Mycobacterium tuberculosis Lipolytic Enzymes as Potential Biomarkers for the Diagnosis of Active Tuberculosis

BACKGROUND: New diagnosis tests are urgently needed to address the global tuberculosis (TB) burden and to improve control programs especially in resource-limited settings. An effective in vitro diagnostic of TB based on serological methods would be regarded as an attractive progress because immunoassays are simple, rapid, inexpensive, and may offer the possibility to detect cases missed by standard sputum smear microscopy. However, currently available serology tests for TB are highly variable in sensitivity and specificity. Lipolytic enzymes have recently emerged as key factors in lipid metabolization during dormancy and/or exit of the non-replicating growth phase, a prerequisite step of TB reactivation. The focus of this study was to analyze and compare the potential of four Mycobacterium tuberculosis lipolytic enzymes (LipY, Rv0183, Rv1984c and Rv3452) as new markers in the serodiagnosis of active TB. METHODS: Recombinant proteins were produced and used in optimized ELISA aimed to detect IgG and IgM serum antibodies against the four lipolytic enzymes. The capacity of the assays to identify infection was evaluated in patients with either active TB or latent TB and compared with two distinct control groups consisting of BCG-vaccinated blood donors and hospitalized non-TB individuals. RESULTS: A robust humoral response was detected in patients with active TB whereas antibodies against lipolytic enzymes were infrequently detected in either uninfected groups or in subjects with latent infection. High specifity levels, ranging from 93.9% to 97.5%, were obtained for all four antigens with sensitivity values ranging from 73.4% to 90.5%, with Rv3452 displaying the highest performances. Patients with active TB usually exhibited strong IgG responses but poor IgM responses. CONCLUSION: These results clearly indicate that the lipolytic enzymes tested are strongly immunogenic allowing to distinguish active from latent TB infections. They appear as potent biomarkers providing high sensitivity and specificity levels for the immunodiagnosis of active TB

Adverse Drug Reaction-Related Hospitalizations in Elderly Australians: A Prospective Cross-Sectional Study in Two Tasmanian Hospitals

© 2017, Springer International Publishing Switzerland. Introduction: Adverse drug reactions (ADRs) have been commonly cited as a major cause of hospital admissions in older individuals. However, despite the apparent magnitude of this problem, there are limited prospective data on ADRs as a cause of hospitalization in elderly medical patients. Objectives: The objective of this study was to evaluate the proportion, clinical characteristics, causality, severity, preventability, and outcome of ADR-related admissions in older patients admitted to two Tasmanian hospitals. Methods: We conducted a prospective cross-sectional study at the Royal Hobart and Launceston General Hospitals in Tasm ania, Australia. A convenience sample of patients, aged 65 years and older, undergoing unplanned overnight medical admissions was screened. ADR-related admissions were determined through expert consensus from detailed review of medical records and patient interviews. The causality, preventability and severity of each ADR-related admission were assessed. Results: Of 1008 admissions, the proportion of potential ADR-related medical admissions was 18.9%. Most (88.5%) ADR-related admissions were considered preventable. Cardiovascular complaints (29.3%) represented the most common ADRs, followed by neuropsychiatric (20.0%) and renal and genitourinary disorders (15.2%). The most frequently implicated drug classes were diuretics (23.9%), agents acting on the renin angiotensin system (16.4%), ß-blocking agents (7.1%), antidepressants (6.9%), and antithrombotic agents (6.9%). Application of the Naranjo algorithm found 5.8% definite, 70.1% probable, and 24.1% possible ADRs. ADR severity was rated moderate and severe in 97.9% and 2.1% of admissions, respectively. For most (93.2%) ADR-related admissions the ADR resolved and the patient recovered. Conclusion: Hospitalization due to an ADR is a common occurrence in this older population. There is need for future studies to implement and evaluate interventions to reduce the risk of ADR-related admissions in elderly populations

Prediction of hospitalization due to adverse drug reactions in elderly community-dwelling patients (The PADR-EC score)

© 2016 Parameswaran Nair et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background Adverse drug reactions (ADRs) are the major cause of medication-related hospital admissions in older patients living in the community. This study aimed to develop and validate a score to predict ADR-related hospitalization in people aged =65 years. Methods ADR-related hospitalization and its risk factors were determined using a prospective, cross-sectional study in patients aged =65 years admitted to two hospitals. A predictive model was developed in the derivation cohort (n = 768) and the model was applied in the validation cohort (n = 240). ADR-related hospital admission was determined through expert consensus from comprehensive reviews of medical records and patient interviews. The causality and preventability of the ADR were assessed based on the Naranjo algorithm and modified Schumock and Thornton criteria, respectively. Results In the derivation sample (mean [±SD] age, 80.1±7.7 years), 115 (15%) patients were admitted due to a definite or probable ADR; 92.2% of these admissions were deemed preventable. The number of antihypertensives was the strongest predictor of an ADR followed by presence of dementia, renal failure, drug changes in the preceding 3 months and use of anticholinergic medications; these variables were used to derive the ADR prediction score. The predictive ability of the score, assessed from calculation of the area under the receiver operator characteristic (ROC) curve, was 0.70 (95% confidence interval (CI) 0.65-0.75). In the validation sample (mean [±SD] age, 79.6±7.6 years), 30 (12.5%) patients' admissions were related to definite or probable ADRs; 80% of these admissions were deemed preventable. The area under the ROC curve in this sample was 0.67 (95% CI 0.56-0.78). Conclusions This study proposes a practical and simple tool to identify elderly patients who are at an increased risk of preventable ADR-related hospital admission. Further refinement and testing of this tool is necessary to implement the score in clinical practice