Understanding tuberculosis transmission and progression: A prospective cohort study of index cases and close contacts in Moldova.

Objectives: This study aims to determine the progression rate, risk factors and timeline for the progression from exposure to active tuberculosis (TB) in a high-risk population. Using a prospective cohort in the Republic of Moldova, we investigated pulmonary TB disease progression among close contacts of patients with TB in a low-burden country with high rates of drug-resistant TB.

Methods: Close contacts of patients with newly diagnosed TB were recruited and monitored to evaluate for progression rates to active TB.

Prospective exploratory evaluation of Cepheid Xpert Mycobacterium tuberculosis host response cartridge: a focus on adolescents and young adults.

Background: An accurate, rapid, non-sputum-based triage test for diagnosing tuberculosis (TB) is needed.

Methods: A prospective evaluation of the Xpert-MTB-HR cartridge, a prototype blood-based host-response mRNA signature assay, among individuals presenting with TB-like symptoms was performed in Pakistan and results were compared to three reference standards: Xpert MTB/RIF Ultra, bacteriological confirmation (Xpert MTB/RIF Ultra and/or culture positivity), and composite clinical diagnosis (clinician diagnosis, treatment initiation, Xpert MTB/RIF Ultra, and/or culture positivity). Analyses were conducted both for the entire study cohort and separately in the adolescent and young adult cohort (ages 10-24).

Predicting stringent QuantiFERON-TB Gold Plus conversions in contacts of tuberculosis patients.

Objectives: To assess associations between disease severity in index TB patients and QuantiFERON-TB Gold Plus (QFT-Plus) results in contacts, and predictors for QFT-Plus conversion in contacts over 6-12 months.

Methods: TB patients (n = 295) and the contacts (n = 1051) were enrolled during 2018-2021 with QFT-Plus performed at baseline and months 6 and 12. A strong CD8 response was defined as TB2 interferon gamma (IFN-γ) response minus TB1 >0.

Cost-Effectiveness of Humidified High-Flow Therapy (HHFT) for COPD Patients on Long-Term Oxygen Therapy.

Purpose: Chronic obstructive pulmonary disease (COPD) is the third leading cause of mortality, and is associated with significant respiratory impairment, decreased quality of life, and high health care costs. Recent evidence indicates significant clinical benefit results from adding humidified high-flow therapy (HHFT) to standard long-term oxygen therapy (LTOT) as a home-based therapy in persons with severe COPD. The objective was to evaluate the cost-effectiveness of adding HHFT to standard treatment of COPD patients using LTOT with US healthcare cost estimates.

Clinical Evaluation of the XDR-LFC Assay for the Molecular Detection of Isoniazid, Rifampin, Fluoroquinolone, Kanamycin, Capreomycin, and Amikacin Drug Resistance in a Prospective Cohort.

While the goal of universal drug susceptibility testing has been a key component of the WHO End TB Strategy, in practice, this remains inaccessible to many. Rapid molecular tests for tuberculosis (TB) and antituberculosis drug resistance could significantly improve access to testing. In this study, we evaluated the accuracy of the Akonni Biosystems XDR-TB (extensively drug-resistant TB) TruArray and lateral-flow-cell (XDR-LFC) assay (Akonni Biosystems, Inc.

Rapid Detection of Extensively Drug-Resistant Tuberculosis in Clinical Samples Using a Novel Tabletop Platform: Protocol for a Prospective Clinical Study.

Background: The lack of accurate and efficient diagnostic devices for extensively drug-resistant tuberculosis (XDR-TB) makes it a severe threat to global public health. A prospective clinical study in an intended-use cohort was designed to evaluate the Akonni Biosystems XDR-TB TruArray and lateral flow cell (XDR-LFC) to address this gap in tuberculosis diagnostics.

Objective: This paper presents the protocol for a study that aims to document the conceptualization and design of this evaluation method for early dissemination while data collection and analysis are ongoing.

Laboratory Evaluation of a Lateral-Flow Cell for Molecular Detection of First-Line and Second-Line Antituberculosis Drug Resistance.

Despite the WHO's call for universal drug susceptibility testing for all patients being evaluated for tuberculosis (TB), a lack of rapid diagnostic tests which can fully describe TB resistance patterns is a major challenge in ensuring that all persons diagnosed with drug-resistant TB are started on an appropriate treatment regime. We evaluated the accuracy of the Akonni Biosystems XDR-TB TruArray and lateral-flow cell (XDR-LFC), a novel multiplex assay to simultaneously detect mutations across seven genes that confer resistance to both first- and second-line anti-TB drugs. The XDR-LFC includes 271 discrete three-dimensional gel elements with target-specific probes for identifying mutations in , promoter, and promoter (isoniazid), (rifampin), (fluoroquinolones), and promoter (kanamycin), and (capreomycin and amikacin).

Cost-Effectiveness of a Pharmacogenetic Test to Guide Treatment for Major Depressive Disorder.

Background: Recent clinical trials indicate that pharmacogenetic-guided treatment of major depressive disorder (MDD) results in higher treatment response rates by genetically matching patients to medications and avoiding a trial-and-error process.

Objective: To evaluate the cost-effectiveness of a pharmacogenetic test (IDGx) that has demonstrated effectiveness compared with standard of care (SOC) medication management among patients with varied MDD severity.

Methods: Data from a large prospective, randomized controlled trial of treatment-naive patients or patients with inadequately controlled MDD in general practice and psychiatric treatment settings were used to build a Markov state-transition probability model.

Cost analysis of rapid diagnostics for drug-resistant tuberculosis.

Background: Growth-based drug susceptibility testing (DST) is the reference standard for diagnosing drug-resistant tuberculosis (TB), but standard time to result (TTR) is typically ≥ 3 weeks. Rapid tests can reduce that TTR to days or hours, but accuracy may be lowered. In addition to the TTR and test accuracy, the cost of a diagnostic test may affect whether it is adopted in clinical settings.

Performance Comparison of Three Rapid Tests for the Diagnosis of Drug-Resistant Tuberculosis.

Background: The aim of this study was to compare the performance of several recently developed assays for the detection of multi- and extensively drug-resistant tuberculosis (M/XDR-TB) in a large, multinational field trial.

Methods: Samples from 1,128 M/XDR-TB suspects were examined by Line Probe Assay (LPA), Pyrosequencing (PSQ), and Microscopic Observation of Drug Susceptibility (MODS) and compared to the BACTEC MGIT960 reference standard to detect M/XDR-TB directly from patient sputum samples collected at TB clinics in India, Moldova, and South Africa.

Results: Specificity for all three assays was excellent: 97-100% for isoniazid (INH), rifampin (RIF), moxifloxacin (MOX) and ofloxacin (OFX) and 99-100% for amikacin (AMK), capreomycin (CAP) and kanamycin (KAN) resistance.

The Global Consortium for Drug-resistant Tuberculosis Diagnostics (GCDD): design of a multi-site, head-to-head study of three rapid tests to detect extensively drug-resistant tuberculosis.

Background: Drug-resistant tuberculosis (DR-TB) remains a threat to global public health, owing to the complexity and delay of diagnosis and treatment. The Global Consortium for Drug-resistant Tuberculosis Diagnostics (GCDD) was formed to develop and evaluate assays designed to rapidly detect DR-TB, so that appropriate treatment might begin more quickly. This paper describes the methodology employed in a prospective cohort study for head-to-head assessment of three different rapid diagnostic tools.