Professor Lakkana ThaikrueaCommunity Medicine Department,

Faculty of Medicine, Chiang Mai University, Thailand

Case definition

Answer two questions

1) Can researcher allocate primary exposure?exposure?

• No

• Yes

If ‘Yes’

2) Does researcher allocating 2) Does researcher allocating participants using randomization?

• No

• Yes

Randomization

• To prevent potential bias on the part • To prevent potential bias on the part of researcher (assigns participants into different exposure groups)

• Increase comparability (BUT not guarantee)

– measurable variables

– non-measurable variables

AssignExposure

Conduct Randomization

Yes NoYes No

Yes Experiment Quasi Experiment

No -------- Observational Study

● Researcher conducts under controlledcircumstances.circumstances.

● Researcher manipulates the conditions to ascertain what effect has on the observation.

● It must have control group.● Experimental and control groups must● Experimental and control groups must

have similar pre-intervention risk ofdeveloping the outcome.

• Clinical trial: Patients are participants in randomized controlled participants in randomized controlled trial (RCT).

• Field trial: Healthy people are participants.

• Community trial: Groups of people in

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• Community trial: Groups of people in communities are participants (exposures are assigned to the groups).

Conducting research1. Ethical considerations

- Uncertainty about the relative merits ofnew VS and standard interventions

- Current knowledge do not prove that- Current knowledge do not prove thateither arm is superior

- Ethical if they have a reasonablelikelihood of producing the correctanswer to the research question

- Ethic committees- Ethic committees

2. Study design3. Study population

4. Data collection

5. Data analysis

PopulationPopulation

2. Study design

Basic structure

Population

Sample

Assignment

Population

Select study population

Assignment by researcher

Randomization

Experiment Control

Outcome Experimental Group

Outcome Control Group

Administration

Measures outcome

3. Population

• Define population / setting• Study population• Sample size

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• Sample size• Sampling methodology• Selecting participants

- Inclusion criteria (Define the main characteristics to join the study)- Exclusion criteria (Define characteristics

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- Exclusion criteria (Define characteristicsmaking individuals not suitable to jointhe study although fulfilling the inclusion criteria)

Exclusion criteria consideration:

Any conditions of;• The study intervention

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• The study intervention – clearly indicated– contraindicated / would be harmful

• Participants have no benefit from study intervention

• Practical problems with participating in

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• Practical problems with participating inthe Protocol (i.e. Impaired mental status, language barrier, etc)

Sample Size Estimation:

● Enough for important effect thatneeds to be detectedneeds to be detected

● Parameters - Retrieved from literature reviews, previous study, pilot study, etc.

- Acceptable type I error (level of- Acceptable type I error (level ofsignificance)

- Acceptable type II (power)

4. Data collection

1) Define exposure - Effectiveness VS safety- Control (No treatment,

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- Control (No treatment, placebo, standard treatment)

2) Define outcome - Primary, Secondary, Adverse - Single or composite- Relevant/ bio-possibility

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- Relevant/ bio-possibility - No / minimal co-operation of

participants

3) Define factor(s) affects prognosis - Characteristics- Strong confounders

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- Strong confounders4) Procedures and measurements

- Validity- Bias

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Bias● Exposure allocation by randomization

- Concealment: Unawareness of exposureallocation BEFORE randomizationallocation BEFORE randomization- Sequentially numbered, opaque, sealed

envelopes - Pharmacy preparing● Blinding of exposure allocation- Single, double, triple- Unawareness of exposure assignment AFTER- Unawareness of exposure assignment AFTER

randomization- Ensure comparability AFTER randomization- Not always possible

● Maximizing adherence and follow-up- Loss of power of the trial- Bias; non-adherent participants/lost

to follow-up havedifferent prognosis to follow-up havedifferent prognosis from others

- Consider the number lost to follow-up to the number of outcome events

- Small effect: Number lost to FU << Number outcome Number outcome

- Minimizing crossover

● Analysis using intention-to-treatprinciple- Analysis of outcomes based on the

exposure arm to which participants exposure arm to which participants were randomized (Not they actually received)

- Preserve randomization value- Results reflecting true population

effect (When intervention is used in effect (When intervention is used in real practice)

● Difference

- No - Some degree difference (The probabilitythat the observed difference is only by

5. Data analysis

that the observed difference is only by chance- p-value)- Statistical tests are based on outcome variables (i.e. categories, continuous, time-to-event) and data distributions

● Magnitude● Magnitude

- Point estimate (95% confidence interval)- Binary (Relative risk, Risk difference,Hazard ratio, number of patients who would need to be treated, etc)

Randomization

• To prevent potential bias on the part of researcher (assigns participants of researcher (assigns participants into different exposure groups)

• Cannot predict the next assignment

• Increase comparability (BUT not guarantee)guarantee)

– measurable variables

– non-measurable variables

Randomization procedure:● Simple randomization

- Coin tossing; Random-number table, Computer generated randomization list- Risk of imbalance in number of participant - Risk of imbalance in number of participant assigned to each group and confounders

● Block randomization- Avoid serious imbalance in the number of participants assigned to each groupparticipants assigned to each group

● Stratified randomization

● Adaptive randomization

● Cluster randomization

● Block randomization- Avoid serious imbalance in the number

of participants assigned to each arm.- Order of exposure within the block and - Order of exposure within the block and

order of consecutive blocks are at random.

- Assignment to the last person in each block can be known if treatment is not blind (Solving: randomly varying block blind (Solving: randomly varying block sizes)

Block of 4 ECEC CEEC CCEE CECEEECC . . . .

● Stratified Randomization- Avoid imbalance in confounders

between groups

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between groups- Participants are categorized into

stratum based on stratification factors (strong confounders)

- Block randomization is conductedfor each stratum

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for each stratum

● Cluster randomization

- Randomization with groups or clusterof participants as units of randomization (nursery, university,

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randomization (nursery, university,communities, etc.)

- All participants in the same clusterreceive the same exposure.

- Appropriate for exposure that cannot

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- Appropriate for exposure that cannotbe delivered to each individual.

•• Evaluating the efficacy of therapeuticEvaluating the efficacy of therapeutic•• Causal relationship Causal relationship

Advantages Advantages

•• Internal validityInternal validity

•• Ethical violation in some situations Ethical violation in some situations of randomizationof randomization

Disadvantages Disadvantages

of randomizationof randomization

•• Effect is observed in artificial settingEffect is observed in artificial setting

•• External validity (generalizability)External validity (generalizability)

Randomized controlled trials

Used for evaluating

1. New forms of intervention before it 1. New forms of intervention before it is approved and recommended for use

2. Interventions that are

- highly controversial - highly controversial

- widely used or recommended without having been appropriate evaluated.

Music Therapy Music Therapy Sound TherapySound TherapySound TherapySound Therapy

The effect of music with and without binaural beat audio on operative anxiety in patients

undergoing cataract surgery: a randomized controlled trial.

Eye. 2016;3(11): doi: 10.1038/eye.2016.160. Eye. 2016;3(11): doi: 10.1038/eye.2016.160.

Wiwatwongwana D, Vichitvejpaisal P, Thaikruea L, Klaphajone J, Tantong A, Wiwatwongwana A

BB and Brain

To investigate the anxiolytic effects of binaural beat embedded audio in

Objective

of binaural beat embedded audio in patients undergoing cataract surgery under local anesthesia.

Methods

• Study design: • Experiment- RCT

• Study population:• Study population:• Sample size; 141 patients undergoing

cataract surgery under local anesthesia • Sampling methods; block randomization - Binaural beat music group (BB)- Plain music intervention group (MI)- Plain music intervention group (MI)- Control group (Ear phones with no music)

20 Hz20 Hz10 Hz10 Hz

Data collection

10 Hz10 Hz

Binaural Beat (BB)

Beta waveBeta waveAlpha waveAlpha wave

0 min0 min 10 min10 min 20 min20 min

10 Hz10 Hz

5 min5 min

ResultsResults

Mean different STAIMean different STAI--S ScoresS Scores

Anxiolytic effect

Mean different STAIMean different STAI--S ScoresS Scores(SD)(SD)

P valueP value

ControlControl(n=(n=4747))

MIMI(n=44)(n=44)

BBBB(n=44)(n=44)

Control Control vs MIvs MI

Control Control vs BBvs BB

MI vs BBMI vs BB

* p-value <0.05 (ANOVA with Sidak) * p-value <0.05 (ANOVA with Sidak)

--2.9 2.9 (4.4)(4.4)

--7.0 7.0 (4.8)(4.8)

--9.0 9.0 (4.2)(4.2)

<0.05*<0.05* <0.05*<0.05* 0.090.09

Physical effect

A significant reduction in heart rate A significant reduction in heart rate was seen only in the BB group

• BB vs control (P-value = 0.004) • BB vs MI (P-value = 0.050)• MI vs control (P-value = 0.303)• MI vs control (P-value = 0.303)

Conclusion

• Music, both with and without BB:

– decrease anxiety level and lower – decrease anxiety level and lower systolic BP

• Patients who received BB:

– decrease in heart rate

• BB embedded musical intervention • BB embedded musical intervention may have benefit over musical intervention alone in decreasing operative anxiety

Superimposed Binaural Beat

Effects of New Superimposed Binaural Beat on Anxiety in University Students in Thailand:

A Randomized Controlled Trial.

Journal of Natural Sciences. 2019:18;122-130.

Chairinkama W, Thaikrueaa L, Klaphajoneb J, Klaphajoneb J, Lerdtrakernnont P.

Mental Disorders among University Students

(http://www.amarintv.com/news-update/news-update-thai/news-7996/175465/)

• 2014-2017*: survey mental disorders among first-year college studentscollege students

• 31% positive for at least one 12-month disorder

• Need for mental health servicesservices

• Major challenge to institutions of higher education

(* WHO, J Abnorm Psychol 2018)

What was the prevalence of depression and anxiety in health science students of UP?

2016*2016*Depression 35.53%

Anxiety 49.07% Depression and/or anxiety 60.00%

(*Thaikruea L, Chairinkam W. The Effect of His Majesty King Bhumibol Adulyadej’s Passing Away on Mental Health of University Students in Northern Thailand. Merit Res. J. Med. Med. Sci. 2017)

Anxiety coping in university student

• Watching TV (45.9%)*

• Play games/internet (37.7%)*• Play games/internet (37.7%)*

• Listen to music (33.5%)*

• Alcohol (13.9%) **

*Patai, T (2553) **Chairak, S (2553)

Anxiety intervention

• Psychotherapies

• Medicine • Medicine

• Anxiolytic drug 705 millions tab/year and 56% not treated by doctors***

• Cognitive Behavioral Therapy

• Mindfulness• Mindfulness

• Meditation

• Music therapy

*** Inksatis, A (2549)

• Music therapy:

- Suitable for university students

- Alternative choice

• Binaural Beat (BB):

- 2 tones with slightly different frequencies are presented separately, one to each ear

- Embedded in music

• Superimposed Binaural Beat (SBB) innovation (Klaphajone J)innovation (Klaphajone J)

• SBB and BB Hypothesis:

- Enhance the power of brainwave entrainment

- Expected better quality and efficiency

BB SBB

Superimposed Binaural Beats for This RCT

Rt. ear Lt. ear

(A=450 Hz)(A=440 Hz)

Rt. ear

Sa- lor

Seung

Thai flute

Constant

frequency track

Drum and percussions

Electone

To compare the effects of SBB and

Objective

To compare the effects of SBB and music therapy on anxiety in university students with anxiety

Methods

• Study design: • RCT

3 arms• 3 arms• Study population:

• Health Science students with anxiety (STAI > 40) of Phayao University in year 2016 (539)

• Sample size; Add 5% = 45/group• Sampling methods; • Sampling methods;

block randomization (sealed envelop)- SBB group - Plain music listening group (ML)- Control group (blank audio)

Study population

N= 539

Simple random sampling

Sample sizeN=134

Simple random sampling

Block randomization

ML groupN=45

SBB groupN=45

Control groupN=44

Data collection

Inclusion criteria- Studying in school - Studying in school

of health science- Age above 18

Exclusion criteria- Unwilling- Unwilling- Depression

1. Mp3 player and headphone

2. Relaxation chair in controlled temperature room

3. Intervention- Control = relaxation treatment - Control = relaxation treatment

- ML = Relaxation +Thai Traditional music that recommended for anxiolytic (ลอ่งแมปิ่ง สรอ้ยเวยีงพงิค)์

- SBB= ML + SBB 10 Hz

4. 20 minutes/session/day * 5 consecutive daysconsecutive days

5. Anxiety assessment at the end of each session (STAI)

6. Double-blind allocation

Control of Confounding factors (study design and monitoring time

dependent variables)dependent variables)

– Descriptive analysis: percentage, mean (SD), or median (Range)

Data analysis

mean (SD), or median (Range) depend on data distribution

– Univariate analysis: paired t-test, Fisher’s exact test, Kruskal-Wallis test with alpha 0.05test with alpha 0.05

Results

Treatment

Group

Different STAI-S Scores* P-value

Anxiety Levels by Treatment Group

Group Median (Range)

SBB -20.00

(-3.00 to -40.00)

SBB versus ML:

0.02**

ML -16.00 ML versus Control:

(1.00 to -32.00) 0.81

Control -15.00

(0 to-50.00)

Control versus

SBB: 0.04**

* Pre and post tests ** Kruskal-Wallis test

Comparison of Anxiety Normal Rates after Completed Treatment

Treatment n normal P-

Group n (%) value*

SBB 45 45 (100.00) 0.005

ML 45 43 (95.56)

Control 44 37 (84.09)

* Fisher's exact test

Effects of Combined Physical Movement and Multifaceted Cognitive Training in Older People

with Mild Cognitive Impairment in a rural Thailand

Assistant Professor Jiranan Griffiths, OT PhD StudentProfessor Dr. Lakkana Thaikruea, M.D., Epidemiologist Professor Nahathai Wongpakaran, M.D., Psychiatrist

Assistant Professor Peeraya Munkhetvit, PhD. OT Dr. Adisak Kittisares, Neurologist Ms. Pairada Varnado, Psychologist

Older People with Mild Cognitive Impairment

To determine effects of combined

Objective

To determine effects of combined physical movement and multifaceted cognitive training (MC) on attention, memory, executive function, and quality of life in older people with MCI

Methods • Study design:

• Experiment- RCT• Study population:

• Sample size; 78 people aged at least 60 • Sample size; 78 people aged at least 60 years who resided in rural area of Chiang Mai province

• Sampling methods; block randomization, stratified by gender and age - MC group - MC group - Control group

Sampling step of Phase 1-2

Total Older People Population: 1096

Sample: 579

482

Stratified sampling

97 Excluded;Psychiatrics =54Hearing =8Thyroid=4CVA=7Eyes problem=3Eyes problem=3Dementia=14Sleeping pill=3Stress pill=3

Sampling step (cont)

482

MCI344

138Normal

Movement problems =10Movement problems =10

334

Phase 2Exclude=31Heart disease=1TB=1Athma=2Phathological grief=1Brain injury=4

Willing to continue Phase 2

101

70

Brain injury=4ALC use disorders =6Depression =4Mood disorders=1MR=1Nerve compression affects movement=2Major NCD =1Eye problems =1Vascular disease=1Drug induce=3Hearing Hearing Impairment=1Withdraw the group=1

35 35

Block Randomized

Diagnosis: MCI by DSM V (2weeks in May)

• Data collection

DSM-5 approach (2013)Diagnosis criteria for MCI/

mild neurocognitive disorders

Pre Test

• Attention: TMT-A, TMT-B

• Memory: Digit Span• Memory: Digit Span

• Verbal Fluency: Alphabet, Name

• Words list recall: immediate recall and delay recall

• Executive Function: Block design

• IADL: Lawton

• Quality of Life: SF36

Program:

• 2 times/week for 3 months

• Physical activity:• Physical activity:

• Cognitive Activity:

• Executive Function:

• Duration and difficulty increased over timetime

Physical activity:

1st Month

1. Bamboo movement with music 20 minutes

2. Warm up, Stretching and Flexibility 5 minutesminutes

3. Aerobic Physical Activity 10 minutes

4. Cool down, relaxation 5 minute

VDO 2

Cognitive Activity:

1. Visual Attention:

1st: Walking and 1 : Walking and remembering surrounding objects quickly

2nd: Picture Cards

2. Memory:

1st: Immediate recall, Delay 1st: Immediate recall, Delay recall (number, name, people)

2nd:Word Fluency (Fruit, vegetable, animal)

Executive Function:

1st: Telephone Used1 : Telephone Used

2nd: Meal preparation

• planning and organization

• Cooking activity

- Initiation- Initiation

- Direct and monitor

Physical activity:

• Bamboo movement

Cognitive Activity:

Auditory Attention; 1st: Words list recognition

2nd Month

• Bamboo movement with music 25 minutes

• Warm up, Stretching and Flexibility 6 minutes

• Aerobic Physical

1st: Words list recognition on the conversation story2nd: Words recognition in songMemory;1st: Visual recognition/Matching • Aerobic Physical

Activity 12 minutes• Coll down, relaxation

7 minutes

recognition/Matching GameDeclarative memory;Message taking from friend2nd: Word Recall: Word lists

Executive Function:

• 1st Telephone Used and transportation

• Family / taxi diver• Family / taxi diver

• 2nd Housekeeping and laundry

• Productive activity

-Planning

- Initiation- Initiation

- Direct and monitor

Physical activity:

• Bamboo movement with

Cognitive Activity:

Visual and Auditory

3rd Month

• Bamboo movement with music 30 minutes

• Warm up, Stretching andFlexibility 7 minutes

• Aerobic Physical Activity 15 minutes

• Cool down, relaxation 8

Visual and Auditory Attention: 1. Colour recognition2. Visual Attention: Identify detail in photographs and tell the differences between 2 similar photographsVisual and Auditory • Cool down, relaxation 8

minuteVisual and Auditory Attention:Identify number on the card(Bingo)

Memory:

• 1st: Immediate Recall: Telephone numbers

Executive Function:

• 1st: money management and shoppingnumbers

• Delay Recall: Identify objects with their location

• 2nd: Memory training: Method of

shopping

• 2nd: Productive activity

- Planning

- Initiation

- Direct and monitortraining: Method of loci:

• Linking a place with each item to be remembered

- Direct and monitor

• Creative activity

Data analysis• Descriptive analysis:

– describe the characteristics of participants

– (proportion, ratio, mean (sd)/median(min-max)

• Univariate analysis:• Univariate analysis:

1. Determine association of risk factors and MCI

– Chi-square test, Fisher’s exact test, independent t-test, non-parametric test

2. Comparison between pre and post intervention

- Within group; Pair Sample T-test / Wilcoxon signed rank test- Within group; Pair Sample T-test / Wilcoxon signed rank test

- Between group; Independent T-test /Man-Whitney U Test

3. Intentional to treat analysis;

- 97% and 3% of participants could joined 80 %

and 54% of the program

Results of Phase Results of Phase 22• Attention

– Improved (TMT-A= Rx-w)

• Memory• Memory

– Improved (Digit Scale= Rx-w; VF Alphabet = Both-w, Rx > CT; VF Name= Rx-w; WLL Immediate and Delay Recall = Both-w, Rx > CT of both immediate and delay)

• Executive Function• Executive Function– Improved (BD Scale = Rx-w)

• IADL– Rx improved more than CT (Man-Whitney U Test

0.030)

ConclusionConclusion

Combined Physical Movement and Multifaceted Cognitive Training Multifaceted Cognitive Training

• Increased attention, memory and executive functions in MCI

• Enhanced cognitive functions and IADL in elderly people with MCIIADL in elderly people with MCI

• Non Pharmacological intervention

Thank You

Quiz

VDO 3

ผูป่้วยที�มปีญัหาดา้นรา่งกายหรอืจติใจ

VDO 1

Assessment of Music Therapy for Rehabilitation Among Physically Disabled People in Chiang

Mai Province: A Pilot Study. Music and Medicine. 2013;5(1):23-30.

Klaphajone J, Thaikruea L, Thaikruea L,

Boontrakulpoontawee M, Vivatwongwana P,

Kanongnuch S, Tantonget A.

To apply music components as a therapeutic tool for improving muscle

Objective

therapeutic tool for improving muscle strength, spasticity, lung capacity, self-esteem, and quality of life (QOL) among children with physical disabilities.

Methods

• Study design: ???

• Study population:Sample size; 39 eligible children with physical disabilities from SrisangwanChiang Mai School in ThailandChiang Mai School in Thailand

• Data collection

• 18-month program• 18-month program• Play therapeutic songs that were

selected to match his/her instrument, physical capacity, and music capability

• Therapeutic musical notes: Designed to Designed to improve the children’s capability by means of routine music practices music practices

• Practice andrehearsals: rehearsals: Improve outcomes

• Performances in public: Promote social integrationsocial integration

• Improve grip strength, increase lung capacity, reduce muscle spasticity Increase self-esteem

Results

• Increase self-esteem • Increase QOL score

Musical intervention - provide a holistic approach - provided an observable spirit boost and

Conclusion

- provided an observable spirit boost and improved self-esteem for the children involved and their caregivers during the musical performances.

Methods

• Study design: Prospective cohort study with pre Prospective cohort study with pre and post test