Developments in Personalised Medicince

Question 1

Define personalised medicine

Answer 1

The concept that managing a pateint’s health should be based on the individual patient’s specific charcateristics, including age, gender, height/weight, diet, environment etc

Question 2

Define stratified medicine

Answer 2

The process by which therapies are matched with specific patient population charcateristics using clinical biomarkers

Question 3

Define predictive medicine

Answer 3

A rapidly emerging field that entails predicting disease and instituting preventive measures in order to either prevent the disease altogether or significantly decrease its impact upon the patient

Question 4

Define theranostics

Answer 4

Term used to describe the proposed process of diagnostic therapy for individual patients

Question 5

Define pharmacogenetics

Answer 5

The study of clinical testing of genetic variation that gives rise to differing response to drugs

Question 6

What is the scope of personalised medicine?

Answer 6

Treatment efficacy in specific patients
Determine optimal drug dosages
ID of patients who may suffer severe adverse drug reactions
Assess the extent or progression of disease
Examine surrogate measures for clinical outcomes
Identify patients who can benefit from specific preventative measures

Question 7

What are the characteristics of a poor responder?

Answer 7

Decreased absorption
Increased metabolism/reduced pro-drug activation
Increased clearance/competition for transport molecule
Impaired receptor response
Reduced intracellular effects

Question 8

What are the characteristics of an ADR?

Answer 8

Increased absorption
Accumulated toxic metabolites
Reduced clearance
Increased receptor response
Enhanced intracelullar effects

Question 9

What are the two categories of drug metabolising enzymes?

Answer 9

Catalytic-mainly oxidative

Conjugative

Question 10

What sort of metabolisers are those homozygous for CYP2D6?

Answer 10

Poor metabolisers

Question 11

What sort of metabolisers are those heterozygous for CYP2D6?

Answer 11

Intermediate metabolisers

Question 12

What sort of metabolisers are those who have gene duplications for CYP2D6?

Answer 12

Ultrarapid metabolisers

Question 13

What are the substrates for CYP2D6?

Answer 13

Anti-depressants
Anti-psycotics
Anti-arrhythmics
Beta-blockers
Anti-hypertensives

Question 14

Why are immunsuppressants needed?

Answer 14

Untreated, the body will identify new tissues as ‘non-self’ this will lead to an immune response producing IL-2 and rejection of the organ

Question 15

Describe chronic allograft dysfunction

Answer 15

Usually a gradual process, although both the time of onset and the rate of progression vary
May develop as early as within a few months of the transplant or it may emerge after several years
Course is generally unremitting and ultiately leads to total loss of graft function, necessitating re-transplantation or a return to dialysis

Question 16

Describe acute rejection

Answer 16

Usually first few weeks after transplantation but can occur at any time if the level of immunosuppression becomes inadequate
Cell-mediated response leads to injury or destruction of the funtioning cellular structures of the transplant
Reversible

Question 17

What is involved in triple therapy?

Answer 17

A calcineurin inhibitor
An antiproliferative agent
A corticosteroid

Question 18

What does Thiopurine Methyl Transferase (TpMT) do?

Answer 18

Metabolises Azathioprine

Question 19

What are the effects of TPMT deficiency?

Answer 19

Profound bone marrow suppression- opportunistic infections, sepsis, death
Gastrointestinal effects- Nausea, vomiting, abnormal liver function

Question 20

What are the complications of long-term immunosuppression?

Answer 20

Infection
Cancer
CVD
Recurrent disease
Toxicity
Hirsutism

Question 21

In which patients are BCCs most common?

Answer 21

White and fair-skinned

Question 22

What is the ratio of incidence of BCC:SCC in normal patients?

Answer 22

4:1 ratio of BCC;SCC

Question 23

What is the ratio of incidence of BCC:SCC in transplant patients?

Answer 23

4:1 ratio of SCC:BCC

Question 24

What is the behaviour of NMSC in a normal patient?

Answer 24

Usually 1-2 lesions per person
Grow slowly
Rarely metastasise
Low mortality

Question 25

What is the behaviour of NMSC in a transplant patient?

Answer 25

``` More aggressive behaviour Present earlier More numerous Grow more reapidly Metastasise earlier ```

Question 26

What are the clinical risk factors of NMSC associated with UV?

Answer 26

Latitude- incidence much higher in hot countries Exposure- outdoor exposure, sunbathing habits, cumulative sun exposure, holidays abroad Host response- gender, skin typ, eye colour, hair colour Premalignant lesions Burning in childhood

Question 27

What are the clinical risk factors of NMSC associated with immunosuppression?

Answer 27

Degree Regimen Duration

Question 28

What are the clinical risk factors of NMSC associated with chemical exposure?

Answer 28

Smoking- ever vs never, how may packs? | Arsenic exposure

Question 29

What are the clinical risk factors of NMSC associated with genetic factors?

Answer 29

``` UV-induced oxidative stress Melanisation Immune modulation Detocification of smoking derived chemicals Cell-cycle control ```

Question 30

How would you go about developing a screening strategy for newly transplanted patients?

Answer 30

Use tumour latency as an end point Check individual parameters for significance Applying a step-wise model to generate significant set of predictors Dichotomisation Generating the predictive index Simplifying the index Grouping PI scores to generate screening groups Model validation

Question 31

What are the screening groups for NMSC and their parameters?

Answer 31

PI7 - Frequent (6 months)