Masitinib for mild-to-moderate Alzheimer's disease: results from a randomized, placebo-controlled, phase 3, clinical trial.

BACKGROUND: Masitinib is an orally administered tyrosine kinase inhibitor that targets activated cells of the neuroimmune system (mast cells and microglia). Study AB09004 evaluated masitinib as an adjunct to cholinesterase inhibitor and/or memantine in patients with mild-to-moderate dementia due to probable Alzheimer's disease (AD). METHODS: Study AB09004 was a randomized, double-blind, two parallel-group (four-arm), placebo-controlled trial. Patients aged ≥50 years, with clinical diagnosis of mild-to-moderate probable AD and a Mini-Mental State Examination (MMSE) score of 12-25 were randomized (1:1) to receive masitinib 4.5 mg/kg/day (administered orally as two intakes) or placebo. A second, independent parallel group (distinct for statistical analysis and control arm), randomized patients (2:1) to masitinib at an initial dose of 4.5 mg/kg/day for 12 weeks that was then titrated to 6.0 mg/kg/day, or equivalent placebo. Multiple primary outcomes (each tested at a significance level of 2.5%) were least-squares mean change from baseline to week 24 in the Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog), or the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory scale (ADCS-ADL). Safety for each masitinib dose level was compared against a pooled placebo population. RESULTS: Masitinib (4.5 mg/kg/day) (n=182) showed significant benefit over placebo (n=176) according to the primary endpoint of ADAS-cog, -1.46 (95% CI [-2.46, -0.45]) (representing an overall improvement in cognition) versus 0.69 (95% CI [-0.36, 1.75]) (representing increased cognitive deterioration), respectively, with a significant between-group difference of -2.15 (97.5% CI [-3.48, -0.81]); p<0.001. For the ADCS-ADL primary endpoint, the between-group difference was 1.82 (97.5% CI [-0.15, 3.79]); p=0.038 (i.e., 1.01 (95% CI [-0.48, 2.50]) (representing an overall functional improvement) versus -0.81 (95% CI [-2.36, 0.74]) (representing increased functional deterioration), respectively). Safety was consistent with masitinib's known profile (maculo-papular rash, neutropenia, hypoalbuminemia). Efficacy results from the independent parallel group of titrated masitinib 6.0 mg/kg/day versus placebo (n=186 and 91 patients, respectively) were inconclusive and no new safety signal was observed. CONCLUSIONS: Masitinib (4.5 mg/kg/day) may benefit people with mild-to-moderate AD. A confirmatory study has been initiated to substantiate these data. TRIAL REGISTRATION: EudraCT: 2010-021218-50. CLINICALTRIALS: gov : NCT01872598.

When law and science part ways: the criminalization of breastfeeding by women living with HIV.

Stigma and discrimination are a constant reality for the 37.7 million people living with human immunodeficiency virus (HIV) around the globe. Fear over vertical transmission has fuelled HIV criminalization: laws that target people living with HIV for acts deemed to be a transmission risk. Research has now shown that many of these behaviours, including breastfeeding, pose an extremely low risk of transmission when people have proper medical care, access to treatment and open relationships with medical professionals. Yet, we are witnessing a wave of criminal cases against women living with HIV for breastfeeding, an act which is actively promoted worldwide as the best infant feeding strategy. In this review, we will place the criminalization of breastfeeding within the context of current medical recommendations and cultural views of breastfeeding. We will highlight the criminal cases against women living with HIV for breastfeeding around the globe and the criteria for justifiable criminalization. Finally, we will provide recommendations for moving towards decriminalization, removing this barrier to HIV prevention, treatment and care.

The Role of Pharmaceutical Scientists in the Formation of a Healthy Lifestyle as a Value Orientation.

This article focuses on the role pharmaceutical scientists play in achieving social well-being, in particular in the formation of a healthy lifestyle as a value orientation among students and the public in historical retrospect. The following set of research methods was used: a general scientific method, and a historical (chronological, logico-historical, retrospective), personalized, empirical method (including the questioning of pharmaceutical interns and the analytical processing of questionnaires). The territorial boundaries of the study cover Slobozhanshchyna, a historical and geographical region centered in Kharkiv. The educational activities of Slobozhanshchyna's pharmaceutical scientists during the 19th and early-20th centuries, as well as in the modern period, are presented. Attention is drawn to the fact that the role of pharmaceutical scientists in forming the environment for the development of a harmonious, spiritually and physically developed personality in historical retrospect is important. It is noted that the founders of pharmaceutical education in Ukraine initiated educational activity as a means for promoting the formation of a healthy lifestyle in the educational space and outside of the Imperial Kharkov University. The changes in the public and educational activities recommended for forming a healthy lifestyle among Slobozhanshchyna's medical scientists and naturalists during the Imperial era have been generalized. The analysis of the research sources and questionnaires of pharmaceutical interns allowed us to assert that, in modern times, Slobozhanshchyna's pharmaceutical scientists are trying to organize socially useful activities, taking into account the best achievements of the founders of pharmaceutical education in Ukraine. The "orientation to a healthy lifestyle of representatives of the institution of higher pharmaceutical education" has been proposed. This includes the adoption of a set of material, social, and spiritual benefits and ideals considered to be objects of purpose in the pursuit of a healthy lifestyle by employees and students (i.e., part of the implementation of the mission of the University), and using these as tools to meet the needs of both university representatives and ordinary citizens. This article contains a number of factors that mediated the formation of a healthy lifestyle as a value orientation of an individual, including: (a) the circumstances of the individual's life (the conditions of education of the individual); (b) the individual's consciousness reflecting the general and specific conditions of their personality formation; (c) the motivation of the real behavior mediated by the subject's activities. The presence of these factors was identified as typical for the health-saving educational environment. This article provides recommendations regarding the following measures for the organization and effective promotion of a healthy lifestyle by modern pharmaceutical scientists: provide an opportunity to study the peculiarities of the organization of educational activities by scientists of the past to students and specialists in the pharmaceutical field; open museum expositions devoted to the problem of healthcare; conduct master class lectures and educational events devoted to the problem of forming a comprehensively developed personality; involve students in joint research on the problem of active longevity; provide informational support to educators and the public through scientific and popular science publications; conduct awareness-raising work with the population in order to create a health-saving environment.

What will it take to achieve the sexual and reproductive health and rights of women living with HIV?

This article outlines progress in realizing the sexual and reproductive health and rights of women and girls living with HIV over the last 30 years from the perspective of women living with HIV. It argues that the HIV response needs to go beyond the bio-medical aspects of HIV to achieve our sexual and reproductive health and rights, and considers relevant Joint United Nations Programme on HIV/AIDS (UNAIDS), World Health Organization, United States President's Emergency Plan for AIDS Relief (PEPFAR), Global Fund and other guidelines, what engagement there has been with women living with HIV and whether guidelines/strategies have been adopted. It has been written by women living with HIV from around the world and a few key supporters. Co-authors have sought to collate and cite materials produced by women living with HIV from around the world, in the first known effort to date to do this, as a convergence of evidence to substantiate the points made in the article. However, as the article also argues, research led by women living with HIV is seldom funded and rarely accepted as evidence. Combined with a lack of meaningful involvement of women living with HIV in others' research on us, this means that formally recognized evidence from women's own perspectives is patchy at best. The article argues that this research gap, combined with the ongoing primacy of conventional research methods and topics that exclude those most affected by issues, and the lack of political will (and sometimes outright opposition) in relation to gender equality and human rights, adversely affect policies and programmes in relation to women's rights. Thus, efforts to achieve an ethical, effective and sustainable response to the pandemic are hindered. The article concludes with a call to action to all key stakeholders.