TITLE: The Medication Pass Nutritional Supplement Program in Patients Receiving Medication: A Review of Clinical Effectiveness and Guidelines

Transcription

1 TITLE: The Medicatin Pass Nutritinal Supplement Prgram in Patients Receiving Medicatin: A Review f Clinical Effectiveness and Guidelines DATE: 25 March 2015 CONTEXT AND POLICY ISSUES Malnutritin is a prblematic issue in the healthcare system, especially in the elderly ppulatin. Amng the hspitalized lder ppulatin in Eurpe, United States and Suth Africa, the prevalence f malnutritin is estimated t 22.8%, with 39 t 47% being at risk. 1 In lng-term care in the United States, 74% f residents are estimated t be at risk fr pr nutritinal status. 2 Malnutritin is assciated with weight lss, increased mrbidity and mrtality, increased risk f pressure ulcer develpment, increased risk f infectins, and increased length f stay due t cmplicatins. 3,4 Malnutritin may be caused by many factrs including taste and smell alteratins, fd preferences and textures, inability t self-feed, dysphagia, dentitin/ral prblems, depressin and ther mental disrders, degenerative diseases, intestinal malabsrptin, and medicatin side effects. 3,5 Oral liquid supplementatin (OLS) is typically the first and easiest interventin t administer when weight lss and malnutritin are bserved. Yet, the utcmes f this interventin are rarely investigated. 5 In a meta-analysis f 55 randmized studies n nutritinal supplements t prevent malnutritin in lder, high-risk patients shwed nly mdest imprvement in percentage weight change. 6 Amng the issues raised fr cnventinal OLS, decreased cnsumptin f fd, thereby decreasing ttal daily calric intake, and high wastage f OLS (lw cmpliance) are mentined. The medicatin pass nutritinal supplement prgram (Med-Pass) suggests distributing small amunts (60 ml) f calrically dense supplements (2 kcal/ml) in between meals, during the distributin f medicatin, three r fur times daily. 7 This strategy avids duplicate effrt by using an existing system and may prevent residents frm cnsuming supplements in lieu f fd, thus prmting weight gain. The purpse f this review is t assess evidences n Med-Pass in terms f clinical effectiveness and evidence-based clinical practice guidelines, including evidence frm all institutinalized settings. Disclaimer: The Rapid Respnse Service is an infrmatin service fr thse invlved in planning and prviding health care in Canada. Rapid respnses are based n a limited literature search and are nt cmprehensive, systematic reviews. The intent is t prvide a list f surces f the best evidence n the tpic that CADTH culd identify using all reasnable effrts within the time allwed. Rapid respnses shuld be cnsidered alng with ther types f infrmatin and health care cnsideratins. The infrmatin included in this respnse is nt intended t replace prfessinal medical advice, nr shuld it be cnstrued as a recmmendatin fr r against the use f a particular health technlgy. Readers are als cautined that a lack f gd quality evidence des nt necessarily mean a lack f effectiveness particularly in the case f new and emerging health technlgies, fr which little infrmatin can be fund, but which may in future prve t be effective. While CADTH has taken care in the preparatin f the reprt t ensure that its cntents are accurate, cmplete and up t date, CADTH des nt make any guarantee t that effect. CADTH is nt liable fr any lss r damages resulting frm use f the infrmatin in the reprt. Cpyright: This reprt cntains CADTH cpyright material and may cntain material in which a third party wns cpyright. This reprt may be used fr the purpses f research r private study nly. It may nt be cpied, psted n a web site, redistributed by r stred n an electrnic system withut the prir written permissin f CADTH r applicable cpyright wner. Links: This reprt may cntain links t ther infrmatin available n the websites f third parties n the Internet. CADTH des nt have cntrl ver the cntent f such sites. Use f third party sites is gverned by the wners wn terms and cnditins.

2 RESEARCH QUESTIONS 1. What is the clinical effectiveness f using the Medicatin Pass Nutritinal Supplement prgram (Med-Pass) in patients receiving medicatin in an institutinalized setting? 2. What are the evidence-based guidelines assciated with the use f Med-Pass in patients receiving medicatin in an institutinalized setting? KEY FINDINGS Evidence retrieved frm ne randmized cntrlled trial (RCT), tw nn-randmized cmparative trials, fur befre-after studies and 2 clinical practice guidelines (CPGs) was in favr f clinical benefits due t Med-Pass in elderly hspitalized patients. Hwever, limitatins identified in the studies prevent us t draw a firm cnclusin. As highlighted in a CPG based n a systematic review, high quality research is further needed fr specific interventins f ral liquid supplementatin. METHODS Literature Search Methds A limited literature search was cnducted n key resurces including PubMed, The Cchrane Library (2015, Issue 2), University f Yrk Centre fr Reviews and Disseminatin (CRD) databases, CINHAL via the EBSCOHOST platfrm, Canadian and majr internatinal health technlgy agencies, as well as a fcused Internet search. N filters were applied t limit the retrieval by study type. Where pssible, retrieval was limited t the human ppulatin. The search was als limited t English language dcuments and n date limit was impsed. Rapid Respnse reprts are rganized s that the evidence fr each research questin is presented separately. Selectin Criteria and Methds One reviewer screened citatins and selected studies. In the first level f screening, titles and abstracts were reviewed and ptentially relevant articles were retrieved and assessed fr inclusin. The final selectin f full-text articles was based n the inclusin criteria presented in Table 1 in which publicatins were limited t health technlgy assessments, systematic reviews, meta-analyses, RCTs, nn-randmized studies and CPGs. The Medicatin Pass Nutritinal Supplement Prgram in Patients Receiving Medicatin 2

3 Table 1: Selectin Criteria Ppulatin Patients receiving medicatin in any institutinalized setting (e.g., acute care, lng-term care, hspitals [emergency rms]) Interventin Medicatin Pass Nutritinal Supplement prgram (Med-Pass) Cmparatr Standard f care (i.e., nt using Med-Pass, administering medicatin with water, juice, r ginger ale) N cmparatr Outcmes Clinical effectiveness and safety (e.g., patient harms and benefits, ptential fd/drug interactins) Evidence-based guidelines Study Designs Health technlgy assessments, systematic reviews, meta-analyses, randmized cntrlled trials, nn-randmized studies and evidencebased guidelines. Exclusin Criteria Articles were excluded if they did nt meet the selectin criteria utlined in Table 1 r if they were duplicate publicatins. Critical Appraisal f Individual Studies The included nn-randmized studies and RCTs were critically appraised using the Dwns and Black checklist. 8 Items evaluated included clear study bjectives, clear study inclusin and exclusin criteria, clear descriptin f ptential cnfunders, descriptin f lsses t fllw up, blinding, apprpriate statistical tests used, accuracy f the utcme measures, and whether pwer was sufficient t detect a difference if ne existed. CPGs were assessed using the Appraisal f Guidelines fr Research and Evaluatin II (AGREE II) instrument. 9 The items included in the AGREE II instrument are scpe and purpse f the guideline, stakehlder invlvement, rigur f develpment, clarity and presentatin, applicability, and editrial independence. Summary scres were nt calculated fr the included studies; rather, a review f the strengths and limitatins f each included study were described narratively. SUMMARY OF EVIDENCE Details f study characteristics, critical appraisal, and study findings are lcated in Appendices 2, 3, and 4, respectively. Quantity f Research Available A ttal f 153 citatins were identified in the literature search. Fllwing screening f titles and abstracts, 144 citatins were excluded and nine ptentially relevant reprts frm the electrnic search were retrieved fr full-text review. Seven ptentially relevant publicatins were retrieved frm the grey literature search and hand search. Of these 16 ptentially relevant articles, five publicatins were excluded fr varius reasns, while 11 publicatins met the inclusin criteria and were included in this reprt. Appendix 1 describes the PRISMA flwchart f the study selectin. The Medicatin Pass Nutritinal Supplement Prgram in Patients Receiving Medicatin 3

4 Additinal reference f ptential interest is prvided in appendix 5. Summary f Study Characteristics Study Design A ttal f eight publicatins reprting n seven studies were identified that evaluated the clinical effectiveness f Med-Pass. Of these studies, ne was a RCT, 10 tw were cmparative nnrandmized trials 11,12 and fur were befre-after studies (reprted in five publicatins) In additin, tw CPGs disseminated in three publicatins were identified that addressed the interventin f Med-Pass Cuntry f Origin The RCT riginated frm Sctland. 10 The nn-randmized trials were frm Australia. 11,12 The befre-after studies were cnducted in Canada 13 and in the United States The CPGs were develped in the United States 18,19 and in Australia. 20,21 Patient Ppulatin Fur studies included elderly patients nly. One study included patients wh culd be aged between 26 and 104 years ld. 14 Acrss these five studies, the mean age ranged frm t years f age. Tw studies did nt reprt the age f patients, but were cnducted in settings where lder patients are expected Studies reprted a prprtin f females between 100% 13 and 48.5% 11, whereas three studies 10,15-17 did nt disclse the gender f patients. Five studies 11-14,16,17 enrlled malnurished patients and thse at risk f malnutritin. Tw studies 10,15 enrlled patients regardless f their nutritinal status. Fur studies 11,13-15 were held in a lngterm care setting, tw 10,12 were held in an acute care setting and ne was dne in a transitinal care unit. 16,17 The sample size was ranging frm t patients. The ppulatin studied in ne CPG was the elderly hspitalized ppulatin. 20,21 The ther included CPG further fcused n hspitalized lder adults wh are malnurished r at risk f malnutritin. 18,19 Interventins and Cmparatrs Mst f the studies used the cmmn Med-Pass prgram with 60 ml f a 2 kcal/ml supplement served three r fur times a day. One RCT 10 used a slightly different Med-Pass prtcl with 120 ml servings f a 1.5 kcal/ml supplement three times a day. Anther befreafter study 16,17 used 90 ml f a patient-specific supplement (1.5 kcal/ml) three times a day (n average) as Med-Pass. When a cmparatr was used, it was n supplement, 10 traditinal OLS between meals, 11,12 r a snack trlley between meals. 11 The duratin f the interventin culd vary frm a fixed duratin f 2 weeks 11 t 6 mnths 13 r fr the whle duratin f the stay. 10,12,16,17 The Medicatin Pass Nutritinal Supplement Prgram in Patients Receiving Medicatin 4

5 One CPG cnsidered the interventins used fr the assessment f nutritinal status and the management f a pr nutritinal status. 18,19 The ther CPG cnsidered all types f interventins aimed at minimizing undernutritin. 20,21 Outcmes The mst cmmn utcmes assessed were weight change, ttal energy intake (including fd cnsumptin), supplement cmpliance, skin integrity, serum prtein (albumin r pre-albumin), staff perceptin, waste, and cst. One RCT 10 als evaluated functinal recvery, arm muscle circumference, mrtality, discharge placement, and length f stay. A nn-randmized trial 11 assessed health related quality f life (EQ-5D) and patient satisfactin. Anther nnrandmized study 12 used the Mini Nutritinal Assessment (MNA) instrument t capture data n anthrpmetry and n general, dietary and self-subjective assessments. One CPG included dietary measures, anthrpmetry and bdy cmpsitin measures, bichemical indicatrs, clinical utcmes (including length f stay, mrtality, prevalence/incidence f malnutritin), and functinal indicatrs. 20,21 The ther CPG cnsidered utcmes reflecting the nutritinal status, the functinal status and the general well-being. 18,19 Years f publicatin The years f publicatin f the studies ranged frm 1998 t The CPGs were published in ,21 and in ,19 Summary f Critical Appraisal The RCT 10 was generally well cnducted with a clear descriptin f bjectives, inclusin criteria, utcmes, interventins, and findings. Althugh the patients and the ward staff were nt blinded, the investigatrs invlved in data cllectin and assessment were blinded. Als, mst f utcme measures were bjective, patient were representative f the targeted ppulatin, n patients withdrew frm the study, an adequate sample sized was used, P values were prvided and adjusted analyses were dne fr sensitivity purpses. In terms f limitatins, the study 10 did nt cmprehensively reprt the baseline characteristics f patients, the study did nt investigate ptential adverse events and the investigatrs carried ut a multiplicity f analyses in the subgrups withut an adequate statistical plan. Tw nn-randmized trials 11,12 were identified. Bth studies had a clear descriptin f bjectives, inclusin criteria, patient characteristics, utcmes and interventins. Bth studies recrded ptential adverse events. In the Jukkla et al. study, 12 patients were deemed representative f the general ppulatin and patients were nt aware f the nging study. Neither study used an ITT analysis, and sme utcmes were subjective. The study f Campbell et al. 11 had the fllwing limitatins: it was pen label; it had unclear external validity (i.e exclusin f patients with cgnitive prblems r renal impairment); the grups were nt studied in parallel; it had a limited study duratin (2 weeks); and althugh a pwer calculatin was prvided, the findings and their statistics were nt clearly reprted. The ther nnrandmized trial 12 was limited by the absence f a pwer calculatin, the multiplicity f analyses withut a statistical plan, the fact that each grup was in a different ward, the lw prprtin (22%) f patients wh filled the questinnaire at endpint, the subjectivity f many utcmes, the absence f blinding fr investigatrs and their stated rle in encuraging patients t cmply with the Med-Pass. The Medicatin Pass Nutritinal Supplement Prgram in Patients Receiving Medicatin 5

6 The fur befre-after studies had many limitatins. These included the absence f blinding, nt reprting patient characteristics, a small sample size, the absence f a pwer calculatin, unclear external validity r unclear rate f patients wh cnsented t participate in study, 13,15-17 uncertain methd fr estimatin f fd intake, 15 a ttal energy intake that is nt recrded, 13,16,17 unclear estimatin f wastage, 14 findings r inferential statistics that were nt crrectly reprted, 13,15-17 lack f ITT analysis, utilizatin f serum albumin as a surrgate utcme fr nutritinal status, 13,14 n capture f ptential adverse events, and n reprting f cmpliance Nevertheless, mst f the studies clearly described the bjectives, inclusin criteria, utcmes and interventins Other strengths included a clear descriptin f findings, 13,14 a representative ppulatin, 14,16,17 and n discntinuatins during the study. 14 The CPG frm the Janna Briggs Institute (JBI) 20,21 was based n a systematic review while it was nt clear whether the review n which the CPG frm the Hartfrd Institute fr Geriatric Nursing (HIGN) 18,19 was based was systematic. Bth CPGs clearly reprted the bjectives, health questins, target ppulatins, end users, and recmmendatins. The CPG frm JBI had a clear methdlgy descriptin including a search strategy, explicit selectin criteria, duplicate article selectin, critical appraisal and methds fr frmulating recmmendatins. An expert cmmittee was invlved in its develpment and it was externally reviewed thereafter. Cnflicts f interest were disclsed. All these features were lacking in the CPG frm HIGN where nly general methdlgy was prvided. This latter CPG further lacked tls fr implementatin and a prcedure fr updating the guideline. Neither CPG sught input frm the target ppulatin, and resurce implicatins were nt addressed. Summary f Findings The clinical effectiveness f using Med-Pass in patients receiving medicatin in an institutinalized setting The RCT reprted that Med-Pass increased bdy weight (+1.0%, 95% cnfidence interval [CI] 0.5 t 3.4%, P = 0.003) cmpared t cntrl grup (n supplement) in elderly patients admitted at hspital after a median length f stay between 16 and 18 days. 10 In agreement with this finding, tw befre-after studies in elderly patients with pr nutritinal status reprted bdy weight increases f 2.6 kg (6.4% f bdy weight, but n statistical inference was prvided) 13 and 2.4 lbs (P < 0.01) 14 after 6 mnths and 4 weeks in lng-term care, respectively. A nnrandmized study fund n significant weight change in lder malnurished patients after tw weeks in lng-term care. 11 Tw befre-after studies shwed maintenance f weight in mst f the patients after 4 weeks in lng-term care 15 r 11 days (n average) in transitinal care, 16,17 respectively. In the RCT, ttal energy intake increased with Med-Pass (+319 kcal/day, 95% CI 133 t 506 kcal/day, P = 0.001) cmpared t cntrl grup (n supplement). 10 A nn-randmized trial reprted a required energy intake f 109 ± 28% and a required prtein intake f 126 ± 28% with Med-Pass. 11 This was an imprvement cmpared t a mid-meal trlley snack (P < 0.001), but this was nt different frm traditinal supplementatin. A befre-after study mentined an increase in meal intake f 7.3% ± 13.4% (P < 0.005) after implementatin f Med-Pass. 14 In cntrast, anther befre-after study reprted a 17% decrease in ttal energy intake explained by a 29% decrease in supplement energy intake, but a 19% increase in fd intake. 15 The Medicatin Pass Nutritinal Supplement Prgram in Patients Receiving Medicatin 6

7 In terms f skin integrity, a nn-randmized trial shwed n difference in the presence r degree f pressure ulcers cmpared t traditinal supplementatin after tw weeks. 11 Tw befre-after studies reprted benefits fr chrnic pressure ulcers after 6 mnths 13 and 11 days (n average), 16,17 respectively. In a nn-randmized study, Med-Pass imprved the visual analg scale (VAS) and the index scre f Eur Quality f life-5 dimensins (EQ-5D) significantly frm baseline. 11 A statistically significant difference was bserved fr the VAS nly when cmparing t cnventinal supplement. 11 Using the NMA questinnaire, a nn-randmized trial fund increased weight scres, number f meals cnsumed scres and prtein intake scres in malnurished (r at risk) elderly patients in acute care after a mean stay between 23 and 36 days. 12 Hwever, there was n difference in verall scre. In the RCT, mrtality (dds rati [OR] 0.32, 95% CI 0.1 t 1.0, P < 0.05) and functinality (P < 0.04) were fund t be imprved nly in the mst prly nurished patients, but nt in the verall ppulatin f hspitalized elders in emergency unit r in ther sub-grups based n nutritinal status. 10 In the RCT, Med-Pass decreased the length f stay in hspital f the adequately nurished patients (13.5 vs 21.0 days, P < 0.05) cmpared t n supplement, but this finding was nt bserved in ther nutritinal status sub-grups r the verall sample. 10 In a nn-randmized trial, patients in the Med-Pass grup had a shrter length f stay (23 ± 9 vs. 36 ± 18 days, P = 0.044) cmpared t cnventinal supplementatin. 12 Studies revealed a psitive staff perceptin f Med-Pass in general, 12,13,15 but ne study mentined cncerns n the decreased ttal energy intake. 15 Staff members als mentined an increased wrklad f 5 t 20 min per medicatin pass rund when giving supplements as part f the Med-Pass. 13 Anther study stated that Med-Pass is time saving cmpared t traditinal supplementatin. 11 In terms f cmpliance t supplement, studies reprted an increase 12,14 r n difference 11 in cmpliance when using Med-Pass cmpared t traditinal supplementatin r simply reprted a gd cmpliance with Med-Pass. 10,13 Evidence-based guidelines assciated with the use f Med-Pass in patients receiving medicatin in an institutinalized setting The tw identified CPGs fcused n the elderly ppulatin, with the JBI CPG fcusing further n acute care. 20,21 Based n high quality evidence, the JBI CPG stated that interventins with ral supplement in general have been fund t prmte weight gain and increase lean bdy mass in under- r malnurished elderly patients. 20,21 Ensuring that the prescribed nutritinal interventin is apprpriately implemented was deemed critical fr psitive utcmes. When giving OLS, HIGN recmmended that the supplement is served at apprpriate temperature withut a packaging barrier. Supplements were recmmended t be prvided between meals. And mnitring the intake f the supplement was recmmended. 18,19 Encuraging patients t cnsume the fds and beverages served, giving assistance when necessary, was thught t imprve intake level. 20,21 Supplementatin served as sip prtins and as part f the medicatin prtcl (Med-Pass) was recmmended. 18,19 The Medicatin Pass Nutritinal Supplement Prgram in Patients Receiving Medicatin 7

8 CPGs agree that the cause f malnutritin r weight lss shuld be investigated in rder t prvide a useful slutin. They suggest that, depending n the underlying cause, ral supplementatin might nt be the apprpriate interventin. Successful strategies are recmmended t invlve agreement by a multidisciplinary team, including, but nt restricted t, a dietitian and a pharmacist. 18,19 If available, the input frm nutritin services shuld be requested as sn as pssible. 20,21 Cnsulted CPGs als prvided guidelines n the assessment f the patient and fllw-up mnitring. Of nte, serum albumin used as an evaluatin f nutritinal status was either mentined with warnings 18,19 r discuraged. 20,21 JBI als highlighted the fact that high quality research is further needed n specific interventins in that field. 20,21 Limitatins Mst f the studies and the tw CPGs included in this review nly fcused n the hspitalized elderly ppulatin. Therefre, the generalizability f the results t a ppulatin f all ages is uncertain. In mst f the cases, drug interactins with the nutritinal supplement were ruled ut by a pharmacist at the beginning f the study, s this issue was nt investigated in any study. Als, n study mentined the investigatin f the underlying cause f malnutritin befre the study. S it is pssible that patients included in studies may nt find ptential benefit frm an OLS prgram. Imprtant methdlgical limitatins have been nted in many studies. The main cncerns were relative t the lack f randmizatin, the absence f a cmparatr grup, a high chance f bias due t lack f blinding, and lack f ITT analysis 11-13,15-17 in studies where sme f the utcmes were subjective in nature ,15-17 External validity 11,13,15 and the meaning f a multiplicity f analyses 10,12 were als questined in sme studies. In ne study, 15 patients had t receive medicatin 3 t 4 times a day in rder t be included in Med-Pass, which excluded apprximately 50% f the patients receiving OLS. It is nt clear hw this kind f criterin culd be a barrier fr implementatin f Med-Pass. Encuragement fr cnsuming the supplement given specifically t patients in the Med-Pass grup were explicitly stated in sme studies. 12,13 Als, cmpliance fr supplement cnsumptin was mnitred, but nly in the Med-Pass grup. 10,12 Taken tgether, this is raising dubts abut whether the utcmes f the interventin are due t encuragement r are due t the supplementatin prgram. Tw CPGs were identified but neither fcused specifically n Med-Pass. The CPG develped by HIGN lacked a specific descriptin f methdlgy fr the chapter f interest (nutritin in hspitalized lder malnurished adults) and external reviewing was nt mentined. 18,19 Als, the link between the evidence and the recmmendatins culd nt be assessed. Fr bth CPGs, input frm all stakehlders were at least in part lacking and resurce implicatins were nt discussed. CONCLUSIONS AND IMPLICATIONS FOR DECISION OR POLICY MAKING One RCT, tw nn-randmized cmparative trials, fur befre-after studies and tw CPGs were included in this review f Med-Pass. All f the publicatins fcused n an elderly ppulatin (n The Medicatin Pass Nutritinal Supplement Prgram in Patients Receiving Medicatin 8

9 average). Five studies included nly malnurished (r at risk) patients. Fur studies were carried ut in a lng-term care setting, tw in acute care and ne in transitinal care. In the three studies where a cmparatr was used, n supplementatin, traditinal OLS r even a snack trlley between meals were cmpared t Med-Pass. Even thugh the cmparative studies had sme limitatins, they were deemed f higher quality cmpared t befre-after studies which had many serius limitatins. The mst cmmnly reprted utcmes were weight change, ttal energy intake (including fd cnsumptin), supplement cmpliance, skin integrity, serum prtein (albumin r pre-albumin), staff perceptin, supplement waste and cst. The cnclusins f the studies supprted weight maintenance r small weight gain after Med- Pass. The ttal energy intake r meal intake was fund t be increased in ne RCT, ne nnrandmized trial and ne befre-after study. In cntrast, anther befre-after study reprted a numerical decrease in ttal energy intake explained by a numerical decrease in supplement energy intake. This latter result culd ptentially be explained by a lw cmpliance with Med- Pass r a pr estimatin f fd cnsumptin. Even thugh this utcme is prne t subjective assessment, skin integrity was assessed in three studies where a nn-randmized trial shwed n difference and tw befre-after studies reprted an imprvement. One nn-randmized trial investigated the effect f Med-Pass n quality f life and revealed n difference when cmpared t traditinal supplementatin. One RCT assciated imprvements n mrtality and n length f stay with Med-Pass, but nly in specific sub-grups where a multiplicity f analyses were made. Nevertheless, the psitive impact f Med-Pass n the length f stay has been bserved in a nn-randmized trial as well. Overall, Med-Pass left a psitive impressin n the staff invlved in the studies. Accrding t the included studies, Med-Pass is likely t benefit the ppulatin studied, i.e. the hspitalized elderly ppulatin. Hwever, many issues were raised n the internal validity f mst f the studies and the external validity f sme studies. The lack f randmizatin, lack f a cmparatr, lack f blinding, and lack f ITT analysis rendered the studies prne t biases in favr f the interventin, especially when sme utcmes were subjective in nature. In sme studies, patients having Med-Pass were either directly encuraged by the staff t cnsume the supplement r mnitred fr cmpliance. Again, this may skew the results in favr f Med-Pass, althugh it may als be cnsidered as part f the interventin. Depending n the underlying cause f malnutritin, ral supplementatin might nt be the apprpriate interventin. Guidelines state that successful strategies have t be implemented by a multidisciplinary team as sn as pssible. A rigrus implementatin f nutritinal interventin was strngly recmmended. The CPGs further recmmend that when distributing OLS, ne must make sure that: the supplement is served at apprpriate temperature, there is n packaging barrier, supplements are prvided between meals, the intake f supplement is mnitred, patients are encuraged t cnsume the fds and beverages served, assistance is given when necessary, supplementatin is served as sip prtins as part f the medicatin prtcl. Of nte, the use f serum albumin as an evaluatin f nutritinal status was deemed inapprpriate. In cnclusin, evidence retrieved frm ne RCT, tw nn-randmized cmparative trials, fur befre-after studies and tw CPGs was in favr f clinical benefits f Med-Pass in elderly hspitalized patients. Hwever, limitatins identified in the studies prevent us t draw a firm cnclusin. As highlighted in a CPG based n a systematic review, high quality research is further needed fr specific interventins f ral liquid supplementatin. The Medicatin Pass Nutritinal Supplement Prgram in Patients Receiving Medicatin 9

10 PREPARED BY: Canadian Agency fr Drugs and Technlgies in Health Tel: The Medicatin Pass Nutritinal Supplement Prgram in Patients Receiving Medicatin 10

11 REFERENCES 1. Kaiser MJ, Bauer JM, Ramsch C, Uter W, Guigz Y, Cederhlm T, et al. Frequency f malnutritin in lder adults: a multinatinal perspective using the mini nutritinal assessment. J Am Geriatr Sc Sep;58(9): Turic A, Grdn KL, Craig LD, Ataya DG, Vss AC. Nutritin supplementatin enables elderly residents f lng-term-care facilities t meet r exceed RDAs withut displacing energy r nutrient intakes frm meals. J Am Diet Assc Dec;98(12): Bender S, Pusateri M, Ck A, Fergusn M, Hall JC. Malnutritin: rle f the TwCal HN Med Pass prgram. Medsurg Nurs Dec;9(6): Ritchie C. Geriatric nutritin: Nutritinal issues in lder adults Jul 10 [cited 2015 Mar 3]. In: UpTDate [Internet]. Versin Waltham (MA): UpTDate; Available frm: 5. Lari C. Weight lss amng the elderly in lng-term care: is the Med-Pass prgram a slutin? Canadian Jurnal f Dietetic Practice & Research. 2004;65(2):7. 6. Rand WM, Pellett PL, Yung VR. Meta-analysis f nitrgen balance studies fr estimating prtein requirements in healthy adults. Am J Clin Nutr Jan;77(1): Kerrigan ER, ER Kerrigan & Assciates, Maxwell J, Siegei C. Dispensing f a calrically dense ral supplement with medicatin pass: a creative apprach t ral supplementatin. J Am Diet Assc Jul 26;98(9 Suppl):A Dwns SH, Black N. The feasibility f creating a checklist fr the assessment f the methdlgical quality bth f randmised and nn-randmised studies f health care interventins. J Epidemil Cmmunity Health [Internet] Jun [cited 2015 Mar 12];52(6): Available frm: 9. Bruwers M, Kh ME, Brwman GP, Burgers JS, Cluzeau F, Feder G, et al. AGREE II: advancing guideline develpment, reprting and evaluatin in healthcare. CMAJ [Internet] Dec [cited 2015 Mar 24];182(18):E839-E842. Available frm: Ptter JM, Rberts MA, McCll JH, Reilly JJ. Prtein energy supplements in unwell elderly patients--a randmized cntrlled trial. JPEN J Parenter Enteral Nutr Nv;25(6): Campbell KL, Webb L, Vivanti A, Varghese P, Fergusn M. Cmparisn f three interventins in the treatment f malnutritin in hspitalised lder adults: a clinical trial. Nutritin & Dietetics Dec;70(4): Jukkla K, MacLennan P. Imprving the efficacy f nutritinal supplementatin in the hspitalised elderly. Australas J Ageing. 2005;24(2): The Medicatin Pass Nutritinal Supplement Prgram in Patients Receiving Medicatin 11

12 13. Dll-Shankaruk M, Yau WN, Oelke C. Implementatin and effects f a medicatin pass nutritinal supplement prgram in a lng-term care facility: a pilt study. J Gerntl Nurs May;34(5): Welch P, Prter J, Endres J. Efficacy f a medicatin pass supplement prgram in lngterm care cmpared t a traditinal system. Jurnal f Nutritin fr the Elderly. 2003;22(3): Remsburg RE, Sbel T, Chen A, Kch C, Radu C. Des a liquid supplement imprve energy and prtein cnsumptin in nursing hme residents? Geriatr Nurs Nv;22(6): Lewis D, Byle KD. Gaining strength: supplements revised. Nurs Manage Sep;29(9): Lewis DA, Byle KD. Nutritin management in hme health and lng-term care. Nutritinal supplement use during medicatin administratin: selected case studies. Jurnal f Nutritin fr the Elderly. 1998;17(4): DiMaria-Ghalili RA. Nutritin in aging. 4th. In: Bltz M, Capezuti E, Fulmer TT, Zwicker D, O'Meara A, editrs. Evidence-based geriatric nursing prtcls fr best practice. New Yrk: Springer; p Levin RF, Jacbs SK. Develping and evaluating clinical practice guidelines: a systematic apprach. 4th. In: Bltz M, Capezuti E, Fulmer TT, Zwicker D, O'Meara A, editrs. Evidence-based geriatric nursing prtcls fr best practice. New Yrk: Springer; p Vanderkrft D, Cllins CE, FitzGerald M, Lewis S, Capra S. Effectiveness f interventins fr undernurished lder inpatients in the hspital setting. JBI Best Practice Technical Reprts. 2007;3(2). 21. Vanderkrft D, Cllins CE, FitzGerald M, Lewis S, Neve M, Capra S. Minimising undernutritin in the lder inpatient. JBI Libr Syst Rev. 2007;5(3): The Medicatin Pass Nutritinal Supplement Prgram in Patients Receiving Medicatin 12

13 APPENDIX 1: Selectin f Included Studies 153 citatins identified frm electrnic literature search and screened 144 citatins excluded 9 ptentially relevant articles retrieved fr scrutiny (full text, if available) 7 ptentially relevant reprts retrieved frm ther surces (grey literature, hand search) 16 ptentially relevant reprts 5 reprts excluded: -cnference abstract (1) -narrative review/article (4) 11 reprts included in review The Medicatin Pass Nutritinal Supplement Prgram in Patients Receiving Medicatin 13

14 APPENDIX 2: Characteristics f Included Publicatins First Authr, Publicatin Year, Cuntry, Study Name Ptter, 2001, 10 Sctland Campbell, 2013, 11 Australia Jukkla, 2005, 12 Australia Table A1: Characteristics f Included Clinical Studies Study Design Patient Interventin(s) Cmparatr(s) Clinical Characteristics Outcmes Randmized cntrlled trial in elderly emergency unit f hspital Nnrandmized trial within geriatric and rehabilitatin wards (single facility). Nnrandmized trial in acute care hspital setting (acute geriatric medical ward) 381 elderly (ver 60 y) patients admitted at emergency. Median age: 83 years. Patients had a BMI < 75 th percentile. Patients culd be severely undernurished, mderately undernurished r adequately nurished. 98 inpatients (60 y and lder) assessed as mildly t severely malnurished (SGA B r C). Mean age ranging frm 75.8 t 80.6 years f age. Prprtin f females ranging frm 48.5% t 68.8%. Cnvenient sample f 200 elderly patients (65 y and lder). Mean age f 84 years, prprtin f females f 60.5%. Patients had t be either malnurished (MNA scre < 17) r at risk (MNA scre 17 t 23.5) t be Med-Pass (120 ml, 1.5 kcal/ml) three times daily until discharged hme, death r referral fr institutinal placement. N = 186 patients. Fr tw weeks: Med-Pass (60mL, 2 kcal/ml) fur times a day. N =32 patients. Med-Pass (60mL, 2 kcal/ml) fur times a day (N = 75 patients) until discharged frm hspital N supplement (n placeb available) fr the time they stayed at emergency. N = 195 patients. Fr tw weeks: Traditinal liquid supplements prvided inbetween meals, tw times a day. N = 33 patients. Snack trlley ffered between meals, tw times a day. N = 33 patients. Traditinal liquid supplements prvided inbetween meals, in a variety f flavrs (N = 77 patients) until discharged frm hspital. Weight Arm muscle circumferen ce Mrtality Functinal recvery (Barthel scre) Discharge placement Length f stay Cmpliance Ttal energy intake Weight change Supplement cmpliance Fd cnsumptin Energy and prtein intake Quality f life (EQ-5D) Patient satisfactin Cst Nutritinal status Cmpliance with supplement Changes in MNA scres assessed frtnightly r at discharge Nursing staff survey The Medicatin Pass Nutritinal Supplement Prgram in Patients Receiving Medicatin 14

15 First Authr, Publicatin Year, Cuntry, Study Name Dll- Shankaruk, 2008, 13 Canada Welch, 2003, 14 United States Remsburg, 2001, 15 United States Table A1: Characteristics f Included Clinical Studies Study Design Patient Interventin(s) Cmparatr(s) Clinical Characteristics Outcmes Befre-after study in a lng-term care facility Befre-after study in a lng-term care facility Befre-after study in an universityaffiliated lngterm care setting Lewis, Befre-after 1998, 16,17 study in a further included in nutritinal prtcl. 11 female residents (80 y and lder) wh had a significant undesirable weight lss, a cnsistent inadequate intake f meals r a cnditin that increases metablic needs. Mean age was 88 years. 30 residents aged between 26 and 104 y ld wh had fair t pr meal and supplement intake, demnstrated significant weight lss r demnstrated cmprmised weight status. Mean age f 84 years, 90% were females, 1/3 were feeding dependent. 20 residents were eligible, i.e., had ral nutritinal supplementatin, had at least ne medicatin t be dispensed 3 t 4 times per day and that culd be ingested with a fd prduct. 105 residents having at least Med-Pass (60mL, 2 kcal/ml) fur times a day fr 6 mnths Med-Pass (60mL, 2 kcal/ml) fur times a day fr 4 weeks Med-Pass (60mL, 2 kcal/ml) three r fur times a day fr 4 weeks. Fllw up n weight fr 1 mnth. Med-Pass (90 ml, 1.5 Nne Nne Nne Nne Weight change Skin integrity Serum albumin and ttal prtein Resident adherence Staff perceptin Prealbumin Weight Meal intake Supplement waste and cst Weight Meal intake Supplement cnsumptin, waste and cst Staff perceptin Weight Skin The Medicatin Pass Nutritinal Supplement Prgram in Patients Receiving Medicatin 15

16 First Authr, Publicatin Year, Cuntry, Study Name United States Table A1: Characteristics f Included Clinical Studies Study Design Patient Interventin(s) Cmparatr(s) Clinical Characteristics Outcmes transitinal care unit f a cmmunity hspital tw f: lw bdy weight, lw ral intake, skin breakdwn, primary r secndary diagnsis f malnutritin, lw serum albumin level, recent significant weight lss. kcal/ml) three times per day (n average) f a specific supplement fr each patient, until discharged. integrity BMI = bdy mass index; EQ-5D = Eur Quality f Life-5 Dimensins; kcal = kilcalries; Med-Pass = Medicatin pass nutritinal supplement prgram; ml = milliliters; MNA = Mini Nutritinal Assessment tl; RCT = randmized cntrlled trial; SGA = Subjective Glbal Assessment; y = years. Intended users/ Target ppulatin Table A2: Characteristics f Included Guidelines Objectives Methdlgy Interventin Majr Evidence Evidence Recmmendati and Outcmes cllectin, Quality ns Practice Cnsidered Selectin and develpment and Cnsidered and Strength Evaluatin Synthesis DiMaria-Ghalili, ,19 Hartfrd Institute fr Geriatric Nursing Nurses, dietitians, health care prviders and physicians wrking with hspitalized lder malnurishe d adults Assessment f nutritinal status and management f malnutritin Nutritinal status, functinal status and general wellbeing Search f electrnic database and hand search with PICO criteria, classificati n f citatins Vanderkrft, ,21 The Janna Briggs Institute Base level health prfessinnal s in acute care hspital setting, fcus n elderly ppulatin Interventins aiming at minimizing undernutriti n. Dietary intake, anthrpmet ry measures, bichemical indicatrs, clinical utcmes, functinal Systematic review, metaanalyses Rating scheme frm level I (best) t level VI (wrse) Used the JBI experiment al Critical Appraisal Frm 4.1 indicatrs JBI = Janna Briggs Institute; PICO = Ppulatin, Interventin, Cmparatr, Outcmes Expert cnsensus Made by the develpers with an expert advisry panel, based n evidence when pssible. Recmmendati ns were graded. Guidelin e Validati n Internal and external peer review Internal and external peer review The Medicatin Pass Nutritinal Supplement Prgram in Patients Receiving Medicatin 16

17 APPENDIX 3: Critical Appraisal f Included Publicatins Table A3: Strengths and Limitatins f Clinical Studies using the Dwns and Black checklist 8 Strengths Limitatins Ptter, 2001, 10 Sctland Clear descriptins f bjective, inclusin criteria, utcmes, interventins, findings (with 95% CIs) were prvided. Baseline characteristics f patients were nt cmprehensively reprted. Unbalance fr age has been mentined. Investigatrs wh were invlved in data cllectin and assessments were blinded. Ptential adverse events were nt investigated. Subjects were randmized. Subjects (n placeb) and ward staff were Mst f utcme measures were bjective. nt blinded t interventin. Patients were representative f ppulatin. Multiplicity f analyses in sub-grups. N patients withdraw frm study. Pwer calculatin and descriptin f statistical methds were prvided. P values were prvided. ITT analysis. Adjusted analyses were dne, fr sensitivity purpses. Campbell, 2013, 11 Australia Clear descriptins f bjective, inclusin criteria, patient characteristics, utcmes, and interventins. Sme ptential adverse effects were captured. Pwer calculatin were prvided. Jukkla, 2005, 12 Australia Clear descriptins f bjective, inclusin criteria, patient characteristics, utcmes, interventins and findings. Patients were representative f ppulatin. Sme adverse effects were recrded. Patients were nt aware f the interventin. Findings and their assciated statistical tests (P values) were nt clearly reprted. N statistical plan. Unbalance fr weight, BMI, energy and prtein requirements at baseline, but the statistical methd was adjusted fr this. Patients with cgnitive prblems r renal impairment were excluded which may cause external validity issue. Nt ITT analysis, many patients were discharged befre endpint. 2 patients discntinued. Grups were nt studied in parallel. Limited perid f fllw-up (2 weeks). Nn-randmized, pen-label study. Sme utcmes were subjective. Grups were in a different ward. Reassessment with the MNA questinnaire (endpint) has been dne in nly 22% f included patients. Multiplicity f analyses. Investigatrs were nt blind and patients in the Med-Pass grup were clearly encuraged t cmply t supplement. Many utcmes in the MNA and the survey were subjective. The Medicatin Pass Nutritinal Supplement Prgram in Patients Receiving Medicatin 17

18 Table A3: Strengths and Limitatins f Clinical Studies using the Dwns and Black checklist 8 Strengths Limitatins Nt ITT analysis. Nn-randmized study. N pwer calculatin. Dll-Shankaruk, 2008, 13 Canada Clear descriptins f bjective, inclusin criteria, patient characteristics, utcmes, Subjects and investigatrs were nt blinded. interventin and findings. Very small sample. Tw peple (18%) died Cmpliance was high. during the study. Nt ITT analysis. Nt clear whether patients were representative f ppulatin. Only descriptive results are presented, n inferential statistics were calculated. Relevance f albumin levels is questined in the literature. Sme utcmes (staff perceptin and skin integrity) might be subjective. Ttal energy intake was nt recrded. N ptential adverse events were mnitred. N pwer calculatin. Welch, 2003, 14 United States Clear descriptins f bjective, inclusin criteria, patient characteristics, utcmes, Subjects and investigatrs were nt blinded. interventin and findings (including P values). Nt clear whether 100% f the patients asked prvided cnsent. Objective utcmes. Relevance f albumin levels is questined Representative ppulatin. in the literature. N discntinuatins. Relatively small sample. Wastage assessed during the first tw weeks f the Med-Pass. May have increased with time. N ptential adverse events were mnitred. N pwer calculatin. Remsburg, 2001, 15 United States Clear descriptins f bjective, inclusin criteria, utcmes, and interventin. Subjects and investigatrs were nt blinded. Staff perceptin is subjective. Patient characteristics were nt disclsed. Less than 50% f patients receiving ral liquid supplementatin were included. Cmpliance t Med-Pass was nt reprted. Findings were nt well reprted. N estimates f variability r statistical inferences were prvided. The Medicatin Pass Nutritinal Supplement Prgram in Patients Receiving Medicatin 18

19 Table A3: Strengths and Limitatins f Clinical Studies using the Dwns and Black checklist 8 Strengths Limitatins N ptential adverse events were mnitred. N pwer calculatin. Small sample. Nt ITT analysis. The time f the study when the mealtime fd cnsumptin (ver 3 days) was recrded was nt mentined. N ptential adverse events were mnitred. Lewis, 1998, 16,17 United States Clear descriptins f bjective, inclusin criteria, and interventin. Subjects and investigatrs were nt blinded. Inclusin criteria suggest that patients were representative f the ppulatin. Skin integrity might be subjective in absence f blinding. Patient characteristics were nt disclsed. The % f participatin is nt prvided. Cmpliance was nt reprted. Outcmes and findings were nt well described. N estimates f variability r statistical inferences were prvided. N ptential adverse events were mnitred. N pwer calculatin. Nt ITT analysis. The ttal energy intake was nt recrded. N ptential adverse events were mnitred. BMI = Bdy Mass Index; ITT = Intentin t treat; Med-Pass = Medicatin pass nutritinal supplement prgram; MNA = Mini Nutritinal Assessment. The Medicatin Pass Nutritinal Supplement Prgram in Patients Receiving Medicatin 19

20 Table A4: Strengths and Limitatins f Guidelines using AGREE II 9 Strengths Limitatins DiMaria-Ghalili, ,19 Hartfrd Institute fr Geriatric Nursing Evidence-based, but nt clear if review was systematic. Nt clear if all relevant stakehlders were invlved. Clear descriptin f bjectives, health questins, ppulatin, end user, recmmendatins and their different General methdlgy fr develpment fllwing AGREE II was stated, but nthing specific t the tpic f interest. ptins. Nt clear if it was reviewed externally. Resurce implicatins r tls fr implementatin have nt been addressed. Nr was prcedure fr guideline update. N disclsure f cnflict f interest. Vanderkrft, ,21 The Janna Briggs Institute Based n a systematic review Clear descriptin f bjectives, health questins, ppulatin, end user, recmmendatins. Selectin criteria, critical appraisal, and methds fr frmulating recmmendatins were reprted. An expert cmmittee was invlved in the develpment. Externally reviewed. Cnflicts f interest have been addressed. AGREE = Appraisal f Guidelines fr Research and Evaluatin N input frm target ppulatin. Ptential side-effects have nt been cnsidered. Barriers t implementatin and resurce implicatins have nt been addressed. The Medicatin Pass Nutritinal Supplement Prgram in Patients Receiving Medicatin 20

21 APPENDIX 4: Main Study Findings and Authr s Cnclusins Table A5: Summary f Findings f Included Studies Main Study Findings Authr s Cnclusins Ptter, 2001, 10 Sctland Median lengths f stay were f 16.0 days fr the Med-Pass grup and 18.0 days fr the cntrl grup. Results with pled nutritinal categries (Med-Pass vs cntrl grup): Med-Pass increased ttal energy intake (319 kcal/d, 95% CI 133 t 506 kcal/d, P = 0.001). Weight gain (+1.0%, 95% CI 0.5 t 3.4%, P = 0.003). Similar results were fund fr weight change when adjusted fr ptential cnfunding cnditins. N statistically significant effect n arm muscle circumference (+1.2 %, 95% CI -0.2 t 2.7 %). N effect was bserved n mrtality (OR 0.62, 95% CI 0.35 t 1.13). N effect n functinality, n place f discharge r n length f stay was fund. Cmpliance was gd verall. In the mst prly nurished patients: Med-Pass reduced mrtality (OR 0.32, 95% CI 0.1 t 1.0, P < 0.05). Med-Pass increased the number f patients with imprved Barthel scre (functinality) (68% vs 39%, P < 0.04). In the adequately nurished patients: Med-Pass decreased the length f stay at hspital (13.5 vs 21.0 d, P < 0.05) Campbell, 2013, 11 Australia Seventy-fur f the 98 patients cmpleted tw weeks. Amng grups, weight change was nt different after tw weeks (less than 1.5% change) QOL with EQ-5D: VAS imprved significantly frm baseline with Med-Pass and mid-meal trlley interventin (P = 0.05), but did nt change with traditinal interventin. Cmpared t traditinal supplements, the Med-Pass shwed better QOL (P < 0.05). This study shws that rutine prescriptin f prtein calrie nutritinal supplements can prevent weight lss and imprve energy intake in elderly nn-bese emergency admissins. Our data als supprt the evidence fr a reductin in mrtality nted in many ther studies f nutritinal supplementatin, which was seen in the frailest grup. These are imprtant. [ ] this interventin is feasible in the average ward setting t accrue clinical benefit fr this patient grup. (p. 329) In a ppulatin f malnurished lder adults admitted t hspital, the tw alternative strategies fr prviding nutritin supprt resulted in patientcentred benefits ver traditinal nutritin supplements. Patients achieved recmmended intakes with Med-Pass, t a similar degree t traditinal supplements; hwever, higher satisfactin and QOL was achieved with mid-meal trlley at a lwer cst. Althugh the present investigatin did nt appear t present ne ptin as best ver any The Medicatin Pass Nutritinal Supplement Prgram in Patients Receiving Medicatin 21

22 Table A5: Summary f Findings f Included Studies Main Study Findings Authr s Cnclusins Index scre imprved significantly frm baseline with Med-Pass and mid-meal trlley (P = 0.04). Mid-meal trlley interventin ffered better imprvement in index scre cmpared t traditinal supplements (P < 0.05). Cnsumptin f supplement in the midmeal trlley grup was significantly higher than in the traditinal supplements grup (P < 0.05). Percentage f required energy and prtein intake: Traditinal supplements: 107 ± 26% fr energy and 128 ± 35% fr prtein. Higher than mid-meal trlley (P = 0.003). Med-Pass: 109 ± 28% fr energy and 126 ± 38% fr prtein. Higher than midmeal trlley (P < 0.001). Mid-meal trlley: 85 ± 25% fr energy and 88 ± 26% fr prtein. Serum albumin and presence (r degree) f pressure ulcers did nt change significantly between grups. Satisfactin and perceived benefit: The mid-meal trlley shwed significant increase f satisfactin fr 8 f the 13 dmains. Mid meal trlley was the mst csteffective with lwer ttal labur and prduct cst per 100 kcal cnsumed ($AU0.81), fllwed by Med-Pass ($AU0.89). Jukkla, 2005, 12 Australia Thirty percent f patients were malnurished, a further 42% were at risk. Cmpliance with Med-Pass was 95%. 35% f cnventinal supplements were left untuched. MNA questinnaire: N significant change ( fr Med- Pass vs fr cntrl) in verall scre between grups. Patients in Med-Pass had better imprvement in scres fr the number f meals cnsumed (P = 0.01), prtein intake (P = 0.007), and weight scre (P ther, it des highlight the ptential benefit f having a flexible system with multiple nutritin supprt strategies available. This will thereby facilitate the ability t implement interventins that best meet individual s needs and preferences and will best vercme individual barriers t adequate intake (p. 330) There is a high prevalence f malnutritin in the hspitalised elderly. (p. 123) Rutine nutritin screening is essential t identify and priritise treatment fr thse at greater risk. (p. 123) Oral supplementatin has been fund t be effective in preventing further decline in nutritinal status. (p. 123) A frmal nutritin as medicatin prgram is a highly effective way t prvide ral supplementatin. (p. 123) The Medicatin Pass Nutritinal Supplement Prgram in Patients Receiving Medicatin 22