Caregiver Adverse Childhood Experiences and Pediatric Infection-Related Outcomes.

BACKGROUND: Higher caregiver adverse childhood experiences (ACEs) have been associated with multiple adverse pediatric outcomes. However, no studies have examined links between caregiver ACEs and infectious outcomes like antibiotic prescriptions or infection-related clinical encounters. METHODS: We conducted a retrospective cohort study including patients from two pediatric primary care sites, serving predominantly non-Hispanic Black, publicly-insured populations. Our outcomes were antibiotic prescriptions and infection-related ambulatory clinical encounters for children 0-3 years old. We captured these outcomes and additional covariates (demographics, health-related social risk screen results, and socioeconomic deprivation index scores linked to geocoded street addresses), from the electronic health record. High (≥4) or low (≤3) caregiver ACEs, and individual ACE question answers, were our exposures. Multivariable logistic regression was used to determine associations with any antibiotic use. Cox proportional hazards regression was used to assess time to first antibiotic exposure and first infection-related visit. RESULTS: A total of 1,465 children 0-3 years were included (50.0% female, 75.0% Black, 2.6% Hispanic). High caregiver ACEs were not associated with pediatric antibiotic exposure. The presence of caregiver-witnessed parental abuse was associated with higher likelihood of any antibiotic exposure (odds ratio [OR 1.90]; 95% confidence interval [CI] 1.2, 3.2) and time to first antibiotic exposure (hazard ratio [HR] 1.77; 95%CI 1.23, 2.56). Sexual abuse of the caregiver was associated with time to first infection-related clinical visit (HR 1.27; 95%CI 1.05, 1.53). CONCLUSIONS: Certain caregiver ACEs were associated with pediatric antibiotic use and infection-related visits. Future studies need to evaluate underlying mechanisms and test effective clinical responses.

Complete Blood Count Values Over Time in Young Children During the Dengue Virus Epidemic in the Dominican Republic From 2018 to 2020.

Background: Dengue fever (DF) is a mosquito-borne illness with substantial economic and societal impact. Understanding laboratory trends of hospitalized Dominican Republic (DR) pediatric patients could help develop screening procedures in low-resourced settings. We sought to describe laboratory findings over time in DR children with DF and DF severity from 2018 to 2020. Methods: Clinical information was obtained prospectively from recruited children with DF. Complete blood count (CBC) laboratory measures were assessed across Days 1-10 of fever. Participants were classified as DF-negative and DF-positive and grouped by severity. We assessed associations of DF severity with demographics, clinical characteristics, and peripheral blood studies. Using linear mixed-models, we assessed if hematologic values/trajectories differed by DF status/severity. Results: A total of 597 of 1101 with a DF clinical diagnosis were serologically evaluated, and 574 (471 DF-positive) met inclusion criteria. In DF, platelet count and hemoglobin were higher on earlier days of fever (p < = 0.0017). Eighty had severe DF. Severe DF risk was associated with thrombocytopenia, intraillness anemia, and leukocytosis, differing by fever day (p < = 0.001). Conclusions: In a pediatric hospitalized DR cohort, we found marked anemia in late stages of severe DF, unlike the typically seen hemoconcentration. These findings, paired with clinical symptom changes over time, may help guide risk-stratified screenings for resource-limited settings.

High Caregiver Adverse Childhood Experiences Are Associated With Pediatric Influenza and COVID-19 Vaccination Uptake.

BACKGROUND: Factors surrounding vaccine uptake are complex. Although anxiety, which could influence vaccination decisions, has been associated with adverse childhood experiences (ACEs), little is known about links between caregiver ACEs and pediatric vaccine uptake. We evaluated associations between caregivers' ACEs and decisions to vaccinate their children with influenza and coronavirus disease (COVID-19) vaccines. METHODS: A cross-sectional study of caregivers of patients ≥6 months at one pediatric primary care center (PPCC) was performed. Caregivers completed a 19-question survey examining caregiver ACEs, influenza vaccine acceptance and beliefs, and intention to vaccinate their child with the COVID-19 vaccine. Demographic characteristics, social risks (eg, housing and food insecurity), and vaccination data for children present with each caregiver were extracted from the electronic health record (EHR). Statistical analyses included χ2 tests for categorical variables and t-tests for continuous variables. RESULTS: A total of 240 caregivers participated, representing 283 children (mean age of 5.9 years, 47% male). Twenty-four percent (n = 58) had high ACEs (≥4). Of those with high ACEs, 55% accepted pediatric influenza vaccination compared with 38% with low ACEs (P = .02). Those with high ACEs had more positive attitudes toward influenza vaccine safety and efficacy (P ≤ .02). Those with high, compared with low, ACEs were also more likely to accept COVID-19 vaccination (38% vs 24%; P = .04). CONCLUSIONS: Pediatric influenza vaccination rates and intention to vaccinate children against COVID-19 differed between caregivers with high and low ACEs: those with more ACEs were more likely to vaccinate. Further studies assessing the role of caregiver ACEs on vaccine decision-making are warranted.

The 2019-2020 Dengue Fever Epidemic: Genomic Markers Indicating Severity in Dominican Republic Children.

We performed an observational cohort study to assess associations between genetic factors of dengue fever (DF) severity in children in the Dominican Republic. A total of 488 participants had serologically confirmed DF. We replicated the association between the IFIH1 gene (rs1990760) and severe DF (n = 80/488, p = 0.006) and identified novel associations needing further investigation.

Declining influenza vaccination rates in an underserved pediatric primary care center during the COVID-19 pandemic.

BACKGROUND: Influenza vaccination rates are decreasing in the United States. Disinformation surrounding COVID-related public health protections and SARS-CoV-2 vaccine roll-out may have unintended consequences impacting pediatric influenza vaccination.We assessed influenza vaccination rates before and during the COVID-19 pandemic in one pediatric primary care center, serving a minoritized population. METHODS: A cross-sectional study assessed influenza vaccination rates for children aged 6 months to 12 years over the following influenza seasons (September-May): 1) 2018-19 and 2019-20 (pre-pandemic), and 2) 2020-21 and 2021-22 (intra-pandemic). Demographics and responses to social risk questionnaires were extracted from electronic health records. Total tetanus vaccinations across influenza seasons served as approximations of general vaccination rates. Generalized linear regression models with robust standard errors evaluated differences in demographics, social risks, and influenza vaccination rates by season. Multivariable logistic regression with robust standard errors evaluated associations between influenza season, demographics, social risks, and influenza vaccination. RESULTS: Most patients were young (mean age âˆ¼ 6 years), non-Hispanic Black (∼80%), and publicly insured (∼90%). Forty-two percent of patients eligible to receive the influenza vaccine who were seen in 2019-20 influenza season received the influenza vaccine, compared to 30% in 2021-22. Influenza and tetanus vaccination rates decreased during the COVID-19 pandemic (p < 0.01). The 2020-21 and 2021-22 influenza seasons, older age, Black race, and self-pay were associated with decreased influenza vaccine administration (p < 0.05). CONCLUSIONS: Influenza vaccination rates within one pediatric primary care center decreased during the COVID-19 pandemic and have not rebounded, particularly for older children, those identifying as Black, and those without insurance.

Lethal Pediatric Cerebral Vasculitis Triggered by Severe Acute Respiratory Syndrome Coronavirus 2.

BACKGROUND: We report the clinical, radiological, laboratory, and neuropathological findings in support of the first diagnosis of lethal, small-vessel cerebral vasculitis triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a pediatric patient. PATIENT DESCRIPTION: A previously healthy, eight-year-old Hispanic girl presented with subacute left-sided weakness two weeks after a mild febrile illness. SARS-CoV-2 nasopharyngeal swab was positive. Magnetic resonance imaging revealed an enhancing right frontal lobe lesion with significant vasogenic edema. Two brain biopsies of the lesion showed perivascular and intraluminal lymphohistiocytic inflammatory infiltrate consistent with vasculitis. Despite extensive treatment with immunomodulatory therapies targeting primary angiitis of the central nervous system, she experienced neurological decline and died 93 days after presentation. SARS-CoV-2 testing revealed positive serum IgG and positive cerebrospinal fluid IgM. Comprehensive infectious, rheumatologic, hematologic/oncologic, and genetic evaluation did not identify an alternative etiology. Postmortem brain autopsy remained consistent with vasculitis. CONCLUSION: This is the first pediatric presentation to suggest that SARS-CoV-2 can lead to a fatal, postinfectious, inflammatory small-vessel cerebral vasculitis. Our patient uniquely included supportive cerebrospinal fluid and postmortem tissue analysis. While most children recover from the neurological complications of SARS-CoV-2, we emphasize the potential mortality in a child with no risk factors for severe disease.

Exploring Careers in Medicine: Implementation and Perceived Value of a Multi-Specialty Elective.

INTRODUCTION: Choosing a medical specialty is one of the most crucial and difficult decisions made during medical school. Given that specialty exposure is among the most important factors in decision-making, the Careers in Medicine (CiM) multi-specialty elective was designed to provide clerkship students an avenue to explore three or more specialties of interest during a single elective. METHODS: A cross-sectional study was conducted at Vanderbilt University School of Medicine using anonymous surveys and de-identified written reflections submitted by students enrolled in the CiM course between August 2015 and June 2018. Data were analyzed using a mixed-methods approach. RESULTS: The majority of students reported the elective guided them in ruling out (80%) and ruling in (65%) specialties. About half (51%) of students decided between the procedural versus critical-thinking dichotomy. Finally, 80% of students reported that they would take the course again rather than a focused elective. Major themes identified from student reflections included course attributes, specialty impacts, and student values. DISCUSSION: Implementation of a multi-specialty elective during the clerkship year was an effective way to help students understand their career values, gain early exposure to specialties not featured in core clinical curriculums, and determine future fields of interest. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40670-021-01311-0.

Contraceptive Methods and the Impact of Menstruation on Daily Functioning in Women with Sickle Cell Disease.

OBJECTIVES: Women with sickle cell disease (SCD) are living longer as a result of advances in the care of their underlying disease. With the population growing of women living with SCD, reproductive health issues in this population have become an emphasized area of medical care. We sought to describe current patterns of contraception use, menstruation, and quality-of-life (QOL) measures in women with SCD. METHODS: Using a cross-sectional study design, we administered paper surveys at two academic medical centers to women aged 10 to 55 years with SCD to capture current contraceptive use, characteristics of menstrual cycles, and QOL metrics. RESULTS: Of the 103 women who participated, 12.7% (13/102) experienced a duration of menses >7 days (defined here as prolonged menstrual bleeding). Approximately half of women (51.5%, 53/103) used some form of contraception, with depot medroxyprogesterone acetate injections and condoms being the most common. During their last menstrual periods, women with both dysmenorrhea and prolonged menstrual bleeding (6.9%, 7/102) were more likely to experience more days of poor QOL, with more nights with sleep disturbance (P = 0.001) and more days with trouble taking care of themselves (P = 0.003), as well as being unable to do things they previously enjoyed (P = 0.001), compared with those with neither phenomenon (28.2%, 29/103). CONCLUSIONS: Dysmenorrhea and prolonged menstrual bleeding negatively affect the QOL of women with SCD. Menstrual histories and preventive measures for menstruation-related morbidity should be incorporated into routine evaluations of women with SCD.

Acute Vaso-Occlusive Pain is Temporally Associated with the Onset of Menstruation in Women with Sickle Cell Disease.

BACKGROUND: Acute vaso-occlusive pain episodes in sickle cell disease (SCD) are associated with increased rates of hospitalization and early mortality. Despite the observation that women have higher rates of acute vaso-occlusive pain episodes than men, sex-specific risk factors for acute vaso-occlusive pain have not been identified. We tested the hypothesis that acute vaso-occlusive pain is temporally associated with the onset of menstruation in women with SCD. METHODS: Initially, using a cross-sectional study design, we administered questionnaires, including validated measures of SCD pain frequency and severity within the last 30 days, as well as menstrual symptoms in a discovery group (n = 103). We then confirmed our findings by administering the same questionnaires online in a replication group (n = 118). A validated questionnaire was used to define dysmenorrhea. RESULTS: In the initial discovery group, 28% (29 of 103) reported acute vaso-occlusive pain episodes temporally associated with menstruation, and 72% (74 of 103) did not. Of the 29 reporting acute vaso-occlusive pain associated with menstruation, 90% (26) and 10% (3) did and did not meet criteria for dysmenorrhea, respectively. In the replication group, 36% (43 of 118) reported acute vaso-occlusive pain temporally associated with menstruation. Of the 43 reporting acute vaso-occlusive pain associated with menstruation, 60% (26) and 40% (17) did and did not meet criteria for dysmenorrhea, respectively. CONCLUSIONS: In both the discovery and replication groups, we demonstrate that acute vaso-occlusive pain is temporally associated with the onset of menstruation that women with SCD can distinguish from dysmenorrhea.

Children with HbSß0 thalassemia have higher hemoglobin levels and lower incidence rate of acute chest syndrome compared to children with HbSS.

BACKGROUND: Based on the presumed clinical similarity between the two most severe sickle cell disease (SCD) genotypes, hemoglobin (Hb) Sß0 thalassemia and HbSS, randomized controlled trials (RCTs) have included both genotypes. Our group has demonstrated that healthcare providers inadequately distinguish the two diagnoses through clinical and laboratory parameters. PROCEDURE: In a retrospective cohort study utilizing data from the Silent Cerebral Infarct Transfusion trial (NCT00072761), we tested the hypothesis that children with genotypic diagnoses of HbSß0 thalassemia, when compared to HbSS, have significantly different rates of SCD comorbidities. Exclusion criteria included those with previous overt stroke or treatment with hydroxyurea or regular blood transfusion therapy. RESULTS: Among children with HbSß0 thalassemia (n = 22) and HbSS (n = 786), the mean hemoglobin was higher in children with HbSß0 thalassemia (9.2 g/dl) compared to HbSS (8.1 g/dl, P < 0.001). In children with HbSß0 thalassemia, when compared to HbSS, the incidence rate of acute chest syndrome (ACS) was 3.0 and 14.4 events per 100 patient-years (P = 0.028), and mean transcranial Doppler (TCD) velocities were 112.6 and 135.6 cm/sec, respectively (P = 0.026). The number of children with HbSß0 thalassemia and HbSS with conditional TCD velocities were zero (0%) and 26 (4.9%), respectively (P = 1.00), and the number with silent cerebral infarcts were five (27.8%) and 209 (30.8%), respectively (P = 0.78). CONCLUSIONS: We have provided preliminary evidence that clinically relevant differences occur in ACS rates and TCD velocities between children with HbSß0 thalassemia and HbSS. Future SCD RCTs should consider balanced allocation of these SCD genotypes, particularly when ACS and abnormal TCD velocities are primary outcome measures.

Fertility challenges for women with sickle cell disease.

INTRODUCTION: Sickle cell disease (SCD) represents one of the most common monogenic blood disorders worldwide, with an incidence of over 300,000 newborns affected per year. Reproductive challenges for men and women with SCD have been previously reviewed; however, evidence-based strategies to prevent and manage infertility and increase fecundity are lacking in women with SCD, which is one of the most important factors for quality of life. Areas covered: This review article summarizes the known risk factors for infertility, low fecundity, and premature menopause related to SCD. Expert commentary: Women with SCD have unique risk factors that may impact their ability to conceive, including chronic inflammation, oxidative stress, transfusion-related hemochromatosis, and ovarian sickling, causing ischemia and reperfusion injury to the ovary. Contraception is strongly recommended while on hydroxyurea therapy during reproductive years and discontinuing hydroxyurea for family planning and during pregnancy based on teratogenicity in animal studies. Hematopoietic stem cell transplantation (HSCT), the only curative therapy, sometimes involves conditioning regimens containing alkylating agents and total body irradiation that contribute to infertility and premature ovarian failure. Prior to HSCT or gene therapy, we strongly recommend referral to a reproductive endocrinologist to discuss fertility preservation and surrogacy options for all women with SCD.