Health Profile of Afghan Pediatric Refugees Resettled to Philadelphia in 2021-2022.

To elucidate the physical and psychosocial health needs of newly arrived Afghan children, we conducted a retrospective chart review of patients 0 to 19 years re-settled to Philadelphia with ≥1 outpatient visit during August 2021 to August 2022. Findings on 121 patients include dental caries (74%), elevated lead (32%), eosinophilia (29%), malnutrition (25%), schistosomiasis (6%), strongyloidiasis (8%), latent tuberculosis (7%), and two cases of cutaneous leishmaniasis. Mental health symptoms include poor sleep in 16%, low energy in 10%, and behavioral concerns in 13%. Families with low English proficiency were more often met with delayed medical care (26.7% vs 11.5% P = .12). Parents with less than a high school education were more likely to experience delayed care (38.5% vs 9.1%; P = .001). We conclude that recently arrived Afghan children have unique physical and mental health needs that need to be addressed.

Impact of Group Prenatal Care on Contraceptive Use at Twelve Weeks Postpartum.

OBJECTIVES: To compare the prevalence of highly effective contraceptive use by 12 weeks postpartum among participants of Centering Pregnancy®, a model of group prenatal care (GPC), and traditional prenatal care (TPC), and to investigate differences in contraceptive method choice by type of prenatal care. METHODS: We performed a retrospective review of all eligible patients who participated in GPC (n = 143) and a random sample of patients participating in TPC (n = 290) who followed up at our institution within 12 weeks of delivery. Our primary outcome was the proportion of participants using a highly effective contraceptive method within 12 weeks postpartum. Contraceptives were classified in tiers (Tier 1, long-acting reversible and permanent contraception; Tier 2, oral contraceptive pills, transdermal patch, vaginal ring, or injection; Tier 3, barrier and fertility awareness methods, withdrawal, spermicide; and no method). Tier 1 and Tier 2 methods were considered highly effective. RESULTS: The prevalence of highly effective contraceptive use by 12 weeks postpartum was 63.6% (91 of 143) and 63.1% (183 of 290) among participants in GPC and TPC, respectively (p = 0.99). We found no difference in Tier 1 versus other method use (adjusted odds ratio (aOR) 1.05, 95% CI 0.95-1.15, p = 0.34) or Tier 2 versus other method use between groups (aOR 0.98, 95% CI 0.89-1.08, p = 0.69), in a multivariable model controlling for demographic and clinical factors. CONCLUSIONS FOR PRACTICE: The prevalence of highly effective contraceptive use at 12 weeks postpartum was not different between GPC and TPC participants in this study. GPC was not associated with increased use of Tier 1 or Tier 2 contraceptive methods.

Pregnancies lost and found: a quality improvement project to increase follow-up for early pregnancy complications.

Pregnancy of unknown location (PUL) and medically managed ectopic pregnancy (EP) require longitudinal surveillance to avoid adverse outcomes; however, patients with PUL/EP in the United States (U.S.) are often unable to adhere to recommended treatment plans. This quality improvement (QI) project sought to improve PUL/EP follow-up using a three-pronged intervention: standardised recall procedures, direct patient-provider communication and electronic medical record (EMR) documentation templates and tracking. We compared patients with PUL/EP managed before and after the QI project. Our primary outcome was completion of PUL/EP clinical care. Demographics, initial diagnoses and adverse outcomes were similar between 87 pre-QI and 81 post-QI patients. Significantly more patients completed PUL/EP clinical care post-QI (80.2 vs. 65.5% p = .03). Post-QI, more providers contacted patients at standard intervals (100 vs. 57.1%, p < .0001), and EMR documentation was improved (100 vs. 69.0%, p < .001). Simple changes to PUL/EP management improved completion of clinical care and compliance with standardised recall and documentation.IMPACT STATEMENTWhat is already known on this subject? Pregnancy of unknown location (PUL) and medically managed ectopic pregnancy (EP) require longitudinal surveillance to avoid adverse outcomes; however, patients with PUL/EP in the United States (U.S.) are often unable to adhere to recommended treatment plans.What do the results of this study add? By standardising recall procedures, ensuring direct communication between patients and providers using a dedicated cell phone, and integrating case tracking and documentation into the electronic medical record (EMR), this quality improvement (QI) project improved completion of clinical follow-up for patients with PUL/EP (overall, 80.2 vs. 65.5% pre-QI, p=.03) and for the subgroup with medically managed EP not requiring surgery (76.5 vs. 36.4% pre-QI, p= .05). We also improved providers' compliance with standardised recall procedures and EMR documentation post-QI (p < .0001). There was no difference in the number of attempts to contact patients, or in the number of surveillance blood draws actually performed. Post-QI, survey responses indicated that patients were easily able to contact their provider and understood the importance of follow-up processes.What are the implications of these findings for clinical practice and/or research? Early pregnancy care providers can utilise simple strategies to improve follow-up of patients with PUL and medically managed EP, without increasing burdens to their health systems. Patients' favourable experiences with this management support its implementation.

Timeliness of Immunizations in CenteringParenting.

OBJECTIVE: To evaluate the timeliness of immunizations of children in CenteringParenting (Centering), a group well-child model, compared to children in individual well-child care. METHODS: We conducted a retrospective cohort study of infants born October 1, 2014 to February 18, 2019 with a 2-month and subsequent well-child visit, both Centering or individual, at an academic pediatric practice in an urban, low-income community. In Centering, same age infants/mothers and a provider meet for 10, 2-hour group visits, and facilitated discussions. Providers are trained in group facilitation and participate in both Centering and individual visits. Primary outcome was timeliness of immunizations at 7, 13, 19, and 25 months. Analyses were by intention to treat. RESULTS: The study population included 1735 children (Centering n = 342, individual n = 1393). By 25 months, 62% of children in Centering were up to date with all recommended immunizations compared to 44.2% of children in individual care, a 17.8% higher rate (P < .001). By 25 months, children in Centering made 3 additional well-child visits (9.2 vs 6.2, P < .001). Mediation analysis showed 82% of the effect on up to date status was due to increased attendance to well-child visits (P < .001); the remaining 18% was due to a Centering effect beyond the visit increase. CONCLUSIONS: Our study showed a strong association of CenteringParenting with timeliness of immunizations and adherence to well-child visits compared to individual visits in a low income community. These findings warrant further exploration of the impact of Centering in reducing health disparities in communities at risk.

Outpatient antibiotic prescribing patterns in pediatric academic and community practices.

Little is known about antibiotic prescribing differences between academic and community outpatient settings. This retrospective, cross-sectional chart review compares compliance with Infectious Diseases Society of America and American Academy of Pediatrics prescribing guidelines for otitis media, sinusitis, and pharyngitis in academic and affiliated community practices. The study results for correct antibiotic prescribing rate in the academic setting (67%) compared with the community setting (21%) demonstrate the urgent need for stewardship in community outpatient clinics.

Impact of a Baby-Friendly-Aligned Pacifier Policy on Pacifier Use at 1 Month of Age.

OBJECTIVE: Pacifier use decreases the risk of sudden infant death syndrome, but its impact on breastfeeding remains controversial. We evaluated the impact of a pacifier policy aligned with the World Health Organization and United Nations Children's Fund Baby-Friendly Hospital Initiative on subsequent pacifier use and breastfeeding at 1 month of age. METHODS: We conducted a prospective 2-stage (pre- and post-implementation) cohort study of newborns at a birth hospital before and after implementation of a Baby-Friendly-aligned pacifier policy. Consecutive mothers of newborns admitted to the nursery participated in a telephone survey when the infants were 1 month of age. RESULTS: In total, 342 mothers participated (190 before and 152 after implementation of the policy). Pacifier adoption was delayed in the post-implementation group, but pacifier use by 1 month of age was comparable (78.9% pre-implementation vs 77.6% post-implementation; P = .793). In the pre-implementation group, female and male infants used pacifiers at comparable rates; however, in the post-implementation group, females were significantly less likely to use a pacifier compared to males after controlling for insurance, race, parity, and delivery mode (adjusted odds ratio, 0.35; 95% confidence interval, 0.15-0.83; P = .02). In the post-implementation group, exclusive breastfeeding rates at discharge increased significantly (from 40% to 51.3%; P = .04), but rates were not different at 1 month (23.7% pre-implementation vs 24.3% post-implementation; P = .89). CONCLUSION: A Baby-Friendly-aligned pacifier policy delayed pacifier adoption but did not impact overall pacifier use or breastfeeding rates at 1 month of age. The finding of lower pacifier use rates among female infants post-intervention requires verification in other populations before evaluating public heath relevance.

Qualitative Evaluation of Individual and Group Well-Child Care.

OBJECTIVE: Individual well care (IWC) is the standard delivery model for well-child care in the United States. Alternative models, such as group well care (GWC), may create opportunities to enhance care for babies. The purpose of this study was to evaluate parents' perceptions of social/wellness benefits and system challenges of IWC and GWC. METHODS: Since 2014, we have provided both IWC and GWC at an urban academic practice serving a low-income minority community. We conducted a mixed method study involving surveys and 18 focus groups (11 IWC groups, n = 32 parents; 7 GWC groups, n = 33 parents). Parents completed surveys before convening focus group discussions. Survey results were analyzed using independent t tests; focus groups were digitally recorded, transcribed, and analyzed to identify themes. RESULTS: Both groups had similar demographics: parents were mostly female (91%) and black (>80%); about half had incomes < $20,000. Parents' mean age was 27 years; children's mean age was 11 months. There were no significant differences in overall scores measuring trust in physicians, parent empowerment, or stress. IWC parents' themes highlighted ways to improve care delivery, while GWC parents highlighted both satisfaction with care delivery and social/wellness benefits. GWC parents strongly endorsed this model and reported unique benefits, such as garnering social support and learning from other parents. CONCLUSIONS: Parents receiving both models of care identified ways to improve primary care delivery. Given some of the benefits reported by GWC parents, this model may provide the means to enhance resilience in parents and children in low-income communities.

Developmental Test of Visual-Motor Integration (VMI): An Effective Outcome Measure for Handwriting Interventions for Kindergarten, First-Grade, and Second-Grade Students?

We determined whether a widely used assessment of visual-motor skills, the Beery-Buktenica Developmental Test of Visual-Motor Integration (VMI), is appropriate for use as an outcome measure for handwriting interventions. A two-group pretest-posttest design was used with 207 kindergarten, first-grade, and second-grade students. Two well-established handwriting measures and the VMI were administered pre- and postintervention. The intervention group participated in the Size Matters Handwriting Program for 40 sessions, and the control group received standard instruction. Paired and independent-samples t tests were used to analyze group differences. The intervention group demonstrated significant improvements on the handwriting measures, with change scores having mostly large effect sizes. We found no significant difference in change scores on the VMI, t(202)=1.19, p=.23. Results of this study suggest that the VMI may not detect changes in handwriting related to occupational therapy intervention.

Low-density lipoprotein receptor overexpression enhances the rate of brain-to-blood Aß clearance in a mouse model of ß-amyloidosis.

The apolipoprotein E (APOE)-ε4 allele is the strongest genetic risk factor for late-onset, sporadic Alzheimer's disease, likely increasing risk by altering amyloid-ß (Aß) accumulation. We recently demonstrated that the low-density lipoprotein receptor (LDLR) is a major apoE receptor in the brain that strongly regulates amyloid plaque deposition. In the current study, we sought to understand the mechanism by which LDLR regulates Aß accumulation by altering Aß clearance from brain interstitial fluid. We hypothesized that increasing LDLR levels enhances blood-brain barrier-mediated Aß clearance, thus leading to reduced Aß accumulation. Using the brain Aß efflux index method, we found that blood-brain barrier-mediated clearance of exogenously administered Aß is enhanced with LDLR overexpression. We next developed a method to directly assess the elimination of centrally derived, endogenous Aß into the plasma of mice using an anti-Aß antibody that prevents degradation of plasma Aß, allowing its rate of appearance from the brain to be measured. Using this plasma Aß accumulation technique, we found that LDLR overexpression enhances brain-to-blood Aß transport. Together, our results suggest a unique mechanism by which LDLR regulates brain-to-blood Aß clearance, which may serve as a useful therapeutic avenue in targeting Aß clearance from the brain.

Quantitative proteomic analysis of distinct mammalian Mediator complexes using normalized spectral abundance factors.

Components of multiprotein complexes are routinely determined by using proteomic approaches. However, this information lacks functional content except when new complex members are identified. To analyze quantitatively the abundance of proteins in human Mediator we used normalized spectral abundance factors generated from shotgun proteomics data sets. With this approach we define a common core of mammalian Mediator subunits shared by alternative forms that variably associate with the kinase module and RNA polymerase (pol) II. Although each version of affinity-purified Mediator contained some kinase module and RNA pol II, Mediator purified through F-Med26 contained the most RNA pol II and the least kinase module as demonstrated by the normalized spectral abundance factor approach. The distinct forms of Mediator were functionally characterized by using a transcriptional activity assay, where F-Med26 Mediator/RNA pol II was the most active. This method of protein complex visualization has important implications for the analysis of multiprotein complexes and assembly of protein interaction networks.

Principles and applications of multidimensional protein identification technology.

Multidimensional chromatography coupled to tandem mass spectrometry is an emerging technique for the analysis of proteomes and is rapidly being implemented by many researchers for proteomic analysis. In this technology profile, a particular proteomic approach known as multidimensional protein identification technology (MudPIT) is discussed. In MudPIT, a biphasic microcapillary column is packed with high-performance liquid chromatography grade reversed phase and strong cation exchange packing materials, loaded with a complex peptide mixture and placed in line with quaternary high-performance liquid chromatography and a tandem mass spectrometer. MudPIT has the capability to analyze highly complex proteomic mixtures such as whole proteomes, organelles and protein complexes.

Stem of SL1 RNA in HIV-1: structure and nucleocapsid protein binding for a 1 x 3 internal loop.

The 5'-leader of HIV-1 RNA controls many viral functions. Nucleocapsid (NC) domains of gag-precursor proteins select genomic RNA for packaging by binding several sites in the leader. One is likely to be a stem defect in SL1 that can adopt either a 1 x 3 internal loop, SL1i (including G247, A271, G272, G273) or a 1 x 1 internal loop (G247 x G273) near a two-base bulge (A269-G270). It is likely that these two conformations are both present and exchange readily. A 23mer RNA construct described here models SL1i and cannot slip into the alternate form. It forms a 1:1 complex with NCp7, which interacts most strongly at G247 and G272 (K(d) = 140 nM). This demonstrates that a linear G-X-G sequence is unnecessary for high-affinity binding. The NMR-based structure shows an easily broken G247:A271 base pair. G247 stacks on both of its immediate neighbors and A271 on its 5'-neighbor; G272 and G273 are partially ordered. A bend in the helix axis between the SL1 stems on either side of the internal loop is probable. An important step in maturation of the virus is the transition from an apical loop-loop interaction to a dimer involving intermolecular interactions along the full length of SL1. A bend in the stem may be important in relieving strain and ensuring that the strands do not become entangled during the transition. A stem defect with special affinity for NCp7 may accelerate the rate of the dimer transformation. This complex could become an important target for anti-HIV drug development, where a drug could exert its action near a high-energy intermediate on the pathway for maturation of the dimer.

Affinities of the nucleocapsid protein for variants of SL3 RNA in HIV-1.

Efficient packaging of genomic RNA into new HIV-1 virus particles requires that nucleocapsid domains of precursor proteins bind the SL3 tetraloop (G317-G-A-G320) from the 5'-untranslated region. This paper presents the affinities of 35 RNA variants of SL3 for the mature 55mer NC protein, as measured by fluorescence quenching of tryptophan-37 in the protein by nucleobases. The 1:1 complexes that form in 0.2 M NaCl have dissociation constants ranging from 8 nM (GGUG) to 20 microM (GAUA). The highly conserved (GGAG) sequence for the wild type is not the most stable (K(d) = 28 nM), suggesting that other selective pressures beyond the stability of the complex must be satisfied. The leading requirement for strong interaction is for G320, followed closely by G318. Replacing either with U, A, or C reduces affinity by a factor of 15-120. NC-domains from multiple proteins combine to recognize unpaired G(2)-loci, where two guanines are in close proximity. We have previously measured affinities of the NC protein for the important stem-loops of the major packaging domain [Shubsda, M. F., Paoletti, A. C., Hudson, B. S., and Borer, P. N. (2002) Biochemistry 41, 5276-82]. Comparison with the present work shows that the nature of the stem also modulates NC-RNA interactions. Placing the G(2)-loci from the apical SL2 or SL1 loops on the SL3 stem increases affinity by a factor of 2-3, while placing the SL4 loop on the SL3 stem reduces affinity 50-fold. These results are interesting in the context of RNA-protein interaction, as well as for the discovery of antiNC agents for AIDS therapy.

Affinities of packaging domain loops in HIV-1 RNA for the nucleocapsid protein.

To design anti-nucleocapsid drugs, it is useful to know the affinities the protein has for its natural substrates under physiological conditions. Dissociation equilibrium constants are reported for seven RNA stem-loops bound to the mature HIV-1 nucleocapsid protein, NCp7. The loops include SL1, SL2, SL3, and SL4 from the major packaging domain of genomic RNA. The binding assay is based on quenching the fluorescence of tryptophan-37 in the protein by G residues in the single-stranded loops. Tightly bound RNA molecules quench nearly all the fluorescence of freshly purified NCp7 in 0.2 M NaCl. In contrast, when the GGAG-tetraloop of tight-binding SL3 is replaced with UUCG or GAUA, quenching is almost nil, indicating very low affinity. Interpreting fluorescence titrations in terms of a rapidly equilibrating 1:1 complex explains nearly all of the experimental variance for the loops. Analyzed in this way, the highest affinities are for 20mer SL3 and 19mer SL2 hairpin constructs (K(d) = 28 +/- 3 and 23 +/- 2 nM, respectively). The 20mer stem-UUCG-loop and GAUA-loop constructs have <0.5% of the affinity for NCp7 relative to SL3. Affinities relative to SL3 for the other stem-loops are the following: 10% for a 16mer construct to model SL4, 30% for a 27mer model of the 9-residue apical loop of SL1, and 20% for a 23mer model of a 1 x 3 asymmetric internal loop in SL1. A 154mer construct that includes all four stem-loops binds tightly to NCp7, with the equivalent of three NCp7 molecules bound with high affinity per RNA; it is also possible that two strong sites and several weaker ones combine to give the appearance of three strong sites.