ABSTRACT
BACKGROUND: The molecular genetic basis of pulmonary arterial hypertension (PAH) is heterogeneous, with at least 26 genes displaying putative evidence for disease causality. Heterozygous variants in the ATP13A3 gene were recently identified as a new cause of adult-onset PAH. However, the contribution of ATP13A3 risk alleles to child-onset PAH remains largely unexplored. METHODS AND RESULTS: We report three families with a novel, autosomal recessive form of childhood-onset PAH due to biallelic ATP13A3 variants. Disease onset ranged from birth to 2.5 years and was characterised by high mortality. Using genome sequencing of parent-offspring trios, we identified a homozygous missense variant in one case, which was subsequently confirmed to cosegregate with disease in an affected sibling. Independently, compound heterozygous variants in ATP13A3 were identified in two affected siblings and in an unrelated third family. The variants included three loss of function variants (two frameshift, one nonsense) and two highly conserved missense substitutions located in the catalytic phosphorylation domain. The children were largely refractory to treatment and four died in early childhood. All parents were heterozygous for the variants and asymptomatic. CONCLUSION: Our findings support biallelic predicted deleterious ATP13A3 variants in autosomal recessive, childhood-onset PAH, indicating likely semidominant dose-dependent inheritance for this gene.
Subject(s)
Pulmonary Arterial Hypertension , Adenosine Triphosphatases/genetics , Adult , Child, Preschool , Familial Primary Pulmonary Hypertension/genetics , Heterozygote , Homozygote , Humans , Membrane Transport Proteins/genetics , MorbidityABSTRACT
BACKGROUND: Severe acute respiratory syndrome coronavirus 2, the disease-causing pathogen of the coronavirus disease 2019 pandemic, has resulted in morbidity and mortality worldwide. Pregnant women are more susceptible to severe coronavirus disease 2019 and are at higher risk of preterm birth than uninfected pregnant women. Despite this evidence, the immunologic effects of severe acute respiratory syndrome coronavirus 2 infection during pregnancy remain understudied. OBJECTIVE: This study aimed to assess the impact of severe acute respiratory syndrome coronavirus 2 infection during pregnancy on inflammatory and humoral responses in maternal and fetal samples and compare antibody responses to severe acute respiratory syndrome coronavirus 2 among pregnant and nonpregnant women. STUDY DESIGN: Immune responses to severe acute respiratory syndrome coronavirus 2 were analyzed using samples from pregnant (n=33) and nonpregnant (n=17) women who tested either positive (pregnant, 22; nonpregnant, 17) or negative for severe acute respiratory syndrome coronavirus 2 (pregnant, 11) at Johns Hopkins Hospital. We measured proinflammatory and placental cytokine messenger RNAs, neonatal Fc receptor expression, and tetanus antibody transfer in maternal and cord blood samples. In addition, we evaluated antispike immunoglobulin G, antispike receptor-binding domain immunoglobulin G, and neutralizing antibody responses to severe acute respiratory syndrome coronavirus 2 in serum or plasma collected from nonpregnant women, pregnant women, and cord blood. RESULTS: Pregnant women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection expressed more interleukin-1 beta, but not interleukin 6, in blood samples collected within 14 days vs >14 days after performing severe acute respiratory syndrome coronavirus 2 test. Pregnant women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection also had reduced antispike receptor-binding domain immunoglobulin G titers and were less likely to have detectable neutralizing antibody than nonpregnant women. Although severe acute respiratory syndrome coronavirus 2 infection did not disrupt neonatal Fc receptor expression in the placenta, maternal transfer of severe acute respiratory syndrome coronavirus 2 neutralizing antibody was inhibited by infection during pregnancy. CONCLUSION: Severe acute respiratory syndrome coronavirus 2 infection during pregnancy was characterized by placental inflammation and reduced antiviral antibody responses, which may impact the efficacy of coronavirus disease 2019 treatment in pregnancy. In addition, the long-term implications of placental inflammation for neonatal health require greater consideration.
Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , Inflammation/virology , Interleukin-1beta/genetics , Pregnancy Complications/virology , SARS-CoV-2/immunology , Adult , Antibodies, Viral/immunology , Arabidopsis Proteins/blood , COVID-19/complications , Female , Fetal Blood/chemistry , Gene Expression , Humans , Immunoglobulin G/blood , Interleukin-6/genetics , Membrane Proteins/blood , Placenta Diseases/virology , Pregnancy , Pregnancy Complications/immunology , Spike Glycoprotein, Coronavirus/immunologyABSTRACT
BACKGROUND/OBJECTIVE: Herpes simplex virus (HSV) infection acquired in utero may present with non-vesicular dermatologic findings in affected newborns, which may pose a diagnostic dilemma. We aimed to describe and assess the range of non-vesiculobullous skin lesions that neonates with intrauterine HSV infection may manifest at birth. METHODS: We collected a multicenter case series and conducted a literature review of neonates with intrauterine HSV infection presenting with non-vesiculobullous cutaneous lesions. RESULTS: Twenty-two cases were reviewed, including six managed clinically by members of our team and 16 identified in the literature. Four (18%) were associated with twin pregnancies, and thirteen (59%) cases occurred in premature infants. Only four (18%) mothers had a documented history of HSV infection. Twelve (55%) cases resulted in poor outcomes, including long-term neurologic sequelae or death. Cutaneous manifestations included erosions, ulcerations, crusted papules or plaques, calcinosis cutis, excoriations, macules (erythematous, hypopigmented, or hyperpigmented), cutaneous atrophy, contractures, and bruising. About one-third of neonates developed new-onset vesicular lesions within a week of birth; in each of these cases, accurate diagnosis and therapy were delayed until appearance of vesicles. CONCLUSIONS: The range of dermatologic findings associated with intrauterine HSV is extremely broad, and the various morphologies present at birth likely reflect different stages of the ongoing evolution of an HSV infection that began in utero. Clinicians should have a low threshold for HSV testing in premature neonates born with atypical cutaneous lesions, since early detection and treatment of HSV may reduce morbidity and mortality from systemic complications.
Subject(s)
Herpes Simplex , Infant, Newborn, Diseases , Pregnancy Complications, Infectious , Skin Abnormalities , Female , Herpes Simplex/complications , Herpes Simplex/diagnosis , Humans , Infant, Newborn , Multicenter Studies as Topic , PregnancyABSTRACT
Zika virus is a single-stranded RNA virus from the Flaviviridae family. Transmission is typically from the bite of an infected mosquito though mother-to-child, sexual and blood donation transmissions can occur. Although maternal symptoms are uncommon and rarely severe, the consequences of congenital infections are devastating. The emergence of congenital Zika syndrome is a world-wide public health crisis. The Centers for Disease Control and Prevention, ACOG, and SMFM have developed algorithms for screening and managing women exposure to and diagnosed with Zika virus infection. Prevention is the mainstay of infection control as there is currently no vaccine or therapy available.
Subject(s)
Infectious Disease Transmission, Vertical/prevention & control , Pregnancy Complications, Infectious/diagnosis , Zika Virus Infection/diagnosis , Abnormalities, Multiple/virology , Female , Humans , Pregnancy , Pregnancy Complications, Infectious/therapy , RNA, Viral/isolation & purification , Ultrasonography, Prenatal , Zika Virus/genetics , Zika Virus Infection/congenital , Zika Virus Infection/therapy , Zika Virus Infection/transmissionABSTRACT
Medicaid is the largest single source of health insurance coverage in the United States, providing insurance for more than 62 million persons and families in 2013. The Patient Protection and Affordable Care Act sought to expand Medicaid eligibility to nearly all low-income persons with incomes up to 138% of the federal poverty level. However, the U.S. Supreme Court ruled that states' expansion would be optional. Although more than half of the states and the District of Columbia have opted to expand Medicaid starting in 2014, many states continue to oppose increasing access to the program. This article will discuss the basic provisions of the expansion and the benefits and challenges patients and physicians may face as Medicaid grows.
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Health Policy/legislation & jurisprudence , Medicaid/economics , Medicaid/legislation & jurisprudence , Patient Protection and Affordable Care Act , Economics, Hospital , Federal Government , Financing, Government , Humans , Poverty , Reimbursement Mechanisms , State Government , Uncompensated Care , United StatesABSTRACT
OBJECTIVES: Clinical reasoning with generation and prioritization of differential diagnoses (DDx) is a key skill for medical students, but no consensus exists on the best method to teach these skills. Meta-memory techniques (MMTs) may be useful, but the efficacy of individual MMTs is unclear. METHODS: We designed a 3-part curriculum for pediatric clerkship students to teach one of 3 MMTs and provide practice in DDx generation through case-based sessions. Students submitted DDx lists during two sessions and completed pre- and post-curriculum surveys assessing self-reported confidence and perceived helpfulness of the curriculum. Results were analyzed using ANOVA with multiple linear regression. RESULTS: A total of 130 students participated in the curriculum, with 96â¯% (125/130) completing at least one DDx session, and 44â¯% (57/130) completing the post-curriculum survey. On average, 66â¯% of students rated all three sessions as "quite helpful" (4/5 on 5-point Likert scale) or "extremely helpful" (5/5) without difference between MMT groups. Students generated an average of 8.8, 7.1 and 6.4 diagnoses using the VINDICATES, Mental CT, and Constellations methods, respectively. When controlling for case, case order, and number of prior rotations, students using VINDICATES produced 2.8 more diagnoses than those using Constellations (95â¯% CI [1.1,4.5], p<0.001). There was no significant difference between VINDICATES and Mental CT (Δ=1.6, 95â¯% CI [-0.2,3.4], p=0.11) or Mental CT and Constellations (Δ=1.2, 95â¯% CI [-0.7,3.1], p=0.36). CONCLUSIONS: Medical education should include curricula focused on enhancing DDx development. Although VINDICATES helped students produce the most DDx, further research is needed to identify which MMT generates more accurate DDx.
Subject(s)
Metacognition , Humans , Child , Diagnosis, Differential , Dichlorodiphenyl Dichloroethylene , Clinical ReasoningABSTRACT
Introduction Medical students rotate on various clinical disciplines with the same professional goal of learning medical documentation. This study investigated differences between medical student notes on inpatient general and subspecialty pediatric services by comparing note quality, length, and file time. Methods In a single-site, observational cohort study, medical students in the Core Clerkship in Pediatrics (CCP) from July 2020 to June 2021 participated in a note-writing didactic course. We compared notes from medical students completing their inpatient assignment on a general pediatric service to those who completed it on a pediatric subspecialty service. Primary outcomes were note quality measured by Physician Documentation Quality Instrument-9 (PDQI9), note length (measured by line count), and file time (measured by hours to completion since 6 AM on the morning of note initiation). Results We evaluated 84 notes from 84 medical students on the general pediatric services and 50 notes from 49 medical students on the pediatric subspecialty services. Note quality measured by PDQI9 was significantly higher for general pediatric service notes compared to pediatric subspecialty service notes (p = 0.03). General pediatric service notes were significantly shorter (p < 0.001). We found no difference in file time (p = 0.23). Conclusion Medical student notes on pediatric subspecialty services scored significantly lower in quality and were longer compared to general pediatric services, demonstrating the need for a more tailored note-writing curriculum and note template based on service.
ABSTRACT
PURPOSE: To determine whether a formal note-writing session and note template for medical students (MS) during the Core Clerkship in Pediatrics (CCP) increase note quality, shortens note length, and decreases time of documentation. METHODS: In this single site, prospective study, MS participating in an 8-week CCP received a didactic session on note-writing in the electronic health record (EHR) and utilized EHR template developed for the study. We assessed note quality (measured by Physician Documentation Quality Instrument-9 [PDQI-9]), note length and note documentation time in this group compared to MS notes on the CCP in the prior academic year. We used descriptive statistics and Kruskal-Wallis tests for analysis. RESULTS: We analyzed 121 notes written by 40 students in the control group and 92 notes writing by 41 students in the intervention group. Notes from the intervention group were more "up to date," "accurate," "organized," and "comprehensible" compared to the control group (P = 0.02, P = 0.04, P = 0.01, and P = 0.02, respectively). Intervention group notes received higher cumulative PDQI-9 scores compared to the control group (median score 38 (IQR 34-42) versus 36 (IQR 32-40) out of 45 total, P = 0.04). Intervention group notes were approximately 35% shorter than the control group notes (median 68.5 lines vs 105 lines, P < 0.0001) and were signed earlier than control group notes (median file time 316 minute vs 352 minute, P = 0.02). CONCLUSIONS: The intervention successfully decreased note length, improved note quality based on standardized metrics, and reduced time to completion of note documentation.
Subject(s)
Students, Medical , Humans , Child , Prospective Studies , Electronic Health Records , Documentation , WritingABSTRACT
Cognitive hypnotherapy, also known as cognitive-behavioral hypnotherapy (CBH), is applied to the treatment of anxiety disorders. Specific techniques are described and illustrated. The research on CBH is discussed. CBH seems to be at least as effective as behavior therapy (BT) and cognitive-behavior therapy (CBT) treatments that employ imagery and relaxation techniques for anxiety disorders. However, more research is needed because of the lack of adequate studies comparing CBH with BT and CBT. Clinical implications and suggestions for future research are offered.
Subject(s)
Anxiety Disorders/therapy , Cognitive Behavioral Therapy/methods , Hypnosis/methods , Humans , Imagery, Psychotherapy/methods , Relaxation Therapy/methodsABSTRACT
We assessed breastfeeding outcomes for a cohort of infants born to women living with HIV (WLHIV) at an urban health care center in the United States. Ten infants were exclusively breastfed for a mean duration of 4.4 (1.0-8.6) months. All had negative HIV RNA PCRs at a median age of 16 months.
Subject(s)
Breast Feeding , HIV Infections , Cohort Studies , Female , HIV Infections/drug therapy , Humans , Infant , United StatesABSTRACT
Most (57.6%) of the extremely premature infants were born at a hospital without the availability of neonatal and MFM specialists, and 38.4% of the very premature were born at a hospital without a neonatologist. Increasing evidence indicates that delivery at a Level 3 facility results in better survival for these high risk infants. Health professionals, administrators and policy leaders could fashion new approaches to obstetrical care in Arkansas to improve neonatal outcomes.
Subject(s)
Certification/statistics & numerical data , Neonatology/statistics & numerical data , Neonatology/standards , Outcome Assessment, Health Care/statistics & numerical data , Premature Birth/mortality , Arkansas , Female , Hospitals/statistics & numerical data , Humans , Infant, Newborn , PregnancyABSTRACT
The coronavirus disease 2019 (COVID-19) pandemic has uncovered long-standing health disparities in marginalized communities, including racial and ethnic minorities and children with underlying medical and social problems. African Americans, Hispanics, and Native Americans have higher rates of COVID-19 infections and deaths than their population percentages in the United States. Unique populations of children, including children with developmental disabilities, children in the foster care system, children with chronic medical problems, and children who are homeless are particularly vulnerable to COVID-19 infection. This article explores how the COVID-19 pandemic superimposed on health disparities directly and indirectly affects children, adolescents, and their caregivers.
Subject(s)
COVID-19/epidemiology , Ethnicity/statistics & numerical data , Health Status Disparities , Healthcare Disparities/statistics & numerical data , Adolescent , Child , Humans , United StatesABSTRACT
Introduction Assessing clinical performance, such as managing respiratory distress, in clinical trainees is challenging yet important. Our objective was to describe and evaluate an integrative and iterative approach to developing a checklist measuring simulated clinical performance for infant respiratory distress. Methods We implemented a five-step modified Delphi process with an embedded qualitative component. An implementation period occurred followed by a second qualitative data collection. Validity evidence was collected throughout the process. Results A 19-item assessment checklist was developed for managing infant respiratory distress by medical student learners in a simulation-based setting. The iterative process provided content validity while the qualitative data provided response process validity. Cohen kappa was 0.82 indicating strong rater agreement. The assessment checklist was found to be easy to use and measure what was intended. Conclusion We developed an accurate and reliable assessment checklist for medical student learners in a simulation-based learning setting with high interrater reliability and validity evidence. Given its ease of use, we encourage medical educators and researchers to utilize this method to develop and implement assessment checklists for their interventions.
ABSTRACT
IMPORTANCE: The effects of SARS-CoV-2 infection on immune responses during pregnancy have not been systematically evaluated. OBJECTIVE: To assess the impact of SARS-CoV-2 infection during pregnancy on inflammatory and humoral responses in maternal and fetal samples and compare antibody responses to SARS-CoV-2 among pregnant and non-pregnant women. DESIGN: Immune responses to SARS-CoV-2 were analyzed using samples from pregnant and non-pregnant women who had either tested positive or negative for SARS-CoV-2. We measured, proinflammatory and placental cytokine mRNAs, neonatal Fc receptor (FcRn) receptor expression, and tetanus antibody transfer in maternal and cord blood samples. Additionally, we measured anti-spike (S) IgG, anti-S-receptor binding domain (RBD) IgG, and neutralizing antibody (nAb) responses to SARS-CoV-2 in serum or plasma collected from non-pregnant women, pregnant women, and cord blood. SETTING: Johns Hopkins Hospital (JHH). PARTICIPANTS: Pregnant women were recruited through JHH outpatient obstetric clinics and the JHH Labor & Delivery unit. Non-pregnant women were recruited after receiving outpatient SARS-CoV-2 testing within Johns Hopkins Health System, USA. Adult non-pregnant women with positive RT-PCR results for SARS-CoV-2, within the age range of 18-48 years, were included in the study. EXPOSURES: SARS-CoV-2. MAIN OUTCOMES AND MEASURES: Participant demographic characteristics, antibody titers, cytokine mRNA expression, and FcRn receptor expression. RESULTS: SARS-COV-2 positive pregnant women expressed more IL1ß , but not IL6 , in blood samples collected within 14 days versus > 14 days after a confirmed SARS-CoV-2 test, with similar patterns observed in the fetal side of placentas, particularly among asymptomatic pregnant women. Pregnant women with confirmed SARS-CoV-2 infection also had reduced anti-S-RBD IgG titers and were less likely to have detectable nAb as compared with non-pregnant women. Although SARS-CoV-2 infection did not disrupt FcRn expression in the placenta, maternal transfer of nAb was inhibited by SARS-CoV-2 infection during pregnancy. CONCLUSIONS AND RELEVANCE: SARS-CoV-2 infection during pregnancy was characterized by placental inflammation and reduced antiviral antibody responses, which may impact the efficacy of COVID-19 therapeutics in pregnancy. The long-term implications of placental inflammation for neonatal health also requires greater consideration.
ABSTRACT
IMPORTANCE: The maxillary labial frenulum and its potential contribution to breastfeeding difficulty may substantially affect public health. However, objective studies of the frenulum are limited. OBJECTIVE: To measure the variations in length, thickness, and attachments of the maxillary labial frenulum in healthy newborns and to identify which anatomic measurements could be used in further research investigating the maxillary labial frenulum. DESIGN, SETTING, AND PARTICIPANTS: This prospective cross-sectional study conducted measurements on images of maxillary labial frenula captured by digital photography from 150 healthy newborns admitted to the newborn nursery at a tertiary care children's hospital in Maryland between September 1, 2017, and April 1, 2018. MAIN OUTCOMES AND MEASURES: The primary outcome was the measurement of numerous frenulum morphologic components. RESULTS: Of 150 newborns enrolled, 77 were female, the mean (SD) gestational age was 38.60 (1.72) weeks, and the mean (SD) birth weight was 3180 (570) g. The means and SDs of the morphologic components of the frenulum with the broadest distributions, which were most helpful in differentiating degrees of lip tethering, included the following: alveolar edge to frenulum gingival attachment, 1.53 (0.85) mm; frenulum length on stretch, 5.19 (1.68) mm; frenulum gingival attachment thickness, 0.84 (0.36) mm; frenulum labial attachment thickness, 2.83 (1.33) mm; and the percentage of free lip to total lip length, 87.38% (7.67%). Gingival attachment mean (SD) thickness differed between late-preterm (0.69 [0.24] mm) and term (0.88 [0.37] mm) infants (Cohen d, -0.52; 95% CI, -0.94 to -0.10). CONCLUSIONS AND RELEVANCE: To our knowledge, this cross-sectional study was the first to objectively measure the numerous morphologic components of the upper lip anatomy in healthy newborns. Variations in maxillary labial frenulum morphology were identified, and some combination of the stated measurements may be used to create a more robust classification system to advance quality research in the association of lip-tie with breastfeeding difficulty.
Subject(s)
Cesarean Section/statistics & numerical data , Medicaid/statistics & numerical data , Pregnancy Complications/epidemiology , Pregnancy Complications/prevention & control , Reimbursement, Incentive/statistics & numerical data , Arkansas/epidemiology , Female , Humans , Pregnancy , Prevalence , Risk Factors , United States/epidemiologyABSTRACT
Zika virus was considered an innocent pathogen while restricted to the African and Asian population; however, after reaching the Americas in March 2015, it became a global threat. Despite usually causing mild or no symptoms in infected adults, Zika virus displays a different behavior toward fetuses. When infected during gestation, fetuses have their immature neural cells killed by the virus and consequently have devastating findings at birth. In the past year the drastic effects of Zika virus infection in newborns include neurological, ophthalmological, audiological, and skeletal abnormalities. These findings represent a new entity called congenital Zika syndrome. We summarize the ocular findings of congenital Zika Syndrome, as well as the current understanding of the illness, systemic manifestations, laboratory investigation, differential diagnosis, prophylaxis, and treatment for this disorder.
Subject(s)
Disease Outbreaks/statistics & numerical data , Eye Infections, Viral , Zika Virus Infection , Zika Virus , Eye Infections, Viral/epidemiology , Eye Infections, Viral/transmission , Eye Infections, Viral/virology , Global Health , Humans , Zika Virus Infection/epidemiology , Zika Virus Infection/transmission , Zika Virus Infection/virologyABSTRACT
There are a number of clinical reports and a body of research on the effectiveness of hypnotherapy in the treatment of irritable bowel syndrome (IBS). Likewise, there exists research demonstrating the efficacy of cognitive-behavioral therapy (CBT) in the treatment of IBS. However, there is little written about the integration of CBT and hypnotherapy in the treatment of IBS and a lack of clinical information about IBS-induced agoraphobia. This paper describes the etiology and treatment of IBS-induced agoraphobia. Cognitive, behavioral, and hypnotherapeutic techniques are integrated to provide an effective cognitive-behavioral hypnotherapy (CBH) treatment for IBS-induced agoraphobia. This CBH approach for treating IBS-induced agoraphobia is described and clinical data are reported.