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HIV‐exposed and HIV‐uninfected (HEU) infants may be at increased risk of poor health and growth outcomes. We characterized infant growth trajectories in a cohort of HEU infants to identify factors associated with healthy growth. HIV‐positive women participating in prevention of mother‐to‐child HIV transmission programmes in Kigali, Rwanda, were followed until their infants were 2 years old. Infant anthropometrics were regularly collected. Latent class analysis was used to categorize infant growth trajectories. Multiple logistic regression was used to estimate the odds of infants belonging to each growth trajectory class. On average, this population of HEU infants had moderate linear growth faltering, but only modest faltering in weight, resulting in mean weight‐for‐length z‐score (WLZ) above the World Health Organization (WHO) median. Mean WLZ was 0.53, and mean length‐for‐age z‐score (LAZ) was −1.14 over the first 2 years of life. We identified four unique WLZ trajectories and seven trajectories in LAZ. Low neonatal weight‐for‐age and a high rate of illness increased the likelihood that infants were in the lightest WLZ class. Shorter mothers were more likely to have infants with linear growth faltering. Female infants who were older at the end of exclusive breastfeeding were more likely to be in the second tallest LAZ class. In conclusion, the current WHO recommendations of Option B+ and extended breastfeeding may induce higher WLZ and lower LAZ early in infancy. However, there is considerable heterogeneity in growth patterns that is obscured by simply analysing average growth trends, necessitating the analysis of growth in subpopulations. [ABSTRACT FROM AUTHOR]

SeqSero, launched in 2015, is a software tool for Salmonella serotype determination from whole-genome sequencing (WGS) data. Despite its routine use in public health and food safety laboratories in the United States and other countries, the original SeqSero pipeline is relatively slow (minutes per genome using sequencing reads), is not optimized for draft genome assemblies, and may assign multiple serotypes for a strain. Here, we present SeqSero2 (github.com/denglab/Seq- Sero2; denglab.info/SeqSero2), an algorithmic transformation and functional update of the original SeqSero. Major improvements include (i) additional sequence markers for identification of Salmonella species and subspecies and certain serotypes, (ii) a k-mer based algorithm for rapid serotype prediction from raw reads (seconds per genome) and improved serotype prediction from assemblies, and (iii) a targeted assembly approach for specific retrieval of serotype determinants from WGS for serotype prediction, new allele discovery, and prediction troubleshooting. Evaluated using 5,794 genomes representing 364 common U.S. serotypes, including 2,280 human isolates of 117 serotypes from the National Antimicrobial Resistance Monitoring System, SeqSero2 is up to 50 times faster than the original SeqSero while maintaining equivalent accuracy for raw reads and substantially improving accuracy for assemblies. SeqSero2 further suggested that 3% of the tested genomes contained reads from multiple serotypes, indicating a use for contamination detection. In addition to short reads, SeqSero2 demonstrated potential for accurate and rapid serotype prediction directly from long nanopore reads despite base call errors. Testing of 40 nanopore-sequenced genomes of 17 serotypes yielded a single H antigen misidentification. IMPORTANCE Serotyping is the basis of public health surveillance of Salmonella. It remains a first-line subtyping method even as surveillance continues to be transformed by whole-genome sequencing. SeqSero allows the integration of Salmonella serotyping into a whole-genome-sequencing-based laboratory workflow while maintaining continuity with the classic serotyping scheme. SeqSero2, informed by extensive testing and application of SeqSero in the United States and other countries, incorporates important improvements and updates that further strengthen its application in routine and large-scale surveillance of Salmonella by whole-genome sequencing. [ABSTRACT FROM AUTHOR]

Abstract: The design and profile of a series of adamantyl-containing long acting β2-adrenoreceptor agonists are described. An optimal pharmacokinetic profile of low oral bioavailability was combined with a strong pharmacology profile when assessed using a guinea pig trachea tissue model. A focus was then placed on developing a robust synthetic route to ensure rapid delivery of material for clinical trials. [Copyright &y& Elsevier]

Abstract: The design and profile of a series of indole containing long acting β2-adrenoceptor agonists is described. Evaluation of these analogues using an in vitro guinea pig trachea tissue model demonstrates that analogues within this series have salmeterol-like duration of action with potential for long duration of action in humans. [Copyright &y& Elsevier]

Abstract: The design and profile of a series of saligenin containing long acting β2-adrenoreceptor agonists is described. Evaluation of these analogues using a guinea-pig tissue model demonstrates that analogues within this series have significantly longer durations of action than salmeterol and have the potential for a once daily profile in human. [Copyright &y& Elsevier]

Mentoring is important to the development and enhancement of the medical profession and to organizational performance. The challenge is to implement a mentoring program within your organization. Leaders can use this article to assist in training both mentors and mentees. This article reminds people that the mindsets and skills necessary to become good mentor and mentee improve with practice, thus engage, learn, and improve. The time invested in mentoring relationships enhances patient care, creates positive work environment within organizations, improves individual and organizational performance, and creates a brighter future for the medical profession., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Ceftolozane/tazobactam (C/T), a novel antipseudomonal cephalosporin plus β-lactamase inhibitor, is used in multidrug-resistant Gram-negative infections. Continuous infusion (CI) of C/T is an attractive concept for aiding in transitions of care and maximising the pharmacodynamics of cephalosporins (T >MIC ). This was a single-centre retrospective analysis of CI C/T use in adults from December 2016 to June 2019 in the inpatient or outpatient setting. Safety and effectiveness were assessed. When therapeutic drug monitoring (TDM) was performed, area under the concentration-time curve (AUC) and target attainment were calculated. Summary statistics were used to describe the data. CI C/T was used in seven unique regimens over the 31-month evaluation period. Patient age ranged from 23-70 years and the indication was primarily for treatment of deep-seated infections caused by multidrug-resistant Pseudomonas aeruginosa. Four regimens (57%) were used for outpatient transitions of care. The typical dose was 6 g every 24 h, although a renally adjusted dose was used in two instances (29%). TDM was performed in four uses (57%) and target attainment was confirmed in each. Ceftolozane AUC ranged from 365.7-818.2 μg•(h/mL). All patients had positive outcomes with no significant adverse events. One patient developed acute gout flares. One patient had recurrent infection with C/T-resistant P. aeruginosa after ~3 months of reduced dose for suppression. CI C/T was successfully utilised for deep-seated infections in inpatient and outpatient settings. TDM confirmed that CI C/T achieved pharmacodynamic targets for the entire dosing interval, suggesting an effective alternative dosing regimen applicable across the continuum of care., (Copyright © 2020 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Background: HIV-uninfected infants of HIV-positive women may experience worse growth and health outcomes than infants of HIV-negative women, but this has not been thoroughly investigated under the World Health Organization's most recent recommendations to reduce vertical transmission., Objective: To determine whether HIV-exposed and -uninfected (HEU) infants whose mothers received Option B+ have higher odds of experiencing suboptimal growth trajectories than HIV-unexposed, -uninfected infants, and if this relationship is affected by food insecurity., Design: Repeated anthropometric measures were taken on 238 infants (HEU = 86) at 1 week and 1, 3, 6, 9, and 12 months after delivery in Gulu, Uganda. Latent class growth mixture modeling was used to develop trajectories for length-for-age z-scores, weight-for-length z-scores, mid-upper arm circumference, sum of skinfolds, and arm fat area. Multinomial logistic models were also built to predict odds of trajectory class membership, controlling for socioeconomic factors., Results: HEU infants had greater odds of being in the shortest 2 length-for-age z-scores trajectory classes [odds ratio (OR) = 3.80 (1.22-11.82), OR = 8.72 (1.80-42.09)] and higher odds of being in smallest sum of skinfolds trajectory class [OR = 3.85 (1.39-10.59)] vs. unexposed infants. Among HEU infants, increasing food insecurity was associated with lower odds of being in the lowest sum of skinfolds class [OR = 0.86 (0.76-0.98)]., Conclusions: There continues to be differences in growth patterns by HIV-exposure under the new set of World Health Organization guidelines for the prevention of mother-to-child transmission of HIV and the feeding of HEU infants in low-resource settings that are not readily identified through traditional mixed-effects modeling. Food insecurity was not associated with class membership, but differentially affected adiposity by HIV-exposure status.

Background: The Partnership for HIV-Free Survival (PHFS) in Uganda used a quality improvement (QI) approach to integrate the prevention of mother-to-child transmission (MTCT) of HIV, maternal and child health, and nutrition services, with the goal of increasing the retention of mother-baby pairs in care and decreasing vertical transmission of HIV., Methods: This evaluation of PHFS used a retrospective longitudinal design to assess the program's association with 4 outcomes. Data were extracted from patient records from 2011 (before the program) to 2018 (after the program) at 18 demonstration, 18 scale-up, and 24 comparison facilities. Difference-in-differences analyses were conducted with significance set at P < 0.15 during and P > 0.15 or a significant continued improvement after PHFS., Results: PHFS was associated with an increase in exclusive breastfeeding (EBF) (P = 0.08), 12-month retention in care (P < 0.001), and completeness of child 18-month HIV test results (P = 0.13) at demonstration facilities during program implementation. MTCT at 18 months decreased, but did not differ between groups. Increases in EBF (P = 0.67) and retention in care (P = 0.16) were sustained, and data completeness (P = 0.10) continued to increase at demonstration facilities after the program. PHFS was associated with an increase in EBF (P < 0.001) at scale-up facilities, but there was no difference between groups for retention in care, MTCT, or data completeness. Gains in EBF were lost (P = 0.08) and retention in care declined (P < 0.001) at scale-up facilities after the program., Conclusion: PHFS' quality improvement approach increased EBF, retention in care, and data completeness in demonstration facilities during the program and these benefits were sustained.

Despite the high incidence of diabetic ketoacidosis (DKA) there is no consensus on the most appropriate way to manage insulin therapy. This study was conducted to evaluate the effect of an insulin bolus on the resolution of DKA. A retrospective chart review of patients admitted between 1 September 2014 and 30 June 2016 with a diagnosis of DKA was conducted. Patients were assigned to the bolus or no bolus group based on provider preference. All patients were initiated on a 0.1 unit/kilogram (kg)/hour (h) intravenous (IV) regular insulin infusion, and patients in the bolus group were treated with a 0.1 unit/kg IV regular insulin bolus. Of the 145 admissions evaluated, 58 received a bolus and 87 did not. There was no difference in baseline demographics, except baseline blood glucose was higher in the bolus group (653 vs. 591 milligrams (mg)/deciliter (dL), p = 0.04). The time to resolution of DKA from emergency department admission did not differ between the bolus and no bolus group (15 vs. 15.9 h; p = 0.24). There was no difference in total insulin received (1.3 vs. 1.1 units/kg, p = 0.18), incidence of hypoglycemia (2 vs. 7%, p = 0.64), hypokalemia (16 vs. 29%, p = 0.65), or length of hospital stay (3.2 vs. 2.7 days, p = 0.27). The insulin bolus administration was not associated with reduced time to resolution of DKA.

This article examines the role and impact of EMTALA on the ethical delivery of hospital-based emergency services, primarily through close inspection of three of the core EMTALA mandates: the medical screening examination, the duty to accept patients in transfer from less capable facilities, and the requirement that the hospital provide on-call physician services to the emergency department to help stabilize patients with emergencies or help accept patients in transfer. Hospital and physician responses to these mandates, such as triaging/screening patients away from the emergency department, avoiding the application of EMTALA, refusing to accept inpatients with emergencies in transfer, and devising ways to avoid on-call duties, are analyzed in some detail.

The process change described is an ongoing project in the HICN. Through this process we found that developmentally sensitive care can be accomplished as early as the time of birth by minimizing trauma to ELBW infants, keeping them nested with minimal handling. This also supports the goal for this population of minimizing cold stress and its effects. Gentle ventilation can be achieved in the delivery room by understanding physiology and the effects of ventilation on the ELBW lung tissue.

Nonequilibrium concentration type curves are numerically developed and sensitivity analyses are performed to examine the relationships between effluent concentrations in partially penetrating monitoring/extraction wells, the vertical plume shape, and the mass transfer characteristics of the aquifer. The governing two-dimensional, axisymmetric nonequilibrium solute transport equation is solved in three stages using an operator-splitting approach. In the first two stages, the advection and dispersion terms are solved with the Eulerian-Lagrangian method, based on the backward method of characteristics for advection and the standard implicit Galerkin finite element method for dispersion. In the third step, the first-order, immobile-mobile domain mass transfer term is computed analytically for both two-site and lognormally distributed, multirate models. Effluent concentration variations with time and contour plots of the pore water concentration distribution in the aquifer are compared for a wide range of field- and laboratory-measured mass transfer rates, various plume shapes, and relevant physical/chemical parameter values, including pumping rate, vertical anisotropy ratio, retardation factor, and porosity. The simulation results show that rate-limited mass transfer can have a significant impact on sample and aquifer pore water concentrations during three-dimensional transport to a partially penetrating well. An alternative dimensionless form of the nonequilibrium solute transport equation is derived to illustrate the key parameter groupings that quantify rate-limited sorption effects and show the relative importance of individual parameters. A hypothetical field application example demonstrates the fitting of dimensional type curves to discrete-interval sampling data in order to evaluate the mass transfer characteristics of an aquifer and shows how type curve superposition can be used to model complex plume shapes.