialogue with residents/relatives. Furthermore, discourse between healthcare practitioners is needed beforehand about the level of comprehensiveness intervention targets, and inter-professional collaboration.
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http://dx.doi.org/10.3389/fphar.2019.01026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759938PMC
September 2019

Feasibility, acceptability and potential effectiveness of an information technology-based, pharmacist-led intervention to prevent an increase in anticholinergic and sedative load among older community-dwelling individuals.

Ther Adv Drug Saf 2019 30;10:2042098618805881. Epub 2018 Oct 30.

University of Groningen, Groningen, The Netherlands.

Background: Anticholinergic/sedative medications are frequently used by older people, despite their negative impacts on cognitive and physical function. We explore the feasibility, acceptability and potential effectiveness of an innovative information technology (IT)-based intervention to prevent an increase in anticholinergic/sedative load in older people.

Methods: This was a prospective study in 51 Dutch community pharmacies. Pharmacists used an IT-based tool to identify patients aged ⩾65 years, with existing high anticholinergic/sedative loads (drug burden index ⩾2) and a newly initiated anticholinergic/sedative medication. We determined the following. Feasibility: number of eligible patients identified. Acceptability: pharmacists' satisfaction with the intervention, pharmacists' time investment and patients' willingness to reduce medication use. Potential effectiveness: number of recommendations, rate of agreement of general practitioners (GPs) with proposed recommendations and factors associated with agreement. To evaluate the latter, pharmacists conducted medication reviews and proposed recommendations to GPs for 5-10 patients selected by the IT-based tool.

Results: We included 305 patients from 47 pharmacies. Feasibility: a mean of 17.0 (standard deviation, 8.8) patients were identified per pharmacy. Acceptability: 43 pharmacists (91.5%) were satisfied with the intervention. The median time investment per patient was 33 min (range 6.5-210). Of 35 patients, 30 (85.7%) were willing to reduce medication use. Potential effectiveness: pharmacists proposed 351 recommendations for 212 patients (69.5%). GPs agreed with recommendations for 108 patients (35.4%). Agreement to stop a medication was reached in 19.8% of recommendations for newly initiated medications (37 of 187) and for 15.2% of recommendations for existing medications (25 of 164). Agreement was more likely for recommendations on codeine [odds ratio (OR) 3.30; 95% confidence interval (CI) 1.14-9.57] or medications initiated by a specialist (OR 2.85; 95% CI 1.19-6.84) and less likely for pharmacies with lower level of collaboration with GPs (OR 0.15; 95% CI 0.02-0.97).

Conclusion: This innovative IT-based intervention was feasible, acceptable and potentially effective. In one-third of patients an increase in anticholinergic/sedative load was prevented within reasonable time investment.
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http://dx.doi.org/10.1177/2042098618805881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463339PMC
October 2018

Distinct Profiles on Subjective and Objective Adherence Measures in Patients Prescribed Antidepressants.

Drugs 2019 Apr;79(6):647-654

Division of Pharmacoepidemiology and Clinical Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.

Objective: A recurrent observation is that associations between self-reported and objective medication adherence measures are often weak to moderate. Our aim was therefore to identify patients with different profiles on self-reported and objective adherence measures.

Study Design And Setting: This was an observational study of 221 community pharmacy patients who were dispensed antidepressants. Adherence profiles were estimated with Latent Profile Analysis (LPA) using data on self-reported adherence (Medication Adherence Rating Scale) complemented with data on medication beliefs (perceived necessity and concerns measured with the Beliefs about Medicines Questionnaire) and data from objective adherence measures (electronic monitoring of medication taking and the Medication Possession Ratio calculated from pharmacy dispensing data).

Results: 'Goodness-of-fit' statistics indicated the presence of three classes: "concordantly high adherent" (83%, high adherence on all measures), "concordantly suboptimal adherent" (11%, low adherence on all measures), and "discordant" (6%, high self-reported adherence but lower adherence on objective measures).

Conclusion: Most patients had concordant outcomes on self-reported and objective measures of adherence. A small discordant class had high self-reported but low objective adherence. LPA will enable sensitivity analyses in future studies, for example excluding patients from the discordant class.
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http://dx.doi.org/10.1007/s40265-019-01107-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6483946PMC
April 2019

Anticholinergic and sedative medication use in older community-dwelling people: A national population study in the Netherlands.

Pharmacoepidemiol Drug Saf 2019 03 12;28(3):315-321. Epub 2019 Feb 12.

PharmacoTherapy, Epidemiology and Economics, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, the Netherlands.

Purpose: To identify the proportion of older adults with a high anticholinergic/sedative load and to identify patient subgroups based on type of central nervous system (CNS)-active medication used.

Methods: A cross-sectional study of a nationwide sample of patients with anticholinergic/sedative medications dispensed by 1779 community pharmacies in the Netherlands (90% of all community pharmacies) in November 2016 was conducted. Patients aged older than 65 years with a high anticholinergic/sedative load defined as having a drug burden index (DBI) greater than 1 were included. Proportion of patients with a high anticholinergic/sedative load was calculated by dividing the number of individuals in our study population by the 2.4 million older patients using medications dispensed from study pharmacies. Patient subgroups based on type of CNS-active medications used were identified with latent class analysis.

Results: Overall, 8.7% (209 472 individuals) of older adults using medications had a DBI greater than 1. Latent class analysis identified four patient subgroups (classes) based on the following types of CNS-active medications used: "combined psycholeptic/psychoanaleptic medication" (class 1, 57.9%), "analgesics" (class 2, 17.9%), "antiepileptic medication" (class 3, 17.8%), and "anti-Parkinson medication" (class 4, 6.3%).

Conclusions: A large proportion of older adults in the Netherlands had a high anticholinergic/sedative load. Four distinct subgroups using specific CNS-active medication were identified. Interventions aiming at reducing the overall anticholinergic/sedative load should be tailored to these subgroups.
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http://dx.doi.org/10.1002/pds.4698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6593836PMC
March 2019

Long-Term Exposure to Anticholinergic and Sedative Medications and Cognitive and Physical Function in Later Life.

J Gerontol A Biol Sci Med Sci 2020 01;75(2):357-365

Department of PharmacoTherapy, -Epidemiology & -Economics, Faculty of Science and Engineering, University of Groningen, The Netherlands.

Background: Anticholinergic and sedative medications are frequently prescribed to older individuals. These medications are associated with short-term cognitive and physical impairment, but less is known about long-term associations. We therefore examined whether over 20 years cumulative exposure to these medications was related to poorer cognitive and physical functioning.

Methods: Older adult participants of the Longitudinal Aging Study Amsterdam (LASA) were followed from 1992 to 2012. On seven measurement occasions, cumulative exposure to anticholinergic and sedative medications was quantified with the drug burden index (DBI), a linear additive pharmacological dose-response model. Cognitive functioning was assessed with the Mini-Mental State Examination (MMSE), Alphabet Coding Task (ACT, three trials), Auditory Verbal Learning Test (AVLT, learning and retention condition), and Raven Colored Progressive Matrices (RCPM, two trials). Physical functioning was assessed with the Walking Test (WT), Cardigan Test (CT), Chair Stands Test (CST), Balance Test (BT), and self-reported Functional Independence (FI). Data were analyzed with linear mixed models adjusted for age, education, sex, living with a partner, BMI, depressive symptoms, comorbidities (cardiovascular disease, diabetes, cancer, COPD, osteoarthritis, CNS diseases), and prescribed medications.

Results: Longitudinal associations were found of the DBI with poorer cognitive functioning (less items correct on the three ACT trials, AVLT learning condition, and the two RCPM trials) and with poorer physical functioning (longer completion time on the CT, CST, and lower self-reported FI).

Conclusions: This longitudinal analysis of data collected over 20 years, showed that higher long-term cumulative exposure to anticholinergic and sedative medications was associated with poorer cognitive and physical functioning.
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http://dx.doi.org/10.1093/gerona/glz019DOI Listing
January 2020

Non-adherence to antidepressants among older patients with depression: a longitudinal cohort study in primary care.

Fam Pract 2019 01;36(1):12-20

Department of General Practice, University Medical Center Groningen, University of Groningen, Groningen.

Background: Depression is common among older adults and is typically treated with antidepressants.

Objective: To determine the non-adherence rates to antidepressants among older adults in primary care, based on non-initiation, suboptimal implementation or non-persistence.

Methods: We selected all patients aged ≥60 years and diagnosed with depression in 2012, from the Netherlands Institute for Health Services Research (NIVEL) Primary Care Database. Non-initiation was defined as no dispensing within 14 days of the first prescription; suboptimal implementation, as fewer than 80% of the days covered by dispensed dosages; and non-persistence, as discontinuation within 294 days after first dispense. First, we determined the antidepressant non-initiation, suboptimal implementation and non-persistence rates. Second, we examined whether comorbidity and chronic drug use were associated with non-adherence by mixed-effects logistic regression (non-initiation or suboptimal implementation as dependent variables) and a clustered Cox regression (time to non-persistence).

Results: Non-initiation, suboptimal implementation and non-persistence rates were 13.5%, 15.2% and 37.1%, respectively. As the number of chronically used drugs increased, the odds of suboptimal implementation (odds ratio, 0.89; 95% confidence interval, 0.83-0.95) and of non-persistence (hazard ratio, 0.87; 95% confidence interval, 0.82-0.92) reduced.

Conclusions: Non-adherence to antidepressants is high among older patients with depression in primary care settings. Adherence is better when patients are accustomed to taking larger numbers of prescribed drugs, but this only provides partial explanation of the variance. GPs should be aware of the high rates of non-adherence. Emphasizing the importance of adhering to the optimal length of antidepressant therapy might be prudent first steps to improving adherence.
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http://dx.doi.org/10.1093/fampra/cmy106DOI Listing
January 2019

Non-adherence to cardiovascular drugs in older patients with depression: A population-based cohort study.

Int J Cardiol 2019 Jan 1;274:366-371. Epub 2018 Sep 1.

University of Groningen, University Medical Center Groningen, Department of General Practice, Groningen, the Netherlands; NIVEL, Netherlands Institute for Health Services Research, Utrecht, the Netherlands.

Background: Depression is common among patients with cardiovascular disease and has been associated with both drug non-adherence and increased mortality. Non-adherence can occur because of non-initiation, suboptimal implementation, or non-persistence. We aimed to determine if depression increased the risk of any of these components of non-adherence among older patients prescribed cardiovascular drugs in primary care.

Methods: A longitudinal analysis of routine primary care data from the Nivel Primary Care Database was performed using data for 2011-2013. A total of 1512 patients aged ≥60 years diagnosed with depression in 2012 were compared with age- and sex-matched groups with either other psychological diagnoses (N = 1457) or mentally healthy controls (N = 1508), resulting in the inclusion of 4477 patients. Non-adherence was classified as non-initiation, suboptimal implementation, or non-persistence. Regression analyses were performed to determine the association between mental health status and non-initiation, suboptimal implementation, and non-persistence.

Results: Mixed-effects logistic regression analyses showed increased odds for suboptimal implementation of beta-blockers among depressed patients (2.18; 95% CI 1.29-3.69). For non-persistence, a clustered Cox regression analysis demonstrated that, compared with controls, there was an increased hazard ratio for depressed patients to discontinue beta-blockers (2.31; 95% CI 1.58-3.37) and calcium antagonists (1.74; 95% CI 1.23-2.46).

Conclusions: It is likely that older patients in primary care diagnosed with depression are at increased risk of non-persistence with cardiovascular drug therapy. Because non-adherence is associated with increased cardiovascular mortality, it is important that physicians ensure that older depressed patients persevere with therapy.
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http://dx.doi.org/10.1016/j.ijcard.2018.08.100DOI Listing
January 2019

Reducing the anticholinergic and sedative load in older patients on polypharmacy by pharmacist-led medication review: a randomised controlled trial.

BMJ Open 2018 07 19;8(7):e019042. Epub 2018 Jul 19.

Groningen Research Institute of Pharmacy, Unit of PharmacoTherapy, Epidemiology and Economics, University of Groningen, Groningen, Netherlands.

Objective: To evaluate if a pharmacist-led medication review is effective at reducing the anticholinergic/sedative load, as measured by the Drug Burden Index (DBI).

Design: Randomised controlled single blind trial.

Setting: 15 community pharmacies in the Northern Netherlands.

Participants: 157 community-dwelling patients aged ≥65 years who used ≥5 medicines for ≥3 months, including at least one psycholeptic/psychoanaleptic medication and who had a DBI≥1.

Intervention: A medication review by the community pharmacist in collaboration with the patient's general practitioner and patient.

Primary And Secondary Outcomes Measures: The primary outcome was the proportion of patients whose DBI decreased by at least 0.5. Secondary outcomes were the presence of anticholinergic/sedative side effects, falls, cognitive function, activities of daily living, quality of life, hospital admission and mortality. Data were collected at baseline and 3 months follow-up.

Results: Mean participant age was 75.7 (SD, 6.9) years in the intervention arm and 76.6 (SD, 6.7) years in the control arm, the majority were female (respectively 69.3% and 72.0%). Logistic regression analysis showed no difference in the proportion of patients with a≥0.5 decrease in DBI between intervention arm (17.3%) and control arm (15.9%), (OR 1.04, CI 0.47 to 2.64, p=0.927). Intervention patients scored higher on the Digit Symbol Substitution Test, measure of cognitive function (OR 2.02, CI 1.11 to 3.67, p=0.021) and reported fewer sedative side effects (OR 0.61, CI 0.40 to 0.94, p=0.024) at follow-up. No significant difference was found for other secondary outcomes.

Conclusions: Pharmacist-led medication review as currently performed in the Netherlands was not effective in reducing the anticholinergic/sedative load, measured with the DBI, within the time frame of 3 months. Preventive strategies, signalling a rising load and taking action before chronic use of anticholinergic/sedative medication is established may be more successful.

Trial Registration Number: NCT02317666.
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http://dx.doi.org/10.1136/bmjopen-2017-019042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6059312PMC
July 2018

Discontinuing Inappropriate Medication Use in Nursing Home Residents: A Cluster Randomized Controlled Trial.

Ann Intern Med 2017 Nov 10;167(9):609-617. Epub 2017 Oct 10.

From University of Groningen and University Medical Center Groningen, Groningen, and VU University Medical Center, Amsterdam, the Netherlands.

Background: Inappropriate prescribing is a well-known clinical problem in nursing home residents, but few interventions have focused on reducing inappropriate medication use.

Objective: To examine successful discontinuation of inappropriate medication use and to improve prescribing in nursing home residents.

Design: Pragmatic cluster randomized controlled trial, with clustering by elder care physicians and their wards. (ClinicalTrials.gov: NCT01876095).

Setting: 59 Dutch nursing home wards for long-term care.

Patients: Residents with a life expectancy greater than 4 weeks who consented to treatment with medication.

Intervention: Multidisciplinary Multistep Medication Review (3MR) consisting of an assessment of the patient perspective, medical history, critical appraisal of medications, a meeting between the treating elder care physician and the pharmacist, and implementation of medication changes.

Measurements: Successful discontinuation of use of at least 1 inappropriate drug (that is, without relapse or severe withdrawal symptoms) and clinical outcomes (neuropsychiatric symptoms, cognitive function, and quality of life) after 4 months of follow-up.

Results: Nineteen elder care physicians (33 wards) performed the 3MR, and 16 elder care physicians (26 wards) followed standard procedures. A total of 426 nursing home residents (233 in the intervention group and 193 in the control group) were followed for an average of 144 days (SD, 21). In an analysis of all participants, use of at least 1 inappropriate medication was successfully discontinued for 91 (39.1%) residents in the intervention group versus 57 (29.5%) in the control group (adjusted relative risk, 1.37 [95% CI, 1.02 to 1.75]). Clinical outcomes did not deteriorate between baseline and follow-up.

Limitations: The 3MR was done only once. Some withdrawal symptoms or relapses may have been missed.

Conclusion: The 3MR is effective in discontinuing inappropriate medication use in frail nursing home residents without a decline in their well-being.

Primary Funding Source: Netherlands Organisation for Health Research and Development.
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http://dx.doi.org/10.7326/M16-2729DOI Listing
November 2017

Association between workarounds and medication administration errors in bar-code-assisted medication administration in hospitals.

J Am Med Inform Assoc 2018 04;25(4):385-392

Faculty of Science and Engineering, Department of PharmacoTherapy, PharmacoEpidemiology and PharmaEconomics, University of Groningen, Groningen, the Netherlands.

Objective: To study the association of workarounds with medication administration errors using barcode-assisted medication administration (BCMA), and to determine the frequency and types of workarounds and medication administration errors.

Materials And Methods: A prospective observational study in Dutch hospitals using BCMA to administer medication. Direct observation was used to collect data. Primary outcome measure was the proportion of medication administrations with one or more medication administration errors. Secondary outcome was the frequency and types of workarounds and medication administration errors. Univariate and multivariate multilevel logistic regression analysis were used to assess the association between workarounds and medication administration errors. Descriptive statistics were used for the secondary outcomes.

Results: We included 5793 medication administrations for 1230 inpatients. Workarounds were associated with medication administration errors (adjusted odds ratio 3.06 [95% CI: 2.49-3.78]). Most commonly, procedural workarounds were observed, such as not scanning at all (36%), not scanning patients because they did not wear a wristband (28%), incorrect medication scanning, multiple medication scanning, and ignoring alert signals (11%). Common types of medication administration errors were omissions (78%), administration of non-ordered drugs (8.0%), and wrong doses given (6.0%).

Discussion: Workarounds are associated with medication administration errors in hospitals using BCMA. These data suggest that BCMA needs more post-implementation evaluation if it is to achieve the intended benefits for medication safety.

Conclusion: In hospitals using barcode-assisted medication administration, workarounds occurred in 66% of medication administrations and were associated with large numbers of medication administration errors.
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http://dx.doi.org/10.1093/jamia/ocx077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646849PMC
April 2018

Preferences of Patients and Pharmacists with Regard to the Management of Drug-Drug Interactions: A Choice-Based Conjoint Analysis.

Drug Saf 2018 02;41(2):179-189

SIR Institute for Pharmacy Practice and Policy, Theda Mansholtstraat 5B, 2331 JE, Leiden, The Netherlands.

Introduction: The management of drug-drug interactions (DDIs) is a complex process in which risk-benefit assessments should be combined with the patient's perspective.

Objective: The aim of this study was to determine patients' and pharmacists' preferences regarding DDI management.

Methods: We conducted a choice-based conjoint survey about a fictitious DDI concerning the combination of a cardiovascular drug and an antibiotic for pneumonia. Patients and pharmacists had to choose 12 times between two management options. The options were described by five attributes, including risk, benefit and practical consequences. Each attribute could have two different levels, which were varied over the choice tasks. Latent class analysis was used to identify potential classes of respondents with distinct patterns of similar preferences.

Results: In total, 298 patients and 178 pharmacists completed the questionnaire. The latent class model for both patients and pharmacists resulted in three classes. For patients, in one class the most importance was attached to avoiding switch of medication (class probability 20%), in a second class to fewer adverse events (41%), and in a third class to blood sampling (39%). For pharmacists, again one class attached the highest importance to avoiding switch of medication (31%). The other classes gave priority to curing pneumonia (31%) and avoiding blood sampling (38%).

Conclusion: The results showed diverging preferences regarding DDI management among both patients and pharmacists. Different groups attached different value to risk and benefit versus practical considerations. Awareness of existing variability in preferences among and between pharmacists and patients is a step towards shared decision making in DDI management.
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http://dx.doi.org/10.1007/s40264-017-0601-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5808046PMC
February 2018

Blended care vs. usual care in the treatment of depressive symptoms and disorders in general practice [BLENDING]: study protocol of a non-inferiority randomized trial.

BMC Psychiatry 2017 06 13;17(1):218. Epub 2017 Jun 13.

Department of General Practice, University of Groningen, University Medical Center Groningen, PO Box 196, 9700 AD, Groningen, the Netherlands.

Background: The majority of patients with depressive disorders are treated by general practitioners (GPs) and are prescribed antidepressant medication. Patients prefer psychological treatments but they are under-used, mainly due to time constraints and limited accessibility. A promising approach to deliver psychological treatment is blended care, i.e. guided online treatment. However, the cost-effectiveness of blended care formatted as an online psychological treatment supported by the patients' own GP or general practice mental health worker (MHW) in routine primary care is unknown. We aim to demonstrate non-inferiority of blended care compared with usual care in patients with depressive symptoms or a depressive disorder in general practice. Additionally, we will explore the real-time course over the day of emotions and affect, and events within individuals during treatment.

Methods: This is a pragmatic non-inferiority trial including 300 patients with depressive symptoms, recruited by collaborating GPs and MHWs. After inclusion, participants are randomized to either blended care or usual care in routine general practice. Blended care consists of the 'Act and Feel' treatment: an eight-week web-based program based on behavioral activation with integrated monitoring of depressive symptomatology and automatized feedback. GPs or their MHWs coach the participants through regular face-to-face or telephonic consultations with at least three sessions. Depressive symptomatology, health status, functional impairment, treatment satisfaction, daily activities and resource use are assessed during a follow-up period of 12 months. During treatment, real-time fluctuations in emotions and affect, and daily events will be rated using ecological momentary assessment. The primary outcome is the reduction of depressive symptoms from baseline to three months follow-up. We will conduct intention-to-treat analyses and supplementary per-protocol analyses.

Discussion: This trial will show whether blended care might be an appropriate treatment strategy for patients with depressive symptoms and depressive disorder in general practice.

Trial Registration: Netherlands Trial Register: NTR4757; 25 August 2014. http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4757 . (Archived by WebCite® at http://www.webcitation.org/6mnXNMGef ).
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http://dx.doi.org/10.1186/s12888-017-1376-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5470276PMC
June 2017

Physical Activity and Cognitive Function of Long-Distance Walkers: Studying Four Days Marches Participants.

Rejuvenation Res 2017 Oct 24;20(5):367-374. Epub 2017 Jul 24.

4 Department of Physiology, Radboud University Medical Centre , Nijmegen, The Netherlands .

Studies show physical activity to be beneficial for cognitive function. However, studies usually included individuals who were not particularly inclined to exercise. Following research among master athletes, we examined associations between physical activity and cognitive function in participants of the International Nijmegen Four Days Marches. These individuals are also inclined to exercise. On 4 consecutive days >40,000 participants walk a daily distance of 30-50 km (120-200 km or 75-125 miles in total). Four Days Marches participants and less active or inactive control participants from the Nijmegen Exercise Study were examined. Self-reported current and lifelong physical activities were quantified in Metabolic Equivalent of Task minutes/day, and training walking speed was estimated in km/h. Cognitive functioning in the domains of working memory, executive function, and visuospatial short-term memory was assessed using the validated Brain Aging Monitor. Data from 521 participants (mean age 54.7, standard deviation 12.9) showed neither positive associations between lifelong physical activity and working memory, executive function, and visuospatial short-term memory nor positive associations between current physical activity and cognitive functioning in these domains (p-values >0.05). However, a positive association between training walking speed and working memory was revealed (age adjusted β = 0.18, p-value <0.01). Walking speed as a surrogate marker of fitness, but not lifelong and current physical activity levels was associated with cognitive function. Therefore, walking speed deserves more attention in research aimed at unraveling associations between physical activity and cognitive function.
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http://dx.doi.org/10.1089/rej.2016.1876DOI Listing
October 2017

Cross-national comparison of medication use in Australian and Dutch nursing homes.

Age Ageing 2017 03;46(2):320-323

Macquarie University Ringgold Standard Institution, Australian Institute for Health Innovation, North Ryde, New South Wales 2109, Australia.

Background: cross-national comparisons can be used to explore therapeutic areas and identify potential medication issues.

Methods: we used cross-sectional pharmacy supply data to explore medication use for nursing home residents in Australia (AU n = 26 homes, 1,560 residents) and the Netherlands (NL n = 6 homes, 2,037 residents). Binary logistic regression analysis was used to calculate the sex and aged adjusted odds ratios (OR) and associated 95% confidence intervals with a flexible Bonferroni-Holm procedure used to adjust for multiple hypothesis testing.

Results: total use of antipsychotics (AU: 37.7%, NL: 40.3%; OR 0.91 (0.79-1.04, P = 0.16) and antibacterials (66.8% AU, 62.4% NL, OR 1.08 (0.93-1.24, P = 0.31) was similar, but choice of individual agents differed between the two countries. Differences were observed in the use of antithrombotics (46.7% AU, 64.7% NL, OR 0.48 (0.42-0.56, P > 0.01), ophthalmologicals (44.3% AU, 22.1% NL, OR 2.80 (2.42-3.24, P < 0.001), laxatives (77.1% AU, 65.8% NL, OR 1.65 (1.41-1.92, P < 0.001).

Conclusion: while the general prevalence of medication use in nursing home residents was similar across the two countries, distinct differences existed in the choice of agent among therapeutic groups. Comparing use between countries identified a number of potential medication related problem areas that need further exploration.
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http://dx.doi.org/10.1093/ageing/afw218DOI Listing
March 2017

Screening for Mild Cognitive Impairment and Dementia with Automated, Anonymous Online and Telephone Cognitive Self-Tests.

J Alzheimers Dis 2017 ;56(1):249-259

Department of General Practice and Elderly Care Medicine, EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.

Background: Many older people worry about cognitive decline. Early cognitive screening in an anonymous and easily accessible manner may reassure older people who are unnecessarily worried about normal cognitive aging while it may also expedite help seeking in case of suspicious cognitive decline.

Objective: To develop and validate online and telephone-based automated self-tests of cognitive function.

Methods: We examined the feasibility and validity of the self-tests in a prospective study of 117 participants of whom 34 had subjective cognitive decline (SCD), 30 had mild cognitive impairment (MCI), and 53 had dementia. The ability of these self-tests to accurately distinguish MCI and dementia from SCD was examined with ROC curves. Convergent validity was examined by calculating rank correlations between the self-tests and neuropsychological tests.

Results: Both the online and telephone cognitive self-tests were feasible, because the majority of participants (86% and 80%, respectively) were able to complete them. The online self-test had adequate diagnostic accuracy in the screening for MCI and dementia versus SCD with an Area under the Curve (AUC) of 0.86 (95% CI: 0.78-0.93). The AUC of the MMSE was 0.82 (95% CI: 0.74-0.89). By contrast, the telephone self-test had lower diagnostic accuracy (AUC = 0.75, 95% CI: 0.64-0.86). Both self-tests had good convergent validity as demonstrated by moderate to strong rank correlations with neuropsychological tests.

Conclusion: We demonstrated good diagnostic accuracy and convergent validity for the online self-test of cognitive function. It is therefore a promising tool in the screening for MCI and dementia.
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http://dx.doi.org/10.3233/JAD-160566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389042PMC
February 2018

Quantification of anticholinergic and sedative drug load with the Drug Burden Index: a review of outcomes and methodological quality of studies.

Eur J Clin Pharmacol 2017 Mar 1;73(3):257-266. Epub 2016 Dec 1.

Department of PharmacoTherapy, -Epidemiology & -Economics [PTEE], Groningen Research Institute of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, Netherlands.

Purpose: The Drug Burden Index (DBI) is a non-invasive method to quantify patients' anticholinergic and sedative drug burden from their prescriptions. This systematic review aimed to summarise the evidence on the associations between the DBI and clinical outcomes and methodological quality of studies.

Methods: A search in PubMed and Embase (search terms: 'drug', 'burden', and 'index') was performed and experts were contacted. We excluded publications that did not report empirical results or clinical outcomes. Methodological quality was assessed using the Newcastle-Ottawa Scale. Potential omissions of relevant clinical outcomes and populations were studied.

Results: Of the 2998 identified publications, 21 were eligible. Overall, methodological quality of studies was good. In all but one study, adjustment was made for prevalent co-morbidity. The DBI was examined in diverse older individuals, i.e. both males and females from different settings and countries. However, no studies were conducted in other relevant patient groups, e.g. psychiatric patients. Exposure to anticholinergic and sedative drugs was thoroughly ascertained, though the specific calculation of the DBI differed across studies. Outcomes were assessed from medical records, record linkage or validated objective tests or questionnaires. Many studies found associations between the DBI and outcomes including hospitalisation, physical and cognitive function. Cognitive function and quality of life were understudied and the number and scope of longitudinal studies was limited.

Conclusions: An accumulating body of evidence supports the validity of the DBI. Longitudinal studies of cognitive function and quality of life and in other patient groups, e.g. psychiatric patients, are warranted.
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http://dx.doi.org/10.1007/s00228-016-2162-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5306241PMC
March 2017

Associations Between Personality Traits and Adherence to Antidepressants Assessed Through Self-Report, Electronic Monitoring, and Pharmacy Dispensing Data: A Pilot Study.

J Clin Psychopharmacol 2016 Oct;36(5):465-71

From the *Department of Pharmacy, Unit of Pharmacotherapy and Pharmaceutical Care, Groningen Research Institute of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Groningen, Groningen; †Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University; and ‡Division Laboratory and Pharmacy, Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht, The Netherlands.

Treatment with antidepressants is often compromised by substantial nonadherence. To understand nonadherence, specific medication-related behaviors and beliefs have been studied, but less is known about broader and temporally stable personality "traits." Furthermore, adherence has often been assessed by a single method. Hence, we investigated associations between the Big Five personality traits and adherence assessed by self-report, electronic drug use monitoring, and dispensing data. Using the Big Five Inventory, we assessed the personality traits "openness," "conscientiousness," "extraversion," "agreeableness," and "neuroticism" of patients treated with antidepressants who were invited through community pharmacies. Self-reported adherence was assessed with the Medication Adherence Rating Scale (score >24), electronic monitoring with medication event monitoring system (MEMS) devices (therapy days missed ≤ 10% and < 4 consecutive days missed), and dispensing data (medication possession ratio ≥ 80%). One hundred four women and 33 men participated (mean age, 51; standard deviation, 14). Paroxetine was most frequently prescribed (N = 53, 38%). Logistic regression analysis revealed that of the personality traits, the third and fourth quartiles of "conscientiousness" were associated with better self-reported adherence (odds ratio, 3.63; 95% confidence interval, 1.34-9.86 and odds ratio, 2.97; 95% confidence interval, 1.09-8.08; P ≤ 0.05). No relationships were found between personality traits and adherence assessed through electronic drug use monitoring or dispensing data. We therefore conclude that adherence to antidepressant therapy seems to be largely unrelated to personality traits.
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http://dx.doi.org/10.1097/JCP.0000000000000541DOI Listing
October 2016

Neurocognitive function of lymphoma patients after treatment with chemotherapy.

Acta Oncol 2016 Sep - Oct;55(9-10):1121-1125. Epub 2016 Jun 22.

c Department of Psychosocial Research and Epidemiology , Netherlands Cancer Institute , Amsterdam , The Netherlands.

Background: Chemotherapy has been shown to cause brain changes and to compromise cognitive function in cancer survivors. Knowledge about this matter is of vital importance for good clinical practice and insights into neurological aging. However, most studies have been conducted among breast cancer patients. Less is known about the effects of chemotherapy on the cognitive function of lymphoma patients.

Material And Method: We studied patients with non-Hodgkin or Hodgkin lymphoma who had been treated with standard dose chemotherapy or with supplementary high dose chemotherapy when standard dose chemotherapy had been unsuccessful. Age- and sex-matched relatives and friends were invited to participate as control participants. All participants underwent a cognitive examination with a battery of validated neuropsychological tests.

Results: Matching of patients with control participants was found to be successful. Regression analysis did not reveal worse cognitive functioning of patients (N = 106) compared to matched controls (N = 53) on the overall group level (All Bonferroni-Holm corrected p-values >0.05). However, a subgroup of 16% of patients had deviant performance according to a chance-corrected criterion based on Ingraham and Aiken's probability curves, i.e. 1.5 standard deviations below the norm on three of 14 tests. Exploratory analyses showed that this subgroup of patients was lower educated and had lower estimated premorbid intelligence.

Conclusion: Chemotherapy may compromise the function of the brain in a subgroup of lymphoma patients. We hypothesize protection of the brain by 'cognitive or brain reserve' as a possible explanation.
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http://dx.doi.org/10.1080/0284186X.2016.1189092DOI Listing
January 2018

Understanding Statin Non-Adherence: Knowing Which Perceptions and Experiences Matter to Different Patients.

PLoS One 2016 25;11(1):e0146272. Epub 2016 Jan 25.

Division of Pharmaco-epidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.

Background: Non-adherence to statins is substantial and is associated with numerous perceptions and experiences. However, time limits in clinical practice constrain in depth explorations of these perceptions and experiences.

Objectives: To propose and examine a strategy aimed at an efficient assessment of a wide array of perceptions and experiences regarding the efficacy, side effects, and practical problems of statins. Furthermore, to assess associations between this wide array of experiences and perceptions and non-adherence and to examine whether patients' 'perceived self-efficacy' moderated these associations.

Methods: Patients were recruited through community pharmacies. A wide array of specific patient perceptions and experiences was efficiently assessed using the electronic Tailored Medicine Inventory that allows people to skip irrelevant questions. Adherence was measured through self-report and pharmacy refill data.

Results: Of the two-hundred twenty-nine patients who participated (mean age 63.9, standard deviation 10.2), 40%-70% doubted the necessity of or lacked knowledge about the efficacy of statins, 20%-35% of the patients were worried about joint and muscle side effects or had experienced these, and 23% had encountered practical problems regarding information about statins, intake of tablets, the package, or the blister. Experiencing more practical problems was associated with increased unintentional non-adherence (Odds ratio 1.54, 95%CI:1.13-2.10, P < 0.01), whereas worrying about side effects was associated with increased intentional non-adherence (Odds ratio 1.90, 95%CI:1.17-3.08, P < 0.01). Higher 'perceived self-efficacy' did not moderate these associations.

Conclusions: Insight into patients' specific barriers with regard to appropriate statin use may reveal personal reasons for being non-adherent. The Tailored Medicine Inventory is a promising tool to devise individualized intervention strategies aimed at improving adherence by the clinician-patient alliance.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0146272PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4726652PMC
July 2016

Decreasing the load? Is a Multidisciplinary Multistep Medication Review in older people an effective intervention to reduce a patient's Drug Burden Index? Protocol of a randomised controlled trial.

BMJ Open 2015 Dec 23;5(12):e009213. Epub 2015 Dec 23.

Department of Pharmacy, Section of Pharmacotherapy and Pharmaceutical Care, Groningen Research Institute of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Groningen, Groningen, The Netherlands.

Introduction: Older people often use medications with anticholinergic or sedative side effects which increase the risk of falling and worsen cognitive impairment. The Drug Burden Index (DBI) is a measure of the burden of anticholinergic and sedative medications. Medication reviews are typically done by a pharmacist in collaboration with a general practitioner to optimise the medication use and reduce these adverse drug events. We will evaluate whether a Multidisciplinary Multistep Medication Review (3MR) is an effective intervention to reduce a patient's DBI.

Methods: A randomised controlled trial including 160 patients from 15 community pharmacies will be conducted. Per pharmacy, 1 pharmacist will perform a structured 3MR in close collaboration with the general practitioner, including the objective to reduce the DBI.

Analysis: Primary outcome--the difference in proportion of patients having a decrease in DBI ≥ 0.5 in the intervention and control groups at follow-up. Secondary outcomes--anticholinergic and sedative side effects, falls, cognitive function, activities of daily living, quality of life, hospital admission, and mortality.

Ethics And Dissemination: The burden of patients will be kept at a minimum. The 3MR can be considered as usual care by the pharmacist and general practitioner. Medical specialists will be consulted, if necessary. The intervention is specifically aimed at older community-dwelling patients in an attempt to optimise prescribing, in particular, to reduce medication with anticholinergic and sedative properties. Study results will be published in peer-reviewed journals and will be distributed through information channels targeting professionals.

Trial Registration Number: NCT02317666; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2015-009213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691761PMC
December 2015

Individualized evaluation of cholinesterase inhibitors effects in dementia with adaptive cognitive testing.

Int J Methods Psychiatr Res 2016 09 24;25(3):190-8. Epub 2015 Aug 24.

Department of Neurology, Academic Medical Centre, Amsterdam, The Netherlands.

Computerized Adaptive Testing (CAT) of cognitive function, selects for every individual patient, only items of appropriate difficulty to estimate his or her level of cognitive impairment. Therefore, CAT has the potential to combine brevity with precision. We retrospectively examined the evaluation of treatment effects of cholinesterase inhibitors by CAT using longitudinal data from 643 patients from a Dutch teaching hospital who were diagnosed with Alzheimer disease or Lewy Body disease. The Cambridge Cognitive Examination (CAMCOG) was administered before treatment initiation and after intervals of six months of treatment. A previously validated CAT was simulated using 47 CAMCOG items. Results demonstrated that the CAT required a median number of 17 items (inter-quartile range 16-20), or a corresponding 64% test reduction, to estimate patients' global cognitive impairment levels. At the same time, intraclass correlations between global cognitive impairment levels as estimated by CAT or based on all 47 CAMCOG items, ranged from 0.93 at baseline to 0.91-0.94 at follow-up measurements. Slightly more people had substantial decline on the original CAMCOG (N = 31/285, 11%) than on the CAT (N = 17/285, 6%). We conclude that CAT saves time, does not lose much precision, and therefore deserves a role in the evaluation of treatment effects in dementia. Copyright © 2015 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/mpr.1484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6877216PMC
September 2016

Walking speed and cognition in later life: findings from older participants of the Nijmegen 4 Days Marches.

J Am Geriatr Soc 2015 Apr;63(4):820-1

Department of Pharmacy, Unit of Pharmacotherapy and Pharmaceutical Care, Groningen Research Institute of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Groningen, Groningen, the Netherlands.

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http://dx.doi.org/10.1111/jgs.13364DOI Listing
April 2015

Discontinuing inappropriate medication in nursing home residents (DIM-NHR Study): protocol of a cluster randomised controlled trial.

BMJ Open 2014 Oct 8;4(10):e006082. Epub 2014 Oct 8.

Department of Pharmacy, Unit of Pharmacotherapy and Pharmaceutical Care, Groningen Research Institute of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Groningen, Groningen, The Netherlands.

Introduction: Nursing home residents often have a high number of comorbidities resulting in polypharmacy. Inappropriate prescribing is therefore likely to occur, which in turn is expected to worsen cognitive impairment, to increase the fall risk and to decrease residents' quality of life. The objective of the 'Discontinuing Inappropriate Medication in Nursing Home Residents' (DIM-NHR) study is to examine the efficacy and cost-effectiveness of the Multidisciplinary Multistep Medication Review (3MR) that is aimed at optimising prescribing and discontinuing inappropriate medication.

Methods: A cluster randomised controlled trial will be conducted. Elderly care physicians and their wards (clusters) will be randomised. Data will be collected at baseline and 4 months after the 3MR has taken place. Six hundred nursing home residents will be recruited of whom more than half are expected to suffer from dementia. The 3MR will be based on consensus criteria and the relevant literature and will be performed by the patient's elderly care physician in collaboration with a pharmacist.

Analysis: Primary outcomes-the difference in proportion of residents who successfully discontinued inappropriate medication between the intervention and control group at follow-up. Secondary outcomes-undertreatment, exposure to anticholinergic and sedative medicines, neuropsychiatric symptoms, cognitive function, falls, hospital admission, quality of life and cost-effectiveness.

Ethics And Dissemination: Participant burden will be kept at a minimum. The elderly care physician will remain free to adjust medication when symptoms relapse or adverse events occur, rendering serious adverse events highly unlikely. Study findings will be published in peer-reviewed journals and a 3MR toolkit will be developed.

Trial Registration Number: This study has been registered at http://www.ClinicalTrials.gov (trial registration number: NCT01876095).
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http://dx.doi.org/10.1136/bmjopen-2014-006082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4194752PMC
October 2014

Do the benefits of statins outweigh their drawbacks? Assessing patients' trade-off preferences with conjoint analysis.

Int J Cardiol 2014 Oct 5;176(3):1220-2. Epub 2014 Aug 5.

Department of Medical Decision Making, Leiden University Medical Center, Leiden, The Netherlands.

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http://dx.doi.org/10.1016/j.ijcard.2014.07.219DOI Listing
October 2014

Endocrine therapy for breast cancer: assessing an array of women's treatment experiences and perceptions, their perceived self-efficacy and nonadherence.

Clin Breast Cancer 2014 Dec 2;14(6):460-467.e2. Epub 2014 Jun 2.

NIVEL, Netherlands Institute for Health Services Research, Utrecht, The Netherlands.

Background: Although adjuvant endocrine therapy effectively prevents breast cancer recurrence, nonadherence rates are substantial. We therefore examined associations of women's experiences and perceptions regarding the efficacy, side effects, and practical problems of endocrine therapy with nonadherence. Furthermore, we examined whether women's perceived self-efficacy moderated these associations.

Patients And Methods: Two hundred forty-one breast cancer patients participated. Using the electronic Tailored Medicine Inventory, which enables skipping of irrelevant items, experiences and perceptions were assessed in a comprehensive yet feasible manner. Adherence was assessed according to self-report and evaluated for agreement with adherence estimated from pharmacy refill data.

Results: A substantial number of women doubted the efficacy of endocrine therapy, were worried about and/or had experienced hot flushes, loss of libido, joint ache, and/or practical problems with regard to information, intake, and packaging. Experience of practical problems (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.0-5.8) and perceived self-efficacy with regard to medicine intake (OR, 0.5; 95% CI, 0.4-0.7) were associated with unintentional nonadherence. Number of side effects experienced (OR, 1.2; 95% CI, 1.05-1.4) and perceived self-efficacy with regard to learning about medication (OR, 0.6; 95% CI, 0.4-0.96) were associated with intentional nonadherence. Perceived self-efficacy did not moderate associations between women's treatment experiences and perceptions and nonadherence.

Conclusion: Endocrine therapy is challenging for many women. Targeting women's specific experiences and perceptions and improving their perceived self-efficacy is likely to decrease intentional and unintentional nonadherence.
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http://dx.doi.org/10.1016/j.clbc.2014.04.005DOI Listing
December 2014
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