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original article evaluation of biochemical markers effectiveness in elderly malnutrition assessment 1 2 3 4 5 larisa gavran jelena pavlovi maja rai nedeljka ivkovi ksenija tusek bunc 1department of family ...

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                        ORIGINAL ARTICLE
                        Evaluation of biochemical markers effectiveness in elderly 
                        malnutrition assessment
                                        1                  2              3                   4                       5
                        Larisa Gavran , Jelena Pavlović , Maja Račić , Nedeljka Ivković , Ksenija Tušek Bunc
                        1Department of Family Medicine, School of Medicine, University of Zenica, 2Department of Nursing, School of Medicine, University of 
                                     3                                                                                       4
                        East Sarajevo,  Department of Primary Health Care and Public Health, School of Medicine, University of East Sarajevo,  Department of 
                        Oral Rehabilitation, School of Medicine, University of East Sarajevo; Bosnia and Herzegovina, 5Department for Public Health School of 
                        Medicine, University of Maribor, Slovenia
                                                                  ABSTRACT
                                                                  Aim To systematically review the scientific evidence of biomarker 
                                                                  validity, reliability, specificity and sensitivity in identifying mal-
                                                                  nutrition in the elderly. 
                                                                  Methods Peer-reviewed journals were searched using PUBMED 
                                                                  and EBSCO from January 1998 to April 2018. The articles inclu-
                                                                  ded description of the association between malnutrition blood bi-
                                                                  omarkers and validated nutritional status assessment instruments 
                                                                  and studies were conducted among community-dwelling elderly 
                                                                  or nursing home residents. 
                        Corresponding author:                     Results The research strategy identified a total of 293 studies. This 
                        Jelena Pavlović                           literature review picked out seven articles for follow-up evaluati-
                        Department of Nursing,                    on. A total of sixteen blood biomarkers were identified. Six studies 
                        School of Medicine of Foča,               found a significant association between the nutritional assessment 
                                                                  score and albumin level. 
                        University of East Sarajevo
                        Studentska 5, 73 300 Foča,                Conclusion Combining serum concentrations of malnutrition bio-
                        Bosnia and Herzegovina                    markers with nutritional status assessment tools has a great poten-
                        Phone:  +387 58 210 420;                  tial in identifying the risk of malnutrition in the elderly, while also 
                                                                  increasing sensitivity and specificity. 
                        Fax: +387 58 210 007;
                        E-mail:  pjelena551@gmail.com             Keywords:  aged, biomarkers, geriatric assessment, humans, mal-
                        ORCID ID:  https://ordic.org/0000-0002-   nutrition
                        8591-4316
                        Original submission:
                        09 May 2019;
                        Revised submission:
                        13 May 2019;
                        Accepted:
                        16 May 2019.
                        doi: 10.17392/1039-19
                        Med Glas (Zenica) 2019; 16(2): 351-358
                                                                                                                                             351
                                  Medicinski Glasnik, Volume 16, Number 2, August 2019
                                  INTRODUCTION                                                           MATERIALS AND METHODS 
                                  Good nutrition is a fundamental component of he-                       Study design
                                  alth, independence and quality of life of elderly per-
                                  sons (1).  Malnutrition may cause health problems                      The  systematic  literature  overview  was  made 
                                  such as the increased risk of morbidity (chronic di-                   according to the Preferred Reporting Items for 
                                  seases, pathological fractures, impaired wound he-                     Systematic  Reviews  and  Meta-Analyses  (PRI-
                                  aling, slow post-operative recovery, development                       SMA) statement (8). 
                                  of decubitus ulcers, weakened functionality, lack                      We considered observational, longitudinal, retros-
                                  of  appetite),  and  increased  hospitalization  rate,                 pective, and cross-sectional studies that reported 
                                  number of hospital treatment days and mortality                        an association between blood biomarkers levels 
                                  rate (2). Studies have shown that the prevalence of                    and  validated  nutrition  assessment  instruments, 
                                  malnutrition after the age of 65 has been on the rise                  such  as  anthropometric  measurements  (body 
                                                                                          
                                  reaching a range of between 15-85% (2-4). Accor-                       mass index – BMI, or skinfold thickness). Additi-
                                  ding to Bedogni et al. (5), nutritional status is a re-                onally, it followed screening questionnaires: Mini 
                                  sult of the interaction of three variables: food inge-                 Nutrition  Assessment-Short  Form  (MNA-SF), 
                                  stion, absorption, and the use of nutrients. It clearly                Malnutrition Universal Screening Tool (MUST), 
                                  follows from the described definition that an ideal                    Nutritional  Risk  Screening  2002  (NRS-2002), 
                                  nutritional status assessment and malnutrition scre-                   Geriatric  Nutritional  Risk  Index  (GNRI),  Nu-
                                  ening instrument should include the assessment of                      tritional  Risk  Index  (NRI),  Instant  Nutritional 
                                  dietary, anthropometric, functional indicators, and                    Assessment (INA), Nutrition Screening Initiati-
                                  laboratory biomarkers in the blood (Figure 1) (5,6).                   ve (NSI), Short Nutritional Assessment Questi-
                                  A recent systematic review has shown that multiple                     onnaire (SNAQ), Subjective Global Assessment 
                                  biochemical parameters (albumin, prealbumin, he-                       (SGA), and the Nutritional Risk Screening Tool 
                                  moglobin, total cholesterol, and total protein) may                    (NRST). Inclusion criteria were studies conduc-
                                  be used in diagnosing malnutrition in the elderly                      ted  among  community-dwelling  elderly  and/or 
                                  (7).   However, it remains unknown which are the                       nursing home residents. Country and English-lan-
                                  reference cut-off values of these biomarker blood                      guage restrictions were not applied. Outcomes of 
                                  parameters, and which biomarker is usable, precise                     interest were the sensitivity and specificity of blo-
                                  and reproducible, acceptable to the patient, easy for                  od biomarkers, as well as their ability to identify 
                                  clinical interpretation, and cost-effective, while ha-                 malnutrition risk among the elderly (Table 1). 
                                  ving the high sensitivity and specificity necessary 
                                  for the expected outcome. Such a biomarker would 
                                  have a promising potential for the malnutrition di-                    Table 1. Study inclusion and exclusion criteria
                                  agnosing system.                                                       Variable           Inclusion criteria       Exclusion criteria
                                                                                                                        People over the age of 60,  People under the age of 
                                                                                                                        well-oriented in time and  60, persons with dementia, 
                                                                                                         Population     space, without malign di- persons with malign disea-
                                                                                                                        seases, dementia, chronic  ses and with chronic renal 
                                                                                                                           renal insufficiency         insufficiency
                                                                                                                        People living in commu-   People in hospital envi-
                                                                                                         Environment      nity or in gerontology         ronment
                                                                                                                               institution 
                                                                                                                          Observational, longi-
                                                                                                         Study type       tudinal, retrospective,  Non-empirical studies
                                                                                                                               transversal
                                                                                                                          Identification of bio-    Non-identification of 
                                                                                                         Outcome          chemical malnutrition   biochemical malnutrition 
                                                                                                                                markers                   markers
                                  Figure 1. Definition of nutritional status indicators                  Development           Described               Not described
                                                                                                         and validation
                                  The aim of this systematic review was to study,                                         Abstract availability,    Abstract and full text 
                                  investigate, analyse, and synthetize the scientific                    Other             year of publication     unavailability, year of 
                                  evidence of biomarker validity, reliability, speci-                                          from1998,          publication before 1998
                                                                                                                            full text available 
                                  ficity and sensitivity in identifying malnutrition 
                                  in elderly patients. 
                          352
                                                                                 Gavran et al. Elderly malnutrition assessment
                       Methods                                                form in order to facilitate comparison. Each study 
                       Malnutrition was defined as deficiency or imba-        included the name of author(s), publication year, 
                       lances in an intake of energy and macro/micro nu-      sample size, study design, methodology, identified 
                       trients (5). The studies were downloaded via the       biochemical markers, and results (Table 2).
                       electronic databases PUBMED and EBSCO, and             RESULTS
                       by manual search of relevant studies from a list       The research strategy identified a total of 293 stu-
                       of reference key articles. The electronic databa-      dies. Following data deduplication and selection 
                       ses were searched from the period January 1998         of papers based on titles and abstracts, a total of 
                       to April 30 2018 by defining key words adapted         277 papers were excluded because they were not 
                       for each database (malnutrition, nutrition, blood      focused on malnutrition, the population was un-
                       markers, serum, elderly), and words from MESH          der the age of 60, the authors did not use labora-
                       (Medical Subject Headings) and Boolean ope-            tory analysis to identify malnutrition, or the stu-
                       rators,  AND/OR  words  establishing  a  logical       dies did not undergo a validation process. Nine of 
                       connection  with  the  paper  search  concepts  at     the remaining studies were included for a full text 
                       Medline. There was an advanced search moda-            review, of which 7 were selected for extrapolati-
                       lity. The manual search of original papers, loo-       on and final analysis (Figure 2).
                       king for additional acceptable studies, was con-
                       ducted through the Electronic Journals Library. 
                       Papers were searched through various journals 
                       (Nutrition, The American Journal of Clinical Nu-
                       trition, Nutrients, Nutrition Reviews, Journal of 
                       Nutrition, and European Journal of Clinical Nu-
                       trition). Titles and abstracts were reviewed and, if 
                       an abstract met the inclusion criteria, the full text 
                       was downloaded. In accordance with the search 
                       criteria, the full texts of papers selected were in-
                       dependently assessed by two investigators and, in 
                       case of any doubt before the final decision, the in-
                       vestigators sought a third investigator’s opinion.
                       During this step, the application of the final criteria 
                       for inclusion of papers into the analysis resulted     Figure 2. Flow diagram of the research and selection process
                       in the selection of biomarker research studies with    Sixteen biomarkers were identified in the litera-
                       validated instruments in identifying malnutrition      ture review. Most commonly analysed were albu-
                       in persons over 60 years of age. The data from         min and total cholesterol. Other biomarkers found 
                       each paper using a data extrapolation form based       were lymphocyte count, leucocytes, haemoglobin, 
                       on the Best Evidence Medical Education (BEME)          prealbumin, triglycerides, zinc, copper, transthyre-
                       coding sheet (9) were pulled out. After investiga-     tin, leptin, orosomucoid, insulin-like growth fac-
                       tors checked the extrapolated data, they focused       tor-1 (IGF-1), IGF binding protein-1 (IGFBP-1), 
                       on biochemical markers, study methodology, and         and C-reactive protein (CRP).
                       results. No exact meta-analysis could be done due 
                       to  discrepancy  between  the  methods  used,  the     The biomarkers values were evaluated against 
                                                                              GNRI                                        
                       different statistical analyses of the studies included        (10) ,  NRST  (11),  MNA  (12,13) ,  SGA 
                       in the final analysis, the difference in measurement   (13,14),  MNA-SF/NRS2010  (15),  and  antro-
                       outcomes, different biomarker validity values in       pometric  measurements  (BMI  and  skinfold 
                       relation to the instruments used, as well as the lack  thickness) (16). 
                       of reliable borderline values of biomarkers for el-    Biochemical  concentrations  were  measured 
                       derly persons. The synthesis showed the ability of     using well-accepted methods, with variations de-
                       blood biomarkers in identifying an elderly indivi-     pending on the setting. Three studies detected a 
                       dual with malnutrition or at high risk of malnutriti-  significant, positive correlation between nutritio-
                       on. The extrapolated data are presented in a tabular   nal assessment and albumin level (10-12) and, in 
                                                                                                                                  353
                   Medicinski Glasnik, Volume 16, Number 2, August 2019
                          e)
                                                                      ymphocytes r=0.01; p=0.935
                                                    10; p=0.212;  and biomarkerse and biomarketsoteins levelsoteins levels
                        esult                                        scor
                        The r              17.12 ±22.45; p=0.154;      f point <17) for hypoalbuminemia (<3.5 g /dL)- 0.810f point <17) for hypoalbuminemia (<3.5 g /dL)-0.860f point <17)  for hypocholesterolemia (<150 mg/dL) 0.786f point <17) for hypocholesterolemia (<150 mg/dL) 0.822
                                         Zinc: 93.76 ± 17.59; p=0.882; otal protein: r=0.161; p=0.557; ymphocytes: r=0.093; p=0.157; Albumin: r=0.463; p<0.001; riglycerides: r=0.004; p=0.965; Zinc: r=0.004; p=0.965;Albumin r=0.60; p<0.001; L cutof cutof cutof cutof class and serum pr class and serum pr
                             ymphocytes: 1.55±0.67;  p=0.637; Copper : 1TLHaemoglobin: r=0.052; p=0557; Prealbumin: r= -0.1otal cholesterol: r=0.128; p=0.171; T
                            WBCs (103/cm): 8.56 ±6.21; p=0.448; Lotal protein (g/dL)- 6.39 ± 0.78; p=0.243; Albumin (g/dL): 2.66 ±0.46; p<0.001; Prealbumin (mg/dL):-6 (3-10) ; p=0.902; Telations between NRSTotal cholesterol (mg/dL): r=0.057; p=0.012;Serum albumin (g/dL): r=0.094; p<0.001elation between MNASGAMNA
                               Haemoglobin (g/dL): 10.95 ± 3.01; p=0.026; Triglycerides (mg/dL): 79 (57-107) ; p=0.882; elations between GNRI and biomarkers valuesT
                                      otal cholesterol (mg/dL): 142.1±.74.2, p=0.213; TCorr
                                      T     Corr                    Corr
                          verage values of biomarkers in malnutrition (GNRI scor
                          A
                                                                      otal cholesterol r=0.36; p<0.001; ransthyretin (g/L): 0.24±0.06 (well-nourished),  0.23±0.06 (risk), 0.19±0.06 (malnourished)Albumin (g/ L): 35.8±4.5(well-nourished), 34.5±5.0(risk), 30.2±5.6 (malnourished)  
                                                                      TSensitivity of malnutrition (MNASpecificity of malnutrition (MNASensitivity of malnutrition (MNASpecificity of malnutrition (MNAransthyretin (g/l): 0.24±0.06 (well-nourished), 0.22±0.06 (moderate), 0.19±0.06 (severe malnutrition)Albumin (g/ L): 35.0±5.0 (well-nourished), 4.0±5.0 (moderate),  31.0±6.0 (severe malnutrition)T
                                                                                 T
                        Markerotal proteinymphocytesAlbuminotal proteinPrealbuminriglyceridesZincCopperCholesterolAlbuminAlbuminCholesterolymphocytesAlbuminransthyretin
                          T LHaemoglobinTotal cholesterolT              L        T
                                    T
                          -                                 -       -          -
                        InstrumentmentsGNRI                  mentsNRSTGNRIMNA-SFmentsMNAMNA-SFmentsSGAMNA
                          Anthropometric measure            Anthropometric measureAnthropometric measureAnthropometric measure
                        Design studystudy                    study
                          Prospective cohort                Prospective cohort Cross section studyCross section study
                                                            1, 2015 
                       , year
                    able 2. Identified biochemical markers for the evaluation of nutritional status in the elderly
                    T  Author(sample size, n)Abd-El-Gawad, et al.10, 2004  (n = 131)Htun NC, et al.1(n = 1921)Kuzuya M, et al.12, 2005 (n = 226)Christensson L, et al.13, 2002 (n = 261)
               354
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...Original article evaluation of biochemical markers effectiveness in elderly malnutrition assessment larisa gavran jelena pavlovi maja rai nedeljka ivkovi ksenija tusek bunc department family medicine school university zenica nursing east sarajevo primary health care and public oral rehabilitation bosnia herzegovina for maribor slovenia abstract aim to systematically review the scientific evidence biomarker validity reliability specificity sensitivity identifying mal nutrition methods peer reviewed journals were searched using pubmed ebsco from january april articles inclu ded description association between blood bi omarkers validated nutritional status instruments studies conducted among community dwelling or home residents corresponding author results research strategy identified a total this literature picked out seven follow up evaluati on sixteen biomarkers six foa found significant score albumin level studentska conclusion combining serum concentrations bio with tools has great p...

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