RISK

What does risk mean?

Smoking is the risk factor for lung cancer, it is not necessarily a cause but it is usually associated with that disease, so we cannot confirm that one risk factor is the cause of that disease, but it is associated, and we know that people who are heavy smokers eventually they develop lung cancer, so we can say that smokers or smoking is a risk factor.

Risk is the probability of some untoward event, untoward means unwanted.

Lung cancer is an untoward event.

Definition The probability that people who are exposed to certain risk factors will subsequently develop the disease more often than similar unexposed people.

So risk is a probability, it is an estimation ,it is a probability that people who are exposed to certain risk factor like smoking will subsequently develop a disease like lung cancer. These people will develop diseases more often than similar people, same age same food same environment, but are unexposed, so thats why people who are exposed will develop the problem more often than the people who are not exposed.
Smokers will develop lung cancer more often than people who are non smokers although both of these people or both of these groups are similar in the environmental things except for the smoking.

Risk factors Factors associated with an increased risk of becoming diseased

Slide3: This lecture The lecture describes how estimates of risk are obtained by observing the relationship between exposure to possible risk and the subsequent development of the disease; we have two ways for that: Looking forwards

If we want to do a research which will start at the present and will progress in the future, we are looking forward.

Looking backwards

We can check the record of a patient, and check the files of the patient for example from the year 2000 till the year 2010 and see those who develop cancers among smokers, so this is looking backward .

Looking forward is called prospected research, looking backward is called retrospective. (Dis cussed la ter on)

Slide4: Risk Factors Physical environment factors Toxin, infectious agents, gas, pollutants

Toxin like smoking, the tar presents in the cigarette; tar is a toxin, so it is a risk factor Social environment factors Emotional illness, stress, loss of family members, culture

Emotional illness, stress: Sometimes if you are in a bad mood or if you have some stress you may develop ulcers in the mouth, like students who are under stress like in the exams, so we say here that emotional stress is a risk factor for ulcer. Cultural problem: if you move to a western country you will be shocked, we call this cultural shock because this is a new environment, so you may develop some diseases, you may develop some ulcers in your mouth for example because of this shock, so this is the effect of cultural change. 2

Behavioral factors Smoking, driving without seat belts, inactivity

Driving without seat belts: is a risk factor for death because of car incidence, although that is not a disease by itself but it is a bad behavior practiced by some people that lead to death or problems or to incidence Etc Inactivity: people who dont make activity or exercises, this is the risk factor for developing extra weight, obesity is a risk factor for diabetes, high cholesterol etc

Inherited factors, Sometimes you do nothing but you get the risk factor from your parents Diabetes, cholesterol, triglyceride Slide5: Exposure to risk factors

The exposed person Has come in contact with risk factor Or has manifested the factor in question

Cervical caries is a risk factor for periodontitis, so he developed caries at the cervical margin of the enamel which lead to peidontitis, so because he manifested the factor which is caries we say that he is not in contact, he manifested the factor. But being in contact is something else, like smoking you are in contact with smoking.

Before becoming ill

Smoking is a risk factor till the person develops lung cancer .

Duration of exposure At a single point in time Example: nuclear bomb in Hiroshima Over a period of time Example: smoking

Slide6: Amount of exposure Relevant questions As it is common in our dental practice we collect information about smoking, because we know that smoking is an important factor effecting oral problems like gingivitis or periodontitis, or leading to squamus cell carcinoma, so this is why we want to ask the patient about his habit. Ever been exposed Do you smoke? How long have you been smoking? Current dose How many cigarettes do you take per a day? Largest dose taken Have u been smoking a large quantity for a certain period of time? Some people have been a smoker for a long period of time, then they stop it, and then they return back smoking but they smoke at this moment less than what they have been smoking before, so we want to know the modification in the amount of dose. Total cumulative dose Years of exposure Years since first exposure When did you first start smoking? This is an important. So these are important thing which we have to collect information about.

Slide7: Measures of risk factor-disease relationship Exposure dose-disease relationship may not exist with all risk factors It is not necessarily that the relationship between the risk factor and the disease is very clear; sometimes the relationship between the risk factor and the disease is not clear Relationship: cumulative doses of sun exposure & non-melanoma skin cancer

We know that the non-melanoma skin cancers, like basal cell carcinoma or squamus cell carcinoma, is related to the amount of sun exposure, and this is a true relationship, the more sun exposure that you have been exposed to the more become the potential to develop skin cancer, so the relationship is linear in this case, people who stay for a long period of time at the beaches and are exposed to direct sun lights have a potential of developing skin cancer, this relationship is very clear. 4

No relationship: episodes of severe sunburn & melanoma

Melanoma is related to episodes of severe sun burn, if you are subjected to sun lights not for a long period of time but for episodes, let say for fifty times, but in these fifty times you were exposed to very very big amount of sun light, so in this case we say that this relationship is not clear, it is not linier.

Thus, correct measure has to be chosen to confirm the association between risk factor and disease We have to know the correct major, and how to measure the relationship, we have to know whether the relationship is leaner or not, whether it is clear or not.

Slide8: Choice of appropriate measures Based on Clinical and biological effects Pathophysiology of the disease Previous epidemiological studies

We have previous researches, so we may know that many researches about the association between smoking and lungs cancer were done in certain population, and they proved that for example smoking is a risk factor for lung cancer, so I know that when my patient that I am treating now is a heavy smoker and he may develop lung cancer. So I will warn my patient that you have to stop smoking, and that is why we have to look for previous epidemiological studies.

Slide9-16: Recognizing risk It is easy to recognize the association of acute disease and risk factors clinically Examples: radiation, sunburn, acute poisoning
Acute poisoning: like when you ate shawerma, and the mayonnaise was poisoned, and after few hours you were admitted to the hospital, so the association is very easy here, shawerma was the risk factor for poisoning, so this is acute.

It is more difficult to establish association between risk factors and chronic conditions clinically

WHY? Because 1. 2. 3. 4. 5. 6. Long latency period between exposure and disease Frequent exposure to risk factors Low incidence of disease Small risk from exposure Common disease Multiple causes of a disease 1-Long latency period between exposure and disease Chronic diseases have long latency period between the exposure and the 1 st manifestation of the disease It might be years later E.g., Hypertension & heart disease

Hypertension and heart disease, some people may develop hypertension at the age of forty, but the first sign of cardiac problem developed at the age of sixty, so we have a big latency period between the onset and the development of the disease.

The original exposure might be forgotten The link between the disease and the risk factors is not readily clear
You have hypertension but not at a very high levels, let's say 140 over 95, and you got this hypertension at the age of 35 and you are living your live normally, and at the age of 65 you have heart attack or angina pectorals lasama7alla, sometimes you may not remember that you have something related to the disease, like hypertension, because it is minimal and because it affected you long period of time.

2-Common exposure to risk factors Common risk factors Smoking, cholesterol in Heart disease

Sometimes we may have other factors leading to heart disease, but because we have very common risk factor like smoking and cholesterol, all the time we think about these risk factors, and we dont think of the others possible risk factors that have less potential.

Comparing patterns of disease between Those with the risk factors Those without the risk factors (certain population subgroup s) E.g., All Mormons (no smoking) E.g., Vegetarians (no fat diet)

Mormons are special groups of Christians, by these people smoking is inhibited, so none of these people are smokers, for this reason we can study on them the effects of risk factors on heart disease, other than smoking. Muslims dont drink alcohol, so we can study the effect of factors other than alcohol on carcinoma, or on liver cirrhoses. Vegetarian, they dont eat meat so we can study the effect of factors other than cholesterol the development of heart disease, so if we have a vegetarian person that developed cardiac problem, we dont have to think of about the effect of cholesterol because we know that this person Is a vegetarian he doesnt eat meat, so on this person we have to look for other reasons other than cholesterol that actually produced heart attack on him.

Comparisons through cross-sectional studies, It is very important to compare people that are subjected to risk factors with people that are not subjected to risk factors . Investigating subgroups with low exposure to risk factors gives more information about the true risk-disease association 3-Low incidence of disease The incidence of diseases is very low (even with common diseases) Lung cancer in heavy smokers is 2/1000
Lung cancer which is one of the common diseases is not as common as caries for example; here in this theater we may find 80 of you who have caries but lung cancer even we said that lung cancer is common we find 2 cases in 1000.

Doctors might witness some rare disease once or few times in their practice
I have been e dentist for 12 years and up till this moment I have seen let's say more than 10000 patient but I have not seen a patient with cancer yet because cancer is a rare disease.

It is difficult to draw a conclusion about infrequent events

4-Small risk Chronic disease caused by several risk factors acting together
Cardiac problems or congestive heart failure is caused by six risk factors, hypertension is one, smoking is two, diabetes obesity etc, so this problem is not caused by one single risk factor we have more than one risk factor acting together.

The risk of a single factor alone is very small

If I exclude all the risk factor and I kept only high cholesterol, high cholesterol is not a strong factor in developing the disease by itself, but if u have a high cholesterol level and you are a smoker and you have diabetes etc it is very likely that you will develop heart disease.

If the risk is small, then large number of cases is needed to demonstrate the association of disease and risk factors Example: coffee and heart diseases

People who are addicted to coffee and may develop heart disease is very rare, we may see one case in one million people, so how can we study the effect of coffee on heart disease if we only have one or two cases, so you need a large number of cases, so thats another reason why sometimes it is difficult to study the relationship between the disease and risk factor in chronic disease.

If the risk is high you can establish conclusion easily Hepatitis B and hepatoma

People with hepatitis B may easily develop hepatoma (cancer in the liver), so in this condition, you know that hepatitis B is the strongest factor, so if you take 1000 cases with hepatitis B you will have a good number of people having hepatoma, so this is a good relationship.

5-Common disease If the disease is ordinary or commonly occurring and its risk factor is already known There is no incentive to find new risk factors

Heart disease is caused by six factors, no need to search for minor ineffective factors, so we dont study the relationship between these less effective risk factors and the disease, because we have more common risk factors.

If the disease is rare, careful investigation about risk factors are carried out 6-Multiple causes and effects There is no one-to-one relationship between a risk factor and a disease E.g., Hypertension & CHD(coronary heart disease)

Can you confirm that any person with hypertension develop CHD? NO. One-to-one: if I shoot you, you will die. :O

Some people with HT develop CHD while others dont Some people without HT develop CHD

Multiple risk factors for each particular disease Dental caries is a multifactorial disease Bacterial Carbohydrate Host factor TIME

So it's not easy to study caries. Slide17-22: Uses of risk

1. 2. 3. 4. 5.

Prediction of the occurrence of disease Search for cause Diagnosis Screening Prevention

1-Prediction of the occurrence of disease The quality of prediction depends on similarity of an individual patient with A large number of patients Who have past experience of the condition With similar risk factors
If I know that smoking causes lung cancer, I can predict that the patient that I am treating now who is a heavy smoker may develop lung cancer .

On an individual level, presence of a strong risk factor does not mean that the person is very likely to get the disease Prediction is expressed as a probability No better way than to use probability to guide clinical decision making at the individual level
We cannot confirm that this smoker will develop lung cancer, but prediction is the best way to give information about the probability, so it is a probability guide for making a decision.

2-Search for cause Search for risk factor is search for cause Causes Immediate. E.g., virus infection
Immediate: virus is the risk factor of infection, and also virus causes infection, so it is a risk factor and at the same time it is also a causal factor.

Distant. E.g., maternal education low birth wt

Distant: maternal education and low birth weight, it is not a direct relationship, mothers who are none educated, their babies will have low birth weight, because they dont look after their babies while they are pregnant, it is not a direct relationship, but it is an indirect one.

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A risk factor predicting disease is not necessarily a causal factor

When we say that smokers will develop lung cancer, can we say that smoking causes lung cancer? NO, it is difficult, but at least we say heavy smokers are associated with having lung cancer, so we cannot confirm that it is a cause. But we can say that virus is a risk factor for infection, so virus is the cause of infection, because up until this moment we they are studying the effect of smoking on lung cancer, so they dont know exactly what smoking does, so in this case they dont say that smoking causes lung cancer, but smoking is associated with lung cancer, so that is why the non casual risk factor is called marker.

Marker: non-causal risk factor Risk factor may mark the disease outcome indirectly It is called marker because it marks the increase probability of the disease

Smoking on lung cancer, or hypertension on heart disease, it is not a cause of heart disease, it is associated in increases the probability to develop disease.

3-Diagnosis The presence of a risk factor increase the probability that a disease is present Therefore, knowledge of risk factor can be used in the diagnosis process

The absence of risk factor helps to rule out a disease Absence of high fluoride intake rules out fluorosis and strengthens other possibilities

When you are examining your patient, and you notice that your patient have hypominiralization and hypoplasia, and you know that one common cause of hypominiralization and hypoplasia is fluorosis, you ask your patient where he is living, and you confirm that he is not living in an area where he had been using water with high flourosis when he was young, because of that you can rule out flourusis. And that is how I rule out fluorosis from my own practice, I ask my patient and my patient says no I live in irbid or I used filter water or I have been using filter water all my live , so I start thinking of other causes of hypominiralization and hypoplasia . 11

4-Screening Knowledge of risk factors improves the efficiency of screening programs By selecting subgroups at high risk E.g., Risk of breast cancer is high among women with affected young women relatives

When a woman has relatives with breast cancer at young age, I know that this woman is at risk, so I start screening this woman, I start to ask this woman to come to the hospital and I do investigation to check that she doesnt have breast cancer, this is called Screening.

5-Prevention Removal of risk factor can prevent the disease regardless whether or not the mechanism of action of the risk factor in known Stopping drinking of certain water (risk factor) prevents cholera infection in people

I can prevent the disease when I know that these people who had drinking certain water for a long period of time always develop cholera, and I ask these people to drink something else, so I started to prevent people from cholera.

Stopping water with F > 1 ppm prevents fluorosis

I start examine a child who is ten years old and I found fluorosis, so I ask his family and they say yes we actually drink out of a spring, or a small river that they have, and it is high in fluoride, so I start advising this family not to use the same water in order to prevent the disease.

Slide23: Studies of risk We want to study a risk by conducting an experiment, to determine whether exposure to a potential risk develops disease So I have to do a research in order to know if the exposure to a certain risk factor develops a disease or not, and I have to study the effect, Is it a cause or a marker. When you remember we took this type of studies, and we called it randomized studies, or experimental studies.

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People without disease divided into 2 groups One subjected to risk factor The other group is not, and then we compare the results Otherwise the 2 groups are treated the same Slide24: When arent experiments possible? Unethical to impose hazardous risk factors on healthy people for the purpose of a scientific research
Can I collect two groups and ask one group to smoke and the other not to smoke, and then study the effect of smoke on lung cancer? NO, it's not ethical.

People hate to have their behavior modified by others for long period of time, So even if you are not exposing your subjects to risk factor, they maybe become unhappy in being in a research for a long period of time, so they just drop out. Experiments can be expensive to run This type of study is better in dealing with bias (it minimizes bias) but it is not always possible, therefore, the choice goes in these situations towards observational studies Slide25: Observational studies We discussed this type of study before. Are clinical studies in which the researcher gathers data by simply observing events as they happened. Have more potential for bias than experimental studies Most studies of risk factor are observational and not randomized studies, because we cannot expose people who are healthy to risk factors . Types Cohort studies Case-control studies

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Slide26-36: Cohort studies Cohort: a group of people with something in common in assembly (when we assemble them) who are observed for a period of time to see what happens to them. Two condition to conduct cohort study They do not have the disease at the time they are assembled, when we start our research they should be healthy and free of the disease.
In the quiz that I gave you, there was a question about the incidence, I asked you about women with cervical cancer, and at the beginning of the research there was 10% who already had the disease, so you should exclude them, if you want to study the incidence, so cohort study can be used to examine the incidence of a disease.

They should be observed for a meaningful period of time in the nature history of the disease in question, Enough time for the risk to be expressed All member of the cohort should be observed over the full period of time
I want to study the effect of smoking on lung cancer, so I bring one thousand people for example and none of them should have lung cancer at the beginning, and I examine these people for ten years for example, and all subjects should remain from the begin of the study until the end of it.

These are the factors that we use in cohorts, like for example the age , date of birth, exposure, disease, prevention and intervention and therapeutic intervention, these are factors that you have to control at the beginning of your study, it is important that they have similarities, the only difference between these people is the exposure to risk actor otherwise they should be the same. 14

People assembled has not experienced the outcome but have equal susceptibility to develop the outcome
The people that belong to your group should have equal chance of developing the risk factor. You cannot bring women who have removed their uterus to include them to study cervical cancer, because these women will not have the possibility of, so that is why you have to exclude these people from your study.

People are then observed over a period of time Examine which people experience the outcome Other synonyms Incidence studies Longitudinal studies Prospective studies

Types of cohort studies Concurrent (prospective) Historical (retrospective)

I want to see the effect of cariogenic food on caries, I can have my groups at present and I have to follow them up for the future (prospective). Or I can go back to the files of the patient starting from the year2005 and then to see what happened in their file, and what the doctors have provided, and what treatment they were receiving from 2005 till 2010, if you want to do a research in the past you dont see the people you just have to see the records of them (retrospective). 15

Concurrent cohort The group of people (cohort) are assembled in the present and followed in the future The data are collected for the purpose of the study with full anticipation of what is needed

Bias can be avoided Accuracy can be increased, because you can control bring the people and follow
them up in the future.

Historical cohort studies Cases are assembled in the past and followed forward to the present The data are collected from available past records of patients Data may not be of sufficient quality for rigorous research
Because here you cannot control these people, you are just looking for the history, you dont have any control on that.

Example: study cohort using dental records

The dr. started reading without explaining: Advantages of Cohort studies The only way of establishing incidence directly Can assess the relationship between exposure and many diseases Best substitutes for true experimental studies when not possible Follow the same logic as a clinical trial Allow measurement of exposure to a risk factor Avoid bias because the unknown but expected outcome develops after exposure to risk factor not vice versa
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Disadvantages of cohort studies Need large number of people at risk The people must remain under the study for a long period of time Cannot be used for rare diseases Expensive to run Subjects are free living and not under control as in experimental studies Expensive to keep track of them Need resources employed for a long time Usually limited to life-threatening diseases to justify the big budget

Dr. ashraf shaw eesh, thanx for every thing Done by your colleague: Ammar anagreh Good luck in your finals

THE END

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