The substrate for the hydrolytic activity of membrane-bound pyrophosphatase is the PP(i)-Mg2+ complex. The enzyme has no activity when the free Mg2+ concentration is lower than 10 microM (at 0.5 mM-PP(i)-Mg2+), and therefore free Mg2+ is an essential activator of the hydrolytic activity. The Km for the substrate changes in response to variation in free Mg2+ concentration, from 10.25 to 0.6 mM when free Mg2+ is increased from 0.03 to 1.0 mM respectively. The Km for Mg2+ depends on the substrate concentration: the Km decreases from 0.52 to 0.14 mM from 0.25 to 0.75 mM-PP(i)-Mg2+ respectively. The extrapolated Km for Mg2+ in the absence of the substrate is 0.73 mM. Imidodiphosphate-Mg2+ and free Ca2+ were used as competitive inhibitors of substrate and activator respectively. The equilibrium binding kinetics suggest an ordered mechanism for the activator and the substrate: Mg2+ ions bind the enzyme before PP(i)-Mg2+ in the formation of the catalytic complex, membrane-bound pyrophosphatase-(Mg2+)-(PP(i)-Mg2+).

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ImportanceLatin America has implemented the world’s largest and most consolidated conditional cash transfer (CCT) programs during the last 2 decades. As a consequence of the COVID-19 pandemic, poverty rates have markedly increased, and a large number of newly low-income individuals, especially children, have been left unprotected.ObjectiveTo evaluate the association of CCT programs with child health in Latin American countries during the last 2 decades and forecast child mortality trends up to 2030 according to CCT alternative implementation options.Design, Setting, and ParticipantsThis cohort study used a multicountry, longitudinal, ecological design with multivariable negative binomial regression models, which were adjusted for all relevant demographic, socioeconomic, and health care variables, integrating the retrospective impact evaluations from January 1, 2000, to December 31, 2019, with dynamic microsimulation models to forecast potential child mortality scenarios up to 2030. The study cohort included 4882 municipalities from Brazil, Ecuador, and Mexico with adequate quality of civil registration and vital statistics according to a validated multidimensional criterion. Data analysis was performed from September 2022 to February 2023.ExposureConditional cash transfer coverage of the target (lowest-income) population categorized into 4 levels: low (0%-29.9%), intermediate (30.0%-69.9%), high (70.0%-99.9%), and consolidated (≥100%).Main Outcomes and MeasuresThe main outcomes were mortality rates for those younger than 5 years and hospitalization rates (per 1000 live births), overall and by poverty-related causes (diarrheal, malnutrition, tuberculosis, malaria, lower respiratory tract infections, and HIV/AIDS), and the mortality rates for those younger than 5 years by age groups, namely, neonatal (0-28 days), postneonatal (28 days to 1 year), infant (<1 year), and toddler (1-4 years).ResultsThe retrospective analysis included 4882 municipalities. During the study period of January 1, 2000, to December 31, 2019, mortality in Brazil, Ecuador, and Mexico decreased by 7.8% in children and 6.5% in infants, and an increase in coverage of CCT programs of 76.8% was observed in these Latin American countries. Conditional cash transfer programs were associated with significant reductions of mortality rates in those younger than 5 years (rate ratio [RR], 0.76; 95% CI, 0.75-0.76), having prevented 738 919 (95% CI, 695 641-782 104) child deaths during this period. The association of highest coverage of CCT programs was stronger with poverty-related diseases, such as malnutrition (RR, 0.33; 95% CI, 0.31-0.35), diarrhea (RR, 0.41; 95% CI, 0.40-0.43), lower respiratory tract infections (RR, 0.66, 95% CI, 0.65-0.68), malaria (RR, 0.76; 95% CI, 0.63-0.93), tuberculosis (RR, 0.62; 95% CI, 0.48-0.79), and HIV/AIDS (RR, 0.32; 95% CI, 0.28-0.37). Several sensitivity and triangulation analyses confirmed the robustness of the results. Considering a scenario of moderate economic crisis, a mitigation strategy that will increase the coverage of CCTs to protect those newly in poverty could reduce the mortality rate for those younger than 5 years by up to 17% (RR, 0.83; 95% CI, 0.80-0.85) and prevent 153 601 (95% CI, 127 441-180 600) child deaths by 2030 in Brazil, Ecuador, and Mexico.Conclusions and RelevanceThe results of this cohort study suggest that the expansion of CCT programs could strongly reduce childhood hospitalization and mortality in Latin America and should be considered an effective strategy to mitigate the health impact of the current global economic crisis in low- and middle-income countries.

This study determined the efficiency of two different models of diabetes care (traditional units and multidisciplinary units), estimated quality levels, and identified management practices associated with better quality and efficiency of both models in Mexico. A random sample consisting of 40 units (20 for each type of unit), allowed us to estimate technical efficiency using data envelopment analysis (DEA) after we calculated quality scores (performance and competence). We mapped the relationship between efficiency and quality score, and using a positive deviance approach, we studied managerial determinants of best performance in terms of both efficiency and quality. We found that efficiency in multidisciplinary units was higher than in traditional units; traditional units scored very low in terms of efficiency. Likewise, in terms of the different quality metrics, the multidisciplinary units were much better evaluated than the traditional units. We found important differences in the quality scores for the different health care models. Two-thirds of the multidisciplinary units were in the best-performing group (above-median efficiency and above-median performance), and almost half of them were mapped to the high-competence quadrant. On the other hand, only 10% of the traditional units managed to position themselves in the best performance quadrant. Managerial characteristics were positively correlated with the probability of belonging to the group with the highest performance. Our findings indicate that multidisciplinary medical care can lead to better outcomes for patients with diabetes compared to traditional medical care. In both types of units, however, there is substantial opportunity to improve efficiency and quality levels.