The purpose of this analysis was to quantify the magnitude of death and disability from drowning and near-drowning worldwide and to provide epidemiological data on which to base prevention efforts. All data are from the Global Burden of Disease 2000 (Version 1) estimates in which deaths and disabilities are based on the WHO International Classification of Diseases. Extrapolations were made by age, sex, and WHO region. The six WHO regions of the world were further divided into high-income, and low- and middle-income based on the 1998 World Development indicators. According to the GBD 2000 data, an estimated 449,000 people drowned worldwide (7.4 per 100,000 population) and a further 1.3 million Disability Adjusted Life Years (DALYs) were lost as a result of premature death or disability from drowning. 97% of drownings occurred in low- and middle-income countries. Although 38% of drownings occurred in the Western Pacific Region, Africa had the highest drowning mortality rate (13.1 per 100,000 population). Males had higher drowning mortality rates than females for all ages and in all regions. Children under the age of 5 years had the highest drowning mortality rate for both sexes in all of the WHO regions except for Africa, where children aged 5 to 14 years had the highest mortality rate. Worldwide, for children under the age of 15 years, drowning accounted for a higher mortality rate than any other cause of injury. Drowning is a significant problem worldwide particularly for children under the age of 15 years. Low- and middle-income countries have the highest rates of drowning and account for more than 90% of such fatalities. Primary prevention efforts should thus be focused on these countries where many children who cannot swim drown in large bodies of water.
AGS-004 consists of matured autologous dendritic cells co-electroporated with in vitro transcribed RNA encoding autologous HIV antigens. In an open-label, single arm sub-study of AGS-004-003, AGS-004 was administered monthly to suppressed participants who started antiretroviral therapy (ART) during acute HIV infection. HIV-1 specific T cell responses were measured by multicolor flow cytometry after 3-4 doses. The frequency of resting CD4+ T-cell infection (RCI) was measured by quantitative viral outgrowth assay. Participants demonstrating increased immune response postvaccination were eligible for analytic treatment interruption (ATI). AGS-004 induced a positive immune response defined as ‡2-fold increase from baseline in the number of multifunctional HIV-1 specific CD28+ /CD45RA -CD8 + effector/memory cytoxic T-lymphocytes (CTLs) in all six participants. All participants underwent ATI with rebound viremia at a median of 29 days. Immune correlates between time to viral rebound and the induction of effector CTLs were determined. Baseline RCI was low in most participants (0.043-0.767 IUPM). One participant had a >2-fold decrease (0.179-0.067 infectious units per million [IUPM]) in RCI at week 10. One participant with the lowest RCI had the longest ATI. AGS-004 dendritic cell administration increased multifunctional HIV-specific CD28 + /CD45RA -CD8 + memory T cell responses in all participants, but did not permit sustained ART interruption. However, greater expansion of CD28 -/CCR7 -/CD45RA -CD8 + effector T cell responses correlated with a longer time to viral rebound. AGS-004 may be a useful tool to augment immune responses in the setting of latency reversal and eradication strategies.
Pre-exposure prophylaxis (PrEP) is an effective HIV prevention method, but many primary care physicians (PCPs) have not incorporated PrEP into practice. While PrEP may be a key strategy to reducing high HIV transmission rates in the southern US, knowledge about PrEP prescribing patterns among PCPs in this region is lacking. An online survey was sent to a large network of PCPs at an academic medical center in North Carolina in October 2015. The survey was repeated in September 2016, after an educational intervention that included on-site trainings at 14 PCP offices. Chi-square tests were used to compare PrEP prescribing patterns among providers. The initial survey was sent to 389 PCPs, with 115 (30%) responding. Of these, 78% reported seeing men who have sex with men (MSM). Only 17% had prescribed PrEP. The most frequently identified barrier was lack of knowledge (60%). When the survey was repeated after the educational initiative, 79 PCPs (20%) responded. Of these, 90% reported seeing MSM, and 35% had prescribed PrEP. PCPs who had attended a training were more likely to have prescribed PrEP (OR 4.84, CI 1.77-13.21). In conclusion, PrEP prescribing among PCPs in the southern US is low. A survey among PCPs identified lack of knowledge as a barrier to prescribing, motivating an institutional-wide educational campaign in response. Further efforts are needed to continue to raise awareness and educate PCPs in the South about PrEP.
Previous studies have revealed that HIV-infected individuals possess circulating CD4+CD8+ double-positive (DP) T cells specific for HIV Ags. In the present study, we analyzed the proliferation and functional profile of circulating DP T cells from 30 acutely HIV-infected individuals and 10 chronically HIV-infected viral controllers. The acutely infected group had DP T cells that showed more proliferative capability and multifunctionality than did both their CD4+ and CD8+ T cells. DP T cells were found to exhibit greater proliferation and higher multifunctionality compared with CD4 T cells in the viral controller group. The DP T cell response represented 16% of the total anti-HIV proliferative response and >70% of the anti-HIV multifunctional response in the acutely infected subjects. Proliferating DP T cells of the acutely infected subjects responded to all HIV Ag pools with equal magnitude. Conversely, the multifunctional response was focused on the pool representing Nef, Rev, Tat, VPR, and VPU. Meanwhile, the controllers’ DP T cells focused on Gag and the Nef, Rev, Tat, VPR, and VPU pool for both their proliferative and multifunctional responses. Finally, we show that the presence of proliferating DP T cells following all HIV Ag stimulations is well correlated with proliferating CD4 T cells whereas multifunctionality appears to be largely independent of multifunctionality in other T cell compartments. Therefore, DP T cells represent a highly reactive cell population during acute HIV infection, which responds independently from the traditional T cell compartments.
Initiation of ART during acute HIV-1 infection may prevent persistent immune activation. We analyzed longitudinal CD38+HLA-DR+ CD8+ T cell percentages in 31 acutely infected individuals who started early (median 43 days since infection) and successful ART, and maintained viral suppression through 96 weeks. Pre-therapy a median of 72.6% CD8+ T cells were CD38+HLA-DR+, and while this decreased to 15.6% by 96 weeks, it remained substantially higher than seronegative controls (median 8.9%, p=0.008). Shorter time to suppression predicted lower activation at 96 weeks. These results support the hypothesis that very early events in HIV-1 pathogenesis may result in prolonged immune dysfunction.
Background-More needs to be known about the prevalence of risk and protective factors for fires, burns, and carbon monoxide poisoning in U.S. households.
Initiating ART during AHI at higher baseline CD4 cell counts and CD4/CD8 ratios was associated with shorter time to CD4/CD8 ratio normalization.
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