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Although tuberculosis (TB) is not a major public health issue in low-burden countries, severe cases are still a matter of concern.

RESULTS: The mean age was 47.4 ± 14.7 years; 40 patients were human immunodeficiency virus (HIV) infected, with a median CD4 cell count of 74 cells/mm(3). The survival analysis showed that 21 patients died during their time in the ICU. The observed risk factors for ICU mortality were organ failure, high Simplified Acute Physiology Score II (SAPS II) and Sequential Organ Failure Assessment scores, and concomitant non-tuberculous infection. In multivariate analysis, only SAPS II score was significantly associated with mortality.

CONCLUSION: Risk factors identified in this study are different from those in high-burden countries, and were not associated with the site of TB disease. There was no difference in TB presentation between HIV-infected and non-HIV-infected patients, and HIV was not a mortality risk factor. Low-burden countries still experience high death rates due to severe TB.

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Drug susceptibility testing (DST) against second-line tuberculosis drugs (SLDs) is essential for improving outcomes among multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) cases.

OBJECTIVE: To evaluate the potential cost-effectiveness of rapid DST for SLDs.
DESIGN: We constructed a decision analysis model of Xpert(®) MTB/RIF-based TB diagnosis in East and South-East Asia to compare culture-based DST vs. a hypothetical rapid SLD DST system for specimens resistant to rifampin. Our primary outcomes were the effectiveness and incremental cost-effectiveness of a rapid SLD DST assay relative to culture-based DST.

RESULTS: For rapid SLD DST to be more effective than culture-based DST, treating individuals with pre-XDR/XDR-TB with a standardized MDR-TB regimen while awaiting culture-based DST must incur at least 30% excess XDR-TB mortality (100% = treatment with first-line drugs); rapid SLD DST should attain an aggregate sensitivity and specificity for all pre-XDR/XDR mutations of 88% and 96%, respectively. The unit cost of the rapid SLD DST assay must approach that of culture to achieve common thresholds for cost-effectiveness in low-income countries.

CONCLUSION: Rapid SLD DST has the potential to be cost-effective, but must meet stringent criteria for accuracy and costs, and requires that standardized second-line treatment for pre-XDR/XDR-TB incur substantial excess mortality before the return of culture results.

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Distinguishing non-purulent complicated parapneumonic pleural effusions (CPPE) from uncomplicated parapneumonic pleural effusions (UPPE) is challenging. We aimed to determine whether serum C-reactive protein (sCRP), alone or in combination with classical pleural fluid parameters, is useful in making such discrimination.

METHODS: The study was composed of a total of 104 consecutive patients, of whom 47 had UPPE and 57 had CPPE. Standard biochemical pleural fluid data along with sCRP were measured.

RESULTS: sCRP at the time of thoracentesis or chest tube insertion was significantly higher in CPPE (238 mg/L) than UPPE (147 mg/L). At the optimum cutoff value of 200 mg/L, sCRP had a sensitivity, specificity, likelihood ratio positive, likelihood ratio negative, and area under the receiver-operating characteristic curve for diagnosing CPPE of 58 %, 81 %, 3.1, 0.52, and 0.67, respectively. The combination of sCRP >200 mg/L with pleural fluid glucose <60 mg/dL using an "and" rule achieved a specificity of 98 %, whereas both parameters combined in an "or" rule had a sensitivity of 81 %, which was higher than that of pleural fluid pH (57 %) or glucose (54 %).

CONCLUSIONS: sCRP, when combined with classical pleural fluid biochemistries, improves the diagnostic accuracy in identifying those patients with non-purulent parapneumonic effusions who need chest drainage.

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Drug delivery to the lungs by inhalation offers a targeted drug therapy for respiratory diseases. However, the therapeutic efficacy of inhaled drugs is limited by their rapid clearance in the lungs. Carriers providing sustained drug release in the lungs can improve therapeutic outcomes of inhaled medicines because they can retain the drug load within the lungs and progressively release the drug locally at therapeutic levels.

This review presents the different formulation strategies developed to control drug release in the lungs including microparticles and the wide array of nanomedicines. Large and porous microparticles offer excellent aerodynamic properties. Their large geometric size reduces their uptake by alveolar macrophages, making them a suitable carrier for sustained drug release in the lungs. Similarly, nanocarriers present significant potential for prolonged drug release in the lungs because they largely escape uptake by lung-surface macrophages and can remain in the pulmonary tissue for weeks. They can be embedded in large and porous microparticles in order to facilitate their delivery to the lungs. Conjugation of drugs to polymers as polyethylene glycol can be particularly beneficial to sustain the release of proteins in the lungs as they allow high protein loading.

Drug conjugates can be readily delivered to respiratory airways by any current nebulizer device. Nonetheless, liposomes represent the formulation most advanced in clinical development. Liposomes can be prepared with lipids endogenous to the lungs and are particularly safe. Their composition can be adjusted to modulate drug release and they can encapsulate both hydrophilic and lipophilic compounds with high drug loading.

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