Summary of doctor of medicine thesis validation of sarcopenia screening tools among older paptients

1 INTRODUCTION Sarcopenia is defined as a progressive and generalized loss of muscle mass and physical function Sarcopenia is now recognized as an independent disease and has its own International Sarcopenia is independently associated with health adverse outcomes, such as falls and fractures, dependences, hospitalization, and mortality Three extensive and valuable screening tools, including SARC-F questionnaire, SARC-F adding calf circumference (SARCCalF) and Ishii’s formula, were recommended by international sarcopenia working groups that could be used to initially screen for sarcopenia However, in the literature, no study on comparison of their reliability and validity has yet been performed in the same study population And there has been no study on the application of these screening tools in older patients in Vietnam Therefore, we conducted the study “Validation of sarcopenia screening tools among older paptients” with three aims: Assess the prevalence of sarcopenia and associated factors in patients attending geriatric clinics in Vietnam Evaluate the diagnostic accuracy of the SARC-F, SARC-CalF and Ishii’s formula in the screening for sarcopenia among older patients Investigate the relation between value of three screening tools with health adverse outcomes among older patients after 18 months follow-up Necessity of the thesis Most of diagnostic tools are not widely available, especially in lowmiddle income countries such as Vietnam It has been proposed that a valuable, simple and inexpensive tool could be used to initially screen for sarcopenia Some screening methods were developed by research teams with the aim to rapidly identify individuals who require a diagnostic examination for sarcopenia Indeed, the early identification of older adults likely to suffer from sarcopenia would allow them to implement, at an early stage, preventive strategies including protein supplementation and physical activity in combination Three extensive and valuable screening tools, including SARC-F questionnaire, SARC-F adding calf circumference (SARC- CalF) and Ishii’s formula, were recommended by AWGS 2019 and EWGSOP2 that could be used to initially screen for sarcopenia They have been shown to be valid in a number of studies New contributions of the thesis Prevalence of sarcopenia among older patients 61.2%, higher in male and advance age Related factors for sarcopenia: age, male, underweight, low physical activity, being malnourished and chronic lung disease Screening tools including SARC-F, SARC-CalF and Ishii’formular has acceptable sarcopenia diagnostic value for older patients, in comparision with gold standard AWGS 2019 criteria Of three screening tools, Ishii’s formula showed the best sensitivity, negative predictive value, accuracy and the largest area under the receiver operating curve to identify sarcopenia in older outpatients High value of Ishii’s formular at baseline was related with increasing short-term health-related outcomes among older patients (all causes mortality, incidence of fall or dependence of activities daily living) Thesis outline The thesis consits of 126 pages, including: introduction (2 pages), overview (34 pages), object and methods (28 pages), results (30 pages), discussion (29 pages), conclusion (2 pages) and recommendation (1 page) 158 English and Vietnames references Chapter LITERATURE RIVIEW 1.1 Definition of sarcopenia Sarcopenia is a syndrome characterised by progressive and generalized loss of skeletal muscle mass and strength with a risk of adverse outcomes such as physical disability, poor quality of life and death 1.2 Prevalence of sarcopenia Prevalence of sarcopenia in the world was evaluated in a systematic review and meta- analysis of general population studies The studies that reported the prevalence of sarcopenia in people aged ≥ 60 years in community setting based on the EWGSOP, the International Working Group on Sarcopenia (IWGS) and AWGS criteria, were selected With a total of 58404 individuals, the overall estimates of sarcopenia prevalence was 10% (95%CI: 8-12%) in male and 10% - (95%CI: 8-13%) in female, respectively The prevalence was higher among non- Asian than Asian individuals in both genders (11% vs 10% in male, 13% vs 9% in female) The global prevalence of sarcopenia was around 6-22 % in people aged 65 years or older, increased with age and varied across regions In Western countries, the prevalence of sarcopenia was around 20% among people aged ≥65 years, and 50%-60% in people aged ≥80 In Asian countries, the review of epidemiology studies that used AWGS 2014 criteria discovered that the prevalence of sarcopenia ranged from 5.5% to 25.7%, with male predominance (5.1%-21.0% in male vs 4.1%-16.3% in female) 1.3 The recommendation of screening for sarcopenia The guidelines of screening for sarcopenia were developed upon the best available evidence from systematic reviews paired with consensus statements by international working groups on sarcopenia (1) Older adults aged 65 years and older should be screened for sarcopenia annually, or after the occurrence of major health events There is currently no direct evidence in support of a specific frequency for sarcopenia screening, and it is likely that new research evidence would impact on the certainty of this recommendation Regular screening for sarcopenia should be applied for older people with several reasons: All older adults are at risk of developing sarcopenia, particularly those with low physical activity levels Sarcopenia is common across all older populations and may be transient in its early stages Sarcopenia places a heavy burden on the individual, their care-giver, and the healthcare system Screening for sarcopenia is effective (2) Screening tools for sarcopenia Screening tests for sarcopenia need to be rapid and easy to use According to AWGS 2019 Consensus Update on Sarcopenia Diagnosis and Treatment, calf circumference, SARC-F or SARCCalf questionnaire were the choosing tools for sarcopenia case finding in: - - + Primary health care or community preventive services settings + and Acute to chronic health care or clinical research settings In revised European consensus on definition and diagnosis of sarcopenia + SARC-F questionnaire was proposed as choosing tools for sarcopenia case finding in clinical practice and in research; + Ishii screening tool was recommended to use in clinical practice Gait speed is well recognised as a screening tool for sarcopenia according to EWGSOP recommendation in 2010 (3) Individuals screened as positive for sarcopenia should be referred for further assessment to confirm the presence of the disease All international consensus statements agree with the importance of an assessment referral after a positive screening There are two main reasons for this recommendation: - Unmanaged sarcopenia can quickly increase risk for mortality and functional decline - Detection of sarcopenia in its early stages may significantly contribute to less morbidity and mortality related to the condition Chapter MATERIALS AND METHOD 2.1 Study population Consecutive patients aged 60 years or above visiting the Outpatient Department of the National Geriatric Hospital in Hanoi, Vietnam were recruited 2.1.1 Inclusion criteria Study participants had all the criteria: Aged 60 years or above; Have ability to perform all physical examinations 2.1.2 Exclusion criteria Study participants having one of following criteria were excluded: - Blind or deaf; - Pace-maker implanted or had metal medical devices; - Severe illness (receiving intensive care) - Unable to provide consent or refused to participate in the study 5 2.2 Study design Observational study was conducted: + Objectives and 2: Cross-sectional study + Objective 3: Longitudinal study 2.3 Sample size Consecutive patients aged 60 years or above visiting 05 outpatient clinics, National Geriatric Hospital were recruited 2.3.1 Sample size for estimation prevalence of sarcopenia in older patients (Cross-sectional study 1) The sample size was determined using a single population proportion formula: As there has been no study on sarcopenia in geriatric patients in Vietnam, we assumed p to be 50% Therefore, the sample size for our study was calculated to be at least 384 participants 2.3.2 Sample size for test on validity of sarcopenia screening tools (cross-sectional study 2) N for sensitivity 95% was 132, and N for specificity 80% was 550 We interested in both sensitivity and specificity, then we take the higher number (N=550) Our expected rate of missing data was 10% The sample size of crosssectional study for test on validity of sarcopenia screening tools was at least 605 2.3.3 Sample size for assessment the sarcopenia-related adverse outcomes (Longitudinal study 3) Formular calculation for hypothesis test for two population proportion (two side test): N = 166 Our expected dropout rate was 20% Thus, the sample size for the longitudinal study was at least 200 2.4 Study setting - Location: Outpatient Department, National Geriatrics Hospital - Time: From January 2018 to April 2020 2.5 Data collection Data was collected from medical records, patient interviews and physical examination Trained interviewers collected the data from participants via face-to-face interviews Anthropometric measurements and other physical assessments were performed by five well-trained clinical research assistants Follow up data was obtained by telephone interview and clinical visits 2.5.1 Diagnosis of sarcopenia based on “gold standard”, Asian Working Group on Sarcopenia (AWGS) criteria In our studies, sarcopenia was defined as low muscle mass plus low muscle strength using cut-points suggested by the Asian Working Group on Sarcopenia (AWGS) [19] 2.5.1.1 Muscle mass Muscle mass assessed by Appendicular skeletal muscle adjusted by height square (ASM/height2) + Each participant received a whole body dual X-ray absorptiometry scan (DXA Medic DR C12, Mauguio, France) to measure regional lean mass (kg), total body fat (kg), and total body fat percentage (%) It took 15 – 20 minutes for each person to this examination  Appendicular skeletal muscle (ASM, kg) was defined as the sum of the lean soft tissue masses of the arms and legs [71] + Height: Participants were measured against a convenient flat wall Participants were barefoot with arms hanging freely at the side and eyes looking straight ahead 2.5.1.2 Muscle strength Muscle strength was evaluated by hand grip strength test + Handgrip strength (HGS, kg) was measured using a dynamometer (Jamar TM Hidraulic Hand Dynamometer 5030 J1 made in USA) + Participants were asked to sit on a chair, bend the elbow at a 90 – degree angle and not touch the body The participants gripped the dynamometer as much as possible with each hand, twice a hand The highest value was used Handgrip dynamometer was calibrated regularly to ensure reliable and accurate results of muscle strength  According to “gold standard” AWGS, sarcopenia was defined as having (1) low muscle mass, plus (2) low muscle strength [19]: (1) Low muscle mass was defined by ASM/height 2: < 7.0 kg/m2 in male; < 5.4 kg/m2 in female (2) Low muscle strength: Low HGS cut-points were: < 28 kg in male; < 18 kg in female 2.5.2 Sarcopenia screening tools: SARC-F, SARC-CalF and Ishii’s formula 2.5.2.1 Translation and adaption of the SARC-F questionnaire Participants self-completed the SARC-F questionnaires The SARC-F composed of components including strength, assitance in walking, rise from the chair, climb stairs and falls The Vietnamese version of the SARC-F was adapted following standardized forward–backward translation procedure Two independent geriatricians translated the English version into Vietnamese language In Vietnam, people use the unit of "kg" instead of "pound", therefore question “How much difficulty you have in lifting and carrying 10 pounds?” was modified to “How much difficulty you have in lifting and carrying 4.5 kg?” An English native speaker who had no knowledge of the wording from the original English version conducted backward translation The two translations were compared item by item and revised upon agreement among the authors and the three translators The English and Vietnamese versions of the SARC-F are shown  The total score of the SARC-F questionnaire ranges from to 10 points, and a score ≥ indicates sarcopenia 2.5.2.2 SARC-CalF tools The SARC-CalF was developed adding calf circumference (CC) to the SARC-F questionnaire: (1) Each components of SARC-F questionnaire are scored as above (0 – scores each question) (2) Calf circumference (CC): CC measurement was made at the maximum circumference of the lower non-dominant leg with the participant’s leg bent 90° degrees at the knee The measurement was conducted in both legs and the higher value of the two measurements was used for the analysis Scoring of CC was as bellows: Male: > 34 cm = point ≤ 34 cm = 10 points Female: > 33 cm = point ≤ 33 cm = 10 points 2.5.2.4  The total score was calculated as sum of score of five questions and of CC score A SARC-CalF score ≥ 11 indicates sarcopenia [22] 2.5.2.3 Ishii’ formula Ishii’s formula was based on age, calf circumference (CC) and handgrip strength (HGS) [21] Sarcopenia score was calculated HGS and CC were evaluated as above The formula to calculate the total scores were as follows: In male: 0.62 × (age − 64) − 3.09 × (HGS − 50) − 4.64× (CC − 42); In female: 0.80 × (age − 64) − 5.09 × (HGS − 34) − 3.28× (CC − 42)  The cut-points of total Ishii scores for defining sarcopenia were: ≥ 105 for male; ≥120 for female Short-term health-related outcomes: at and 18 months follow-up Follow-up data were collected by telephone and clinical visits combined with the medical record The data were collected by welltrained clinical research assistants Loss to follow-up was considered when participants did not have a new admit to the outpatient clinics, National Geriatrics Hospital or if the participants could not be reached by at least 05 telephone calls at different times during the follow-up period The follow-up time was calculated from the enrolment and all participants were followed up for 18 months A total of 05 patients (2%) was loss follow-up at 18 months follow-up  All-causes mortality At 09 and 18 months during the follow-up period, the survival status of the participants obtained via telephone interviews All the mortality events were confirmed and the period (month) from the first investigation to the date of mortality was recorded  Incidence of fall Incidence of fall was obtained for participants who did not have the history of falls in the last 12 months in the baseline investigation At 09 and 18 months follow-up after the baseline investigation, we asked each participant the following questions: “Have you fallen in the past nine months?” Fall was defined as “unintentionally coming to rest on the ground, floor or other lowerlevel”  Incidence of dependences Incidence of ADL and IADL dependences was obtained for participants who did not have dependences in the baseline Incidence of daily activities activity was defined as progression from those without limitation at baseline to having limitation at follow-up The rates of incidence of dependences were noted 2.6 Statistical analysis Data were managed in Redcap Analysis of the data was performed using SPSS for Windows 20.0 (IBM Corp., Armonk, NY, USA) Continuous variables are presented as mean (± standard deviation), and categorical variables as frequency and percentage Comparisons between participants with and without sarcopenia or between male and female were assessed using Chi-square tests for categorical variables and Student’s t-tests for continuous variables Two-tailed P values < 0.05 were considered statistically significant The internal consistency of the SARC-F was assessed by Cronbach’s alpha and item to total correlation coefficients The value of Cronbach’s alpha ≥0.70 indicating an acceptable level of internal consistency The item-total correlation coefficients are Pearson’s correlation which ranges from to 1, with the higher value indicating the better consistency To assess the validity of, such as SARC-F, SARC-CalF and Ishii’s formula, the AWGS criteria was used as the gold standard for diagnosing of sarcopenia And thus the receiver operator curve (ROC) was applied to evaluate the evaluate sensitivity (Se), specificity (Sp), and area under the curve (AUC) of three screening tools for cut-off points that proposed in preliminary studies The accuracy measures the proportion of correct classifications over the total number of classifications The positive predictive value (PPV) is the probability of having sarcopenia defined by the AWGS in participants with sarcopenia defined by screening tools (true positive) The negative predictive value (NPV) is the probability of not having sarcopenia (defined by the AWGS) in participants without sarcopenia defined by screening tools (true negative) The higher values of accuracy, PPV and NPV indicate the higher diagnostic validity of SARC-F 10 Multivariate logistic regression was also used to determine the effect of sarcopenia on health adverse outcomes, including: (1) All-causes mortality (Adjusted by living alone, having history of hospitalization in the last 12 months, dependences in instruments activities daily living, frailty, depression, low Time up and go test, diabetes and hypertension) (2) Incidence of fall (Adjusted by age, gender, history of hospitalization in the last 12 months, malnutrition, low physical activity level, dependence in activities daily living, frailty, depression, cognitive impairment, diabetes and hypertension) 2.7 Ethical consideration The study was approved by the National Geriatric Hospital Ethics Committee, Hanoi, Vietnam (No.1235/QD-BVLKTW November 15 2017) Written informed consent was obtained from participants before starting the study Chapter RESULTS 3.1 Prevalence of sarcopenia and related factors among older patients 3.1.1 Prevalence of sarcopenia During the study period, 916 were approached, of whom 802 (87.6%) agreed to take part in the study Due to missing data on physical examination or DXA measurement, 38 participants (4.7%) were excluded Thus, the final study population comprised 764 participants Figure 3.1 The proportion of sarcopenia according to gender based on different criteria The proportion of sarcopenia was 61.2% (72.2% in male and 52.8% in female) based on AWGS criteria (Figure 3.3) Using SARCF and SARC-CalF questionnaire, 49.2% and 59.4% were defined as having sarcopenia, respectively According to Ishii’s formula, the proportion of sarcopenia was 65.5% 11 Figure 3.2 Prevalence of sarcopenia according to age groups Prevalence of sarcopenia was statistically increasing with age, ptrend