The Method of Comparison, Experiments, and Observational Studies

The next few questions refer to a research article by W.J. Spangler, B.S., G.R. Cosgrove, M.D., H.T. Ballantine Jr., M.D., E.H. Cassem, M.D., S.L. Rauch, M.D., A. Nierenberg, M.D., and B.H. Price, M.D., 1996. Magnetic Resonance Image-guided Cingulotomy for Intractable Psychiatric Disease, Neurosurgery, 38, 1071-1078. The article reports on 34 patients who underwent MRI-guided cingulotomies to treat refractory psychiatric disease at Massachusetts General Hospital between May, 1991, and February, 1995.

The 34 patients, 18 male, 16 female, ages 16-71, mean age 37, had all been referred by their treating psychiatrists and reviewed by the MGH Cingulotomy Assessment Committee (comprised principally of a subset of the authors) to become candidates for the procedure. The committee had to agree unanimously that the patient should undergo the procedure, and the patient had to give his or her informed consent. Prerequisites for the committee to favor treatment included patient's resistance to pharmacotherapy, psychotherapy, behavior therapy, and electro-convulsive therapy (when applicable), and the symptoms had to be severe and unremitting for at least one year. All patients had a documented DSM III-R disease that interfered significantly with normal functioning (e.g., major affective disorder with unipolar depression (10 patients), or bipolar depression (5 patients), undiagnosible developmental disorders (1 patient), and obsessive-compulsive disorder with major depression (15 patients)). For some patients whose condition failed to improve 6 months after surgery, additional cingulotomies were performed.

The cingulotomy procedure is to insert a pair of electrodes into holes drilled in the skull just above the hairline, to a pre-determined position in the brain (guided by MRI). Radio-frequency electricity is passed through the electrodes, to raise the temperature in the part of the brain between the electrodes to 85°C (185°F) for 90 seconds, essentially cooking part of the brain between them. (This causes what is called a radio-frequency thermocoagulation lesion). The basic procedure was changed in 1993 to include a larger part of the brain.

Of the 34 subjects, 31 were available for follow-up assessment of some sort; of the 31, two had committed suicide. Follow-up assessment was done two ways: either the referring psychiatrist or the treating psychiatrist completed two questionnaires---the Clinical Global Improvement Scale, and the Current, Global, Psychiatric-Social Status Scale---or, if the patient was no longer seeing a psychiatrist, the most recent correspondence with the patient was used to assign ratings. I could not find a reference to the number of patients who were in each of these categories. On the basis of these ratings, each patient was classified as a "responder" (R), a "possible responder" (P), or a "non-responder" (N).

Fourteen of the patients who had not responded six months after the initial procedure underwent multiple procedures. The categorized responses were as follows:

The article breaks down the responses further by type of mental illness.

Problem A. Therapy for Smoking Cessation

This problem refers to an article by RD Hurt, LC Dale, PA Fredrickson, CC Caldwell, GA Lee, KP Offord, GG Lauger, Z Marusic, LW Neese, and TG Lundberg, 1994, "Nicotine patch therapy for smoking cessation combined with physician advice and nurse follow-up," Journal of the American Medical Association, v. 271, 595-600.

There is no longer any doubt that smoking cigarettes is hazardous to your health and the health of those around you. Therefore, with the accumulating evidence that smoking is bad for you, millions of people have either quit smoking or are trying to quit. Yet despite the many efforts that some people make to quit, it is often very difficult for those addicted to smoking. Nicotine patches are one popular form of medication prescribed by doctors to help people quit smoking. One of the objectives of the study by Hurt et al. was to determine the efficacy of a 22-mg nicotine patch combined with the National Cancer Institute program for physician advice and nurse follow-up in 1-year cessation outcome.

Subjects were randomly selected from among volunteers who responded to a news release in the local media. 240 of those selected passed the physical and psychological screening and were included in the study. Subjects had to be between ages 20 and 65, ahve a history of smoking at least 20 cigarettes per day for the last year, have expired carbon monoxide levels of 10ppm or greater, be motivated to stop smoking, be in "good health" according to a doctor's examination, have no non-nicotine chemical dependencies, and use no other forms of nicotine besides cigarettes. Subjects were randomly assigned either to recieve an active nicotine patch combined with physician advice and nurse follow-up or to receive an inactive (placebo) patch combined with physician advice and nurse follow-up; 120 in each group. Patch therapy was completed at the end of 8 weeks. The nurse follow-up was face-to-face once a week during the patch phase, and a weekly phone call for the remainder of the study. Neither the subjects nor the doctors and nurses knew who had been assigned to which groups.

Smoking cessation was defined as self-reported abstinance (not even a puff) since the last visit and an expired air carbon monoxide level of 8ppm or less. Subjects with missing information or who dropped out of the study for any reason were considered smokers. For the first 8 weeks, this represented weekly point prevalence, and for 3, 6, 9, and 12 months this represented 3-month point prevalence.

Some of the baseline characteristics (i.e., characteristics after random assignment, but before the stop-smoking date) are shown in the following table.

The following table shows smoking cessation rates for different point prevalences.
 
 

1. The nicotine patch study was

an uncontrolled experiment a controlled experiment a randomized experiment  a randomized, controlled experiment 
2. The purpose of the study was to determine how smoking cessation is effected by

physician advice and nurse follow-up a nicotine patch a randomized experiment  a nicotine patch combined with physician advice and nurse follow-up  baseline characteristics 
3. The doctors required a carbon monoxide test as part of the smoking cessation criterion most likely to

verify abstinance from smoking check on the success of the randomization determine if the patch was working 
4. The numbers in table 1 show that the random assignment did not work because they are not exactly the same for each characteristic.

True  False 
5. The numbers in table 2 do not steadily decrease because

there was an error in the calculations of percentages  the percentages are not cumalative  there were a lot of dropouts  people lied about their smoking cessation 
6. A reasonable conclusion of the study is that

the randomization failed and thus no valid results are available  the combined patch and counseling therapy made no difference  significant smoking cessation can be achieved using combined patch and counseling therapy 

Reading: In 1853-54 the cholera epidemic in London, England, claimed the lives of more than 500 people - all from the Soho section of London - within a 10-day period. John Snow, a local physician, had been studying cholera and believed that the disease was being spread through food or water. Link to the Centers for Disease Control and Prevention (CDC) web page on Snow and read the background to his investigation on the cause and transmission of cholera.

To aid his investigation on his theory that cholera was waterborne, Snow made a map of every death in the Soho district. For every death he determined the water company that was serving the deceased individual. Snow found that those being served by the Southwark and Vauxhall company had a higher death rate than those served by the Lambeth company. This was very suggestive evidence of cholera being waterborne.

Now link to Snow's map showing deaths and locations of water pumps. There you can see that most of the deaths were clustered around the water pump at Broad Street and Lexington Street. As told in the CDC article, once the handle to this water pump was removed the epidemic was contained. However, this was not the end of the story, for it seemed that the number of deaths per day due to cholera was dropping anyway. According to John Snow:

Although the above facts shown in the table above afford very strong evidence of the powerful influence which the drinking of water containing the sewage of a town exerts over the spread of cholera, when that disease is present, yet the question does not end here; for the intermixing of the water supply of the Southwark and Vauxhall Company with that of the Lambeth Company, over an extensive part of London, admitted of the subject being sifted in such a way as to yield the most incontrovertible proof on one side or the other. In the subdistricts enumerated in the above table as being supplied by both Companies, the mixing of the supply is of the most intimate kind. The pipes of each company go down all the streets, and into nearly all the courts and alleys. A few houses are supplied by one Company and a few by the other, according to the decision of the owner or occupier at that time when the Water Companies were in active competition. In many cases a single house has a supply different from that on the either side. Each Company supplies both rich and poor, both large houses and small; there is no difference either in the condition or occupation of the persons receiving the waters of the different Companies.

Now it must be evident that, if the dimunition of cholera in the districts partly supplied with improved water, depended on this supply, the houses receiving it would be the houses enjoying the whole benefit of the dimunitions of the malady, whilst the houses supplied by the water from Battersea Fields would suffer the same mortality as they would if the improved water supply did not exist at all. As there is no difference whatever in the houses or the people receiving the supply of the two Water Companies, or in any of the physical conditions with which they are surrounded, it obvious that no experiment could have been devised which would more thoroughly test the effect of water supply on the progress of cholera than this, which circumstances placed ready made before the observer.

With these observations John Snow was convinced that cholera was indeed waterborne.

1. Based on the given information, what data did Snow collect on each cholera case? (Select all choices that apply--use the "shift" or "control" key to make multiple selections.)

residency  age water provider clinical symptoms 
2. What did Snow compare to support his research hypothesis that choloera is water-borne?

water consumption by cholera cases and non-cholera cases  number of cholera cases served by each of the water companies  death rates of cholera cases among each of the water companies' customers  death rates along each street in the Soho section 
3. Snow found that the customers of the Southwark and Vauxhall company had a higher death rate than those of the Lambeth company. If Snow has based his conclusions on just this information, he would have been wrong in concluding that the difference in death rates was caused by water because

of possible confounding factors, such as socioeconomic status  people really didn't know which company provided their water  both companies were served by the Thames River  Snow knew chloroform could have been causing the cholera 

4. Snow was convinced that the difference in death rates between the two water companies was due to their water supply becuase

he had proved it in his lab he recognized that the customers of the companies essentially differed only with respect to their water supplier   both companies were served by the Thames River of autopsy records the Southwark and Vauxhall company was downstream of sewage deposits 
5. Suppose Snow had not collected any data on cholera cases, but simply removed the handle from the water pump on Broad Street. True or false: The subsequent diesease containment would have been convincing evidence that cholera was waterborne.

True False