Meta-analysis of Pregnancy Events in Biomedical HIV Prevention Trials in Sub-Saharan Africa: Implications for Gender Transformative Trials.

Historically, pregnant and lactating populations (PLP) have been excluded or disenrolled from biomedical HIV prevention trials, despite being more likely to acquire HIV during pregnancy and the post-partum period. We conducted a meta-analysis of pregnancy events in biomedical HIV prevention trials in sub-Saharan Africa to support trialists moving toward more inclusive clinical and implementation studies. We searched peer-reviewed literature reporting pregnancy events and contraceptive requirements in HIV prevention trials between 2001 and 2022. We hypothesized four variables to explain variation: contraceptive requirements, study start year, study product, and sub-region. We fit a meta-analytic model to estimate individual effect sizes and sampling variances, then conducted sub-group analyses to assess moderating effects. We identified 38 references for inclusion, across which the proportion of pregnancy events was 8% (95% confidence interval [CI]: 6-10%) with high heterogeneity (I2 = 99%). Studies not requiring contraceptives (21%, 95%CI: 7-48%) reported a significantly higher proportion of pregnancy events than studies requiring two methods (5%, 95%CI: 2-10%). Studies launched between 2001 and 2007 (11%, 95%CI: 8-16%), microbicide gel trials (12%, 95%CI: 8-18%), and studies conducted in Western Africa (28%, 95%CI: 13-51%) reported higher proportions of pregnancy events than reference groups. Together, these variables have a moderating effect on pregnancy events (p < 0.0001), explaining 63% of heterogeneity in trials. Results describe how, over time, more stringent contraceptive requirements reduced pregnancy events, which ensured necessary statistical power but limited reproductive choice by participants. With the move toward continuing PLP on experimental products, trialists can utilize estimated pregnancy events reported here to inform strategies that accommodate participants' changing fertility preferences.

HIV Prevention Product Acceptability and Preference Among Women in Sub-Saharan Africa to Inform Novel Biomedical Options in Development: A Systematic Review.

The availability of several HIV prevention options may allow women to choose a product that suits their lifestyle and preferences. Product attributes and contextual factors influence product acceptability, which affects uptake and effective use. We conducted a systematic review of acceptability and preference for biomedical HIV prevention products among women in sub-Saharan Africa (SSA) to inform the development of novel products. We used a comprehensive strategy to search three databases for peer-reviewed literature from SSA published between January 2015 and December 2023. A two-stage review process assessed references against eligibility criteria. Data were abstracted using a standardized spreadsheet, then organized by constructs from two theoretical frameworks of acceptability. Results were synthesized based on product classes defined by route of administration. We identified 408 unique references; 100 references met eligibility criteria. References assessed oral PrEP (n = 65), vaginal ring (n = 44), long-acting systemic products (injectable, implant, microarray patch) (n = 28), and other vaginal products (film, insert, gel) (n = 20). Over two-thirds reported qualitative or mixed-methods data, primarily from adolescent girls and young women. Frequent dosing, especially noted for daily oral PrEP, and perceived/experienced side effects were notably negative influences. Most end-users preferred long-acting products (systemically or vaginally delivered), though on-demand products offering user control were also valued. Influencing factors, especially partners, shaped end-user perceptions of product attributes and acceptability. All products were linked to at least some barriers to uptake and/or use, highlighting the need to provide end-users with a range of options and assist them in identifying one that best suits their circumstances and needs. Biomedical HIV prevention development should advance products that address gaps in available options while optimizing favorable product attributes to achieve high acceptability that ultimately supports adoption and use.

Oral toxicity evaluation of Bacillus clausii M31 isolated from the children's feces in the northern province of Vietnam.

This study investigated the acute and repeated 28-day dose toxicity profiles of Bacillus clausii M31, isolated from children's feces, in Swiss rats and New Zealand rabbits. To investigate acute toxicity, rats were given varied doses of B. clausii M31 (1 × 1011 CFU/mL, 3 × 1011 CFU/mL, and 5 × 1011 CFU/mL) orally once daily for 14 days, in accordance with OECD recommendations No. 423. To evaluate toxicity, rabbits were given either a low dosage (1 × 1011 CFU/mL) or a high dose (5 × 1011 CFU/mL) during a 28-day period using the OECD Test Guideline 407 protocol. Neither death nor significant abnormalities were observed in the rats during the experiment. The microscopic examination of key organs revealed no substantial changes in organ morphology. Furthermore, analyses of serum biochemistry and hematological parameters did not reveal any treatment-associated variations. In sum, these findings suggest that the oral intake of B. clausii M31 at concentrations up to 5 × 1011 CFU/mL for 28 days poses no discernible risks.

An Effective Health System Approach to End TB: Implementing the Double X Strategy in Vietnam.

Countries that are high burden for TB must reverse the COVID-19 pandemic's devastating effects to accelerate progress toward ending TB. Vietnam's Double X (2X) strategy uses chest radiography (CXR) and GeneXpert (Xpert) rapid diagnostic testing to improve early detection of TB disease. Household contacts and vulnerable populations (e.g., individuals aged 60 years and older, smokers, diabetics, those with alcohol use disorders, and those previously treated for TB) with and without TB symptoms were screened in community campaigns using CXRs, followed by Xpert for those with a positive screen. In public non-TB district facilities, diabetics, respiratory outpatients, inpatients with lung disease, and other vulnerable populations underwent 2X evaluation. During COVID-19 restrictions in Vietnam, the 2X strategy improved access to TB services by decentralization to commune health stations, the lowest level of the health system, and enabling self-screening using a quick response mobile application. The number needed to screen (NNS) with CXRs to diagnose 1 person with TB disease was calculated for all 2X models and showed the highest yield among self-screeners (11 NNS with CXR), high yield for vulnerable populations in communities (60 NNS) and facilities (19 NNS), and moderately high yield for household contacts in community campaigns (154 NNS). Computer-aided diagnosis for CXRs was incorporated into community and facility implementation and improved physicians' CXR interpretations and Xpert referral decisions. Integration of TB infection and TB disease evaluation increased eligibility for TB preventive treatment among household contacts, a major challenge during implementation. The 2X strategy increased the rational use of Xpert, employing a health system-wide approach that reached vulnerable populations with and without TB symptoms in communities and facilities for early detection of TB disease. This strategy was effectively adapted to different levels of the health system during COVID-19 restrictions and contributed to post-pandemic TB recovery in Vietnam.

Active case finding to detect symptomatic and subclinical pulmonary tuberculosis disease: implementation of computer-aided detection for chest radiography in Viet Nam.

Objective: In Viet Nam, tuberculosis (TB) prevalence surveys revealed that approximately 98% of individuals with pulmonary TB have TB-presumptive abnormalities on chest radiographs, while 32% have no TB symptoms. This prompted the adoption of the "Double X" strategy, which combines chest radiographs and computer-aided detection with GeneXpert testing to screen for and diagnose TB among vulnerable populations. The aim of this study was to describe demographic, clinical and radiographic characteristics of symptomatic and asymptomatic Double X participants and to assess multilabel radiographic abnormalities on chest radiographs, interpreted by computer-aided detection software, as a possible tool for detecting TB-presumptive abnormalities, particularly for subclinical TB. Methods: Double X participants with TB-presumptive chest radiographs and/or TB symptoms and known risks were referred for confirmatory GeneXpert testing. The demographic and clinical characteristics of all Double X participants and the subset with confirmed TB were summarized. Univariate and multivariable logistic regression modelling was used to evaluate associations between participant characteristics and subclinical TB and between computer-aided detection multilabel radiographic abnormalities and TB. Results: From 2020 to 2022, 96 631 participants received chest radiographs, with 67 881 (70.2%) reporting no TB symptoms. Among 1144 individuals with Xpert-confirmed TB, 51.0% were subclinical. Subclinical TB prevalence was higher in older age groups, non-smokers, those previously treated for TB and the northern region. Among 11 computer-aided detection multilabel radiographic abnormalities, fibrosis was associated with higher odds of subclinical TB. Discussion: In Viet Nam, Double X community case finding detected pulmonary TB, including subclinical TB. Computer-aided detection software may have the potential to identify subclinical TB on chest radiographs by classifying multilabel radiographic abnormalities, but further research is needed.

Systematic review of the values and preferences regarding the use of injectable pre-exposure prophylaxis to prevent HIV acquisition.

INTRODUCTION: Pre-exposure prophylaxis (PrEP) is an important HIV prevention option. Two randomized trials have provided efficacy evidence for long-acting injectable cabotegravir (CAB-LA) as PrEP. In considering CAB-LA as an additional PrEP modality for people at substantial risk of HIV, it is important to understand community response to injectable PrEP. We conducted a systematic review of values, preferences and perceptions of acceptability for injectable PrEP to inform global guidance. METHODS: We searched nine databases and conference websites for peer-reviewed and grey literature (January 2010-September 2021). There were no restrictions on location. A two-stage review process assessed references against eligibility criteria. Data from included studies were organized by constructs from the Theoretical Framework of Acceptability. RESULTS: We included 62 unique references. Most studies were observational, cross-sectional and qualitative. Over half of the studies were conducted in North America. Men who have sex with men were the most researched group. Most studies (57/62) examined injectable PrEP, including hypothetical injectables (55/57) or placebo products (2/57). Six studies examined CAB-LA specifically. There was overall interest in and often a preference for injectable PrEP, though there was variation within and across groups and regions. Many stakeholders indicated that injectable PrEP could help address adherence challenges associated with daily or on-demand dosing for oral PrEP and may be a better lifestyle fit for individuals seeking privacy, discretion and infrequent dosing. End-users reported concerns, including fear of needles, injection site pain and body location, logistical challenges and waning or incomplete protection. DISCUSSION: Despite an overall preference for injectable PrEP, heterogeneity across groups and regions highlights the importance of enabling end-users to choose a PrEP modality that supports effective use. Like other products, preference for injectable PrEP may change over time and end-users may switch between prevention options. There will be a greater understanding of enacted preference as more end-users are offered anti-retroviral (ARV)-containing injectables. Future research should focus on equitable implementation, including real-time decision-making and how trained healthcare providers can support choice. CONCLUSIONS: Given overall acceptability, injectable PrEP should be included as part of a menu of prevention options, allowing end-users to select the modality that suits their preferences, needs and lifestyle.

Safety and efficacy of long-acting injectable cabotegravir as preexposure prophylaxis to prevent HIV acquisition.

OBJECTIVE: HIV remains a significant burden, despite expanding HIV prevention tools. Long-acting injectable cabotegravir (CAB-LA) is a new preexposure prophylaxis (PrEP) product. We reviewed existing evidence to determine the efficacy and safety of CAB-LA as PrEP to inform global guidelines. DESIGN: Systematic review and meta-analysis. METHODS: We systematically reviewed electronic databases and conference abstracts for citations on CAB-LA from January 2010 to September 2021. Outcomes included HIV infection, adverse events, drug resistance, pregnancy-related adverse events, and sexual behavior. We calculated pooled effect estimates using random-effects meta-analysis and summarized other results narratively. RESULTS: We identified 12 articles/abstracts representing four multisite randomized controlled trials. Study populations included cisgender men, cisgender women, and transgender women. The pooled relative risk of HIV acquisition comparing CAB-LA to oral PrEP within efficacy studies was 0.21 (95% confidence interval: 0.07-0.61), resulting in a 79% reduction in HIV risk. Rates of adverse events were similar across study groups. Of 19 HIV infections among those randomized to CAB-LA with results available, seven had integrase strand transfer inhibitor (INSTI) resistance. Data on pregnancy-related adverse events were sparse. No studies reported on sexual behavior. CONCLUSIONS: CAB-LA is highly efficacious for HIV prevention with few safety concerns. CAB-LA may lead to an increased risk of INSTI resistance among those who have acute HIV infection at initiation or become infected while taking CAB-LA. However, results are limited to controlled studies; more research is needed on real-world implementation. Additional data are needed on the safety of CAB-LA during pregnancy (for mothers and infants) and among populations not included in the trials.

Electrochemical degradation of indigo carmine, P-nitrosodimethylaniline and clothianidin on a fabricated Ti/SnO2-Sb/Co-ßPbO2 electrode: Roles of radicals, water matrices effects and performance.

In this study, the kinetic degradation of several typical organic pollutants was performed on a synthetic electrode (Ti/SnO2-Sb/Co-ßPbO2). The surface structure and the electrochemical properties of the prepared electrode were investigated, confirming the successful preparation of the electrode using an electrochemical deposition method. The outer layer (Co-ßPbO2) played an important role in reducing the resistance of the electrode and improving its degradation efficiency. The results showed that indigo carmine (IC), p-nitrosodimethylaniline (RNO), and clothianidin (CLO) were effectively degraded within 20 min of electrolysis. Their degradation in the electrochemical process followed the first-order kinetic model with the degradation rate constant of IC being higher than that of RNO and CLO. This was proved by the difference in the reactivity of the target pollutants toward oxidizing radicals (i.e., •OH, SO4•-, and Cl•). Their second-order rate constant towards radicals were in the range of 109 - 1010 M-1 s-1 with the highest value being that for IC: k·OH,IC = 15.1 × 109 M-1 s-1 and [Formula: see text]  = 7.4 × 109 M-1 s-1. The study calculated the contribution of some oxidizing species, including direct electron transfer (DET), •OH, SO4•-, and other reactive oxygen species (ROS). Solution pH, supporting electrolyte, and water matrix affected the degradation efficiency of pollutants and the contribution of the oxidizing species. Br- and I- ions enhanced the degradation rate of organic pollutants, while Fe2+, HCO3-, and humic acid (HA) reduced it. In addition, the toxicity, total organic carbon (TOC) removal, mineralization current efficiency (MCE), energy consumption, recyclability and stability of the prepared electrode were studied, suggesting that the prepared Ti/SnO2-Sb/Co-ßPbO2 is a good candidate for treating organic pollutants using the electrochemical oxidation process.

Computer-Aided Detection for Chest Radiography to Improve the Quality of Tuberculosis Diagnosis in Vietnam's District Health Facilities: An Implementation Study.

In Vietnam, chest radiography (CXR) is used to refer people for GeneXpert (Xpert) testing to diagnose tuberculosis (TB), demonstrating high yield for TB but a wide range of CXR abnormality rates. In a multi-center implementation study, computer-aided detection (CAD) was integrated into facility-based TB case finding to standardize CXR interpretation. CAD integration was guided by a programmatic framework developed for routine implementation. From April through December 2022, 24,945 CXRs from TB-vulnerable populations presenting to district health facilities were evaluated. Physicians interpreted all CXRs in parallel with CAD (qXR 3.0) software, for which the selected TB threshold score was ≥0.60. At three months, there was 47.3% concordance between physician and CAD TB-presumptive CXR results, 7.8% of individuals who received CXRs were referred for Xpert testing, and 858 people diagnosed with Xpert-confirmed TB per 100,000 CXRs. This increased at nine months to 76.1% concordant physician and CAD TB-presumptive CXRs, 9.6% referred for Xpert testing, and 2112 people with Xpert-confirmed TB per 100,000 CXRs. Our programmatic CAD-CXR framework effectively supported physicians in district facilities to improve the quality of referral for diagnostic testing and increase TB detection yield. Concordance between physician and CAD CXR results improved with training and was important to optimize Xpert testing.

Implementation Outcomes Assessment of a Digital Clinical Support Tool for Intrapartum Care in Rural Kenya: Observational Analysis.

BACKGROUND: iDeliver, a digital clinical support system for maternal and neonatal care, was developed to support quality of care improvements in Kenya. OBJECTIVE: Taking an implementation research approach, we evaluated the adoption and fidelity of iDeliver over time and assessed the feasibility of its use to provide routine Ministry of Health (MOH) reports. METHODS: We analyzed routinely collected data from iDeliver, which was implemented at the Transmara West Sub-County Hospital from December 2018 to September 2020. To evaluate its adoption, we assessed the proportion of actual facility deliveries that was recorded in iDeliver over time. We evaluated the fidelity of iDeliver use by studying the completeness of data entry by care providers during each stage of the labor and delivery workflow and whether the use reflected iDeliver's envisioned function. We also examined the data completeness of the maternal and neonatal indicators prioritized by the Kenya MOH. RESULTS: A total of 1164 deliveries were registered in iDeliver, capturing 45.31% (1164/2569) of the facility's deliveries over 22 months. This uptake of registration improved significantly over time by 6.7% (SE 2.1) on average in each quarter-year (P=.005), from 9.6% (15/157) in the fourth quarter of 2018 to 64% (235/367) in the third quarter of 2020. Across iDeliver's workflow, the overall completion rate of all variables improved significantly by 2.9% (SE 0.4) on average in each quarter-year (P<.001), from 22.25% (257/1155) in the fourth quarter of 2018 to 49.21% (8905/18,095) in the third quarter of 2020. Data completion was highest for the discharge-labor summary stage (16,796/23,280, 72.15%) and lowest for the labor signs stage (848/5820, 14.57%). The completion rate of the key MOH indicators also improved significantly by 4.6% (SE 0.5) on average in each quarter-year (P<.001), from 27.1% (69/255) in the fourth quarter of 2018 to 83.75% (3346/3995) in the third quarter of 2020. CONCLUSIONS: iDeliver's adoption and data completeness improved significantly over time. The assessment of iDeliver' use fidelity suggested that some features were more easily used because providers had time to enter data; however, there was low use during active childbirth, which is when providers are necessarily engaged with the woman and newborn. These insights on the adoption and fidelity of iDeliver use prompted the team to adapt the application to reflect the users' culture of use and further improve the implementation of iDeliver.

Transfer from spatial education to verbal reasoning and prediction of transfer from learning-related neural change.

Current debate surrounds the promise of neuroscience for education, including whether learning-related neural changes can predict learning transfer better than traditional performance-based learning assessments. Longstanding debate in philosophy and psychology concerns the proposition that spatial processes underlie seemingly nonspatial/verbal reasoning (mental model theory). If so, education that fosters spatial cognition might improve verbal reasoning. Here, in a quasi-experimental design in real-world STEM classrooms, a curriculum devised to foster spatial cognition yielded transfer to improved verbal reasoning. Further indicating a spatial basis for verbal transfer, students' spatial cognition gains predicted and mediated their reasoning improvement. Longitudinal fMRI detected learning-related changes in neural activity, connectivity, and representational similarity in spatial cognition-implicated regions. Neural changes predicted and mediated learning transfer. Ensemble modeling demonstrated better prediction of transfer from neural change than from traditional measures (tests and grades). Results support in-school "spatial education" and suggest that neural change can inform future development of transferable curricula.

Investigation of TNT red wastewater treatment technology using the combination of advanced oxidation processes.

Different types of advanced oxidation processes and their combinations such as O3/H2O2/UV, O3/Fenton/UV, O3/TiO2/UV, Fenton/H2O2/UV, Fenton/TiO2/UV, TiO2/H2O2/UV, TiO2/H2O2/O3/UV, TiO2/O3/Fenton/UV, TiO2/H2O2/Fenton/UV and O3/H2O2/Fenton/UV were studied for the treatment of undiluted red wastewater from Z113 Factory. The treatment efficiency was evaluated by analyzing chemical oxygen demand (COD) reduction, % degradation of α-TNT, 2,4-DNT, 2,6-DNT, 2,4-DNT-3-SO3Na and 2,4-DNT-5-SO3Na. Among studied processes Fenton/TiO2/O3/UV was the most effective technology to treat red wastewater. It allows to reduce >99% of COD, α-TNT, 2,4-DNT, 2,6-DNT, 2,4-DNT-3-SO3Na and 2,4-DNT-5-SO3Na after 30 h of treatment with optimum operating conditions: rotation speed of 600 rpm, pH of 4 and temperature of 40 °C. According to the chromatograms obtained by gas chromatograph/mass spectrometer (GC/MS), intermediates of the decomposition of pollutants in red wastewater were identified. GC/MS, HPLC, UV-vis and Bacterial Toxicity test were used to assess effluent quality changes before and after treatment. By economic analysis, the studied process had the potential to apply in practice to treat real wastewater at the Z113 Factory.