Disparities in Dolutegravir Uptake Affecting Females of Reproductive Age With HIV in Low- and Middle-Income Countries After Initial Concerns About Teratogenicity : An Observational Study.

BACKGROUND: The transition to dolutegravir-containing antiretroviral therapy (ART) in low- and middle-income countries (LMICs) was complicated by an initial safety signal in May 2018 suggesting that exposure to dolutegravir at conception was possibly associated with infant neural tube defects. On the basis of additional evidence, in July 2019, the World Health Organization recommended dolutegravir for all adults and adolescents living with HIV. OBJECTIVE: To describe dolutegravir uptake and disparities by sex and age group in LMICs. DESIGN: Observational cohort study. SETTING: 87 sites that began using dolutegravir in 11 LMICs in the Asia-Pacific; Caribbean, Central and South America network for HIV epidemiology (CCASAnet); and sub-Saharan African regions of the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. PATIENTS: 134 672 patients aged 16 years or older who received HIV care from January 2017 through March 2020. MEASUREMENTS: Sex, age group, and dolutegravir uptake (that is, newly initiating ART with dolutegravir or switching to dolutegravir from another regimen). RESULTS: Differences in dolutegravir uptake among females of reproductive age (16 to 49 years) emerged after the safety signal. By the end of follow-up, the cumulative incidence of dolutegravir uptake among females 16 to 49 years old was 29.4% (95% CI, 29.0% to 29.7%) compared with 57.7% (CI, 57.2% to 58.3%) among males 16 to 49 years old. This disparity was greater in countries that began implementing dolutegravir before the safety signal and initially had highly restrictive policies versus countries with a later rollout. Dolutegravir uptake was similar among females and males aged 50 years or older. LIMITATION: Follow-up was limited to 6 to 8 months after international guidelines recommended expanding access to dolutegravir. CONCLUSION: Substantial disparities in dolutegravir uptake affecting females of reproductive age through early 2020 are documented. Although this disparity was anticipated because of country-level restrictions on access, the results highlight its extent and initial persistence. PRIMARY FUNDING SOURCE: National Institutes of Health.

Screen technology exposure and infant cognitive development: A scoping review.

PROBLEM: There has been some concern that screen exposure is harmful to an infant's cognitive development, but the effects of screen technologies on cognition are not fully understood. A scoping review was conducted to determine what evidence exists about screen exposure and cognitive development in children ages birth to 24 months. ELIGIBILITY CRITERIA: Inclusion = 1) English language; 2) studies focusing on children under 24 months of age; 3) cognitive development; 4) screen exposure. Exclusion = 1) articles over 25 years old; 2) structure, function and physiology of the brain; 3) social development; 4) psychosocial development; 5) motor development; 6) abnormal development/mental health; 7) behavior; 8) content only, not screen exposure e.g., social media; 9) secondary sources. SAMPLE: Ten studies met the inclusion criteria. Articles included one retrospective chart review, six longitudinal studies, two cross-sectional studies, and one prospective study. RESULTS: Of the ten studies in this review, six reported correlations between screen exposure and cognitive delay, one study reported positive cognitive outcomes and three reported no significant positive or negative outcomes. CONCLUSIONS: From the evidence in this scoping review, no causal relationship has been found between screen exposure and infant cognitive harm. Some correlations between screen exposure and cognitive delay were reported. Some positive cognitive outcomes were also reported. IMPLICATIONS: Future research should focus on the context of screen viewing as opposed to dosage or exposure. More robust methodologies should be used to assess infant cognition and screen usage.

Clinical and programmatic outcomes of HIV-exposed infants enrolled in care at geographically diverse clinics, 1997-2021: A cohort study.

BACKGROUND: Although 1·3 million women with HIV give birth annually, care and outcomes for HIV-exposed infants remain incompletely understood. We analyzed programmatic and health indicators in a large, multidecade global dataset of linked mother-infant records from clinics and programs associated with the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. METHODS AND FINDINGS: HIV-exposed infants were eligible for this retrospective cohort analysis if enrolled at <18 months at 198 clinics in 10 countries across 5 IeDEA regions: East Africa (EA), Central Africa (CA), West Africa (WA), Southern Africa (SA), and the Caribbean, Central, and South America network (CCASAnet). We estimated cumulative incidences of DNA PCR testing, loss to follow-up (LTFU), HIV diagnosis, and death through 24 months of age using proportional subdistribution hazard models accounting for competing risks. Competing risks were transfer, care withdrawal, and confirmation of negative HIV status, along with LTFU and death, when not the outcome of interest. In CA and EA, we quantified associations between maternal/infant characteristics and each outcome. A total of 82,067 infants (47,300 EA, 10,699 CA, 6,503 WA, 15,770 SA, 1,795 CCASAnet) born from 1997 to 2021 were included. Maternal antiretroviral therapy (ART) use during pregnancy ranged from 65·6% (CCASAnet) to 89·5% (EA), with improvements in all regions over time. Twenty-four-month cumulative incidences varied widely across regions, ranging from 12·3% (95% confidence limit [CL], 11·2%,13·5%) in WA to 94·8% (95% CL, 94·6%,95·1%) in EA for DNA PCR testing; 56·2% (95% CL, 55·2%,57·1%) in EA to 98·5% (95% CL, 98·3%,98·7%) in WA for LTFU; 1·9% (95% CL, 1·6%,2·3%) in WA to 10·3% (95% CL, 9·7%,10·9%) in EA for HIV diagnosis; and 0·5% (95% CL, 0·2%,1·0%) in CCASAnet to 4·7% (95% CL, 4·4%,5·0%) in EA for death. Although infant retention did not improve, HIV diagnosis and death decreased over time, and in EA, the cumulative incidence of HIV diagnosis decreased substantially, declining to 2·9% (95% CL, 1·5%,5·4%) in 2020. Maternal ART was associated with decreased infant mortality (subdistribution hazard ratio [sdHR], 0·65; 95% CL, 0·47,0·91 in EA, and sdHR, 0·51; 95% CL, 0·36,0·74 in CA) and HIV diagnosis (sdHR, 0·40; 95% CL, 0·31,0·50 in EA, and sdHR, 0·41; 95% CL, 0·31,0·54 in CA). Study limitations include potential misclassification of outcomes in real-world service delivery data and possible nonrepresentativeness of IeDEA sites and the population of HIV-exposed infants they serve. CONCLUSIONS: While there was marked regional and temporal heterogeneity in clinical and programmatic outcomes, infant LTFU was high across all regions and time periods. Further efforts are needed to keep HIV-exposed infants in care to receive essential services to reduce HIV infection and mortality.

Early Pleistocene stratigraphy, sedimentary environments, and formation contexts at Dmanisi in the Georgian Caucasus.

The Early Pleistocene site of Dmanisi is now well known for its large number of fossils of early Homo erectus as well as associated artifacts and faunal remains, recovered mainly in pipe-related geologic features. Testing in the M5 unit 100 m to the west of the main excavations revealed a thick stratigraphy with no evidence of pipes or gullies, indicating that the geologic record at Dmanisi included spatially distinct sedimentary environments that needed further investigation. Here we report the results of a geoarchaeological program to collect data bearing on contexts and formation processes over a large area of the promontory. That work has defined over 40,000 m2 of in situ deposits with artifacts and faunas. Stratum A ashes bury the uppermost Mashavera Basalt, which we have dated to 1.8 Ma in the M5 block. The Stratum A deposits contain stratified occupations that accumulated quickly and offer good potential for recovery of in situ materials. Stratum B1 deposits above the A/B unconformity include all of the pipe and gully facies at Dmanisi, reflecting a brief but very intense phase of geomorphic change. Those deposits contain the majority of faunas and all of the hominin fossils. B1 slope facies offer excellent formation contexts away from the piped area, and all B1 deposits are sealed by Stratum B2 over the whole promontory. Strata B2 to B5 register a return to slope facies, with no further evidence of pipes or gullies. Those deposits also present excellent contexts for recovery of in situ occupations. Overall, Dmanisi's geologic history preserves an exceptional record of the activities and environmental context of occupations during the first colonization of Eurasia.

Retention in care and viral suppression in the PMTCT continuum at a large referral facility in western Kenya.

Medical records of pregnant and postpartum women living with HIV and their infants attending a large referral facility in Kenya from 2015 to 2019 were analyzed to identify characteristics associated with retention in care and viral suppression. Women were stratified based on the timing of HIV care enrollment: known HIV-positive (KHP; enrolled pre-pregnancy) and newly HIV-positive (NHP; enrolled during pregnancy). Associations with retention at 18 months postpartum and viral suppression (< 1000 copies/mL) were determined. Among 856 women (20% NHP), retention was 83% for KHPs and 53% for NHPs. Viral suppression was 88% for KHPs and 93% for NHPs, but 19% of women were missing viral load results. In a competing risk model, viral suppression increased by 18% for each additional year of age but was not associated with other factors. Overall, 1.9% of 698 infants with ≥ 1 HIV test result were HIV-positive. Tailored interventions are needed to promote retention and viral load testing, particularly for NHPs, in the PMTCT continuum.

Integrated Hydrogeological, Hydrochemical, and Isotopic Assessment of Seawater Intrusion into Coastal Aquifers in Al-Qatif Area, Eastern Saudi Arabia.

Seawater intrusion (SWI) is the main threat to fresh groundwater (GW) resources in coastal regions worldwide. Early identification and delineation of such threats can help decision-makers plan for suitable management measures to protect water resources for coastal communities. This study assesses seawater intrusion (SWI) and GW salinization of the shallow and deep coastal aquifers in the Al-Qatif area, in the eastern region of Saudi Arabia. Field hydrogeological and hydrochemical investigations coupled with laboratory-based hydrochemical and isotopic analyses (18O and 2H) were used in this integrated study. Hydrochemical facies diagrams, ionic ratio diagrams, and spatial distribution maps of GW physical and chemical parameters (EC, TDS, Cl-, Br-), and seawater fraction (fsw) were generated to depict the lateral extent of SWI. Hydrochemical facies diagrams were mainly used for GW salinization source identification. The results show that the shallow GW is of brackish and saline types with EC, TDS, Cl-, Br- concentration, and an increasing fsw trend seaward, indicating more influence of SWI on shallow GW wells located close to the shoreline. On the contrary, deep GW shows low fsw and EC, TDS, Cl-, and Br-, indicating less influence of SWI on GW chemistry. Moreover, the shallow GW is enriched in 18O and 2H isotopes compared with the deep GW, which reveals mixing with recent water. In conclusion, the reduction in GW abstraction in the central part of the study area raised the average GW level by three meters. Therefore, to protect the deep GW from SWI and salinity pollution, it is recommended to implement such management practices in the entire region. In addition, continuous monitoring of deep GW is recommended to provide decision-makers with sufficient data to plan for the protection of coastal freshwater resources.

Pediatric Occupational Therapists and Occupational Stress: A Scoping Review.

The purpose of this scoping review was to provide further insight into the stress and the stressors experienced by pediatric occupational therapists in the work environment. Using the Arksey and O'Malley framework, the search was conducted in eight databases, nine electronic journals, and eight gray literature sources to identify articles related to stress and stressors of pediatric occupational therapists. Review selection and characterization were performed by two independent reviewers. Twelve articles published from 2011 to 2020 were identified and varied in terms of purpose, population, and results although the articles all shared similar methodologies and outcome measures. Only 25% of the articles (3/12) addressed pediatric occupational therapy stress and stressors directly while the remaining addressed occupational stress, but with varying levels of attention to pediatric occupational therapists. Stress and stressors experienced by pediatric occupational therapists have been studied to a limited extent. Occupational stress is associated with increased burnout, decreased health, and decreased job satisfaction and performance. Several knowledge gaps have been identified, as well as priorities for future research into pediatric occupational therapists and occupational stress.

The value of a comprehensive primary outcome - results of a negative randomized control trial in the non-muscle invasive bladder cancer population.

INTRODUCTION American Urological Association (AUA) guidelines recommend intravesical chemotherapy to be given following transurethral resection of a bladder tumor. Prior studies have shown the benefit of mitomycin as well as gemcitabine. However, no study has compared the two agents. MATERIALS AND METHODS: The study was designed as an open label 1:1:1 randomized controlled trial, comparing intravesical mitomycin, gemcitabine and saline as a single intraoperative instillation immediately following transurethral resection of suspected bladder tumor. Primary endpoint was any grade ≥ 3 events according to NCI CTCAE Version 4.03, this captures any return trip to the operating room for recurrence of cancer or other event (benign bladder/urethra). Secondary endpoints were progression free survival for urothelial cell carcinoma and adverse events. RESULTS: A total of 82 patients were enrolled and randomized, unfortunately the trial was suspended early due to protocol deviations. In an intention to treat analysis, freedom from grade > 3 events at 2 years was 74.8% in the no treatment arm, 51.0% in the mitomycin arm, and 56.0% in the gemcitabine arm (p = 0.81). Freedom from cancer recurrence for all patients was 62.3%. In the no treatment arm, it was 78.8%, and 50.7% and 63.6% in the mitomycin arm and gemcitabine arm respectively. (p = 0.28). In a univariate analysis, the only patient variable significantly associated with the primary outcome was pathologic T stage (p < 0.002). CONCLUSION: This study provides an example of a novel, patient centered primary outcome with the goal of determining which treatment paradigms provide the greatest oncologic and clinic benefit.

5-Aryltetrazoles from Direct C-H Arylation with Aryl Bromides.

A mild, direct C-H arylation of 1-substituted tetrazoles to 5-aryltetrazoles is developed using a Pd/Cu cocatalytic system with readily available aryl bromides. The methodology avoids late-stage usage of azides and tolerates a wide range of functionalities.

2,2,2-Trifluoroethoxy Aromatic Heterocycles: Hydrolytically Stable Alternatives to Heteroaryl Chlorides.

Herein we describe the 2,2,2-trifluoroethoxy group as an alternative leaving group for hydrolytically unstable heteroaryl chlorides. This group provides improved shelf stability by years while maintaining reactivity toward nucleophiles in SNAr reactions. A highlighted trifluoroethyl ether was shown to be tolerant to aqueous Suzuki conditions, permitting sequential Suzuki/SNAr processes inaccessible to the heterocyclic chlorides. The strategic use of trifluoroethyl ethers enables storage of otherwise unstable heterocyclic chlorides and limits costly decomposition.

Synthesis of Pyridopyrazine-1,6-dione γ-Secretase Modulators via Selective 4-Methylimidazole N1-Buchwald Arylation.

An efficient synthesis of pyridopyrazine-1,6-dione γ-secretase modulators (GSMs) is described. Our route features the construction of a crystalline lactone intermediate via a selective palladium-catalyzed 4-methylimidazole N1-arylation using the Buchwald Xantphos Pd G4 precatalyst, which does not require a preactivation step. The weak inorganic base KHCO3 was employed to minimize saponification of a particularly sensitive lactone substrate. Additional key transformations include DABAL-Me3-mediated lactone aminolysis and a mild TBD/ethyl trifluoroacetate mediated lactam ring closure to afford a representative GSM in high yield.

Protocol for the Direct Conversion of Lactones to Lactams Mediated by 1,5,7-Triazabicyclo[4.4.0]dec-5-ene: Synthesis of Pyridopyrazine-1,6-diones.

We present an operationally simple lactone-to-lactam transformation utilizing diverse amine nucleophiles. The key steps of amidation, alcohol activation, and cyclization are all mediated by one reagent (TBD) in a single vessel at room temperature. We illustrate the convenience of this protocol by synthesizing a wide range of N-alkyl, N-aryl, and N-hetereoaryl pyridopyrazine-1,6-diones, an important class of medicinally significant lactams. Furthermore, the reported methodology can be applied to the synthesis of milligram to hundred gram quantities of pyridopyrazine-1,6-diones without the use of specialized equipment.

Luteinizing Hormone Causes Phosphorylation and Activation of the cGMP Phosphodiesterase PDE5 in Rat Ovarian Follicles, Contributing, Together with PDE1 Activity, to the Resumption of Meiosis.

The meiotic cell cycle of mammalian oocytes in preovulatory follicles is held in prophase arrest by diffusion of cGMP from the surrounding granulosa cells into the oocyte. Luteinizing hormone (LH) then releases meiotic arrest by lowering cGMP in the granulosa cells. The LH-induced reduction of cGMP is caused in part by a decrease in guanylyl cyclase activity, but the observation that the cGMP phosphodiesterase PDE5 is phosphorylated during LH signaling suggests that an increase in PDE5 activity could also contribute. To investigate this idea, we measured cGMP-hydrolytic activity in rat ovarian follicles. Basal activity was due primarily to PDE1A and PDE5, and LH increased PDE5 activity. The increase in PDE5 activity was accompanied by phosphorylation of PDE5 at serine 92, a protein kinase A/G consensus site. Both the phosphorylation and the increase in activity were promoted by elevating cAMP and opposed by inhibiting protein kinase A, supporting the hypothesis that LH activates PDE5 by stimulating its phosphorylation by protein kinase A. Inhibition of PDE5 activity partially suppressed LH-induced meiotic resumption as indicated by nuclear envelope breakdown, but inhibition of both PDE5 and PDE1 activities was needed to completely inhibit this response. These results show that activities of both PDE5 and PDE1 contribute to the LH-induced resumption of meiosis in rat oocytes, and that phosphorylation and activation of PDE5 is a regulatory mechanism.

Discovery of indole-derived pyridopyrazine-1,6-dione γ-secretase modulators that target presenilin.

Herein we describe design strategies that led to the discovery of novel pyridopyrazine-1,6-dione γ-secretase modulators (GSMs) incorporating an indole motif as a heterocyclic replacement for a naphthyl moiety that was present in the original lead 9. Tactics involving parallel medicinal chemistry and in situ monomer synthesis to prepare focused libraries are discussed. Optimized indole GSM 29 exhibited good alignment of in vitro potency and physicochemical properties, and moderate reduction of brain Aß42 was achieved in a rat efficacy model when dosed orally at 30mg/kg. Labeling experiments using a clickable, indole-derived GSM photoaffinity probe demonstrated that this series binds to the presenilin N-terminal fragment (PS1-NTF) of the γ-secretase complex.

Evaluating Diatomaceous Earth for Long-Term Use in Hydrogen Storage.

Efficient hydrogen storage is essential for its use as a sustainable energy carrier. Diatomaceous earth, a high-surface-area siliceous geomaterial, shows potential as a physisorption material for hydrogen storage. This study analyzes diatomaceous earth's long-term characteristics when subjected to high-pressure hydrogen injection. The diatomaceous earth was subjected to a hydrogen pressure of 1200 psi for a period of 80 days at room temperature. Neither notable morphological or mineralogical changes were observed. Nevertheless, there was a slight reduction in fine particles and a slight increase in larger particles. The Brunauer-Emmett-Teller (BET) surface area decreased slightly with a significant decrease in pore width. However, the hydrogen adsorption at 77 K temperature was increased significantly (45.5%) after the hydrogen storage test. Moreover, there was a delayed release of molecular water as the temperature increased. These changes suggest that a condensation reaction has occurred involving some of the opal-A silanol groups (Si-O-H), producing molecular water. Bonding through siloxane bridges (Si-O-Si) results in a significant decrease in pore width and increased hydrophobicity (i.e., the interaction between diatomaceous surface and H2 was increased), thereby enhancing hydrogen adsorption capacity. These findings indicate that diatomaceous earth holds promise as a material for hydrogen storage, with the potential for its hydrogen adsorption capacity to improve over time.

Hydrochemical Characterization, Geothermometry, and Origin of Ain Al-Harrah Hot Spring and Its Relationship to Al-Lith Geothermal System, Saudi Arabia.

The Al-Lith geothermal field in western Saudi Arabia is a characteristic medium-high enthalpy geothermal system, exhibiting features associated with tectonic activities linked to the Red Sea rifting. Ain Al-Harrah hot spring is located in the Al-Lith field, with discharge temperatures varying from 56 to 81 °C. The determination of water temperature and composition in a geothermal reservoir is critical to the design of utilization strategies, surface production facilities, and choice of materials. This research presents a comprehensive hydrochemical characterization of the Ain Al-Harrah hot spring and its relationship with the underlying geothermal system. This study was conducted in two main phases; first, the fieldwork involved the collection of water samples from the hot spring, measuring the temperature, pH, and electrical conductivity (EC) of the water. The second phase involved laboratory analyses of the collected samples, including major and trace element analyses, isotopic analysis, and geothermometry. The dominant hydrogeochemical processes in the region were determined by analyzing the hydrochemistry of the water samples. Thermal waters analyzed exhibited high concentrations of Na+ (410-463 mg/L), HCO3 - (64.48-90 mg/L), and Cl- (472.76-581.95 mg/L), intermediate levels of K+ (50.2-93.0 mg/L), and low levels of Mg2+ (1.27-2.04 mg/L). The total dissolved solids (TDS) concentration ranges between 1830 and 2055 mg/L. The hot spring is categorized as Na-HCO3 type facies that are moderately alkaline, with pH values ranging between 7.9 and 8.2. Analysis of trace element concentrations revealed that the hydrochemical processes were primarily governed by the abundance and solubility of trace elements in the rocks surrounding the hot spring, the pH, and the temperature of the hot spring water. The stable isotope data for δD (-12.36 to 15.21%) and δ18O (-2.84 to -3.38%) provided evidence that the thermal spring is of meteoric origin. Based on Na-K-Ca, K2/Mg, and quartz geothermometers, the temperature range of the reservoir was determined to be between 150 and 205 °C. The temperature range suggests a medium-to-high enthalpy geothermal system.

Suitability of treated wastewater for irrigation and its impact on groundwater resources in arid coastal regions: Insights for water resources sustainability.

Water scarcity threatens agriculture and food security in arid regions like Saudi Arabia. The nation produces significant quantities of municipal wastewater, which, with adequate treatment, could serve as an alternative water source for irrigation, thereby reducing reliance on fossil and non-renewable groundwater. This study assessed the appropriateness of using treated wastewater (TWW) for irrigation in a dry coastal agricultural region in Eastern Saudi Arabia and its impact on groundwater resources. Field investigations were conducted in Qatif to collect water samples and field measurements. A multi-criteria approach was applied to evaluate the TWW's suitability for irrigation, including complying with Saudi Standards, the Irrigation Water Quality Index (IWQI), the National Sanitation Foundation water quality index (NSFWQI), and the individual irrigation indices. In addition, the impact of TWW on groundwater was assessed through hydrogeological and isotope approaches. The results indicate that the use of TWW in the study area complied with the Saudi reuse guidelines except for nitrate, aluminum, and molybdenum. However, irrigation water quality indices classify TWW as having limitations that necessitate the use for salt-tolerant crops on permeable and well-drained soils. Stable isotopic analysis (δ2H, δ18O) revealed that long-term irrigation with TWW affected the shallow aquifer, while deep aquifers were minimally impacted due to the presence of aquitard layer. The application of TWW irrigation has successfully maintained groundwater sustainability in the study area, as evidenced by increased groundwater levels up to 2.3 m. Although TWW contributes to crop productivity, long term agricultural sustainability could be enhanced by improving effluent quality, regulating irrigation practices, implementing buffer zones, and monitoring shallow groundwater. An integrated approach that combines advanced wastewater treatment methods, community involvement, regulatory oversight, and targeted monitoring is recommended to be implemented.

Impact of Maternal Viral Suppression on Growth Patterns for HIV-Exposed Uninfected Infants in Kenya.

Background and Objective: Children born to mothers living with human immunodeficiency virus (HIV) are at risk for poor health outcomes but data characterizing these associations are limited. Our objective was to determine the impact of maternal viral suppression on growth patterns and malnutrition for infants who are HIV-exposed but uninfected (HEU). Methods: We conducted a retrospective cohort analysis of clinical data for infants who were HEU and their mothers (September 2015 - March 2019) in Kenya. Infants were stratified based on maternal viral suppression status (≥ or <1000 copies/mL); t-tests were used to compare groups. Growth indicators were evaluated with Chi-square, Fisher's exact, and area under the curve. Moderate-to-severe underweight status, stunting, and wasting were defined by weight-for-age (WFA), height-for-age (HFA), and weight-for-height (WFH), z-scores ≤2, and were used to define malnutrition. Multivariate logistic regression analyses were performed to evaluate potential associations with malnutrition indicators between WFH and HFA. Results: Among 674 infants who were HEU, 48.7% were male and 85.0% had mothers who were virally suppressed. The median age at first and last clinic visits was 1.5 and 16.4 months, respectively. WFA and HFA z-scores over time differed by sex, and WFA and HFA differed based on maternal viral suppression (P < 0.05). Male infants had higher adjusted odds for stunted status, and as children aged, they had slightly increased odds of becoming underweight or stunted. Maternal viral suppression and timing of maternal antiretroviral therapy initiation in relation to the prevention of vertical transmission (PVT) enrollment did not significantly affect malnutrition indicators. Conclusion and Global Health Implications: Maternal viral suppression status was not associated with increased odds of more severe malnutrition indicators in children who were HEU. However, overall growth patterns over time, measured by z-scores of growth indicators, did differ based on maternal viral suppression status, and to a lesser degree, by gender.

Understanding Women's Preferences for Prevention of Mother-to-Child HIV Transmission Services in Kenya.

Background and Objective: Understanding the preferences of women living with HIV (WLH) for the prevention of mother-to-child HIV transmission (PMTCT) services is important to ensure such services are person-centered. Methods: From April to December 2022, we surveyed pregnant and postpartum WLH enrolled at five health facilities in western Kenya to understand their preferences for PMTCT services. WLH were stratified based on the timing of HIV diagnosis: known HIV-positive (KHP; before antenatal clinic [ANC] enrollment), newly HIV-positive (NHP; on/after ANC enrollment). Multivariable logistic regression was used to determine associations between various service preferences and NHP (vs. KHP) status, controlling for age, facility, gravidity, retention status, and pregnancy status. Results: Among 250 participants (median age 31 years, 31% NHP, 69% KHP), 93% preferred integrated versus non-integrated HIV and maternal-child health (MCH) services; 37% preferred male partners attend at least one ANC appointment (vs. no attendance/no preference); 54% preferred support groups (vs. no groups; 96% preferred facility - over community-based groups); and, preferences for groups was lower among NHP (42%) versus KHP (60%). NHP had lower odds of preferring support groups versus KHP (aOR 0.45, 95% CI 0.25-0.82), but not the other services. Conclusion and Global Health Implications: Integrated services were highly preferred by WLH, supporting the current PMTCT service model in Kenya. Further research is needed to explore the implementation of facility-based support groups for WLH as well as the reasons underlying women's preferences.

Pharmacovigilance in Pregnancy Studies, Exposures and Outcomes Ascertainment, and Findings from Low- and Middle-Income Countries: A Scoping Review.

INTRODUCTION: Pharmacovigilance (PV), or the ongoing safety monitoring after a medication has been licensed, plays a crucial role in pregnancy, as clinical trials often exclude pregnant people. It is important to understand how pregnancy PV projects operate in low- and middle-income countries (LMICs), where there is a disproportionate lack of PV data yet a high burden of adverse pregnancy outcomes. We conducted a scoping review to assess how exposures and outcomes were measured in recently published pregnancy PV projects in LMICs. METHODS: We utilized a search string, secondary review, and team knowledge to review publications focusing on therapeutic or vaccine exposures among pregnant people in LMICs. We screened abstracts for relevance before conducting a full text review, and documented measurements of exposures and outcomes (categorized as maternal, birth, or neonatal/infant) among other factors, including study topic, setting, and design, comparator groups, and funding sources. RESULTS: We identified 31 PV publications spanning at least 24 LMICs, all focusing on therapeutics or vaccines for infectious diseases, including HIV (n = 17), tuberculosis (TB; n = 9), malaria (n = 7), pertussis, tetanus, and diphtheria (n = 1), and influenza (n = 3). As for outcomes, n = 15, n = 31, and n = 20 of the publications covered maternal, birth, and neonatal/infant outcomes, respectively. Among HIV-specific publications, the primary exposure-outcome relationship of focus was exposure to maternal antiretroviral therapy and adverse outcomes. For TB-specific publications, the main exposures of interest were second-line drug-resistant TB and isoniazid-based prevention therapeutics for pregnant people living with HIV. For malaria-specific publications, the primary exposure-outcome relationship of interest was antimalarial medication exposure during pregnancy and adverse outcomes. Among vaccine-focused publications, the exposure was assessed during a specific time during pregnancy, with an overall interest in vaccine safety and/or efficacy. The study settings were frequently from Africa, designs varied from cohort or cross-sectional studies to clinical trials, and funding sources were largely from high-income countries. CONCLUSION: The published pregnancy PV projects were largely centered in Africa and concerned with infectious diseases. This may reflect the disease burden in LMICs but also funding priorities from high-income countries. As the prevalence of non-communicable diseases increases in LMICs, PV projects will have to broaden their scope. Birth and neonatal/infant outcomes were most reported, with fewer reporting on maternal outcomes and none on longer-term child outcomes; additionally, heterogeneity existed in definitions and ascertainment of specific measures. Notably, almost all projects covered a single therapeutic exposure, missing an opportunity to leverage their projects to cover additional exposures, add scientific rigor, create uniformity across health services, and bolster existing health systems. For many publications, the timing of exposure, specifically by trimester, was crucial to maternal and neonatal safety. While currently published pregnancy PV literature offer insights into the PV landscape in LMICs, further work is needed to standardize definitions and measurements, integrate PV projects across health services, and establish longer-term monitoring.