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

Three extensive and valuable screening tools, includingSARC-F questionnaire, SARC-F adding calf circumference SARC-CalF and Ishii’s formula, were recommended by internationalsarcopenia w

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 isindependently associated with health adverse outcomes, such as fallsand fractures, dependences, hospitalization, and mortality

Three extensive and valuable screening tools, includingSARC-F questionnaire, SARC-F adding calf circumference (SARC-CalF) and Ishii’s formula, were recommended by internationalsarcopenia working groups that could be used to initially screen forsarcopenia However, in the literature, no study on comparison oftheir reliability and validity has yet been performed in the same studypopulation And there has been no study on the application of thesescreening tools in older patients in Vietnam Therefore, we conducted

the study “Validation of sarcopenia screening tools among older paptients” with three aims:

1 Assess the prevalence of sarcopenia and associated factors in patients attending geriatric clinics in Vietnam

2 Evaluate the diagnostic accuracy of the SARC-F, SARC-CalF and Ishii’s formula in the screening for sarcopenia among older patients.

3 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

low-middle income countries such as Vietnam It has been proposed that avaluable, simple and inexpensive tool could be used to initiallyscreen for sarcopenia Some screening methods were developed byresearch teams with the aim to rapidly identify individuals whorequire a diagnostic examination for sarcopenia Indeed, the earlyidentification of older adults likely to suffer from sarcopenia wouldallow them to implement, at an early stage, preventive strategiesincluding protein supplementation and physical activity incombination Three extensive and valuable screening tools, includingSARC-F questionnaire, SARC-F adding calf circumference (SARC-

CalF) and Ishii’s formula, were recommended by AWGS 2019 andEWGSOP2 that could be used to initially screen for sarcopenia Theyhave 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 maleand advance age Related factors for sarcopenia: age, male,underweight, low physical activity, being malnourished and chroniclung disease

Screening tools including SARC-F, SARC-CalF and Ishii’formularhas acceptable sarcopenia diagnostic value for older patients, incomparision 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 receiveroperating curve to identify sarcopenia in older outpatients

High value of Ishii’s formular at baseline was related with increasingshort-term health-related outcomes among older patients (all causesmortality, 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 (30pages), discussion (29 pages), conclusion (2 pages) andrecommendation (1 page) 158 English and Vietnames references

Chapter 1 LITERATURE RIVIEW

1.1. Definition of sarcopenia

Sarcopenia is a syndrome characterised byprogressive and generalized loss of skeletal muscle mass andstrength with a risk of adverse outcomes such as physicaldisability, poor quality of life and death

1.2.Prevalence of sarcopenia

Prevalence of sarcopenia in the world was evaluated in a systematicreview and meta- analysis of general population studies The studiesthat reported the prevalence of sarcopenia in people aged ≥ 60 years

in community setting based on the EWGSOP, the InternationalWorking Group on Sarcopenia (IWGS) and AWGS criteria, wereselected With a total of 58404 individuals, the overall estimates ofsarcopenia prevalence was 10% (95%CI: 8-12%) in male and 10%

(95%CI: 8-13%) in female, respectively The prevalence was higheramong non- Asian than Asian individuals in both genders (11% vs10% in male, 13% vs 9% in female).

The global prevalence of sarcopenia was around 6-22 % in peopleaged 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 InAsian countries, the review of epidemiology studies that used AWGS

2014 criteria discovered that the prevalence of sarcopenia rangedfrom 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, particularlythose with low physical activity levels

- Sarcopenia is common across all older populations and may betransient 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 SarcopeniaDiagnosis and Treatment, calf circumference, SARC-F or SARC-Calf questionnaire were the choosing tools for sarcopenia casefinding 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 ofsarcopenia

+ 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 sarcopeniaaccording 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 significantlycontribute to less morbidity and mortality related to the condition

Chapter 2 MATERIALS AND METHOD2.1. Study population

Consecutive patients aged 60 years or above visiting theOutpatient Department of the National Geriatric Hospital in Hanoi,Vietnam were recruited

- Pace-maker implanted or had metal medical devices;

- Severe illness (receiving intensive care)

- Unable to provide consent or refused to participate in the study

2.2. Study design

Observational study was conducted:

+ Objectives 1 and 2: Cross-sectional study

+ Objective 3: Longitudinal study

2.3. Sample size

Consecutive patients aged 60 years or above visiting 05outpatient 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 proportionformula:

As there has been no study on sarcopenia in geriatric patients inVietnam, 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 thehigher number (N=550)

Our expected rate of missing data was 10% The sample size of

cross-sectional 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 populationproportion (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 andphysical examination Trained interviewers collected the data fromparticipants via face-to-face interviews Anthropometric

measurements and other physical assessments were performed byfive well-trained clinical research assistants Follow up data wasobtained 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 massplus low muscle strength using cut-points suggested by the AsianWorking Group on Sarcopenia (AWGS) [19]

 Appendicular skeletal muscle (ASM, kg) was defined as the sum ofthe lean soft tissue masses of the arms and legs [71]

+ Height: Participants were measured against a convenientflat wall Participants were barefoot with arms hanging freely at theside 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 adynamometer (Jamar TM Hidraulic Hand Dynamometer 5030 J1made in USA)

+ Participants were asked to sit on a chair, bend the elbow at

a 90 – degree angle and do not touch the body The participantsgripped the dynamometer as much as possible with each hand, twice

a hand The highest value was used Handgrip dynamometer wascalibrated regularly to ensure reliable and accurate results of musclestrength

 According to “gold standard” AWGS, sarcopenia was

defined as having (1) low muscle mass, plus (2) low musclestrength [19]:

(1) Low muscle mass was defined by ASM/height2: < 7.0 kg/m2

in male; < 5.4 kg/m2 in female

(2) Low muscle strength: Low HGS cut-points were: < 28 kg inmale; < 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 TheSARC-F composed of 5 components including strength, assitance inwalking, rise from the chair, climb stairs and falls

The Vietnamese version of the SARC-F was adapted followingstandardized forward–backward translation procedure Twoindependent geriatricians translated the English version intoVietnamese language In Vietnam, people use the unit of "kg" instead

of "pound", therefore question 1 “How much difficulty do you have

in lifting and carrying 10 pounds?” was modified to “How muchdifficulty do you have in lifting and carrying 4.5 kg?” An Englishnative speaker who had no knowledge of the wording from theoriginal English version conducted backward translation The twotranslations were compared item by item and revised upon agreementamong the authors and the three translators The English andVietnamese versions of the SARC-F are shown

 The total score of the SARC-F questionnaire ranges from 0

to 10 points, and a score ≥ 4 indicates sarcopenia

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 legsand the higher value of the two measurements was used for theanalysis Scoring of CC was as bellows:

Male: > 34 cm = 0 point ≤ 34 cm = 10 points

Female: > 33 cm = 0 point ≤ 33 cm = 10 points

 The total score was calculated as sum of score of fivequestions and of CC score A SARC-CalF score ≥ 11indicates 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 sarcopeniawere: ≥ 105 for male; ≥120 for female

2.5.2.4 Short-term health-related outcomes: at 9 and 18 months follow-up

Follow-up data were collected by telephone and clinical visitscombined with the medical record The data were collected by well-trained clinical research assistants

Loss to follow-up was considered when participants did nothave a new admit to the outpatient clinics, National GeriatricsHospital or if the participants could not be reached by at least 05telephone calls at different times during the follow-up period Thefollow-up time was calculated from the enrolment and all participantswere followed up for 18 months A total of 05 patients (2%) was lossfollow-up at 18 months follow-up

 All-causes mortality

At 09 and 18 months during the follow-up period, thesurvival status of the participants obtained via telephone interviews.All the mortality events were confirmed and the period (month) fromthe first investigation to the date of mortality was recorded

 Incidence of fall

Incidence of fall was obtained for participants who did nothave the history of falls in the last 12 months in the baselineinvestigation At 09 and 18 months follow-up after the baselineinvestigation, 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 level”

lower- 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 wasperformed using SPSS for Windows 20.0 (IBM Corp., Armonk, NY,USA)

Continuous variables are presented as mean (± standarddeviation), and categorical variables as frequency and percentage.Comparisons between participants with and without sarcopenia orbetween male and female were assessed using Chi-square tests forcategorical 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 byCronbach’s alpha and item to total correlation coefficients The value

of Cronbach’s alpha ≥0.70 indicating an acceptable level of internalconsistency The item-total correlation coefficients are Pearson’scorrelation which ranges from 0 to 1, with the higher value indicatingthe better consistency

To assess the validity of, such as SARC-F, SARC-CalF andIshii’s formula, the AWGS criteria was used as the gold standard fordiagnosing 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 screeningtools for cut-off points that proposed in preliminary studies Theaccuracy measures the proportion of correct classifications over thetotal number of classifications The positive predictive value (PPV) isthe probability of having sarcopenia defined by the AWGS inparticipants with sarcopenia defined by screening tools (truepositive) The negative predictive value (NPV) is the probability ofnot having sarcopenia (defined by the AWGS) in participants withoutsarcopenia defined by screening tools (true negative) The highervalues of accuracy, PPV and NPV indicate the higher diagnosticvalidity of SARC-F

Multivariate logistic regression was also used to determine theeffect of sarcopenia on health adverse outcomes, including:

(1) All-causes mortality (Adjusted by living alone, havinghistory of hospitalization in the last 12 months, dependences ininstruments activities daily living, frailty, depression, low Time upand go test, diabetes and hypertension)

(2) Incidence of fall (Adjusted by age, gender, history ofhospitalization in the last 12 months, malnutrition, low physicalactivity 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 HospitalEthics Committee, Hanoi, Vietnam (No.1235/QD-BVLKTWNovember 15 2017) Written informed consent was obtained fromparticipants before starting the study

Chapter 3 RESULTS3.1. 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 onphysical examination or DXA measurement, 38 participants (4.7%)were excluded Thus, the final study population comprised 764participants

Figure 3.1 The proportion of sarcopenia according to gender based

Figure 3.2 Prevalence of sarcopenia according to age groups

Prevalence of sarcopenia was statistically increasing withage, ptrend <0.001 (Figure 3.1.) Sarcopenia was accounted for 42.7%

in 60 – 69 years old group The proportion of sarcopenia was 59.3%

in 70 – 79 years old group And 90.2% of patients aged ≥ 80 yearswere sarcopenia

Figure 3.3 Prevalence of sarcopenia according to nutritional status,

physical activity level and frailty status

The vast majority of study participants with malnutritionstatus (91.7%) or frailty (92.5%) were diagnosed with sarcopenia

The proportion of people with sarcopenia was more commonamong low physical activity level group (76.1%) than amongmoderate-to-high physical activity level group (51.8%)

3.1.2 Related factors with sarcopenia among older patients

Table 3.1 Potential factors associated with sarcopenia on

multivariate logistic regression

Variables

Adjusted odds ratios for sarcopenia (95%CI)

COPD, chronic obstructive pulmonary disease

In multivariate logistic regression, age, underweight, beingmalnourished, chronic lung diseases were significantly associatedwith sarcopenia defined by AWGS criteria (Table 3.6.)

3.2.1.1 Reliability of SARC-F questionnaire

Over all, the SARC-F score was 3.2 ± 2.4 on average