Clinical Practice Points
Cerebral lesions that are 3 mm or larger on imaging are associated with incident stroke,
but smaller lesions are typically considered clinically insignificant. This cohort
study of a biracial population found that the presence of lesions smaller than 3 mm,
lesions 3 mm or larger, and white matter hyperintensities may all confer a heightened
risk for incident stroke and mortality.
Use this study to:
- Review with your learners how a cohort study works. Ask what the “exposure”
was in this cohort. What were the outcomes of interest, and how were they ascertained?
How might the definitions used for the exposure and outcomes affect the study's results?
- Ask your learners what the limitations of the study are. Why might it be important
that one quarter of the cohort's participants declined to have baseline magnetic resonance
- Plan a visit with your team to the neuroradiology reading room. Ask a neuroradiologist
to review basic neuroanatomy with your team, as well as examples of imaging from patients
with hemorrhagic and nonhemorrhagic stokes. Ask what T1- and T2-weighted images demonstrate.
What is white matter hyperintensity? Can the neuroradiologist show examples of “subclinical”
lesions smaller than 3 mm?
- Ask if you should do anything differently for patients with the types of subclinical
lesions studied here. What further studies are required before these research findings
should alter clinical practice?
This systematic review found that early initiation of ART improves survival of patients
with tuberculosis and HIV infection with CD4+ T-cell counts less than 0.050 × 109 cells/L, but evidence is insufficient when the counts are lower. Another paper reviews
the successes and persistent challenges in the global fight to control tuberculosis.
The authors note that despite substantial gains, tuberculosis remains a major threat
to health around the world and that its control must be seen as both a public health
imperative and a vital component of economic development plans.
Use these papers to:
- Start a teaching session with a multiple-choice question. We've provided one below.
- Ask your learners what the “immune reconstitution syndrome” is and why
there has been concern regarding when to initiate ART for HIV in patients diagnosed
with tuberculosis. What other problems might simultaneous ART and anti-TB therapies
pose? What drug–drug interactions need to be considered? Will adherence be
- Review how to treat TB in HIV-infected patients. Use the information in ACP Smart
Medicine's HIV Disease and Tuberculosis.
- Review why the “risk of bias” assessment in a systematic review is important.
How does it shape how we should consider the results? Look at Figure 2 in the systematic
review of ART in patients with TB. Ask your learners to define each of the potential
biases listed (allocation concealment, selective reporting, etc.) and how their presence
could affect the results.
- Discuss the challenges to controlling drug-resistant TB.
PCSK9 is an enzyme involved in the degradation of low-density lipoprotein (LDL) receptors,
and drugs inhibiting its function are being reviewed by the FDA for the treatment
of hypercholesterolemia. This meta-analysis of phase 2 and phase 3 trials in adults
with hypercholesterolemia found that PCSK9 inhibitors produced profound reductions
in LDL cholesterol and lipoprotein(a); caused few serious adverse events; and, although
data were sparse, seemingly reduced myocardial infarction rates and all-cause mortality.
Use this paper to:
- Review current therapies for hypercholesterolemia.
- Review lipid metabolism, noting where PCSK9 functions and how its inhibition might
be expected to affect LDL levels.
- Invite a colleague who has expertise in clinical trials to review with your learners
the process of testing and obtaining approval for a new drug. Review what each of
the phases of drug trials assesses (e.g., phase 2, 3).
A 33-year-old man is evaluated after learning that a person living in his home was
recently found to have active tuberculosis. The patient has no acute symptoms. He
was recently diagnosed with HIV infection, and his CD4 cell count is 250/µL.
He is a U.S. citizen and has no history of incarceration, homelessness, or travel
to areas with an increased prevalence of tuberculosis. He takes no medications but
had been planning to begin antiretroviral therapy at his next office visit.
On physical examination, vital signs are normal. The remainder of the examination,
including cardiopulmonary findings, is normal.
A tuberculin skin test induces 0 mm of induration. A chest radiograph is normal.
Which of the following is the most appropriate next step in the management of this
A. Begin isoniazid and pyridoxine
B. Begin isoniazid, rifampin, pyrazinamide, pyridoxine, and ethambutol
C. Begin rifampin and pyrazinamide
D. No additional evaluation or therapy is needed
A. Begin isoniazid and pyridoxine
Regardless of their response to a tuberculin skin test or interferon-γ release
assay, patients with HIV infection who have had a known recent exposure to a close
contact with active tuberculosis should receive treatment for latent tuberculosis
infection after active disease has been excluded.
Manage an immunocompromised patient who has been exposed to a close contact with active
Isoniazid and pyridoxine should be started for treatment of latent tuberculosis infection
(LTBI). This patient has HIV infection and was recently exposed to a close contact
with active tuberculosis. Patients with HIV infection or other serious immunocompromising
conditions who are close contacts of persons with active tuberculosis should be treated
for LTBI regardless of the results of a tuberculin skin test or interferon-γ
release assay (IGRA) once active disease has been excluded. This patient is asymptomatic
and has a normal chest radiograph, which exclude active disease. Patients with LTBI
are typically treated with a 9-month regimen of isoniazid. Pyridoxine may also be
given to certain patients at risk for developing peripheral neuropathy secondary to
isoniazid. These include patients with HIV infection, diabetes mellitus, uremia, alcoholism,
malnutrition, and seizure disorders, as well as pregnant women. In this patient, the
tuberculin skin test or IGRA should be repeated 8 to 10 weeks after the most recent
exposure. If results are still negative, isoniazid and pyridoxine can be discontinued.
However, some experts recommend a complete course of treatment for LTBI in patients
with HIV infection, who may not be able to mount a positive tuberculin skin test or
IGRA response because of anergy.
Isoniazid, rifampin, pyrazinamide, pyridoxine, and ethambutol are used to treat active
tuberculosis. This patient is asymptomatic and has a normal chest radiograph, making
active disease highly unlikely.
The use of rifampin and pyrazinamide for treatment of LTBI is not recommended by the
Centers for Disease Control and Prevention and the American Thoracic Society because
of associated hepatic toxicity, which results in increased rates of hospitalization
This patient with HIV infection and a recent exposure to a close contact with active
tuberculosis requires treatment for latent tuberculosis infection, regardless of the
results of a tuberculin skin test or IGRA; providing no further evaluation or treatment
would not be appropriate.
National Tuberculosis Controllers Association; Centers for Disease Control and Prevention
(CDC). Guidelines for the investigation of contacts of persons with infectious tuberculosis:
Recommendations from the National Tuberculosis Controllers Association and CDC. MMWR
Recomm Rep. 2005;54(RR-15):1-47. PMID: 16357823
This question was derived from MKSAP® 16, the latest edition of the Medical Knowledge Self-Assessment Program.