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    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

    Theprobabilitythat people who are exposed to certain risk factors willsubsequently 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

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    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 forwardsIf we want to do a research which will start at the present and will progress

    in the future, we are looking forward.

    Looking backwardsWe 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 developcancers among smokers, so this is looking backward.

    Looking forward is called prospected research, looking backward is called

    retrospective. (Discussed later 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, cultureEmotional 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 thisshock, so this is the effect of cultural change.

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    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 fromyour parents

    Diabetes, cholesterol, triglycerideSlide5: 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 thecervical 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 illSmoking 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

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    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 exposedDo you smoke? How long have you been smoking?

    Current doseHow many cigarettes do you take per a day?

    Largest dose takenHave 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 cancerWe 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.

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    No relationship: episodes of severe sunburn & melanomaMelanoma 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 inthis 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, andthey 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

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    WHY? Because

    1. Long latency period between exposure and disease2. Frequent exposure to risk factors3. Low incidence of disease4. Small risk from exposure5. Common disease6. Multiple causes of a disease

    1-Long latency period between exposure and disease

    Chronic diseases have long latency period between the exposure and the 1st

    manifestation of the disease

    It might be years later

    E.g., Hypertension & heart diseaseHypertension 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 diseaseSometimes 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.

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    Comparing patterns of disease between

    Those with the risk factors Those without the risk factors (certain population subgroups) 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 2/1000Lung 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

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    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 diseasesPeople 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 largenumber 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 hepatomaPeople 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 havinghepatoma, so this is a good relationship.

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    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 factorsHeart 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. Prediction of the occurrence of disease2. Search for cause3. Diagnosis4. Screening5. Prevention

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    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 infectionImmediate: 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 wtDistant: maternal education and low birth weight, it is not a directrelationship, 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 processThe absence of risk factor helps to rule out a disease

    Absence of high fluoride intake rules out fluorosis and strengthens otherpossibilities

    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.

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    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-PreventionRemoval 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 cholerainfection 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 riskfactor 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, whenwe 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 naturehistory 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 oftime

    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 otherwisethey should be the same.

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    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 yo u dont see thepeople you just have to see the records of them (retrospective).

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    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 everything Done by your colleague:

    Ammar anagreh

    Good luck in your finals

    THE