Evaluating the impact of point-of-care HIV viral load assessment on linkage to care in Baltimore, MD: a randomized controlled trial.

BACKGROUND: Integration of a sensitive point-of-care (POC) HIV viral load (VL) test into screening algorithms may help detect acute HIV infection earlier, identify people with HIV (PWH) who are not virally suppressed, and facilitate earlier referral to antiretroviral therapy (ART), or evaluation for pre-exposure prophylaxis (PrEP). This report describes a randomized clinical trial sponsored by the Centers for Disease Control and Prevention (CDC): "Ending the HIV Epidemic Through Point-of-Care Technologies" (EHPOC). The study's primary aim is to evaluate the use of a POC HIV VL test as part of a testing approach and assess the impact on time to linkage to ART or PrEP. The study will recruit people in Baltimore, Maryland, including patients attending a hospital emergency department, patients attending an infectious disease clinic, and people recruited via community outreach. The secondary aim is to evaluate the performance characteristics of two rapid HIV antibody tests approved by the United States Food and Drug Administration (FDA). METHODS: The study will recruit people 18 years or older who have risk factors for HIV acquisition and are not on PrEP, or PWH who are not taking ART. Participants will be randomly assigned to either the control arm or the intervention arm. Participants randomized to the control arm will only receive the standard-of-care (SOC) HIV screening tests. Intervention arm participants will receive a POC HIV VL test in addition to the SOC HIV diagnostic screening tests. Follow up will consist of an interim phone survey conducted at week-4 and an in-person week-12 visit. Demographic and behavioral information, and oral fluid and blood specimens will be collected at enrollment and at week-12. Survey data will be captured in a Research Electronic Data Capture (REDCap) database. Participants in both arms will be referred for either ART or PrEP based on their HIV test results. DISCUSSION: The EHPOC trial will explore a novel HIV diagnostic technology that can be performed at the POC and provide viral assessment. The study may help inform HIV testing algorithms and contribute to the evidence to support same day ART and PrEP recommendations. TRIAL REGISTRATION: NIH ClinicalTrials.gov NCT04793750. Date: 11 March 2021.

Cortical Bone Loss Following Gastric Bypass Surgery Is Not Primarily Endocortical.

Roux-en Y gastric bypass (RYGB) surgery is an effective treatment for obesity; however, it may negatively impact skeletal health by increasing fracture risk. This increase may be the result not only of decreased bone mineral density but also of changes in bone microstructure, for example, increased cortical porosity. Increased tibial and radial cortical porosity of patients undergoing RYGB surgery has been observed as early as 6 months postoperatively; however, local microstructural changes and associated biological mechanisms driving this increase remain unclear. To provide insight, we studied the spatial distribution of cortical porosity in 42 women and men (aged 46 ± 12 years) after RYGB surgery. Distal tibias and radii were evaluated with high-resolution peripheral quantitative computed tomography (HR-pQCT) preoperatively and at 12 months postoperatively. Laminar analysis was used to determine cortical pore number and size within the endosteal, midcortical, and periosteal layers of the cortex. Paired t tests were used to compare baseline versus follow-up porosity parameters in each layer. Mixed models were used to compare longitudinal changes in laminar analysis outcomes between layers. We found that the midcortical (0.927 ± 0.607 mm-2 to 1.069 ± 0.654 mm-2 , p = 0.004; 0.439 ± 0.293 mm-2 to 0.509 ± 0.343 mm-2 , p = 0.03) and periosteal (0.642 ± 0.412 mm-2 to 0.843 ± 0.452 mm-2 , p < 0.0001; 0.171 ± 0.101 mm-2 to 0.230 ± 0.160 mm-2 , p = 0.003) layers underwent the greatest increases in porosity over the 12-month period at the distal tibia and radius, respectively. The endosteal layer, which had the greatest porosity at baseline, did not undergo significant porosity increase over the same period (1.234 ± 0.402 mm-2 to 1.259 ± 0.413 mm-2 , p = 0.49; 0.584 ± 0.290 mm-2 to 0.620 ± 0.299 mm-2 , p = 0.35) at the distal tibia and radius, respectively. An alternative baseline-mapping approach for endosteal boundary definition confirmed that cortical bone loss was not primarily endosteal. These findings indicate that increases in cortical porosity happen in regions distant from the endosteal surface, suggesting that the underlying mechanism driving the increase in cortical porosity is not merely endosteal trabecularization. © 2022 American Society for Bone and Mineral Research (ASBMR).

Longitudinal Evolution of Bone Microarchitecture and Bone Strength in Type 2 Diabetic Postmenopausal Women With and Without History of Fragility Fractures-A 5-Year Follow-Up Study Using High Resolution Peripheral Quantitative Computed Tomography.

Introduction: Diabetic bone disease is characterized by an increased fracture risk which may be partly attributed to deficits in cortical bone quality such as higher cortical porosity. However, the temporal evolution of bone microarchitecture, strength, and particularly of cortical porosity in diabetic bone disease is still unknown. Here, we aimed to prospectively characterize the 5-year changes in bone microarchitecture, strength, and cortical porosity in type 2 diabetic (T2D) postmenopausal women with (DMFx) and without history of fragility fractures (DM) and to compare those to nondiabetic fracture free controls (Co) using high resolution peripheral quantitative computed tomography (HR-pQCT). Methods: Thirty-two women underwent baseline HR-pQCT scanning of the ultradistal tibia and radius and a FU-scan 5 years later. Bone microarchitectural parameters, including cortical porosity, and bone strength estimates via µFEA were calculated for each timepoint and annualized. Linear regression models (adjusted for race and change in BMI) were used to compare the annualized percent changes in microarchitectural parameters between groups. Results: At baseline at the tibia, DMFx subjects exhibited the highest porosity of the three groups (66.3% greater Ct.Po, 71.9% higher Ct.Po.Volume than DM subjects, p < 0.022). Longitudinally, porosity increased significantly over time in all three groups and at similar annual rates, while DMFx exhibited the greatest annual decreases in bone strength indices (compared to DM 4.7× and 6.7× greater decreases in failure load [F] and stiffness [K], p < 0.025; compared to Co 14.1× and 22.2× greater decreases in F and K, p < 0.020). Conclusion: Our data suggest that despite different baseline levels in cortical porosity, T2D women with and without fractures experienced long-term porosity increases at a rate similar to non-diabetics. However, the annual loss in bone strength was greatest in T2D women with a history of a fragility fractures. This suggests a potentially non-linear course of cortical porosity development in T2D bone disease: major porosity may develop early in the course of disease, followed by a smaller steady annual increase in porosity which in turn can still have a detrimental effect on bone strength-depending on the amount of early cortical pre-damage.

Bone remodeling following MR-guided focused ultrasound: Evaluation with HR-pQCT and FTIR.

Magnetic resonance-guided focused ultrasound (MRgFUS) is a novel non-invasive ablation technique that uses focused sound energy to destroy focal tumors, primarily via heat deposition. It is widely used for palliation of pain from bone metastases and has also recently gained popularity as a technique for ablation of benign bone tumors and facet degenerative joint disease (rhizotomy). Clinically, in a subset of patients who have undergone MRgFUS of bone, a variety of treatment responses have been noted on follow-up imaging, including focal sclerosis within the target lesion or more exuberant proliferative changes associated with the periosteum. In this study, high resolution peripheral quantitative CT (HR-pQCT) was used to evaluate remodeling of bone following ablation in a swine model of MRgFUS and compared to samples from a control, non-treated femur. Within each treated femur, two lesions were created: a higher energy focused ultrasound dose was used for one lesion compared to a lower energy dose for the second lesion. Exuberant, extra-cortical bone formation was detected at the higher energy ablation zones, with volumes ranging from 340 mm3 to 1040 mm3. More subtle endosteal and cortical changes were detected in the lower energy ablation zones, however cortical thickness was significantly increased at these sites compared to control bone. For both high and low energy lesions, lower bone mineral density and tissue mineral density was noted in treated regions compared to control regions, consistent with the formation of newly mineralized tissue. Following HR-pQCT analysis, Fourier transform infrared (FTIR) spectroscopy was subsequently used to detect biochemical changes associated with remodeling of bone following MRgFUS, and compared to samples from the control, non-treated femur. Findings were compared with histopathologic examination following hematoxylin-eosin staining. FTIR analysis demonstrated lower mineral/phosphate ratio and increased crystallinity compared to the control samples (p = 0.013). Histopathologic review demonstrated associated areas of endosteal inflammation, scarring, fat necrosis, and new extra-cortical bone formation associated with the ablations. Overall, these findings provide novel characterization of new bone formation following MRgFUS ablation.

High-Impact Mechanical Loading Increases Bone Material Strength in Postmenopausal Women-A 3-Month Intervention Study.

Bone adapts to loading in several ways, including redistributing bone mass and altered geometry and microarchitecture. Because of previous methodological limitations, it is not known how the bone material strength is affected by mechanical loading in humans. The aim of this study was to investigate the effect of a 3-month unilateral high-impact exercise program on bone material properties and microarchitecture in healthy postmenopausal women. A total of 20 healthy and inactive postmenopausal women (aged 55.6 ± 2.3 years [mean ± SD]) were included and asked to perform an exercise program of daily one-legged jumps (with incremental number, from 3×10 to 4×20 jumps/d) during 3 months. All participants were asked to register their performed jumps in a structured daily diary. The participants chose one leg as the intervention leg and the other leg was used as control. The operators were blinded to the participant's choice of leg for intervention. The predefined primary outcome was change in bone material strength index (BMSi), measured at the mid tibia with a handheld reference probe indentation instrument (OsteoProbe). Bone microstructure, geometry, and density were measured with high-resolution peripheral quantitative computed tomography (XtremeCT) at the ultradistal and at 14% of the tibia bone length (distal). Differences were analyzed by related samples Wilcoxon signed rank test. The overall compliance to the jumping program was 93.6%. Relative to the control leg, BMSi of the intervention leg increased 7% or 0.89 SD (p = 0.046), but no differences were found for any of the XtremeCT-derived bone parameters. In conclusion, a unilateral high-impact loading program increased BMSi in postmenopausal women rapidly without affecting bone microstructure, geometry, or density, indicating that intense mechanical loading has the ability to rapidly improve bone material properties before changes in bone mass or structure. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.

Trabecular bone microstructure is impaired in the proximal femur of human immunodeficiency virus-infected men with normal bone mineral density.

BACKGROUND: There is evidence that human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) are independent risk factors for osteoporosis and fracture which is not solely explained by changes in bone mineral density. Thus, we hypothesized that the assessment of trabecular microstructure might play an important role for bone quality in this population and might explain the increased fracture risk. In this study, we have assessed bone microstructure in the proximal femur using high-resolution magnetic resonance imaging (MRI) as well as in the extremities using high resolution peripheral quantitative computed tomography (HR-pQCT) in HIV-infected men and healthy controls and compared these findings to those based on areal bone mineral density (aBMD) derived from dual X-ray absorptiometry (DXA) which is the standard clinical parameter for the diagnosis of osteoporosis. METHODS: Eight HIV-infected men and 11 healthy age-matched controls were recruited and informed consent was obtained before each scan. High-resolution MRI of the proximal femur was performed using fully balanced steady state free precession (bSSFP) on a 3T system. Three volumes of interest at corresponding anatomic locations across all subjects were defined based on registrations of a common template. Four MR-based trabecular microstructural parameters were analyzed at each region: fuzzy bone volume fraction (f-BVF), trabecular number (Tb.N), thickness (Tb.Th), and spacing (Tb.Sp). In addition, the distal radius and distal tibia were imaged with HR-pQCT. Four HR-pQCT-based microstructural parameters were analyzed: trabecular bone volume fraction (BV/TV), Tb.N, Tb.Th, and Tb.Sp. Total hip and spine aBMD were determined from DXA. RESULTS: Microstructural bone parameters derived from MRI at the proximal femur and from HR-pQCT at the distal tibia showed significantly lower bone quality in HIV-infected patients compared to healthy controls. In contrast, DXA aBMD data showed no significant differences between HIV-infected patients and healthy controls. CONCLUSIONS: Our results suggest that high-resolution imaging is a powerful tool to assess trabecular bone microstructure and can be used to assess bone health in HIV-infected men who show no differences to healthy males by DXA aBMD. Advances in MRI technology have made microstructural imaging at the proximal femur possible. Further studies in larger patient cohorts are clearly warranted.

Effects of Gastric Bypass Surgery on Bone Mass and Microarchitecture Occur Early and Particularly Impact Postmenopausal Women.

Roux-en-Y gastric bypass (RYGB) surgery is a highly effective treatment for obesity but negatively affects the skeleton. Studies of skeletal effects have generally examined areal bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA), but DXA may be inaccurate in the setting of marked weight loss. Further, as a result of modestly sized samples of mostly premenopausal women and very few men, effects of RYGB by sex and menopausal status are unknown. We prospectively studied the effects of RYGB on skeletal health, including axial and appendicular volumetric BMD and appendicular bone microarchitecture and estimated strength. Obese adults (N = 48; 27 premenopausal and 11 postmenopausal women, 10 men) with mean ± SD body mass index (BMI) 44 ± 7 kg/m2 were assessed before and 6 and 12 months after RYGB. Participants underwent spine and hip DXA, spine QCT, radius and tibia HR-pQCT, and laboratory evaluation. Mean 12-month weight loss was 37 kg (30% of preoperative weight). Overall median 12-month increase in serum collagen type I C-telopeptide (CTx) was 278% (p < 0.0001), with greater increases in postmenopausal than premenopausal women (p = 0.049). Femoral neck BMD by DXA decreased by mean 5.0% and 8.0% over 6 and 12 months (p < 0.0001). Spinal BMD by QCT decreased by mean 6.6% and 8.1% (p < 0.0001); declines were larger among postmenopausal than premenopausal women (11.6% versus 6.0% at 12 months, p = 0.02). Radial and tibial BMD and estimated strength by HR-pQCT declined. At the tibia, detrimental changes in trabecular microarchitecture were apparent at 6 and 12 months. Cortical porosity increased at the radius and tibia, with more dramatic 12-month increases among postmenopausal than premenopausal women or men at the tibia (51.4% versus 18.3% versus 3.0%, p < 0.01 between groups). In conclusion, detrimental effects of RYGB on axial and appendicular bone mass and microarchitecture are detectable as early as 6 months postoperatively. Postmenopausal women are at highest risk for skeletal consequences and may warrant targeted screening or interventions. © 2017 American Society for Bone and Mineral Research.