Commercial Nucleic-Acid Amplification Tests for Diagnosis of Pulmonary Tuberculosis in Respiratory Specimens: Meta-Analysis and Meta-Regression

BACKGROUND: Hundreds of studies have evaluated the diagnostic accuracy of nucleic-acid amplification tests (NAATs) for tuberculosis (TB). Commercial tests have been shown to give more consistent results than in-house assays. Previous meta-analyses have found high specificity but low and highly variable estimates of sensitivity. However, reasons for variability in study results have not been adequately explored. We performed a meta-analysis on the accuracy of commercial NAATs to diagnose pulmonary TB and meta-regression to identify factors that are associated with higher accuracy. METHODOLOGY/PRINCIPAL FINDINGS: We identified 2948 citations from searching the literature. We found 402 articles that met our eligibility criteria. In the final analysis, 125 separate studies from 105 articles that reported NAAT results from respiratory specimens were included. The pooled sensitivity was 0.85 (range 0.36-1.00) and the pooled specificity was 0.97 (range 0.54-1.00). However, both measures were significantly heterogeneous (p<.001). We performed subgroup and meta-regression analyses to identify sources of heterogeneity. Even after stratifying by type of commercial test, we could not account for the variability. In the meta-regression, the threshold effect was significant (p = .01) and the use of other respiratory specimens besides sputum was associated with higher accuracy. CONCLUSIONS/SIGNIFICANCE: The sensitivity and specificity estimates for commercial NAATs in respiratory specimens were highly variable, with sensitivity lower and more inconsistent than specificity. Thus, summary measures of diagnostic accuracy are not clinically meaningful. The use of different cut-off values and the use of specimens other than sputum could explain some of the observed heterogeneity. Based on these observations, commercial NAATs alone cannot be recommended to replace conventional tests for diagnosing pulmonary TB. Improvements in diagnostic accuracy, particularly sensitivity, need to be made in order for this expensive technology to be worthwhile and beneficial in low-resource countries

[Characteristics, diagnosis and treatment of non-tuberculous mycobacteria in non-immunocomprised patients.]

Non-tuberculous mycobacteria (NTM) can be the etiologic agents of chronic pulmonary disease, lymphadenitis, skin and soft-tissue infection and disseminated disease in non-immunocompromised patients. The recognition of disease needs repeated isolation of the NTM from bronchopulmonary secretions or from tissue biopsies, and its identification by specific laboratory methods. A wide spectrum of clinical presentations and severity of disease can be found, from spontaneous healing to progressive and destructive lung disease, and death, according to predisposing conditions and mycobacterial species. The choice of surgical and drug treatment will depend on identification of specific pathogen and clinical evaluation

Ionic, Electrical, and Secretory Effects of Inhibitors of Arachidonic-acid Metabolism in Mouse Pancreatic Beta-cells

Mouse islets were used to study the effects of inhibitors of cyclooxygenase and lipoxygenase pathways on insulin release, ionic fluxes, and beta-cell membrane potential. The cyclooxygenase inhibitors, Na-salicylate and Na-acetylsalicylate, potentiated glucose-induced insulin release, despite a decrease in Ca influx evidenced by inhibition of the Ca-dependent electrical activity in beta-cells and Ca-45 efflux from islets perifused with a medium containing Ca. This paradox can probably be explained by a mobilization of intracellular Ca (acceleration of Ca-45 efflux in the absence of Ca) with subsequent activation of K+ channels (acceleration of Rb-86 efflux) and repolarization of the membrane. These effects of salicylate could not be ascribed to a change in intracellular pH because they were not mimicked by 2-Cl-benzoate, which has a similar pK as salicylate but increased insulin release by stimulating Ca influx in beta-cells. Among the other cyclooxygenase inhibitors tested, indomethacin caused a slight potentiation of insulin release accompanied by marginal increases in Ca-45 efflux and electrical activity, whereas flurbiprofen and ibuprofen were ineffective. Among the lipoxygenase inhibitors, compound BW 755c reversibly decreased glucose-induced insulin release by inhibiting Ca influx in beta-cells, but nordihydroguaiaretic acid had no effect. Inhibitors of arachidonic acid metabolism have effects on ionic fluxes and beta-cell membrane potential, which may explain some of the changes in insulin release they produce

Miniatelier pedagogico sulla Medicina narrativa

Quaderni delle Conferenze Permanenti della Facoltà di Medicina e Chirurgi