June 2010: Volume 36, Number 6
Interferon-g Release Assays Out-Perform Tuberculin Skin Tests in Detecting Active TB
A new meta-analysis comparing interferon-g release assays (IGRAs) for detecting active tuberculosis (TB) found that in comparison to the tuberculin skin test (TST), the newest commercial IGRAs are superior for detecting the disease, particularly in developed countries (Chest 2010; 137:952–68). According to the authors, the findings support the primary use of IGRAs, especially in high-risk groups such as immunosuppressed individuals with high potential for TB reactivation. Due to the poor accuracy of TST among patients with TB, two-step screening strategies with TST as a first test and IGRA as a second should be considered for contact tracing.
The authors conducted the study in response to a plethora of recent research about IGRAs, which followed an earlier meta-analysis that summarized studies involving a second-generation Quanti-FERON Gold whole blood ELISA test with a variety of ELISpot assays using different cutoffs and preparations. With Food and Drug Administration approval of both the T-Spot.TB ELISpot, and a new QuantiFERON-Gold In-Tube assay incorporating a third RD-11 antigen, TB 7.7, the authors sought to establish performance benchmarks that laboratorians can expect when using the products.
From an initial 679 potentially relevant studies, the authors included 124 in their final analysis. Overall, the pooled sensitivity of TST was 70% versus 81% for Quanti-FERON-Gold In-Tube and 88% for T-Spot.TB. Sensitivities for the latter two increased to 84% and 89%, respectively, when results were restricted to developed countries. Pooled specificity was 99% and 86% for the QuantiFERON-Gold In-Tube and T-Spot.TB, respectively. The researchers also found that there was a lower frequency of indeterminate results among individuals tested with QuantiFERON-Gold In-Tube in comparison to T-Spot.TB, regardless of whether the patient was immunocompetent or immunocompromised.
iFOBT Superior to gFOBT in Detecting Colorectal Cancer
A randomized trial found that immunochemical fecal occult blood testing (iFOBT) not only had higher detection rates for colorectal cancer, adenomas, and advanced adenomas, but also higher screening participation rates in a general population than guaiac-based FOBT (gFOBT) (Gut 2010;59:62–68). The study also showed that while fewer patients opted for flexible sigmoidoscopy (FS), it detected significantly more advanced neoplasias and had a significantly higher diagnostic yield per 100 subjects than either iFOBT or gFOBT. Based on these findings, the authors suggest that iFOBT should be “strongly preferred over gFOBT screening” but that a dual-screening algorithm consisting of FS first and iFOBT as an alternative should be considered.
The study involved an initial sample of 15,011 individuals age 50-74 randomized in a 1:1:1 ratio to gFOBT, iFOBT, or FS, who, after stratification by age, sex and socioeconomic status, were invited to participate in the trial. Of those invited, there was an overall participation rate of 48%, with 49.5%, 61.5%, and 32.4% participating in gFOBT, iFOBT, and FS, respectively. Corresponding detection rates were 1.1%, 2.4%, and 8% for gFOBT, iFOBT, and FS, respectively. In comparison to gFOBT, the odds ratios of iFOBT and FS in detecting advanced neoplasia were 2.0 and 7.0, respectively, and in detecting colorectal cancer were 1.8 and 2.2, respectively.
Study Quantifies Risk Factors for Gout in Women
A new study that analyzed prospective data from the Framingham Heart Study indicates that higher levels of serum uric acid increase the risk of gout in women, but the rate of increase is lower than in men (Arthritis Rheum 2010;62:1069–76). This research, which had a 52-year follow-up period, may be the first to provide prospective, quantitative data on the relationship between serum uric acid levels and the risk of incident gout in women.
Gout generally is considered a disease of men, but an expanding evidence base suggests that it is increasingly prevalent in older women. One previous study found that the incidence of gout has doubled in women during the past 20 years. While serum uric acid concentration has been prospectively studied as a predictor of gout in men, no corresponding data has been published for women. Previous case series studies showed higher mean uric acid levels in women with gout than in men with gout, but since women generally have lower baseline levels of serum uric acid, the researchers sought to fill in the knowledge gap surrounding women and gout with this prospective analysis.
The study involved a subset of 2,476 women and 1,961 men who participated in the Framingham Heart Study and were gout-free at baseline and for whom there was complete follow-up data. There were 104 incident cases of gout in women and 200 in men, for a 1.4 per 1,000 person-years incidence in women and 4.0 per 1,000 person-years in men. The risk of gout was 46 times higher in women with the highest versus lowest serum uric acid levels (≥8 mg/dL compared with <5 mg/dL). Other risk factors that persisted after multivariate analysis included increasing age, obesity, alcohol intake, hypertension, and diuretic use. The magnitude of these risk factors was not significantly different in women than in men, except for a stronger age association in women.
BNP-Guided Care Reduces All-Cause Mortality in Chronic Heart Failure
A meta-analysis of chronic heart failure treatment guided by plasma levels of B-type natriuretic peptides (BNP) indicates that BNP-guided therapy reduces all-cause mortality compared with usual care, especially in patients less than age 75 (Arch Intern Med 2010;170:507–14). The researchers undertook the analysis because, although the lowering of BNP plasma levels represents a putative therapeutic target, studies exploring this approach generally have been underpowered to assess its impact on major cardiovascular and mortal events. In addition, there has been some variability in prior findings.
The meta-analysis involved eight randomized controlled trials with a total of 1,726 patients and mean duration of 16 months. The researchers found that overall, there was a significantly lower risk of all-cause mortality, with a relative risk of 0.76, for patients who received BNP-guided therapy versus those in the control group. In the subgroup of patients younger than age 75 the relative risk of all-cause mortality was even lower, 0.52, when compared with usual care subjects. However, this positive association with BNP-guided care did not extend to patients older than age 75. The risk of all-cause hospitalization and survival free of any hospitalization also was not significantly different between BNP-guided care and usual care.
The researchers noted that in patients who received BNP-guided care, there was an increase in prescription of heart failure medications such as spironolactone, ACE inhibitors and β-blockers, so the mechanism behind the decreased mortality observed in these patients could be due to more of them achieving the targeted dosage of drugs with proven prognostic efficacy. The authors called for further studies with larger populations and careful matching of key clinical variables to definitively address the effectiveness of BNP-guided care in treating heart chronic failure.