Efficacy and Safety of an Ad26.RSV.preF-RSV preF Protein Vaccine in Older Adults.

BACKGROUND: Respiratory syncytial virus (RSV) can cause serious lower respiratory tract disease in older adults, but no licensed RSV vaccine currently exists. An adenovirus serotype 26 RSV vector encoding a prefusion F (preF) protein (Ad26.RSV.preF) in combination with RSV preF protein was previously shown to elicit humoral and cellular immunogenicity. METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 2b, proof-of-concept trial to evaluate the efficacy, immunogenicity, and safety of an Ad26.RSV.preF-RSV preF protein vaccine. Adults who were 65 years of age or older were randomly assigned in a 1:1 ratio to receive vaccine or placebo. The primary end point was the first occurrence of RSV-mediated lower respiratory tract disease that met one of three case definitions: three or more symptoms of lower respiratory tract infection (definition 1), two or more symptoms of lower respiratory tract infection (definition 2), and either two or more symptoms of lower respiratory tract infection or one or more symptoms of lower respiratory tract infection plus at least one systemic symptom (definition 3). RESULTS: Overall, 5782 participants were enrolled and received an injection. RSV-mediated lower respiratory tract disease meeting case definitions 1, 2, and 3 occurred in 6, 10, and 13 vaccine recipients and in 30, 40, and 43 placebo recipients, respectively. Vaccine efficacy was 80.0% (94.2% confidence interval [CI], 52.2 to 92.9), 75.0% (94.2% CI, 50.1 to 88.5), and 69.8% (94.2% CI, 43.7 to 84.7) for case definitions 1, 2, and 3, respectively. After vaccination, RSV A2 neutralizing antibody titers increased by a factor of 12.1 from baseline to day 15, a finding consistent with other immunogenicity measures. Percentages of participants with solicited local and systemic adverse events were higher in the vaccine group than in the placebo group (local, 37.9% vs. 8.4%; systemic, 41.4% vs. 16.4%); most adverse events were mild to moderate in severity. The frequency of serious adverse events was similar in the vaccine group and the placebo group (4.6% and 4.7%, respectively). CONCLUSIONS: In adults 65 years of age or older, Ad26.RSV.preF-RSV preF protein vaccine was immunogenic and prevented RSV-mediated lower respiratory tract disease. (Funded by Janssen Vaccines and Prevention; CYPRESS ClinicalTrials.gov number, NCT03982199.).

Phase 1/2a Safety and Immunogenicity of an Adenovirus 26 Vector Respiratory Syncytial Virus (RSV) Vaccine Encoding Prefusion F in Adults 18-50 Years and RSV-Seropositive Children 12-24 Months.

BACKGROUND: Respiratory syncytial virus (RSV) remains a leading cause of pediatric morbidity, with no approved vaccine. We assessed the safety and immunogenicity of the Ad26.RSV.preF vaccine candidate in adults and children. METHODS: In this randomized, double-blind, phase 1/2a, placebo-controlled study, 12 adults (18-50 years) and 36 RSV-seropositive children (12-24 months) were randomized 2:1 to Ad26.RSV.preF (1 × 1011 viral particles [vp] for adults, 5 × 1010 vp for children) or placebo, at day 1 and 29, with 6-month immunogenicity and 1-year safety follow-up. Respiratory syncytial virus infection was an exploratory outcome in children. RESULTS: In adults, solicited adverse events (AEs) were generally mild to moderate, with no serious AEs. In children, no vaccination-related serious AEs were reported; fever was reported in 14 (58.3%) Ad26.RSV.preF recipients. Baseline pediatric geometric mean titers for RSV A2 neutralization increased from 121 (95% confidence interval [CI], 76-191) to 1608 (95% CI, 730-3544) at day 29, and 2235 (95% CI, 1586-3150) at day 57, remaining elevated over 7 months. Respiratory syncytial virus infection was confirmed in fewer children receiving Ad26.RSV.preF (1, 4.2%) than placebo (5, 41.7%). CONCLUSIONS: Ad26.RSV.preF demonstrated immunogenicity in healthy adults and toddlers, with no safety concerns raised. Evaluations in RSV-seronegative children are underway.

A Double-Blind, Randomized, Placebo-Controlled Phase 1 Study of Ad26.ZIKV.001, an Ad26-Vectored Anti-Zika Virus Vaccine.

BACKGROUND: Zika virus (ZIKV) may cause severe congenital disease after maternal-fetal transmission. No vaccine is currently available. OBJECTIVE: To assess the safety and immunogenicity of Ad26.ZIKV.001, a prophylactic ZIKV vaccine candidate. DESIGN: Phase 1 randomized, double-blind, placebo-controlled clinical study. (ClinicalTrials.gov: NCT03356561). SETTING: United States. PARTICIPANTS: 100 healthy adult volunteers. INTERVENTION: Ad26.ZIKV.001, an adenovirus serotype 26 vector encoding ZIKV M-Env, administered in 1- or 2-dose regimens of 5 × 1010 or 1 × 1011 viral particles (vp), or placebo. MEASUREMENTS: Local and systemic adverse events; neutralization titers by microneutralization assay (MN50) and T-cell responses by interferon-γ enzyme-linked immunospot and intracellular cytokine staining; and protectivity of vaccine-induced antibodies in a subset of participants through transfer in an exploratory mouse ZIKV challenge model. RESULTS: All regimens were well tolerated, with no safety concerns identified. In both 2-dose regimens, ZIKV neutralizing titers peaked 14 days after the second vaccination, with geometric mean MN50 titers (GMTs) of 1065.6 (95% CI, 494.9 to 2294.5) for 5 × 1010 vp and 956.6 (595.8 to 1535.8) for 1 × 1011 vp. Titers persisted for at least 1 year at a GMT of 68.7 (CI, 26.4-178.9) for 5 × 1010 vp and 87.0 (CI, 29.3 to 258.6) for 1 × 1011 vp. A 1-dose regimen of 1 × 1011 vp Ad26.ZIKV.001 induced seroconversion in all participants 56 days after the first vaccination (GMT, 103.4 [CI, 52.7 to 202.9]), with titers persisting for at least 1 year (GMT, 90.2 [CI, 38.4 to 212.2]). Env-specific cellular responses were induced. Protection against ZIKV challenge was observed after antibody transfer from participants into mice, and MN50 titers correlated with protection in this model. LIMITATION: The study was conducted in a nonendemic area, so it did not assess safety and immunogenicity in a flavivirus-exposed population. CONCLUSION: The safety and immunogenicity profile makes Ad26.ZIKV.001 a promising candidate for further development if the need reemerges. PRIMARY FUNDING SOURCE: Janssen Vaccines and Infectious Diseases.

Phase 1 Safety and Immunogenicity Study of a Respiratory Syncytial Virus Vaccine With an Adenovirus 26 Vector Encoding Prefusion F (Ad26.RSV.preF) in Adults Aged ≥60 Years.

BACKGROUND: Despite the high disease burden of respiratory syncytial virus (RSV) in older adults, there is no approved vaccine. We evaluated the experimental RSV vaccine, Ad26.RSV.preF, a replication-incompetent adenovirus 26 vector encoding the F protein stabilized in prefusion conformation. METHODS: This phase 1 clinical trial was performed in healthy adults aged ≥60 years. Seventy-two participants received 1 or 2 intramuscular injections of low-dose (LD; 5 × 1010 vector particles) or high-dose (HD; 1 × 1011 vector particles) Ad26.RSV.preF vaccine or placebo, with approximately 12 months between doses and 2-year follow-up for safety and immunogenicity outcomes. RESULTS: Solicited adverse events were reported by 44% of vaccine recipients and were transient and mild or moderate in intensity. No serious adverse events were related to vaccination. After the first vaccination, geometric mean titers for RSV-A2 neutralization increased from baseline (432 for LD and 512 for HD vaccine) to day 29 (1031 for LD and 1617 for HD). Pre-F-specific antibody geometric mean titers and median frequencies of F-specific interferon γ-secreting T cells also increased substantially from baseline. These immune responses were still maintained above baseline levels 2 years after immunization and could be boosted with a second immunization at 1 year. CONCLUSIONS: Ad26.RSV.preF (LD and HD) had an acceptable safety profile and elicited sustained humoral and cellular immune responses after a single immunization in older adults.

NLRP3 inflammasome induces chemotactic immune cell migration to the CNS in experimental autoimmune encephalomyelitis.

The NLRP3 inflammasome is a multiprotein complex consisting of three kinds of proteins, NLRP3, ASC, and pro-caspase-1, and plays a role in sensing pathogens and danger signals in the innate immune system. The NLRP3 inflammasome is thought to be involved in the development of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). However, the mechanism by which the NLRP3 inflammasome induces EAE is not clear. In this study, we found that the NLRP3 inflammasome played a critical role in inducing T-helper cell migration into the CNS. To gain migratory ability, CD4(+) T cells need to be primed by NLRP3 inflammasome-sufficient antigen-presenting cells to up-regulate chemotaxis-related proteins, such as osteopontin, CCR2, and CXCR6. In the presence of the NLRP3 inflammasome, dendritic cells and macrophages also induce chemotactic ability and up-regulate chemotaxis-related proteins, such as α4ß1 integrin, CCL7, CCL8, and CXCL16. On the other hand, reduced Th17 cell population size in immunized Nlrp3(-/-) and Asc(-/-) mice is not a determinative factor for their resistance to EAE. As currently applied in clinical interventions of MS, targeting immune cell migration molecules may be an effective approach in treating MS accompanied by NLRP3 inflammasome activation.

Anticipating early fatality: friends', schoolmates' and individual perceptions of fatality on adolescent risk behaviors.

Past research indicates that anticipating adverse outcomes, such as early death (fatalism), is associated positively with adolescents' likelihood of engaging in risky behaviors. Health researchers and criminologists have argued that fatalism influences present risk taking in part by informing individuals' motivation for delaying gratification for the promise of future benefits. While past findings highlight the association between the anticipation of early death and a number of developmental outcomes, no known research has assessed the impact of location in a context characterized by high perceptions of fatality. Using data from Add Health and a sample of 9,584 adolescents (51% female and 71% white) nested in 113 schools, our study builds upon prior research by examining the association between friends', school mates', and individual perceptions of early fatality and adolescent risk behaviors. We test whether friends' anticipation of being killed prior to age 21 or location in a school where a high proportion of the student body subscribes to attitudes of high fatality, is associated with risky behaviors. Results indicate that friends' fatalism is positively associated with engaging in violent delinquency, non-violent delinquency, and drug use after controlling for individual covariates and prior individual risk-taking. Although friends' delinquency accounts for much of the effect of friends' fatalism on violence, none of the potential intervening variables fully explain the effect of friends' fatalism on youth involvement in non-violent delinquency and drug use. Our results underscore the importance of friendship contextual effects in shaping adolescent risk-taking behavior and the very serious consequences perceptions of fatality have for adolescents' involvement in delinquency and drug use.

Psychiatry resident outpatient clinic supervision: how training directors are balancing patient care, education, and reimbursement.

OBJECTIVE: Recent literature on psychiatry resident outpatient clinic supervision is sparse. In designing outpatient supervision, training directors must balance optimization of patient care, education, and reimbursement. The authors sought to describe current practices for supervision within psychiatry resident outpatient clinics. METHODS: Directors of US psychiatric residency training programs were surveyed to examine methods used for supervision and billing in psychiatry resident outpatient clinics. RESULTS: Seventy of 183 (38%) training directors responded. Most programs utilize live supervision for medication management visits, but psychotherapy supervision is more varied. Billing practices are variable among programs. CONCLUSIONS: This report is intended to help training directors consider options for optimizing patient care and resident education in their outpatient clinics, while maintaining financial solvency. Ultimately, programs should have a way of ensuring all patient cases have some form of ongoing supervision, with possible modification based on training level, resident ability, patient acuity, and appointment type.

The role of stigma and spirituality on mental health help-Seeking behavior: an experimental approach.

BACKGROUND: The purpose of this research is to examine how social marketing messages can be developed to reduce the stigma associated with seeking help for mental health conditions. It also explores the role that spirituality plays in an individual's propensity to pursue help for mental health challenges. METHODS: A two-factor between-subjects experiment (ad message: destigmatizing and control × spirituality: high and low) between-subjects design was conducted with 275 participants from the millennial generational cohort in the United States. Responses were collected using an online consumer panel. RESULTS: Findings indicate that when presented with an advertisement that reduces the stigma associated with mental illness, individuals have a more favorable emotional reaction toward seeking help for a mental health condition. In addition, spirituality moderates the effect of advertising on mental health help-seeking behavior. Individuals with more intrinsic spirituality are more likely to seek care for a mental health issue, whereas those who report less intrinsic spirituality may need the help of destigmatizing messages. Specifically, individuals who report less intrinsic spirituality have more favorable attitudes toward an advertisement that destigmatizes mental illness, and as a result express greater intentions to seek care for a mental health condition. CONCLUSIONS: This research contributes to discussions centered on better understanding how to break down barriers to seeking aid for mental illness. Messaging which destigmatizes mental illness might start by targeting those who are less inclined to believe in transcendence. Moreover, since spirituality also includes a search for meaning, connectedness, and growth, such messaging might also be beneficial to those who are less likely to engage in activities which link the mind, body and spirit, such as meditation, mindfulness and yoga.

Effect of Pharmacy Involvement in Transitions of Care for Children With Medical Complexity.

OBJECTIVE: The purpose of this study is to evaluate the effects of pharmacy integration into care transitions for children with medical complexity. These children are at a higher risk for medication errors and adverse effects because of their complex medication regimens. In addition, care transitions increase the risk for medication errors, especially during hospital-to-home transitions. METHODS: This was a retrospective chart review of patients enrolled in a complex care clinic who were discharged between September 1, 2021, and December 31, 2021, and who had received a discharge medication evaluation. Intervention categories were predetermined (medication reconciliation and clinical interventions) and documented. The primary outcome was to quantify and characterize the types of interventions made by the pharmacist. Descriptive statistics were used for data analysis. Continuous data were analyzed using Wilcoxon rank sum test, and correlation was measured using Spearman correlation values. RESULTS: A total of 92 clinic encounters for 60 patients were included, with a median patient age of 7 years (IQR, 5-12.3), median length of stay of 3.2 days (IQR, 1.2-5.7), and a median number of 18 discharge medications (IQR, 14.8-25). A total of 283 interventions were made, consisting of 192 (68%) clinical interventions and 91 (32%) medication reconciliation interventions. In addition, 82 (89%) of the clinic encounters had at least one pharmacist intervention. CONCLUSIONS: Pharmacist evaluation of a patient's discharge medication regimen clarifies and better optimizes the patient's medication regimen.

Effectiveness of Screening for Household Gun Ownership in an Urban Primary Care Clinic.

Gun-related suicide and homicide are leading causes of death among children. Little is known about the effectiveness of screening for gun ownership in primary care. We examined positive gun ownership screens over a 2.5-year period in a pediatric primary care clinic. The main outcome was a positive screen for gun ownership. The main predictors included insurance type, neighborhood median income, number of clinic visits, and other social needs. Of 19 163 patients, 474 (2.5%) screened positive for gun ownership. Patients with private insurance and from higher income neighborhoods had 2 to 3 times higher odds of a positive screen. Patients with more visits and with food insecurity had approximately 2 to 4 times the odds of a positive screen for household gun ownership. In conclusion, the rate of positive gun ownership screens was very low and far below known gun ownership rates. Improved screening methods could better identify opportunities for gun safety advocacy.

Accuracy of the Exeter Hospitalizations-Office Visits-Medical Conditions-Extra Care-Social Concerns Index for Identifying Children With Complex Chronic Medical Conditions in the Clinical Setting.

OBJECTIVE: Our objective was to determine the accuracy of a point-of-care instrument, the Hospitalizations-Office Visits-Medical Conditions-Extra Care-Social Concerns (HOMES) instrument, in identifying patients with complex chronic conditions (CCCs) compared to an algorithm used to identify patients with CCCs within large administrative data sets. METHODS: We compared the HOMES to Feudtner's CCCs classification system. Using administrative algorithms, we categorized primary care patients at a children's hospital into 3 categories: no chronic conditions, non-complex chronic conditions, and CCCs. We randomly selected 100 patients from each category. HOMES scoring was completed for each patient. We performed an optimal cut-point analysis on 80% of the sample to determine which total HOMES score best identified children with ≥1 CCC and ≥2 CCCs. Using the optimal cut points and the remaining 20% of the study population, we determined the odds and area under the curve (AUC) of having ≥1 CCC and ≥2 CCCs. RESULTS: The median (interquartile range [IQR]) age was 4 (IQR: 0, 8). Using optimal cut points of ≥7 for ≥1 CCC and ≥11 for ≥2 CCCs, the odds of having ≥1 CCC was 19 times higher than lower scores (odds ratio [OR] 19.1 [95% confidence interval [CI]: 9.75, 37.5]) and of having ≥2 CCCs was 32 times higher (OR 32.3 [95% CI: 12.9, 50.6]). The AUCs were 0.76 for ≥1 CCC (sensitivity 0.82, specificity 0.80) and 0.74 for ≥2 CCCs (sensitivity 0.92, specificity 0.74). CONCLUSIONS: The HOMES accurately identified patients with CCCs.

Surfactant protein-A inhibits mycoplasma-induced dendritic cell maturation through regulation of HMGB-1 cytokine activity.

During pulmonary infections, a careful balance between activation of protective host defense mechanisms and potentially injurious inflammatory processes must be maintained. Surfactant protein A (SP-A) is an immune modulator that increases pathogen uptake and clearance by phagocytes while minimizing lung inflammation by limiting dendritic cell (DC) and T cell activation. Recent publications have shown that SP-A binds to and is bacteriostatic for Mycoplasma pneumoniae in vitro. In vivo, SP-A aids in maintenance of airway homeostasis during M. pneumoniae pulmonary infection by preventing an overzealous proinflammatory response mediated by TNF-α. Although SP-A was shown to inhibit maturation of DCs in vitro, the consequence of DC/SP-A interactions in vivo has not been elucidated. In this article, we show that the absence of SP-A during M. pneumoniae infection leads to increased numbers of mature DCs in the lung and draining lymph nodes during the acute phase of infection and, consequently, increased numbers of activated T and B cells during the course of infection. The findings that glycyrrhizin, a specific inhibitor of extracellular high-mobility group box-1 (HMGB-1) abrogated this effect and that SP-A inhibits HMGB-1 release from immune cells suggest that SP-A inhibits M. pneumoniae-induced DC maturation by regulating HMGB-1 cytokine activity.

Influencing controlled substance prescribing: attending and resident physician use of a state prescription monitoring program.

OBJECTIVE: The purpose of this study is to evaluate the influence of attending physician awareness and utilization of a state prescription monitoring program on resident physician behavior. DESIGN: Twenty-five attending physicians and 70 residents in Emergency Medicine, Internal Medicine, Neurology, Pediatrics, and Psychiatry completed an 11-item questionnaire assessing awareness and utilization of a state prescription drug monitoring program. RESULTS: Residents who used the system had, on average, a higher proportion of supervising attendings using the system; residents required to utilize the system had the highest proportion of attendings using the system. Overall, almost 90% of the physicians who utilized the system did so due to concerns surrounding prescription drug abuse. Over one third of attending physicians reported increasing the quantity or amount of medication prescribed after utilizing the system, while no residents reported similar outcomes. Through the behavioral influence of supervising attending physicians, residents were significantly more likely to utilize the system. If system utilization is desired, attendings should use the system and require resident participation.

Between a Rock and a Hard Place: COVID Concerns and Partnered U.S. Mothers' Employment during the COVID-19 Pandemic.

Shutdowns of in-person school and childcare in spring 2020 in response to the coronavirus disease 2019 (COVID-19) pandemic were associated with substantial reductions in mothers' labor force participation (LFP). By fall 2020, in-person school and daycare were more widely available, but mothers' LFP remained as low as it was in spring. Coincidently, by fall 2020, daily COVID deaths had also began to peak. Using unique panel survey data from partnered U.S. mothers (n = 263), the authors use structural equation modeling to analyze how mothers' concerns over COVID shaped their LFP in fall 2020. Findings show that mothers' COVID concerns were associated with reduced LFP via children's time at home, perceived stress, and remote work. Concerned mothers were more likely to keep children home, but this resulted in less paid work likely vis-à-vis work-family conflicts. The findings illuminate one reason mothers' LFP failed to rebound in fall 2020 despite increased access to in-person school and daycare.

Blimp-1/PRDM1 mediates transcriptional suppression of the NLR gene NLRP12/Monarch-1.

NLR (nucleotide-binding domain, leucine-rich repeat) proteins are intracellular regulators of host defense and immunity. One NLR gene, NLRP12 (NLR family, pyrin domain containing 12)/Monarch-1, has emerged as an important inhibitor of inflammatory gene expression in human myeloid cells. This is supported by genetic analysis linking the loss of a functional NLRP12 protein to hereditary periodic fever. NLRP12 transcription is diminished by specific TLR stimulation and myeloid cell maturation, consistent with its role as a negative regulator of inflammation. The NLRP12 promoter contains a novel Blimp-1 (B lymphocyte-induced maturation protein-1)/PRDM1 (PR domain-containing 1, with ZNF domain) binding site, and Blimp-1 reduces NLRP12 promoter activity, expression, and histone 3 acetylation. Blimp-1 associates with the endogenous NLRP12 promoter in a TLR-inducible manner and mediates the down-regulation of NLRP12 expression by TLR agonists. As expected, the expression of NLRP12 and Blimp-1 is inversely correlated. Analysis of Blimp-1(-/-) murine myeloid cells provides physiologic evidence that Blimp-1 reduces NLRP12 gene expression during cell differentiation. This demonstrates a novel role for Blimp-1 in the regulation of an NLR gene.

The role of surfactant protein A in bleomycin-induced acute lung injury.

RATIONALE: Surfactant protein A (SP-A) is a collectin family member that has multiple immunomodulatory roles in lung host defense. SP-A levels are altered in the bronchoalveolar lavage (BAL) fluid and serum of patients with acute lung injury and acute respiratory distress syndrome, suggesting the importance of SP-A in the pathogenesis of acute lung injury. OBJECTIVES: Investigate the role of SP-A in the murine model of noninfectious lung injury induced by bleomycin treatment. METHODS: Wild-type (WT) or SP-A deficient (SP-A(-/-)) mice were challenged with bleomycin, and various indices of lung injury were analyzed. MEASUREMENTS AND MAIN RESULTS: On challenge with bleomycin, SP-A(-/-) mice had a decreased survival rate as compared with WT mice. SP-A(-/-) mice had a higher degree of neutrophil-dominant cell recruitment and the expression of the inflammatory cytokines in BAL fluid than did WT mice. In addition, SP-A(-/-) mice had increased lung edema as assessed by the increased levels of intravenously injected Evans blue dye leaking into the lungs. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling and active caspase-3 staining suggested the increased apoptosis in the lung sections from SP-A(-/-) mice challenged with bleomycin. SP-A also specifically reduced bleomycin-induced apoptosis in mouse lung epithelial 12 cells in vitro. Moreover, intratracheal administration of exogenous SP-A rescued the phenotype of SP-A(-/-) mice in vivo. CONCLUSIONS: These data suggest that SP-A plays important roles in modulating inflammation, apoptosis, and epithelial integrity in the lung in response to acute noninfectious challenges.

Hospital-level compliance with asthma care quality measures at children's hospitals and subsequent asthma-related outcomes.

CONTEXT: The Children's Asthma Care (CAC) measure set evaluates whether children admitted to hospitals with asthma receive relievers (CAC-1) and systemic corticosteroids (CAC-2) and whether they are discharged with a home management plan of care (CAC-3). It is the only Joint Commission core measure applicable to evaluate the quality of care for hospitalized children. OBJECTIVES: To evaluate longitudinal trends in CAC measure compliance and to determine if an association exists between compliance and outcomes. DESIGN, SETTING, AND PATIENTS: Cross-sectional study using administrative data and CAC compliance data for 30 US children's hospitals. A total of 37,267 children admitted with asthma between January 1, 2008, and September 30, 2010, with follow-up through December 31, 2010, accounted for 45,499 hospital admissions. Hospital-level CAC measure compliance data were obtained from the National Association of Children's Hospitals and Related Institutions. Readmission and postdischarge emergency department (ED) utilization data were obtained from the Pediatric Health Information System. MAIN OUTCOME MEASURES: Children's Asthma Care measure compliance trends; postdischarge ED utilization and asthma-related readmission rates at 7, 30, and 90 days. RESULTS: The minimum quarterly CAC-1 and CAC-2 measure compliance rates reported by any hospital were 97.1% and 89.5%, respectively. Individual hospital CAC-2 compliance exceeded 95% for 97.9% of the quarters. Lack of variability in CAC-1 and CAC-2 compliance precluded examination of their association with the specified outcomes. Mean CAC-3 compliance was 40.6% (95% CI, 34.1%-47.1%) and 72.9% (95% CI, 68.8%-76.9%) for the initial and final 3 quarters of the study, respectively. The mean 7-, 30-, and 90-day postdischarge ED utilization rates were 1.5% (95% CI, 1.3%-1.6%), 4.3% (95% CI, 4.0%-4.5%), and 11.1% (95% CI, 10.5%-11.7%) and the mean quarterly 7-, 30-, and 90-day readmission rates were 1.4% (95% CI, 1.2%-1.6%), 3.1% (95% CI, 2.8%-3.3%), and 7.6% (95% CI, 7.2%-8.1%). There was no significant association between overall CAC-3 compliance (odds ratio [OR] for 5% improvement in compliance) and postdischarge ED utilization rates at 7 days (OR, 1.00; 95% CI, 0.98-1.02), 30 days (OR, 0.97; 95% CI, 0.90-1.04), and 90 days (OR, 0.96; 95% CI, 0.77-1.18). In addition, there was no significant association between overall CAC-3 compliance (OR for 5% improvement in compliance) and readmission rates at 7 days (OR, 1.00; 95% CI, 0.99-1.02), 30 days (OR, 0.99; 95% CI, 0.96-1.02), and 90 days (OR, 1.01; 95% CI, 0.90-1.12). CONCLUSION: Among children admitted to pediatric hospitals for asthma, there was high hospital-level compliance with CAC-1 and CAC-2 quality measures and moderate compliance with the CAC-3 measure but no association between CAC-3 compliance and subsequent ED visits and asthma-related readmissions.

Nonmarital Childbearing, Union History, and Women's Health at Midlife.

Despite high rates of nonmarital childbearing in the U.S., little is known about the health of women who have nonmarital births. We use data from the NLSY79 to examine differences in age 40 self-assessed health between women who had a premarital birth and those whose first birth occurred within marriage. We then differentiate women with a premarital first birth according to their subsequent union histories and estimate the effect of marrying or cohabiting versus remaining never-married on midlife self-assessed health, paying particular attention to the paternity status of the mother's partner and the stability of marital unions. To partially address selection bias, we employ multivariate propensity score techniques. Results suggest that premarital childbearing is negatively associated with midlife health for white and black (but not Hispanic) women. We find no evidence that these negative health consequences of nonmarital childbearing are mitigated by either marriage or cohabitation for black women. For other women, only enduring marriage to the biological father is associated with better health than remaining unpartnered.

Consequences of black exceptionalism? Interracial unions with blacks, depressive symptoms, and relationship satisfaction.

Using data from Wave 4 (2008) of the National Longitudinal Study of Adolescent Health (N = 7,466), we examine potential consequences of black exceptionalism in the context of interracial relationships among nonblack respondents. While increasing racial diversity and climbing rates of interracial unions have fostered the notion that racial boundaries within the United States are fading, our results add to the accumulating evidence that racial/ethnic boundaries persist in U.S. society. Results suggest that among non-Black respondents there is more stigma and disapproval attached to relationships with Blacks than there are to relationships with members of other racial/ethnic groups. Specifically, our results indicate that nonblack individuals with black partners have significantly more depressive symptoms and less relationship satisfaction than their counterparts with nonblack partners, regardless of respondent race and whether the nonblack partner is the same versus a different race from the respondent. Further, the relationship between partner race and depressive symptoms is partially and significantly mediated by relationship satisfaction.

Pharmacist Integration Into Care for Patients With Medical Complexity: An Intervention to Optimize Complex Therapeutic Regimens Through Medication Services.

Children with medical complexity have a significant impact on health care cost and outcomes. Children with medical complexity are at risk for substantial polypharmacy and inherent drug-related dangers. In this special article, we describe the integration of clinical pharmacy services into our clinic for children with medical complexity. We review the process that yields results by effectively managing patients' medications across the continuum of care while also possibly improving health care spending and outcomes.