Timing of Antiretroviral Therapy: Initiation and Birth Outcomes Among Pregnant Women With Human Immunodeficiency Virus in Tanzania

BACKGROUND: Combination antiretroviral therapy (cART) initiation during pregnancy reduces the risk of perinatal human immunodeficiency virus (HIV) transmission; however, studies have suggested that there may be unintended adverse consequences on birth outcomes for selected cART regimens. METHODS: We analyzed adverse birth outcomes among a prospective cohort of 1307 pregnant women with HIV in Dar es Salaam who initiated cART during the first or second trimester of a singleton pregnancy. Our primary analysis compared birth outcomes by gestational age at cART initiation among these women initiating cART in pregnancy. RESULTS: Among women who initiated cART in pregnancy, there was no relationship of gestational age at cART initiation with the risk of fetal death or stillbirth. However, women who initiated cART before 20 weeks of gestation compared with after 20 weeks had increased risk of preterm birth (risk ratio [RR], 1.30; 95% confidence interval [CI], 1.03-1.67) but decreased risk of small-for-gestational age birth (RR, 0.71; 95% CI, .55-.93). CONCLUSIONS: With increasing use of cART preconception and early in pregnancy, clinicians should be aware of the benefits and potential risks of cART regimens to optimize birth outcomes.

Perspectives from Young South African and Zimbabwean Women on Attributes of Four (Placebo) Vaginal Microbicide Delivery Forms.

INTRODUCTION: Incorporating end-user input into the design of new vaginal microbicides for women is key to optimizing their uptake, consistent use, and, ultimately, success in combatting the heterosexual HIV epidemic. METHODS: The Quatro Study assessed four placebo forms of vaginally inserted HIV-microbicides among young microbicide-naïve African women: on-demand film, insert and gel, and monthly ring. Participants randomly used each product for 1 month and provided product satisfaction ratings (1-5 scale), and opinions on product attributes and potential alternative designs. Qualitative data were collected through focus group discussions at study exit. Multivariable associations between attribute opinions and overall product rating were examined using Poisson regression models with robust standard errors to assess the attributes most influential to satisfaction. RESULTS: Overall opinions of products and their individual attributes were generally positive; all products were rated either 4 or a 5 by ≥ 50% of participants. Attributes related to ease of use and interference with normal activities were the most salient predictors of satisfaction. Preferences for duration of use tended toward relatively shorter use periods for the ring (i.e., 1-3 months vs. 12 months) and for coitally independent dosing for the on-demand products. CONCLUSIONS: How well a product fit in with participants' lifestyles was important to their overall satisfaction. For on-demand products, greater flexibility around timing of use was desired, to avoid coital dependency of the dosing.

How fluorescent labelling alters the solution behaviour of proteins.

A complete understanding of the role of molecular anisotropy in directing the self assembly of colloids and proteins remains a challenge for soft matter science and biophysics. For proteins in particular, the complexity of the surface at a molecular level poses a challenge for any theoretical and numerical description. A soft matter approach, based on patchy models, has been useful in describing protein phase behaviour. In this work we examine how chemical modification of the protein surface, by addition of a fluorophore, affects the physical properties of protein solutions. By using a carefully controlled experimental protein model (human gamma-D crystallin) and numerical simulations, we demonstrate that protein solution behaviour defined by anisotropic surface effects can be captured by a custom patchy particle model. In particular, the chemical modification is found to be equivalent to the addition of a large hydrophobic surface patch with a large attractive potential energy well, which produces a significant increase in the temperature at which liquid-liquid phase separation occurs, even for very low fractions of fluorescently labelled proteins. These results are therefore directly relevant to all applications based on the use of fluorescent labelling by chemical modification, which have become increasingly important in the understanding of biological processes and biophysical interactions.

Health Insurance Coverage, Clinical Outcomes, and Health-Related Quality of Life Among Youth Born to Women Living With HIV.

BACKGROUND: Although sustained access to health care is essential, little is known about the relationship between insurance coverage and health among people born to women living with HIV (WLHIV). SETTING: Prospective cohort studies of youth and young adults born to WLHIV from 2007 to 2019. METHODS: We used adjusted generalized estimating equation models to estimate mean differences in, and relative risks (RRs) of, health-related quality of life (HR-QoL) and HIV disease measures over time by insurance status. HR-QoL scales with limited variability were dichotomized. Modified Poisson models were used to estimate RRs. RESULTS: Six hundred sixty-nine Adolescent Master Protocol (AMP) youth [66% living with perinatally-acquired HIV (PHIV), 72% Black] and 939 AMP Up/AMP Up Lite young adults (89% PHIV, 68% Black) reported insurance. Most were publicly insured (87% youth, 67% young adults). Privately insured young adults living with PHIV had lower risk of antiretroviral therapy nonadherence [adjusted RR (aRR): 0.82, 95% CI: 0.70 to 0.97] than those with public insurance. There was a lower risk of suboptimal role functioning for young adults with private insurance (aRR: 0.58, 95% CI: 0.35 to 0.97) and those unaware of their coverage (aRR: 0.41, 95% CI: 0.21 to 0.78). Young adults with private insurance had higher health perception scores than those with public insurance (adjusted mean difference: 3.87, 95% CI: 0.37 to 7.38). For youth, we observed no differences in HR-QOL and HIV disease measures by insurance. CONCLUSION: These findings suggest meaningful differences in antiretroviral therapy adherence and some HR-QoL outcomes by health insurance coverage among young adults born to WLHIV.

Neonatal abstinence syndrome and mother's own milk at discharge.

OBJECTIVE: To describe factors impacting receipt of mother's own milk (MOM) at discharge among California infants diagnosed with neonatal abstinence syndrome (NAS). STUDY DESIGN: Cohort study of the California Perinatal Quality Care Collaborative's Maternal Substance Exposure Database for infants with NAS and gestational age ≥ 34 weeks from 2019 to 2020. RESULT: 245 infants with NAS were identified. Variables with an increased likelihood of being discharged on MOM included maternal medication assisted treatment (p = 0.001), use of maternal addiction services (p < 0.001), receiving donor human milk (p = 0.001), being treated in the well baby unit (p < 0.001), rooming-in (p < 0.001), and kangaroo care (p < 0.001). Among infants with NAS for whom MOM was recommended (n = 84), rooming-in was the only factor associated with being discharged on MOM (p = 0.002); receiving formula was the only inversely associated factor (p < 0.001). CONCLUSION: Results suggest supporting the mother-infant dyad and using non-pharmacologic treatment methods, such as rooming-in, increase receipt of MOM at discharge.

Non-specific effects of BCG and DTP vaccination on infant mortality: An analysis of birth cohorts in Ghana and Tanzania.

BACKGROUND: Vaccines may induce non-specific effects on survival and health outcomes, in addition to protection against targeted pathogens or disease. Observational evidence suggests that infant Baccillus Calmette-Guérin (BCG) vaccination may provide non-specific survival benefits, while diphtheria-tetanus-pertussis (DTP) vaccination may increase the risk of mortality. Non-specific vaccine effects have been hypothesized to modify the effect of neonatal vitamin A supplementation (NVAS) on mortality. METHODS: 22,955 newborns in Ghana and 31,999 newborns in Tanzania were enrolled in two parallel, randomized, double-blind, placebo-controlled trials of neonatal vitamin A supplementation from 2010 to 2014 and followed until 1-year of age. Cox proportional hazard models were used to estimate associations of BCG and DTP vaccination with infant survival. RESULTS: BCG vaccination was associated with a decreased risk of infant mortality after controlling for confounders in both countries (Ghana adjusted hazard ratio (aHR): 0.51, 95% CI: 0.38-0.68; Tanzania aHR: 0.08, 95% CI: 0.07-0.10). Receiving a DTP vaccination was associated with a decreased risk of death (Ghana aHR: 0.39, 95% CI: 0.26-0.59; Tanzania aHR: 0.19, 95% CI: 0.16-0.22). There was no evidence of interaction between BCG or DTP vaccination status and infant sex or NVAS. CONCLUSION: We demonstrated that BCG and DTP vaccination were associated with decreased risk of infant mortality in Ghana and Tanzania with no evidence of interaction between DTP or BCG vaccination, NVAS, and infant sex. Our study supports global recommendations on BCG and DTP vaccination and programmatic efforts to ensure all children have access to timely vaccination. CLINICAL TRIALS REGISTRATION: Ghana (Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12610000582055) and Tanzania (ANZCTR: ACTRN12610000636055).

Impact of hypothermia on implementation of CPAP for neonatal respiratory distress syndrome in a low-resource setting.

BACKGROUND: Neonatal hypothermia is widely associated with increased risks of morbidity and mortality, but remains a pervasive global problem. No studies have examined the impact of hypothermia on outcomes for preterm infants treated with CPAP for respiratory distress syndrome (RDS). METHODS: This retrospective analysis assessed the impact of hypothermia on outcomes of 65 neonates diagnosed with RDS and treated with either nasal oxygen (N = 17) or CPAP (N = 48) in a low-resource setting. A classification tree approach was used to develop a model predicting survival for subjects diagnosed with RDS. FINDINGS: Survival to discharge was accurately predicted based on three variables: mean temperature, treatment modality, and mean respiratory rate. None of the 23 neonates with a mean temperature during treatment below 35.8°C survived to discharge, regardless of treatment modality. Among neonates with a mean temperature exceeding 35.8°C, the survival rate was 100% for the 31 neonates treated with CPAP and 36.4% for the 11 neonates treated with nasal oxygen (p<0.001). For neonates treated with CPAP, outcomes were poor if more than 50% of measured temperatures indicated hypothermia (5.6% survival). In contrast, all 30 neonates treated with CPAP and with more than 50% of temperature measurements above 35.8°C survived to discharge, regardless of initial temperature. CONCLUSION: The results of our study suggest that successful implementation of CPAP to treat RDS in low-resource settings will require aggressive action to prevent persistent hypothermia. However, our results show that even babies who are initially cold can do well on CPAP with proper management of hypothermia.

Bilateral incisional gastropexies for treatment of intermittent gastroesophageal intussusception in a puppy.

Intermittent gastroesophageal intussusception was diagnosed in an 8-week-old puppy that had had recurrent regurgitation since it was acquired at 6 weeks old. Abnormalities were not detected on survey radiographs or positive-contrast esophagograms; the intussusception was evident only during endoscopic examination of the esophagus. Treatment consisted of bilateral incisional gastropexies attaching the gastric fundus and body to the left and right body walls, respectively. Clinical signs resolved completely after surgery. Gastroesophageal intussusception is rare in dogs, and most dogs with gastroesophageal intussuception have severe clinical abnormalities, including collapse, respiratory difficulties, and shock. However, for dogs with intermittent gastroesophageal intussusception, the only clinical sign may be recurrent regurgitation. Bilateral incisional gastropexies appear to be useful for preventing recurrence of gastroesophageal intussusception in dogs.

Realignment of the radius in canine antebrachial growth deformities treated with corrective osteotomy and bilateral (type II) external fixation.

OBJECTIVE: To identify factors affecting radial alignment after oblique corrective osteotomy stabilized with a type II external fixator and to evaluate the results of this treatment for antebrachial growth deformities. STUDY DESIGN: Retrospective study SAMPLE POPULATION: Twenty-eight dogs with unilateral antebrachial growth deformities treated with acute corrective osteotomy stabilized with a type II external fixator. METHODS: Medical records and preoperative and postoperative radiographs of the affected and contralateral limb were reviewed. Cause of deformity, age, weight, and gender were recorded. Radial length, varus/valgus angulation, and cranial/caudal angulation were measured from radiographs of the treated and contralateral limbs. Preoperative and postoperative angulation and length discrepancy were compared between affected and contralateral limbs. RESULTS: Correction of varus/valgus angle discrepancy was achieved by using acute corrective osteotomy stabilized with type II external skeletal fixation. No significant change was noted for correction of cranial/caudal angle discrepancy or length discrepancy between the affected and control limb. CLINICAL RELEVANCE: Varus/valgus angle deformities can be treated successfully with type III external fixation after oblique corrective osteotomy. Patients with significant length or cranial/caudal angle discrepancies or both that negatively impact function may require the use of hinged circular fixators or other dynamic techniques to achieve adequate correction.

Suppression of polyclonal, tumor cell and alloantigen-induced proliferation: identification of cyclooxygenase pathway dependent and independent mechanisms.

Polyclonal T cell activation, syngeneic tumor cell and alloantigen-induced proliferative responses were studied to determine if the regulation of these responses in normal and tumor-bearing NBR rats is mediated through products of the cyclooxygenase pathway and prostaglandin E2 (PGE2) in particular. Young rats and tumor-bearing rats have previously been shown to produce poor proliferative responses to PHA, Con A and syngeneic methylcholanthrene (MCA)-induced fibrosarcoma cells. The poor responses to PHA and Con A are mediated by PGE2 in unfractionated ( UNF ) and nylon wool adherent (ADH) cells. The same relationship was also established in the mixed leukocyte tumor cell (MLTC) response to MCA tumor cells although it appears to be of only minor significance as the enhancement following indomethacin (IND) treatment is still a relatively poor response. Indomethacin generally had no effect on the proliferative responses of tumor-bearing animals indicating that the suppression was not mediated through the cyclooxygenase pathway. We have also extended a previous observation in which UNF cells were found to be unresponsive to alloantigen stimulation. This suppression does not appear to be mediated through cyclooxygenase products as IND treatment does not enhance the UNF response although it does enhance the ADH response. These data indicate that a complex network of cyclooxygenase dependent and independent regulation exists in normal and tumor-bearing NBR rats.