Mechanisms of Damage to the Gastrointestinal Tract From Nonsteroidal Anti-Inflammatory Drugs.

Nonsteroidal anti-inflammatory drugs (NSAIDs) can damage the gastrointestinal tract, causing widespread morbidity and mortality. Although mechanisms of damage involve the activities of prostaglandin-endoperoxide synthase 1 (PTGS1 or cyclooxygenase [COX] 1) and PTGS1 (COX2), other factors are involved. We review the mechanisms of gastrointestinal damage induction by NSAIDs via COX-mediated and COX-independent processes. NSAIDs interact with phospholipids and uncouple mitochondrial oxidative phosphorylation, which initiates biochemical changes that impair function of the gastrointestinal barrier. The resulting increase in intestinal permeability leads to low-grade inflammation. NSAID inhibition of COX enzymes, along with luminal aggressors, results in erosions and ulcers, with potential complications of bleeding, protein loss, stricture formation, and perforation. We propose a model for NSAID-induced damage to the gastrointestinal tract that includes these complex, interacting, and inter-dependent factors. This model highlights the obstacles for the development of safer NSAIDs.

Grant Performance and Health Financing: Analysis of 12 Years of Financing Decisions at the Global Fund to Fight AIDS, Tuberculosis and Malaria.

Abstract-The Global Fund to Fight AIDS, Tuberculosis and Malaria ("the Global Fund") was established to attract, manage, and disburse additional financial resources toward Millennium Development Goal (MDG) 6. To increase the efficiency and impact of resources provided, performance-based financing (PBF) was included among the founding principles of the Global Fund. Since 2002, the Global Fund has disbursed over 28 billion USD to 145 countries or regional programs worldwide. This article investigates the degree to which PBF principles were followed in practice as well as the equity implications for the Global Fund's grant portfolio. We obtained performance and financial data on all disbursements (N = 6,064) and grant renewals (N = 892) between 2003 and 2014. Multivariate regression analysis was used to estimate the associations between performance ratings and financing amounts. The dependent variable was the fraction of original budgeted amount disbursed or renewed by the Global Fund. The main independent variable was the performance rating received by the grant. We also compared average funding shares by country income group before and after PBF adjustments. Our analysis found that lower performance ratings were associated with a smaller amount of the next period's budget disbursed; in addition, lower ratings were associated with a higher probability of the grant not being renewed after two years of implementation and a smaller proportion of recommitted funds. Low and lower-middle income countries obtained marginally lower grant performance ratings but still received 90% of the total grant renewal amounts from the Global Fund. These results suggest that the Global Fund has succeeded in implementing PBF principles over the past 12 years without shifting resources away from lower-income countries. Larger impact may be possible in the long run if health outcomes rather than only outputs or coverage indicators are also incentivized in PBF contracts between countries and the Global Fund.

Health Aid governance in fragile states: the global fund experience

Fragile states represent key challenges for global health governance. This study analyzes Global Fund grant data from 122 recipient countries as an initial exploration into how well these grants are performing in fragile states as compared to other countries. Since 2002, the Global Fund has invested nearly US$ 5 billion in 41 fragile states, and most grants have been assessed as performing well. Nonetheless, statistically significant differences in performance exist between fragile states and other countries, which were further pronounced in states with humanitarian crises. This indicates that further investigation of this issue is warranted: variations in performance may be unavoidable given the complexities of health governance in fragile states, but may also have implications for how the Global Fund and others provide aid. For example, faster aid disbursements might allow for a better response to rapidly changing contexts, and there may need to be more of a focus on building capacity and strengthening health governance in these countries.