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Objectives: Disinvestment of existing healthcare technologies that deliver low or no health benefit for their cost can be used as a tool to improve access to effective technologies, while ensuring the long-term sustainability of healthcare systems. The objective of this research was to identify disinvestment initiatives in Latin American countries (LAC)., Methods: First, a systematic literature review (SLR) was conducted. In February 2015, MEDLINE, MEDLINE In-Process, EMBASE, The Cochrane Library, and LILACS were searched for relevant journal articles, including terms related to "disinvestment," "reallocation," "obsolete technologies," and "Latin America." Additionally, a manual search of documents from Latin American health technology assessment agencies was performed. Second, an online questionnaire was sent to experts in LAC to assess whether unpublished real-life disinvestment initiatives exist. Questionnaire results were collected in September 2015., Results: From the SLR, 350 records were selected for screening following de-duplication and eleven articles fulfilled inclusion criteria. Only two of these reported information on initiatives potentially identifiable as disinvestment-investment activities in Brazil and Peru. Nine respondents completed the questionnaire, and four reported that disinvestment initiatives had been conducted in their respective organizations in Argentina, Brazil, and Mexico. This lack of agreement between the SLR and the questionnaire responses shows that disinvestment initiatives are ongoing, despite being under reported., Conclusions: Many challenges need to be overcome for a disinvestment initiative to be successful, and sharing particular experiences with the international community would increase the chances of positive outcomes. The present study highlights the need for publication of such experiences in LAC.

Background: A lack of decisive evidence on the impact of telemedicine on financial and clinical outcomes has not prohibited significant investment in developing countries. Understanding characteristics that facilitate effective telemedicine programs is required to allow telemedicine to be used to its full potential. This systematic review aimed to identify organizational, technological, and financial features of successful telemedicine programs providing direct clinical care in developing countries., Materials and Methods: Databases were searched, and the results were reviewed systematically according to predefined inclusion/exclusion criteria. Information on location(s), measure of success, and organizational, technological, and financial characteristics were extracted. This review was impeded by inadequate program reporting, and so a concise checklist was developed to aid improved reporting, enabling future reviews to identify key characteristics of effective programs., Results: This systematic review identified 46 articles reporting 36 programs that fulfilled the inclusion/exclusion criteria. Programs were distributed globally, including regional, national, and international programs. Technological modalities included synchronous technology, real-time teleconsultations, and asynchronous technology. Program integration with existing systems and twinning of international institutions were identified as factors enabling program success. Other factors included simple and easy-to-use technology, ability to reduce the burden on healthcare professionals, and technology able to maintain functionality in challenging environmental circumstances. Reports describing effectiveness and costs were limited., Conclusions: This systematic review identified key factors associated with telemedicine program success. However, inconsistencies in reporting represent an obstacle to establishment of successful programs in developing countries by limiting the application of previous experiences. Adhering to the guidelines suggested here may allow more quantitative assessments of effectiveness and impact for future programs.

Mycobacterium tuberculosis (MTB) remains a major challenge to global health made worse by the spread of multidrug resistance. We therefore examined whether stimulating intracellular killing of mycobacteria through pharmacological enhancement of macroautophagy might provide a novel therapeutic strategy. Despite the resistance of MTB to killing by basal autophagy, cell-based screening of FDA-approved drugs revealed two anticonvulsants, carbamazepine and valproic acid, that were able to stimulate autophagic killing of intracellular M. tuberculosis within primary human macrophages at concentrations achievable in humans. Using a zebrafish model, we show that carbamazepine can stimulate autophagy in vivo and enhance clearance of M. marinum, while in mice infected with a highly virulent multidrug-resistant MTB strain, carbamazepine treatment reduced bacterial burden, improved lung pathology and stimulated adaptive immunity. We show that carbamazepine induces antimicrobial autophagy through a novel, evolutionarily conserved, mTOR-independent pathway controlled by cellular depletion of myo-inositol. While strain-specific differences in susceptibility to in vivo carbamazepine treatment may exist, autophagy enhancement by repurposed drugs provides an easily implementable potential therapy for the treatment of multidrug-resistant mycobacterial infection., (© 2014 The Authors. Published under the terms of the CC BY 4.0 license.)

Diseases of failed inflammation resolution are common and largely incurable. Therapeutic induction of inflammation resolution is an attractive strategy to bring about healing without increasing susceptibility to infection. However, therapeutic targeting of inflammation resolution has been hampered by a lack of understanding of the underlying molecular controls. To address this drug development challenge, we developed an in vivo screen for proresolution therapeutics in a transgenic zebrafish model. Inflammation induced by sterile tissue injury was assessed for accelerated resolution in the presence of a library of known compounds. Of the molecules with proresolution activity, tanshinone IIA, derived from a Chinese medicinal herb, potently induced inflammation resolution in vivo both by induction of neutrophil apoptosis and by promoting reverse migration of neutrophils. Tanshinone IIA blocked proinflammatory signals in vivo, and its effects are conserved in human neutrophils, supporting a potential role in treating human inflammation and providing compelling evidence of the translational potential of this screening strategy.

The inflammatory response is integral to maintaining health by functioning to resist microbial infection and repair tissue damage. Large numbers of neutrophils are recruited to inflammatory sites to neutralize invading bacteria through phagocytosis and the release of proteases and reactive oxygen species into the extracellular environment. Removal of the original inflammatory stimulus must be accompanied by resolution of the inflammatory response, including neutrophil clearance, to prevent inadvertent tissue damage. Neutrophil apoptosis and its temporary inhibition by survival signals provides a target for anti-inflammatory therapeutics, making it essential to better understand this process. GM-CSF, a neutrophil survival factor, causes a significant increase in mRNA levels for the known anti-apoptotic protein serum and glucocorticoid-regulated kinase 1 (SGK1). We have characterized the expression patterns and regulation of SGK family members in human neutrophils and shown that inhibition of SGK activity completely abrogates the antiapoptotic effect of GM-CSF. Using a transgenic zebrafish model, we have disrupted sgk1 gene function and shown this specifically delays inflammation resolution, without altering neutrophil recruitment to inflammatory sites in vivo. These data suggest SGK1 plays a key role in regulating neutrophil survival signaling and thus may prove a valuable therapeutic target for the treatment of inflammatory disease.

Human tissue inflammation is terminated, at least in part, by the death of inflammatory neutrophils by apoptosis. The regulation of this process is therefore key to understanding and manipulating inflammation resolution. Previous data have suggested that the short-lived pro-survival Bcl-2 family protein, Mcl-1, is instrumental in determining neutrophil lifespan. However, Mcl-1 can be cleaved following caspase activity, and the possibility therefore remains that the observed fall in Mcl-1 levels is due to caspase activity downstream of caspase activation, rather than being a key event initiating apoptosis in human neutrophils.We demonstrate that apoptosis in highly purified neutrophils can be almost completely abrogated by caspase inhibition with the highly effective di-peptide caspase inhibitor, Q-VD.OPh, confirming the caspase dependence of neutrophil apoptosis. Effective caspase inhibition does not prevent the observed fall in Mcl-1 levels early in ultrapure neutrophil culture, suggesting that this fall in Mcl-1 levels is not a consequence of neutrophil apoptosis. However, at later timepoints, declines in Mcl-1 can be reversed with effective caspase inhibition, suggesting that Mcl-1 is both an upstream regulator and a downstream target of caspase activity in human neutrophils.