Direct benefit transfer for nutritional support of patients with TB in India-analysis of national TB program data of 3.7 million patients, 2018-2022.

BACKGROUND: Patients with TB have additional nutritional requirements and thus additional costs to the household. Ni-kshay Poshan Yojana(NPY) is a Direct Benefit Transfer (DBT) scheme under the National Tuberculosis Elimination Programme(NTEP) in India which offers INR 500 monthly to all notified patients with TB for nutritional support during the period of anti-TB treatment. Five years after its implementation, we conducted the first nationwide evaluation of NPY. METHODS: In our retrospective cohort study using programmatic data of patients notified with TB in nine randomly selected Indian states between 2018 and 2022, we estimated the proportion of patients who received at least one NPY instalment and the median time to receive the first instalment. We determined the factors associated (i) with non-receipt of NPY using a generalised linear model with Poisson family and log link and (ii) with time taken to receive first NPY benefit in 2022 using quantile regression at 50th percentile. RESULTS: Overall, 3,712,551 patients were notified between 2018 and 2022. During this period, the proportion who received at least one NPY instalment had increased from 56.9% to 76.1%. Non-receipt was significantly higher among patients notified by private sector (aRR 2.10;2.08,2.12), reactive for HIV (aRR 1.69;1.64,1.74) and with missing/undetermined diabetic status (aRR 2.02;1.98,2.05). The median(IQR) time to receive the first instalment had reduced from 200(109,331) days in 2018 to 91(51,149) days in 2022. Patients from private sector(106.9;106.3,107.4days), those with HIV-reactive (103.7;101.8,105.7days), DRTB(104.6;102.6,106.7days) and missing/undetermined diabetic status (115.3;114,116.6days) experienced longer delays. CONCLUSIONS: The coverage of NPY among patients with TB had increased and the time to receipt of benefit had halved in the past five years. Three-fourths of the patients received at least one NPY instalment, more than half of whom had waited over three months to receive the first instalment. NTEP has to focus on timely transfer of benefits to enable patients to meet their additional nutritional demands, experience treatment success and avoid catastrophic expenditure.

A Dose-Finding Study to Guide Use of Verapamil as an Adjunctive Therapy in Tuberculosis.

Induction of mycobacterial efflux pumps is a cause of Mycobacterium tuberculosis (Mtb) drug tolerance, a barrier to shortening antitubercular treatment. Verapamil inhibits Mtb efflux pumps that mediate tolerance to rifampin, a cornerstone of tuberculosis (TB) treatment. Verapamil's mycobacterial efflux pump inhibition also limits Mtb growth in macrophages in the absence of antibiotic treatment. These findings suggest that verapamil could be used as an adjunctive therapy for TB treatment shortening. However, verapamil is rapidly and substantially metabolized when co-administered with rifampin. We determined in a dose-escalation clinical trial of persons with pulmonary TB that rifampin-induced clearance of verapamil can be countered without toxicity by the administration of larger than usual doses of verapamil. An oral dosage of 360 mg sustained-release (SR) verapamil given every 12 hours concomitantly with rifampin achieved median verapamil exposures of 903.1 ng.h/mL (area under the curve (AUC)0-12 h ) in the 18 participants receiving this highest studied verapamil dose; these AUC findings are similar to those in persons receiving daily doses of 240 mg verapamil SR but not rifampin. Moreover, norverapamil:verapamil, R:S verapamil, and R:S norverapamil AUC ratios were all significantly greater than those of historical controls receiving SR verapamil in the absence of rifampin. Thus, rifampin administration favors the less-cardioactive verapamil metabolites and enantiomers that retain similar Mtb efflux inhibitory activity to verapamil, increasing overall benefit. Finally, rifampin exposures were 50% greater after verapamil administration, which may also be advantageous. Our findings suggest that a higher dosage of verapamil can be safely used as adjunctive treatment in rifampin-containing treatment regimens.

A dose-finding study to guide use of verapamil as an adjunctive therapy in tuberculosis.

Induction of mycobacterial efflux pumps is a cause of Mycobacterium tuberculosis (Mtb) drug tolerance, a barrier to shortening antitubercular treatment. Verapamil inhibits Mtb efflux pumps that mediate tolerance to rifampin, a cornerstone of tuberculosis treatment. Verapamil's mycobacterial efflux pump inhibition also limits Mtb growth in macrophages in the absence of antibiotic treatment. These findings suggest that verapamil could be used as an adjunctive therapy for TB treatment shortening. However, verapamil is rapidly and substantially metabolized when co-administered with rifampin. We determined in a dose-escalation clinical trial that rifampin-induced clearance of verapamil can be countered without toxicity by the administration of larger than usual doses of verapamil. An oral dosage of 360 mg sustained-release (SR) verapamil given every 12 hours concomitantly with rifampin achieved median verapamil exposures of 903.1 ng.h/ml (AUC 0-12h), similar to those in persons receiving daily doses of 240 mg verapamil SR but not rifampin. Norverapamil:verapamil, R:S verapamil and R:S norverapamil AUC ratios were all significantly greater than those of historical controls receiving SR verapamil in the absence of rifampin, suggesting that rifampin administration favors the less-cardioactive verapamil metabolites and enantiomers. Finally, rifampin exposures were significantly greater after verapamil administration. Our findings suggest that a higher dosage of verapamil can be safely used as adjunctive treatment in rifampin-containing treatment regimens.

Mesoporous ferromagnetic manganese ferrite nanoparticles for enhanced visible light mineralization of azoic dye into nontoxic by-products.

In this study, a one pot facile synthesis of ferromagnetic manganese ferrite nanoparticles (MnFe2O4) was carried out using chemical co-precipitation method for mineralization of azo dye (Congo red (CR)) in aqueous solution under visible light irradiation. The synthesized MnFe2O4 nanoparticles were highly crystalline and showed face-centred cubic (FCC) structure with average particle size of 58 ± 4 nm. The BET analysis of the MnFe2O4 nanoparticles revealed the mesoporous distribution of material with high surface area can provide large electro active sites and short diffusion paths for the transport of ions which plays a vital role in the photocatalytic degradation of CR. The point of zero charge (pHPZC) was observed to be 6.7 indicating favourable condition for material-anionic dye interaction. The XPS studies revealed that the large amounts of oxygen vacancies were produced due to the defects in the lattice oxygen. The MnFe2O4 nanoparticles mineralised 98.3 ± 0.2% of 50 mg/L CR within 30 min when tested in photocatalytic reactor under 565 nm. The particles were recoverable under the influence of an external magnet after the photocatalytic reaction and were reusable. The recovered nanoparticles showed 96% of CR degradation efficiency even after five cycles of reuse. The by-product analysis with GC-MS indicated mineralization of CR into simple alcohols and acids. The aqueous solution containing mineralised CR was nontoxic to Trigonella foenumgraecum and Vigna mungo seeds and favoured increased germination, plumule and radicle length when compared to untreated CR.

One pot facile green synthesis of crystalline bio-ZrO2 nanoparticles using Acinetobacter sp. KCSI1 under room temperature.

In this study, crystalline ZrO2 nanoparticles were synthesized in one pot at room temperature using an extremophilic Acinetobacter sp. KCSI1 and characterized using various techniques to study its structural, optical and crystalline properties. The average size of the ZrO2 nanoparticles was found to be 44 ±â€¯7 nm. The XRD and Raman spectra showed the crystalline structure of ZrO2. HRTEM and SAED images showed well aligned ordered crystal lattice nanoparticles. The zeta potential of Bio-NP of ZrO2 has been found to be 36.5 ±â€¯5.46 mV. The mechanical behaviour such as hardness and Young's modulus of Bio-ZrO2 NPs were determined using atomic force microscopy (AFM) and found to be 9.206 ±â€¯2.22 and 0.285 ±â€¯0.13 GPa, respectively. No significant cytotoxicity for ZrO2 nanoparticles was observed when tested with mouse fibroblast cells (L929), suggesting that the synthesized ZrO2 nanoparticle is biocompatible and safe for environmental applications.