CEE-154/NUTR-204: Fall 2012

Case reports, case series and crosssectional studies

Case Reports and Case Series:

The most basic of the descriptive designs. Case reports are usually generated by clinicians and describe an unusual grouping of symptoms or the appearance of a rare disease in a single individual. If several case reports are generated over a comparatively short period of time, then we have a case series, which is just a description of several individuals with a similar disease or set of symptoms. Following is the beginning of a CDC case report form for rickettsial tick-borne disease. Is a tick-borne disease a zoonotic disease?

Trichotillomania in Childhood: Case Series From the Article Abstract:

Trichotillomania is a relatively common cause of childhood alopecia. We report our observations of 10 children with trichotillomania seen over a 2-year period at Texas Children's Hospital. Patient ages ranged from 9 to 14 years (mean: 11.3 years) with an equal gender ratio. The duration of hair-pulling ranged from 1 month to 10 years (median: 4.6 months).

Abstract (continued)
The scalp alone was affected in 8 cases, the scalp and eyelashes in 1 case, and the eyelashes alone in 1 case. The frontal scalp and vertex were the most common sites affected. Associated findings included nailbiting in 2 cases, "picking" of the skin in 1 case, and headaches in another case. Noted precipitating factors in 3 patients included "stress" at home and school. Associated psychopathology included major depression in 1 case, attentiondeficit/hyperactivity disorder in 1 case, and an "anxious and nervous personality" in 1 case.

Abstract (continued)
The most important differential diagnosis to exclude from trichotillomania is alopecia areata, which was seen concomitantly in 1 patient and preceded the onset of hair-pulling by 11 months. Eight patients were referred to a child psychologist for additional management, of which 2 were subsequently treated with antidepressant medication.

Conclusions (from Abstract):

Trichotillomania is a disorder of multifaceted pathology, and an interdisciplinary approach to management is often helpful. The common prepubertal age of onset provides an important opportunity for the pediatrician to lend support to affected patients and their families.

Imported Measles Case Associated with Nonmedical Vaccine Exemption --- Iowa, March 2004
On March 13, 2004, the Iowa Department of Public Health (IDPH) reported to CDC that a male student aged 19 years with measles in the infectious stage had flown from New Delhi, India, to Cedar Rapids, Iowa, on March 12. Because of a nonmedical exemption, the student had not received measles-containing vaccine (MCV). This report describes the measles case, the public health response to prevent secondary cases, and the impact on the public health system. Health-care providers and state and local public health departments should be alert to possible cases of measles in persons who traveled with this student or their contacts. Parents considering nonmedical exemptions for their children should be aware of the potential risk for disease both for their children and the public.

The index case is described first

The index patient was a member of a group of approximately 28 students and two supervisors from college A in Iowa who had traveled to India, where approximately 52,000 cases of measles were reported in 2002. A high percentage of students from college A are reported to be unvaccinated because of nonmedical exemptions. Six measles cases occurred among the students while they were in India. The group had been scheduled to return to the United States on March 7. To avoid potential spread during the prolonged airline flights, IDPH recommended that these six students stay in India for at least 4 days after rash onset (i.e., the period of infectivity). Contacts of these infectious students who lacked immunity for measles were asked to stay in India for 18 days after the last possible exposure. Despite these recommendations, the index patient, who was an unvaccinated contact, returned to the United States early, flying on March 12 from New Delhi through Amsterdam and the Detroit Metro Airport to Cedar Rapids, Iowa. During his travel, he had a cough and conjunctivitis, and within 24 hours of his arrival in Iowa on March 13, he had a rash. A local physician reported the case to IDPH. Subsequently, measles was confirmed serologically, and throat swab and urine specimens were collected for viral isolation.

Actions in response to the index case

On March 13, IDPH and the Michigan Department of Community Health (MDCH) issued press releases to alert air passengers, visitors, and employees who had been in the involved airports about their risk for measles exposure and state health advisories to alert physicians and enhance surveillance. On March 18, CDC issued a health advisory recommending that every person who had been on the plane with the student or who had been in one of the involved airports at the same time be evaluated and, if determined to be susceptible, receive MCV or immune globulin according to the recommendations of the Advisory Committee on Immunization Practices (ACIP). Measles vaccination clinics were held on March 14 at the office of Linn County Public Health (LCPH) in Iowa and on March 15 in Michigan. Passenger lists were subpoenaed from the airline, and LCPH, IDPH, and MDCH attempted to contact all passengers on flights with the index patient. Other states in which exposed passengers reside also are taking public health measures to control the potential spread of measles.

Warnings and recommendations plus source of report

The occurrence of six cases in this group of students who traveled abroad demonstrates the high transmissibility of measles when susceptible persons are exposed. The majority of states require 2 doses of MCV for children attending school and post-high school educational institutions; however, nonmedical exemptions are permitted in some states. Persons who have chosen a nonmedical exemption from vaccination are >22 times more likely to acquire measles than persons who are vaccinated. In addition, increases in the number of persons who have chosen to be exempt increase the risk of disease in nonexempt persons. To reduce the risk of infection among travelers, ACIP recommends that all international travelers be immune to measles because the disease is endemic or epidemic in many parts of the world. This case demonstrates the importance of following the ACIP recommendations and underscores the impact of nonmedical exemptions on the public health system. Physicians, public health authorities, and school personnel who counsel parents considering nonmedical exemptions for their children should ensure that parents understand the risk that opting out of vaccination places upon their children and the public. Reported by: Linn County Public Health, Cedar Rapids; Iowa Dept of Public Health. MG Stobiersky, DVM, R Swanson, MPH, ML Boulton, MD, Michigan Dept of Community Health. GH Dayan, MD, C LeBaron, MD, Epidemiology and Surveillance Div, National Immunization Program, CDC.

Uses of Case Reports/Series

Little utility in terms of establishing causal relationships because of their anecdotal nature. Can be very useful to the state, regional, and federal offices responsible for protecting the publics health since they sometimes are the harbinger of new types of epidemics, or warn that well-known diseases are suddenly on the rise, either across-the-board or in specific age, race, or sex groups. Example: The measles case report/series above. The US Centers for Disease Control (CDC) rely on case reports and case series to help keep epidemiologists in their Epidemic Intelligence Service (EIS) informed of possible new shifts in disease patterns well before they become actual epidemics or even substantial health threats at all.

 Marta Guerra Assignments: Worked to contain Ebola outbreak in Uganda, investigated Q fever outbreak in Wyoming, and hopes to educate the public on rabies during her time as an EIS officer. Education: University of Pennsylvania (B.A., 1979); University of Florida (D.V.M., 1985); University of South Florida (M.P.H., 1995); University of Illinois, Champaign/Urbana (Ph.D., 2000). Where She Is Today: Guerra lives in Atlanta, where she is currently serving as an EIS officer.

Requirements to apply to EIS

Physician (MD or DO) with at least 1 year of clinical training and an active medical license in the United States (i.e., U.S. citizen or permanent resident). A recipient of a doctoral degree (PhD or DrPH or equivalent) in health-related fields (e.g., epidemiology; biostatistics; the biological, environmental, social, behavioral, nutritional, or other relevant sciences). Nurse, physician assistant, dentist, and pharmacist, with a master of public health (MPH) or equivalent degree and an active license in the United States (U.S. citizen or permanent resident). Veterinarian with an MPH or equivalent degree or demonstrated public health experience or course work and an active license in the United States (U.S. citizens or permanent residents).

A famous case series

A well-known example of a case series began in Los Angeles in 1981. Five previously healthy male homosexuals under 40 had succumbed to Pneumocystis pneumonia, a rare and virulent form of pneumonia that, before this case series, had been seen exclusively in the very old and sick, or in individuals with compromised immune systems (e.g., transplant patients). Once notified, the CDC used its EIS arm to search out other similar cases and found some in a few large cities. Analytic studies (case-control, in this instance) were quickly planned and implemented to try and determine what the cause was of this new immunosuppressive disease, and the HIV/AIDS story began to unfold.

The fun of the chimney sweeps

Sir Percival Pott and Chimney Sweeps

Pott was perhaps the first occupational epidemiologist Spent much of his time trying to help workers in dirty jobs. Note the master sweep and his boy.

Percival Potts Observations on Scrotal Cancer in Young Chimney Sweeps = Classic Case Series in late 18th Century

Pott noted high rates of a rare cancer in an unusual population. Did not have the knowledge or techniques to pursue cause and effect. Attributed high rates as probably due to irritation (at least partly correct).

Young sweeps
The young sweeps carried heavy extender pipes to reach areas into which even they could not crawl. So they would not be punished, young sweeps frequently worked naked and greased, exposing their entire bodies to carcinogens. The grease would the hold the carcinogens in place.

Pott wrote:
...The fate of these people is particularly hard...they are thrust up narrow, sometimes hot chimneys where they are bruised, burned and almost suffocated; and when they get to puberty, become particularly liable to a most noisome, painful, and fatal disease...of the scrotum and testicles.

Pott also noted that:

Soot lodged in the folds of the scrotum of the boys was most possibly the cause of the disease. Operative treatment was not successful if carried out after the tumor spread. While Pott correctly surmised that cancer was ...a disease of the habit, it was the Danish and not the English that first acted on his results. Danish chimney sweeps were required to wear protective clothing and wash regularly and levels of scrotal cancer was sharply reduced. The British continued with their weekly bath and the occurrence of soot-wart cancers continued unabated for many years.

More on young sweeps

Boys were frequently sold to master sweeps when they were 6-8 years old. Slept on bags of soot. Scrotal cancer not the only risk. Boys sometimes suffocated or burned to death or fell down rotting chimneys and were killed or crippled. Nearly 100 years after Pott, a 10 pound fine was finally established for using climbing boys.

Typical chimney sweeps, 19th century

Even in modern times...

The tradition of shaking hands with a sweep at any important event has grown over the years, and even been continued by our own Royal Family. The night before Prince Philip married the Queen in 1947, he remembers slipping out of my apartment to shake hands with a sweep who just happened to be passing! A wedding is not complete without a real chimney sweep and Dale Hill Hotel is pleased to provide this tradition complementary.

Industrial sweeps today

Modern sweeps No kids, at least Better protective clothing Still using face-wrapping to protect from fumes Masks too awkward and expensive

CROSS-SECTIONAL STUDIES:
Cross-sectional studies are often called prevalence surveys. In their most basic form, a researcher recruits a group of people and obtains measurements of some kind at one particular point in time. There is no concept of prospective or retrospective time. Are on the border between analytic and descriptive studies.

continued
Cross-sectional studies are sort of on the border between analytic studies and descriptive studies. Data are at the individual level, so cross-sectional studies are sometimes viewed as analytic. Since there is no time element, however, crosssectional studies are usually best viewed as hybrid studies. Following is a generic schematic of a cross-sectional study. Note that everything happens at once and we have no element of time.

Start with a defined population

Gather information on exposure and outcome

Put all subjects into proper cells

A cell (E+ and O+)

B cell (E+ and O-)

C cell (E- and O+)

D cell (E- and O-)

Cross-sectional data on physical activity and metabolic syndrome (HHS, 6/08 Report)
From the cross-sectional studies in which minutes per week of moderate-intensity physical activity for each category were provided or could be estimated, 120, 150, and 180 minutes or more per week of moderate intensity activity have all been reported as minimum amounts associated with reduced prevalence of metabolic syndrome. Studies used different methods of activity assessment, the activity categories have large ranges, and the cut-points for the activity categories were not that similar. None of the studies was designed or powered to analyze the minimal dose of activity to prevent metabolic syndrome. However, the cross-sectional data supports that obtaining at least 120 to 180 minutes per week of moderate-intensity physical activity is consistently associated with a lower prevalence of metabolic syndrome.

Cross-sectional data on physical activity and metabolic syndrome

Uses of Cross-Sectional Studies

Quick, inexpensive, and straightforward to do. Can warn of situations where causality is secondary to an imminent health danger. In the example above, if the children had very high blood lead levels, the public health team involved would be most interested in quick remedial action to lower them. If limited to the above, cross-sectional studies can be very valuable. However, their easily understood procedures, coupled with their short time and low monetary investment, can encourage scientists to substitute cross-sectional investigations where they are simply not very useful. Cross-sectional studies are particularly vulnerable to the chicken and egg syndrome, in which it is by no means clear that an exposure preceded the observed outcome or whether the outcome actually preceded the exposure.

Cross-sectional data on moderate to vigorous exercise and decreased risk of CHD in older men:

CHD Exercise Yes No Total Yes 54 112 166 No 1503 853 2355 Total 1556 965 2521

OR = (54 x 853) / (112 x 1503) = 0.27. This would be a very strong finding in terms of branding moderate to vigorous exercise in older men a protective factor against CHD. Some researchers interpreted the data in just this manner.

Continued
Unfortunately, it turned out that many of the men in the non-exercising group were there because, at some point in the past, they had developed cardiovascular symptoms indicative of CHD and had to quit intensive exercise. It took long-term cohort studies to better characterize that exercise was indeed a protective factor against CHD, although not as strong as cross-sectional data had suggested.

In the past...
Large population of exercising middle-aged men

Some develop symptoms of CHD during exercise and quit (symptoms group)

Some do not develop CHD symptoms and continue exercising (no symptoms group)

At the time of the study

Population of hospitalized middleaged men with and without CHD

Exercisers (most come from no symptoms group)

Non-exercisers (most come from symptoms group)

The c cell is inflated with men from the symptoms group. This makes b x c biased in favor of rejecting the null hypothesis.