A prospective multicentre diagnostic accuracy study for the Truenat tuberculosis assays.

BACKGROUND: Bringing reliable and accurate tuberculosis (TB) diagnosis closer to patients is a key priority for global TB control. Molbio Diagnostics have developed the Truenat point-of-care molecular assays for detection of TB and rifampicin (RIF) resistance. METHODS: We conducted a prospective multicentre diagnostic accuracy study at 19 primary healthcare centres and seven reference laboratories in Peru, India, Ethiopia and Papua New Guinea to estimate the diagnostic accuracy of the point-of-care Truenat MTB, MTB Plus and MTB-RIF Dx assays for pulmonary TB using culture and phenotypic drug susceptibility testing as the reference standard, compared with Xpert MTB/RIF or Ultra. RESULTS: Of 1807 enrolled participants with TB signs/symptoms, 24% were culture-positive for Mycobacterium tuberculosis, of which 15% were RIF-resistant. In microscopy centres, the pooled sensitivity of Truenat MTB and Truenat MTB Plus was 73% (95% CI 67-78%) and 80% (95% CI 75-84%), respectively. Among smear-negative specimens, sensitivities were 36% (95% CI 27-47%) and 47% (95% CI 37-58%), respectively. Sensitivity of Truenat MTB-RIF was 84% (95% CI 62-95%). Truenat assays showed high specificity. Head-to-head comparison in the central reference laboratories suggested that the Truenat assays have similar performance to Xpert MTB/RIF. CONCLUSION: We found the performance of Molbio's Truenat MTB, MTB Plus and MTB-RIF Dx assays to be comparable to that of the Xpert MTB/RIF assay. Performing the Truenat tests in primary healthcare centres with very limited infrastructure was feasible. These data supported the development of a World Health Organization policy recommendation of the Molbio assays.

Evaluation of metformin in combination with rifampicin containing antituberculosis therapy in patients with new, smear-positive pulmonary tuberculosis (METRIF): study protocol for a randomised clinical trial.

INTRODUCTION: Shorter duration of treatment for the management of drug-susceptible pulmonary tuberculosis (TB) would be a significant improvement in the care of patients suffering from the disease. Besides newer drugs and regimens, other modalities like host-directed therapy are also being suggested to reach this goal. This study's objective is to assess the efficacy and safety of metformin-containing anti-TB treatment (ATT) regimen in comparison to the standard 6-month ATT regimen in the treatment of patients with newly diagnosed sputum smear-positive drug-sensitive pulmonary TB. METHODS AND ANALYSIS: We are conducting a multicentric, randomised open-label controlled clinical trial to achieve the study objective. The intervention group will receive isoniazid (H), rifampicin (R), ethambutol (E) and pyrazinamide (Z) along with 1000 mg of daily metformin (Met) for the first 2 months while the control group will receive only HRZE. After 2 months, both the groups will receive HRE daily for 4 months. The primary endpoint is time to sputum culture conversion. Secondary endpoints will include time to detection of Mycobacterium tuberculosis in sputum, pharmacokinetics and pharmacogenomics of study drugs, drug-drug interactions, safety and tolerability of the various combinations and measurement of autophagy and immune responses in the study participants. ETHICS AND DISSEMINATION: The ethics committee of the participating institutes have approved the study. Results from this trial will contribute to evidence towards constructing a shorter, effective and safe regimen for patients with TB. The results will be shared widely with the National Programme managers, policymakers and stakeholders through open access publications, dissemination meetings, conference abstracts and policy briefs. This is expected to provide a new standard of care for drug-sensitive patients with pulmonary TB who will not only reduce the number of clinic visits and lost to follow-up of patients from treatment but also reduce the burden on the healthcare system. TRIAL REGISTRATION NUMBER: CTRI/2018/01/011176; Pre-results.

A district general hospital experience of palliative biliary stenting.

BACKGROUND: Palliative management of malignant pancreaticobiliary (PB) disease typically takes the form of endoscopic biliary stenting with a covered metal stent. We set out to assess outcomes from endoscopic biliary stenting (endoscopic retrograde cholangiopancreatography, ERCP) for malignant disease in our district general hospital (DGH). METHODS: We identified patients with malignant PB disease who underwent primary ERCP between 2011 and 2012. Case notes were reviewed for clinical outcomes and involvement of palliative care. RESULTS: 38 patients underwent biliary stenting in this period. Median age was 75.6 years (53.6-99.8 years). 35 stents were placed for primary PB malignancy. 31 of these stents were covered metal stents and 6 were uncovered. Bilirubin decreased from a median of 218 to 112 µmol/L (median decrease 55 µmol/L). Complications occurred in the following 13 cases: 7 blocked stents (18.9%), 2 of which were associated with sepsis; 2 cases of stent migration (8.1%); 3 cases of biliary sepsis (8.1%) and 1 episode of pancreatitis (2.7%). Subsequently, 12 patients underwent a single repeat ERCP and 1 patient underwent 3 further ERCPs. Median survival following ERCP and stent was 78 days (10-806). 28 patients (76%) were known to the hospital palliative care team. CONCLUSIONS: Our DGH provides local service with complication rates comparable to those described in the literature. This allows care of patients with limited prognosis to be treated close to home. The majority of stent complications and mortality occur within 3 months. Input from the palliative care team is useful when considering whether a patient has a prognosis long enough to benefit from the procedure.