BackgroundMultistage stepwise HIV testing and treatment initiation procedures can result in lost opportunities to provide timely antiretroviral therapy (ART). Incomplete patient engagement along the continuum of HIV care translates into high levels of preventable mortality. We aimed to evaluate the ability of a simplified test and treat structural intervention to reduce mortality.Methods and FindingsIn the “pre-intervention 2010” (from January 2010 to December 2010) and “pre-intervention 2011” (from January 2011 to December 2011) phases, patients who screened HIV-positive at health care facilities in Zhongshan and Pubei counties in Guangxi, China, followed the standard-of-care process. In the “post-intervention 2012” (from July 2012 to June 2013) and “post-intervention 2013” (from July 2013 to June 2014) phases, patients who screened HIV-positive at the same facilities were offered a simplified test and treat intervention, i.e., concurrent HIV confirmatory and CD4 testing and immediate initiation of ART, irrespective of CD4 count. Participants were followed for 6–18 mo until the end of their study phase period. Mortality rates in the pre-intervention and post-intervention phases were compared for all HIV cases and for treatment-eligible HIV cases. A total of 1,034 HIV-positive participants (281 and 339 in the two pre-intervention phases respectively, and 215 and 199 in the two post-intervention phases respectively) were enrolled. Following the structural intervention, receipt of baseline CD4 testing within 30 d of HIV confirmation increased from 67%/61% (pre-intervention 2010/pre-intervention 2011) to 98%/97% (post-intervention 2012/post-intervention 2013) (all p < 0.001 [i.e., for all comparisons between a pre- and post-intervention phase]), and the time from HIV confirmation to ART initiation decreased from 53 d (interquartile range [IQR] 27–141)/43 d (IQR 15–113) to 5 d (IQR 2–12)/5 d (IQR 2–13) (all p < 0.001). Initiation of ART increased from 27%/49% to 91%/89% among all cases (all p < 0.001) and from 39%/62% to 94%/90% among individuals with CD4 count ≤ 350 cells/mm3 or AIDS (all p < 0.001). Mortality decreased from 27%/27% to 10%/10% for all cases (all p < 0.001) and from 40%/35% to 13%/13% for cases with CD4 count ≤ 350 cells/mm3 or AIDS (all p < 0.001). The simplified test and treat intervention was significantly associated with decreased mortality rates compared to pre-intervention 2011 (adjusted hazard ratio [aHR] 0.385 [95% CI 0.239–0.620] and 0.380 [95% CI 0.233–0.618] for the two post-intervention phases, respectively, for all newly diagnosed HIV cases [both p < 0.001], and aHR 0.369 [95% CI 0.226–0.603] and 0.361 [95% CI 0.221–0.590] for newly diagnosed treatment-eligible HIV cases [both p < 0.001]). The unit cost of an additional patient receiving ART attributable to the intervention was US$83.80. The unit cost of a death prevented because of the intervention was US$234.52.ConclusionsOur results demonstrate that the simplified HIV test and treat intervention promoted successful engagement in care ...
So far, the connections between obesity and skeleton have been extensively explored, but the results are inconsistent. Obesity is thought to affect bone health through a variety of mechanisms, including body weight, fat volume, bone formation/resorption, proinflammatory cytokines together with bone marrow microenvironment. In this review, we will mainly describe the effects of adipokines secreted by white adipose tissue on bone cells, as well as the interaction between brown adipose tissue, bone marrow adipose tissue, and bone metabolism. Meanwhile, this review also reviews the evidence for the effects of adipose tissue and its distribution on bone mass and bone-related diseases, along with the correlation between different populations with obesity and bone health. And we describe changes in bone metabolism in patients with anorexia nervosa or type 2 diabetes. In summary, all of these findings show that the response of skeleton to obesity is complex and depends on diversified factors, such as mechanical loading, obesity type, the location of adipose tissue, gender, age, bone sites, and secreted cytokines, and that these factors may exert a primary function in bone health.
Osteoporosis and sarcopenia are two age-related diseases that affect the quality of life in the elderly. Initially, they were thought to be two independent diseases; however, recently, increasing basic and clinical data suggest that skeletal muscle and bone are both spatially and metabolically connected. The term “osteosarcopenia” is used to define a condition of synergy of low bone mineral density with muscle atrophy and hypofunction. Bone and muscle cells secrete several factors, such as cytokines, myokines, and osteokines, into the circulation to influence the biological and pathological activities in local and distant organs and cells. Recent studies reveal that extracellular vesicles containing microRNAs derived from senescent skeletal muscle and bone cells can also be transported and aid in regulating bone-muscle crosstalk. In this review, we summarize the age-related changes in the secretome and extracellular vesicle-microRNAs secreted by the muscle and bone, and discuss their interactions between muscle and bone cells during aging.
The mammalian skeleton is a metabolically active organ that continuously undergoes bone remodeling, a process of tightly coupled bone resorption and formation throughout life. Recent studies have expanded our knowledge about the interactions between cells within bone marrow in bone remodeling. Macrophages resident in bone (BMMs) can regulate bone metabolism via secreting numbers of cytokines and exosomes. This review summarizes the current understanding of factors, exosomes, and hormones that involved in the communications between BMMs and other bone cells including mensenchymal stem cells, osteoblasts, osteocytes, and so on. We also discuss the role of BMMs and potential therapeutic approaches targeting BMMs in bone remodeling related diseases such as osteoporosis, osteoarthritis, rheumatoid arthritis, and osteosarcoma.
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