Prof Marvin Reid, MB BS, PhDconference.src.gov.jm/wp-content/uploads/2018/12/... · “The main...
Transcript of Prof Marvin Reid, MB BS, PhDconference.src.gov.jm/wp-content/uploads/2018/12/... · “The main...
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Prof Marvin Reid, MB BS, PhD
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THE END
Prof Marvin Reid, MB BS, PhD
“The main weapons in the prevention and
treatment of disease and human carelessness
will probably always be food and exercise.”
― Dr. Blake F. Donaldson, Strong Medicine
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OBJECTIVES
Screening & Treatment – Sickle Cell Disease
Nutrition, Epigenetics & Personalized
Medicine
Treatment – Diet & Physical Activity
Prof Marvin Reid, MB BS, PhD
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DIAGNOSTIC-TREATMENT
CONTINUUM
Awareness & Accessing
Care
Clinical Evaluation diagnosis &
Staging
Access to treatment
Prof Marvin Reid, MB BS, PhD
Not AI or Robotics
Screening Programmes
Point of Care Testing
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WHO RECOMMENDATION
Prof Marvin Reid, MB BS, PhD
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Prof Marvin Reid, MB BS, PhD
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NEONATAL SCREENING -PRACTICE
Cord Blood – Guthrie cards
• Transported to CAIHR
Initial Diagnostic
• HPLC Electrophoresis
Follow-up
• IEF
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JAMAICA
Sickle trait ~400,000
Sickle Births ~240/year
~2.9M
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SURVIVAL TO YEAR 10
Dr. Marvin Reid
King L, et al J Med Screen. 2007;14(3):117-22.
• NBS
• Chronic Disease Model-
(Engaged Clients; Primary
Care Physician)
• Conservative Transfusion
Policy
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Prof. Marvin Reid 10
Strokes in SCD
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STROKE
Stroke is common - incidence of 7.8% by the
age of 14 years. (Balkaran B et al. J Pediatr. 1992:360-6).
Stroke recurrence in 50 -90% within 3 years
[Ohene-Fremong et al 1998]
TCD velocities are a major risk factor for
Stroke
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STROKE RISK
STRATIFICATION BY TCD
Normal
TCD < 169 cm/sec
Conditional
TCD= 170-199 cm/sec
Abnormal
TCD > 200cm/sec
12
2-5% per year 9% per year
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TRANSCRANIAL DOPPLER
ULTRASONOGRAPHY
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PREVALENCE OF TCD GROUPS
80%
13% 7%
TCD Group
Normal Conditional Abnormal
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Classification of TAMV by the 5-vessel criteria Total
Classification of TAMV by
the 2-vessel criteria
Normal
<170 cm/sec
Conditional
170-199
cm/sec
Abnormal
≥200 cm/sec
Normal (<170 cm/sec) 287 3 0 290
Conditional (170-199
cm/sec) 0 44 0 44
Abnormal (≥200 cm/sec) 0 0 24 24
Total 287 47 24 358
CLASSIFICATION OF TCD GROUP
BY NUMBER OF VESSELS
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CHRONIC TRANSFUSION
Effective in primary and secondary prevention of stroke
In Jamaican context - Not an option • Cost –(transfusion, extended matching, iron
chelation)
• Safety
• Availability
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HYDROXYUREA -INDICATIONS
Recurrent vaso-occlusive crises i.e. - 3 or more
painful crises
2 or more Recurrent acute chest syndrome
Severe symptomatic anaemia.
Children following acute neurological events or
abnormal TCD
All patients who have a severe course
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1st stroke
N=43
HU
N=10
NO Re-stroke
N=9
Re-stroke *
N=1 (10%)
No HU
N=33
NO Re-stroke
N=13
Re-stroke
N=20 (60.6%)
Age at 1st stroke: 6.83 ± 3.77yrs
(range: 1.2 - 15.6 yrs)
Male: Female - 20:24
Genotype – SS:42, Sβ0:1, SC:1
43 followed : 4.26 ± 2.72 yrs
(range: 0.3-9.6 yrs)
Time to 1st re-stroke: 1.08 ±
1.53yrs
N = 44 (1died at time of 1st Stroke)
Jan. 31st, 2000 –
Sept. 30th, 2009
Ali SB, et al. Am J Hematol. 2011;86:846-50.
HU DOSE 25.4 ± 3.4 mg/kg
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PROBABILITY OF RESTROKE ON HU
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COST EFFECTIVENESS IN
PREVENTING 1 STROKE
0
20000
40000
60000
80000
100000
120000
140000
160000
180000
200000
TCD & Transfusion HU
USD178640
USD1900
Cherry et al Health Technol Assess 2012;16:1–129.
Cunningham-Myrie C, et al Pediatr Blood Cancer. 2015;1862-4.
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PRIMARY PREVENTION - SCATE
1. Hankins JS, et al . Am J Hematol. 2015;90(12):1099-105.
15.2 cm/sec 10.2 cm/sec
HU @ 25 mg/kg/d
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HU PROTOCOL
Start 15mg/kg
↑ 5 mg/kg q8wks
until MTD
Use weekly
cumulative dosing
when using capsules
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HEALTH POLICY
Objective 3
• Strengthen national capacity for NCD
surveillance and high quality research for
prevention and control of non-
communicable diseases
• NBS –Islandwide (2016)
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NATIONAL HEALTH FUND
NHF – Insurance fund to
subsidize costs of
selected disease to
clients
SCD added 2015
• FOC @ Public facilities
• HU retail ~0.09 to 0.39 USD
/Subsidy ~0.08 USD per
500 mg Capsule Minimum wage =USD 48 weekly
60 capsules monthly =12% of income
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HUMAN NUTRITION
March 2016 -Prof Marvin Reid
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Nutrition
Environmental Intrinsic
March 2016 -Prof Marvin Reid
• Genes
• Gene Expression (Epigenetics)
• Life stage
• Mood
• Appetite
• Lifestyle
• Symbiosis
• Disease
• Culture & Personal Beliefs
• Food access/security
• Economic
• Food preparation
• Climate
• Government policies
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N N N N
mRNA
Protein Molecule
Transcription
Translation
N N N N N N N N
Gene 1 Gene 2 Gene 3
Chromosome
GENETIC FACTORS
March 2016 -Prof Marvin Reid
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EPIGENETIC VARIATION
Physical and/or chemical factors can
produce heritable changes in gene
expression without alteration of the DNA
sequence itself.
These changes are referred to as
epigenetic changes.
March 2016 -Prof Marvin Reid
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TYPES OF EPIGENETIC
CHANGES
March 2016 -Prof Marvin Reid
N N N N
mRNA
Protein Molecule
Transcription
Translation
N N N N N N N N
Gene 1 Gene 2 Gene 3
Chromosome
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GENETICALLY IDENTICAL
3-MONTH-OLD AVY
MICE SPANNING A FIVE COAT COLOUR
PHENOTYPE (FROM DOLINOY ET AL., 2007)
March 2016 -Prof Marvin Reid
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EPIGENETICS – PRECISION
MEDICINE
Nutrigenomics – Nutrition / Genes & their expression /
Biomarkers
Test – Assess disease specific changes and thus define
disease sub-types
Epigenetic Age – 71 Blood DNA methylation markers.
Prof Marvin Reid, MB BS, PhD
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Fig. 1
EBioMedicine 2016 5, 68-73DOI: (10.1016/j.ebiom.2016.02.008)
Copyright © 2016 The Authors Terms and Conditions
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NUCLEAR MEDICINE
SPECT/CT - Single Photon
Emission Computed
Tomography (SPECT) is used
for imaging organ function.
Heart Disease /
Thyroid Disease /Sickle Cell/
Cancer /Kidney Diseases
Prof Marvin Reid, MB BS, PhD
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March 2016 -Prof Marvin Reid
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0
N
Normal Weight for age
0
N
Low weight for age
L 0
N
Low weight for age
L 0
N
Low or Normal
weight for age
L
We
igh
t fo
r A
ge
March 2016 -Prof Marvin Reid
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STUNTING & ITS EFFECTS
Low height for age (4.8 % in children under 5)
Chronic or long term undernutrition
Associated with increased rates of illness, death, reduced
cognitive outcomes and school achievement, adult work
capacity, and increased cardiovascular risk and disease in
adulthood
Promotion of breast feeding, appropriate weaning foods; food
and micronutrient supplementations reduces prevalence of
stunting
March 2016 -Prof Marvin Reid
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BREASTFEEDING PRACTICES
AT 6WEEKS
March 2016 -Prof Marvin Reid
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2H
2O DOSE-TO-MOTHER
TECHNIQUE
March 2016 -Prof Marvin Reid
• The mother consumes
an accurately weighed
dose (30 g) D2O
• The D2O mixes with the
mother’s body water
• The baby consumes
D2O in its mother’s milk
• Saliva is sampled from
the mother and from
the baby for 2 weeks
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BREAST MILK INTAKE
13, 37%
22, 63%
Breast Milk Intake in Urban Mothers
Exclusive Breast Milk intake
Non-exclusive Breastmilk intake
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BREAST MILK
CONSUMPTION
March 2016 -Prof Marvin Reid
Variables Non-
Exclusive
Exclusive
Birth weight kg 3.2 (0.4) 3.4(0.3)
Breast Milk Intake
g
704+349 956+304
Total Protein from
breast milk g
1.15 (0.13) 1.23(0.25)
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weight for age z score
0 2 4 6 8 10 12-0.50
-0.25
0.00
0.25
0.50
0.75Non-Exclusive
Exclusive
Month
z s
co
re
Height for Age Z Scores
0 2 4 6 8 10 12-1.00
-0.75
-0.50
-0.25
0.00
0.25
0.50
0.75Non-Exclusive
Exclusive
Month
Z s
co
res
March 2016 -Prof Marvin Reid
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SEVERE CHILDHOOD
UNDERNUTRITION
March 2016 -Prof Marvin Reid Marasmus
Kwashiorkor
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GLUTATHIONE (GSH)
A tripeptide
composed of
glutamic acid,
cysteine and
glycine found in
millimolar
quantities in all
mammalian cells
O
O
OH
O
NH2
O
NH
SH
O
O
NH
OH
-Glutamate
March 2016 -Prof Marvin Reid
Cysteine
Glycine
+
+
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THE EFFECT OF CYSTEINE
SUPPLEMENT
March 2016 -Prof Marvin Reid
Conc
Alanine Cysteine0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
Supplement
mm
ol/
l
Synthesis
Alanine Cysteine0.00
0.25
0.50
0.75
1.00
Supplementm
mo
l/l/
d
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March 2016 -Prof Marvin Reid
Loss of oedema
Alanine Cysteine0
5
10
15
20
25
Supplement
days
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Prof Marvin Reid, MB BS, PhD
Sheppard et al 2017 EBioMedicine. 2017 Apr; 18: 274–280
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Prof Marvin Reid, MB BS, PhD
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URBAN RURAL
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STUDY DESIGN
Observational, longitudinal study (~2years)
2 sites: Urban (Kingston); Rural (St Mary).
Procedure
• Participants brought into clinic fasted, ~6a.m.
• Day 1
– Anthropometry, BIA
– REE
– Isotope dose & timed urine collection
– Blood pressure, blood draw
– Actical placement
• Day 6 & day 12 - Urine collection
• FFQ
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ADJUSTED ESTIMATES OF THE EFFECT OF LOCATION (URBAN-
RURAL) ON TIME SPENT IN DIFFERENT PA INTENSITIES
Characteristic
Sedentary
activities (minutes)
Light activities
(minutes)
Moderate &
vigorous activities
(minutes)
β
P-value
β
P-value
β
P-value
Total (U-R)*
19.4
0.48
64.1
0.003
-83.5
<0.0001
Males (U-R)*
33.9
0.34
110.6
0.002
-144.5
<0.0001
Females (U-R)* 11.2 0.80 8.8 0.69 -20.0 0.51
P-value (ANCOVA) represents the difference between urban and rural; Significant difference, p<0.05.
* U-R- difference in urban and rural participants. Adjusted for age, sex, weight and education level.
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CARBOHYDRATE INTAKE BY LOCATION AND SEX.
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FAT INTAKE BY LOCATION AND SEX.
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DIFFERENCES IN PROTEIN INTAKE BY LOCATION AND SEX.
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DIETARY INTAKE IN
JAMAICANS
There are no major differences in the dietary patterns between
persons living in rural and urban communities and in both
communities vegetable and fruit consumption are low.
90% of Jamaicans eat less than the recommended three
servings of either fruit or vegetables in a day
March 2016 -Prof Marvin Reid
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OBESITY
Diet Physical
Activity
March 2016 -Prof Marvin Reid
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March 2016 -Prof Marvin Reid
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NUTRITION TIPS THROUGH
LIFE COURSE
In Infancy – breastfeed for minimum 6 months.
Weaning food needs to be energy dense
Elderly – Sarcopenia - A dietary protein intake of 1.0-1.2
g/kg & weights training
Obese =that low-carbohydrate (<20% of total energy)
interventions led to significantly greater weight loss
than did low-fat interventions
Specific Nutritional Interventions
Reduce Systemic Inflammation
Reduce Oxidative Stress
Modify the metabolism of hormones eg estrogen
March 2016 -Prof Marvin Reid
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PUBLIC HEATH MEASURES
Infant Policy with appropriate laws to
support breastfeeding
Collaboration of Government & Industry to
promote “healthy” foods to children,
pregnant mothers
Ensuring access to balanced nutrition for
Pregnant Mothers
Physical environments to promote activity
March 2016 -Prof Marvin Reid
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CHANGE IN PHYSICAL
ACTIVITY LEVELS
Prof Marvin Reid, MB BS, PhD
August 2014
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JHLS2 & NEIGHBOURHOOD
•There was significant clustering in PA, overweight/obesity, and DM
across Jamaican neighborhoods with neighborhood characteristics
having a greater effect in women.
•Greater levels of neighborhood disorder, home disorder, and
counterintuitively recreational space availability were associated
with higher levels of low/no PA among women.
•Better levels of neighborhood infrastructure were associated with
overweight/obesity in men.
Prof Marvin Reid, MB BS, PhD
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SYSTEM FOR OBSERVING PLAY AND
RECREATION IN COMMUNITIES (SOPARC)
August
2014
Prof Marvin Reid, MB BS, PhD
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THANK YOU
August
2014
Prof Marvin Reid, MB BS, PhD