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  Medication appropriateness tool for co-morbid healthconditions in dementia: consensus recommendationsfrom a multidisciplinary expert panel A. T. Page, 1 K. Potter, 1 R. Clifford, 1 A. J. McLachlan 2 and C. Etherton-Beer  1 1 School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, and  2 Faculty of Pharmacy and Centre for Educationand Research on Ageing, University of Sydney and Concord Hospital, Sydney, New South Wales, Australia Key words dementia, prescribing criteria, older adults,cognitive impairment. Correspondence Amy Page, School of Medicine andPharmacology, University of Western Australia,Perth, WA 6009, Australia.Email: Amy.page@uwa.edu.auReceived 2 May 2016; accepted 13 July 2016. doi:10.1111/imj.13215 Abstract  Background:  Medication management for people living with dementia is a complextask as it is unclear what constitutes optimal medication management in this populationdue to the shifting focus of health priorities and the balance between the bene 󿬁 ts andharms of medications. Aim:  This study sought expert opinion to create a consensus list to de 󿬁 ne appropriatemedication management of co-morbidities for people with dementia. Methods:  This study used the Delphi technique. We invited multidisciplinaryexperts in geriatric therapeutics including pharmacists, doctors, nurse practi-tioners, a patient advocate and a psychologist to participate. Participants wereasked to engage into three or more rounds of questioning. Round 1 was a ques-tionnaire comprised of one question de 󿬁 ning dementia and seven open-endedquestions about appropriate management of co-morbidities in people withdementia. Two investigators qualitatively analysed the responses to questionsfrom Round 1 using thematic analysis. The results of this analysis were providedto participants as statements in the Round 2 survey. The participants were askedto rate their agreement with each statement on a 5-point Likert scale. Themedian and interquartile range (IQR) were calculated for the responses to eachstatement. Consensus was pre-speci 󿬁 ed as an IQR less than or equal to 1. State-ments where consensus was not achieved were presented to participants inRound 3. The Round 2 median and IQR values were provided and participantswere again asked to rate their agreement with each statement on a 5-point Likertscale. The statements where participants agreed or strongly agreed were includedin the Medication Appropriateness Tool for Co-morbid Health conditions inDementia criteria. Results:  Fifty-seven experts agreed to participate in the study, of whom 58% werepharmacists and 36% were medical practitioners. Fifty- 󿬁 ve participants completed theRound 1 (95% response rate). A total of 128 statements was included in the Round2 survey. Consensus was reached on 93 statements in Round 2 ( n  = 48 responders,84% response rate) and on 18 statements in Round 3 ( n  = 43 responders, 75%response rate). The participants reached consensus on 111 of 128 statements. Of thesestatements, 67 statements were included in the Medication Appropriateness Tool forCo-morbid Health conditions in Dementia criteria. The statements were in the broadthemes of preventative medication, symptom management, disease progression, psy-choactive medication, treatment goals, principles of medication use, side-effects andmedication reviews. Discussion:  This research provides consensus-based guidance for clinicians who man-age co-morbid health conditions in people with dementia.Funding: A. T. Page had support from a University Postgraduate Award from the University of Western Australia, Australia andK. Potter had support from a National Health and Medical Research Council (NHMRC) Early Career Fellowship for the submittedwork. A. J. McLachlan and C. Etherton-Beer are investigators on the NHMRC Centre for Research Excellence Medicines and Ageing.Con 󿬂 ict of interest: None. © 2016 The Authors. Internal Medicine Journal by Wiley Publishing Asia Pty Ltd on behalf of Royal Australasian College of Physicians.  1189 This is an open access article under the terms of the Creative Commons Attribution ‐ NonCommercial License, which permits use, distribution and reproduction in anymedium, provided the srcinal work is properly cited and is not used for commercial purposes.  Introduction Dementia is a life-limiting disease with anaverage survivaltime of less than 5 years from diagnosis. 1,2 It is the thirdleading cause of death and the leading cause of disability burden in adults aged 65 years and over in Australia. 3,4 Co-morbidities and polypharmacy are common in peoplewith dementia, though evidence is scarce for medicationsafety, tolerability and ef 󿬁 cacy in this population. 5 – 7 People with dementia have as many co-morbidities astheir peers (cognitively intact people of a comparableage) and take a mean of  󿬁 ve or more medicationsdaily. 8 – 14 However, people with dementia are more likelythan their peers to use certain medication classes, such asantihypertensives, laxatives, diuretics, antidepressantsand antipsychotics. 15,16 This medication use may re 󿬂 ectrisk factors for dementia and common co-morbiditiessuch as cardio and renovascular disease. 6,17 – 19 Age-related pharmacokinetic changes occur in all olderpeople, 20 – 22 and an altered blood-brain permeability inpeople with dementia means that they may be more sen-sitive to neurological and cognitive effects of medicationsthan their peers. 23,24 These pharmacokinetic changes areadditional to drug-disease interactions that occur indementia. 25 The safety pro 󿬁 le and ef 󿬁 cacy of many medi-cations in people with dementia are undetermined due totheir active exclusion from 85% of published clinicaltrials. 26 Furthermore, the tendency for people withdementia to under-report disease-related symptomsmeans that it is likely they also under-report side-effects. 27 Research in people with dementia focuses on treat-ments that prevent or delay dementia onset and/or pro-gression and manage dementia-speci 󿬁 c symptoms, 28 suchas the neuropsychiatric or behavioural symptoms com-mon in people with dementia. 29,30 Evidence for the ef 󿬁 -cacy of these medications is con 󿬂 icting, 31,32 and the harmsof some, such as antipsychotics and benzodiazepines,make them potentially inappropriate in this population. 33 Despite the frequency of co-morbidities and medica-tion use among people with dementia, appropriate medi-cation management in this life-limiting condition isinfrequently studied and poorly understood. Studies ofantihypertensives, hypoglycaemics, statins and anti-in 󿬂 ammatories mainly assess their ability to delaydementia onset. 34 – 41 After dementia onset, medicationappropriateness to manage co-morbidities is complicated by a relative absence of evidence. 5 – 7 Preventive treat-ments may require a treatment time to bene 󿬁 t thatexceeds life expectancy, 42 or may target treatment goalsthat are not relevant to the individual or their families. 43 This is combined with a shifting focus on the priorities ofhealthcare in this patient cohort and the balance between the bene 󿬁 ts and harms of medicines. 44 Medication management is subsequently complicatedfor people with dementia, and careful considerationshould be given to initiation and continuation of all medi-cations. Medication management decisions for people withdementia are often based on data collected in youngeradults or peers, which may not be generalisable or rele-vant to this population. The existing explicit prescribingcriteria developed for older people do not account for theadditional complexities of dementia or its life-limitingnature. 45 – 49 Consensus-basedguidance speci 󿬁 callyfor peo-ple with dementia would assist clinicians with decision-making in this population. 50,51 This study aimed to elicitopinion and gain consensus on appropriate medicationmanagement of co-morbidities in people with dementia.The intended outcome was to create a consensus-based listof statements to de 󿬁 ne appropriate medication manage-ment of co-morbidities in people with dementia namedthe Medication Appropriateness Tool for Co-morbidHealth conditions in Dementia (MATCH-D) criteria. Methods The methods for this study have been previouslydescribed in detail,  52 and are brie 󿬂 y described here.Ethical approval was granted from the University ofWestern Australia ’ s Human Research Ethics Committee(HREC) (reference: RA/4/1/7172). Expert panel selection Clinical and research based experts with relevant back-grounds were eligible for inclusion on the multidiscipli-nary expert panel. Participants were identi 󿬁 ed using amultipronged approach. 52 Relevant professional associa-tions and networks were approached to distribute anadvertisement for recruitment to their membership.Individuals identi 󿬁 ed as potentially eligible participantsthrough their peer-reviewed publications, participationin relevant conferences or peer-nominated, were sentpersonalised letters of invitation to participate. Con 󿬂 ictsof interest were declared and assessed. Data collection The Delphi technique consisted of three rounds (Fig. 1),which were administered via Qualtrics: Online SurveySoftware & Insight Platform. 53 A cover sheet that statedthe intention of the rounds was included. Page  et al. © 2016 The Authors. Internal Medicine Journal by Wiley Publishing Asia Pty Ltd on behalf of Royal Australasian College of Physicians. 1190  Round 1  –  survey design The survey questions were developed by three investiga-tors (AP, CEB and KP). The Round 1 questionnaireasked seven open-ended questions with respect to phar-macotherapeutic management of co-morbidities for peo-ple with dementia. The questionnaire included onestatement that measured agreement on a 5-point Likertscale. This statement was to de 󿬁 ne dementia. The ques-tions asked the expert panelists their opinion on theapproach to medication management of co-morbiditiesfor people with dementia (Supporting Information,Appendix S1). Figure 1  Flow chart to illustrate the process of the three rounds of the Delphi technique. MATCH-D © 2016 The Authors. Internal Medicine Journal by Wiley Publishing Asia Pty Ltd on behalf of Royal Australasian College of Physicians.  1191  Round 1  –  survey pilot  The survey was piloted with all the investigators (threepharmacists, a general practitioner and a geriatrician/clinical pharmacologist). Adjustments were made to thequestions and format of the survey based on their feed- back. The pilot process was repeated with  󿬁 ve seniorclinical pharmacists in November 2014. The survey wasfurther adjusted based on their feedback. Round 1  –  survey administration The survey was administered to the expert panel in Mayand June 2015. Round 1  –  data analyses The responses to the open-ended questions collectedduring Round 1 were analysed thematically. Tworesearchers independently coded the data using contentanalysis to organise the data into themes and collabo-rated to discuss any disagreement to reach a consensus.The Round 1 analysis was used to develop statements topresent to participants in the Round 2 survey. Statementswere amalgamated where the researchers agreed that thestatements had the same or very similar meaning. Rounds 2 and 3 Round 2  –  survey design The Round 2 survey consisted of statements generated inresponse to the open-ended questions in the Round1 survey. Participants were asked to state the extent towhich they agree with the statements using a 5-pointLikert scale from  strongly disagree  to  strongly agree .Statements with quantitative thresholds were repeatedwith different sensitivities to clarify agreement where rele-vant. For example, participants were asked if they agreedwith the statements that a medication review (otherwiseknown as a medicines use review (MUR)) should be trig-gered by (i)  󿬁 ve or more medications, (ii) eight or moremedications and (iii) ten or more medications.Statements were referenced to early, mid and latestages of dementia. The stages were de 󿬁 ned for the parti-cipants as:Early-stage dementia:  “ mild cognitive impairmentwith a preserved ability to self-care and undertakeactivities of daily living. ” Mid-stage dementia:  “ moderate cognitive impairmentwith physical function often preserved. People withmid-stage dementia may be living with support in thecommunity or a low-care residential aged care setting. ” Late-stage dementia:  “ severe cognitive impairmentand declining function (inability to recognise lovedones, unable to ambulate independently, incontinentof urine or faeces). ” Round 3  –  survey design Statements to which agreement was reached in Round2 were removed from the survey for Round 3. Theremaining statements to which the agreement was notreached in Round 2 were resubmitted to the panel in theRound 3 survey. Rounds 2 and 3  –  survey administration The Round 2 survey was administered in September andOctober 2015, and the Round 3 survey was administeredin November 2015. Rounds 2 and 3  –  data analyses The quantitative data (responses to the Likert scales)were entered into  SPSS  v22 (IBM, Armonk, NY, USA) forMacintosh statistical software for analysis. 54 To undertake the quantitative analysis, the Likert scaleresponses were coded numerically as:  strongly disagree  =1,  disagree  = 2,  neither agree nor disagree  = 3,  agree  = 4 and  strongly agree  = 5. Descriptive statistics were undertakenon the entire data set to determine the median and inter-quartile range (IQR) for each statement. Where themedian was not a whole number, it was rounded to thenearest whole unit so that it remained consistent with aresponse of strongly disagree, disagree, neither agree nordisagree, agree or strongly agree. De 󿬁 nition of consensus Consensus for an individual statement was pre-de 󿬁 nedas an IQR less than or equal to 1. 52 Statement synthesis for the MATCH-D criteria The statements were condensed to produce the  󿬁 nalMATCH-D criteria. Statements were included in theMATCH-D criteria for clinical application where the par-ticipant consensus was agreed or strongly agreed. State-ments were not included in the MATCH-D criteria wherethe participants reached agreement that they neitheragreed nor disagreed, disagreed or strongly disagreed.Statements where participants agreed that it was rele-vant for early, mid and late stage dementia were com- bined to indicate that these remained relevant regardlessof dementia stage. These were collated under the head-ing  ‘ all stages ’ . For statements with multiple quantitativethresholds, we reported the lowest of the thresholds Page  et al. © 2016 The Authors. Internal Medicine Journal by Wiley Publishing Asia Pty Ltd on behalf of Royal Australasian College of Physicians. 1192  where more than one response elicited the sameconsensus-based response (i.e. agree or strongly agree). Results The multidisciplinary expert panel consisted of 57 expertswith quali 󿬁 cations and experience in relevant  󿬁 elds(Fig.2; Table 1). De 󿬁 nition of people with dementia for thecriteria Experts agreed on the draft de 󿬁 nition in Round 1 but sug-gested modi 󿬁 cations in free text comments. They agreedon the re 󿬁 ned de 󿬁 nition in Round 2. The  󿬁 nal consensusde 󿬁 nition of dementia for use in the criteria was:Dementia is a clinical syndrome characterised by achronic progressive decline in neurocognitive function,speci 󿬁 cally affecting memory, cognition, language, beha-viour, emotional control, and social functioning beyondthe expected effects of physiological ageing and notattributable to an intercurrent illness. The speci 󿬁 c signsand symptoms of dementia and the rate of progressionvary accordingly to the aetiology and individual. One ormore aetiology may be present at the same time; themost common forms of dementia are Alzheimer ’ s, vas-cular, Lewy body, and fronto-temporal dementia. Agreement on the proposed criteria The panel considered 128 statements in eight domains forthe Round 2 survey. Consensus was reached on 93 (73%)of the 128 proposed statements considered by the expertpanel in Round 2: disagree ( n  = 4), neither agree nor disa-gree ( n  = 8), agree ( n  = 45) and strongly agree ( n  = 36).The panel considered 36 statements for the Round3 survey. Consensus was reached on 19 (53%) of the36 proposed statements that were re-administered inRound 3: disagree ( n  = 8), neither agree nor disagree( n  = 1) and agree ( n  = 4). Table 1  Participant characteristicsAge 20 – 29 years  n  = 4, 7%30 – 39 years  n  = 15, 26%40 – 49 years  n  = 15, 26%50 – 59 years  n  = 16, 28%60 – 69 years  n  = 7, 12%Gender Male  n  = 21, 37%Quali 󿬁 cations as an expert Authored one or more papers connected to medicine use in olderpeople in the last 10 years? n  = 28, 49%Credentialed in an area related to medicine use in older people (CGP,AACP, Geriatrician etc.) n  = 39, 68%Practised in a relevant  󿬁 eld for 5 or more years?  n  = 48, 85%Participated in an invitation only symposium or focus group relatedto geriatric medicine use n  = 29, 51%Received a personally addressed letter inviting you to participate inthis study. n  = 36, 63%Health profession or background Pharmacist  n  = 33, 58%General practitioner  n  = 4, 7%Clinical pharmacologist  n  = 1, 2%Geriatrician  n  = 9, 16%Physician  n  = 5, 9%General medicine physician  n  = 1, 2%Research psychologist  n  = 1, 2%Registered nurse  n  = 2, 4%Nurse practitioner  n  = 1, 2%Patient advocate  n  = 1, 2%Work environment Research based  n  = 8, 14%Practice based  n  = 28, 49%Both research and practice based  n  = 20, 35%Research, education and practice based  n  = 1, 2%Years experience in managing pharmacotherapyfor people living with dementiaUnder 5 years  n  = 14, 25%5 – 10 years  n  = 9, 16%11 – 20 years  n  = 16, 28%21 – 30 years  n  = 11, 19%31 + years  n  = 4, 7%Numbers are  n  (%). AACP, Australian Association of Consultant Pharmacy; GCP, Certi 󿬁 ed Geriatric Pharmacist. MATCH-D © 2016 The Authors. Internal Medicine Journal by Wiley Publishing Asia Pty Ltd on behalf of Royal Australasian College of Physicians.  1193
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