Week 1 Wrap-Up: Clinical Biostats, ID, Lab Methods

In disease states that are high risk and stakes for proper identification are high, which of the the following statistical measures needs to be maximized (likely at the expense of other measures)?

• Specificity

• Sensitivity

• Likelihood ratios

• Predictive value

Answer explanation

Remember these acronyms:

SnOUT- if a test is highly sensitive a NEGATIVE result essentially rules that disease state OUT.

You want a highly sensitive or touchy test (positive at the drop of a hat) when stakes are HIGH. Think things like troponin I for myocardial infarction- very sensitive test which is important because it is such a high stakes diagnosis you can't afford to miss anyone!

Specificity:

SpIN= A test that is highly specific, when positive, rules the disease state IN. Ultrasound for diagnosis of appendicitis in peds patients is highly specific- if it's positive, your patient has appendicitis, but if it's negative it doesn't mean anything (not very sensitive).

A 70-year-old woman comes to your office because of fatigue, pain in her hands and knees, and intermittent, sharp pains in her chest. Physical examination reveals an otherwise healthy female—the cardiopulmonary examination is normal, and no swelling is present in her joints. A possible diagnosis in this case is systemic lupus erythematosus (SLE). The question is whether to order an ANA (antinuclear antibody) test and, if so, how to interpret the results. The ANA test is 95% sensitive to SLE, and about 50% specific. Your patient has a negative result, how do you interpret this result?

• The diagnosis of SLE has been excluded.

• The test result does not rule out SLE and more testing may be necessary to establish a diagnosis.

• The test should not have been ordered as the results do not inform clinical decision making.

• Make a clinical diagnosis of SLE, the test result is likely a false negative.

Answer explanation

This test has a high sensitivity.

SnOUT- a test that is highly sensitive and is NEGATIVE, rules out disease.

SARS-CoV-2 NAAT's (by RT-PCR) have variable sensitivity (60-70% sensitive) but are known to be highly specific. How do you advise your patient that has a negative COVID PCR test?

• They do not have COVID.

• They have a negative result however it is still possible to have COVID with this result due to false negatives.

• They require repeat testing within 24-48 hours to definitively rule out COVID.

• This is likely a false negative and they likely do have COVID based on community prevalence.

Answer explanation

COVID PCR testing is highly specific- if you're positive, you're positive (SpIN). However this is at the expense of sensitivity, a negative result may very well be a false negative.

PPV and NPV are heavily dependent on ___________ which makes them A LOT less clinically useful than other biostatistical measures.

• Incidence

• Sensitivity and specificity

• Likelihood ratios

• Prevalence

Answer explanation

Predictive values are based upon the prevalence of disease in a population. As the prevalence of disease decreases, the positive predictive value decreases. In the general population, few diseases reach a prevalence of 1% making these parameters less useful.

Which of the following is TRUE regarding likelihood ratios?

• Likelihood ratios are less likely to change with the prevalence of a disorder.

• A negative likelihood ratio means that a test is worthless.

• A likelihood ratio must be > 10 to be considered valuable.

• Positive predictive value is the same as a positive likelihood ratio.

A biochemical company now wants to develop a new diagnostic screening test for breast cancer. What attribute would they most like their new test to have?

• Likelihood ratio approaching 1

• Low PPV

• High specificity

• High sensitivity

Answer explanation

Screening tests need to be highly sensitive (catching everyone who MAY be positive) and referring them then for more specific testing for actual disease rule in.

A 68 yo male patient with a history of type II DM, HTN and HLD present to the ED with a complaint of L chest pressure, L jaw pain and SOB. You are concerned for a myocardial infarction (MI). The troponin I comes back elevated and this test is known to have a +LR of 6.3 for MI. What does this mean to you clinically?

• There is strong evidence to rule-out disease.

• There is weak evidence to rule-in disease.

• There is strong evidence to rule-in disease.

• These results are equivocal.

A patient presents with left leg swelling and shortness of breath to the emergency department. You order a stat d-dimer on the patient to rule out the high stakes diagnosis of pulmonary embolism (PE). This test is known for it's insanely high sensitivity (positive ALL the freaking time!) and low specificity. The test actually comes back negative (yay!). The -LR for this test is known to be 0.09. What does this mean clinically?

• Strong evidence that the diagnosis is not PE.

• Weak evidence that the diagnosis is not PE.

• The result means nothing and more definitive testing needs to be done to rule out this high-stakes condition.

• Strong evidence that the diagnosis is PE.

Answer explanation

The further LR is from 1 in either direction the better the test. Also look at the sensitivity. Highly sensitive test that is negative= disease ruled out, SnOUT.

A 70-year-old woman is transferred from a nursing home to the emergency department (ED) due to fever, cough and shortness of breath. As per her daughter, the patient has had a productive cough for 2 days and became more short of breath and less responsive earlier today. The patient’s past medical history is significant for diabetes mellitus, hypertension, and high cholesterol. Vitals: 38.9°C, 114, 90/65, 28, and O2 sat 87% on RA (96% with 3L oxygen by nasal cannula). On examination, she is awake but slow to answer questions. The daughter states that her mother is usually more alert than this. Her skin is dry and warm to touch. Her heart sounds are regular and mildly tachycardic without any S₃ or S₄. On auscultation, she has rhonchi at the right lung base. She does not have any jugular venous distention, lower extremity edema, or calf tenderness. Based on your concerns, what are your orders?

Answer explanation

You may not be completely confident with this style question yet, and that's ok! Here's what my order set would look like:

-saline lock (IV access)

-Basic labs:

CBC w/diff (concern for sepsis), CMP (check electrolytes, liver function, renal function- again sepsis affects all major end organs)

-U/A (urinalysis-UTI super common reason for sepsis in elderly)

-Blood cultures x2

-Portable chest x-ray (she's hypoxic so probably don't want to send to radiology for the two view)

-Lactic acid

- Procalcitonin (doesn't change my life in the ED but they may care inpatient)

Initial Plan: hang broad spec abx and admit for further management.

-other orders that would be placed but aren't part of your repertoire yet: this could be an MI or PE so troponin I x3, ECG, monitored bed

Don't feel overwhelmed by this list, we will get there! Start thinking critically about what you would order, what COULD it be? What do you need to rule out??

Give me a set of vital signs that are concerning for sepsis:

Answer explanation

Think hypotension (defined as anything less than 90 systolic) plus tachycardia (heart trying to compensate for low BP)-also likely accompanied by fever- know that this 38C and above (38=100.4F=definition of fever). Keep in mind though that the elderly do not always mount a febrile response-their bodies are old and tired, and just generally don't do things like they once did!