Epidemiology

·         John M Last: gave definition of EPIDEMIOLGY- Distribution, determinants, &Frequency of any event.

·         The roots of EBM date to the late 1970s, when a group of clinical epidemiologists, led by David Sackett and his colleagues at McMaster University, began preparing a series of articles advising clinicians how to read clinical journals and apply evidence from the literature to direct patient care.

·         The term EBM was first used by Gordon Guyatt, MD, in 1990 while serving as residency director of the internal medicine program at McMaster.

·         Galen, the great second century physician and anatomist, described wounds as "windows to the body".

·         John Graunt: A self-educated London businessman who, around 1620, noted the wealth of potentially important information available in London's Weekly Bills of Mortality. Graunt began collecting and tabulating the data. In 1662, he published Natural and Political Observations, based on his examination of the Bills of Mortality. This was the first use and publication of a record of vital statistics.

·         Thomas Sydenham was called the English Hippocrates.

·         De Morbis Artificum Diatriba, Written by Ramazzini and published in 1700, it is the first comprehensive work about occupational diseases. He is k/as Father of Occupational Health.

·         Edward Jenner: developed and tested an immunization for smallpox

·         Walter REED demonstrated that Yellow Fever was transmitted by the Aedes mosquitoes.

·         P. C. A. Louis: called "the father of modern clinical epidemiology," he was responsible for the landmark study of the noneffectiveness of bloodletting

·         Ignac Semmelweis: dramatically reduced the rate of childbed fever by the institution of hand-washing

·         Sir Percival Potts was an English surgeon who identified a high rate of scrotal cancer in chimney sweeps.

·         Alfred Grotjahn of Berlin gave the concept of Social Medicine. He gave importance of social factors in the etiology of disease which he called Social Pathology. (jahan=society)

·         The stem-and-leaf diagram, invented by John Tukey, is a unique method of summarizing data without losing the individual data points.

·         The concept of apparent and inapparent infection was conceived by Dr. Charles Jules Henry Nicolle recipient of the 1928 Nobel Prize in Medicine. While conducting research on guinea pigs he had infected with typhus, Nicolle made a rather astonishing discovery: some of the infected guinea pigs, despite displaying no apparent typhus symptoms, were capable of spreading the disease. Today we more commonly term apparent and inapparent infections as symptomatic or asymptomatic infections.

·         Karl Friedrich Gauss (1777-1855) was one of the foremost mathematicians of his time, advancing discoveries in number theory, algebra, geometry, probability, and other areas.

·         Naming of Student's t-test: Copyright laws established by his employer (Guinness Brewery) prevented William Gossett (1876-1937) from naming one of the most commonly used statistical tests after himself. Instead of naming this useful tool Gossett's test, he used the pseudonym "Student" when he wrote his description in 1908 of the t-distribution and what he called the Student's t-Test. As the Guinness Brewery quality control engineer, Gossett used his new t-procedures to compare batches of stout and solidified his employment by helping the brewery produce the cheapest and best beer possible.

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·         IMPORTANT PLACES

1. Broad Street, London: site of John Snow's important research on cholera.
2. Cuba (1898): Walter Reed conducted important research on yellow fever.
3. Tuskegee, Alabama: site of the infamous "Tuskegee Study of Untreated Syphilis in the Negro Male."
4. Framingham, Massachusetts: site of the Framingham Heart Study.

·         1.  Typhoid Mary's name: Mary Mallon.

2.  Devonshire colic: lead poisoning contracted from drinking cider made in Devonshire, where the presses were lined with sheets of lead.

3.  Soot-wart: the name for scrotal cancer common in chimney sweeps in London in the 1700s.

4.  Gaetan Dugas: A Canadian airline steward falsely thought to be the initial case of AIDS in the United States.

·         Muerto Canyon virus is now better known as the sin nombraue virus and the etiologic agent in hantavirus pulmonary syndrome. The disease first came to light when a young, healthy Navajo man living in the southwestern United States became short of breath and rapidly died. His fiancée had died 2 days previously. Researchers documented numerous other cases, and the CDC's labs were able to pinpoint an unknown type of hantavirus.

·         World's largest telephone survey: The Behavioral Risk Factor Surveillance System (BRFSS), which tracks health risks in the United States. The BRFSS questionnaire is designed by a group of state coordinators and CDC staff.

·         Quarantine was first done for Plague.

·         Switzerland is member of WHO but not of UNO.

·         Franklin D Roosevelt , 32^nd President of USA had Poliomyelitis.

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·         Numbers are not reality; they are measurements which contains reality plus error.

·         components of the epidemiologic triangle: Host, agent, and environment

·         The denominator is key in epidemiology: who is "at risk" for a particular event or disease state.

·         Incidence: new cases coming IN

Prevalence: all cases

·         Morbidity rate: rate of disease in a population at risk; refers to both incident and prevalent cases

Mortality rate: rate of death in a population at risk; refers to incident cases only

·         The goal of modern medicine is not to wipe out the disease, but to increase the prevalence of the disease.

·         Remember that, in calculating incidence rate, denominator is the population AT RISK only and not that cured or dead or having the disease and not all population. (Ah.! Do you remember still that chart of USMLE)

·         point of optimum sensitivity = point of optimum negative predictive value

point of optimum specificity = point of optimum positive predictive value

·         Accuracy: total percentage correctly selected; the degree to which a measurement, or an estimate based on measurements, represents the true value of the attribute that is being measured.

Accuracy = (TP + TN)/ (TP + TN + FP + FN) =(true positives + true negatives)/total screened patients

·         Screening teat don’t give us INCIDENCE, they give us PREVALENCE.

·         Sensitivity & Specificity are PreTest Probabilty and they don’t change by prevalence.

·         PPV & NPV are PostTest Probabilty and change by prevalence. PPV & P are proportional; while NPV & P are inverse.

·         A positive skew has the tail to the right and the mean greater than the median. A negative skew has the tail to the left and the median greater than the mean. For skewed distributions, the median is a better representation of central tendency than is the mean.

·         If the given confidence interval contains 1.0, then there is no statistically significant effect of exposure.

·         The confidence interval of the mean can be calculated by: Mean +-  appropriate Z-score x standard error of the mean =X +- Z (S/ rootN)

·         We never accept the null hypothesis. We either reject it or fail to reject it. Saying we do not have sufficient evidence to reject it is not the same as being able to affirm that it is true.

·         If the null hypothesis is rejected, there is no chance of a Type II error. If the null hypothesis is not rejected, there is no chance of a Type I error.

·         Type I error (error of commission) is generally considered worse than Type II error (error of omission).

·         Power is directly related to Type II error: 1- beta = Power

·         A correlation coefficient indicates the degree to which two measures are related, not why they are related. It does not mean that one variable necessarily causes the other. There are two types of correlations.

Types of correlations

Pearson correlation: compares two interval level variables

Spearman correlation: compares two ordinal level variables

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·         According to the CDC, infectivity is the proportion of persons exposed to a causative agent who develop an infectious disease. Infectivity can be measured by secondary attack rate. Pathogenicity is the ability of an organism to cause a disease state (morbidity), whereas virulence is the ability to actually cause death (mortality). The virulence of a pathogen can be altered. For example, the discovery of penicillin in the late 1930s significantly reduced the mortality rate of pneumococcal bacteremia from about 90% to 10%.

·         Twin concordance study: Compare the frequency with which both monozygotic twins or both dizygotic twins develop a disease. Measures heritability.

·         Adoption study: Compare siblings raised by biologic vs. adoptive parents. Measures heritability and influence of environmental factors.

·         Precision is: 1. The consistency and reproducibility of a test (reliability)

2. The absence of random variation in a test

Random error––reduced precision in a test

·         Accuracy is the trueness of test measurements (validity).

Systematic error––reduced accuracy in a test.

·         The LR+ is simply the quotient of the sensitivity over the false positive rate. Note that both of these terms are not influenced by the prevalence; therefore, neither is the LR+.

·         LR- is the quotient of the false-negative rate divided by the specificity. Using the same logic as above, one can qualitatively appreciate that a low LR- is desired because this ratio represents "missed cases" (i.e., false negatives) over appropriately "ruled in" cases.

·         Diagnostic tests with very high sensitivity values are useful for ruling out a given disease or condition when the results are negative. This can be remembered by the mnemonic SnNout: a Sensitive test with a Negative result rules out a disease. Diagnostic tests with a very high specificity values are useful for ruling in a given disease or condition when the results are positive. This can be remembered by the mnemonic SpPin: a Specific test with a Positive result rules in a disease.

·         The NNT is a numerical expression of the number of patients needed to receive an active treatment to demonstrate a benefit over no treatment and prevent one bad outcome. It is a helpful measure used in making medical decisions about an individual patient when summarizing results of clinical trials. NNT is inverse the Incidence rate.

·         EVIDENCE-BASED MEDICINE (EBM)

1.       EBM integrates the current best evidence, clinical expertise, and patient values to optimize clinical outcomes and quality of life.

2.       EBM recognizes that the strength of evidence provided by the unsystematic observations of an individual clinician should not be viewed the same as the evidence provided by systematic and controlled clinical trials. In general, the strength of evidence increases with randomized controlled studies compared with that of observation studies.

3.       Electronic evidence databases, evidence-based journals, and online services are sources that most often provide the current best evidence.

4.       When using an article in the medical literature to answer clinical questions, three useful questions should always be asked: (1) Are the results of the study valid? (2) Is the evidence important? and (3) How can the valid and important results be applied to patient care?

5.        The tools of EBM are most frequently applied in examining clinical issues related to diagnosis and screening, prognosis, therapy, and harm.

·         RESEARCH MODEL DESIGNS

1. The two basic epidemiologic design strategies are the descriptive study design and the analytic study design.
2. Descriptive studies examine the distribution of diseases in populations; analytic studies examine the determinants of diseases in populations.
3. Descriptive studies include correlation studies, case reports, case series, and cross-section surveys.
4. Analytic studies include observational studies and interventional studies.
5. Observational studies examine how exposure to risk factors influences the probability of developing disease; in interventional studies, the investigator controls which treatment each subject receives.
6. Observational studies include cohort and case-control studies and are subject to selection and observation bias.
7. Randomized controlled trials, a type of interventional study, provide the most reliable evidence of treatment effectiveness.

·         Epidemiologists often look at risk in terms of the following:

Absolute risk: the magnitude of the disease risk in a group of people with a specific exposure.

Relative risk: the strength of the association between an exposure and a disease.

Attributable risk: the proportion of disease risk that can be attributed to an exposure.

·         SURVEYS AND SURVEILLANCE

1. Surveys are an effective way of gathering information, although they do not employ the scientific method.
2. Surveys are more likely to capture information about chronic or less severe disease processes.
3. The goal of surveillance is to prevent disease and injury.
4. Surveillance is a cornerstone of public health practice.
5. Baseline rates are made possible by surveillance data.

·         The World Health Organization (WHO) provides a wide range of useful information regarding numerous health programs throughout the globe. This data is best accessed by using either the World Health Organization Library Service (WHOLIS) or the World Health Organization Statistical Information Service (WHOSIS).

·         MEASURING RISK

1.       Absolute risk is probability of an event such as illness, injury, or death.

2.       An absolute risk gives no indication of how its magnitude compares with others'.

3.       The odds ratio closely approximates the relative risk if the disease is rare.

4.       The odds ratio and the relative risk are used to assess the strength of association between risk factor and outcome.

5.       The attributable risk is used to make risk-based decisions for individuals.

6.       Population attributable risk measures are used to inform public health decisions.

·         Stratum matching can be used to make the odds ratio more representative, in which the same number of cases and controls are drawn from each age/sex group. Another technique is to calculate the odds ratio for each group and then summate them.

·         To calculate the odds ratio in a case-control study with matched controls: OR= b/c

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·         Sullivan’s index: This index (expectation of life free of disability) is computed by subtracting from the life expectancy the probable duration of bed disability and inability to perform major activities.

·         Meta-analysis: Pooling data from several studies investigating the same hypothesis to achieve greater statistical power (not able to overcome methodological limitations or bias of an individual study).

·         P < 0.05: Probability is less than 5% that results have occurred by chance

·         Primary Prevention: Prevents the occurrence of disease (e.g., vaccination).

Secondary Prevention: Early detection of disease (e.g., Pap smear, mammogram).

Tertiary Prevention: Reduces disability from disease (e.g., insulin, rehabilitation).

                PDR: Prevent Detect Reduse disability

·         Reliability: A test or measurement produces the same result or score if remeasured.

Validity: A test or measurement truly measures what it is intended to measure.

·         The more prevalent a disease, the more will be its PPV.i.e., less will be it's False Positives.

Less prevalent more false positives.

---- As prevalence Increases --- PPV Increases ---- False +ve Decreases.

---- As prevalence Decreases -- PPV decreases ---- False +ve Increases.

·         Survival analysis is a statistical method for studying the time between an entry into a study and a subsequent event. Unequal observation time through censoring of the subjects under study makes survival analysis unique. Survival analysis is useful in making predictions about a population, comparing the effect of treatment between two groups, and investigating the importance of specific characteristics on survival.

·         Maximum allowable Attrition Rate in Cohort Study: 5%

·         OPEN TRIAL: when BLINDING is not done

·         Bias can be removed by BLINDING.

Confounding can be removed by Matching. (All things matched except RISK FACTOR)

In RCT, Placebo helps in reducing HAWTHARNE BIAS (kind of Subject Bias)

In RCT, RANDOMIZATION removes SELECTION BIAS (making both group comparable OR similar prognostic factors in both groups), known & unknown confounders.

·         Experimenter expectancy (Pygmalion effect): experimenter's expectations inadvertently communicated to subjects,who then produce the desired effects. Can be avoided by double-blind design, where neither the subject nor the investigators who have contact with them know which group receivesthe intervention under study and which group is the control.

·         Late-look bias: individuals with severe disease are less likely to be uncovered in a survey because they die first. Example:a recent survey found that persons with AIDS reported only mild symptoms

·         In CLINICAL TRIAL, only phase 3 is RCT (as controlled group is present-it is compared with best available drug)

GCP (Good Clinical Practice) is required in all phases of RCT. It is not required in PreClinical Trial.

·         Intention to Treat Trial: even results of EXCLUDED PATIENTS, PATIENTS WHO CHANGED GROUP are included. (by mathematical calculation) It is possible in RCT.

·         Hill’s Criteria aka Surgeon General’s Criteria.

A. B. Hill posed these criteria in 1965 as a list of standards, having adapted them from the U.S. Surgeon General's 1964 report on smoking and health. They serve as a general guide, and not all criteria must be fulfilled to establish causation. Although some of the criteria have been criticized in the past 40 years, they remain a reasonable framework through which to determine causal associations.

All of above studies give you ASSOCIATION b/w RISK FACTOR & DISEASE. Then wheather the RISK FACTOR is cause or not is decided by Hill’s Criteria of Causality.

Most imp criteria: TEMPORALITY

Most Difficult Criteria to Establish: Specificity

·         Nested Case Controlled Study is Cohort Study as it still maintains direction FORWARD.

It is a type of case-control study that obtains its cases and controls from a cohort population that has been followed for a period of time.

·         EVALUATION OF HEALTH SERVICES:

EffICAcy: in Ideal Controlled condition

Effectiveness: in real life/community

Efficiency: Input/Output (most imp for final output of programme)

·         MMR, Relative Risk, SAR: RATIO.

CFR, Prevalence: PROPORTION

·         10 steps of an outbreak investigation:

(1) Prepare for field work, (2) establish the existence of an outbreak, (3) verify the diagnosis, (4) define and identify cases, (5) describe and orient the data in terms of time, place, and person, (6) develop hypotheses, (7) evaluate hypotheses, (8) refine hypotheses and carry out additional studies, (9) implement control and prevention measures, and (10) communicate findings.

·         Although vaccinia and smallpox are both orthopoxviruses, they are different organisms. While vaccinia can cause serious reactions such as generalized vaccinia, which may look similar to smallpox, it does not cause the actual disease.

·         Effect modification is not a bias and should not be controlled.

Def: it occurs when the effect of the exposure is different among different subgroups.

Examples:

1. Race and gender modify the effect of obesity on the years of life lost.
2. Obesity appears to be a risk factor for colon CA in premenopausal women while it appears to be protective or unrelated in postmenopausal women.
3. Among white women stage of breast CA at detection is associated with education, however there is no clear pattern among black women.
4. Family Hx of breast CA