Relations between discrimination, rejection sensitivity, negative affect, and decrements in problem-solving ability following social rejection: An experimental investigation.

INTRODUCTION: While negative affect and problem-solving deficits have been consistently linked to suicidal thoughts and behaviors, the latter are often conceptualized and studied as time- and/or context-invariant. Though requiring additional empirical support, theory suggests that discrimination may strengthen the relation between rejection sensitivity and increases in negative affect as well as declines in problem-solving abilities following rejection. The aim of the current study was to test this claim using a social rejection paradigm (i.e., Cyberball) with young adults experiencing past-month suicidal ideation. METHODS: The sample consisted of 50 participants. Lifetime discrimination and rejection sensitivity were assessed prior to Cyberball. Negative affect and problem-solving abilities were assessed pre- and post-Cyberball. SPSS and the PROCESS macro were used to test relations among variables of interest. RESULTS: Rejection sensitivity predicted greater problem-solving decrements, but not negative affect, following rejection among individuals who had experienced higher (vs. lower) levels of lifetime discrimination. CONCLUSION: Addressing rejection sensitivity and sources of discrimination within the context of treatment may reduce the impact of social rejection on problem-solving abilities among young adults at risk for suicide.

Interpersonal stress and proinflammatory activity in emerging adults with a history of suicide risk: A pilot study.

Interpersonal stress during adolescence and young adulthood can threaten healthy developmental trajectories. A "primed" proinflammatory response to acute stress may serve as an underlying process that results in negative outcomes for youth. The present pilot study examined the relation between interpersonal stress and two proinflammatory cytokines in a sample of 42 university-recruited emerging adults with recent suicidal thoughts and behaviors. Participants completed self-report measures of mood, suicidal thoughts and behaviors, recent peer-related stressors, and interpersonal sensitivity. They also participated in an acute laboratory social stress task and provided three saliva samples to measure their proinflammatory responses (IL-6 and TNF-α) to the stressor. Participants reported significant increases in sadness and exclusion, and significant decreases in inclusion, following task participation. Importantly, no participants reported an increase in or onset of suicidal thoughts. No significant associations between interpersonal stress and proinflammatory cytokines were found. Changes in affect during the task coupled with lack of increased suicidal thoughts indicate it is acceptable to use this exclusion and rejection paradigm with this population, with proper debriefing and positive mood induction procedures. Given all other nonsignificant associations, future research considerations are discussed, including impact of COVID-19 on task potency and incorporation of multiple stress response systems.

Facets of social problem-solving as moderators of the real-time relation between social rejection and negative affect in an at-risk sample.

Social rejection predicts negative affect, and theoretical work suggests that problem-solving deficits strengthen this relation in real-time. Nevertheless, few studies have explicitly tested this relation, particularly in samples at risk for suicide. This may be particularly important as social rejection and negative affect are significant predictors of suicide. The aim of the current study was to examine whether cognitive (i.e., perceiving problems as threats) and behavioral (i.e., avoidance) facets of problem-solving deficits moderated the real-time relation between social rejection and negative affect. The sample consisted of 49 young adults with past-month suicidal ideation. Demographic information, social problem-solving deficits, as well as depressive/anxiety symptoms and stress levels were assessed at baseline. Social rejection and negative affect were assessed using ecological momentary assessment over the following 28 days. Dynamic structural equation modeling was used to assess relations among study variables. After accounting for depressive/anxiety symptoms, stress levels, sex, and age, only avoidance of problems bolstered the real-time positive relation between social rejection severity and negative affect (b = 0.04, 95% credibility interval [0.003, 0.072]). Individuals with suicidal ideation who possess an avoidant problem-solving style may be particularly likely to experience heightened negative affect following social rejection and may benefit from instruction in problem-solving skills.

Trajectories of adolescent suicidal ideation and depressive symptoms during partial hospitalization: Clinical and demographic characteristics as predictors of change.

Partial hospital programs (PHPs) are a vital mental health service for youth at risk for suicide. Yet, few studies have examined trajectories of suicidal ideation and depressive symptoms, two important risk factors for suicidal behavior, over the course of care. Moreover, little is known about factors that may impact these trajectories among youth in PHPs. The present study examined trajectories of suicidal ideation and depressive symptoms, as well as clinical and demographic predictors of these changes, among youth enrolled in two PHPs. A sample of 253 youth (Mage = 15.3; SD = 1.4; range = 12-18; 68.8% female; 63.2% White; 75.1% non-Hispanic/Latino/a/x) completed repeated measures of suicidal ideation severity and depressive symptoms during treatment. Trajectories of these outcomes were examined using two separate latent growth models. Recent history of self-injurious behaviors and demographics were tested as predictors of trajectories using a taxonomic approach. Overall, suicidal ideation and depressive symptoms declined over the course of care. Sex, history of self-injury, and sexual identity were associated with variability in one or both trajectories of change. Results suggest individual variability in the rate of change among youth in PHPs. Such information may be used to aid in treatment planning and quality improvement efforts within PHPs. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Examination of proinflammatory activity as a moderator of the relation between momentary interpersonal stress and suicidal ideation.

INTRODUCTION: Peer-related interpersonal stress can increase risk for suicidal thoughts among adolescents and young adults. However, not all individuals who undergo peer-related interpersonal stressors experience suicidal thoughts. Heightened proinflammatory activity is one factor that may amplify the relation between interpersonal stress and suicidal thinking. METHODS: This pilot study examined the relation between interpersonal stress and suicidal ideation in real time, as well as whether proinflammatory cytokine (IL-6 and TNF-α) activity across a laboratory social stressor moderated this association in a sample of 42 emerging adults with recent suicidal ideation. Participants completed 28 days of 6×/daily ecological momentary assessment that assessed for suicidal ideation (presence vs. absence, ideation intensity), occurrence of negative peer events, and feelings of exclusion. RESULTS: There was a trend for within-person increases in feelings of exclusion to be associated with increases in concurrent suicidal ideation intensity. Additionally, within-person increases in negative peer events were associated with increased odds of subsequent suicidal ideation among individuals with very low IL-6 activity. However, this finding is considered preliminary. CONCLUSION: Interventions targeting perceptions of exclusion and increasing social support may be of benefit. However, findings require replication in larger samples, and thus must be interpreted with caution.

School-based self-management interventions for asthma among primary school children: a systematic review.

A Cochrane review of school-based asthma interventions (combining all ages) found improved health outcomes. Self-management skills, however, vary according to age. We assessed effectiveness of primary school-based self-management interventions and identified components associated with successful programmes in children aged 6-12 years. We updated the Cochrane search (March 2020) and included the Global Health database. Two reviewers screened, assessed risk-of-bias and extracted data. We included 23 studies (10,682 participants); four at low risk-of-bias. Twelve studies reported at least one positive result for an outcome of interest. All 12 positive studies reported parental involvement in the intervention, compared to two-thirds of ineffective studies. In 10 of the 12 positive studies, parental involvement was substantial (e.g. attending sessions; phone/video communication) rather than being provided with written information. School-based self-management intervention can improve health outcomes and substantial parental involvement in school-based programmes seemed important for positive outcomes among primary school children.

Interim Estimates of Vaccine Effectiveness of BNT162b2 and mRNA-1273 COVID-19 Vaccines in Preventing SARS-CoV-2 Infection Among Health Care Personnel, First Responders, and Other Essential and Frontline Workers - Eight U.S. Locations, December 2020-March 2021.

Messenger RNA (mRNA) BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccines have been shown to be effective in preventing symptomatic COVID-19 in randomized placebo-controlled Phase III trials (1,2); however, the benefits of these vaccines for preventing asymptomatic and symptomatic SARS-CoV-2 (the virus that causes COVID-19) infection, particularly when administered in real-world conditions, is less well understood. Using prospective cohorts of health care personnel, first responders, and other essential and frontline workers* in eight U.S. locations during December 14, 2020-March 13, 2021, CDC routinely tested for SARS-CoV-2 infections every week regardless of symptom status and at the onset of symptoms consistent with COVID-19-associated illness. Among 3,950 participants with no previous laboratory documentation of SARS-CoV-2 infection, 2,479 (62.8%) received both recommended mRNA doses and 477 (12.1%) received only one dose of mRNA vaccine.† Among unvaccinated participants, 1.38 SARS-CoV-2 infections were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) per 1,000 person-days.§ In contrast, among fully immunized (≥14 days after second dose) persons, 0.04 infections per 1,000 person-days were reported, and among partially immunized (≥14 days after first dose and before second dose) persons, 0.19 infections per 1,000 person-days were reported. Estimated mRNA vaccine effectiveness for prevention of infection, adjusted for study site, was 90% for full immunization and 80% for partial immunization. These findings indicate that authorized mRNA COVID-19 vaccines are effective for preventing SARS-CoV-2 infection, regardless of symptom status, among working-age adults in real-world conditions. COVID-19 vaccination is recommended for all eligible persons.

SARS-CoV-2-specific T cells are rapidly expanded for therapeutic use and target conserved regions of the membrane protein.

T-cell responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been described in recovered patients, and may be important for immunity following infection and vaccination as well as for the development of an adoptive immunotherapy for the treatment of immunocompromised individuals. In this report, we demonstrate that SARS-CoV-2-specific T cells can be expanded from convalescent donors and recognize immunodominant viral epitopes in conserved regions of membrane, spike, and nucleocapsid. Following in vitro expansion using a good manufacturing practice-compliant methodology (designed to allow the rapid translation of this novel SARS-CoV-2 T-cell therapy to the clinic), membrane, spike, and nucleocapsid peptides elicited interferon-γ production, in 27 (59%), 12 (26%), and 10 (22%) convalescent donors (respectively), as well as in 2 of 15 unexposed controls. We identified multiple polyfunctional CD4-restricted T-cell epitopes within a highly conserved region of membrane protein, which induced polyfunctional T-cell responses, which may be critical for the development of effective vaccine and T-cell therapies. Hence, our study shows that SARS-CoV-2 directed T-cell immunotherapy targeting structural proteins, most importantly membrane protein, should be feasible for the prevention or early treatment of SARS-CoV-2 infection in immunocompromised patients with blood disorders or after bone marrow transplantation to achieve antiviral control while mitigating uncontrolled inflammation.

T-Cell Therapeutics Targeting Human Parainfluenza Virus 3 Are Broadly Epitope Specific and Are Cross Reactive With Human Parainfluenza Virus 1.

Human Parainfluenza Virus-3 (HPIV3) causes severe respiratory illness in immunocompromised patients and lacks approved anti-viral therapies. A phase I study of adoptively transferred virus-specific T-cells (VSTs) targeting HPIV3 following bone marrow transplantation is underway (NCT03180216). We sought to identify immunodominant epitopes within HPIV3 Matrix protein and their cross-reactivity against related viral proteins. VSTs were generated from peripheral blood of healthy donors by ex-vivo expansion after stimulation with a 15-mer peptide library encompassing HPIV3 matrix protein. Epitope mapping was performed using IFN-γ ELIspot with combinatorial peptide pools. Flow cytometry was used to characterize products with intracellular cytokine staining. In 10 VST products tested, we discovered 12 novel immunodominant epitopes. All products recognized an epitope at the C-terminus. On IFN-γ ELISpot, individual peptides eliciting activity demonstrated mean IFN-γ spot forming units per well (SFU)/1x105 cells of 115.5 (range 24.5-247.5). VST products were polyfunctional, releasing IFN-γ and TNF-α in response to identified epitopes, which were primarily HLA Class II restricted. Peptides from Human Parainfluenza Virus-1 corresponding to the HPIV3 epitopes showed cross-reactivity for HPIV1 in 11 of 12 tested epitopes (mean cross reactivity index: 1.19). Characterization of HPIV3 epitopes may enable development of third-party VSTs to treat immune suppressed patients with HPIV infection.

Virus-Specific T Cells: Current and Future Use in Primary Immunodeficiency Disorders.

Viral infections are common and can be potentially fatal in patients with primary immunodeficiency disorders (PIDDs). Because viral susceptibility stems from poor to absent T-cell function in most patients with moderate to severe forms of PIDD, adoptive immunotherapy with virus-specific T cells (VSTs) has been used to combat viral infections in the setting of hematopoietic stem cell transplantation in multiple clinical trials. Most trials to date have targeted cytomegalovirus, EBV, and adenovirus either alone or in combination, although newer trials have expanded the number of targeted pathogens. Use of banked VSTs produced from third-party donors has also been studied as a method of expanding access to this therapy. Here we review the clinical experience with VST therapy for patients with PIDDs as well as future potential targets and approaches for the use of VSTs to improve clinical outcomes for this specific patient population.

Interventions for autumn exacerbations of asthma in children.

BACKGROUND: Asthma exacerbations in school-aged children peak in autumn, shortly after children return to school following the summer holiday. This might reflect a combination of risk factors, including poor treatment adherence, increased allergen and viral exposure, and altered immune tolerance. Since this peak is predictable, interventions targeting modifiable risk factors might reduce exacerbation-associated morbidity and strain upon health resources. The peak occurs in September in the Northern Hemisphere and in February in the Southern Hemisphere. OBJECTIVES: To assess the effects of pharmacotherapy and behavioural interventions enacted in anticipation of school return during autumn that are designed to reduce asthma exacerbations in children during this period. SEARCH METHODS: We searched the Cochrane Airways Group Trials Register, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, reference lists of primary studies and existing reviews, and manufacturers' trial registries (Merck, Novartis and Ono Parmaceuticals). We searched databases from their inception to 1 December 2017, and imposed no restriction on language of publication. SELECTION CRITERIA: We included all randomised controlled trials comparing interventions aimed specifically at reducing autumn exacerbations with usual care, (no systematic change in management in preparation for school return). We included studies providing data on children aged 18 years or younger. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors independently screened records identified by the search and then extracted data and assessed bias for trials meeting the inclusion criteria. A third review author checked for accuracy and mediated consensus on disagreements. The primary outcome was proportion of children experiencing one or more asthma exacerbations requiring hospitalisation or oral corticosteroids during the autumn period. MAIN RESULTS: Our searches returned 546 trials, of which five met our inclusion criteria. These studies randomised 14,252 children to receive either an intervention or usual care. All studies were conducted in the Northern Hemisphere. Three interventions used a leukotriene receptor antagonist, one used omalizumab or a boost of inhaled corticosteroids, and the largest study, (12,179 children), used a medication reminder letter. Whilst the risk of bias within individual studies was generally low, we downgraded the evidence quality due to imprecision associated with low participant numbers, poor consistency between studies, and indirect outcome ascertainment.A US study of 513 children with mild/severe asthma and allergic sensitisation was the only study to provide data for our primary outcome. In this study, the proportion of participants experiencing an exacerbation requiring oral corticosteroids or hospital admission in the 90 days after school return was significantly reduced to 11.3% in those receiving omalizumab compared to 21.0% in those receiving placebo (odds ratio 0.48, 95% confidence interval 0.25 to 0.92, moderate-quality evidence). The remaining studies used alternative exacerbation definitions. When data from two leukotriene receptor antagonist studies with comparable outcomes were combined in a random-effects model, there was no evidence of an effect upon exacerbations. There was no evidence that a seasonal medication reminder letter decreased unscheduled contacts for a respiratory diagnosis between September and December.Four studies recorded adverse events. There was no evidence that the proportion of participants experiencing at least one adverse event differed between intervention and usual care groups. Lack of data prevented planned subgroup and sensitivity analyses. AUTHORS' CONCLUSIONS: Seasonal omalizumab treatment from four to six weeks before school return might reduce autumn asthma exacerbations. We found no evidence that this strategy is associated with increased adverse effects other than injection site pain, but it is costly. There were no data upon which to judge the effect of this or other seasonal interventions on asthma control, quality of life, or asthma-related death. In future studies definitions of exacerbations should be provided, and standardised where possible. To investigate possible differential effects according to subgroup, participants in future trials should be well characterised with respect to baseline asthma severity and exacerbation history in addition to age and gender.

Learning to Trust Flu Shots: Quasi-Experimental Evidence from the 2009 Swine Flu Pandemic.

This paper studies consumer learning in influenza vaccination decisions. We examine consumer learning in influenza vaccine demand within a reduced form instrumental variable framework that exploits differences in risk characteristics of different influenza viruses as a natural experiment to distinguish the effects of learning based on previous influenza vaccination experiences from unobserved heterogeneity. The emergence of a new virus strain (influenza A H1N1/09) during the 2009 'Swine flu' pandemic resulted in two different vaccines being recommended for distinct population subgroups with some people, who were not usually targeted by seasonal vaccination programs, being specifically recommended for the new Swine flu vaccine. We use these differences in vaccination targeting to construct instrumental variables for estimating the effect of past influenza vaccination experiences on the demand for pandemic vaccine. We find large causal effects of previous seasonal vaccination on pandemic vaccination. Causal effects of past influenza vaccination experiences on perceived vaccination safety are likely to be an important pathway linking past vaccination experiences with future vaccine uptake. Our results suggest a significant role of learning in vaccination decisions. Current efforts to expand seasonal vaccination may thus have potentially important long-term effects on future influenza vaccination levels and pandemic preparedness. Copyright © 2016 John Wiley & Sons, Ltd.

Quantifying natural variability as a method to detect environmental change: Definitions of the normal range for a single observation and the mean of m observations.

The normal range has been defined as the range that encloses 95% of reference values; in practice this range has been defined as the reference mean ± 2 standard deviations (SD). When sample sizes are small and reference data are not normally distributed, the mean ± 2 SDs do not enclose 95% of data values. Prediction intervals (PI) calculated using sample statistics are used in the present study to define the normal range for a single observation and the mean of m observations. The PIs provide confidence limits for the next randomly selected observation (or mean of m observations) from a population. The PIs are defined using normally distributed reference data; normality can typically be achieved with transformations of the data. Covariates can be used to explain some of the variability in the reference distribution, increasing the ability to detect change. When assumptions of normality are not met, alternative methods of defining the normal range are provided. The normal range can be used to quantify natural variability and assess change from the reference distribution. It can be used as an early warning indicator of change in environmental monitoring to identify the need for further investigation.

Can routine offering of influenza vaccination in office-based settings reduce racial and ethnic disparities in adult influenza vaccination?

BACKGROUND: Influenza vaccination remains below the federally targeted levels outlined in Healthy People 2020. Compared to non-Hispanic whites, racial and ethnic minorities are less likely to be vaccinated for influenza, despite being at increased risk for influenza-related complications and death. Also, vaccinated minorities are more likely to receive influenza vaccinations in office-based settings and less likely to use non-medical vaccination locations compared to non-Hispanic white vaccine users. OBJECTIVE: To assess the number of "missed opportunities" for influenza vaccination in office-based settings by race and ethnicity and the magnitude of potential vaccine uptake and reductions in racial and ethnic disparities in influenza vaccination if these "missed opportunities" were eliminated. DESIGN: National cross-sectional Internet survey administered between March 4 and March 14, 2010 in the United States. PARTICIPANTS: Non-Hispanic black, Hispanic and non-Hispanic white adults living in the United States (N = 3,418). MAIN MEASURES: We collected data on influenza vaccination, frequency and timing of healthcare visits, and self-reported compliance with a potential provider recommendation for vaccination during the 2009-2010 influenza season. "Missed opportunities" for seasonal influenza vaccination in office-based settings were defined as the number of unvaccinated respondents who reported at least one healthcare visit in the Fall and Winter of 2009-2010 and indicated their willingness to get vaccinated if a healthcare provider strongly recommended it. "Potential vaccine uptake" was defined as the sum of actual vaccine uptake and "missed opportunities." KEY RESULTS: The frequency of "missed opportunities" for influenza vaccination in office-based settings was significantly higher among racial and ethnic minorities than non-Hispanic whites. Eliminating these "missed opportunities" could have cut racial and ethnic disparities in influenza vaccination by roughly one half. CONCLUSIONS: Improved office-based practices regarding influenza vaccination could significantly impact Healthy People 2020 goals by increasing influenza vaccine uptake and reducing corresponding racial and ethnic disparities.

Issuance of patient reminders for influenza vaccination by US-based primary care physicians during the first year of universal influenza vaccination recommendations.

To estimate the number of physician-reported influenza vaccination reminders during the 2010-2011 influenza season, the first influenza season after universal vaccination recommendations for influenza were introduced, we interviewed 493 members of the Physicians Consulting Network. Patient vaccination reminders are a highly effective means of increasing influenza vaccination; nonetheless, only one quarter of the primary care physicians interviewed issued influenza vaccination reminders during the first year of universal vaccination recommendations, highlighting the need to improve office-based promotion of influenza vaccination.

The impact of influenza vaccination requirements for hospital personnel in California: knowledge, attitudes, and vaccine uptake.

BACKGROUND: Seasonal influenza infections are a leading cause of illness, death, and lost productivity. Vaccinating health care personnel (HCP) can reduce transmission of influenza virus to patients and reduce influenza-related absenteeism, enabling the health care system to meet elevated demand for care during influenza outbreaks. OBJECTIVES: We evaluated the impact of California's 2006 influenza vaccination requirement for hospital workers (requiring vaccination or signed declinations) on uptake and vaccination-related attitudes, beliefs, and knowledge among hospital HCP. METHODS: We used a causal difference-in-differences approach to compare changes over the prior 10 years in the self-reported frequency of influenza vaccination for California hospital HCP and those from other states without similar laws using data from a stratified sample (N = 3,529) of HCP drawn from online survey panels. We also examined cross-sectional differences in awareness of vaccination policies, promotion efforts, and attitudes toward influenza vaccination. All analyses used propensity score weighting to balance the observable characteristics of the 2 samples. RESULTS: We found that compared with their counterparts in other states, California hospital HCP were (1) more likely to report working under a formal written policy for influenza vaccination, (2) no more likely to be vaccinated, and (3) less likely to report working for an employer who provided financial incentives for vaccination or rewarded or recognized employees for being vaccinated. CONCLUSION: Our results suggest that state-level vaccination requirements such as those enacted by California, may not be sufficient to increase uptake among hospital HCP.

Do workplace wellness programs reduce medical costs? Evidence from a Fortune 500 company.

The recent passage of the Affordable Care Act has heightened the importance of workplace wellness programs. This paper used administrative data from 2002 to 2007 for PepsiCo's self-insured plan members to evaluate the effect of its wellness program on medical costs and utilization. We used propensity score matching to identify a comparison group who were eligible for the program but did not participate. No significant changes were observed in inpatient admissions, emergency room visits, or per-member per-month (PMPM) costs. The discrepancy between our findings and those of prior studies may be due to the difference in intervention intensity or program implementation.

CMS Innovation Center Health Care Innovation Awards: Evaluation Plan.

The Center for Medicare and Medicaid Innovation within the Centers for Medicare & Medicaid Services (CMS) has funded 108 Health Care Innovation Awards, funded through the Affordable Care Act, for applicants who proposed compelling new models of service delivery or payment improvements that promise to deliver better health, better health care, and lower costs through improved quality of care for Medicare, Medicaid, and Children's Health Insurance Program enrollees. CMS is also interested in learning how new models would affect subpopulations of beneficiaries (e.g., those eligible for Medicare and Medicaid and complex patients) who have unique characteristics or health care needs that could be related to poor outcomes. In addition, the initiative seeks to identify new models of workforce development and deployment, as well as models that can be rapidly deployed and have the promise of sustainability. This article describes a strategy for evaluating the results. The goal for the evaluation design process is to create standardized approaches for answering key questions that can be customized to similar groups of awardees and that allow for rapid and comparable assessment across awardees. The evaluation plan envisions that data collection and analysis will be carried out on three levels: at the level of the individual awardee, at the level of the awardee grouping, and as a summary evaluation that includes all awardees. Key dimensions for the evaluation framework include implementation effectiveness, program effectiveness, workforce issues, impact on priority populations, and context. The ultimate goal is to identify strategies that can be employed widely to lower cost while improving care.