A qualitative exploration of barriers to HIV prevention,treatment and support: Perspectives of transgender women and service providers

Transgender (trans) women experience barriers to access to HIV care, which result in their lower engagement in HIV prevention, treatment and support relative to cisgender people living with HIV. Studies of trans women's barriers to HIV care have predominantly focused on perspectives of trans women, while barriers are most often described at provider, organisation and/or systems levels. Comparing perspectives of trans women and service providers may promote a shared vision for achieving health equity. Thus, this qualitative study utilised focus groups and semi-structured interviews conducted 2018–2019 to understand barriers and facilitators to HIV care from the perspectives of trans women (n = 26) and service providers (n = 10). Barriers endorsed by both groups included: (a) anticipated and enacted stigma and discrimination in the provision of direct care, (b) lack of provider knowledge of HIV care needs for trans women, (c) absence of trans-specific services/organisations and (d) cisnormativity in sexual healthcare. Facilitators included: (a) provision of trans-positive trauma-informed care, (b) autonomy and choice for trans women in selecting sexual health services and (c) models for trans-affirming systems change. Each theme had significant overlap, yet nuanced perspective, between trans women and service providers. Specific recommendations to improve HIV care access for trans women are discussed. These recommendations can be used by administrators and service providers alike to work collaboratively with trans women to reduce barriers and facilitators to HIV care and ultimately to achieve health equity for trans women.     

Antigen-induced T-cell changes: Modulation by pharmacologic agents

To determine the effect of pharmacologic modulation of alterations of peripheral blood T-cell subsets caused by antigen-induced bronchoconstriction, we administered albuterol immediately after antigen-induced bronchoconstriction in a double-blind to protocol to 12 atopic asthmatic subjects. We also administered cromolyn sodium before antigen to 7 of the same subjects. Peripheral blood T-cell subset composition (CD4, CD8, la) of a highly purified T-cell preparation was determined before, 24, 48, 72, and 168 h after bronchoconstriction. We found that placebo inhalation immediately after antigen-induced bronchoconstriction did not affect subsequent peripheral blood T-cell subset changes (decrease in CD4+ and increase in Ia+ T lymphocytes). In contrast, inhaled albuterol abolished these T-cell subset changes. Although cromolyn sodium significantly decreased the severity of antigen-induced bronchoconstriction, it did not affect T-cell subset composition changes at the dosage used. We conclude that albuterol can ablate T-cell subset changes associated with antigen-induced bronchoconstriction. Cromolyn sodium ameliorates bronchoconstriction, but has no affect on T-cell subset composition changes. This implies that T-cell changes and bronchoconstriction caused by antigen inhalation are mediated through different pathways.     

Prediction of perinatal outcome in fetuses suspected to have intrauterine growth restriction: Doppler US study of fetal cerebral, renal, and umbilical arteries

PURPOSE: To determine and compare the diagnostic performance of fetal middle cerebral (MCA), renal (RA), and umbilical (UA) arterial Doppler ultrasonography (US) for prediction of adverse perinatal outcome in suspected intrauterine growth restriction (IUGR). MATERIALS AND METHODS: Two hundred ninety-three small-for-gestational age fetuses (24-39 weeks at recruitment and US-estimated weight or abdominal circumference below 10th percentile) were prospectively examined with Doppler US of the UA, MCA, and RA. Clinicians were blinded to MCA and RA Doppler measurements. RESULTS: Seventy-six fetuses (25.9%) had at least one major or minor adverse perinatal outcome. Major outcomes included stillbirth, neonatal death, neurologic complication, and necrotizing enterocolitis. The MCA pulsatility index (PI), compared with the UA PI and RA PI, was more sensitive (72.4% vs 44.7% and 8.3%) but less specific (58.1% vs 86.6% and 92.6%) in predicting adverse outcome. The UA PI had the highest positive likelihood ratio (ratio, 3.3); the MCA PI had the lowest negative likelihood ratio (ratio, 0.48). When gestational age at the first Doppler US examination was less than 32 weeks, the MCA PI had a sensitivity of 95.5% and negative predictive value of 97.7% for major adverse outcome (negative likelihood ratio, 0.10). CONCLUSION: In suspected IUGR, while an abnormal UA PI is a better predictor of adverse perinatal outcome than an abnormal MCA or RA PI, a normal MCA PI may help to identify fetuses without major adverse perinatal outcome, especially before 32 weeks gestational age.     

Biological response modifiers in the management of rheumatoid arthritis.

The management of rheumatoid arthritis (RA) with biological response modifiers (BRMs) is reviewed. RA, an autoimmune disorder affecting 1-2% of the world's population, is characterized by inflammation of synovial tissues, joint swelling, stiffness, and pain that may progress to joint erosion. There is strong evidence that inflammatory mediators, such as tissue necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1), play a critical role in the pathogenesis of this disorder. IL-1-receptor antagonist (IL-1Ra) is produced in healthy subjects and helps to protect against the adverse effects associated with IL-1 overexpression. Administration of IL-1Ra or similar agents may reduce the effects of IL-1 and ameliorate inflammatory conditions. Traditional treatment of RA has been based on symptomatic management with non-steroidal antiinflammatory drugs, disease-modifying antirheumatic drugs, and corticosteroids, each of which has substantial drawbacks in terms of effectiveness or adverse effects. Newer therapeutic strategies for blocking the biological effects of inflammatory cytokines include antibodies directed against TNF (e.g., infliximab), soluble receptors (e.g., etanercept) and receptor antagonists to IL-1 (anakinra) [corrected]. Clinical trials indicate that these BRMs may be more effective than traditional agents because they are able to alter joint remodeling in addition to attenuating symptoms. Anti-TNF therapies may be associated with increased risk for infections, sepsis, tuberculosis reactivation, demyelination disorders, and blood dyscrasias; anakinra appears to be safer. Combination therapy with BRMs may be more appropriate for RA than monotherapy. The role of BRMs in the treatment of RA will evolve as investigators learn more about the drugs and the disorder.     

Estimating numbers of injecting drug users in metropolitan areas for structural analyses of community vulnerability and for assessing relative degrees of service provision for injecting drug users

This article estimates the population prevalence of current injection drug users (IDUs) in 96 large US metropolitan areas to facilitate structural analyses of its predictors and sequelae and assesses the extent to which drug abuse treatment and human immunodeficiency virus (HIV) counseling and testing are made available to drug injectors in each metropolitan area. We estimated the total number of current IDUs in the United States and then allocated the large metropolitan area total among large metropolitan areas using four different multiplier methods. Mean values were used as best estimates, and their validity and limitations were assessed. Prevalence of drug injectors per 10,000 population varied from 19 to 173 (median 60; interquartile range 42–87). Proportions of drug injectors in treatment varied from 1.0% to 39.3% (median 8.6%); and the ratio of HIV counseling and testing events to the estimated number of IDUs varied from 0.013 to 0.285 (median 0.082). Despite limitations in the accuracy of these estimates, they can be used for structural analyses of the correlates and predictors of the population density of drug injectors in metropolitan areas and for assessing the extent of service delivery to drug injectors. Although service provision levels varied considerably, few if any metropolitan areas seemed to be providing adequate levels of services.     

Pharmacist involvement in antimicrobial use at rural community hospitals in four Western states.

PURPOSE: Pharmacist involvement in antimicrobial use at small rural hospitals in four Western states was studied. METHODS: Surveys were mailed in July 2000 to hospitals with a daily patient census of <150 in Idaho, Nevada, Utah, and eastern Washington. RESULTS: Seventy-seven (77%) of 100 hospitals returned completed surveys. Only 5% of the hospitals had onsite pharmacists 24 hours per day. An onsite pharmacist was present for a median of 26 hours per week in hospitals without 24-hour pharmacist coverage (range, 0-116 hr/wk). Many hospitals (71%) had policies for monitoring or controlling antimicrobial use, but only 28% had a system capable of monitoring compliance with such policies. Few hospitals had systems for recommending changes in antimicrobial selection on the basis of susceptibility test results (27%) or for monitoring physician compliance with dosage recommendations by pharmacists (21%). Onsite pharmacist hours were significantly associated with pharmacists being involved in the initial ordering of antibiotics and providing active oversight of antimicrobial use. There was a negative correlation between onsite pharmacist hours and use of third-generation cephalosporins and carbapenems. CONCLUSION: A survey showed that rural hospital pharmacists in four Western states spent relatively little time monitoring and influencing antimicrobial prescribing.     

Vascular modulation through exercise improves chemotherapy efficacy in Ewing sarcoma

Recent studies in mouse models of cancer have shown that exercise improves tumor vascular function, thereby improving chemotherapy delivery and efficacy. However, the mechanisms underlying this improvement remain unclear and the effect of exercise on Ewing sarcoma (ES), a pediatric bone and soft tissue cancer, is unknown. The effect of exercise on tumor vascular hyperpermeability, which inversely correlates with drug delivery to the tumor, has also not been evaluated. We hypothesized that exercise improves chemotherapy efficacy by enhancing its delivery through improving tumor vascular permeability. We treated ES‐bearing mice with doxorubicin with or without moderate treadmill exercise. Exercise did not significantly alter ES tumor vessel morphology. However, compared to control mice, tumors of exercised mice had significantly reduced hyperpermeability, significantly decreased hypoxia, and higher doxorubicin penetration. Compared to doxorubicin alone, doxorubicin plus exercise inhibited tumor growth more efficiently. We evaluated endothelial cell sphingosine‐1‐phosphate receptors 1 and 2 (S1PR1 and S1PR2) as potential mediators of the improved vascular permeability and increased function afforded by exercise. Relative to tumors from control mice, vessels in tumors from exercised mice had increased S1PR1 and decreased S1PR2 expression. Our results support a model in which exercise remodels ES vasculature to reduce vessel hyperpermeability, potentially via modulation of S1PR1 and S1PR2, thereby improving doxorubicin delivery and inhibiting tumor growth more than doxorubicin alone does. Our data suggest moderate aerobic exercise should be tested in clinical trials as a potentially useful adjuvant to standard chemotherapy for patients with ES.     

Surveillance of γδ T Cells Predicts Cytomegalovirus Infection Resolution in Kidney Transplants

Cytomegalovirus (CMV) infection in solid-organ transplantation is associated with increased morbidity and mortality, particularly if a CMV mutant strain with antiviral resistance emerges. Monitoring CMV–specific T cell response could provide relevant information for patient care. We and others have shown the involvement of Vδ2^neg γδ T cells in controlling CMV infection. Here, we assessed if Vδ2^neg γδ T cell kinetics in peripheral blood predict CMV infection resolution and emergence of a mutant strain in high–risk recipients of kidney transplants, including 168 seronegative recipients receiving organs from seropositive donors (D+R−) and 104 seropositive recipients receiving antithymocyte globulins (R+/ATG). Vδ2^neg γδ T cell percentages were serially determined in patients grafted between 2003 and 2011. The growing phase of Vδ2^neg γδ T cells was monitored in each infected patient, and the expansion rate during this phase was estimated individually by a linear mixed model. A Vδ2^neg γδ T cell expansion rate of ˃0.06% per day predicted the growing phase. The time after infection at which an expansion rate of 0.06% per day occurred was correlated with the resolution of CMV DNAemia (r=0.91; P<0.001). At 49 days of antiviral treatment, Vδ2^neg γδ T cell expansion onset was associated with recovery, whereas absence of expansion was associated with recurrent disease and DNAemia. The appearance of antiviral–resistant mutant CMV strains was associated with delayed Vδ2^neg γδ T cell expansion (P<0.001). In conclusion, longitudinal surveillance of Vδ2^neg γδ T cells in recipients of kidney transplants may predict CMV infection resolution and antiviral drug resistance.     

Supratentorial CAPNON associated with WHO grade II meningioma: A case report

Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare benign tumor of uncertain etiology, arising in the craniospinal axis. CAPNON typically arises in isolation, with only two prior reports of a concurrent second neoplasm. Here, we report the case of a male 17‐year‐old who presented with new‐onset seizures. MRIs revealed a 2 cm extra‐axial solid‐cystic mass, arising at the left temporo‐occipital junction and abutting the dura with marked surrounding parenchymal vasogenic edema. The solid components demonstrated dense calcification and avid enhancement. Gross total surgical resection was performed. Histopathological examination revealed central regions showing characteristic features of CAPNON. Toward the periphery, the CAPNON was intimately associated with and sharply demarcated from a meningioma, which showed up to five mitoses per 10 high‐power fields and had invasion into the adjacent brain parenchyma, warranting a WHO grade II designation. This is the first report of CAPNON arising in association with a meningioma. The coexistence of these two tumors raises the possibility of a reactive/dysplastic etiology for CAPNON.