Prof Marvin Reid, MB BS, PhDconference.src.gov.jm/wp-content/uploads/2018/12/... · “The main weapons in the prevention and treatment of disease and human carelessness ... prevention

Prof Marvin Reid, MB BS, PhD

THE END


“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

OBJECTIVES

Screening & Treatment – Sickle Cell Disease

Nutrition, Epigenetics & Personalized

Medicine

Treatment – Diet & Physical Activity


DIAGNOSTIC-TREATMENT

CONTINUUM

Awareness & Accessing

Care

Clinical Evaluation diagnosis &

Staging

Access to treatment


Not AI or Robotics

Screening Programmes

Point of Care Testing

WHO RECOMMENDATION



NEONATAL SCREENING -PRACTICE

Cord Blood – Guthrie cards

• Transported to CAIHR

Initial Diagnostic

• HPLC Electrophoresis

Follow-up

• IEF

JAMAICA

Sickle trait ~400,000

Sickle Births ~240/year

~2.9M

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

Prof. Marvin Reid 10

Strokes in SCD

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

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

TRANSCRANIAL DOPPLER

ULTRASONOGRAPHY

PREVALENCE OF TCD GROUPS

80%

13% 7%

TCD Group

Normal Conditional Abnormal

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

CHRONIC TRANSFUSION

Effective in primary and secondary prevention of stroke

In Jamaican context - Not an option • Cost –(transfusion, extended matching, iron

chelation)

• Safety

• Availability

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

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

PROBABILITY OF RESTROKE ON HU

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.

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

HU PROTOCOL

Start 15mg/kg

↑ 5 mg/kg q8wks

until MTD

Use weekly

cumulative dosing

when using capsules

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)

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

HUMAN NUTRITION

March 2016 -Prof Marvin Reid

Nutrition

Environmental Intrinsic


• Genes

• Gene Expression (Epigenetics)

• Life stage

• Mood

• Appetite

• Lifestyle

• Symbiosis

• Disease

• Culture & Personal Beliefs

• Food access/security

• Economic

• Food preparation

• Climate

• Government policies

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


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.


TYPES OF EPIGENETIC

CHANGES


N N N N

mRNA

Protein Molecule

Transcription

Translation

N N N N N N N N

Gene 1 Gene 2 Gene 3

Chromosome

GENETICALLY IDENTICAL

3-MONTH-OLD AVY

MICE SPANNING A FIVE COAT COLOUR

PHENOTYPE (FROM DOLINOY ET AL., 2007)


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.


Fig. 1

EBioMedicine 2016 5, 68-73DOI: (10.1016/j.ebiom.2016.02.008)

Copyright © 2016 The Authors Terms and Conditions

http://www.elsevier.com/termsandconditions



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



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


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


BREASTFEEDING PRACTICES

AT 6WEEKS


2H

2O DOSE-TO-MOTHER

TECHNIQUE


• 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

BREAST MILK INTAKE

13, 37%

22, 63%

Breast Milk Intake in Urban Mothers

Exclusive Breast Milk intake

Non-exclusive Breastmilk intake

BREAST MILK

CONSUMPTION


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)

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


SEVERE CHILDHOOD

UNDERNUTRITION

March 2016 -Prof Marvin Reid Marasmus

Kwashiorkor

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


Cysteine

Glycine

+

+

THE EFFECT OF CYSTEINE

SUPPLEMENT


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


Loss of oedema

Alanine Cysteine0

5

10

15

20

25

Supplement

days


Sheppard et al 2017 EBioMedicine. 2017 Apr; 18: 274–280


URBAN RURAL

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

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.

CARBOHYDRATE INTAKE BY LOCATION AND SEX.

FAT INTAKE BY LOCATION AND SEX.

DIFFERENCES IN PROTEIN INTAKE BY LOCATION AND SEX.

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


OBESITY

Diet Physical

Activity



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


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


CHANGE IN PHYSICAL

ACTIVITY LEVELS


August 2014

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.


SYSTEM FOR OBSERVING PLAY AND

RECREATION IN COMMUNITIES (SOPARC)

August

2014


THANK YOU

August

2014


Documents

Prof Marvin Reid, MB BS, PhDconference.src.gov.jm/wp-content/uploads/2018/12/... · “The main weapons in the prevention and treatment of disease and human carelessness ... prevention