Incidence and Risk Factors of First-Line HAART Discontinuation: Is it Worth Choosing Competing Risk or Standard Survival Approaches?

International audienceObjectives: To estimate the incidences of first-line HAART discontinuation (for intolerance, treatment failure or treatment simplification) and their risk factors by standard survival (1-KM, Cox model) or competing risk approach (CIF, Fine-Gray model) in HIV infected patients. Methods: We studied 1136 patients receiving first-line Highly Active Antiretroviral Therapies (HAART), aged over 18 years, from the Dat'AIDS cohort, Toulouse, France, between January 2000 and June 2008. Cumulative incidence was estimated with 1-KM and CIF estimators and risk factors with Cox and Fine-Gray models. Results: There were 265 discontinuations for intolerance, 136 simplifications, 101 treatment failure and 274 other reasons. One year incidences were 19.0% versus 16.8%, 8.0% versus 6.0%, 6.3% versus 4.8% and 20.0% versus 17.3%, with the estimators 1-KM and CIF, respectively. For intolerance, both models identified similar risk factors. For risk factors of simplification or treatment failure, results differed by the model. Conclusions: As expected, the 1-KM overestimates the incidence of treatment discontinuation. For early and frequent events such as intolerance, the Cox and the Fine-Gray models appear to give similar results. For late and rare events, potentially exposed to competing risk, results differed. The common or specific nature of a factor may also play a role

Task sharing for family planning services, Burkina Faso

© 2019, World Health Organization. All rights reserved. Problem In Burkina Faso, the coverage of services for family planning is low due to shortage of qualified health staff and limited access to services. Approach Following the launch of the Ouagadougou Partnership, an alliance to catalyse the expansion of family planning services, the health ministry created a consortium of family planning stakeholders in 2011. The consortium adopted a collaborative framework to implement a pilot project for task sharing in family planning at community and primary health-care centre levels in two rural districts. Stakeholders were responsible for their areas of expertise. These areas included advocacy; monitoring and evaluation; and capacity development of community health workers (CHWs) to offer oral and injectable contraceptives to new users and of auxiliary nurses and auxiliary midwives to provide implants and intrauterine devices. The health ministry implemented supportive supervision cascades involving relevant planning and service levels. Local setting In Burkina Faso, only 15% (2563/17 087) of married women used modern contraceptives in 2010. Relevant changes Adoption of new policies and clinical care standards expanded task sharing roles in family planning. The consortium trained a total of 79 CHWs and 124 auxiliary nurses and midwives. Between January 2017 and December 2018, CHWs provided injectables to 3698 new users, and auxiliary nurses or midwives provided 726 intrauterine devices and 2574 implants to new users. No safety issues were reported. Lessons learnt The pilot project was feasible and safe, however, financial constraints are hindering scale-up efforts. Supportive supervision cascades were critical in ensuring success

Mitochondrial Reactive Oxygen Species Are Obligatory Signals for Glucose-Induced Insulin Secretion

OBJECTIVE—Insulin secretion involves complex events in which the mitochondria play a pivotal role in the generation of signals that couple glucose detection to insulin secretion. Studies on the mitochondrial generation of reactive oxygen species (ROS) generally focus on chronic nutrient exposure. Here, we investigate whether transient mitochondrial ROS production linked to glucose-induced increased respiration might act as a signal for monitoring insulin secretion

Modern insulation materials for warming of walls

Biodiversity hotspots understandably attract considerable conservation attention. However, deserts are rarely viewed as conservation priority areas, due to their relatively low productivity, yet these systems are home to unique species, adapted to harsh and highly variable environments. While global attention has been focused on hotspots, the world's largest tropical desert, the Sahara, has suffered a catastrophic decline in megafauna. Of 14 large vertebrates that have historically occurred in the region, four are now extinct in the wild, including the iconic scimitar-horned oryx (Oryx dammah). The majority has disappeared from more than 90% of their Saharan range, including addax (Addax nasomaculatus), dama gazelle (Nanger dama) and Saharan cheetah (Acinonyx jubatus hecki) - all now on the brink of extinction. Greater conservation support and scientific attention for the region might have helped to avert these catastrophic declines. The Sahara serves as an example of a wider historical neglect of deserts and the human communities who depend on them. The scientific community can make an important contribution to conservation in deserts by establishing baseline information on biodiversity and developing new approaches to sustainable management of desert species and ecosystems. Such approaches must accommodate mobility of both people and wildlife so that they can use resources most efficiently in the face of low and unpredictable rainfall. This is needed to enable governments to deliver on their commitments to halt further degradation of deserts and to improve their status for both biodiversity conservation and human well-being. Only by so-doing will deserts be able to support resilient ecosystems and communities that are best able to adapt to climate change. © 2013 John Wiley & Sons Ltd

The plasticity of Plasmodium falciparum gametocytaemia in relation to age in Burkina Faso

BACKGROUND: Malaria transmission depends on the presence of gametocytes in the peripheral blood. In this study, the age-dependency of gametocytaemia was examined by microscopy and molecular tools. METHODS: A total of 5,383 blood samples from individuals of all ages were collected over six cross sectional surveys in Burkina Faso. One cross-sectional study used quantitative nucleic acid sequence based amplification (QT-NASBA) for parasite quantification (n = 412). The proportion of infections with concurrent gametocytaemia and median proportion of gametocytes among all parasites were calculated. RESULTS: Asexual parasite prevalence and gametocyte prevalence decreased with age. Gametocytes made up 1.8% of the total parasite population detected by microscopy in the youngest age group. This proportion gradually increased to 18.2% in adults (p < 0.001). Similarly, gametocytes made up 0.2% of the total parasite population detected by QT-NASBA in the youngest age group, increasing to 5.7% in adults (p < 0.001). This age pattern in gametocytaemia was also evident in the proportion of gametocyte positive slides without concomitant asexual parasites which increased from 13.4% (17/127) in children to 45.6% (52/114) in adults (OR 1.55, 95% CI 1.38-1.74, p < 0.001). CONCLUSIONS: The findings of this study suggest that although gametocytes are most commonly detected in children, the proportion of asexual parasites that is committed to develop into gametocytes may increase with age. These findings underscore the importance of adults for the human infectious reservoir for malaria

COUP-TFII Controls Mouse Pancreatic β-Cell Mass through GLP-1-β-Catenin Signaling Pathways

Background: The control of the functional pancreatic beta-cell mass serves the key homeostatic function of releasing the right amount of insulin to keep blood sugar in the normal range. It is not fully understood though how beta-cell mass is determined

The Nutritional Induction of COUP-TFII Gene Expression in Ventromedial Hypothalamic Neurons Is Mediated by the Melanocortin Pathway

BACKGROUND: The nuclear receptor chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) is an important coordinator of glucose homeostasis. We report, for the first time, a unique differential regulation of its expression by the nutritional status in the mouse hypothalamus compared to peripheral tissues. METHODOLOGY/PRINCIPAL FINDINGS: Using hyperinsulinemic-euglycemic clamps and insulinopenic mice, we show that insulin upregulates its expression in the hypothalamus. Immunofluorescence studies demonstrate that COUP-TFII gene expression is restricted to a subpopulation of ventromedial hypothalamic neurons expressing the melanocortin receptor. In GT1-7 hypothalamic cells, the MC4-R agonist MTII leads to a dose dependant increase of COUP-TFII gene expression secondarily to a local increase in cAMP concentrations. Transfection experiments, using a COUP-TFII promoter containing a functional cAMP responsive element, suggest a direct transcriptional activation by cAMP. Finally, we show that the fed state or intracerebroventricular injections of MTII in mice induce an increased hypothalamic COUP-TFII expression associated with a decreased hepatic and pancreatic COUP-TFII expression. CONCLUSIONS/SIGNIFICANCE: These observations strongly suggest that hypothalamic COUP-TFII gene expression could be a central integrator of insulin and melanocortin signaling pathway within the ventromedial hypothalamus. COUP-TFII could play a crucial role in brain integration of circulating signal of hunger and satiety involved in energy balance regulation

Development of a new version of the Liverpool Malaria Model. II. Calibration and validation for West Africa

<p>Abstract</p> <p>Background</p> <p>In the first part of this study, an extensive literature survey led to the construction of a new version of the <it>Liverpool Malaria Model </it>(LMM). A new set of parameter settings was provided and a new development of the mathematical formulation of important processes related to the vector population was performed within the LMM. In this part of the study, so far undetermined model parameters are calibrated through the use of data from field studies. The latter are also used to validate the new LMM version, which is furthermore compared against the original LMM version.</p> <p>Methods</p> <p>For the calibration and validation of the LMM, numerous entomological and parasitological field observations were gathered for West Africa. Continuous and quality-controlled temperature and precipitation time series were constructed using intermittent raw data from 34 weather stations across West Africa. The meteorological time series served as the LMM data input. The skill of LMM simulations was tested for 830 different sets of parameter settings of the undetermined LMM parameters. The model version with the highest skill score in terms of entomological malaria variables was taken as the final setting of the new LMM version.</p> <p>Results</p> <p>Validation of the new LMM version in West Africa revealed that the simulations compare well with entomological field observations. The new version reproduces realistic transmission rates and simulated malaria seasons are comparable to field observations. Overall the new model version performs much better than the original model. The new model version enables the detection of the epidemic malaria potential at fringes of endemic areas and, more importantly, it is now applicable to the vast area of malaria endemicity in the humid African tropics.</p> <p>Conclusions</p> <p>A review of entomological and parasitological data from West Africa enabled the construction of a new LMM version. This model version represents a significant step forward in the modelling of a weather-driven malaria transmission cycle. The LMM is now more suitable for the use in malaria early warning systems as well as for malaria projections based on climate change scenarios, both in epidemic and endemic malaria areas.</p