Electronic structure and estimation of Curie temperature in Ca\u3csub\u3e2\u3c/sub\u3eBIrO\u3csub\u3e6\u3c/sub\u3e(B = Cr, Fe) double perovskites

We investigate the electronic and magnetic properties of Ca 2 CrIrO 6 and Ca 2 FeIrO 6 by means of density functional theory. These materials belong to a family of recently synthesized Ca 2 CrOsO 6 whose properties show possible applications in a room temperature regime. Upon replacement of Os by Ir in Ca 2 CrOsO 6, we found the system to exhibit a stable ferrimagnetic configuration with a bandgap of ∼0.25 eV and an effective magnetic moment of ∼2.58 μ B per unit cell. Furthermore, when chemical doping is considered by replacing Cr with Fe and Os with Ir, the material retains the insulating state but with a reduced bandgap of 0.13 eV and large increment in the effective magnetic moment of ∼6.68 μ B per unit cell. These observed behaviors are noted to be the consequence of the cooperative effect of spin-orbit coupling; Coulomb correlations from Cr-3d, Fe-3d, and Ir-5d electrons; and the crystal field effect of the materials. These calculations suggest that by chemical tuning, one can manipulate the bandgap and their effective magnetic moment, which may help in material fabrication for device applications. To check further the suitability and applicability of Ca 2 CrIrO 6 and Ca 2 FeIrO 6 at higher temperatures, we estimate the Curie temperature (T C) by calculating the spin-exchange coupling. We found that our findings are in a valid T C trend similar to other perovskites. Our findings are expected to be useful in experimental synthesis and transport measurement for potential applications in modern technological devices

Effect of a female community health volunteer-delivered intervention to increase cervical cancer screening uptake in Nepal:a cluster randomized controlled trial

This study aimed to assess the effect of Female Community Health Volunteer (FCHV)-delivered intervention to increase cervical cancer screening uptake among Nepalese women. A community-based, open-label, 2-group, cluster randomized controlled trial (CRCT) was conducted in a semi-urban setting in Western Nepal. Fourteen clusters (1:1) were randomly assigned to the intervention group, which received a 12-month intervention delivered by FCHVs or the control group (usual care). Between April and June 2019, 690 women aged 30–60 years were recruited for CRCT during the baseline survey. A follow-up assessment was conducted after the completion of the 12 months intervention. The primary outcome was the change in cervical cancer screening from baseline to 12-month follow-up. Of 690 women, 646 women completed the trial. 254 women in the intervention group and 385 women in the control group were included in the primary outcome analysis. There was a significant increase in cervical cancer screening uptake in the intervention group [relative risk (RR), 1.48; 95 % confidence interval (CI) 1.32, 1.66; P < 0.01)], compared to the control group. The secondary outcome was the change in median knowledge score among women that increased from 2 [interquartile range (IQR) 1–4] (baseline) to 6 [IQR 3–9] (follow-up) in the intervention group. However, the median knowledge score remained almost the same among women in the control group 2 [IQR 1–5] to 3 [IQR 2–5]. Our study findings reported that an FCHV-delivered intervention significantly increased cervical cancer screening uptake among women living in a semi-urban setting in Nepal. Trial registration: ClinicalTrials.gov NCT03808064

Safety of Rifampicin at High Dose for Difficult-to-Treat Tuberculosis: Protocol for RIAlta Phase 2b/c Trial

Rifampicin; Tuberculosis; Vulnerable populationRifampicina; Tuberculosis; Población vulnerableRifampicina; Tuberculosi; Població vulnerablePrevious clinical trials for drug-susceptible tuberculosis (DS-TB) have shown that first-line treatment with doses of rifampicin up to 40 mg/kg are safe and increase the early treatment response for young adults with pulmonary tuberculosis. This may lead to a shorter treatment duration for those persons with TB and a good baseline prognosis, or increased treatment success for vulnerable subgroups (age > 60, diabetes, malnutrition, HIV, hepatitis B or hepatitis C coinfection, TB meningitis, stable chronic liver diseases). Here, we describe the design of a phase 2b/c clinical study under the hypothesis that rifampicin at 35 mg/kg is as safe for these vulnerable groups as for the participants included in previous clinical trials. RIAlta is an interventional, open-label, multicenter, prospective clinical study with matched historical controls comparing the standard DS-TB treatment (isoniazid, pyrazinamide, and ethambutol) with rifampicin at 35 mg/kg (HR35ZE group) vs. rifampicin at 10 mg/kg (historical HR10ZE group). The primary outcome is the incidence of grade ≥ 3 Adverse Events or Severe Adverse Events. A total of 134 participants will be prospectively included, and compared with historical matched controls with at least a 1:1 proportion. This will provide a power of 80% to detect non-inferiority with a margin of 8%. This study will provide important information for subgroups of patients that are more vulnerable to TB bad outcomes and/or treatment toxicity. Despite limitations such as non-randomized design and the use of historical controls, the results of this trial may inform the design of future more inclusive clinical trials, and improve the management of tuberculosis in subgroups of patients for whom scientific evidence is still scarce. Trial registration: EudraCT 2020-003146-36, NCT04768231.This study is part of the European South American TB Research Collaborative Network (EUSAT-RCS), a project that has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 823890. A.S.M. is supported by a Juan Rodés (JR18/00022) postdoctoral fellowship from ISCIII

The COVID-19 pandemic in Nepal: Emerging evidence on the effectiveness of action by, and cooperation between, different levels of government in a federal system

A new coronavirus disease (COVID-19) caused by a novel pathogen (SARS-CoV-2) spread rapidly around the world in the early months of 2020, and was declared a pandemic by the World Health Organization (WHO) on 11 March. COVID-19 has, and continues to have, large implications for individuals, societies, and for national health systems across the globe. Due to its novelty and impact, it has challenged all health care systems where the virus has taken hold. The ways in which governments and health systems have responded have varied widely across the world. In the case of Nepal, the pandemic represented a major test for the newly decentralised health system, created as a result of the implementation of the 2015 federal constitution. This paper, which forms a part of our large on-going study of the decentralisation of the health system in the country, presents some of the early evidence on the effectiveness of the actions taken by Federal, Provincial and Local Governments and the levels of cooperation and coordination between them

Dried Blood Spot Sampling to Assess Rifampicin Exposure and Treatment Outcomes among Native and Non-Native Tuberculosis Patients in Paraguay:An Exploratory Study

The aim of this study was to evaluate the difference in drug exposure of rifampicin in native versus non-native Paraguayan populations using dried blood spots (DBS) samples collected utilizing a limited sampling strategy. This was a prospective pharmacokinetic study that enrolled hospitalized tuberculosis (TB) patients from both native and non-native populations receiving oral rifampicin 10 mg/kg once-daily dosing. Steady-state DBS samples were collected at 2, 4, and 6 h after intake of rifampicin. The area under the time concentration curve 0–24 h (AUC0–24) was calculated using a Bayesian population PK model. Rifampicin AUC0–24 &lt; 38.7 mg*h/L was considered as low. The probability of target attainment (PTA) was calculated using AUC0–24/MIC &gt; 271 as a target and estimated MIC values of 0.125 and 0.25 mg/L. In total, 50 patients were included. Native patients (n = 30) showed comparable drug exposure to the non-natives (n = 20), median AUC0–24 24.7 (17.1–29.5 IQR) and 21.6 (15.0–35.4 IQR) mg*h/L (p = 0.66), respectively. Among total patients, only 16% (n = 8) had a rifampicin AUC0–24 &gt; 38.7 mg*h/L. Furthermore, PTA analysis showed that only 12 (24%) of the patients met a target AUC0–24 /MIC ≥ 271, assuming an MIC of 0.125 mg/L, which plummeted to 0% at a wild-type MIC of 0.25 mg/L. We successfully used DBS and limited sampling for the AUC0–24 estimation of rifampicin. Currently, our group, the EUSAT-RCS consortium, is preparing a prospective multinational, multicenter phase IIb clinical trial evaluating the safety and efficacy of high-dose rifampicin (35 mg/kg) in adult subjects using the DBS technique for AUC0–24 estimation.</p

Dried Blood Spot Sampling to Assess Rifampicin Exposure and Treatment Outcomes among Native and Non-Native Tuberculosis Patients in Paraguay: An Exploratory Study

The aim of this study was to evaluate the difference in drug exposure of rifampicin in native versus non-native Paraguayan populations using dried blood spots (DBS) samples collected utilizing a limited sampling strategy. This was a prospective pharmacokinetic study that enrolled hospitalized tuberculosis (TB) patients from both native and non-native populations receiving oral rifampicin 10 mg/kg once-daily dosing. Steady-state DBS samples were collected at 2, 4, and 6 h after intake of rifampicin. The area under the time concentration curve 0–24 h (AUC0–24) was calculated using a Bayesian population PK model. Rifampicin AUC0–24 0–24/MIC > 271 as a target and estimated MIC values of 0.125 and 0.25 mg/L. In total, 50 patients were included. Native patients (n = 30) showed comparable drug exposure to the non-natives (n = 20), median AUC0–24 24.7 (17.1–29.5 IQR) and 21.6 (15.0–35.4 IQR) mg*h/L (p = 0.66), respectively. Among total patients, only 16% (n = 8) had a rifampicin AUC0–24 > 38.7 mg*h/L. Furthermore, PTA analysis showed that only 12 (24%) of the patients met a target AUC0–24 /MIC ≥ 271, assuming an MIC of 0.125 mg/L, which plummeted to 0% at a wild-type MIC of 0.25 mg/L. We successfully used DBS and limited sampling for the AUC0–24 estimation of rifampicin. Currently, our group, the EUSAT-RCS consortium, is preparing a prospective multinational, multicenter phase IIb clinical trial evaluating the safety and efficacy of high-dose rifampicin (35 mg/kg) in adult subjects using the DBS technique for AUC0–24 estimation

Safety of Rifampicin at High Dose for Difficult-to-Treat Tuberculosis: Protocol for RIAlta Phase 2b/c Trial

Previous clinical trials for drug-susceptible tuberculosis (DS-TB) have shown that first-line treatment with doses of rifampicin up to 40 mg/kg are safe and increase the early treatment response for young adults with pulmonary tuberculosis. This may lead to a shorter treatment duration for those persons with TB and a good baseline prognosis, or increased treatment success for vulnerable subgroups (age > 60, diabetes, malnutrition, HIV, hepatitis B or hepatitis C coinfection, TB meningitis, stable chronic liver diseases). Here, we describe the design of a phase 2b/c clinical study under the hypothesis that rifampicin at 35 mg/kg is as safe for these vulnerable groups as for the participants included in previous clinical trials. RIAlta is an interventional, open-label, multicenter, prospective clinical study with matched historical controls comparing the standard DS-TB treatment (isoniazid, pyrazinamide, and ethambutol) with rifampicin at 35 mg/kg (HR35ZE group) vs. rifampicin at 10 mg/kg (historical HR10ZE group). The primary outcome is the incidence of grade ≥ 3 Adverse Events or Severe Adverse Events. A total of 134 participants will be prospectively included, and compared with historical matched controls with at least a 1:1 proportion. This will provide a power of 80% to detect non-inferiority with a margin of 8%. This study will provide important information for subgroups of patients that are more vulnerable to TB bad outcomes and/or treatment toxicity. Despite limitations such as non-randomized design and the use of historical controls, the results of this trial may inform the design of future more inclusive clinical trials, and improve the management of tuberculosis in subgroups of patients for whom scientific evidence is still scarce. Trial registration: EudraCT 2020-003146-36, NCT04768231