Biostatistics Case Studies
CASE 3: Variables
A 33-year-old woman comes to you complaining of lower abdominal pain which she has had for the past day. She left her job as a nurse's aide (her second day on the job) because the pain was so bad. She says the pain began after she had fallen off a stepstool while getting a bedpan off a top shelf. No one saw her fall, but she convinced her supervisor that she had an industrial accident and needed medical attention because of blood in her urine. To prove it, she brings in a urine specimen.
How do you correlate the macroscopic and microscopic findings?
The macroscopic appearance is red, but the test for blood is negative and there are no RBC's microscopically. It is unlikely to be rhabdomyolysis. This specimen could be factitious. It would be a simple matter to have the patient produce another sample (though she might still be carrying the same bottle of red food colouring with her). Remember that various drugs can also produce coloured urine. Eating fresh beets can colour the urine red temporarily.
What do you think is happening?
Although care and concern should be the immediate response of health care workers to a patient, and historical findings should be duly noted, remember that patients may not always be telling you everything, or telling you correctly, particularly when compensation is being sought.
What kind of variables are pH and protein?
These measurements represent a quantitative (measured) variable that is discrete, with a finite number of possible measurements in the range of 5 to 8 for pH and from 0 to 4+ for protein.
The other form of quantitative variable is continuous with an infinite number of possible measurements within a range, as would be typical for a serum chemistry test such as urea nitrogen or creatinine. Categorical variables could be nominal or ordinal. A nominal variable is assigned (not measured) and could be a demographic characteristic such as sex or race. An ordinal variable is a ranking, such as mild, moderate, or severe.
A week later she faints on the job and is taken to the emergency department. No external signs of trauma are noted. Laboratory studies show a negative drugs of abuse screen, normal electrolytes, but a serum glucose of only 24 mg/dL. The ER physician orders a plasma C-peptide, which is low. She is given an intravenous solution containing glucose and she is fine within an hour.
How do you explain this episode?
If insulin is secreted from islets of Langerhans, c-peptide is released simultaneously. Thus, the findings suggest exogenous insulin administration.
The Plot Thickens:
A week later she comes to the emergency department complaining of severe abdominal pain for the past 3 days. She also reports weakness beginning in her hands and feet and moving toward her torso. On examination she has tachycardia and hypertension. She then experiences a tonic-clonic seizure. Laboratory studies show a negative drugs of abuse screen. Her serum glucose is 65 mg/dL. Her urine has a reddish colour, but the person transporting the specimen to the lab noted that it glowed while passing under an ultraviolet light. The pathologist states that she can tie these findings together with an inborn error of metabolism, confirmed by additional testing on the urine.
What is this patient's underlying disease, and what abnormal metabolites were present in her urine?
Acute intermittent porphyria (AIP) is caused by porphobilinogen-deaminase gene mutations that have an autosomal dominant mode of inheritance. Porphyrin precursors, porphobilinogen (PBG) and amino-levulinic acid (ALA), accumulate and are excessively excreted in urine. They are neurotoxins to the CNS and PNS.
Pain and other signs and symptoms are most often mediated by neuropathy. Autonomic neuropathy can lead to colicky abdominal pain, vomiting, and constipation. Cardiovascular effects include hypertension and tachycardia. Peripheral neuropathy is most often motor, leading to weakness, often ascending from limbs. CNS problems include psychiatric manifestations, such as depression, seizures, and focal neurologic deficits.
Ingestion of drugs that increase hepatic cytochrome P450 activity include phenobarbital, sulfonamides, estrogens, and alcohol. Decreased caloric intake with hypoglycemia will also induce hepatic ALA synthase activity to increase PBG and ALA. Increased excretion of porphyrin compounds leads to dark or even reddish urine (and porphyrins fluoresce under ultraviolet light).