Deprescribing potentially inappropriate medications in memory clinic patients (DePIMM): A feasibility study.

BACKGROUND: Medication-related problems and inappropriate medication use are prevalent among people attending memory clinics. There have been no deprescribing intervention studies in this setting. OBJECTIVE: To evaluate the feasibility of a pharmacist-led interdisciplinary deprescribing intervention study in a memory clinic. METHODS: A pre-post-intervention study conducted at an outpatient memory clinic of an Australian tertiary care public hospital. Participants were English-speaking, community-dwelling patients identified as being at risk of a medication-related problem, or their carers. Participants received a medication review in their home from a consultant pharmacist who collaborated with the patient/carer, memory clinic, general practitioner and community pharmacist to develop a plan for optimising medication use. The primary outcome was feasibility, based on i) proportion of memory clinic patients eligible for the study, ii) proportion of eligible patients who consented, and iii) proportion of pharmacist-identified inappropriate/unnecessary medications that were deprescribed (reduced or ceased) at six months. RESULTS: One-third of memory clinic patient/carers were eligible (n = 82/238), 61% (n = 50/82) consented to participate. The median (IQR) age of participants who received the intervention (n = 46) was 80.5 (71.5-85.0) years and median (IQR) number of medications was 11 (8.0-13.3). Pharmacists recommended deprescribing 124 medications, and 53 (42.7%) had been ceased or dose-reduced at six months. CONCLUSION: It was feasible to recruit study participants and deliver a pharmacist-led interdisciplinary deprescribing intervention in this memory clinic setting. A larger, multi-centre study with longer follow-up is needed to confirm effectiveness and clinical outcomes.

Stakeholder perspectives on pharmacist involvement in a memory clinic to review patients' medication management and assist with deprescribing.

BACKGROUND: Memory clinics usually involve a team of health professionals who assess and review people with memory impairment. Memory clinic patients are typically older, have multiple comorbidities and potentially inappropriate polypharmacy. Pharmacists are not typically part of memory clinic teams. OBJECTIVE: To explore stakeholder perspectives on pharmacist involvement in a memory clinic to conduct medication reviews and assist with deprescribing potentially inappropriate/unnecessary medications. METHODS: Quantitative and qualitative evaluation of stakeholder perspectives within a deprescribing feasibility study. Patient/carer questionnaires were administered at 6-month follow-up. Fax-back surveys were sent to general practitioners (GPs) shortly after the pharmacist review. A focus group was conducted with memory clinic staff and semi-structured interviews with pharmacists at conclusion of the study. Focus group/interviews were transcribed and thematically analysed. RESULTS: Most patients/carers found the pharmacist medication review helpful (84%, 31/37) and believed it was important to have pharmacists in the memory clinic (92%, 36/39). Twenty-one (48%) GPs responded to the survey; most found the pharmacist reports useful for identifying inappropriate medication and providing deprescribing recommendations (86% and 81%, respectively), and 90% thought a pharmacist review should be part of the memory clinic service. Feedback from memory clinic staff and pharmacists was largely positive. Questions were raised by some staff about whether deprescribing fell within the clinic's scope of practice. Challenges associated with memory clinic-GP communication were highlighted. CONCLUSION: Patients, GPs and memory clinic staff were receptive to increased pharmacist involvement in the memory clinic. Stakeholder feedback will inform the development and delivery of pharmacist medication reviews and deprescribing in memory clinics.

Potentially Inappropriate Medication, Anticholinergic Burden, and Mortality in People Attending Memory Clinics.

BACKGROUND: There is limited evidence regarding the association between potentially inappropriate medications (PIM) and mortality in older people with cognitive impairment. OBJECTIVE: To examine whether use of medications considered to be potentially inappropriate in older people with cognitive impairment (PIMcog) and anticholinergic cognitive burden (ACB) were associated with mortality in people who attended memory clinics. METHODS: Cross-sectional and longitudinal analyses of data from the Prospective Research In MEmory clinics (PRIME) study. Participants were community-dwelling people who attended nine memory clinics and had a diagnosis of mild cognitive impairment or dementia. PIMcog was defined as any medication considered potentially inappropriate for a person with cognitive impairment according to Beers or STOPP criteria. Anticholinergic burden was calculated using the ACB scale. Time-dependent Cox-proportional hazards regression was used to analyze associations between PIMcog use/ACB score and all-cause mortality over a three-year follow-up period. The regression model included the baseline variables: age, gender, education, cognitive diagnoses, total number of medications, disease-burden, cognition, physical function, and neuropsychiatric symptoms. RESULTS: Of 964 participants, 360 (37.3%) used one or more PIMcog at some time during the study; most commonly anticholinergics and sedatives. 624 (64.7%) participants used a medication with potential or definite anticholinergic properties (ACB>0) at some point during the study. Both PIMcog use (adjusted hazard ratio: 1.42 95% CI: 1.12-1.80) and ACB score (adjusted hazard ratio: 1.18 95% CI: 1.06-1.32) were associated with mortality. CONCLUSION: Use of PIMcogs and medications with anticholinergic properties was common among memory clinic patients and both were associated with mortality.

Simple diagnostic signs in those with cognitive impairment-anything to improve detection of cognitive disorders.

With now over 50 million people worldwide with dementia (Prince et al., 2013), there are almost certainly well over 100 million people with cognitive concerns and many of these will attend their health professional keen to know what is going on. We need those without intensive training in this field to be more confident and correct in their diagnosis when such a concerned person turns up. Many simple diagnostic tests have been proposed and some assessed - these include the walk and talk (divided attention) test (those who stop when asked a question while walking may be cognitively impaired) (Lamoth et al., 2011), the clock drawing test (Brodaty and Moore, 1997), the "handbag" sign (those clutching their personal possessions are more likely to be cognitively impaired) and the "hippopotamus sign" (calling the rhinoceros, in those tests that include this, a hippopotamus). Simple screening tests have been extensively validated and are important to the clinician in formulating a diagnosis (Lorentz et al., 2002). The "head-turning" and the "attended with/alone" signs are frequently observed, and many clinicians assessing such individuals would be well aware of them and probably even unknowingly factor them into their diagnosis. In this issue, Pinar Soysal and colleagues (Soysal et al., 2017) have evaluated these signs and, in those older people attending with cognitive concerns, found they had quite good diagnostic value. They were not very specific but showed good sensitivity and negative predictive value. Indeed, at the recent Alzheimer's Association International Conference in London there were several posters evaluating "soft but simple" signs although not all performed as expected - one group found gait actually sped up in those with cognitive impairment that were asked a question.

Potentially Inappropriate Medications and Anticholinergic Burden in Older People Attending Memory Clinics in Australia.

BACKGROUND: There has been limited research into potentially inappropriate medication (PIM) use and anticholinergic burden in patients attending memory clinics. OBJECTIVES: The aim of this study was to explore the use of PIMs related to cognitive impairment (PIMcog), anticholinergic cognitive burden (ACB) and concomitant use of anticholinergic medications with cholinesterase inhibitors (ChEIs) in patients attending memory clinics. METHODS: Cross-sectional analysis of baseline data from the Prospective Research In MEmory clinics (PRIME) study was performed. Participants were community-dwelling patients who attended nine memory clinics and had a diagnosis of mild cognitive impairment or dementia. PIMcog were defined as any medication considered potentially inappropriate for patients with cognitive impairment according to the Beers or STOPP criteria. Clinically significant ACB was defined as total score of ≥3 on the ACB scale. RESULTS: A total of 964 patients, mean age 77.6 years, were included. PIMcog were used by 206 (21.4%) patients. Anticholinergics and sedatives were the most common PIMcog. PIMcog use was associated with higher number of medications (adjusted OR 1.26; 95% CI 1.19-1.33) and with not having completed secondary level education (adjusted OR 1.71; 95% CI 1.01-2.89). One hundred and thirteen (11.7%) patients had a clinically significant ACB score (≥3). ChEIs were used by 575 patients and 65 (11.3%) of these had an ACB score ≥3. There was no statistically significant difference in ChEI use between patients with and without an ACB score ≥3. CONCLUSION: PIMcog use, clinically significant anticholinergic burden, and concurrent use of anticholinergics with ChEIs were prevalent in patients attending memory clinics. Efforts are needed to improve prescribing for people with cognitive impairment.

Differentiating the frontal presentation of Alzheimer's disease with FDG-PET.

BACKGROUND: Alzheimer's disease (AD) can present with behavioral changes with this syndrome described as frontal variant AD (FvAD). Excess frontal pathology may explain this presentation. Neuroimaging with fluoro-deoxy-glucose positron emission tomography (FDG- PET) can be used to examine the effects of pathology in FvAD. METHODS: We administered an assessment scale for frontal behavioral impairment, the Frontal Behavioral Inventory (FBI), to 53 patients with AD. Scores in the top quartile were defined as FvAD. FDG- PET was analyzed in 8 frontal regions. RESULTS: The Z (SD) score for metabolism was significantly higher (indicating greater hypometabolism) in the FvAD group than the remaining AD group for combined left and right orbitofrontal regions (2.64 (SD 0.99) versus 2.11 (1.22), p < 0.03)) and combined left and right medial frontal regions (2.38 (0.63) versus 1.82 (0.88) p < 0.003) but insignificantly different in combined lateral frontal and superior frontal regions. Statistical parametric mapping revealed these frontal regions to be the only brain regions with significantly different metabolism between the FvAD and the remainder of the AD groups. CONCLUSIONS: Medial and orbital frontal hypometabolism is greater in AD patients presenting with more frontal/behavioral features, likely reflecting a greater pathological load in these brain regions in FvAD patients. These frontal regions may be more linked to behavioral features than other frontal brain regions.

Among vitamin B12 deficient older people, high folate levels are associated with worse cognitive function: combined data from three cohorts.

BACKGROUND: Folate fortification of food aims to reduce the number of babies born with neural tube defects, but has been associated with cognitive impairment when vitamin B12 levels are deficient. Given the prevalence of low vitamin B12 levels among the elderly, and the global deployment of food fortification programs, investigation of the associations between cognitive impairment, vitamin B12, and folate are needed. OBJECTIVE: To investigate the associations of serum vitamin B12, red cell folate, and cognitive impairment. METHODS: Data were collected on 1,354 subjects in two studies investigating cognitive impairment, and from patients attending for assessment or management of memory problems in the Barwon region of south eastern Australia between 2001 and 2011. Eligible subjects who had blood measurements of vitamin B12 and red cell folate taken within six months of cognitive testing were included. Subjects with stroke or neurodegenerative diseases other than Alzheimer's disease were excluded. A Mini-Mental State Examination score of <24 was used to define impaired cognitive function. RESULTS: Participants with low serum vitamin B12 (<250 pmol/L) and high red cell folate (>1,594 nmol/L) levels were more likely to have impaired cognitive performance (adjusted odds ratio (AOR) 3.45, 95% confidence interval (CI): 1.60-7.43, p = 0.002) when compared to participants with biochemical measurements that were within the normal ranges. Participants with high folate levels, but normal serum vitamin B12, were also more likely to have impaired cognitive performance (AOR 1.74, 95% CI: 1.03-2.95, p = 0.04). CONCLUSIONS: High folate or folic acid supplements may be detrimental to cognition in older people with low vitamin B12 levels. This topic is of global significance due to the wide distribution of food fortification programs, so prospective studies should be a high priority.

A randomised single-blind study to improve health-related quality of life by treating anaemia of chronic kidney disease with Aranesp® (darbepoetin alfa) in older people: STIMULATE.

BACKGROUND: The prevalence of chronic kidney disease (CKD) increases with age, and the risk of significant anaemia increases as renal function declines. The objectives of this study were to assess the effect of darbepoetin alfa administration on health-related quality of life (HRQOL) through treatment for anaemia in older patients with CKD. METHODS: In this multicentre, randomised, placebo-controlled trial, older patients (aged ≥ 70 years) with CKD (Stages 3-5, predialysis) and haemoglobin (Hb) < 11.0 g/dL were randomised to darbepoetin alfa (n = 28) or placebo (n = 23). HRQOL was measured using a number of instruments including Short Form-36 (SF-36) and Functional Assessment of Cancer Therapy-Anaemia (FACT-An). RESULTS: The primary endpoint, mean SF-36 Vitality Score at Week 24, was comparable between the darbepoetin alfa (51.4 [95 % CI 48.0, 54.9]) and placebo (46.7 [40.9, 52.5]) groups. Darbepoetin alfa-treated patients experienced statistically significant improvements in some SF-36 and FACT-An Subscale Scores. Mean Hb was higher with darbepoetin alfa (12.5 [12.1, 12.9] g/dL) than with placebo (10.5 [10.1, 11.0] g/dL). The safety profiles were comparable between the treatment groups. The study was limited by only 20 % of the planned patient recruitment being achieved. CONCLUSIONS: Darbepoetin alfa increased Hb and, within study limitations, suggested that improvements in some HRQOL domains in older CKD patients with anaemia may be achieved with more physiological haemoglobin.

Pharmacist-led medication review to identify medication-related problems in older people referred to an Aged Care Assessment Team: a randomized comparative study.

BACKGROUND: Aged Care Assessment Teams (ACATs) in Australia assess the care needs of frail older people. Despite being at high risk of medication-related problems (MRPs), ACAT patients do not routinely receive a comprehensive medication review. OBJECTIVES: The aims of the study were to compare three methods for facilitating a pharmacist-led comprehensive medication review for people referred to an ACAT, and compare MRPs identified via ACAT usual care with those identified via pharmacist-led medication reviews. METHODS: A prospective, randomized, comparative study involving 80 community-dwelling patients (median age 84 years) referred to an ACAT in Melbourne, Australia, was conducted. Following ACAT assessment (usual care), a clinical pharmacist reviewed all participating patients' ACAT files to identify potential MRPs not identified by the ACAT (medication review method 1). Patients were then randomized into two groups. Group A received information about the Australian government-funded, general practitioner (GP)-initiated Home Medicines Review (HMR) programme, and a letter was sent to their GP recommending an HMR (GPHMR; medication review method 2). Group B patients were referred directly to a clinical pharmacist associated with the ACAT for an ACAT-initiated pharmacist home medicines review (APHMR; medication review method 3); the pharmacist arranged a home visit, obtained a thorough medication history and conducted a comprehensive medication review. The main outcome measures were the proportion of patients who received a pharmacist home visit within 28 days; the number of MRPs identified by ACAT usual care, pharmacist review of ACAT files, and APHMR, and their clinical risk (assessed by a geriatrician-pharmacist panel); and patients', GPs' and ACAT clinicians' opinions about pharmacist medication review. RESULTS: Three hundred patients were referred to the ACAT, and 80 were recruited into the study. Thirty-six of 40 APHMR patients (90.0%) received a pharmacist home visit within 28 days, compared with 7/40 GPHMR patients (17.5%).[p < 0.001]. Twenty-one MRPs were identified via ACAT usual care. Pharmacist review of ACAT files identified a further 164 potential MRPs (median 2.0 per patient; inter-quartile range [IQR] 1.0-3.0); however, in patients who received an APHMR, 35/82 potential MRPs (42.7%) turned out not to be actual problems, most commonly because of discrepancies between the patient's ACAT medication list and the medications currently being used by the patient (median 3.0 discrepancies per patient; IQR 2.0-5.5). APHMR identified a further 79 MRPs (median 2.0; IQR 1.0-3.0). One hundred and twenty-two MRPs were included in APHMR reports sent to patients' GPs. Of these, 94 (77.0%) were assessed as being associated with a moderate, high or extreme risk of an adverse event. Sixty-four APHMR recommendations (52.5%) led to changes to patients' medication regimens or medication management. Thirty-six of 39 GPs (92.3%) who provided feedback reported that pharmacist medication reviews were useful. Patients (or their carers) also reported that pharmacist home visits were useful: median rating 4.25 out of 5 (IQR 4.0-5.0). Seven of 11 ACAT clinicians (77.8%) agreed that pharmacist-led medication review should be a standard component of ACAT assessments. CONCLUSIONS: ACAT assessments without pharmacist involvement detected fewer MRPs than any of the evaluated pharmacist-led medication review methods. APHMR was more effective than pharmacist review of routinely collected ACAT data, and more reliable and timely than referral to the patients' GP for a GPHMR.

Medication-related problems in patients referred to aged care and memory clinics at a tertiary care hospital.

AIM: To investigate the prevalence of medication-related problems (MRPs) in patients attending aged care and memory disorder clinics and explore the potential role of a clinical pharmacist to obtain medication histories and identify unresolved MRPs. METHODS: The clinical pharmacist interviewed patients and reviewed their medication regimens in the outpatient clinics. Clinical significance of pharmacist-identified MRPs was rated by an independent expert panel using validated criteria. RESULTS: Forty-six patients (mean age 82 years) were reviewed. They took a median of nine medications, of which three were not recorded in the medical record. One hundred and thirteen MRPs (median 2.0 per patient) were identified by the pharmacist. Independent review rated 35% of MRPs as high or extreme risk. Thirty-seven (33%) MRPs related to medications not recorded in the medical record. CONCLUSIONS: Medication-related problems were present for most patients. Involvement of a clinical pharmacist resulted in a more comprehensive medication history and identified unresolved MRPs.

A Self-Administration of Medications Program to Identify and Address Potential Barriers to Adherence in Elderly Patients.

BACKGROUND: Inpatient self-administration of medications programs (SAMPs) improve the medication knowledge and adherence of elderly patients after their discharge from the hospital. They may also identify patients who will have difficulties managing their medications after discharge; however, no previous study has evaluated the value of a SAMP for detecting and addressing barriers to adherence. OBJECTIVE: To evaluate the usefulness of a SAMP for detecting and addressing barriers to adherence in functionally impaired elderly hospital inpatients, and to identify predictors of patient performance in a SAMP. METHODS: A prospective cohort study was conducted on 2 subacute aged-care wards. Patients who were intending to independently manage their medications after discharge were recruited. Medications were dispensed and labeled with full directions, and the patients were educated about their medications. Each patient was required to request the medications from nursing staff when due, then select and administer them under supervision. Patient performance was documented. Barriers to adherence and interventions used to address these barriers were recorded. Analyses were performed to identify factors associated with failing the SAMP. RESULTS: Of 62 patients who were recruited, 43 (69.4%) passed the program without requiring interventions to address adherence barriers, 7 (11.3%) passed with an intervention implemented to enable them to remain independent with medication management after discharge, and 12 (19.4%) failed and required full assistance with medication management after discharge. Overall, barriers to medication adherence (eg, inability to open containers, inability to request medications without prompting) were identified for 30.6% of patients. Mini-Mental State Examination scores and patient age were independent predictors of whether a patient would fail the SAMP. CONCLUSIONS: An inpatient SAMP effectively detected barriers to medication adherence that otherwise may not have been detected and addressed prior to a patient's discharge from the hospital.

Antithrombotic prescribing in atrial fibrillation: application of a prescribing indicator and multidisciplinary feedback to improve prescribing.

BACKGROUND: Atrial fibrillation is common in older people, and is associated with an increased risk of ischaemic stroke. Antithrombotic therapy reduces stroke-risk, but is known to be under-prescribed. OBJECTIVES: To use an evidence-based indicator to audit antithrombotic prescribing for older hospital inpatients with atrial fibrillation, and to assess whether feedback of audit results to hospital staff increases antithrombotic use. DESIGN: Cross-sectional notes-based audits, before and after feedback. SETTING: Six Aged Care and three General Medicine units at nine Australian public teaching hospitals between September 1998 and May 1999. SUBJECTS: 1416 hospital inpatients aged 65 years and over (median age 81). METHODS: Medication charts were reviewed to identify patients prescribed digoxin or amiodarone. Presence of atrial fibrillation was confirmed by review of the patients' medical notes. To be considered appropriate, patients with atrial fibrillation had to be receiving either warfarin or aspirin (or both), or have documented contraindications to both agents. Feedback of audit results was provided to medical, pharmacy and nursing staff at multidisciplinary meetings. Changes in antithrombotic prescribing 4-8 weeks and 6 months after feedback were assessed. Prescribing 8 weeks prior to feedback was assessed retrospectively. RESULTS: Appropriateness of the decision to prescribe (or not prescribe) antithrombotic therapy increased from 81/112 (72%) immediately prior to feedback to 97/105 (92%) 4-8 weeks later (P<0.0001). Six months after feedback, appropriateness of prescribing declined slightly, to 85% (p=0.36). Over the 8 weeks prior to feedback, appropriateness of prescribing did not change (74% versus 77%, p=0.80). Increased aspirin prescribing accounted for most of the improvement in antithrombotic use after feedback, while warfarin continued to be under-used. CONCLUSIONS: Antithrombotics were under-prescribed for older patients with atrial fibrillation. Audit and multidisciplinary feedback resulted in increased antithrombotic prescribing. The intervention had a greater impact on aspirin prescribing compared with warfarin.