Interconception Care for Adolescent Women During the COVID-19 Pandemic.

BACKGROUND AND OBJECTIVE: Interconception care (ICC) is a means of improving health outcomes for women and children by mitigating maternal risks between pregnancies. Within a pediatric medical home ICC is reliant on adherence to well-child visits (WCVs). We hypothesized that a pediatric-based ICC model would remain successful in providing access to services for adolescent women for those seen during the COVID19 pandemic. The objective of this study was to determine if the COVID19 pandemic influenced LARC use and repeat pregnancy for those seen for ICC in a dyadic pediatric medical home. METHODS: The pre-COVID cohort was comprised of adolescent women seen for ICC from September 2018-October 2019. The COVID cohort was comprised of adolescent women seen for ICC from March 2020-March 2021. The two cohorts were compared across multiple characteristics including sociodemographic factors, age, education, number of visits, contraceptive choice and repeat pregnancy during the study interval. RESULTS: The COVID cohort were significantly more likely to be primiparous, seen with a younger infant, and attend fewer visits than the pre-COVID cohort. The COVID cohort were equally likely to initiate long-acting reversible contraception but less likely to experience a repeat pregnancy. CONCLUSIONS: The COVID19 pandemic limited access to routine healthcare and likely impacted access to ICC for many women. ICC provided during WCVs allowed access to care even amid the restrictions of the COVID19 pandemic. Both effective contraception and decreased repeat pregnancy were maintained, highlighting the effectiveness of this approach for ICC within a dyadic pediatric medical home.

SARS-CoV-2 infection in children evaluated in an ambulatory setting during Delta and Omicron time periods.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and re-emergence of other respiratory viruses highlight the need to understand the presentation of and factors associated with SARS-CoV-2 in pediatric populations over time. The objective of this study was to evaluate the sociodemographic characteristics, symptoms, and epidemiological risk factors associated with ambulatory SARS-CoV-2 infection in children and determine if factors differ by variant type. We conducted a retrospective cohort study of outpatient children undergoing SARS-CoV-2 polymerase chain reaction testing between November 2020 and January 2022. Test-positive were compared with test-negative children to evaluate symptoms, exposure risk, demographics, and comparisons between Omicron, Delta, and pre-Delta time periods. Among 2264 encounters, 361 (15.9%) were positive for SARS-CoV-2. The cohort was predominantly Hispanic (51%), 5-11 years (44%), and 53% male; 5% had received two coronavirus disease 2019 (COVID-19) vaccine doses. Factors associated with a positive test include loss of taste/smell (adjusted odds ratio [aOR]: 6.71, [95% confidence interval, CI: 2.99-15.08]), new cough (aOR: 2.38, [95% CI: 1.69-3.36]), headache (aOR: 1.90, [95% CI: 1.28-2.81), fever (aOR: 1.83, [95% CI: 1.29-2.60]), contact with a positive case (aOR: 5.12, [95% CI: 3.75-6.97]), or household contact (aOR: 2.66, [95% CI: 1.96-3.62]). Among positive children, loss of taste/smell was more predominant during the Delta versus Omicron and pre-Delta periods (12% vs. 2% and 3%, respectively, p = 0.0017), cough predominated during Delta/Omicron periods more than the pre-Delta period (69% and 65% vs. 41%, p = 0.0002), and there were more asymptomatic children in the pre-Delta period (30% vs. 18% and 10%, p = 0.0023). These findings demonstrate that the presentation of COVID-19 in children and most susceptible age groups has changed over time.

Connecting during COVID: The application of teleservices in two integrated perinatal settings.

Integrated perinatal behavioral healthcare provides opportunities to support women and their babies as part of their primary care medical home. The COVID-19 pandemic required significant changes to be made to medical practices to enhance safety and reduce risk, particularly for vulnerable populations, including pregnant women. Previously established modes of mental health service delivery in the HEART program, an integrated behavioral health program embedded in a primary care clinic for adolescent mothers and their babies, and the PROMISE Clinic, an integrated obstetric behavioral health program that serves pregnant women, quickly pivoted to telehealth services because of the pandemic. HEART serves a racially and ethnically diverse patient population, with over 85% of patients publicly insured. The PROMISE Clinic serves a socioeconomically, racially, and ethnically diverse patient population. Behavioral health clinicians implemented a variety of technology-based services including telephone interventions and support, virtual visits using iPads during medical visits, and video visits that patients accessed from their homes. In HEART, behavioral health visits continued at pre-COVID rates during telehealth adaptations. In the PROMISE clinic, the number of perinatal women seen doubled, the total number of patient contacts tripled, and the missed appointment rate significantly decreased during COVID. In the PROMISE clinic, significantly more White and Hispanic perinatal women were seen during COVID and telehealth adaptations, while significantly fewer Black perinatal women were seen during this period. Further research is indicated to examine patient attitudes towards telehealth services, barriers to treatment for Black women, and outcome data.

El cuidado integrado de salud perinatal y del comportamiento ofrece oportunidades para apoyar a las mujeres y sus bebés como parte central del cuidado médico primario. La pandemia del COVID-19 requirió cambios significativos en las prácticas médicas para mejorar la seguridad y reducir el riesgo, particularmente para grupos de población vulnerables, incluyendo las mujeres embarazadas. Las maneras de ofrecer el servicio de salud mental previamente establecidas en la Clínica para Madres Jóvenes (YMC), una clínica de cuidado primario para madres adolescentes y sus bebés, y la Clínica PROMESA, un equipo integrado de salud obstétrica y del comportamiento, rápidamente cambiaron a los servicios de tele-salud a causa de la pandemia. El personal clínico de salud del comportamiento implementó una variedad de servicios con base en la tecnología, incluyendo intervenciones por teléfono, visitas virtuales llevadas a cabo durante visitas médicas, así como visitas grabadas en video a las que las pacientes tenían acceso desde sus casas. En YMC, las visitas de salud del comportamiento continuaron a los niveles de pre-COVID durante las adaptaciones a la tele-salud. En la Clínica PROMESA, significativamente más mujeres blancas e hispanas perinatales fueron vistas durante las adaptaciones de tele-salud, mientras que significativamente menos mujeres negras perinatales fueron vistas durante este período. Se indica una mayor investigación para examinar las actitudes de las pacientes hacia los servicios de tele-salud, las barreras al tratamiento de mujeres negras y los datos de resultados.

Les soins de santé périnatale intégrés offrent des occasions de soutenir les femmes et leurs bébés dans le contexte de leurs services de soin médical à domicile. La pandémie COVID-19 a exigé des changements importants pour les pratiques médicales afin de renforcer la sécurité et de réduire les risques, particulièrement pour les populations vulnérables, y compris les femmes enceintes. Des modes déjà établis de service de santé mentale dans la Clinique des Jeunes Femmes (Young Mothers Clinic, soit YMC), une clinique de soins primaires pour les mères adolescentes et leurs bébés et la Clinique PROMISE, une équipe de santé obstétrique comportementale intégrée ont vite pivoté vers des services de télésanté à cause de la pandémie. Les cliniciens de santé du comportement ont mis en place une variété de services basés sur la technologie y compris des interventions par téléphone, des visites virtuelles faites durant des visites médicales et des visites par vidéo que les parents ont regardé depuis chez eux. Pour ce qui concerne la YMC les visites de santé comportementale ont continué à des taux pré-COVID durant les adaptations de télésanté. Pour ce qui concerne la clinique PROMISE le nombre de femmes périnatales vues a doublé, le nombre total de contacts aux patientes a triplé, et le taux de rendez-vous manqués a considérablement baissé durant le COVID. A la clinique PROMISE bien plus de femmes périnatales blanches et hispaniques ont été vues durant les adaptions de télésanté, alors que bien moins de femmes périnatales noirs ont été vues durant cette période. Nous indiquons des directions de recherches supplémentaires pour examiner les attitudes de la patiente envers les services de télésanté, les barrières au traitement des femmes noires et les données des résultats.

Implementing Interconception Care in a Dyadic Adolescent Mother-Child Clinic.

INTRODUCTION: The birth of a second child to an adolescent woman worsens the adverse medical, socioeconomic, educational, and parenting outcomes for the woman and her children. Despite the known high efficacy of long-acting reversible contraception (LARC), many postpartum adolescents use less effective or no contraception. Interconception care (ICC) focuses on modifying maternal risks between pregnancies and promoting healthy birth spacing to improve outcomes for women and children. Research shows that women regularly attend their child's health care visits even if they do not seek care for themselves between pregnancies. These visits present a potential opportunity for providers to educate women on available LARC options. METHODS: In an adolescent mother-child clinic, demographic and ICC screening data were collected on women presenting for well child visits of children age 0-24 months. These data were analyzed using logistic regression models to identify independent predictors of LARC initiation and repeat pregnancy. RESULTS: Mother-child dyads were screened an average of two times in the study period. Participants with only one visit were less likely to initiate LARC. Of the participants, 5.5% became pregnant again, with patients having only one ICC visit being slightly, but not significantly more likely. Hispanic ethnicity and having ≥ 2 visits were significant independent predictors of LARC initiation. The only independent predictor of repeat pregnancy was not initiating LARC. CONCLUSIONS: This study suggests that optimal ICC may rely on consistent and frequent touch points with providers and not solely on the medical management during the interconception period, making it adaptable to a traditional pediatric medical home. Tying the worlds of pediatric and maternal healthcare is pivotal for successful ICC.

Primary care provider preferences for glucocorticoid management of acute asthma exacerbations in children.

OBJECTIVE: Primary care providers (PCP) frequently care for children with acute asthma exacerbations in the outpatient setting. The objective of this study is to evaluate PCP preferences and perceptions regarding oral glucocorticoids prescribed from both outpatient primary care and ED settings for the treatment of children with acute asthma exacerbations. METHODS: PCPs belonging to the Colorado Chapter of the American Academy of Pediatrics were surveyed between February and May 2019. Survey items were generated by a multidisciplinary team and underwent content and criteria validation and pilot testing. Survey items evaluated PCP preferred oral glucocorticoid and dosing regimen for children with acute asthma exacerbations, provider- and patient-level factors contributing to glucocorticoid preferences, and perception of glucocorticoid regimens in terms of treatment failure, resolution of symptoms and adherence. RESULTS: A total of 109 of 600 (18.2%) PCPs responded. Equal proportions of PCPs reported preferring oral prednisone/prednisolone (50.5%) and oral dexamethasone (49.5%) for children with acute asthma exacerbations. Forty-four percent of PCPs reported no preference in type of glucocorticoid utilized by surrounding emergency departments (EDs). However, for children receiving dexamethasone in the ED but with persistent symptoms on PCP follow-up, 50.5% of PCPs would switch patients to prednisone/prednisolone. PCPs did not perceive more treatment failure or rapid resolution of symptoms with dexamethasone but reported better adherence with dexamethasone. CONCLUSION: There is variability in PCP glucocorticoid management of pediatric acute asthma exacerbations. There is a need for further investigations to evaluate for differences in clinical outcomes based on PCP glucocorticoid treatment choices.

Cartilage oligomeric matrix protein enhances matrix assembly during chondrogenesis of human mesenchymal stem cells.

Cartilage oligomeric matrix protein/thrombospondin-5 (COMP/TSP5) is an abundant cartilage extracellular matrix (ECM) protein that interacts with major cartilage ECM components, including aggrecan and collagens. To test our hypothesis that COMP/TSP5 functions in the assembly of the ECM during cartilage morphogenesis, we have employed mesenchymal stem cell (MSC) chondrogenesis in vitro as a model to examine the effects of COMP over-expression on neo-cartilage formation. Human bone marrow-derived MSCs were transfected with either full-length COMP cDNA or control plasmid, followed by chondrogenic induction in three-dimensional pellet or alginate hydrogel culture. MSC chondrogenesis and ECM production was estimated based on quantitation of sulfated glycosaminoglycan (sGAG) accumulation, immunohistochemistry of the presence and distribution of cartilage ECM proteins, and real-time RT-PCR analyis of mRNA expression of cartilage markers. Our results showed that COMP over-expression resulted in increased total sGAG content during the early phase of MSC chondrogenesis, and increased immuno-detectable levels of aggrecan and collagen type II in the ECM of COMP-transfected pellet and alginate cultures, indicating more abundant cartilaginous matrix. COMP transfection did not significantly increase the transcript levels of the early chondrogenic marker, Sox9, or aggrecan, suggesting that enhancement of MSC cartilage ECM was effected at post-transcriptional levels. These findings strongly suggest that COMP functions in mesenchymal chondrogenesis by enhancing cartilage ECM organization and assembly. The action of COMP is most likely mediated not via direct changes in cartilage matrix gene expression but via interactions of COMP with other cartilage ECM proteins, such as aggrecan and collagens, that result in enhanced assembly and retention.

Biological responses of human mesenchymal stem cells to titanium wear debris particles.

Wear debris-induced osteolysis is a major cause of orthopedic implant aseptic loosening, and various cell types, including macrophages, monocytes, osteoblasts, and osteoclasts, are involved. We recently showed that mesenchymal stem/osteoprogenitor cells (MSCs) are another target, and that endocytosis of titanium (Ti) particles causes reduced MSC proliferation and osteogenic differentiation. Here we investigated the mechanistic aspects of the endocytosis-mediated responses of MSCs to Ti particulates. Dose-dependent effects were observed on cell viability, with doses >300 Ti particles/cell resulting in drastic cell death. To maintain cell viability and analyze particle-induced effects, doses <300 particles/cell were used. Increased production of interleukin-8 (IL-8), but not IL-6, was observed in treated MSCs, while levels of TGF-ß, IL-1ß, and TNF-α were undetectable in treated or control cells, suggesting MSCs as a likely major producer of IL-8 in the periprosthetic zone. Disruptions in cytoskeletal and adherens junction organization were also observed in Ti particles-treated MSCs. However, neither IL-8 and IL-6 treatment nor conditioned medium from Ti particle-treated MSCs failed to affect MSC osteogenic differentiation. Among other Ti particle-induced cytokines, only GM-CSF appeared to mimic the effects of reduced cell viability and osteogenesis. Taken together, these results strongly suggest that MSCs play both responder and initiator roles in mediating the osteolytic effects of the presence of wear debris particles in periprosthetic zones.

Comparison of minimally invasive direct anterior versus posterior total hip arthroplasty based on inflammation and muscle damage markers.

BACKGROUND: A number of surgical approaches are utilized in total hip arthroplasty. It has been hypothesized that the anterior approach results in less muscle damage than the posterior approach. We prospectively analyzed biochemical markers of muscle damage and inflammation in patients treated with minimally invasive total hip arthroplasty with an anterior or posterior approach to provide objective evidence of the local soft-tissue injury at the time of arthroplasty. METHODS: Twenty-nine patients treated with minimally invasive total hip arthroplasty through a direct anterior approach and twenty-eight patients treated with the same procedure through a posterior approach were prospectively analyzed. Perioperative and radiographic data were collected to ensure cohorts with similar characteristics. Serum creatine kinase (CK), C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-1 beta (IL-1ß), and tumor necrosis factor-alpha (TNF-a) levels were measured preoperatively, in the post-anesthesia-care unit (except for the CRP level), and on postoperative days 1 and 2. The Student t test and Fisher exact test were used to make comparisons between the two groups. Independent predictors of elevation in levels of markers of inflammation and muscle damage were determined with use of multivariate logistic regression analysis. RESULTS: The levels of the markers of inflammation were slightly decreased in the direct-anterior-approach group as compared with those in the posterior-approach group. The rise in the CK level in the posterior-approach group was 5.5 times higher than that in the anterior-approach group in the post-anesthesia-care unit (mean difference, 150.3 units/L [95% CI, 70.4 to 230.2]; p < 0.05) and nearly twice as high cumulatively (mean difference, 305.0 units/L [95% CI, -46.7 to 656.8]; p < 0.05). CONCLUSIONS: We believe that the anterior total hip arthroplasty approach used in this study caused significantly less muscle damage than did the posterior surgical approach, as indicated by serum CK levels. The clinical importance of the rise in the CK level needs to be delineated by additional clinical studies. The overall physiologic burden, as demonstrated by measurement of inflammation marker levels, appears to be similar between the anterior and posterior approaches. Objective measurement of muscle damage and inflammation markers provides an unbiased way of determining the immediate effects of surgical intervention in patients treated with total hip arthroplasty.

Interleukin-6 maintains bone marrow-derived mesenchymal stem cell stemness by an ERK1/2-dependent mechanism.

Adult human mesenchymal stem cells (MSCs) hold promise for an increasing list of therapeutic uses due to their ease of isolation, expansion, and multi-lineage differentiation potential. To maximize the clinical potential of MSCs, the underlying mechanisms by which MSC functionality is controlled must be understood. We have taken a deconstructive approach to understand the individual components in vitro, namely the role of candidate "stemness" genes. Our recent microarray gene expression profiling data suggest that interleukin-6 (IL-6) may contribute to the maintenance of MSCs in their undifferentiated state. In this study, we showed that IL-6 gene expression is significantly higher in undifferentiated MSCs as compared to their chondrogenic, osteogenic, and adipogenic derivatives. Moreover, we found that MSCs secrete copious amounts of IL-6 protein, which decreases dramatically during osteogenic differentiation. We further evaluated the role of IL-6 for maintenance of MSC "stemness," using a series of functional assays. The data showed that IL-6 is both necessary and sufficient for enhanced MSC proliferation, protects MSCs from apoptosis, inhibits adipogenic and chondrogenic differentiation of MSCs, and increases the rate of in vitro wound healing of MSCs. We further identified ERK1/2 activation as the key pathway through which IL-6 regulates both MSC proliferation and inhibition of differentiation. Taken together, these findings show for the first time that IL-6 maintains the proliferative and undifferentiated state of bone marrow-derived MSCs, an important parameter for the optimization of both in vitro and in vivo manipulation of MSCs.

Particulate endocytosis mediates biological responses of human mesenchymal stem cells to titanium wear debris.

Continual loading and articulation cycles undergone by metallic (e.g., titanium) alloy arthroplasty prostheses lead to liberation of a large number of metallic debris particulates, which have long been implicated as a primary cause of periprosthetic osteolysis and postarthroplasty aseptic implant loosening. Long-term stability of total joint replacement prostheses relies on proper integration between implant biomaterial and osseous tissue, and factors that interfere with this integration are likely to cause osteolysis. Because multipotent mesenchymal stem cells (MSCs) located adjacent to the implant have an osteoprogenitor function and are critical contributors to osseous tissue integrity, when their functions or activities are compromised, osteolysis will most likely occur. To date, it is not certain or sufficiently confirmed whether MSCs endocytose titanium particles, and if so, whether particulate endocytosis has any effect on cellular responses to wear debris. This study seeks to clarify the phenomenon of titanium endocytosis by human MSCs (hMSCs), and investigates the influence of endocytosis on their activities. hMSCs incubated with commercially pure titanium particles exhibited internalized particles, as observed by scanning electron microscopy and confocal laser scanning microscopy, with time-dependent reduction in the number of extracellular particles. Particulate endocytosis was associated with reduced rates of cellular proliferation and cell-substrate adhesion, suppressed osteogenic differentiation, and increased rate of apoptosis. These cellular effects of exposure to titanium particles were reduced when endocytosis was inhibited by treatment with cytochalasin D, and no significant effect was seen when hMSCs were treated only with conditioned medium obtained from particulate-treated cells. These findings strongly suggest that the biological responses of hMSCs to wear debris are triggered primarily by the direct endocytosis of titanium particulates, and not mediated by secreted soluble factors. In this manner, therapeutical approaches that suppress particle endocytosis could reduce the bioreactivity of hMSCs to particulates, and enhance long-term orthopedic implant prognosis by minimizing wear-debris periprosthethic osteolysis.

Optimization of high-efficiency transfection of adult human mesenchymal stem cells in vitro.

With the advent of recent protocols to isolate multipotent human mesenchymal stem cells (MSCs), there is a need for efficient transfection methodologies for these cells. Most standard transfection methods yield poor transfection efficiencies for MSCs (<1%). Here we have optimized a high-efficiency transfection technique for low passage MSCs derived from adult human bone marrow. This technique is an extension of electroporation, termed amaxa Nucleofection, where plasmid DNA is transfected directly into the cell nucleus, independent of the growth state of the cell. With this technique, we demonstrate up to 90% transfection efficiency of the viable population of MSCs, using plasmid construct containing a standard cytomegalovirus (CMV) early promoter driving expression of green fluorescent protein (GFP). Although little variation in transfection efficiency was observed between patient samples, a 2-fold difference in transfection efficiency and a 10-fold difference in expression levels per cell were seen using two distinct CMV-GFP expression plasmids. By fluorescence-activated cell sorting, the GFP expressing cells were sorted and subcultured. At 2 wk posttransfection, approx 25% of the population of sorted cells were GFP positive, and by 3 wk, nearly 10% of the cells still retained GFP expression. Transfection of these cells with plasmid containing either the collagen type I (Col1a1) promoter or the cartilage oligomeric matrix protein (COMP) promoter, each driving expression of GFP, produced a somewhat lower transfection efficiency (approx 40%), due in part to the lower activity of transcription from these promoters compared to that of CMV. Transfection with the collagen type II (Col2a1) promoter linked to GFP exhibited low expression, due to the fact that collagen type II is not expressed in these cells. Upon culturing of the Col2a1-GFP transfected cells in a transforming growth factor-beta3-containing medium known to induce mesenchymal chondrogensis, a significant enhancement of GFP level was seen, indicating the ability of the transfected cells to differentiate into chondrocytes and express cartilage-specific genes, such as Col2a1. Taken together, these data provide evidence of the applicability of this technique for the efficient transfection of MSCs.

Characterization of multipotential mesenchymal progenitor cells derived from human trabecular bone.

The in vitro culture of human trabecular bone-derived cells has served as a useful system for the investigation of the biology of osteoblasts. The recent discovery in our laboratory of the multilineage mesenchymal differentiation potential of cells derived from collagenase-treated human trabecular bone fragments has prompted further interest in view of the potential application of mesenchymal progenitor cells (MPCs) in the repair and regeneration of tissue damaged by disease or trauma. Similar to human MPCs derived from bone marrow, a clearer understanding of the variability associated with obtaining these bone-derived cells is required in order to optimize the design and execution of applicable studies. In this study, we have identified the presence of a CD73(+), STRO-1(+), CD105(+), CD34(-), CD45(-), CD144(-) cell population resident within collagenase-treated, culture-processed bone fragments, which upon migration established a homogeneous population of MPCs. Additionally, we have introduced a system of culturing these MPCs that best supports and maintains their optimal differentiation potential during long-term culture expansion. When cultured as described, the trabecular bone-derived cells display stem cell-like capabilities, characterized by a stable undifferentiated phenotype as well as the ability to proliferate extensively while retaining the potential to differentiate along the osteoblastic, adipocytic, and chondrocytic lineages, even when maintained in long-term in vitro culture.

Quantitative aspects of signal transduction by the receptor with high affinity for IgE.

Identification of the major components, how these interact with each other, and the modifications that follow in the sequence of events triggered by the receptor with high affinity for IgE, is progressing rapidly. A new challenge is to understand these interactions quantitatively. We present the fundamentals of the mechanistic model we are testing through mathematical modeling. The object is to see if the predictions of the model fit with the experimental results.