Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine response in adults with predominantly antibody deficiency.

Background: Patients with predominantly antibody deficiency (PAD) have lower anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antibody levels after initial 2-dose SARS-CoV-2 vaccination than healthy controls do; however, the anti-spike antibody responses and neutralization function in patients with PAD following subsequent immunizations remain understudied. Objective: We sought to characterize anti-spike antibody responses in adults with PAD over the course of 5 SARS-CoV-2 vaccine doses and identify diagnostic and immunophenotypic risk factors for low antibody response. Methods: We evaluated anti-spike antibody levels in 117 adult patients with PAD and 192 adult healthy controls following a maximum of 5 SARS-CoV-2 immunizations. We assessed neutralization of the SARS-CoV-2 wild-type strain and the Omicron BA.5 variant and analyzed infection outcomes. Results: The patients with PAD had significantly lower mean anti-spike antibody levels after 3 SARS-CoV-2 vaccine doses than the healthy controls did (1,439.1 vs 21,890.4 U/mL [P < .0001]). Adults with secondary PAD, severe primary PAD, and high-risk immunophenotypes had lower mean anti-spike antibody levels following vaccine doses 2, 3, and/or 4 but not following vaccine dose 5. Compared with patients with mild and moderate PAD, patients with severe PAD had a higher rate of increase in anti-spike antibody levels over 5 immunizations. A strong positive correlation was observed between anti-spike antibody levels and neutralization of both the SARS-CoV-2 wild-type strain and the Omicron BA.5 variant. Most infections were managed on an outpatient basis. Conclusions: In all of the patients with PAD, anti-spike antibody levels increased with successive SARS-CoV-2 immunizations and were correlated with neutralization of both the SARS-CoV-2 wild-type strain and the Omicron BA.5 variant. Secondary PAD, severe primary PAD, and high-risk immunophenotypes were correlated with lower mean anti-spike antibody levels following vaccine doses 2 through 4. Patients with severe PAD had the highest rate of increase in anti-spike antibody levels over 5 immunizations. These data suggest a clinical benefit to sequential SARS-CoV-2 immunizations, particularly among high-risk patients with PAD.

The role of neighborhood deprivation in the cervicovaginal microbiota.

BACKGROUND: Lactobacillus-deficient cervicovaginal microbiota is associated with spontaneous preterm birth and is more common among Black individuals. Persistent racial segregation in the United States has led to differential neighborhood exposures by race that can affect pregnancy outcomes. The extent to which neighborhood exposures may explain racial differences in the cervicovaginal microbiota is unknown. OBJECTIVE: This study aimed to determine whether neighborhood deprivation, defined as material community deprivation, is associated with a Lactobacillus-deficient cervicovaginal microbiota in a prospective cohort of pregnant individuals. Our hypothesis was that racial differences in neighborhood deprivation may explain the higher prevalence of Lactobacillus-deficient cervicovaginal microbiota in Black birthing people. STUDY DESIGN: This study analyzed data from Motherhood and Microbiome, a prospective pregnancy cohort enrolled from prenatal clinics in a single hospital system 2013-2016 in which a Lactobacillus-deficient cervicovaginal microbiota was previously shown to be associated with spontaneous preterm birth. This study geocoded addresses to obtain census tract neighborhood deprivation data from the Brokamp Nationwide Community Deprivation Index that uses weighted proportions of poverty, income, public assistance, lack of health insurance, and vacant housing. Generalized linear mixed models quantified associations of deprivation with the cervicovaginal microbiota accounting for geographic clustering by census tract and potential confounders. Because of different distributions of neighborhood deprivation and the cervicovaginal microbiota, race-stratified models were used. Mediation analyses quantified the extent to which deprivation may contribute to racial differences in the cervicovaginal microbiota. RESULTS: Higher neighborhood deprivation was associated with a Lactobacillus-deficient cervicovaginal microbiota. Per standard deviation increment of deprivation, participants had 28% higher adjusted odds (adjusted odds ratio, 1.28; 95% confidence interval, 1.04-1.58) of a Lactobacillus-deficient microbiota. Black participants had higher odds of a Lactobacillus-deficient microbiota than White participants (adjusted odds ratio, 4.00; 95% confidence interval, 2.05-8.26), and mediation analysis revealed that deprivation accounted for 22% (P=.046) of that disparity. CONCLUSION: Neighborhood deprivation was associated with Lactobacillus-deficient cervicovaginal microbiota and may partially explain Black-White disparities in the cervicovaginal microbiota. Mechanistic studies to explore how environmental exposures modify the cervicovaginal microbiota are warranted to identify novel opportunities for future interventional strategies to prevent preterm birth. As the findings demonstrate a potential biological effect from neighborhood conditions, policies that drive urban planning should be explored to improve pregnancy outcomes.

Spatial Patterning of Spontaneous and Medically Indicated Preterm Birth in Philadelphia.

Preterm birth (PTB) remains a key public health issue that disproportionately affects Black individuals. Since spontaneous PTB (sPTB) and medically indicated PTB (mPTB) may have different causes and interventions, we quantified racial disparities for sPTB and mPTB, and we characterized the geographic patterning of these phenotypes, overall and according to race/ethnicity. We examined a pregnancy cohort of 83,952 singleton births at 2 Philadelphia hospitals from 2008-2020, and classified each PTB as sPTB or mPTB. We used binomial regression to quantify the magnitude of racial disparities between non-Hispanic Black and non-Hispanic White individuals, then generated small area estimates by applying a Bayesian model that accounts for small numbers and smooths estimates of PTB risk by borrowing information from neighboring areas. Racial disparities in both sPTB and mPTB were significant (relative risk of sPTB = 1.83, 95% confidence interval: 1.70, 1.98; relative risk of mPTB = 2.20, 95% confidence interval: 2.00, 2.42). The disparity was 20% greater in mPTB than sPTB. There was substantial geographic variation in PTB, sPTB, and mPTB risks and racial disparity. Our findings underscore the importance of distinguishing PTB phenotypes within the context of public health and preventive medicine. Future work should consider social and environmental exposures that may explain geographic differences in PTB risk and disparities.

Systematic Review of Pain Research Among Limited English Proficiency Patient Populations in Health care.

BACKGROUND: Pain remains a global health problem affecting all populations. There is limited knowledge, however, about the effect of limited English proficiency (LEP) on pain care and outcomes. AIM: This systematic review determines the current state of pain research for LEP populations. METHOD: We searched peer-reviewed studies in PubMed, CINAHL, PsychInfo, and Google Scholar from 1970 to 2021. Two authors independently screened abstracts and full texts, evaluated the quality of the studies using the Mixed Methods Appraisal Tool, and extracted study characteristics, content, and findings into Microsoft Excel. RESULTS: Twenty-five studies met our inclusion criteria. Of the 25 articles, 15 were quantitative, three were mixed methods, five were qualitative, one was quasi-experimental, and one was a randomized controlled trial. Four studies addressed all items of the Mixed Methods Appraisal Tool. Most pain research among patients with LEP was conducted in the United States (n = 17) and in hospital settings (n = 16). The majority of studies focused on one language (n = 15) with Spanish (n = 8) being the most studied language. Sample sizes ranged from seven to 18,593. Studies focused on three main themes: pain communication (n = 14), pain management (n =5) and/or outcomes (n = 1), and pain prevalence (n = 3). CONCLUSIONS: The findings revealed that the pain research on LEP populations is still in its infancy, with varied areas of focus using descriptive research designs. More pain intervention research for LEP populations is needed to reduce pain disparities.

Characterizing patterns of substance use in trauma exposed youth.

OBJECTIVE: Previous work investigating the impact of childhood trauma on substance use and co-occurring psychiatric disorders has primarily been conducted in adults or on specific trauma types. This limits understanding of traumas impact in childhood and how different types of traumas play a role. We sought to characterize substance use in a sample of trauma-exposed youth in the context of psychiatric comorbidities. METHOD: 1152 youth from the Texas Childhood Trauma Research Network (TX-CTRN) that were exposed to at least one trauma meeting DSM-5 Criterion A were assessed for current substance use and psychiatric diagnoses. Latent class analysis was used to identify patterns of substance use. To characterize these patterns, we examined if demographics, number of trauma types experienced, or childhood psychiatric disorders predicted class membership. RESULTS: We identified four primary patterns of substance use: Non-use (66.1%), predominantly alcohol use (19.7%), predominantly cannabis use (4.5%), and polysubstance use (9.7%). Compared to the non-users, polysubstance users tended to be older, Non-Hispanic White, have experienced more types of trauma. They were also more likely to have fulfilled diagnostic criteria for suicidality and ADHD. Comparisons among the substance using classes were more nuanced. CONCLUSION: The findings highlight the need for universal assessments of trauma, substance misuse, and mental health symptoms in youth as the presence or absence of their co-occurrence has implications for treatment.

Evaluating and refining a pain quality information visualization tool with patients and interpreters to facilitate pain assessment in primary care settings.

Information visualization (InfoViz) tools offer a potential solution to pain communication challenges. Incongruencies in communication styles between patients with limited English proficiency (LEP), interpreters, and providers contribute to significant disparities in pain care and outcomes. This study's purpose is to evaluate and refine a culturally appropriate InfoViz pain quality assessment tool for LEP Hmong patients. We conducted a three-part iterative user-centered study with LEP Hmong, bilingual Hmong, and Hmong interpreters with (1) participatory design sessions to evaluate and refine pain infographics for inclusion on the tool, (2) card-sorting to organize the infographics to match the mental models of LEP patients, and (3) a tool assessment to identify which tool accurately represented LEP patients' mental models and was preferred in clinical settings. Fifty-five participants provided three common themes for pain infographics refinement: culturally-relevant colors, infographics resembling human anatomy, and action-specific squiggle lines. The card-sorting sessions revealed three organizational themes: sensation (n = 15; 71.4%), localization (n = 6; 28.6%), and severity of pain quality (n = 5; 24.3%). Most participants selected the localization as the most accurate tool and preferred it in clinical settings. Using a multi-step, user-centered approach resulted in a culturally appropriate pain InfoViz tool for LEP Hmong patients.

Associations of neighborhood social vulnerability with emergency department visits and readmissions among infants with bronchopulmonary dysplasia.

OBJECTIVES: To characterize associations of the CDC Social Vulnerability Index (SVI) with medically attended acute respiratory illness among infants with bronchopulmonary dysplasia (BPD). STUDY DESIGN: Retrospective cohort of 378 preterm infants with BPD from a single center. Multivariable logistic regression quantified associations of SVI with medically attended acute respiratory illness, defined as emergency department (ED) visits or hospital readmissions within a year after first hospital discharge. Mediation analysis quantified the extent to which differences in SVI may explain known Black-White disparities in medically attended acute respiratory illness. RESULTS: SVI was associated with medically attended respiratory illness (per SVI standard deviation increment, aOR 1.44, 95% CI: 1.17-1.78). Adjustment for race and ethnicity attenuated the association (aOR 1.27, 95% CI: 0.97-1.64). SVI significantly mediated 31% of the Black-White disparity in ED visits (p = 0.04). CONCLUSIONS: SVI was associated with, and may partially explain racial disparities in, medically attended acute respiratory illness among infants with BPD.

Assessing racial residential segregation as a risk factor for severe maternal morbidity.

PURPOSE: To measure associations of area-level racial and economic residential segregation with severe maternal morbidity (SMM). METHODS: We conducted a retrospective cohort study of births at two Philadelphia hospitals between 2018 and 2020 to analyze associations of segregation, quantified using the Index of Concentration at the Extremes (ICE), with SMM. We used stratified multivariable, multilevel, logistic regression models to determine whether associations of ICE with SMM varied by self-identified race or hospital catchment. RESULTS: Of the 25,979 patients (44.1% Black, 35.8% White), 1381 (5.3%) had SMM (Black [6.1%], White [4.4%]). SMM was higher among patients residing outside (6.3%), than inside (5.0%) Philadelphia (P < .001). Overall, ICE was not associated with SMM. However, ICErace (higher proportion of White vs. Black households) was associated with lower odds of SMM among patients residing inside Philadelphia (aOR 0.87, 95% CI: 0.80-0.94) and higher odds outside Philadelphia (aOR 1.12, 95% CI: 0.95-1.31). Moran's I indicated spatial autocorrelation of SMM overall (P < .001); when stratified, autocorrelation was only evident outside Philadelphia. CONCLUSIONS: Overall, ICE was not associated with SMM. However, higher ICErace was associated with lower odds of SMM among Philadelphia residents. Findings highlight the importance of hospital catchment area and referral patterns in spatial analyses of hospital datasets.

Soluble and cell-based markers of immune checkpoint inhibitor-associated nephritis.

BACKGROUND: Non-invasive biomarkers of immune checkpoint inhibitor-associated acute tubulointerstitial nephritis (ICI-nephritis) are urgently needed. Because ICIs block immune checkpoint pathways that include cytotoxic T lymphocyte antigen 4 (CTLA4), we hypothesized that biomarkers of immune dysregulationpreviously defined in patients with congenital CTLA4 deficiency, including elevated soluble interleukin-2 receptor alpha (sIL-2R) and flow cytometric cell-based markers of B and T cell dysregulation in peripheral blood may aid the diagnosis of ICI-nephritis. METHODS: A retrospective cohort of patients diagnosed with ICI-nephritis was compared with three prospectively enrolled control cohorts: ICI-treated controls without immune-related adverse events, patients not on ICIs with hemodynamic acute kidney injury (hemodynamic AKI), and patients not on ICIs with biopsy proven acute interstitial nephritis from other causes (non-ICI-nephritis). sIL-2R level and flow cytometric parameters were compared between groups using Wilcoxon rank sum test or Kruskal-Wallis test. Receiver operating characteristic curves were generated to define the accuracy of sIL-2R and flow cytometric biomarkers in diagnosing ICI-nephritis. The downstream impact of T cell activation in the affected kidney was investigated using archived biopsy samples to evaluate the gene expression of IL2RA, IL-2 signaling, and T cell receptor signaling in patients with ICI-nephritis compared with other causes of drug-induced nephritis, acute tubular injury, and histologically normal controls. RESULTS: sIL-2R level in peripheral blood was significantly higher in patients with ICI-nephritis (N=24) (median 2.5-fold upper limit of normal (ULN), IQR 1.9-3.3), compared with ICI-treated controls (N=10) (median 0.8-fold ULN, IQR 0.5-0.9, p<0.001) and hemodynamic AKI controls (N=6) (median 0.9-fold-ULN, IQR 0.7-1.1, p=0.008). A sIL-2R cut-off point of 1.75-fold ULN was highly diagnostic of ICI-nephritis (area under the curve >96%) when compared with either ICI-treated or hemodynamic AKI controls. By peripheral blood flow cytometry analysis, lower absolute CD8+T cells, CD45RA+CD8+ T cells, memory CD27+B cells, and expansion of plasmablasts were prominent features of ICI-nephritis compared with ICI-treated controls. Gene expressions for IL2RA, IL-2 signaling, and T cell receptor signaling in the kidney tissue with ICI-nephritis were significantly higher compared with controls. CONCLUSION: Elevated sIL-2R level and flow cytometric markers of both B and T cell dysregulation may aid the diagnosis of ICI-nephritis.

Acid exposure time is sensitive for detecting gastroesophageal reflux disease and is associated with long-term survival after lung transplant.

Gastroesophageal reflux disease (GERD) is common in patients who have undergone lung transplantation and is associated with poorer outcomes, but guidelines are lacking to direct management strategies in this population. We assessed the diagnostic yield of impedance metrics compared to pH-metry alone for detecting GERD among lung transplant recipients and evaluated their association with clinical outcomes. We performed a retrospective cohort study of consecutive patients who underwent lung transplantation. Demographic data, acid exposure time (AET), number of reflux episodes, mean nocturnal baseline impedance (MNBI), post-reflux swallowing-induced peristaltic wave index (PSPWI), and clinical outcomes including mortality were collected. The relationship between GERD metrics and clinical outcomes was assessed using Wilcoxon signed-rank test and Fisher's exact test as appropriate. Of the 76 patients studied, 29 (38%) had GERD based on abnormal AET after lung transplantation. One (1.3%) patient had GERD based on elevated number of reflux episodes and abnormal distal MNBI detected GERD in 19 (26%) patients, resulting in 62% sensitivity and 94% specificity. Two (2.6%) patients had normal PSPWI. Patients with low distal MNBI had significantly decreased forced expiratory volume in 1 second (FEV1) at 3-year posttransplant compared to those without low distal MNBI (P = 0.03). Three-year survival was significantly worse among patients with elevated AET (66.7% vs. 89.1%, P = 0.03) but not with low distal MNBI (68.4% vs. 84.3%, P = 0.18). Abnormal AET is more sensitive for detecting GERD than other reflux metrics studied and is associated with survival, suggesting pH-metry alone may be sufficient to guide GERD management after lung transplant.

Changes in prenatal testing during the COVID-19 pandemic.

Objective: The coronavirus disease 2019 (COVID-19) pandemic disrupted healthcare delivery, including prenatal care. The study objective was to assess if timing of routine prenatal testing changed during the COVID-19 pandemic. Methods: Retrospective observational cohort study using claims data from a regional insurer (Highmark) and electronic health record data from two academic health systems (Penn Medicine and Yale New Haven) to compare prenatal testing timing in the pre-pandemic (03/10/2018-12/31/2018 and 03/10/2019-12/31/2019) and early COVID-19 pandemic (03/10/2020-12/31/2020) periods. Primary outcomes were second trimester fetal anatomy ultrasounds and gestational diabetes (GDM) testing. A secondary analysis examined first trimester ultrasounds. Results: The three datasets included 31,474 pregnant patients. Mean gestational age for second trimester anatomy ultrasounds increased from the pre-pandemic to COVID-19 period (Highmark 19.4 vs. 19.6 weeks; Penn: 20.1 vs. 20.4 weeks; Yale: 18.8 vs. 19.2 weeks, all p < 0.001). There was a detectable decrease in the proportion of patients who completed the anatomy survey <20 weeks' gestation across datasets, which did not persist at <23 weeks' gestation. There were no consistent changes in timing of GDM screening. There were significant reductions in the proportion of patients with first trimester ultrasounds in the academic institutions (Penn: 57.7% vs. 40.6% and Yale: 78.7% vs. 65.5%, both p < 0.001) but not Highmark. Findings were similar with multivariable adjustment. Conclusion: While some prenatal testing happened later in pregnancy during the pandemic, pregnant patients continued to receive appropriately timed testing. Despite disruptions in care delivery, prenatal screening remained a priority for patients and providers during the COVID-19 pandemic.

Changes in preterm birth during the COVID-19 pandemic by duration of exposure and race and ethnicity.

OBJECTIVE: We aimed to determine whether coronavirus-disease-2019 (COVID-19) pandemic exposure duration was associated with PTB and if the pandemic modified racial disparities. STUDY DESIGN: We analyzed Philadelphia births and replicated in New Haven. Compared to matched months in two prior years, we analyzed overall PTB, specific PTB phenotypes, and stillbirth. RESULTS: Overall, PTB was similar between periods with the following exceptions. Compared to pre-pandemic, early pregnancy (<14 weeks') pandemic exposure was associated with lower risk of PTB < 28 weeks' (aRR 0.60 [0.30-1.10]) and later exposure with higher risk (aRR 1.77 [0.78-3.97]) (interaction p = 0.04). PTB < 32 weeks' among White patients decreased during the pandemic, resulting in non-significant widening of the Black-White disparity from aRR 2.51 (95%CI: 1.53-4.16) to aRR 4.07 (95%CI: 1.56-12.01) (interaction P = 0.41). No findings replicated in New Haven. CONCLUSION: We detected no overall pandemic effects on PTB, but potential indirect benefits for some patients which could widen disparities remains possible.

Benzene and NO2 Exposure during Pregnancy and Preterm Birth in Two Philadelphia Hospitals, 2013-2017.

Infants born preterm are at risk of neonatal morbidity and mortality. Preterm birth (PTB) can be categorized as either spontaneous (sPTB) or medically indicated (mPTB), resulting from distinct pathophysiologic processes such as preterm labor or preeclampsia, respectively. A growing body of literature has demonstrated the impacts of nitrogen dioxide (NO2) and benzene exposure on PTB, though few studies have investigated how these associations may differ by PTB subtype. We investigated the associations of NO2 and benzene exposure with sPTB and mPTB among 18,616 singleton live births at two Philadelphia hospitals between 2013 and 2017. Residential NO2 exposure was estimated using a land use regression model and averaged over the patient's full pregnancy. Benzene exposure was estimated at the census tract level using National Air Toxics Assessment (NATA) exposure data from 2014. We used logistic mixed-effects models to calculate odds ratios for overall PTB, sPTB, and mPTB separately, adjusting for patient- and tract-level confounders. Given the known racial segregation and PTB disparities in Philadelphia, we also examined race-stratified models. Counter to the hypothesis, neither NO2 nor benzene exposure differed by race, and neither were significantly associated with PTB or PTB subtypes. As such, these pollutants do not appear to explain the racial disparities in PTB in this setting.

Liver Stiffness by Transient Elastography Correlates With Degree of Portal Hypertension in Common Variable Immunodeficiency Patients With Nodular Regenerative Hyperplasia.

Nodular regenerative hyperplasia (NRH) is associated with high morbidity and mortality in patients with common variable immunodeficiency (CVID). While liver biopsy is the gold standard for NRH diagnosis, a non-invasive technique could facilitate early disease recognition, monitoring, and/or immune intervention. We performed a cross-sectional analysis of ultrasound-based transient elastography (TE) in patients with CVID to evaluate liver stiffness and compared this between patients with (N = 12) and without (N = 6) biopsy-proven NRH. Additionally, these data were compared to a cohort followed at our institution for non-alcoholic fatty liver disease (NAFLD) (N = 527), a disease for which TE has routine diagnostic use. Clinical and pathologic features of NRH were evaluated as correlates of liver stiffness, and receiver operating characteristic curves were used to define a liver stiffness cutoff with diagnostic utility for NRH among CVID patients. CVID patients with NRH had a more severe disease presentation compared to those without. This included increased autoinflammatory disease comorbidities, combined B-cell and T-cell dysfunction, and abnormal liver biochemistries (specifically an increased mean alkaline phosphatase level [proximal to TE, 250 vs. 100 U/L; p = 0.03; peak, 314 vs. 114 U/L; p = 0.02). Results of TE demonstrated a significantly elevated liver stiffness in CVID patients with NRH (mean 13.2 ± 6.2 kPa) as compared to both CVID patients without NRH (mean 4.6 ± 0.9 kPa) and non-CVID patients with NAFLD (mean 6.9 ± 5.5 kPa) (p < 0.01). No single or composite histopathologic feature of NRH correlated with liver stiffness including nodule size, nodule density, sinusoidal dilation, fibrosis, and/or lymphocytosis. In contrast, liver stiffness by TE was significantly correlated with clinical parameters of portal hypertension, including an elevated hepatic venous pressure gradient, an increased splenic longitudinal diameter, presence of varices, and presence of peripheral edema. A liver stiffness of greater than or equal to 6.2 kPa was a clinically significant cutoff for NRH in CVID patients. We propose that TE has diagnostic utility in CVID, particularly in the presence of immunophenotypic features such as combined B-cell and T-cell dysfunction, autoinflammatory comorbidities, and/or abnormal liver tests. Elevated liver stiffness by TE should raise suspicion for NRH in patients with CVID and prompt expedited evaluation by hepatology.

Second trimester short cervix is associated with decreased abundance of cervicovaginal lipid metabolites.

BACKGROUND: A short cervix is a risk factor for preterm birth. The molecular drivers of a short cervix remain elusive. Metabolites may function as mediators of pathologic processes. OBJECTIVE: We sought to determine if a distinct cervicovaginal metabolomic profile is associated with a short cervix (<25 mm) to unveil the potential mechanisms by which premature cervical remodeling leads to a short cervix. STUDY DESIGN: This was a secondary analysis of a completed prospective pregnancy cohort. Cervicovaginal fluid was obtained between 20 and 24 weeks' gestation. The participants selected for metabolomic profiling were frequency-matched by birth outcome and cervicovaginal microbiota profile. This analysis included 222 participants with cervical length measured. A short cervix was defined as one having length <25 mm, as measured by transvaginal ultrasound. Unpaired t-tests were performed with a Bonferroni correction for multiple comparisons. RESULTS: There were 27 participants with a short cervix, and 195 with normal cervical length. Of the 637 metabolites detected, 26 differed between those with a short cervix and those with normal cervical lengths; 22 were decreased, of which 21 belonged to the lipid metabolism pathway (all P<.000079). Diethanolamine, erythritol, progesterone, and mannitol or sorbitol were increased in the cases of short cervix. Among participants with Lactobacillus-deficient microbiota, only diethanolamine and mannitol or sorbitol differed between short cervix (n=17) and normal cervical length (n=75), both increased. CONCLUSION: A short cervix is associated with decreased cervicovaginal lipid metabolites, particularly sphingolipids. This class of lipids stabilizes cell membranes and protects against environmental exposures. Increased diethanolamine-an immunostimulatory xenobiotic-is associated with a short cervix. These observations begin to identify the potential mechanisms by which modifiable environmental factors may invoke cell damage in the setting of biological vulnerability, thus promoting premature cervical remodeling in spontaneous preterm birth.

Response to Severe Acute Respiratory Syndrome Coronavirus 2 Initial Series and Additional Dose Vaccine in Patients With Predominant Antibody Deficiency.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with predominant antibody deficiency (PAD) is associated with high morbidity, yet data regarding the response to SARS-CoV-2 immunization in PAD patients, including additional dose vaccine, are limited. OBJECTIVE: To characterize antibody response to SARS-CoV-2 vaccine in PAD patients and define correlates of vaccine response. METHODS: We assessed the levels and function of anti-SARS-CoV-2 antibodies in 62 PAD patients compared with matched healthy controls at baseline, at 4 to 6 weeks after the initial series of immunization (a single dose of Ad26.COV2.S [Janssen] or two doses of BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna]), and at 4 to 6 weeks after an additional dose immunization, if received. RESULTS: After the initial series of SARS-CoV-2 vaccination, PAD patients had lower mean anti-spike antibody levels compared with matched healthy controls (140.1 vs 547.3 U/mL; P = .02). Patients with secondary PAD (eg, B-cell depletion therapy was used) and those with severe primary PAD (eg, common variable immunodeficiency with autoinflammatory complications) had the lowest mean anti-spike antibody levels. Immune correlates of a low anti-spike antibody response included low CD4+ T helper cells, low CD19+ total B cells, and low class-switched memory (CD27+IgD/M-) B cells. In addition, a low (<100 U/mL) anti-spike antibody response was associated with prior exposure to B-cell depletion therapy, both at any time in the past (odds ratio = 5.5; confidence interval, 1.5-20.4; P = .01) and proximal to vaccination (odds ratio = 36.4; confidence interval, 1.7-791.9; P = .02). Additional dose immunization with an mRNA vaccine in a subset of 31 PAD patients increased mean anti-spike antibody levels (76.3 U/mL before to 1065 U/mL after the additional dose; P < .0001). CONCLUSIONS: Patients with secondary and severe primary PAD, characterized by low T helper cells, low B cells, and/or low class-switched memory B cells, were at risk for low antibody response to SARS-CoV-2 immunization, which improved after an additional dose vaccination in most patients.

Why iPlay: The Relationships of Autistic and Schizotypal Traits With Patterns of Video Game Use.

Video games are popular and ubiquitous aspects of human culture, but their relationships to psychological and neurophysiological traits have yet to be analyzed in social-evolutionary frameworks. We examined the relationships of video game usage, motivations, and preferences with autistic and schizotypal traits and two aspects of neurophysiology, reaction time and targeting time. Participants completed the Autism Quotient, Schizotypal Personality Questionnaire, a Video Game Usage Questionnaire, and two neurophysiological tasks. We tested in particular the hypotheses, motivated by theory and previous work, that: (1) participants with higher autism scores would play video games more, and participants with higher schizotypy scores would play video games less; and (2) autism and positive schizotypy would be associated with opposite patterns of video game use, preferences and motivations. Females, but not males, with higher autism scores played more video games, and exhibited evidence of relatively male-typical video game genre preferences and motivations. By contrast, positive schizotypy was associated with reduced video game use in both genders, for several measures of game use frequency. In line with previous findings, males played video game more than females did overall, preferred action video games, and exhibited faster reaction and targeting times. Females preferred Puzzle and Social Simulation games. Faster reaction and targeting times were associated with gaming motives related to skill development and building behavior. These findings show that gaming use and patterns reflect aspects of psychology, and gender, related to social cognition and imagination, as well as aspects of neurophysiology. More generally, the results suggest that video game use is notably affected by levels of autistic and schizotypal traits, and that video games may provide an evolutionarily novel medium for imaginative play in which immersive play experiences can be decoupled from social interaction.

Racial, Ethnic, and Socioeconomic Disparities in Access to Transcatheter Aortic Valve Replacement Within Major Metropolitan Areas.

Importance: Despite the benefits of high-technology therapeutics, inequitable access to these technologies may generate disparities in care. Objective: To examine the association between zip code-level racial, ethnic, and socioeconomic composition and rates of transcatheter aortic valve replacement (TAVR) among Medicare patients living within large metropolitan areas with TAVR programs. Design, Setting, and Participants: This multicenter, nationwide cross-sectional analysis of Medicare claims data between January 1, 2012, and December 31, 2018, included beneficiaries of fee-for-service Medicare who were 66 years or older living in the 25 largest metropolitan core-based statistical areas. Exposure: Receipt of TAVR. Main Outcomes and Measures: The association between zip code-level racial, ethnic, and socioeconomic composition and rates of TAVR per 100 000 Medicare beneficiaries. Results: Within the studied metropolitan areas, there were 7590 individual zip codes. The mean (SD) age of Medicare beneficiaries within these areas was 71.4 (2.0) years, a mean (SD) of 47.6% (5.8%) of beneficiaries were men, and a mean (SD) of 4.0% (7.0%) were Asian, 11.1% (18.9%) were Black, 8.0% (12.9%) were Hispanic, and 73.8% (24.9%) were White. The mean number of TAVRs per 100 000 Medicare beneficiaries by zip code was 249 (IQR, 0-429). For each $1000 decrease in median household income, the number of TAVR procedures performed per 100 000 Medicare beneficiaries was 0.2% (95% CI, 0.1%-0.4%) lower (P = .002). For each 1% increase in the proportion of patients who were dually eligible for Medicaid services, the number of TAVR procedures performed per 100 000 Medicare beneficiaries was 2.1% (95% CI, 1.3%-2.9%) lower (P < .001). For each 1-unit increase in the Distressed Communities Index score, the number of TAVR procedures performed per 100 000 Medicare beneficiaries was 0.4% (95% CI, 0.2%-0.5%) lower (P < .001). Rates of TAVR were lower in zip codes with higher proportions of patients of Black race and Hispanic ethnicity, despite adjusting for socioeconomic markers, age, and clinical comorbidities. Conclusions and Relevance: Within major metropolitan areas in the US with TAVR programs, zip codes with higher proportions of Black and Hispanic patients and those with greater socioeconomic disadvantages had lower rates of TAVR, adjusting for age and clinical comorbidities. Whether this reflects a different burden of symptomatic aortic stenosis by race and socioeconomic status or disparities in use of TAVR requires further study.

Socioeconomic and Geographic Characteristics of Hospitals Establishing Transcatheter Aortic Valve Replacement Programs, 2012-2018.

BACKGROUND: Despite the benefits of novel therapeutics, inequitable diffusion of new technologies may generate disparities. We examined the growth of transcatheter aortic valve replacement (TAVR) in the United States to understand the characteristics of hospitals that developed TAVR programs and the socioeconomic status of patients these hospitals served. METHODS: We identified fee-for-service Medicare beneficiaries aged 66 years or older who underwent TAVR between January 1, 2012, and December 31, 2018, and hospitals that developed TAVR programs (defined as performing ≥10 TAVRs over the study period). We used linear regression models to compare socioeconomic characteristics of patients treated at hospitals that did and did not establish TAVR programs and described the association between core-based statistical area level markers of socioeconomic status and TAVR rates. RESULTS: Between 2012 and 2018, 583 hospitals developed new TAVR programs, including 572 (98.1%) in metropolitan areas, and 293 (50.3%) in metropolitan areas with preexisting TAVR programs. Compared with hospitals that did not start TAVR programs, hospitals that did start TAVR programs treated fewer patients with dual eligibility for Medicaid (difference of -2.83% [95% CI, -3.78% to -1.89%], P≤0.01), higher median household incomes (difference $2447 [95% CI, $1348-$3547], P=0.03), and from areas with lower distressed communities index scores (difference -4.02 units [95% CI, -5.43 to -2.61], P≤0.01). After adjusting for the age, clinical comorbidities, race and ethnicity and socioeconomic status, areas with TAVR programs had higher rates of TAVR and TAVR rates per 100 000 Medicare beneficiaries were higher in core-based statistical areas with fewer dual eligible patients, higher median income, and lower distressed communities index scores. CONCLUSIONS: During the initial growth phase of TAVR programs in the United States, hospitals serving wealthier patients were more likely to start programs. This pattern of growth has led to inequities in the dispersion of TAVR, with lower rates in poorer communities.

Course of tic disorders over the lifespan.

PURPOSE OF REVIEW: To summarize and update information on the course of tic disorders from childhood through later life. RECENT FINDINGS: Tics tend to improve substantially over the first year after they appear. However, contrary to widespread opinion, tics usually last longer than one year, though usually at minimal severity. Tics often wane to clinical insignificance over the teen years, possibly resurging occasionally over the lifespan. However, in an important minority of patients, tics remain clinically relevant throughout life. Tics rarely first come to clinical attention later in adulthood, but new reports describe additional such cases. SUMMARY: Recent publications have shown tics to persist past a few months more often than previously thought, though often at minimal severity, and recurrence after an asymptomatic period is common. The safety and efficacy of behavior therapy for tics, together with prospective indicators of early prognosis, make feasible the possibility of bettering the lifetime course of tic disorders with early intervention.