Biostatistics Case Studies


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OBJECTIVE:

Apply your knowledge of biostatistical methods to virtual patient cases.



CASE 1

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A normal complete blood count (CBC) and normal peripheral blood smear are obtained.

    Questions:

    1. Identify the mean, median, and mode in the following series of measurements of hematocrit:

      39, 38, 39, 37, 40, 42, 39, 37, 39, 40.




CASE 2

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Clinical History:

A 62-year-old impoverished man living on a subsistence income has never received regular health care. He participates in a health screening program conducted by medical students and is found to have a random serum glucose of 201 mg/dL. On followup of this, his hemoglobin A1C is 10.3%. Based upon these findings, he is referred for vision testing.

Funduscopic Pathology:

The findings on funduscopic examination are consistent with diabetic retinopathy

Questions:

  1. If a study were to be performed to determine risk factors for ocular problems with this man's underlying disease, what kind of variable would be used to record demographic information?

  2. What kind of variable would be used to record his laboratory findings from a blood specimen?




CASE 3

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History:

A 33-year-old woman complains 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.

Macroscopic Urinalysis:



CharacteristicResult
ColorRed
AppearanceClear
Leukocyte EsteraseNeg
NitriteNeg
pH7.0
ProteinNeg
BloodNeg
Specific Gravity1.015
KetonesNeg
GlucoseNeg
BilirubinNeg

Microscopic Urinalysis:

CharacteristicResult
WBC/hpf <2/hpf
RBC/hpf None
Casts Occasional hyaline casts
Other Few squamous epithelial cells

Questions:

  1. How do you correlate the macroscopic and microscopic findings?

  2. What do you think is happening?

  3. What kind of variables are pH and protein?

Further History:

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.

Question

  1. How do you explain this episode?

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 color, 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.

Question

  1. What is this patient's underlying disease, and what abnormal metabolites were present in her urine?




CASE 4

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Clinical History:

A 62-year-old woman has noted decreasing visual acuity, mainly in her peripheral vision, over the past year. She states that "everything just seems to be darker." She goes to her optometrist. The optometrist, using an "air puff" tonometer discovers that she has increased intraocular pressure bilaterally. The cornea and sclera of each eye appear normal. There is no opacification of the crystalline lens. However, on fundoscopy there is cupping of the optic discs.

Findings:

Visual fields show reduced peripheral vision. There is cupping of the optic disk as a consequence of the increased intraocular pressure, leading to atrophy of the optic nerve head.

Questions:

  1. What condition is present? Who is at risk?

  2. How is this condition detected?

  3. How does this condition occur?

  4. If a study were performed comparing drug treatments for this condition, how could one avoid type II error and what would determine the "power" of the study?

  5. For a patient with significant visual impairment who continues to operate a motor vehicle, what should you do?




CASE 5:

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Clinical History:

A 24-year-old woman is pregnant for the 2nd time. She visits you for a prenatal checkup. You order laboratory tests, including TORCH titers, HBsAg, and HIV. Your state requires a specific consent form for HIV testing. She questions you about the need for HIV testing.

Laboratory Findings:

A CBC shows Hgb 13.3 g/dL, Hct 40%, MCV 85 fL, platelet count 244,400/microliter, and WBC count 9070/microliter with differential count of 65 segs, 3 bands, 22 lymphs, 9 monos, and 1 baso. Serum chemistries show sodium 143 mmol/L, potassium 4.3 mmol/L, chloride 107 mmol/L, CO2 27 mmol/L, creatinine 1.0 mg/dL, and glucose 110 mg/dL. The HBsAg test is negative. She is rubella immune. CMV IgG titer is increased, but CMV IgM is not increased. Toxoplasma and HSV I and II titers are not increased. Her HIV EIA test is positive, with the Western blot assay as shown in lane A:

Figure 1: Western blot

The diagnostic sensitivity and specificity of the standard enzyme immunoassay (EIA) initial screening test on patient blood for HIV is illustrated by the following study: In an adult population, 200,000 persons are tested for HIV infection with an EIA test on patient blood for HIV. Of these, 600 are found to test positive by EIA. Of these, 200 are found on subsequent confirmatory Western blot testing to really be infected. Furthermore, follow-up of the original group of patients reveals that there was 1 person who really was infected, but was missed by the initial screening EIA test.

Questions:

  1. Why should the HIV test be ordered in this case?

  2. What is the test sensitivity and specificity calculate from the information given above?




CASE 6

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Clinical History:

A 48-year-old man has become progressively more fatigued at the end of the day. This has been going on for the past 6 months. In the past month he has noted paresthesias with numbness in his hands and feet. On physical examination he has decreased vibration and position sensation in both hands and feet. Laboratory studies include a CBC with peripheral blood smear. His Hgb is 10.6 g/dL, Hct 31.6%, MCV 118, platelet count 578,000/microliter, and WBC count 12,100/microliter.

  1. Describe his peripheral blood smear findings.

  2. What is the diagnosis from these findings?

  3. Which of the following tests would be most useful to determine the etiology:

A. Hemoglobin electrophoresis
B. Reticulocyte count
C. Stool for occult blood
D. Vitamin B12 assay
E. Bone marrow biopsy

Questions:

  1. How do you explain the neurologic findings?

  2. How do treat this condition?

  3. What are issues involved in designing a study to measure the effects of these treatments? Define selection, randomization, assignment, internal validity, external validity.




CASE 7:

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Clinical History:

A 44-year-old African-American man has a long history of poorly controlled hypertension, generally in the range of 145/95 mm Hg.

His blood pressure 5 years later is 160/105 mm Hg. His BUN is currently 45 mg/dl and serum creatinine 3.5 mg/dl. His hemoglobin A1C is 9.5%.

His glomeruli would show areas of amorphous deposition of PAS-positive material typical for nodular glomerulosclerosis (Kimmelstiel-Wilson lesion) and the arterioles at the base of the glomeruli would showextensive thickening consistent with hyaline arteriolosclerosis.

Questions:

  1. What underlying disease process is probably present?

Further History:

Today he has a severe headache, and on arrival in the emergency room his blood pressure is recorded as 220/150 mg Hg.

At this point in time, his kidney would show hyperplastic arteriolosclerosis in which there is lumenal narrowing with prominent intimal proliferation ("onion-skinning"). This lesion is most likely to accompany malignant hypertension. Malignant hypertension, which complicates about 1% of cases of "essential" or "benign" hypertension, is more common in men.

Questions:

  1. What complications are likely to develop?

  2. Describe two mechanisms by which renal artery ischemia produces hypertension.

Statistical Review:

Clinical studies are performed comparing treatment regimens to lower blood pressure in patients with stage 2 hypertension (160-179/100-109 mm Hg). In the chart below, the reduction in diastolic blood pressure (in mm Hg) is given with 95% confidence intervals for each study. Study A consists of patients who went on a low salt diet along with a regular exercise regimen for 3 months. Study B consists of patients who took two drugs. Study C consists of patients who took one drug. Study D consists of patients who took no drugs and made no lifestyle modifications. The "range of clinical indifference" is marked by the yellow bar.

Question:

  1. What do the confidence intervals indicate for these four regimens?




CASE 8

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Clinical History:

A 21-year-old woman from Bangladesh has had decreasing vision in her left eye "for years." Physical examination reveals left corneal and conjunctival scarring. Her eyelashes are partly turned in, scratching the surface of the eye. A conjunctival scraping is made for diagnosis.

A study is performed of 1,000 persons living in this woman's community. It is found that only 55% of persons have access to running water inside their homes. Of those persons with access to running water, 10 had developed the eye disease that the woman in this case had, while 90 persons without running water in their homes had developed the disease.

Microscopic Pathology:

A conjunctival scraping with Wright-Giemsa stain is performed and shows an intracytoplasmic elementary body of Chlamydia trachomatis.

Questions:

  1. What is the diagnosis?

  2. What are risk factors?

  3. What is the treatment?

  4. Name another cause for preventable blindness.

  5. What type of study was performed in this case? What is the relative risk for developing this disease for persons without access to running water at home?




CASE 9

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Clinical History:

A 25-year-old military serviceman reports having respiratory difficulty along with red-tinged sputum, chest pain, chills, and fever for the past 2 days. He then passes dark urine. He goes to see the base physician. Vital signs are recorded as: T 37.9 C, P 83/min, RR 15/min, and BP 145/90 mm Hg. Physical examination findings include crackles over lung bases.


Urine dipstick examination shows 1+ protein and 4+ blood.

Additional laboratory findings include serum creatinine 2.8 mg/dL, urea nitrogen 30 mg/dL, glucose 74 mg/dL, total protein 6.1 g/dL, and albumin 3.6 g/dL

Two days later is serum creatinine is 4 mg/dL and urea nitrogen 43 mg/dL. Further history reveals that he works in a military fuel depot.

A renal biopsy on light microscopy shows crescents in the glomeruli, filling Bowman's space and compressing the residual glomerular tufts.

With immunofluorescence staining for fibrinogen, the crescents within Bowman's space stain for fibrinogen, consistent with severe glomerular injury leading to leakage of fibrinogen that stimulates epithelial cell proliferation and crescent formation.

The immunofluorescence show with staining for IgG shows a linear pattern of staining along the glomerular basement membrane with antibody to IgG. In most cases of Goodpasture syndrome with rapidly progressive glomerulonephritis there is linear staining with IgG, but staining with IgA and IgM can also be present.

Questions:

  1. What is the differential diagnosis?

  2. What is the pathogenesis?

  3. What is the treatment and prognosis?

  4. What long-term type of study can be undertaken to determine what risk factors, if any, play a role in development of this disease in persons working at this man's job?




CASE 10

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Clinical History:

A 26-year-old man with no major medical problems goes to his family physician for a checkup, which includes a urinalysis. The urinalysis findings are shown:

Urine dipstick examination shows 1+ blood. Urine microscopic examination reveals dysmorphic RBCs and RBC casts, but no WBC's.

Additional laboratory findings include serum creatinine 1.8 mg/dL, urea nitrogen 20 mg/dL, glucose 82 mg/dL, total protein 6.6 g/dL, and albumin 4.6 g/dL

Light microscopy of a renal biopsy shows mesangial cell proliferation. The glomerular capillaries and Bowman spaces appear normal. The immunofluorescence with staining for both IgA and C3 shows a predominantly mesangial deposition of IgA and C3. Staining for C1q, IgM, and IgG is negative.<

Urine microscopic examination shows dysmorphic red blood cells. This is an indicator for glomerular disease with a nephritic component.

Questions:

  1. What additional history do you want to know?

  2. What is the differential diagnosis based upon the history?

  3. What additional laboratory tests could be ordered?

  4. What underlying disease(s) might be present? What diagnosis would you consider if the patient had presented with petechiae and purpura of the skin?

  5. What type of study would you perform to determine the risk for developing chronic renal failure in patients with this disease, compared to persons without this disease?




CASE 11

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History:

The patient in case 1 visited her 49-year-old mother and told her about the biopsy and the results. Her mother remarked, "You know, maybe I should go and see my doctor, because my aunt died of breast cancer about my age." She sees her doctor, who palpates a large irregular firm fixed mass in the right breast as well as overlying skin with a rough, reddened appearance. There are enlarged, nontender axillary lymph nodes. Mammographically, the mass has irregular borders. A fine needle aspirate is performed of the mass and then a mastectomy is done. The lesional tissue is tested for estrogen-progesterone receptors and HER2.

The breast mass has irregular borders. The cut surface of the mass has a central irregular whitish scar. There are scattered foci of yellow to white necrosis and calcification. Axillary lymph nodes were also found to be enlarged and firm with similar cut surfaces. A frozen section confirms the diagnosis of malignancy

Microscopic sections of this neoplasm with overlying breast skin show intralymphatic cancer cells, accounting the clinical features of cutaneous inflammation and the "inflammatory carcinoma". This malignant neoplasm has cells which are arranged in nests, cords, and exhibit a poor attempt at gland formation. The stroma around the tumor-cell nests is mildly desmoplastic. Metastatic breast cancer is present in an axillary lymph node.

Questions:

  1. What is the diagnosis?

  2. Why did the skin appear to be inflamed?

  3. What is the significance of the family history?

  4. Why would you want to know the results of testing for estrogen-progesterone receptors and HER2/neu in this lesion?

  5. if there were 16 women in 1000 diagnosed with this disease last year and there were 39 in the same population previously diagnosed with this disease, what is the incidence and prevalence?




CASE 12

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Clinical History:

For the past 3 months, a 53-year-old woman has had decreasing vision in her right eye. Today she has experienced sudden loss of vision on the right, as though a window-shade had been pulled down. Funduscopic examination reveals a 13 mm choroidal mass on the right. The left eye appears normal.

The cross section of the enucleated eye reveals a uveal (choroidal) mass that is darkly pigmented. Microscopically, there are polygonal cells with enlarged nuclei, prominent nucleoli, and cytoplasm with brown granules. The Fontana-Masson stain is positive, indicating that the granules are melanin pigment.

She is enrolled in a study to determine outcomes of therapy. The study shows that, over the past year, there were 25 persons in a population of 2,000,000 people for whom medical records were available for review, who had this disease. During that time (one year) 5 of the affected persons died of their disease, while 7,000 persons died in the entire study population.

Questions:

  1. What is the diagnosis?

  2. What sudden complication did she have?

  3. What is the case fatality rate for her disease? What is the mortality rate for the population as a whole in the study?



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