Mental health service utilization is associated with retention in care among persons living with HIV at a university-affiliated HIV clinic

Background

Concurrent with the UNAIDS 90-90-90 and NHAS plans, the District of Columbia (DC) launched its 90/90/90/50 plan (Plan) in 2015. The Plan proposes that by 2020, 90% of all DC residents will know their HIV status; 90% of residents living with HIV will be in sustained treatment; 90% of those in treatment will reach “Viral Suppression” and DC will achieve 50% reduction of new HIV cases. To achieve these goals targeted prevention strategies are imperative for areas where the relative risk (RR) of not being linked to care (NL), not retained in any care (NRC) and low viral suppression (NVSP) are highest in the District. These outcomes are denoted in this study as poor outcomes of HIV care continuum. This study applies the Bayesian model for RR for area specific random effects to identify the census tracts with poor HIV care continuum outcomes for DC.

Methods

This analysis was conducted using cases diagnosed from 2010 to 2015 and reported to the surveillance system from the District of Columbia Department of Health (DC DOH), HIV/AIDS, Hepatitis, STD and TB Administration. The jurisdictions of the District of Columbia is divided into 179 census tracts. It is challenging to plot sparse data in ‘small’ local administrative areas, characteristically which may have a single-count datum for each geographic area. Bayesian methods overcome this problem by assimilating prior information to the underlying RR, making the predicted RR estimates robust.

Results

The RR of NL is higher in 59 (33%) out of 179 census tracts in DC. The RR of NRC was high in 46 (26%) of the census tracts while 52 census tracts (29%) show a high risk of having NVSP among its residents. This study also identifies clear correlated heterogeneity or clustering is evident in the northern tracts of the district.

Conclusion

The study finds census tracts with higher RR of poor linkage to care outcomes in the District. These results will inform the Plan which aims to increase targeted testing leading to early initiation of antiretroviral therapy. The uniqueness of this study lies in its translational scope where surveillance data can be used to inform local public health programs and enhance the quality of health for the people with HIV.

     

Bioimage analysis of Shigella infection reveals targeting of colonic crypts

Few studies within the pathogenic field have used advanced imaging and analytical tools to quantitatively measure pathogenicity in vivo. In this work, we present a novel approach for the investigation of host–pathogen processes based on medium-throughput 3D fluorescence imaging. The guinea pig model for Shigella flexneri invasion of the colonic mucosa was used to monitor the infectious process over time with GFP-expressing S. flexneri. A precise quantitative imaging protocol was devised to follow individual S. flexneri in a large tissue volume. An extensive dataset of confocal images was obtained and processed to extract specific quantitative information regarding the progression of S. flexneri infection in an unbiased and exhaustive manner. Specific parameters included the analysis of S. flexneri positions relative to the epithelial surface, S. flexneri density within the tissue, and volume of tissue destruction. In particular, at early time points, there was a clear association of S. flexneri with crypts, key morphological features of the colonic mucosa. Numerical simulations based on random bacterial entry confirmed the bias of experimentally measured S. flexneri for early crypt targeting. The application of a correlative light and electron microscopy technique adapted for thick tissue samples further confirmed the location of S. flexneri within colonocytes at the mouth of crypts. This quantitative imaging approach is a novel means to examine host–pathogen systems in a tailored and robust manner, inclusive of the infectious agent.The light microscope is an important tool in resolving the interactions between microbes and their hosts. With the advancement of both optical and computational techniques, quantification of biological events is not only possible, but essential in deciphering the complex interplays between host and pathogen. Acquired images are multidimensional datasets that capture complex biological phenomena, and a major task is to computationally extract statistically relevant data from those images. Such techniques have been readily applied in Cellular Microbiology, a discipline at the interface between cellular biology and microbiology (1). This field is dominated by studies focusing on microbe–host interactions at the in vitro, cellular scale, and a multitude of bioimage analysis tools have been developed and used to decipher pathogenic strategies at the cellular, as well as the molecular, level in high resolution in both space and time (2).The next imaging challenge exists on a much larger scale in the growing field of Tissue Microbiology, which places the pathogen in its native in vivo environment, the host (3). Biologically speaking, this environment is essential for the full understanding of a given pathogen’s invasive strategies and the complex host response; however, this also places additional complexity and limitations in regards to imaging, particularly in maintaining cellular and molecular resolution. Novel tools and studies addressing bacterial infection in vivo are frequently reported in the literature (4, 5). However, emphasis has been traditionally placed on qualitative observations at the expense of extensive quantitative efforts. The importance of bioimage analyses to automatically extract data from medium- to large-scale image sampling of infected tissue is often underappreciated as a method to expand our understanding of pathogens’ strategies and disease progression. In this work, we aim to bring quantitative image analysis into the realm of host–pathogen interactions, specifically examining the progression of tissue invasion by a model enteropathogenic bacterium, Shigella flexneri.S. flexneri is the causative agent of bacillary dysentery, an infectious rectocolitis, which remains a major pediatric public health concern in developing countries. This human-specific pathogen is transmitted via the fecal–oral route, and namely targets the large intestine, resulting in acute inflammation, tissue edema, and erosion of the colonic epithelium (6). The infection strategy of S. flexneri relies on (i) the transfer of bacterial proteins, termed “effectors,” into targeted host cells through the type III secretion apparatus (T3SA), which induces the uptake of the bacteria and perturbs host cellular processes, and (ii) the capacity of the intracellular bacteria to spread from cell to cell using actin microfilament-mediated cytoplasmic movement and reactivation of the T3SA (7–10).Herein, we present a straightforward approach that relies on the combination of light microscopy and computer analyses to study the mucosal invasion of a newly developed in vivo model for shigellosis, S. flexneri intrarectal inoculation of the guinea pig colon (11). Through the application of simple, open-source image analysis tools, we built up a medium-throughput analysis that allows observing and robustly measuring host–pathogen interactions. Most importantly, this approach can be adapted to other host–pathogen systems, thereby providing generic tools that bridge Cellular and Tissue Microbiology.     

Sex-Specific Muscular Mediation of the Relationship Between Physical Activity and Cortical Bone in Young Adults

Muscle mass is a commonly cited mediator of the relationship between physical activity (PA) and bone, representing the mechanical forces generated during PA. However, neuromuscular properties (eg, peak force) also account for unique portions of variance in skeletal outcomes. We used serial multiple mediation to explore the intermediary role of muscle mass and force in the relationships between cortical bone and moderate-to-vigorous intensity PA (MVPA). In a cross-sectional sample of young adults (n = 147, 19.7 ± 0.7 years old, 52.4% female) cortical diaphyseal bone was assessed via peripheral quantitative computed tomography at the mid-tibia. Peak isokinetic torque in knee extension was assessed via Biodex dynamometer. Thigh fat-free soft tissue (FFST) mass, assessed via dual-energy X-ray absorptiometry, represented the muscular aspect of tibial mechanical forces. Habitual MVPA was assessed objectively over 7 days using Actigraph GT3X+ accelerometers. Participants exceeded MVPA guidelines (89.14 ± 27.29 min/day), with males performing 44.5% more vigorous-intensity activity relative to females (p < 0.05). Males had greater knee extension torque and thigh FFST mass compared to females (55.3%, and 34.2%, respectively, all p < 0.05). In combined-sex models, controlling for tibia length and age, MVPA was associated with strength strain index (pSSI) through two indirect pathways: (i) thigh FFST mass (b = 1.11 ± 0.37; 95% CI, 0.47 to 1.93), and (i) thigh FFST mass and knee extensor torque in sequence (b = 0.30 ± 0.16; 95% CI, 0.09 to 0.73). However, in sex-specific models MVPA was associated with pSSI indirectly through its relationship with knee extensor torque in males (b = 0.78 ± 0.48; 95% CI, 0.04 to 2.02) and thigh FFST mass in females (b = 1.12 ± 0.50; 95% CI, 0.37 to 2.46). Bootstrapped CIs confirmed these mediation pathways. The relationship between MVPA and cortical structure appears to be mediated by muscle in young adults, with potential sex-differences in the muscular pathway. If confirmed, these findings may highlight novel avenues for the promotion of bone strength in young adults. © 2019 American Society for Bone and Mineral Research.     

Individual Variation in Adaptive Immune Responses and Risk of Hip Fracture—A NOREPOS Population-Based Cohort Study

Immune-mediated bone loss significantly impacts fracture risk in patients with autoimmune disease, but to what extent individual variations in immune responses affect fracture risk on a population level is unknown. To examine how immune responses relate to risk of hip fracture, we looked at the individual variation in a post-vaccination skin test response that involves some of the immune pathways that also drive bone loss. From 1963 to 1975, the vast majority of the Norwegian adult population was examined as part of the compulsory nationwide Norwegian mass tuberculosis screening. These examinations included standardized tuberculin skin tests (TSTs). Our study population included young individuals (born 1940 to 1960 and aged 14 to 30 years at examination) who had all received Bacille Calmette-Guerin (BCG) vaccination after a negative TST at least 1 year prior and had no signs of tuberculosis upon clinical examination. The study population ultimately included 244,607 individuals, whose data were linked with a national database of all hospitalized hip fractures in Norway from 1994 to 2013. There were 3517 incident hip fractures during follow-up. Using a predefined Cox model, we found that men with a positive or a strong positive TST result had a 20% (hazard ratio [HR] = 1.20, 95% confidence interval [CI] 1.01–1.44) and 24% (HR = 1.24, 95% CI 1.03–1.49) increased risk of hip fracture, respectively, compared with men with a negative TST. This association was strengthened in sensitivity analyses. Total hip bone mineral density (BMD) was available for a limited subsample and similarly revealed a non-significantly reduced BMD among men with a positive TST. Interestingly, no such clear association was observed in women. An increased immune response after vaccination is associated with an increased risk of hip fracture decades later among men, possibly because of increased immune-mediated bone loss. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Factors influencing lower extremity amputation outcomes in people with active foot ulceration in regional Australia: A retrospective cohort study

Australia has the second highest rate of non-traumatic lower extremity amputation (LEA) globally. Australia's large geographical size is one of the biggest challenges facing limb preservation services and may be contributing to LEA. The aim of this study was to determine what factors contribute to the likelihood of LEA in people with active foot ulceration in regional Australia. This retrospective cohort study audited patients with active foot ulceration in a multidisciplinary high risk foot service (HRFS) in regional Australia. Neurological, vascular and wound characteristics were systematically extracted, along with demographic information. Participants were followed for at least 12 months until healing or LEA occurred. Correlations between LEA and clinical and demographic characteristics were assessed using the Pearson's product moment correlation coefficient and chi squared test for independence. Significant variables (p < 0.05) were included in the model. Direct logistic regression assessed the independent contribution of significantly correlated variables on the likelihood of LEA. Of note, 1876 records were hand screened with 476 participants (25%) meeting the inclusion criteria. Geographical distance from the HRFS, toe systolic pressure (TSP), diabetes and infection were all significantly correlated with LEA and included in the logistic regression model. TSP decrease of 1 mmHg (OR 1.02, 95% CI 1.01–1.03), increased geographical distance (1 km) from HRFS (OR 1.006, 95% CI 1.001–1.01) infection (OR 2.08, 95% CI 1.06–4.07) and presence of diabetes (OR 3.77, 95% CI 1.12–12.65) were all significantly associated with increased likelihood of LEA. HRFS should account for the disparity in outcomes between patients living in close proximity to their service, compared to those in rural areas. Optimal management of diabetes, vascular perfusion and control of infection may also contribute to preventing LEA in people with active foot ulceration.