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Majda Azermai Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium Abstract: Dealing with the behavioral and psychological symptoms of dementia (BPSD) is often complex. Given the controversy with regard to antipsychotics for behavioral problems in people with dementia, there has been a renewed emphasis on nonpharmacological interventions, with progress in the design of the relevant studies. Potential nonpharmacological interventions for BPSD are: cognitive training/stimulation, rehabilitative care, activities of daily living, music therapy, massage/touch, physical activity, education/training of professionals, and education and psychosocial support of informal caregivers. Use of antipsychotics in the management of BPSD is controversial due to limited efficacy and the risk of serious adverse effects, but credible alternatives remain scarce. The problem of chronic use of antipsychotics in nursing homes should be tackled. Discontinuation of antipsychotic medication in older individuals with BPSD appears to be feasible. Discontinuation efforts are needed to differentiate between patients for whom antipsychotics have no added value and patients for whom the benefits outweigh the risks. Keywords: behavioral symptoms, psychological symptoms, dementia, interventions, nonpharmacological intervention

Background: Although guidelines put forward non-pharmacological therapies and advise against the chronic use of psychotropic drugs, these are still being prescribed regularly in Belgian nursing homes., Goal: To explore the reasons for initiation, continuation and cessation of psychotropic drug treatment of elderly with dementia and behavioral problems, residing in the nursing home., Method: Twenty-seven interviews from an earlier project were used, in which a semi-structured interview was conducted with the nursing staff, the physicians and the caretakers of eleven randomly selected residents from three nursing homes. A qualitative analysis was performed by three independent researchers according to 'The Qualitative Analysis Guide of Leuven (QUAGOL)'. A first analysis focused on the process of initiation, continuation and cessation of medication. A second analysis compared the different participants of each interview and looked for similarities and differences., Results: Seventeen codes were developed for four themes: (1) To initiate, to continue or to cease?; (2) Behavior; (3) Therapy; and (4) Alternatives. The reasons for initiating psychotropic drugs were reducing disruptive behavior and improving the quality of life of the resident. A comparison between the interviewed showed that psychotropic drugs were initiated at the request of the nursing staff. Neither doctors nor nurses considered the monitoring of the drug therapy their task, and tended to pass on this responsibility. Once psychotropic drugs were started, the treatment was chronic but remained part of a dynamic process in which a balance was sought between benefits and adverse effects. More insights into the behavior of the resident led to a better treatment of the behavioral problems., Conclusion: Nurses play an important role in the initiation and continuation of psychotropic drugs. Physicians should take a more active role in the process of indication and monitoring of psychopharmaceuticals. Discontinuation of psychotropic drugs and the use of non-pharmacological alternatives are important bottlenecks in nursing homes. Education and training, updated practice guidelines, appropriate research, professionalization and management elements can, in a complex interaction, change this situation for the better.

Introduction: Government-funded quality improvement projects aimed to reduce the high psychotropic medication use in Belgian long-term care settings., Design: A pilot project (2013-2014) with a pre-post and follow-up intervention design., Methods: Two nursing homes received three educational courses. In the intervention nursing home (INH) additionally, a transition towards person-centred care through professional support was applied. Drug use was recorded at baseline, after 10 months (post) and after 22 months (follow-up), and coded into the Anatomical Therapeutic Chemical classification., Results: At baseline, the INH residents' (n = 118) mean age at baseline was 82 years, with 71% females. The control nursing home residents' (CNH, n = 275) mean age was 82.7 years, with 75% females. At baseline, mean drug use was 9 (range 1-21) and 8 (range 0-20), predominantly with a high proportion of psychotropic drug users of 73 and 65%, in INH and CNH respectively. At the time of post-measurement, only the proportion of hypno-sedative users decreased significantly in the INH (by 13%, p = 0.048). No significant changes were found in the CNH. At time of the follow-up, the proportion of hypno-sedative (51% vs. 31%; p = 0.005) and antidepressant users (42% vs. 25%, p = 0.007) decreased significantly in the INH. The decrease of antipsychotic drug users was less distinct. In the CNH, the proportion of hypno-sedative, antidepressant and overall psychotropic drug users did not change significantly., Conclusion: This quality improvement initiative led to a significant decrease in the use of psychotropic drugs in the INH, even after 1-year follow-up. Education only had a limited effect.

Aims: Little is known about the impact of inappropriate prescribing (IP) in community-dwelling adults, aged 80 years and older. The prevalence at baseline (November 2008September 2009) and impact of IP (misuse and underuse) after 18 months on mortality and hospitalization in a cohort of community-dwelling adults, aged 80 years and older (n = 503) was studied., Methods: Screening Tool of Older People's Prescriptions (STOPP-2, misuse) and Screening Tool to Alert to Right Treatment (START-2, underuse) criteria were cross-referenced and linked to the medication use (in Anatomical Therapeutic Chemical coding) and clinical problems. Survival analysis until death or first hospitalization was performed at 18 months after inclusion using Kaplan-Meier, with Cox regression to control for covariates., Results: Mean age was 84.4 (range 80-102) years. Mean number of medications prescribed was 5 (range 0-16). Polypharmacy (≥5 medications, 58%), underuse (67%) and misuse (56%) were high. Underuse and misuse coexisted in 40% and were absent in 17% of the population. A higher number of prescribed medications was correlated with more misused medications (r s  = .51, P < 0.001) and underused medications (r s  = .26, P < 0.001). Mortality and hospitalization rate were 8.9%, and 31.0%, respectively. After adjustment for number of medications and misused medications, there was an increased risk of mortality (HR 1.39, 95% CI 1.10, 1.76) and hospitalization (HR 1.26, 95% CI 1.10, 1.45) for every additional underused medication. Associations with misuse were less clear., Conclusion: IP (polypharmacy, underuse and misuse) was highly prevalent in adults, aged 80 years and older. Surprisingly, underuse and not misuse had strong associations with mortality and hospitalization., (© 2016 The British Pharmacological Society.)

Objectives: Polypharmacy is highly prevalent among older people (65+), but little is known on the medication use of the oldest old (80+). This study explores the medication use of the Belgian community-dwelling oldest old in relation to their demographic, clinical and functional characteristics., Methods: Baseline data was used from the BELFRAIL study; a prospective, observational population-based cohort of Belgian community-dwelling patients (80+). General practitioners recorded clinical problems and medications. Medications were coded by the Anatomic Therapeutic Chemical classification., Results: Participants' (n = 503) mean age was 84.4 years (range 80-102) and 61.2% was female. Median chronic medication use was 5 (range 0-16). Polypharmacy (≥5 medications) was high (57.7%), with excessive polypharmacy (≥10 medications) in 9.1%. Most commonly used medication group were antithrombotics, but also benzodiazepines and antidepressants were frequently consumed. Demographics related to polypharmacy (univariate analysis) were female gender, low education and moderate alcohol use. Age, care dependency and cognitive impairment showed no association with polypharmacy. In multivariate analysis, the predominant association with polypharmacy was found for multimorbidity (OR 1.78, 95% CI 1.5-2.1), followed by depression (OR 3.7, 95% CI 4.4-9.7) and physical activity (OR 0.8, 95% CI 0.7-0.9)., Conclusions: Polypharmacy was high among Belgian community-dwelling oldest old (80+). Determinants of polypharmacy were interrelated, but dominated by multimorbidity. On top of the burden of multimorbidity, polypharmacy was independently associated with less physical activity, and with depressive symptoms.

Background: Little is known about the prevalence and clinical importance of potentially inappropriate prescribing instances (PIPs) in the very old (>80 years). The main objective was to describe the prevalence of PIPs according to START (Screening Tool to Alert doctors to Right Treatment; omissions) and,STOPP (Screening Tool of Older Person's Prescriptions; over/misuse) and the Beers list (over/misuse). Secondary objectives were to identify determinants if PIPs and to assess the clinical importance to modify the treatment in case of PIPs., Methods: Cross-sectional analysis of baseline data of the BELFRAIL cohort, which included 567 Belgian patients aged 80 and older in primary care. Two independent researchers applied the screening tools to the study population to detect PIPs. Next, a multidisciplinary panel of experts rated the clinical importance of the PIPs on a subsample of 50 patients., Results: In this very old population (median age 84 years, 63 % female), the screening detected START-PIPs in 59 % of patients, STOPP-PIPs in 41 % and Beers-PIPs in 32 %. Assessment of the clinical importance revealed that the most frequent PIPs were of moderate or major importance. In 28 % of the subsample, the relevance of the PIP was challenged by the global medical, functional and social background of the patient hence the validity of some criteria was questioned., Conclusion: Potentially inappropriate prescribing is highly prevalent in the very old. A good understanding of the patients' medical, functional and social context is crucial to assess the actual appropriateness of drug treatment.

In normal-tension glaucoma (NTG), optic nerve damage occurs despite a normal intraocular pressure. Studies implicating systemic blood pressure or, more recently, arterial stiffness in the pathophysiology of NTG have produced conflicting results. Our aim was to investigate whether NTG is associated with alterations in the macrocirculation or microcirculation, cardiac function, and peripheral and central hemodynamics. Thirty patients with NTG (mean age 65 years, range 46-79) and 33 healthy subjects (mean age 67 years, range 42-79) matched for age and sex were included in the study. Exclusion criteria (for both cases and controls) were history of cardiovascular disease, diabetes mellitus, severe hypertension, and hypercholesterolemia. Aortic stiffness was measured using carotid-femoral pulse wave velocity (PWV), central hemodynamics using carotid artery applanation tonometry, and diameter, stiffness, and intima-media thickness (IMT) of the carotid and femoral artery using echo-tracking. Total peripheral resistance index (TPRI) was derived from mean arterial pressure and cardiac index, measured using ultrasound. There were no statistically significant differences in arterial structure nor function between NTG patients and age and sex-matched controls. NTG versus controls, respectively: brachial blood pressure 126 ± 15/77 ± 8 versus 127 ± 16/76 ± 7 mm Hg, P = 0.81; carotid-femoral PWV 9.8 ± 2.1 versus 10.1 ± 1.9 m/s, P = 0.60; TPRI 1833 ± 609 versus 1779 ± 602 dyne.s/cm5/m2, P = 0.79; and carotid IMT 0.65 ± 0.14 versus 0.68 ± 0.13 mm, P = 0.39. This study could not show an association of NTG with altered IMT, arterial stiffness, total peripheral resistance, cardiac output, and peripheral or central hemodynamics at rest. Although the majority of these NTG patients do exhibit symptoms of vascular dysregulation, in the present study this was not translated into alterations in the microcirculation or macrocirculation at rest.

Purpose: The aim is to describe the process, principles and results of the International Nonproprietary Name (INN) prescribing project in Belgium. The purpose of this project was to operationalize electronic INN prescribing for outpatient care in daily medical practice and to develop a factual database which can be used in electronic INN prescribing applications., Methods: The operationalization process consisted of three phases: (1) expert consultation, (2) review by regulatory authorities and (3) test phase with stakeholders and end-users., Results: The INN prescribing project resulted into (1) operational rules for electronic INN prescribing and (2) a reference database to be implemented in commercial medical software. The operational rules for electronic INN prescribing define valid INN groups as sets of equivalent medicinal products, described by three elements: the therapeutic moiety (the active part of the therapeutic ingredient) or combination of therapeutic moieties, the strength (with standardized denominators), and the method of administration (with simplified but standardized options). The operational rules also define two categories of exemptions for INN prescribing: INN groups where the first choice of treatment should be continued throughout the therapy period (NO SWITCH) and medicinal product groups not suitable for INN prescribing (NO INN). The reference database is the result of the virtual classification of the Belgian therapeutic arsenal into INN groups, according to the operational rules., Conclusions: Defining the operational rules for INN prescribing for and with different stakeholders was a difficult yet feasible assignment. The INN prescribing project resulted into explicit operational rules and a reference database. The Belgian experience may provide important information for other countries planning to operationalize or refine electronic INN prescribing. It can also be used for a thorough evaluation of the impact of the new concept of INN prescribing on daily practice and on medical education., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Antipsychotic agents are often used to treat neuropsychiatric symptoms (NPS) in dementia, although the literature is sceptical about their long-term use for this indication. Their effectiveness is limited and there is concern about adverse effects, including higher mortality with long-term use. When behavioural strategies have failed and drug therapy is instituted, regular attempts to withdraw these drugs are recommended. Physicians, nurses and families of older people with dementia are often reluctant to try to stop antipsychotics, fearing deterioration of NPS. Strategies to reduce antipsychotic use have been proposed, but a systematic review of interventions aimed at withdrawal of antipsychotic agents in older people with dementia has not yet been performed., Objectives: To evaluate whether withdrawal of antipsychotic agents is successful in older people with dementia in community or nursing home settings, to list the different strategies for withdrawal of antipsychotic agents in older people with dementia and NPS, and to measure the effects of withdrawal of antipsychotic agents on behaviour., Search Methods: ALOIS, the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (CDCIG), The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS, clinical trials registries and grey literature sources were searched on 23 November 2012. The search included the following terms: antipsychotic* or neuroleptic* or phenothiazines or butyrophenones or risperidone or olanzapine or haloperidol or prothipendyl or methotrimeprazine or clopenthixol or flupenthixol or clothiapine or metylperon or droperidol or pipamperone or benperidol or bromperidol or fluspirilene or pimozide or penfluridol or sulpiride or veralipride or levosulpiride or sultopride or aripiprazole or clozapine or quetiapine or thioridazine combined wither terms such as discontinu* or withdraw* or cessat* or reduce* or reducing or reduct* or taper* or stop*.ALOIS contains records from all major healthcare databases (The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS), as well as from many clinical trials registries and grey literature sources., Selection Criteria: Randomised, placebo-controlled trials comparing an antipsychotic withdrawal strategy to continuation of antipsychotics in people with dementia., Data Collection and Analysis: Review authors independently assessed trials for inclusion, rated their risk of bias and extracted data., Main Results: We included nine trials with 606 randomised participants. Seven trials were conducted in nursing homes, one trial in an outpatient setting and one in both settings. In these trials, different types of antipsychotics prescribed at different doses were withdrawn. Both abrupt and gradual withdrawal schedules were used. The risk of bias of the included studies was generally low regarding blinding and outcome reporting and unclear for randomisation procedures and recruitment of participants.There was a wide variety of outcome measures. Our primary efficacy outcomes were success of withdrawal (i.e. remaining in study off antipsychotics) and NPS. Eight of nine trials reported no overall significant difference between groups on the primary outcomes, although in one pilot study of people with psychosis and agitation that had responded to haloperidol, time to relapse was significantly shorter in the discontinuation group (Chi(2) = 4.1, P value = 0.04). The ninth trial included people with psychosis or agitation who had responded well to risperidone therapy for four to eight months and reported that discontinuation led to an increased risk of relapse, that is, increase in the Neuropsychiatric Inventory (NPI)-core score of 30% or greater (P value = 0.004, hazard ratio (HR) 1.94, 95% confidence interval (CI) 1.09 to 3.45 at four months). The only outcome that could be pooled was the full NPI-score, used in two studies. For this outcome there was no significant difference between people withdrawn from and those continuing on antipsychotics at three months (mean difference (MD) -1.49, 95% CI -5.39 to 2.40). These two studies reported subgroup analyses according to baseline NPI-score (14 or less versus > 14). In one study, those with milder symptoms at baseline were significantly less agitated at three months in the discontinuation group (NPI-agitation, Mann-Whitney U test z = 2.4, P value = 0.018). In both studies, there was evidence of significant behavioural deterioration in people with more severe baseline NPS who were withdrawn from antipsychotics (Chi(2) = 6.8; P value = 0.009 for the marked symptom score in one study).Individual studies did not report significant differences between groups on any other outcome except one trial that found a significant difference in a measure of verbal fluency, favouring discontinuation. Most trials lacked power to detect clinically important differences between groups.Adverse events were not systematically assessed. In one trial there was a non-significant increase in mortality in people who continued antipsychotic treatment (5% to 8% greater than placebo, depending on the population analysed, measured at 12 months). This trend became significant three years after randomisation, but due to dropout and uncertainty about the use of antipsychotics in this follow-up period this result should be interpreted with caution., Authors' Conclusions: Our findings suggest that many older people with Alzheimer's dementia and NPS can be withdrawn from chronic antipsychotic medication without detrimental effects on their behaviour. It remains uncertain whether withdrawal is beneficial for cognition or psychomotor status, but the results of this review suggest that discontinuation programmes could be incorporated into routine practice. However, two studies of people whose agitation or psychosis had previously responded well to antipsychotic treatment found an increased risk of relapse or shorter time to relapse after discontinuation. Two other studies suggest that people with more severe NPS at baseline could benefit from continuing their antipsychotic medication. In these people, withdrawal might not be recommended.