The impact of free antiretroviral therapy for pregnant non-citizens and their infants in Botswana

Introduction

In December 2019, the Botswana government expanded free antiretroviral therapy (ART) to include non-citizens. We evaluated the impact of this policy change on antenatal care (ANC), antiretroviral therapy coverage and adverse birth outcomes.

Methods

The Tsepamo Surveillance study collects data at up to 18 delivery sites in Botswana. We compared outcomes in citizens and non-citizens living with HIV before and after antiretroviral therapy expansion to non-citizens. Adverse birth outcomes included preterm delivery (PTD) <37 weeks, very preterm delivery (VPTD) <32 weeks, small for gestational age (SGA) <10th percentile, very small for gestational age (VSGA) <3rd percentile, stillbirth and neonatal death. Log-binomial regression models were constructed to generate risk ratios.

Results

From August 2014 to September 2021, 45,576 (96.5%) citizens and 1513 (3.2%) non-citizens living with HIV delivered; 954 (62.9%) non-citizen deliveries were before the antiretroviral therapy expansion, and 562 (37.1%) were after. Non-citizen ANC attendance among pregnant people living with HIV increased from 79.2% pre-expansion to 87.2% post-expansion (p<0.001), and became more similar to citizens (96.0% post-expansion). Non-citizens receiving any antenatal antiretroviral therapy increased from 65.5% pre-expansion to 89.9% post-expansion (p < 0.001), also more similar to citizens (97.2% post-expansion). Infants born to non-citizens with singleton gestations in the pre-expansion period had significantly greater risk of PTD (aRR = 1.28, 95% CI, 1.11, 1.46), VPTD (aRR = 1.89, 95% CI, 1.43, 2.44) and neonatal death (aRR = 1.69, 95% CI, 1.03, 2.60), but reduced SGA risk (aRR = 0.75; 95% CI, 0.62, 0.89) compared with citizens. Post-expansion, greater declines in most adverse outcomes were observed in non-citizens, with largely similar outcomes between non-citizens and citizens. Non-significant differences were observed for non-citizenship in PTD (aRR = 0.84, 95% CI, 0.66, 1.06), VPTD (aRR = 0.57, 95% CI, 0.28, 1.01), SGA (aRR = 0.91, 95% CI, 0.72, 1.13), VSGA (aRR = 0.87, 95% CI, 0.58, 1.25), stillbirth (aRR = 0.71, 95% CI, 0.35, 1.27) and neonatal death (aRR = 1.35, 95% CI, 0.60, 2.62).

Conclusions

Following the expansion of free antiretroviral therapy to non-citizens, gaps narrowed in ANC and antiretroviral therapy use in pregnancy between citizens and non-citizens living with HIV. Disparities in adverse birth outcomes were no longer observed.     

病重特护患者压疮的发生率、预防和治疗

研究背景压疮普遍发生于急性和慢性患者.然而危重疾病患者通常是压疮发生的高风险因素.目标这个研究的主导是评估重症护理患者的压疮发生率,个体进入到病重护理状态下时,影响压疮发生率的因素和压疮过程.设计纵向设计.     

病重特护患者压疮的发生率、预防和治疗

研究背景压疮普遍发生于急性和慢性患者.然而危重疾病患者通常是压疮发生的高风险因素.目标这个研究的主导是评估重症护理患者的压疮发生率,个体进入到病重护理状态下时,影响压疮发生率的因素和压疮过程.设计纵向设计.     

Angiopoietin 2 Is Associated with Vascular Necroptosis Induction in Coronavirus Disease 2019 Acute Respiratory Distress Syndrome

Vascular injury is a well-established, disease-modifying factor in acute respiratory distress syndrome (ARDS) pathogenesis. Recently, coronavirus disease 2019 (COVID-19)–induced injury to the vascular compartment has been linked to complement activation, microvascular thrombosis, and dysregulated immune responses. This study sought to assess whether aberrant vascular activation in this prothrombotic context was associated with the induction of necroptotic vascular cell death. To achieve this, proteomic analysis was performed on blood samples from COVID-19 subjects at distinct time points during ARDS pathogenesis (hospitalized at risk, N = 59; ARDS, N = 31; and recovery, N = 12). Assessment of circulating vascular markers in the at-risk cohort revealed a signature of low vascular protein abundance that tracked with low platelet levels and increased mortality. This signature was replicated in the ARDS cohort and correlated with increased plasma angiopoietin 2 levels. COVID-19 ARDS lung autopsy immunostaining confirmed a link between vascular injury (angiopoietin 2) and platelet-rich microthrombi (CD61) and induction of necrotic cell death [phosphorylated mixed lineage kinase domain-like (pMLKL)]. Among recovery subjects, the vascular signature identified patients with poor functional outcomes. Taken together, this vascular injury signature was associated with low platelet levels and increased mortality and can be used to identify ARDS patients most likely to benefit from vascular targeted therapies.

For decades, vascular injury has been recognized as a key element in the pathogenesis of acute respiratory distress syndrome (ARDS).¹ However, this has not translated into vascular targeted therapies for ARDS. This may, in part, be related to heterogeneity in the vascular response to injury among ARDS subjects, as well as to difficulty in selecting patients most at risk for ARDS vascular injury. Blood proteomics has been proposed as a novel translational approach to better match patients to precision therapies for ARDS.² A better understanding of the blood proteomic changes associated with ARDS vascular injury could therefore help identify patients likely to benefit from vascular therapies.Previous targeted studies of circulating vascular proteins have greatly enhanced the understanding of ARDS vascular injury. For example, measurement of the plasma angiocrine factor angiopoietin 2 (ANGPT2) in patients at the early stages of ARDS demonstrates that vascular injury likely precedes mechanical ventilation³ and is associated with ARDS disease mortality.⁴ However, these ANGPT2-mediated vascular disruptions can be countered. In mice, systemic administration of platelet-derived pericyte chemokines, such as angiopoietin 1 (ANGPT1) and platelet-derived growth factor B (PDGFB), counter ANGPT2-mediated vascular disruption, demonstrating the homeostatic potential of the blood vascular proteome.⁵ Improved understanding of the blood proteomic changes in subjects with ARDS with high or low vascular injury can build on these prior observations, shed further light onto disease pathogenesis, and identify protein targets for further investigation.More recently, vascular injury has been associated with coronavirus disease 2019 (COVID-19) ARDS,^6,7 including the vascular complications of inflammation and thrombosis. In this context, COVID-19–induced injury to the vascular compartment has been associated with complement activation and microvascular thrombosis,8, 9, 10 systemic thrombosis,^9,11 and dysregulated immune responses.^12,13 However, this focus on inflammation and thrombosis limits our insights into other disruptions associated with aberrant vascular activation, including angiogenesis, junctional barrier integrity, the role of activated platelets in vascular injury, and induction of vascular cell death, including specialized receptor-interacting protein kinase 3 (RIPK3)–mediated necrotic cell death. Specifically, although ANGPT2-mediated vascular disruption has been documented in COVID-19,¹⁴ the association between ANGPT2 and induction of vascular cell death remains largely unexplored in ARDS investigations.The purpose of this study was to assess whether aberrant vascular activation in COVID-19 was associated with the induction of necroptotic vascular cell death. To this aim, blood proteomics was performed in three independent COVID-19 cohorts, which enrolled patients at distinct time points in disease pathogenesis and included non–COVID-19 ARDS samples as control. Protein expression was linked to relevant clinical outcomes, vascular injury, and cell death markers in COVID-19 autopsy lung tissue.     

Ursolic acid and SARS-CoV-2 infection: a new horizon and perspective

Inflammopharmacology - SARS-CoV-2 (severe acute respiratory syndrome coronavirus type 2) has been identified as the source of a world coronavirus pandemic in 2019. Covid-19 is considered a main...     

Synthesis and antitumor activity of new pyrido[2,3-d]pyrimidine derivatives

New series of pyrido[2,3-d]pyrimidines such as; 5-(4-aryl-5-sulfanyl-4H-[1,2,4]triazol-3-yl) 1H,3H,8H-pyrido[2,3-d]pyrimidine-2,4,7-triones 6, 7; S-[3-(2,4,7-trioxo-1,2,3,4,7,8-hexahydropyrido[2,3-d]pyrimidin-5-yl)-4-(4-substituted phenyl)-4H-[1,2,4]triazol-5-yl]-2-(4-phenylpiperazin-1-yl)ethanethioates 10, 11; 2,4,7-trioxo-N′-[(4-substituted piperazin-1-yl)acetyl]-1,2,3,4,7,8-hexahydropyrido[2,3-d]pyrimidine-5-carbohydrazides 13–16 and N′-arylidene-2,4,7-trioxo-1,2,3,4,7,8-hexahydropyrido[2,3-d]pyrimidine-5-carbohydrazides 17–19 was synthesized through the reaction of the key intermediate 2,4,7-trioxo-1,2,3,4,7,8-hexahydropyrido[2,3-d]pyrimidine-5-carbohydrazide 3 with different reagents. The structures of the newly synthesized compounds were elucidated through microanalysis, IR, ¹H NMR, ¹³C NMR, and mass spectroscopy. These compounds have been subjected to in vitro antitumor evaluation by bleomycin-dependant DNA damage assay. The most active antitumor compound 6 was selected for further in vivo evaluation of antineoplastic activity against Ehrlich ascites carcinoma in mice. It was observed that our target compound has a potent antitumor activity.     

The lower incisors as a predictor for the size of unerupted canine and premolars in the Iranian ethnicity

The purpose of this study was to find the correlation coefficients between the mesiodistal widths of the permanent mandibular incisors and the permanent canine and premolars for each quadrant and establish a regression equation for prediction of the sum of canine and premolars based on the dimension of the lower incisors. 90 patients 12–20 years old (45 females and 45 males) were selected. The mesiodistal crown diameters of the permanent teeth were measured. The correlation coefficients between the permanent mandibular incisors and the permanent canine and premolars sizes varied from 0.63 to 0.8. An Iranian mixed dentition analysis based on the Tanaka and Johnston method was constructed with linear regression equations; for maxillary arch y = 6.3 + 0.65x (SEE = 0.8 mm) and for mandibular arch y = 5.1 + 0.67x (SEE = 0.8 mm). No significant sexual dimorphism was found in tooth sizes. This study revealed that Iranian population has smaller teeth than white North American. We found that prediction equations of Tanaka and Johnston or Moyers charts cannot accurately predict the size of buccal segment in Iranian population.