A Phase Three Study of the Safety and Immunogenicity of a Four-dose Series of 20-Valent Pneumococcal Conjugate Vaccine in Healthy Infants.

BACKGROUND: The 20-valent pneumococcal conjugate vaccine (PCV20) was developed to extend pneumococcal disease protection beyond 13-valent PCV (PCV13). METHODS: This phase 3, double-blind study conducted in the United States/Puerto Rico evaluated PCV20 safety and immunogenicity. Healthy infants were randomized to receive a 4-dose series of PCV20 or PCV13 at 2, 4, 6 and 12-15 months old. Objectives included demonstrating noninferiority (NI) of PCV20 to PCV13 immunoglobulin G (IgG) geometric mean concentrations after doses 3 and 4 and percentages of participants with predefined IgG concentrations after dose 3, with 7 additional PCV20 serotypes compared with the lowest result among vaccine serotypes in the PCV13 group. Safety assessments included local reactions, systemic events, adverse events, serious adverse events and newly diagnosed chronic medical conditions. RESULTS: Overall, 1991 participants were vaccinated (PCV20, n = 1001; PCV13, n = 990). For IgG geometric mean concentrations 1 month after both doses 3 and 4, all 20 serotypes met NI criteria (geometric mean ratio lower 2-sided 95% confidence interval > 0.5). For percentages of participants with predefined IgG concentrations after dose 3, NI (percentage differences lower 2-sided 95% confidence interval > -10%) was met for 8/13 matched serotypes and 6/7 additional serotypes; 4 serotypes missed the statistical NI criterion by small margins. PCV20 also elicited functional and boosting responses to all 20 serotypes. The safety profile of PCV20 was similar to PCV13. CONCLUSION: A 4-dose series of PVC20 was well tolerated and elicited robust serotype-specific immune responses expected to help protect infants and young children against pneumococcal disease due to the 20 vaccine serotypes. Clinical trial registration: NCT04382326.

Building trust: Leadership reflections on community empowerment and engagement in a large urban initiative.

BACKGROUND: Trust is essential for healthy, reciprocal relationships; creating safe environments; engaging in transparent interactions; successfully negotiating power differentials; supporting equity and putting trauma informed approaches into practice. Less is known, however, about the ways that trust-building may be at the forefront of consideration during community capacity building efforts, what trust-building elements are perceived as essential for optimally engaging communities, and what practices might support these efforts. METHODS: The present study examines an evolving understanding of trust-building over the course of 3 years, from qualitative data derived during interviews with nine agency leads from a large and diverse urban community, who are spearheading community-based partnerships to create more trauma-informed communities and foster resiliency. RESULTS: Data reflected fourteen trust-building elements, captured by three themes: 1) Building relationships and engagement (e.g., behavioral practices such as meeting people "where they are at" and creating safe spaces), 2) Embodying core values of trustworthiness (e.g., traits such as being transparent and embodying benevolence), and 3) Sharing decision-making, championing autonomy, and addressing barriers to trust (e.g., collaborative practices such as creating a shared vision and goals and addressing systemic inequities). These trust-building elements are presented in the Community Circle of Trust-Building, which provides an accessible, visual format that can facilitate capacity building efforts within organizations and with the broader community; guide the selection of training opportunities that support healthy interpersonal relationships; and aid in the identification of relevant, supporting frameworks (e.g., health equity, trauma-informed practices, inclusive leadership models). CONCLUSIONS: Community engagement and trust are essential for overall health and well-being, increasing equitable access to resources, and supporting an effective and connected citizenry. These data shed light on opportunities for trust-building and thoughtful engagement among agencies working directly with community members in large urban areas.

Prefusion F Protein-Based Respiratory Syncytial Virus Immunization in Pregnancy.

BACKGROUND: Respiratory syncytial virus (RSV), a major cause of illness and death in infants worldwide, could be prevented by vaccination during pregnancy. The efficacy, immunogenicity, and safety of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine in pregnant women and their infants are uncertain. METHODS: In a phase 2b trial, we randomly assigned pregnant women, at 24 through 36 weeks' gestation, to receive either 120 or 240 µg of RSVpreF vaccine (with or without aluminum hydroxide) or placebo. The trial included safety end points and immunogenicity end points that, in this interim analysis, included 50% titers of RSV A, B, and combined A/B neutralizing antibodies in maternal serum at delivery and in umbilical-cord blood, as well as maternal-to-infant transplacental transfer ratios. RESULTS: This planned interim analysis included 406 women and 403 infants; 327 women (80.5%) received RSVpreF vaccine. Most postvaccination reactions were mild to moderate; the incidence of local reactions was higher among women who received RSVpreF vaccine containing aluminum hydroxide than among those who received RSVpreF vaccine without aluminum hydroxide. The incidences of adverse events in the women and infants were similar in the vaccine and placebo groups; the type and frequency of these events were consistent with the background incidences among pregnant women and infants. The geometric mean ratios of 50% neutralizing titers between the infants of vaccine recipients and those of placebo recipients ranged from 9.7 to 11.7 among those with RSV A neutralizing antibodies and from 13.6 to 16.8 among those with RSV B neutralizing antibodies. Transplacental neutralizing antibody transfer ratios ranged from 1.41 to 2.10 and were higher with nonaluminum formulations than with aluminum formulations. Across the range of assessed gestational ages, infants of women who were immunized had similar titers in umbilical-cord blood and similar transplacental transfer ratios. CONCLUSIONS: RSVpreF vaccine elicited neutralizing antibody responses with efficient transplacental transfer and without evident safety concerns. (Funded by Pfizer; ClinicalTrials.gov number, NCT04032093.).

Developing trauma resilient communities through community capacity-building.

BACKGROUND: Trauma is a significant public health issue, negatively impacting a range of health outcomes. Providers and administrators in public mental health systems recognize the widespread experience of trauma, as well as their limited ability to address trauma within their communities. In response, the Los Angeles County Department of Mental Health funded nine regionally based community partnerships to build capacity to address trauma. We describe partnership and community capacity-building efforts and examine community impact, defined as successful linkages to resources and changes in stress tolerance capacities among community members. METHODS: We conceptualized community capacity-building as dissemination of trauma-informed education and training, community outreach and engagement, and linkage of community members to resources. We measured trauma-informed trainings among partnership members (N = 332) using the Trauma-Informed Organizational Toolkit. Outreach, engagement and linkages were documented using Event and Linkage Trackers. We examined changes in the type of successful linkage after the issuance of statewide mandatory restrictions in response to COVID-19. We examined changes in stress tolerance capacities among community members (N = 699) who were engaged in ongoing partnership activities using the 10-item Conner-Davidson Resilience Scale; the 28-item Coping Orientation to Problems; and the pictorial Inclusion of Community in Self Scale. RESULTS: Training and education opportunities were widespread: 66% of members reported opportunities for training in 13 or more trauma-informed practices. Partnerships conducted over 7800 community capacity-building events with over 250,000 attendees. Nearly 14,000 successful linkages were made for a wide range of resources, with consistent linkage success prior to (85%) and during (87%) the pandemic. In response to COVID-19, linkage type significantly shifted from basic services and health care to food distribution (p < .01). Small but significant improvements occurred in coping through emotional and instrumental support; and sense of community connectedness (p < .05 each). CONCLUSIONS: Community-based partnerships demonstrated effective capacity-building strategies. Despite the pandemic, community members did not report reduced stress tolerance, instead demonstrating gains in external help-seeking (use of emotional and instrumental supports) and perception of community connectedness. Future work will use qualitative methods to examine the impact of community capacity-building and the sustainability of this approach for addressing the impact of trauma within communities.

A Mixed-method Evaluation of the Behavioral Health Integration and Complex Care Initiative Using the Consolidated Framework for Implementation Research.

BACKGROUND: Integrated behavioral health and primary care can improve the health of persons with complex chronic conditions. The Behavioral Health Integration and Complex Care Initiative (BHICCI) implemented integrated care across a large health system. Whether Behavioral Health Organizations (BHOs) and Federally Qualified Health Centers (FQHCs) implemented the BHICCI differently is unclear. OBJECTIVES: The objective of this study was to evaluate integration under the BHICCI and to understand implementation differences between BHOs and FQHCs. METHODS: We used a convergent parallel mixed-method design. Integration was measured quantitatively using the Maine Health Access Site Self-Assessment (SSA), which was completed by clinic teams at baseline and 24 months, and through n=70 qualitative interviews with initiative stakeholders, which were organized using the Consolidated Framework for Implementation Research. Results were compared to understand how qualitative findings explained quantitative results. RESULTS: Data were collected in 7 clinics (n=2 FQHC; n=5 BHOs). FQHCs reported greatest improvement in the client centered subscale, with a baseline score of 4.6 (SD=0.64) and 7.8 (SD=0.89) at 24 months. BHOs reported greatest improvement in the organizational supports for integration subscale, with a baseline score of 4.8 (SD=1.07) and 7.9 (SD=1.1) at 24 months. Our Consolidated Framework for Implementation Research analysis illustrates contextual factors, such as insurance plan supports and clinic-level challenges, that explain these scores. CONCLUSIONS: All clinical settings received support from the health plan, but differences between BHOs and FQHCs affected integration progress. Study results can help identify organizational practices that advance or undermine the delivery of integrated care across multiple clinical settings.

Impact of the 13-Valent Pneumococcal Conjugate Vaccine on Invasive Pneumococcal Disease After Introduction Into Routine Pediatric Use.

BACKGROUND: In 2010, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced 7-valent PCV (PCV7) for protection against invasive pneumococcal disease (IPD). This study used laboratory surveillance data to examine the effect of PCV13 on IPD before and after PCV13 introduction among children aged 6 weeks to <6 years and those aged ≥6 weeks. METHODS: Observational laboratory-based IPD surveillance data were compared for the periods May 2010-April 2018 and May 2008-April 2010 (the PCV7 period) using a database of Kaiser Permanente Northern California (KPNC) members with laboratory-confirmed IPD. RESULTS: Among children aged 6 weeks to 6 years, overall IPD incidence decreased from 11.57 per 100 000 during the PCV7 period to 4.09 per 100 000 after PCV13 introduction; PCV13-type IPD incidence decreased from 5.12 to 0.84 per 100 000. Non-PCV13-serotype IPD did not change significantly in this age group (PCV7 period, 1.71 per 100 000 and after PCV13, 2.52 per 100 000). Of cases occurring in this group, bacteremia was the most common clinical diagnosis. Across all ages, IPD decreased from 9.49 to 6.23 per 100 000 and PCV13-type IPD decreased from 4.67 to 1.89 per 100 000, changes being mostly due to decreases in serotypes 19A and 7F. IPD caused by non-PCV13 serotypes did not change (3.34 and 3.35 per 100 000). Overall, pneumococci isolated after PCV13 introduction had increased susceptibility to penicillin, cefotaxime, and ceftriaxone.This prospective, laboratory-based surveillance study in Kaiser Permanente Northern California members examined annual IPD incidence before and after PCV13 introduction. In children aged 6 weeks to <6 years, IPD caused by PCV13 serotypes decreased significantly (84%) during the surveillance period. CONCLUSIONS: IPD incidence decreased further in every age group after PCV13 introduction, suggesting both direct vaccination effects in the infant population and indirect effects in adults. CLINICAL TRIALS REGISTRATION: NCT01128439.

Safety and immunogenicity of a novel hexavalent group B streptococcus conjugate vaccine in healthy, non-pregnant adults: a phase 1/2, randomised, placebo-controlled, observer-blinded, dose-escalation trial.

BACKGROUND: Group B streptococcus (GBS) is a major cause of invasive disease in young infants. Infants born to women with sufficient pre-existing anti-GBS capsular IgG antibodies are at reduced risk of GBS disease, making maternal immunisation a potential strategy for prevention. We aimed to assess the safety and immunogenicity of a novel hexavalent (serotypes Ia, Ib, II, III, IV, and V) GBS conjugate vaccine (GBS6). METHODS: This phase 1/2, placebo-controlled, observer-blinded, dose-escalation trial, was done at four clinical research centres in the USA (Kentucky, Georgia, and two sites in Utah). Healthy, non-pregnant adults aged 18-49 years were randomly assigned using an interactive, web-based response technology system. Within each dose group (low, medium, or high), participants in sentinel cohorts were randomly assigned 2:2:1 and expanded cohort participants were randomly assigned 4:4:1 to receive GBS6 with aluminium phosphate (AlPO4), GBS6 without AlPO4, or placebo (saline control). One 0·5 mL dose of either saline placebo or 5 µg capsular polysaccharide per serotype in the low-dose group, 10 µg capsular polysaccharide per serotype in the medium-dose group, or 20 µg capsular polysaccharide per serotype in the high-dose group was administered by intramuscular injection into the deltoid muscle on day 1. The primary outcome was safety up to 6 months after vaccination, including the proportion of sentinel cohort participants with clinical laboratory abnormalities at 1 week, the proportion of all participants reporting solicited local reactions, systemic events, or use of antipyretic or pain medication within 14 days, adverse events up to 1 month, and medically attended or serious adverse events up to 6 months. The secondary outcome was GBS immunogenicity (serotype-specific IgG geometric mean concentrations at 1 month). This study is registered with ClinicalTrials.gov, NCT03170609. FINDINGS: Between June 5, 2017, and June 25, 2018, 365 participants were randomly assigned and 364 (52 in each dose group) were vaccinated and included in the safety analysis. Unsolicited adverse events were reported by 15 (29%) participants in the 5 µg with AlPO4 group, 13 (25%) in the 5 µg without AlPO4 group, 22 (42%) in the 10 µg with AlPO4 group, 12 (23%) in the 10 µg without AlPO4 group, 25 (48%) in the 20 µg with AlPO4 group, 21 (40%) in the 20 µg without AlPO4 group, and 20 (38%) in the placebo group. The most common unsolicited adverse events were in the system organ class of infections and infestations in any dose or formulation of GBS6 (ranging from six [12%] in the 10 µg without AlPO4 group to 15 [29%] in the 20 µg with AlPO4 group and placebo group). Three participants reported at least one serious adverse event during the study, one each in the 5 µg GBS6 with AlPO4 group (diabetic ketoacidosis, two events; resolved), 10 µg GBS6 with AlPO4 group (died by suicide), and 20 µg GBS6 with AlPO4 group (metrorrhagia; resolved). None of these serious adverse events were considered related to the vaccine. 11 of the 365 participants were excluded from the evaluable immunogenicity population, including one participant who did not receive the vaccine, and ten who at 1 month after vaccination were withdrawn for various reasons. GBS serotype-specific IgG geometric mean concentrations increased by 1 week after vaccination for all GBS6 groups, peaked at 2 weeks, stabilised by 1 month, and declined gradually but remained higher than placebo at 6 months. INTERPRETATION: GBS6 was well tolerated in healthy adults and elicited robust immune responses for all dose levels and formulations that persisted 6 months after vaccination. This study supports further evaluation of GBS6 in pregnant women. FUNDING: Pfizer.

Advancing Integrated Care through Practice Coaching.

INTRODUCTION: Practice coaches are skilled consultants who work in health care service delivery systems to make changes designed to improve patient outcomes, yet research is limited regarding their use to support integrated health care. This article describes the use of practice coaches in a large-scale effort to implement integrated care in the United States for patients with complex care needs. THEORY AND METHODS: This immersive, qualitative project involved five implementation team members; eight practice coaches; and 77 staff members from 12 health care organizations. Semistructured interviews were recorded and transcribed verbatim. Thematic and content analyses were applied in multiple stages to understand the use of practice coaches. RESULTS: Qualitative themes about the use of practice coaching in this initiative were: (a) development of "a very rich coaching model"; (b) moving from an organic to standardized coaching approach; and (c) coaches representing the "face of the initiative." DISCUSSION: A rich coaching model that includes an interdisciplinary coaching team can support integrated care transformation but challenges including finding highly qualified coaches and sustaining and disseminating the coaching model exist. Standardization was seen as a way to address such challenges. CONCLUSION: Practice coaches can provide individualized, hands-on guidance to support successful implementation of integrated care.

National impact of 13-valent pneumococcal conjugate vaccine on ambulatory care visits for otitis media in children under 5 years in the United States.

OBJECTIVE: The 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13) were approved in the US in 2000 and 2010, respectively, for active immunization against invasive disease caused by all vaccine serotypes and otitis media (OM) caused by 7 serotypes common to both vaccines, starting at ∼6 weeks of age. This study assessed the impact of PCV13 on OM by evaluating changes in US ambulatory care visit rates between the period before PCV7 (1997-1999), during PCV7 (2001-2009), and after the introduction of PCV13 (2011-2013) among US children <5 years old. METHODS: This ecological study used US National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey data. Trend analyses using weighted least-squares regression and mean visit rates were calculated for OM and two control endpoints not likely to be related to either vaccine (skin rash and trauma). RESULTS: Among children <5 and < 2 years old, the observed reduction in OM visit rates was 22% (95%CI: 12%-32%) and 24% (95%CI: 13%-35%) when comparing PCV13 to PCV7 periods, and 41% (95%CI: 30%-52%) and 48% (95%CI: 37%-59%) when comparing PCV13 to pre-PCV7 periods. Visit rates for skin rash and trauma remained stable. CONCLUSION: Significant reductions in US ambulatory care visit rates for OM were observed among children aged <5 years after introduction of PCV13 compared to the periods before and during PCV7; reductions were greatest among children <2 years old. The reductions beyond the PCV7 period support the effectiveness of the vaccine's 6 additional serotypes in preventing OM.

Evaluation Of The Behavioral Health Integration And Complex Care Initiative In Medi-Cal.

This article reports how a large Medi-Cal managed care plan addressed challenges in accessing health care for approximately 7,000 enrollees with multiple chronic conditions through a project known as the Behavioral Health Integration and Complex Care Initiative. The initiative increased staffing for care management, care coordination, and behavioral health integration. In our evaluation of the initiative, we demonstrated that participation in it was associated with improved clinical indicators for common chronic conditions, reduced inpatient costs in some sites, and improved patient experience in all sites. The initiative may be best understood as a new type of ongoing strategic partnership among the health plan, its providers, and their patients. Changes in funding to support models of value-based care are needed to sustain these efforts in the long term.

Effectiveness of 13-valent pneumococcal conjugate vaccination for protection against acute otitis media caused by Streptococcus pneumoniae in healthy young children: a prospective observational study.

BACKGROUND: With wide use of the seven-valent pneumococcal conjugate vaccine (PCV7) for protection against acute otitis media caused by Streptococcus pneumoniae serotypes included in the vaccine, efficacy testing for the 13-valent vaccine (PCV13) was not feasible. We aimed to assess the effectiveness of PCV13 in preventing acute otitis media caused by the six serotypes in PCV13 that were not in PCV7. METHODS: We did a longitudinal observational study in healthy children seen as outpatients in a private paediatric practice in Rochester, NY, USA. Children aged up to 30 months who had received the full primary series of PCV13 with other recommended vaccines were eligible to participate and were followed up to age 30-36 months to identify episodes of acute otitis media, during which we collected middle-ear fluid (MEF) by tympanocentesis. We assessed MEF for the serotypes common to PCV7 and PCV13 (4, 6B, 9V, 14, 18C, 19F, and 23F) and the six additional serotypes specific to PCV13 (1, 3, 5, 6A, 7F, and 19A). As controls, we included children enrolled in a longitudinal study in the study centre from Oct 1, 2007, to Sept 30, 2009, who had been vaccinated with PCV7, had MEF prospectively collected at the onset of acute otitis media, and been followed up until age 30 months. The primary outcome was the effectiveness of PCV13 to prevent acute otitis media caused by pneumococci expressing the six capsular serotypes not included in PCV7 (1, 3, 5, 6A, 7F, and 19A). This study is registered with ClinicalTrials.gov, number NCT01199016. FINDINGS: From Sept 28, 2010, to Sept 30, 2013, we enrolled 239 children (123 [51%] boys and 116 [49%] girls; median age 6·3 months [IQR 6·1-8·6]) in the PCV13 cohort, and 162 completed the study. Of 348 children (184 [53%] boys and 164 [47%] girls; 6·5 months [6·1-9·1]) included in the PCV7 cohort, 248 completed follow-up. 223 MEF samples were obtained at onset of acute otitis media from 90 children in the PCV13 cohort. 53 (24%) of 223 samples were culture positive for S pneumoniae, compared with 89 (31%) of 284 samples in the PCV7 cohort (p=0·06). Four (8%) of 53 samples in the PCV13 cohort contained pneumococci expressing one of the additional PCV13 capsular serotypes, compared with 46 (52%) of 89 samples in the PCV7 cohort, giving a relative reduction of 86% (95% CI 61-94, p=0·0010). The greatest reduction in MEF samples was in serotype 19A (two [4%] in the PCV13 cohort vs 46 [52%] in the PCV7 cohort; relative reduction 91% [58-97, p=0·0010]). INTERPRETATION: PCV13 prevents acute otitis media caused by S pneumoniae expressing serotypes included in the vaccine. FUNDING: Pfizer.

Health Care Usage and Suicide Risk Screening within 1 Year of Suicide Death.

BACKGROUND: Research indicates patients often seek medical care within 1 year of suicide. Health care encounters are a crucial opportunity for health professionals to identify patients at highest risk and provide preventative services. OBJECTIVE: Study aims were to determine the characteristics of persons seeking health care within 12 months of suicide death and evaluate suicide risk screening (SRS) frequency in the emergency department (ED) vs. clinic settings. METHODS: Medical examiner and hospital data of patients who died by suicide from 2007 to 2013 were evaluated. Descriptive analyses included demographics and frequency of ED vs. clinic visits. We also compared SRS before and after implementation of The Joint Commission's recommendation to assess suicide risk. RESULTS: The 224 deceased patients were primarily single white males (mean age 67 years). Mental health issues, substance abuse, and prior suicide attempts were present alone or in combination in 74%. Visits were primarily behavioral health or substance abuse problems in the ED, and medical issues in the clinic. After implementation of universal SRS in the ED, screening increased from 39% to 92%. Among patients screened in the ED, 73% (37 of 51) screened negative for suicide risk. CONCLUSIONS: Universal SRS increased the number of people screened in the ED. However, negative SRS may not equate to reduced risk for future suicide within 1 year. Future studies might investigate targeted screening of individuals with known suicide risk factors, as well as alternatives to patient self-report of intent to self-harm for patients with mental health or substance abuse problems.

Immunogenicity and safety of 13-valent pneumococcal conjugate vaccine (PCV13) formulated with 2-phenoxyethanol in multidose vials given with routine vaccination in healthy infants: An open-label randomized controlled trial.

BACKGROUND: This open-label randomized controlled trial in infants compared safety, tolerability, and immunogenicity of the 13-valent pneumococcal conjugate vaccine (PCV13) formulated with the preservative 2-phenoxyethanol (2-PE) in a multidose vial (MDV) to the current PCV13 without 2-PE in a single-dose syringe (SDS). METHODS: Gambian infants were randomized 1:1 to receive PCV13 as either MDV or SDS at ages 2, 3, and 4months. Serotype-specific antipneumococcal antibody responses and opsonophagocytic activity ([OPA]; subset) were measured at age 5months. Noninferiority was declared if the lower bound of the 97.5% CI for the difference (MDV-SDS) in proportions of subjects achieving IgG concentrations ≥0.35µg/mL (primary endpoint) was greater than -10%. IgG geometric mean concentrations (GMCs) were noninferior if the lower limit of the two-sided 97.5% CI of the geometric mean ratio (MDV vs SDS) was greater than 0.5. Reactogenicity and other adverse events were collected. RESULTS: 500 participants were randomized and vaccinated; 489 (MDV: n=245; SDS: n=244) completed the trial. Noninferiority of MDV was demonstrated for all serotypes as measured by percentage of subjects achieving antibody responses above ≥0.35µg/mL. IgG GMCs (coprimary endpoint) also demonstrated noninferiority of MDV; OPA results supported these findings. Safety and tolerability were comparable between groups. CONCLUSIONS: PCV13 in MDV was safe and immunogenic when administered according to the routine schedule to infants. MDV was noninferior to SDS for all 13 pneumococcal serotypes. Comparable immunogenicity and safety profiles of PCV13 MDV and SDS suggest PCV13 MDV can help optimize vaccination in resource-limited settings. ClinicalTrials.gov NCT01964716 https://clinicaltrials.gov/ct2/show/NCT01964716.

A randomized study of fever prophylaxis and the immunogenicity of routine pediatric vaccinations.

OBJECTIVE: Prophylactic antipyretic use during pediatric vaccination is common. This study assessed whether paracetamol or ibuprofen prophylaxis interfere with immune responses to the 13-valent pneumococcal conjugate vaccine (PCV13) given concomitantly with the combined DTaP/HBV/IPV/Hib vaccine. METHODS: Subjects received prophylactic paracetamol or ibuprofen at 0, 6-8, and 12-16 h after vaccination, or 6-8 and 12-16 h after vaccination at 2, 3, 4, and 12months of age. At 5 and 13months, immune responses were evaluated versus responses in controls who received no prophylaxis. RESULTS: After the infant series, paracetamol recipients had lower levels of circulating serotype-specific pneumococcal anticapsular immunoglobulin G than controls, reaching significance (P<0.0125) for 5 serotypes (serotypes 3, 4, 5, 6B, and 23F) when paracetamol was started at vaccination. Opsonophagocytic activity assay (OPA) results were similar between groups. Ibuprofen did not affect pneumococcal responses, but significantly (P<0.0125) reduced antibody responses to pertussis filamentous hemagglutinin and tetanus antigens after the infant series when started at vaccination. No differences were observed for any group after the toddler dose. CONCLUSIONS: Prophylactic antipyretics affect immune responses to vaccines; these effects vary depending on the vaccine, antipyretic agent, and time of administration. In infants, paracetamol may interfere with immune responses to pneumococcal antigens, and ibuprofen may reduce responses to pertussis and tetanus antigens. The use of antipyretics for fever prophylaxis during infant vaccination merits careful consideration. ClinicalTrials.gov identifier: NCT01392378https://clinicaltrials.gov/ct2/show/NCT01392378?term=NCT01392378&rank=1.

Circulating Antibody 1 and 2 Years After Vaccination With the 13-Valent Pneumococcal Conjugate Vaccine in Preterm Compared With Term Infants.

BACKGROUND: Premature infants have lower short-term immune responses to vaccination than term infants, but patterns of antibody persistence in preterm infants over longer periods are not well established. This study assessed the persistence of antibody response to the 13-valent pneumococcal conjugate vaccine (PCV13) in formerly preterm versus term infants. METHODS: In total, 100 preterm and 100 term infants received PCV13 with routine vaccines at ages 2, 3, 4 and 12 months. Serotype-specific anticapsular immunoglobulin G (IgG)-binding antibodies and opsonophagocytic activity were determined 1 and 2 years after the last PCV13 dose. RESULTS: At 1 and 2 years after the last vaccination (toddler dose), IgG geometric mean concentrations (GMCs) for all serotypes had declined from levels measured 1 month after the toddler dose but remained above pretoddler dose levels. IgG GMCs were significantly lower in preterm than term subjects for a majority of serotypes at both follow-up time points. IgG GMCs increased in both groups for some serotypes from the 1-year to 2-year follow-up, whereas others declined. Opsonophagocytic activity results supported the IgG results. CONCLUSIONS: The routine (3 + 1) vaccination schedule is likely to offer long-term protection against invasive pneumococcal disease in preterm infants and should be initiated regardless of gestational age or weight at birth, without delay of the toddler dose.

13-valent pneumococcal conjugate vaccine (PCV13) in preterm versus term infants.

OBJECTIVES: This study evaluated the immune response and safety profile of 13-valent pneumococcal conjugate vaccine (PCV13) in preterm infants compared with term infants. METHODS: This Phase IV, open-label, 2-arm, multicenter, parallel-group study enrolled 200 healthy infants (preterm, n = 100; term, n = 100) aged 42 to 98 days. All subjects received PCV13 at ages 2, 3, 4 (infant series), and 12 (toddler dose [TD]) months, together with routine vaccines (diphtheria-tetanus-acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b vaccine and meningococcal group C conjugate vaccine). RESULTS: Most subjects achieved an anticapsular immunoglobulin G (IgG) antibody concentration ≥ 0.35 µg/mL for all serotypes: >85% after the infant series (except preterm infants for serotypes 5, 6A, and 6B) and >97% after TD (except for serotype 3). Preterm infants had overall lower IgG geometric mean concentrations compared with term infants; however, geometric mean fold increases after TD were similar for all serotypes. Opsonophagocytic activity results were consistent with IgG results and titers increased after TD in both groups for all serotypes, including serotype 3. PCV13 was generally well tolerated, with similar safety profiles in all preterm subgroups. CONCLUSIONS: Immune responses were lower in preterm infants than in term infants. However, the majority of subjects in both groups achieved both pneumococcal serotype-specific IgG antibody levels after the infant series that exceeded the World Health Organization-established threshold of protection and functional antibody responses. Responses were uniformly higher after TD, reinforcing the importance of a timely booster dose. PCV13 was well tolerated regardless of gestational age.

Multicenter surveillance of Streptococcus pneumoniae isolates from middle ear and mastoid cultures in the 13-valent pneumococcal conjugate vaccine era.

BACKGROUND: Streptococcus pneumoniae is a common cause of otitis media (OM) in children; mastoiditis remains an important complication of OM. Limited data are available on the impact of the 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal otitis. METHODS: Investigators from 8 children's hospitals in the United States prospectively collected pneumococcal isolates from middle ear or mastoid cultures from children from 2011 to 2013. Serotype and antibiotic susceptibilities were determined and PCV13 doses for children documented. RESULTS: Over the 3-year period, the proportion of isolates included in PCV13 (plus a related serotype) decreased significantly (P = .0006) among the middle ear/mastoid isolates (2011, 50% [74/149]; 2012, 40.5% [47/116]; 2013, 29% [34/118]). The number of serotype 19A isolates in 2013 (n = 12, 10.2% of total) decreased 76% compared with the number of 19A isolates in 2011 (n = 50, 33.6% of total). Of the children from whom serotype 19A was isolated (n = 93), 55% had previously received <3 doses of PCV13. The most common non-PCV13 serotypes for the combined years were 35B (n = 37), 21 (n = 20), 23B (n = 20), 15B (n = 18), 11 (n = 17), 23A (n = 14), 15A (n = 14), and 15C (n = 14). The proportion of isolates with a penicillin minimal inhibitory concentration >2 µg/mL decreased significantly over the 3 years (2011, 22% [35/154]; 2012, 20% [24/118]; 2013, 10% [12/120]; P < .02). CONCLUSIONS: The number of pneumococcal isolates and the percentage of isolates with high-level penicillin resistance from cultures taken from children with OM or mastoiditis for clinical indications have decreased following PCV13 use, largely related to decreases in serotype 19A isolates.

Stigma experienced by people using mental health services in San Diego County.

OBJECTIVE: This paper describes how individuals struggling with severe mental illness experience stigma along multiple dimensions including their experiences of discrimination by others, their unwillingness to disclose information about their mental health, and their internalization or rejection of the negative and positive aspects of having mental health problems. METHODS: This cross-sectional study employs descriptive analyses and linear regression to assess the relationship between demographics, mental health diagnoses and self-reported stigma among people receiving mental health services in a large and ethnically diverse county public mental health system (n = 1,237) in 2009. We used the King Stigma Scale to measure three factors related to stigma: discrimination, disclosure, and positive aspects of mental illness. RESULTS: Most people (89.7 %) reported experiencing some discrimination from having mental health problems. Regression analyses revealed that younger people in treatment experienced more stigma related to mental health problems. Women reported experiencing more stigma than men, but men were less likely to endorse the potentially positive aspects of facing mental health challenges than women. Although people with mood disorders reported more discomfort with disclosing mental illness than people with schizophrenia, they did not report experiencing more discrimination than people with schizophrenia. CONCLUSIONS: Study findings suggest that the multidimensional experiences of stigma differ as a function of age, gender, and diagnosis. Importantly, these findings should inform anti-stigma efforts by describing different potential treatment barriers due to experiences of stigma among people using mental health services, especially among younger people and women who may be more susceptible to stigma.

Decreased immune response to pneumococcal conjugate vaccine after 23-valent pneumococcal polysaccharide vaccine in children.

BACKGROUND: Pneumococcal polysaccharide vaccine (PPV) is used in children at high risk of IPD. PPV is generally not considered to induce immunologic memory, whereas pneumococcal conjugate vaccines (PCVs) elicit protective antibody responses in infants and induce immunologic memory. Little is known about the characteristics of immune responses to PCV in children who previously received PCV and PPV in series. OBJECTIVE: To characterize immune responses to 13-valent pneumococcal CRM197 conjugate vaccine (PCV13; serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) in children vaccinated in infancy with 9-valent pneumococcal-meningococcal C-CRM197 conjugate combination vaccine (PCV9-MnCC), followed by a toddler dose of PCV9-MnCC or 23-valent pneumococcal polysaccharide vaccine (PPV23). METHODS: Children (n=89) who received PCV9-MnCC in infancy and PPV23 or PCV9-MnCC at age 12 months in a previous (2002-2003) study were vaccinated at age 7.5 years with PCV13; groups PPV23/PCV13 (n=50) and PCV9/PCV13 (n=39). Immunoglobulin (Ig)G antibodies, avidity, and opsonophagocytic activity (OPA) were measured before and at 1 and 4 weeks postvaccination. RESULTS: One week postvaccination, IgG levels increased significantly for all serotypes in both groups, and >97% of vaccinees achieved IgG ≥0.35µg/ml 4 weeks after PCV13 vaccination. The PCV9/PCV13 group had higher IgG responses compared with the PPV23/PCV13 group. The upper limits of the 95% confidence intervals of the PPV23/PCV13:PCV9/PCV13 IgG geometric mean concentration ratios were <1.0 for serotypes 1, 4, 5, 9V, 18C, and 23F at 1 week. OPA and avidity results supported these findings. CONCLUSIONS: PPV23 vaccination of toddlers may compromise subsequent responses to pneumococcal conjugate vaccines. The clinical relevance of this finding is unclear.