CASE SERIES An Overview Akbar Soltani Assistant Professor

CASE SERIES: An Overview Akbar Soltani Assistant Professor of Medicine and Endocrinology Evidence Based Medicine Working Team (EBMWT) Tehran University of Medical Sciences (TUMS) Shariati Hospital EBMWT. EMRC A. SOLTANI TUMS

n n n n Introduction to descriptive studies Case series Cross sectional Bias, confounding(sen, sp …), Hill criteria Ecologic study (correlation) Quiz Algorithm EBMWT. EMRC A. SOLTANI TUMS

Descriptive study n A descriptive study is “concerned with and designed only to describe the existing distribution of variables, without regard to causal or other hypotheses. EBMWT. EMRC A. SOLTANI TUMS

The descriptive triad When a statistic is being described or interpreted, we need to reference Who (person) -- what population or subgroup When(time)-- what time point or time period Where (place)-- the geographical location EBMWT. EMRC A. SOLTANI TUMS

The descriptive triad—or pentad? Five “W” questions n n n “W” questions—who, what, why, when, and where—and an implicit sixth question, so what? EBMWT. EMRC A. SOLTANI TUMS

Who n n Who has the disease in question? Age and sex are universally described, but other characteristics might be important too, including race, occupation, or recreational activities. The risk of venous thromboembolism, for example, increases exponentially with age. Only 1% of breast cancers arise in men, but Klinefelter’s syndrome or a family history of breast cancer increase their risk. Race affects the risk of leiomyomas of the uterus. EBMWT. EMRC A. SOLTANI TUMS

What n n What is the condition or disease being studied? Development of a clear, specific, and measurable case definition is an essential step in descriptive epidemiology. Without such a description, the reader cannot interpret the report. Some conditions, such as fractures, Klinefelter’s can be overt. other diagnoses might be challenging: multiple sclerosis, systemic lupus erythematosus, and pelvic inflammatory disease (salpingitis), DVT for example. EBMWT. EMRC A. SOLTANI TUMS

What Generally, stringent criteria for case definitions are desirable. n Although this approach inevitably leads to some loss of information, the trade-off is better specificity. n Example : stringent case definition used for toxic shock syndrome, which requires involvement of multiple organ systems. n EBMWT. EMRC A. SOLTANI TUMS

Why? n n Why did the condition or disease arise? Descriptive studies often provide clues about cause that can be pursued with more sophisticated research designs. EBMWT. EMRC A. SOLTANI TUMS

When n n When is the condition common or rare? time provides important clues about health events. Example: outbreak of gastroenteritis soon after ingestion of staphylococcal toxin. Some temporal relations can be long—eg, vaginal adenosis and clear cell carcinoma of the vagina appeared years after intrauterine exposure to diethylstilboestrol. Osteomalacia in winter EBMWT. EMRC A. SOLTANI TUMS

Where n n n Where does or does not the disease or condition arise? Geography has had a huge effect on health. Latitude plays a part in both multiple sclerosis and vitamin D deficiency; sunlight might decrease or increase cancer risk. Osteoporosis and VD deficiency EBMWT. EMRC A. SOLTANI TUMS

So What? n n So What? The implicit “W” relates to the public health effect. In view of the proliferation of descriptive reports, what is their import? Although many descriptive reports herald new illnesses or monitor health, the net effect of others might be only thicker curricula vitae at the expense of thinner forests. EBMWT. EMRC A. SOLTANI TUMS

Case-series & report EBMWT. EMRC A. SOLTANI TUMS

Case report n n The case report is the least publishable unit in the medical literature. Often, an observant clinician reports an unusual disease or association, which prompts further investigations with more rigorous study designs. Most common types of articles in medical journals are case reports and case series Represent the first clues of new diseases or adverse effects of exposures EBMWT. EMRC A. SOLTANI TUMS

Case report For example, a clinician, among others, reported benign hepatocellular adenomas, a rare tumour, in women who had taken oral contraceptives. n Document unusual medical occurrences n EBMWT. EMRC A. SOLTANI TUMS

In the 26 -35 age bracket, 44% of the cases were OC users compared to only 15% for nonusers! EBMWT. EMRC A. SOLTANI TUMS

All 126 are “cases”, i. e. , they have cancer Problem: What if 44% of healthy women also used OC in this age bracket? This says nothing about any link. EBMWT. EMRC A. SOLTANI TUMS

Case-series report n n n A case-series aggregates individual cases in one report. (>4) Sometimes, the appearance of several similar cases in a short period heralds an epidemic. Example: Creech and Johnson (1974) reported: 3 men with angiosarcoma of the liver among workers at a vinyl chloride plant Hypothesis: “Vinyl chloride” caused “Hepatic angiosarcoma” Later, two analytic studies supported it AIDS from 5 cases recognized as a new disease EBMWT. EMRC A. SOLTANI TUMS

Case report n n Whereas a report of a single unusual case might not trigger further investigation, a case-series of several unusual cases (in excess of what might be expected) adds to the concern. A large case-control study pursued this lead and confirmed a strong association between long-term use of high-dose pills and this rare, but sometimes deadly, tumor. EBMWT. EMRC A. SOLTANI TUMS

n Case-series report & Intervention EBMWT. EMRC A. SOLTANI TUMS

Levels of Evidence n n n n n Systematic Reviews & Meta-Analyses Randomized Controlled Double Blind Studies Cohort Studies Case Control Studies Case Series Case Reports Ideas, Editorials, Opinions Animal Research In Vitro Research Aunt Betty’s opinion! EBMWT. EMRC A. SOLTANI TUMS

case series and intervention Case studies and case series tend to fall fairly low in the hierarchy of evidence n However, in certain situations evidence from this type of research may be all that is available, particularly 1. when the intervention of interest is in the early stages of its development or, conversely 2. when its effectiveness has been well established in the absence of well-conducted RCTs. n EBMWT. EMRC A. SOLTANI TUMS

Size of the effect Study method example size of the effect Observation in single patient penicillin for severe infection ++++ Observation in groups of patients smoking and lung cancer +++ Randomised controlled trials aspirin and SK for heart attacks ++ Systematic reviews steroides for women expected to deliver prematurely EBMWT. EMRC A. SOLTANI + TUMS

Situation where case series are likely to provide valid information : n n n Where the natural history of the condition is understood and it is clear that cases who are untreated will have a poor prognosis. EX: End stage every-disease!, progressive nature? EX: lovastatin and BMD? For situations where the prognosis of untreated cases is not known the information from case series is less helpful. EX: Scan negative thyroid cancer? EBMWT. EMRC A. SOLTANI TUMS

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