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Background and Objectives: Antiplatelet therapy, when prescribed in combination with anticoagulant therapy to older patients with atrial fibrillation and no recent cardiovascular event, is inappropriate and a reversible risk factor of major bleeding. We aimed to assess the trend over time of the prevalence of inappropriate combined antiplatelet and anticoagulant therapy and to determine its associated factors during the direct oral anticoagulant era. Methods: This was a study of consecutive older patients (age ≥ 75 years) with atrial fibrillation, receiving anticoagulant therapy upon admission, and undergoing a comprehensive geriatric assessment during their first admission in a Belgian teaching hospital between 2009 and 2018. Antiplatelet therapy was considered inappropriate in the absence of a recent cardiovascular event. We studied the prevalence of inappropriate combined antiplatelet and anticoagulant therapy by 2-year periods and assessed its associated factors since the year 2013. Results: Inappropriate combined antiplatelet and anticoagulant therapy was identified in 21% of the 654 patients (median age 84 years, 51% women), with a prevalence decreasing (p ≤ 0.01) from 25% (2009–10) to 14.8% (2017–18). Among the 469 patients recruited during the direct oral anticoagulant era, inappropriate combined antiplatelet and anticoagulant therapy (19%) was associated in a multivariable analysis with a history of stroke/transient ischemic attack (odds ratio 2.13, p = 0.007), anticoagulation with low-molecular-weight heparin (odds ratio 3.44, p = 0.015), and a history of vascular disease (odds ratio 5.68, p < 0.001). Conclusions: While inappropriate combined antiplatelet and anticoagulant therapy has declined over the last decade, there is still room for improvement. Antiplatelet deprescribing should be considered in all patients with inappropriate combined antiplatelet and anticoagulant therapy, including those with vascular disease and no recent cardiovascular event. [ABSTRACT FROM AUTHOR]

Background: Diabetes overtreatment is a frequent and major issue in older people with type 2 diabetes but its definition is often inconsistent and may be misleading. This critical review has aimed at examining the definitions of diabetes overtreatment in older people used in research studies. Methods: Studies addressing diabetes overtreatment in people aged 65 or older were identified by searching the PubMed database according to an extensive search equation. Results: Twenty‐two research studies providing a definition of diabetes overtreatment in people aged were found. Overall, 12 different definitions of diabetes overtreatment were used. All studies defined overtreatment according to a HbA1c threshold (varying from <42 mmol/mol [<6.0%] to <64 mmol/mol [<8%]). Amongst them, 2 definitions had no consideration about glucose‐lowering (GL) treatment, 6 required the prescribing of ≥1 GL agent(s), and 4 the prescribing of ≥1 GL agent(s) inducing the high risk of hypoglycaemia (i.e., sulfonylurea(s) or insulin(s)). Only 4 definitions (four studies) were individualised, using varying HbA1c thresholds according to patients' age or health status. Conclusions: Definitions of diabetes overtreatment are heterogeneous across research studies, which is confusing. A standardised definition, based on the individual risk of hypoglycaemia and/or its complications must be promoted in order to bring clarity and greater insight into this field, as well as to improve the quality of management of diabetes in older patients. [ABSTRACT FROM AUTHOR]

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

Background Recommendations for individualised glycaemic management in older people with type 2 diabetes (T2D) have recently been provided in clinical practice guidelines (CPGs) issued by major scientific societies. The aim of this systematic review is to compare the content of these recommendations concerning health assessment, targets for glycaemic control, lifestyle management and glucose-lowering therapy across CPGs. Methods The CPGs on T2D management in people aged ≥65 years published in English after 2015 by major scientific societies were systematically reviewed in accordance with the PRISMA statement. The quality of the CPGs included was assessed using the AGREE-II tool. The recommendations for individualised glycaemic management were extracted, and their level of evidence (LOE) and strength of recommendation recorded. Results Three CPGs of high methodological quality were included, namely those from the American Diabetes Association 2020, the Endocrine Society 2019 and the Diabetes Canada Expert Committee 2018. They made 27 recommendations addressing individualised glycaemic management, a minority of which (40%) had a high LOE. Comparison of the 27 recommendations identified some discrepancies between CPGs, e.g. the individualised values of HbA1c targets. The 13 strong recommendations addressed 10 clinical messages, five of which are recommended in all three CPGs, i.e. assess health status, screen for cognitive impairment, avoid hypoglycaemia, prioritise drugs with low hypoglycaemic effects and simplify complex drug regimens. Conclusions Although there is a consensus on avoiding hypoglycaemia in older patients with T2D, significant discrepancies regarding individualised HbA1c targets exist between CPGs. [ABSTRACT FROM AUTHOR]

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

Background Identifying patients with heart failure (HF) in general practice is challenging. Our aim was to provide an overview of methods used to identify patients with HF in general practice and to assess their impact on patient characteristics. Methods and results A systematic review was conducted using MEDLINE, EMBASE and CENTRAL. Taken together, 105 studies on HF in general practice were included, totalling 196,105 patients. Five main identification methods for HF were distinguished, including 1) echocardiographic assessments, 2) results of echocardiography in general practitioner (GP) charts, 3) GP judgment after chart review, 4) GP judgment of consecutive patients and 5) only chart review. Only 30% of studies used the results of echocardiography. Despite a large heterogeneity between studies the pooled data revealed a predominant phenotype of older women with hypertension rather than ischaemic heart disease. Linear regression analysis showed that the impact of the identification method on patient characteristics was limited. However, study design had a greater impact, with randomized-controlled trials (RCTs) including younger, male patients with ischaemic heart disease and higher HF drug prescription rates at baseline. Conclusion Pooled data of 196,105 patients with HF confirmed a phenotype of older women with hypertension rather than ischaemic heart disease as the predominant HF population in general practice. The lack of a gold standard definition of HF introduced a large heterogeneity in identification methods with remarkably limited impact on patient characteristics. However, RCTs did include patients with a different phenotype, emphasizing the need to promote inclusion of real-world HF patients. [ABSTRACT FROM AUTHOR]

Objective: Our objectives were to (1) describe the evolution of the underuse of anticoagulants in older people with atrial fibrillation (AF) and a CHADS score ≥ 2 since direct oral anticoagulants (DOACs) were introduced to the market and (2) describe factors associated with this underuse. Methods: We conducted a retrospective cross-sectional study including geriatric patients admitted during the pre-DOAC (2008-2011) and post-DOAC (2013-2015) periods in an academic hospital in Belgium. Five inclusion criteria were met: age ≥ 75 years, diagnosis of AF, indication for anticoagulation (CHADS score ≥ 2), risk of functional decline (Identification of Seniors At Risk [ISAR] score ≥ 2), and comprehensive geriatric assessment. The use of anticoagulants and antiplatelets at home before admission was recorded. Risks of stroke and bleeding were calculated using CHADS and HEMORRHAGES scores, respectively. Three different logistic regression models were performed to describe the evolution of and factors associated with the underuse of anticoagulants after DOAC marketing. Results: Anticoagulant underuse, present in 209 of 614 (34%) geriatric patients with AF, was lower in patients with a history of stroke (28.5%) or congestive heart failure (26.9%) but higher in those receiving antiplatelets (56.2%) and in older individuals. Anticoagulant underuse decreased significantly from the pre-DOAC (37.3%) to the post-DOAC (29.7%) era, as shown by two analyses using propensity scores. Conclusion: In older patients with AF, anticoagulant underuse was mainly associated with antiplatelet use. Anticoagulant underuse and antiplatelet use have both decreased since DOAC marketing. Underuse of anticoagulants was still a concern for three in ten geriatric patients with AF at high risk of stroke (CHADS score ≥ 2). [ABSTRACT FROM AUTHOR]

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

A correction is presented to the article "Performance as a Trigger Tool for Detecting Drug-Related Hospital Admissions in Older People: Analysis From the OPERAM Trial" which appeared in the issue of the magazine.

The authors discuss the efforts by the European Union (EU) to negotiate the prices of orphan drugs or drugs for rare diseases and the initiative of Belgium and the Netherlands for orphan drugs pricing negotiation with pharmaceutical companies. Topics discussed include criteria used by European Medicines Agency (EMA) in granting orphan designation for medicines, and potential threat faced in sustainability of EU health-care systems with more new orphan drugs marketed annually.

Background: Haemophilia is a rare hereditary haemorrhagic disease that requires regular intravenous injections of clotting factor (CF) concentrates. This study sought to estimate the health and economic burden of haemophilia in Belgium. This is the first study of its type to be conducted, and reflects the Belgian authorities’ growing interest for haemophilia as part of their priority planning for rare and chronic diseases. Methods: A probabilistic model was developed in order to estimate the lifetime haemophilia burden for the 2011 birth-year Belgian cohort. The health burden was initially expressed in terms of disability-adjusted life years (DALYs), the number of healthy life years lost due to living with disability and dying prematurely. An incidence perspective was used in line with World Health Organization recommendations. The economic burden calculated from direct and indirect haemophilia-related costs was expressed in euros. Data were drawn from the literature if none were available from federal institutions or health insurance. Disability weights for DALY calculation were derived using generic quality-of-life tools such as SF-6D from the SF-36 (36-item Short-Form Health Survey; for adults) and KINDL (generic quality-of-life instrument; for children) compared to population norms. Analyses were stratified according to haemophilia type and severity. Results: In Belgium, haemophilia resulted in 145 undiscounted and unweighted DALYs in total (95% credible interval [CrI] = 90-222), which represents an average of 11 DALYs per incident case with haemophilia (95% CrI = 8-15) during his life, varying according to haemophilia severity (17 DALYs for severe haemophilia, 12 DALYs for moderate, and 4 DALYs for mild). Mean total lifetime costs reached €7.8 million per people with haemophilia, 94.3% being direct costs and 5.7% indirect costs. Clotting factors accounted for 82.5% of direct costs. Conclusions: Haemophilia represents both an economic and health burden, especially regarding individual health on an individual patient level. Initiatives to counteract this burden should be clearly identified and given full support, as this burden is likely to increase in the future, especially from an economic perspective. Our study may also contribute towards a better global evaluation of haemophilia in the future. [ABSTRACT FROM AUTHOR]

Background. Coronary artery calcification (CAC) independently predicts cardiovascular events (CVE) in the general population. Whether this applies to renal transplant recipients (RTR) is unknown. This prospective study assessed the prognostic impact of CAC on CVE in RTR.Methods. We followed up a published cohort of 281 prevalent RTR. At baseline, 16-slice chest spiral computerized tomography scan was performed and classical as well as CKD-related risk factors were recorded. Major CVE (MCVE) was defined as cardiovascular death, myocardial infarction, stroke or transient ischaemic attack. All CVE (ACVE) included MCVE and revascularizations. Prognostic factors were assessed by univariate and multivariate Cox regression.Results. During 2.3 ± 0.5 years of follow-up, 16 patients died from CV (n = 8) or non-CV causes (n = 8). Thirty-one RTR developed at least one CVE (first CVE cardiac in 15, peripheral in 12 and cerebrovascular in 4) for a total of 36 CVE. Thirty-month CV survival, MCVE-free survival and ACVE-free survival was 96.4, 93.9 and 87.9%, respectively. By multivariate analysis, the independent predictors of ACVE were CAC score (hazards ratios [HR] = 1.40 [1.12; 1.75] for a 2.72-fold increase in CAC, P < 0.003) and history of CVE (HR = 2.76 [1.21; 6.39], P < 0.02).Conclusion. Our study shows for the first time that CAC is a strong independent predictor of CVE in RTR. [ABSTRACT FROM AUTHOR]

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

Objectives Caregiving is often associated with burden and chronic stress. Sense of coherence (SOC) may help the caregivers in coping with their stress and was identified as a positive factor for health outcomes and quality of life. We aimed to study the links between SOC, burden, depression and positive affects among caregivers of frail older patients. Methods Seventy-nine spousal caregivers were recruited via the geriatric outpatient clinic. Data collected: Zarit Burden Inventory, SOC-13, Geriatric Depression Scale, Caregiver Reaction Assessment (CRA), sleep, time of supervision, Katz Index, Global Deterioration Scale and Neuropsychiatric Inventory. Analyses: Caregiver’s characteristics were analyzed by burden severity and SOC level. Multivariable logistic regressions were used in order to identify the variable that best predict caregiver burden and high SOC. Results The mean age was 79.4 ± 5.3; 53% were women. Among care-recipient, 82% had cognitive impairment and the median Katz Index was 3. Caregivers with a high SOC and an older age reported a lower burden (Odds Ratio (OR) 0.18, 95% confidence interval (CI) 0.04–0.65 and OR 0.87, 95% CI 0.76–0.98, respectively). A higher burden was associated with patient functional limitations (OR 8.69, 95% CI 2.28–40.46). Discussion Having a high sense of coherence seems to be a protective factor against the burden. To support caregivers, health providers should recognize the expertise of the caregivers and the meaningfulness of this care situation. [ABSTRACT FROM AUTHOR]

Background: Haemophilia is a rare hereditary haemorrhagic disease that requires regular intravenous injections of clotting factor (CF) concentrates. This study sought to estimate the health and economic burden of haemophilia in Belgium. This is the first study of its type to be conducted, and reflects the Belgian authorities' growing interest for haemophilia as part of their priority planning for rare and chronic diseases.Methods: A probabilistic model was developed in order to estimate the lifetime haemophilia burden for the 2011 birth-year Belgian cohort. The health burden was initially expressed in terms of disability-adjusted life years (DALYs), the number of healthy life years lost due to living with disability and dying prematurely. An incidence perspective was used in line with World Health Organization recommendations. The economic burden calculated from direct and indirect haemophilia-related costs was expressed in euros. Data were drawn from the literature if none were available from federal institutions or health insurance. Disability weights for DALY calculation were derived using generic quality-of-life tools such as SF-6D from the SF-36 (36-item Short-Form Health Survey; for adults) and KINDL (generic quality-of-life instrument; for children) compared to population norms. Analyses were stratified according to haemophilia type and severity.Results: In Belgium, haemophilia resulted in 145 undiscounted and unweighted DALYs in total (95% credible interval [CrI] = 90-222), which represents an average of 11 DALYs per incident case with haemophilia (95% CrI = 8-15) during his life, varying according to haemophilia severity (17 DALYs for severe haemophilia, 12 DALYs for moderate, and 4 DALYs for mild). Mean total lifetime costs reached €7.8 million per people with haemophilia, 94.3% being direct costs and 5.7% indirect costs. Clotting factors accounted for 82.5% of direct costs.Conclusions: Haemophilia represents both an economic and health burden, especially regarding individual health on an individual patient level. Initiatives to counteract this burden should be clearly identified and given full support, as this burden is likely to increase in the future, especially from an economic perspective. Our study may also contribute towards a better global evaluation of haemophilia in the future. [ABSTRACT FROM AUTHOR]

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

Background Over the last few years, the Screening Tool of Older Person's Prescriptions (STOPP) and Screening Tool to Alert doctors to Right Treatment (START) criteria have been increasingly used to evaluate the prevalence of inappropriate prescribing. However, very few studies have evaluated the link between these criteria and clinical outcomes. Objectives The objectives of this study were to evaluate the prevalence of inappropriate prescribing according to STOPP and START in a population of frail elderly persons admitted acutely to hospital; to evaluate whether these inappropriate prescribing events contributed to hospital admissions; and to identify determinants of hospital admissions potentially related to inappropriate prescribing. Methods This was a cross-sectional study including all frail older patients admitted to a 975-bed teaching hospital over a 12-month period. A pharmacist and a geriatrician independently detected events of prescribing of potentially inappropriate medication (PIM) and potential prescribing omission (PPO), using the STOPP and START criteria, respectively, in all patients included in the study. They determined whether the inappropriate prescribing event was the main cause or a contributory cause of hospital admission. Demographic, clinical and geriatric clinical syndromes (i.e. cognitive impairment, falls) were evaluated as potential determinants of hospital admissions related to inappropriate prescribing, using multivariate methods (i.e. logistic regression and a classification tree). Results 302 frail older persons (median age 84 years) were included in the study. PIMs (prevalence 48 %) mainly involved overuse and/or misuse of benzodiazepines, aspirin and opiates. PPOs (prevalence 63 %) were mainly related to underuse of calcium and vitamin D supplementation, aspirin and statins. Overall, inappropriate prescribing according to STOPP (54 PIM5) and/or START (38 PPOs) led or contributed to hospital admission in 82 persons (27 %). The multivariate analyses indicated a relation between PIM-related admissions and a history of previous falls (p < 0.001), while the PPO-related admissions were associated with a history of osteoporotic fracture (p <0.001) and atrial fibrillation (p = 0.004). Conclusions Using the STOPP and START criteria, it was found that inappropriate prescribing events (both PIMs and PPOs) were frequent and were associated with a substantial number of acute hospital admissions in frail older persons. Fall-induced osteoporotic fracture was the most important cause of hospital admission related to inappropriate prescribing and should be a priority for pharmacological optimization approaches. [ABSTRACT FROM AUTHOR]

Background: The STOPPFrail criteria were developed to assist physicians in deprescribing medications among frail patients approaching end of life. We aimed to measure the prevalence of potentially inappropriate medications (PIMs) and to describe changes over time, using STOPPFrail, in frail nursing home residents (NHRs) with limited life expectancy included in a medication review trial. Methods: We conducted a post-hoc analysis of the COME-ON study, a cluster-controlled trial that evaluated the effect of a complex intervention on appropriateness of prescribing in Belgian nursing homes. We identified NHRs eligible for the application of STOPPFrail based on functional status, comorbidities, level of care and survival. PIM use was measured at baseline and at 8 months. Changes over time were compared in the control group (CG) and intervention group (IG). Results: At baseline, 308 NHRs met the STOPPFrail eligibility criteria, of whom 196 (64.1%) had one or more PIM. At 8 months, among the 218 NHRs who were alive, there was an absolute reduction in the prevalence of PIMs of 9.1% in the CG (p < 0.05) and 10.2% in the IG (p < 0.05). We found large reductions for some medications (e.g. proton pump inhibitors) but no reduction for others (e.g. calcium). The percentage of NHRs with one or more PIM discontinued without a new PIM initiated was higher in the IG than the CG but the difference was not significant (35.1% vs 23.6%, p = 0.127). Conclusion: Among frail NHRs with poor survival prognosis, a significant and encouraging decrease in PIM prevalence over time was observed, probably facilitated by medication reviews. The overall prevalence of PIMs remained high, however. [ABSTRACT FROM AUTHOR]

Background: The 2019 Endocrine Society guidelines for treatment of diabetes in older people define individualised HbA1c targets for glucose-lowering therapy (GLT) in older people with type 2 diabetes (T2D) according to their health status. Our study assessed the association between GLT appropriateness according to these guidelines (appropriate, overuse, underuse) and one-year mortality. Methods: Retrospective study of all inpatients ≥75 years with T2D and GLT admitted to a geriatric ward of an academic hospital (Brussels) between 2008-2015. Factors associated with one-year mortality were tested in multivariable Cox proportional hazards regression. Results: Among the 318 patients (84 years; 54% women), GLT overuse was detected in 57.2% and underuse in 17.9%. In multivariable analysis, one-year mortality was associated with poor health (HR: 1.59, p=0.033) and GLT overuse (HR: 1.73, p=0.023). One-year survival was the highest in patients in intermediate health with appropriate GLT and the lowest in those in poor health with GLT overuse (Figure 1; one-year survival [95%CI]: 0.87 [0.76-1.00] and 0.53 [0.45-0.62], respectively). Conclusion: GLT overuse and poor health status are independent predictors of one-year mortality in geriatric patients with type 2 diabetes. As many of these patients met these two conditions, there is room to improve GLT individualisation and deprescribing. Disclosure: A. Christiaens: None. B.J. Boland: None. S. Henrard: None. Funding: Fund for Scientific Research (FC23595) [ABSTRACT FROM AUTHOR]

Introduction: Health-related quality of life evaluation is recognized as an important outcome in the assessment of boys with haemophilia. In fact, reliable health-related quality of life data are even more critical in developing countries to advocate for government agencies to develop national haemophilia care programmes. However, validated tools are not yet available in sub-Saharan African countries.Aims: The purpose of this study was to complete the cultural adaptation and validation of the Canadian Haemophilia Outcomes-Kids' Life Assessment Tool version2.0 (CHO-KLAT2.0) in Côte d'Ivoire.Methods: The process included four steps: a linguistic adaptation, cognitive debriefing interviews with children and their parents, a validity assessment with the Pediatric Quality of Life Inventory (PedsQL) as a comparator, and a test-retest reliability assessment.Results: The initial Ivoirian version of the CHO-KLAT2.0 was developed through a linguistic adaptation performed in close collaboration with members of the local medical team and haemophilia community. Cognitive debriefings were completed with five boys and their parents, with the final Ivoirian version of the CHO-KLAT2.0 developed in September 2017. The validation process included 37 boys with haemophilia (mean age: 11.4 years; 34 with severe and three with moderate forms of haemophilia, all treated on demand) and their parents. Among the child-reported population (n = 20), we observed a mean CHO-KLAT2.0 score of 51.3 ± 9.2; there was a moderate correlation between the CHO-KLAT2.0 and PedsQL scores (r = 0.581; p = 0.007) and an inverse correlation of the CHO-KLAT2.0 and PedsQL scores with the global rating of the degree to which the boys were bothered by their haemophilia. The mean parent proxy CHO-KLAT2.0 score (n = 17) was 53.5 ± 9.8. Among the parents, we found no significant correlation between the Ivoirian CHO-KLAT2.0 and PedsQL scores or between the parent-reported scores and the parent global ratings of bother. The test-retest intraclass correlation coefficient was 0.879 (95% CI: 0.673; 0.954) for the child-reported questionnaires and 0.880 (95% CI: 0.694; 0.955) for the proxy-reported questionnaires.Conclusions: A cross-culturally adapted and validated version of the CHO-KLAT2.0 for Côte d'Ivoire is now available that enables baseline values to be obtained and intervention outcomes (namely, prophylaxis) to be measured in Ivoirian boys with haemophilia. [ABSTRACT FROM AUTHOR]

To investigate the impact of a complex multifaceted intervention on the appropriateness of prescribing for Belgian nursing home (NH) residents. A multicenter, nonblinded, cluster-randomized controlled trial, with randomization at the NH level, was set up [Cluster-Controlled Trial of an Intervention to Improve Prescribing in Nursing Homes (COME-ON) Study]. The complex intervention consisted of repeated interdisciplinary case conferences (ICCs) involving the general practitioner, pharmacist, and nurse, aimed at performing a medication review for each NH resident included. The ICCs were supported by a blended training program and local interdisciplinary meetings (discussion of the appropriate use of specific medication classes at the NH level). Control NHs delivered usual care. (isrctn.com: ISRCTN66138978). Belgian NHs with at least 35 NH residents were eligible to participate. Eligible residents were those aged 65 years or over, not receiving palliative care, and being treated by a participating general practitioner. The primary outcome measure related to appropriateness of prescribing at resident level and was considered successful when at least 1 potentially inappropriate medication (PIM) or potential prescribing omission (PPO) present at baseline had been solved at the end of study and when there were no new PIMs or PPOs at the end of study compared with baseline. Secondary outcomes included clinical outcomes, medication use, criterion-specific prevalence of PIMs and PPOs, and ICC outcomes. In total, 54 NHs (24 intervention; 30 control) and 1804 NH residents (847 intervention; 957 control) participated. Using a 3-level mixed-effects model accounting for data clustering, a significant effect in favor of the intervention was observed (odds ratio 1.479 [95% confidence interval 1.062-2.059, P =.021]). There was no significant difference between groups for most clinical outcomes. The median number of medications did not change over time in either group. The complex multifaceted intervention tested in the COME-ON study successfully improved appropriateness of prescribing in NHs. [ABSTRACT FROM AUTHOR]

Background: Older persons are at significant risk of drug-related admissions (DRAs). We previously demonstrated that 27% of hospitalizations in geriatric patients were associated with potentially inappropriate medicines (PIMs) and/or potential prescribing omissions (PPOs) identified by the Screening Tool of Older People's Prescriptions/Screening Tool to Alert to Right Treatment (STOPP/START) criteria version 1 (v1). The updated STOPP/START criteria version 2 (v2) comprised a 31% increase in prescribing criteria. Objective: As a secondary analysis of our study conducted in 2008, we aimed to compare the prevalence and types of DRAs identified by STOPP/START.v1 and STOPP/START.v2. Methods: We applied the STOPP/START.v2 criteria to a subset of 100 consecutively admitted geriatric patients selected from our original cross-sectional study of 302 patients. A geriatrician and a pharmacist adjudicated whether the identified PIMs and PPOs were related to acute hospitalization. Admissions were defined as DRAs if the identified PIM(s) and/or PPO(s) were related to the main cause of admission or played a significant contributory role in the admission. Results: The median patient age was 83 years and the median number of medications at home was 8. Compared with STOPP/START.v1, STOPP/START.v2 not only yielded more instances of inappropriate prescribing but also targeted significantly more PIMs and PPOs associated with preventable DRAs (23% vs. 40% of all admissions, p < 0.001). PIMs of fall-risk-increasing drugs, and PPOs of musculoskeletal and cardiovascular system drugs, were most frequently associated with DRAs. Conclusion: The latter instances of inappropriate prescribing with major clinical relevance warrant particular attention during medication review in older persons. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this paper was to describe the time trends in the prevalence of multimorbidity and polypharmacy in Flanders (Belgium) between 2000 and 2015, while controlling for age and sex. Methods: Data were available from Intego, a Flemish-Belgian general practice-based morbidity registration network. The practice population between 2000 and 2015 was used as the denominator, representing a mean of 159,946 people per year. Age and gender-standardised prevalence rates were used for the trends of multimorbidity and polypharmacy in the total population and for subgroups. Joinpoint regression analyses were used to analyse the time trends and breaks in trends, for the entire population as well as for specific age and sex groups. Results: Overall, in 2015, 22.7% of the population had multimorbidity, while the overall prevalence of polypharmacy was 20%. Throughout the study period the standardised prevalence rate of multimorbidity rose for both sexes and in all age groups. The largest relative increase in multimorbidity was observed in the younger age groups (up to the age of 50 years). The prevalence of polypharmacy showed a significant increase between 2000 and 2015 for all age groups except the youngest (0–25 years). Conclusion: For all adult age groups multimorbidity and polypharmacy are frequent, dynamic over time and increasing. This asks for both epidemiological and interventional studies to improve the management of the resulting complex care. [ABSTRACT FROM AUTHOR]

Abstract Background/objectives Our aim was to describe the prevalence of potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) in Belgian nursing homes and to identify characteristics of residents, general practitioners (GPs), and nursing homes (NHs) that are associated with the number of PIMs and PPOs. Design A cross-sectional study. Setting and Participants: Nursing home residents (NHRs), aged ≥65 years, not in palliative care were included in 54 Belgian NHs participating in the COME-ON study. Measures Instances of PIMs were detected using a combination of the STOPP v2 and AGS 2015 Beers criteria. Instances of PPOs were detected using START v2. To assess factors associated with the number of PIMs and PPOs, a multivariate binomial negative regression analysis was performed. Results A total of 1410 residents, with a median age of 87 years, was included. The median number of medications taken was 9. PIMs were detected in 88.3% of NHRs and PPOs in 85.0%. Use of benzodiazepines (46.7%) and omission of vitamin D (51.5%) were the most common PIM and PPO, respectively. The factor most strongly associated with increased PIMs was the use of 5 to 9 drugs or ≥10 drugs [relative risk (RR) (95% confidence interval [CI]: 2.27 (1.89, 2.76) and 4.04 (3.37, 4.89), respectively]. The resident's age was associated with both decreased PIMs and increased PPOs. PIMs and PPOs were also associated with some NH characteristics, but not with GP characteristics. Conclusion Implications: The high prevalence of PIMs and PPOs remains a major challenge for the NH setting. Future interventions should target in priority residents taking at least 10 medications and/or those taking psychotropic drugs. Future studies should explore factors related to organizational and prescribing culture. Moreover, special attention must be paid to the criteria used to measure inappropriate prescribing, including criteria relative to underuse. [ABSTRACT FROM AUTHOR]

Background: Various methods exist to estimate disease prevalences. The aim of this study was to determine whether dispensed, self-reported and prescribed medication data could be used to estimate the prevalence of diabetes mellitus and thyroid disorders. Second, these pharmaco-epidemiological estimates were compared with prevalences based on self-reported diagnoses and doctor-registered diagnoses. Methods: Data on medication for diabetes and thyroid disorders were obtained from three different sources in Flanders (Belgium) for 2008: a purely administrative database containing data on dispensed medication, the Belgian National Health Interview Survey for self-reported medication and diagnoses, and a patient record database for prescribed medication and doctor- registered diagnoses. Prevalences were estimated based on medication data and compared with each other. Cross-tabulations of dispensed medication and self-reported diagnoses, and prescribed medication and doctor-registered diagnoses, were investigated. Results: Prevalences based on dispensed medication were the highest (4.39 and 2.98% for diabetes and thyroid disorders, respectively). The lowest prevalences were found using prescribed medication (2.39 and 1.72%, respectively). Cross-tabulating dispensed medication and self-reported diagnoses yielded a moderate to high sensitivity for diabetes (90.4%) and thyroid disorders (77.5%), while prescribed medication showed a low sensitivity for doctor-registered diagnoses (56.5 and 43.6%, respectively). The specificity remained above 99% in all cases. Conclusions: This study was the first to perform cross-tabulations for disease prevalence estimates between different databases and within (sub)populations. Purely administrative database was shown to be a reliable source to estimate disease prevalence based on dispensed medication. Prevalence estimates based on prescribed or self-reported medication were shown to have important limitations. [ABSTRACT FROM AUTHOR]

Background: Ageing has become a worldwide reality and presents new challenges for the health-care system. Research has shown that potentially inappropriate prescribing, both potentially inappropriate medications and potentially prescribing omissions, is highly prevalent in older people, especially in the nursing home setting. The presence of potentially inappropriate medications/potentially prescribing omissions is associated with adverse drug events, hospitalisations, mortality and health-care costs. The Collaborative approach to Optimise MEdication use for Older people in Nursing homes (COME-ON) study aims to evaluate the effect of a complex, multifaceted intervention, including interdisciplinary case conferences, on the appropriateness of prescribing of medicines for older people in Belgian nursing homes.Methods/design: A multicentre cluster-controlled trial is set up in 63 Belgian nursing homes (30 intervention; 33 control). In each of these nursing homes, 35 residents (≥65 years) are selected for participation. The complex, multifaceted intervention comprises (i) health-care professional education and training, (ii) local concertation (discussion on the appropriate use of at least one medication class at the level of the nursing home) and (iii) repeated interdisciplinary case conferences between general practitioner, nurse and pharmacist to perform medication review for each included nursing home resident. The control group works as usual. The study period lasts 15 months. The primary outcome measures relate to the appropriateness of prescribing and are defined as (1) among residents who had at least one potentially inappropriate medication/potentially prescribing omission at baseline, the proportion of them for whom there is a decrease of at least one of these potentially inappropriate medications/potentially prescribing omissions at the end of study, and (2) among all residents, the proportion of them for whom at least one new potentially inappropriate medication/potentially prescribing omission is present at the end of the study, compared to baseline. The secondary outcome measures include individual components of appropriateness of prescribing, medication use, outcomes of the case conferences, clinical outcomes and costs. A process evaluation (focusing on implementation, causal mechanisms and contextual factors) will be conducted alongside the study.Discussion: The COME-ON study will contribute to a growing body of knowledge concerning the effect of complex interventions on the use of medicines in the nursing home setting, and on factors influencing their effect. The results will inform policymakers on strategies to implement in the near future.Trial Registration: Current Controlled Trials ISRCTN66138978. [ABSTRACT FROM AUTHOR]

Studies estimating the added value of natriuretic peptide levels and electrocardiographic findings beyond all relevant clinical information to identify cardiac dysfunction remain scarce. The aim of this study was to assess the presence of clinically relevant cardiac dysfunction in an unselected population of subjects aged 80 years. A cross-sectional analysis using an "intention-to-diagnose" strategy was performed within the BELFRAIL study (n = 567). Baseline B-type natriuretic peptide and N-terminal pro--B-type natri-uretic peptide levels were determined and echocardiography was performed at subjects' homes. Logistic regression analysis and classification and regression tree analysis were used as complementary analytic tools. Cardiac dysfunction was present in 17% of subjects without and 31% of subjects with chronic atrial fibrillation (AF) or pacemaker. In subjects without chronic AF or pacemaker, the clinical model showed a C-statistic of 0.79 (95% confidence interval 0.74 to 0.85). The combination of natriuretic peptides with normal results on electrocardiography increased, only marginally, the C-statistic. In subjects with chronic AF or pacemaker, the clinical model showed a very high C-statistic of 0.90 (95% confidence interval 0.82 to 0.98). Classification and regression tree analysis showed that an additional 58 subjects (13%) were correctly classified using natriuretic peptides and elec-trocardiographic findings among those without chronic AF or pacemaker. Of participants with chronic AF or pacemaker, ≥90% were correctly classified. In conclusion, in a large population-based sample of patients aged à80 years, the clinical model possessed high accuracy to identify cardiac dysfunction in daily practice. Among subjects without chronic AF or pacemaker, a larger number were correctly classified by integrating natriuretic peptides and electrocardiographic findings in the strategy. [ABSTRACT FROM AUTHOR]

Background: Older patients with type 2 diabetes mellitus represent a heterogeneous group in terms of metabolic profile. It makes glucose-lowering-therapy (GLT) complex to manage, as it needs to be individualised according to the patient profile. This study aimed to identify and characterize subgroups existing among older patients with diabetes. Methods: Retrospective observational cohort study of outpatients followed in a Belgian diabetes clinic. Included participants were all aged ≥75 years, diagnosed with type 2 diabetes, Caucasian, and had a Homeostasis Model Assessment (HOMA2). A latent profile analysis was conducted to classify patients using the age at diabetes diagnosis and HOMA2 variables, i.e. insulin sensitivity (HOMA2%-S), beta-cell-function (HOMA2%-β), and the product between both (HOMA2%-βxS; as a measure of residual beta-cell function). GLT was expressed in defined daily dose (DDD). Results: In total, 147 patients were included (median age: 80 years; 37.4% women; median age at diabetes diagnostic: 62 years). The resulting model classified patients into 6 distinct cardiometabolic profiles. Patients in profiles 1 and 2 had an older age at diabetes diagnosis (median: 68 years) and a lesser decrease in HOMA2%-S, as compared to other profiles. They also presented with the highest HOMA2%-βxS values. Patients in profiles 3, 4 and 5 had a moderate decrease in HOMA2%-βxS. Patients in profile 6 had the largest decrease in HOMA2%-β and HOMA2%-βxS. This classification was associated with significant differences in terms of HbA1c values and GLT total DDD between profiles. Thus, patients in profiles 1 and 2 presented with the lowest HbA1c values (median: 6.5%) though they received the lightest GLT (median GLT DDD: 0.75). Patients in profiles 3 to 5 presented with intermediate values of HbA1c (median: 7.3% and GLT DDD (median: 1.31). Finally, patients in profile 6 had the highest HbA1c values (median: 8.4%) despite receiving the highest GLT DDD (median: 2.28). Other metabolic differences were found between profiles. Conclusions: This study identified 6 groups among patients ≥75 years with type 2 diabetes by latent profile analysis, based on age at diabetes diagnosis, insulin sensitivity, absolute and residual β-cell function. Intensity and choice of GLT should be adapted on this basis in addition to other existing recommendations for treatment individualisation. [ABSTRACT FROM AUTHOR]