Evaluating WHO-Recommended Interventions for Preterm Birth: A Mathematical Model of the Potential Reduction of Preterm Mortality in Sub-Saharan Africa.

Background: Preterm birth, a leading cause of neonatal mortality, has the highest burden in low-income countries. In 2015, the World Health Organization (WHO) published recommendations for interventions to improve preterm outcomes. Our analysis uses the Maternal and Neonatal Directed Assessment of Technology (MANDATE) model to evaluate the potential effects that WHO-recommended interventions could have had on preterm mortality in sub-Saharan Africa in 2015.

The Novelty of Inhalable Medications: Interest, Use, and Impact of Inhalant Medications in Low-Resource Settings.

Introduction: Postpartum haemorrhage (PPH) claims more than 100,000 maternal lives annually worldwide, most of them in low-resource settings. To address morbidity and mortality from PPH, the global health community is exploring novel drug formulations, such as inhalable medicine, to improve treatment availability and use, especially in community settings with limited access to skilled birth attendants. A major limitation in the ability to prevent or treat PPH in resource-limited settings is that the most effective medications for prevention and treatment are injectables, which require administration by skilled birth attendants.

Maternal and Neonatal Directed Assessment of Technologies (MANDATE): Methods and Assumptions for a Predictive Model for Maternal, Fetal, and Neonatal Mortality Interventions.

Maternal, fetal, and neonatal mortality disproportionately impact low- and middle-income countries, and many current interventions that can save lives are often not available nor appropriate for these settings. Maternal and Neonatal Directed Assessment of Technologies (MANDATE) is a mathematical model designed to evaluate which interventions have the greatest potential to save maternal, fetal, and neonatal lives saved in sub-Saharan Africa and India. The MANDATE decision-support model includes interventions such as preventive interventions, diagnostics, treatments, and transfers to different care settings to compare the relative impact of different interventions on mortality outcomes.

Interventions to reduce neonatal mortality: a mathematical model to evaluate impact of interventions in sub-Saharan Africa.

Aim: To determine which interventions would have the greatest impact on reducing neonatal mortality in sub-Saharan Africa in 2012.

Methods: We used MANDATE, a mathematical model, to evaluate scenarios for the impact of available interventions on neonatal deaths from primary causes, including: (i) for birth asphyxia - obstetric care preventing intrapartum asphyxia, newborn resuscitation and treatment of asphyxiated infants; (ii) for preterm birth - corticosteroids, oxygen, continuous positive air pressure and surfactant; and, (iii) for serious newborn infection - clean delivery, chlorhexidine cord care and antibiotics.

Results: Reductions in infection-related mortality have occurred.

Resuscitation and Obstetrical Care to Reduce Intrapartum-Related Neonatal Deaths: A MANDATE Study.

To evaluate the impact of neonatal resuscitation and basic obstetric care on intrapartum-related neonatal mortality in low and middle-income countries, using the mathematical model, Maternal and Neonatal Directed Assessment of Technology (MANDATE). Using MANDATE, we evaluated the impact of interventions for intrapartum-related events causing birth asphyxia (basic neonatal resuscitation, advanced neonatal care, increasing facility birth, and emergency obstetric care) when implemented in home, clinic, and hospital settings of sub-Saharan African and India for 2008. Total intrapartum-related neonatal mortality (IRNM) was acute neonatal deaths from intrapartum-related events plus late neonatal deaths from ongoing intrapartum-related injury.

Evaluation of the pharmacokinetic interaction between repeated doses of rifapentine or rifampin and a single dose of bedaquiline in healthy adult subjects.

This study assessed the effects of rifapentine or rifampin on the pharmacokinetics of a single dose of bedaquiline and its M2 metabolite in healthy subjects using a two-period single-sequence design. In period 1, subjects received a single dose of bedaquiline (400 mg), followed by a 28-day washout. In period 2, subjects received either rifapentine (600 mg) or rifampin (600 mg) from day 20 to day 41, as well as a single bedaquiline dose (400 mg) on day 29.

Reducing maternal mortality from preeclampsia and eclampsia in low-resource countries--what should work?

Objective: Preeclampsia/eclampsia (PE/E) remains a major cause of maternal death in low-income countries. We evaluated interventions to reduce PE/E-related maternal mortality in sub-Saharan Africa.

Design: Mathematical model to assess impact of interventions on PE/E-related maternal morbidity and mortality.

Tranexamic acid to reduce postpartum hemorrhage: A MANDATE systematic review and analyses of impact on maternal mortality.

Objective: Postpartum hemorrhage (PPH) is a major cause of maternal mortality, with almost 300,000 cases and ~72,000 PPH deaths annually in sub-Saharan Africa. Novel prevention methods practical in community settings are required. Tranexamic acid, a drug to reduce bleeding during surgical cases including postpartum bleeding, is potentially suitable for community settings.

Evaluation of pharmacokinetic interaction between PA-824 and midazolam in healthy adult subjects.

This study assessed the safety, tolerability, and pharmacokinetic interaction between PA-824, a novel antitubercular nitroimidazo-oxazine, and midazolam, a CYP3A4 substrate, in 14 healthy adult male and female subjects. The study followed up on observations in vitro that PA-824 caused weak and time-dependent inhibition of CYP3A4. Subjects received a single oral dose of midazolam (2 mg), followed by a 2-day washout.

The MANDATE model for evaluating interventions to reduce postpartum hemorrhage.

Objective: To create a comprehensive model of the comparative impact of various interventions on maternal, fetal, and neonatal (MFN) mortality.

Methods: The major conditions and sub-conditions contributing to MFN mortality in low-resource areas were identified, and the prevalence and case fatality rates documented. Available interventions were mapped to these conditions, and intervention coverage and efficacy were identified.

WITHDRAWN: Maintaining the momentum of antitubercular drug discovery.

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Early bactericidal activity and pharmacokinetics of PA-824 in smear-positive tuberculosis patients.

PA-824 is a novel nitroimidazo-oxazine being evaluated for its potential to improve tuberculosis (TB) therapy. This randomized study evaluated safety, tolerability, pharmacokinetics, and extended early bactericidal activity of PA-824 in drug-sensitive, sputum smear-positive, adult pulmonary tuberculosis patients. Fifteen patients per cohort received 1 of 4 doses of oral PA-824: 200, 600, 1,000, or 1,200 mg per day for 14 days.

Assessment of the effects of the nitroimidazo-oxazine PA-824 on renal function in healthy subjects.

The mechanism underlying a dose-dependent, reversible increase in serum creatinine (SC) caused by the administration of PA-824, a novel nitroimidazo-oxazine, was evaluated in 47 healthy male and female volunteers. Subjects were administered either 800 or 1,000 mg PA-824 or matching placebo once daily for 8 days. The following renal function parameters were determined before and during dosing and after a 7-day washout: SC, glomerular filtration rate (GFR; measured as the iohexol clearance), effective renal plasma flow (ERPF; measured as the para-amino hippurate clearance), filtration fraction (FF), creatinine clearance (CrCl), extraglomerular creatinine excretion (EGCE; defined as CrCl minus GFR), blood urea nitrogen (BUN), and uric acid (UA) levels.

Safety, tolerability, and pharmacokinetics of PA-824 in healthy subjects.

PA-824 is a novel antibacterial agent that has shown in vitro activity against both drug-sensitive and drug-resistant Mycobacterium tuberculosis. The compound's MIC is between 0.015 and 0.