Different perceptual worlds: Parent and youth perspectives on parenting outcome trajectories from a Latino family-based program.

Discrepancies between parent and youth perceptions of their relationship are a common aspect of generational acculturation gaps influencing immigrant families. Programs designed to strengthen parenting practices among immigrant Latino families commonly address immigration stresses, including differences between parent and youth perceptions, but little is known about discrepancies in their appraisals of program effects on parenting behavior. A randomized trial was conducted examining effects on parent behavior of a program for immigrant families with youth aged 10-14, developed through community-based participatory research principles. Families (346 parents and youth) were recruited by organizations serving Latino families in a Midwestern metropolitan area and randomly assigned to the eight-session psychoeducation and skill-building program or a waitlist control. Parents and youth completed self-report measures at pre-intervention, post-intervention (4 months), and a 6-month follow-up regarding parents' expression of acceptance, efforts to solicit information about the child's experiences, and consistency of discipline, key foci of the program. Based on social cognition theory, the study focused on possible differences in parents' and youths' perceptions of change in parenting behavior. Parents in the treatment group reported pre-post improved acceptance, consistent discipline, and solicitation, whereas youth reported improvement only in parental solicitation, a pattern maintained at follow-up. In the control group, the only change was youth-reported reduction in parental acceptance. Parents' perceptions of improvement are encouraging, but overall lack of improvements from the youth perspective poses a potential problem for impact on parent-child relations. Interventions may need to target both parent and youth cognitions about behavior changes directly.

Perceived importance and interest in research by Chilean primary care providers.

BACKGROUND: Primary care providers (PCPs) are relevant stakeholders for primary care research (PCR). OBJECTIVE: We report the perceived importance and interest in PCR of a national sample of Chilean PCPs. METHODS: We conducted a cross-sectional study targeting Chilean PCPs. An electronic survey assessing perceived relevance of PCR, research training and experience, training interests, and demographics was disseminated through emails and WhatsApp messages. Descriptive statistics were used to summarize data. Logistic regression models were used to estimate adjusted probabilities and 95% confidence intervals for high interest in PCR, high interest in using research methods, and high interest in receiving research training, and predictors of these outcomes. RESULTS: A total of 387 providers completed the online survey. Only 26.4% of PCPs had research experience as a principal or co-investigator. However, most clinicians perceived PCR as very important (92.5%) and were interested in using research methods (90.7%) and receiving training (94.3%). There were no statistically significant differences in these perceptions between provider's discipline, role, sex, age, and geographical location after adjusting for covariates. CONCLUSIONS: Despite few Chilean PCPs have research training, a large majority perceive it as important, are interested in using it in their practice and would like to receive training.

Development of the ¡Vamos por Mas! parenting program to prevent substance use among Chilean adolescents.

In Chile, the prevalence of tobacco, alcohol and drug use among adolescents is very high. Decades of research indicate that parenting interventions reduce these risky behaviors. However, there are no parenting interventions validated in Chile to prevent adolescent substance use. This article reports the development of the ¡Vamos por Mas! (¡VxM!) program following the recommendations of the Medical Research Council's framework for designing and evaluating complex interventions. After identifying key intervention components, a preliminary version of a substance-use prevention program was designed. The preliminary intervention targeted families with adolescents in fifth and sixth grade and had four components: personalized feedback, in-person workshops, virtual engagement, and family support, to deliver positive-youth development and family-strengthening content. Then, students, guardians, school staff and community experts from different school systems (N = 111) evaluated the preliminary version of the program through a convergent parallel mixed methods study, including focus groups (N = 14) and surveys (N = 101). In general, all participants had positive perceptions of the program and valued its purpose, strategies, objectives and contents. Suggestions included expanding the purpose to promote healthy relationships, focusing on schools with low and intermediate socioeconomic vulnerability, including self-control content, removing the personalized feedback component and adding two additional components: school partnership and external supervision, among other improvements. With this information, the final version of the ¡VxM! program was developed. After a rigorous intervention development process, the ¡VxM! program is ready to be piloted and evaluated in a randomized trial.

Chile has high rates of tobacco, alcohol and drug use among adolescents. Parenting interventions have shown to reduce these risky behaviors. However, there are no parenting interventions validated in Chile to prevent adolescent substance use. This article reports the development of the ¡Vamos por Mas! (¡VxM!) program to strengthen family relations and prevent adolescent substance use following the recommendations of the Medical Research Council's framework for designing and evaluating complex interventions. In the first phase, key intervention components were identified. Then, a preliminary version of the intervention was designed. In the second phase, perceptions of key stakeholders were collected through focus groups (N = 14) and surveys (N = 101) including adolescents, guardians, school staff and community experts. These participants evaluated the preliminary version of the program and provided feedback. In the final phase of the intervention development process, stakeholder opinions were integrated into the proposal. The final version of the ¡VxM! program included five components: (i) school partnership, (ii) in-person workshops, (iii) virtual engagement, (iv) family support and (v) external supervision. This version is ready to be piloted to evaluate feasibility and preliminary efficacy, before being assessed in a randomized trial.

Mixed-Methods Evaluation of the Initial Implementation of Advanced Home Visits in Chile.

Home visiting programs are evidence-based interventions that have a myriad outcomes for mothers and newborns. Chile offers these services as part of the Chile Crece Contigo, a nationwide program. However, implementing home visiting programs in community settings is difficult. In this study, we report clinic, provider, and participant engagement with the implementation of advanced home visits (ViDAs) in Chilean primary care clinics. ViDAs include a high number of visits, external supervision, and the use of technology. In this study, qualitative and quantitative data were collected to assess the initial implementation of the home visiting strategy. Qualitative data consisted of individual interviews and focus groups with directors of city health departments, clinic managers, and providers conducting home visits. Quantitative data included clinic, provider, and participant recruitment. City health departments were approached to authorize the participation of primary care clinics in the ViDAs program. Then, clinic directors were invited to approve the implementation of the home visiting program at their health centers. In total, 16 clinics, 42 practitioners, and 185 participants were recruited. A large amount of resources was needed to recruit clinics, providers, and participants. The intervention had low acceptability, low adoption, and a high implementation cost. Initial program implementation experienced several challenges. Identified facilitators and barriers both highlighted the need for community engagement at all levels for the successful implementation of an innovation in Chilean primary care clinics. In addition, this article provides recommendations for practitioners and researchers regarding the conduct of research in community-based settings.

A cluster randomized trial of interferon ß-1a for the reduction of transmission of SARS-Cov-2: protocol for the Containing Coronavirus Disease 19 trial (ConCorD-19).

BACKGROUND: SARS-CoV-2 infection rapidly spreads in populations due to the high rates of community transmission. Interrupting the shedding of SARS-CoV-2 may reduce the incidence of Coronavirus Disease 19 (COVID-19). Herein we provide a protocol for a cluster randomized trial that will examine the effectiveness of treatment with interferon (IFN) ß-1a compared to standard of care in limiting the transmission of SARS-CoV-2. Co-primary objectives are to determine whether IFN therapy reduces (a) the proportion of infected cases shedding SARS-CoV-2 at day 11 post randomization and (b) the incidence of transmission of SARS-CoV-2 infection from index cases to treatment-eligible household post-exposure contacts at day 11 after randomization. Secondary objectives include assessing the impact of IFN treatment on duration of viral clearance, hospitalizations and fatalities, and evaluating the safety of IFN treatment. METHODS: Three hundred and ten households, each including an index case with a recent COVID-19 diagnosis and at least one asymptomatic treatment-eligible household contact, will be randomized to receive 3 doses of 125 µg IFN ß-1a by subcutaneous administration (days 1, 6, and 11), or standard of care. All participants will be followed until day 29. DISCUSSION: The results from this trial will identify whether IFN ß treatment of mild or moderate COVID-19 cases accelerates viral clearance and prevents disease progression and whether IFN ß treatment of post-exposure contacts of COVID-19 cases reduces transmission of infection. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov NCT04552379; date of registration September 17, 2020.

System-Wide Accelerated Implementation of Telemedicine in Response to COVID-19: Mixed Methods Evaluation.

BACKGROUND: As the COVID-19 pandemic disrupted medical practice, telemedicine emerged as an alternative to outpatient visits. However, it is not known how patients and physicians responded to an accelerated implementation of this model of medical care. OBJECTIVE: The aim of this study is to report the system-wide accelerated implementation of telemedicine, compare patient satisfaction between telemedicine and in-person visits, and report provider perceptions. METHODS: This study was conducted at the UC Christus Health Network, a large private academic health network in Santiago, Chile. The satisfaction of patients receiving telemedicine care in March and April 2020 was compared to those receiving in-person care during the same period (concurrent control group) as well as in March and April 2019 (retrospective control group). Patient satisfaction with in-person care was measured using the Net Promoter Score (NPS) survey. Patient satisfaction with telemedicine was assessed with an online survey assessing similar domains. Providers rated their satisfaction and responded to open-ended questions assessing challenges, strategies used to address challenges, the diagnostic process, treatment, and the patient-provider relationship. RESULTS: A total of 3962 patients receiving telemedicine, 1187 patients from the concurrent control group, and 1848 patients from the retrospective control group completed the surveys. Satisfaction was very high with both telemedicine and in-person services. Overall, 263 physicians from over 41 specialties responded to the survey. During telemedicine visits, most providers felt their clinical skills were challenged (61.8%). Female providers felt more challenged than male providers (70.7% versus 50.9%, P=.002). Surgeons, obstetricians, and gynecologists felt their clinical skills were challenged the least, compared to providers from nonsurgical specialties (P<.001). Challenges related to the delivery modality, diagnostic process, and patient-provider relationship differed by provider specialty (P=.046, P<.001, and P=.02, respectively). CONCLUSIONS: Telemedicine implemented in response to the COVID-19 pandemic produced high patient and provider satisfaction. Specialty groups perceived the impact of this new mode of clinical practice differently.

Latinx Mental Health Scholars' Experiences with Cultural Adaptation and Implementation of Systemic Family Interventions.

An increasing number of culturally adapted family-level interventions address mental health disparities with marginalized populations in the United States. However, with these developments many barriers have arisen, such as challenges with degree of cultural fit, engagement, and sustainability. We conducted 12 elite phenomenological interviews with mental health scholars involved in prevention and intervention family research with various Latinx communities within and outside of the United States. These scholars discussed their experiences of overcoming barriers in their research. We used thematic analysis to code and analyze participant responses, and our findings support the gaps in previous literature and highlight potential pathways to overcoming barriers in cultural adaptation research. Themes included the need for: (a) better understanding of the intersection between culture and context; (b) community-centered approaches to addressing implementation challenges; and (c) structural changes within institutional, governmental, and political levels. We discuss implications for researchers and practitioners working with Latinx families.

Un número cada vez mayor de intervenciones adaptadas culturalmente a nivel familiar abordan las desigualdades en la salud mental con poblaciones marginadas en los Estados Unidos. Sin embargo, con estos avances han surgido muchos obstáculos, como las dificultades con el grado de integración cultural, la participación y la sostenibilidad. Realizamos veinte entrevistas fenomenológicas selectas con investigadores de la salud mental dedicados a la investigación familiar en materia de prevención e intervenciones con varias comunidades latinas dentro y fuera de los Estados Unidos. Estos investigadores comentaron sus experiencias de superación de los obstáculos en su investigación. Utilizamos el análisis temático para decodificar y analizar las respuestas de los participantes; nuestros resultados respaldan la falta de datos en publicaciones previas y destacan las posibles vías para superar los obstáculos en la investigación sobre la adaptación cultural. Los temas incluyeron la nacesidad de: (a) una mejor comprensión del enlace entre la cultura y el contexto; (b) enfoques centrados en la comunidad para abordar las dificultades de implementación; y (c) cambios estructurales dentro de los niveles institucionales, gubernamentales y políticos. Debatimos las implicancias para los investigadores y los profesionales que trabajan con familias latinas.

Adaptive Recruitment and Parenting Interventions for Immigrant Latino Families with Adolescents.

Parenting programs are an effective strategy to prevent multiple risky outcomes during adolescence. However, these programs usually enroll one caregiver and have low attendance. This study evaluated the preliminary results, cost, and satisfaction of adaptive recruitment and parenting interventions for immigrant Latino families. A mixed methods study was conducted integrating a pre-post design with embedded qualitative and process evaluations. Fifteen immigrant Latino families with an adolescent child aged 10-14 were recruited. Two-caregiver families received a home visit to increase enrollment of both caregivers. All families participated in an adaptive parenting program that included group sessions and a one-to-one component (online videos plus follow-up telephone calls) for those who did not attend the group sessions. The intervention addressed positive parenting practices using a strengths-based framework. Primary outcomes were the proportion of two-parent families recruited and intervention participation. Secondary outcomes were change in parenting self-efficacy, practices, fidelity, costs, and satisfaction. Participants completed questionnaires and interaction tasks before and after participating in the intervention. In addition, participants and program facilitators completed individual interviews to assess satisfaction with the program components. Overall, 23 parents participated in the intervention; 73% of two-parent families enrolled with both parents. Most participants completed 75% or more of the intervention. Fathers were more likely to use the one-to-one component of the intervention than mothers (p = .038). Participants were satisfied with program modifications. In sum, adaptive recruitment and parenting interventions achieved high father enrollment and high participation. These findings warrant further evaluation in randomized trials.

Sexual (Dis)satisfaction and Its Contributors Among People Living with HIV Infection in Sweden.

Earlier research reports lower sexual satisfaction among people living with HIV (PLHIV) compared to HIV-negative persons. A number of psychosocial factors directly associated with sexual dissatisfaction have been identified. Little is known about sexual satisfaction and their contributors among PLHIV in Sweden. The aim of this study was to examine direct and indirect effects of variables within sociodemographic, clinical HIV-related, psychological, and sexual domains on sexual (dis)satisfaction among PLHIV in Sweden. Data for this study were derived from a nationally representative, anonymous survey among PLHIV conducted in 2014 (n = 1096). Statistical analysis included four steps: descriptive analyses, identification of variables associated with sexual (dis)satisfaction, identification of variables associated with those contributors of sexual (dis)satisfaction, and a path model integrating all these analyses. A total of 49% of participants reported being sexually dissatisfied, and no significant differences were observed when non-heterosexual men, heterosexual men, and women were compared. Among women, a negative change in sex life after HIV diagnosis and distress with orgasmic difficulties was directly associated with sexual dissatisfaction. For men, hopelessness, high HIV stigma, sexual inactivity in the last 6 months, and a negative change in sex life after HIV diagnosis were directly associated with sexual dissatisfaction. Path analyses showed in both men and women significant indirect associations between not being involved in an intimate relationship, lower self-reported CD4 cell counts, and perceiving obligation to disclose HIV status to sexual partners as a barrier to look for a long-term partner and sexual dissatisfaction. Our results show that despite good treatment outcomes, the HIV diagnosis has a negative bearing on sexual satisfaction. The need for gender-tailored interventions and clinical implications of these findings are discussed.

For Whom Do Parenting Interventions to Prevent Adolescent Substance Use Work?

Adolescent substance use continues to be a significant public health problem. Parent training interventions are effective preventive strategies to reduce youth substance use. However, little is known about differences in effectiveness for youth across demographic characteristics. This review assessed the effectiveness of parent training programs at reducing adolescent substance use by participant gender, age, and race/ethnicity. Pubmed/MEDLINE, ERIC, CINAHL, and PsycINFO were searched from database origin to October 31, 2016. We included randomized controlled trials that evaluated parent training interventions; reported youth initiation or use of tobacco, alcohol, or other illicit substances; and included adolescents aged 10 to 19. Two independent reviewers extracted data. Disagreements were resolved by consensus or a third researcher. Data were synthesized using harvest plots stratified by participant demographics. A total of 1806 publications were identified and reviewed; 38 unique studies were included. Risk of bias of included studies was high. No studies targeted male teens or youth in late adolescence. Few studies targeted Asian-American, Black/African-American, or Hispanic/Latino adolescents. Overall, interventions including male and female youth and youth in early adolescence (age 10 to 14 or in 5th to 8th grade) were more beneficial than interventions including female-only or both young and older adolescents. Programs tailored to specific racial/ethnic groups, as well as programs designed for youth from multiple races/ethnic groups, were effective. Current evidence supports the benefits of offering parenting guidance to all families with adolescent children, regardless of the gender, age, or race/ethnicity of the adolescent.

[Model of comprehensive care in family and community health in primary care in ChileModelo de atenção integral na saúde da família e da comunidade na atenção básica chilena]. / Modelo de atención integral en salud familiar y comunitaria en la atención primaria chilena.

OBJECTIVE: Describe the current status of the implementation of the Model of Comprehensive Care in Family and Community Health (MAIS, by its acronym in Spanish) in primary care in Chile. METHODS: Cross-sectional study that evaluated the implementation of MAIS in a total of 1 263 primary care facilities. Through correlations, the relationship between internal self-evaluation and external evaluation of health services for each center was studied. The factors of facilities, communes and regions associated with the level of implementation of the MAIS were evaluated with multilevel analyses. RESULTS: The correlation between internal self-evaluation and the external evaluation of the total implementation of the MAIS was very high (0.819, p <0.001). The technology axis presented the highest implementation (83.0% compliance), and family focus the lowest (37.8% compliance). The facilities with the highest implementation were family health centers, the urban communes, those with the highest number of enrollees and those with the lowest poverty index. A statistically significant association was not identified between the implementation of the MAIS and the total community expenses (p = 0.122) nor specific health expenditures (p = 0.244). CONCLUSIONS: Most of the primary care health facilities have evaluated the level of implementation of the MAIS. The accompanying strategies for its implementation are priorities for primary care facilities located in rural areas and with a low number of registered users. Improving the family focus and the quality of care -key aspects of health care- are still a challenge.

OBJETIVO: Descrever o estado atual da implementação do Modelo de Assistência Integral em Saúde da Família e da Comunidade (MAIS) na atenção primária no Chile. MÉTODOS: Estudo transversal que avaliou a implementação do MAIS em um total de 1 263 estabelecimentos de atenção primária. Por meio de correlações, foi estudada a relação entre a autoavaliação (interna) e a avaliação dos serviços de saúde (externa) para cada centro. Os fatores dos estabelecimentos, municípios e regiões associados ao nível de implementação do MAIS foram avaliados com análises multiníveis. RESULTADOS: A correlação entre a autoavaliação interna e a avaliação externa da implementação total do MAIS foi muito alta (0,819, p <0,001). O eixo tecnológico apresentou maior implementação (83,0% de cumprimento) e foco familiar o menor (37,8% de cumprimento). Os centros de saúde da família, as comunas urbanas, aqueles com maior número de inscritos e com o menor índice de pobreza, foram os estabelecimentos que apresentaram a maior implementação. Não foi identificada associação estatisticamente significativa entre a implementação do MAIS e as despesas totais da comunidade (p = 0,122) nem gastos específicos com saúde (p = 0,244). CONCLUSÕES: A maioria dos estabelecimentos de atenção primária avaliaram o nível de implementação do MAIS. As estratégias de acompanhamento para sua implementação são prioritárias para estabelecimentos de atenção primária em áreas rurais e com baixo número de usuários cadastrados. Enfatiza-se o desafio de avançar na instalação do enfoque familiar e na qualidade de atenção.

Bi-national cross-validation of an evidence-based conduct problem prevention model.

OBJECTIVES: To (a) explore the preferences of Mexican parents and Spanish-speaking professionals working with migrant Latino families in Minnesota regarding the Mexican-adapted brief model versus the original conduct problems intervention and (b) identifying the potential challenges, and preferred solutions, to implementation of a conduct problems preventive intervention. METHOD: The core practice elements of a conduct problems prevention program originating in the United States were adapted for prevention efforts in Mexico. Three focus groups were conducted in the United States, with Latino parents (n = 24; 2 focus groups) and professionals serving Latino families (n = 9; 1 focus group), to compare and discuss the Mexican-adapted model and the original conduct problems prevention program. Thematic analysis was conducted on the verbatim focus group transcripts in the original language spoken. RESULTS: Participants preferred the Mexican-adapted model. The following key areas were identified for cultural adaptation when delivering a conduct problems prevention program with Latino families: recruitment/enrollment strategies, program delivery format, and program content (i.e., child skills training, parent skills training, child-parent activities, and child-parent support). For both models, strengths, concerns, barriers, and strategies for overcoming concerns and barriers were identified. CONCLUSIONS: We summarize recommendations offered by participants to strengthen the effective implementation of a conduct problems prevention model with Latino families in the United States. This project demonstrates the strength in binational collaboration to critically examine cultural adaptations of evidence-based prevention programs that could be useful to diverse communities, families, and youth in other settings. (PsycINFO Database Record

Reconciling research and community priorities in participatory trials: application to Padres Informados/Jovenes Preparados.

Background: Participatory research (PR) trials aim to achieve the dual, and at times competing, demands of producing an intervention and research process that address community perspectives and priorities, while establishing intervention effectiveness. Objective: To identify research and community priorities that must be reconciled in the areas of collaborative processes, study design and aim and study implementation quality in order to successfully conduct a participatory trial. We describe how this reconciliation was approached in the smoking prevention participatory trial Padres Informados/Jovenes Preparados (Informed Parents/Prepared Youth) and evaluate the success of our reconciled priorities. Methods: Data sources to evaluate success of the reconciliations included a survey of all partners regarding collaborative group processes, intervention participant recruitment and attendance and surveys of enrolled study participants assessing intervention outcomes. Results: While we successfully achieved our reconciled collaborative processes and implementation quality goals, we did not achieve our reconciled goals in study aim and design. Due in part to the randomized wait-list control group design chosen in the reconciliation process, we were not able to demonstrate overall efficacy of the intervention or offer timely services to families in need of support. Conclusion: Achieving the goals of participatory trials is challenging but may yield community and research benefits. Innovative research designs are needed to better support the complex goals of participatory trials.

Cultural Contributors to Smoking Susceptibility Outcomes Among Latino Youth: The Padres Informados/Jovenes Preparados Participatory Trial.

Padres Informados/Jovenes Preparados is a community-based participatory, family-focused tobacco prevention intervention for immigrant Latino families of adolescents. We conducted a participatory randomized controlled trial including 352 Latino families. Parents and youth in the intervention condition engaged in eight family skill building sessions. Participants completed baseline and 6-month postintervention surveys assessing smoking susceptibility and contextual factors. While the intervention did not affect smoking susceptibility overall, it resulted in lower smoking susceptibility among youth in families with less adherence to traditional Latino cultural values. This family cultural orientation is a key consideration for tobacco prevention interventions focused on Latino youth.

Squeezing observational data for better causal inference: Methods and examples for prevention research.

Randomised controlled trials (RCTs) are typically viewed as the gold standard for causal inference. This is because effects of interest can be identified with the fewest assumptions, especially imbalance in background characteristics. Yet because conducting RCTs are expensive, time consuming and sometimes unethical, observational studies are frequently used to study causal associations. In these studies, imbalance, or confounding, is usually controlled with multiple regression, which entails strong assumptions. The purpose of this manuscript is to describe strengths and weaknesses of several methods to control for confounding in observational studies, and to demonstrate their use in cross-sectional dataset that use patient registration data from the Juan Pablo II Primary Care Clinic in La Pintana-Chile. The dataset contains responses from 5855 families who provided complete information on family socio-demographics, family functioning and health problems among their family members. We employ regression adjustment, stratification, restriction, matching, propensity score matching, standardisation and inverse probability weighting to illustrate the approaches to better causal inference in non-experimental data and compare results. By applying study design and data analysis techniques that control for confounding in different ways than regression adjustment, researchers may strengthen the scientific relevance of observational studies.

Understanding Attendance in a Community-Based Parenting Intervention for Immigrant Latino Families.

Community-based participatory research (CBPR) can help increase the attendance in community programs. Padres Informados, Jovenes Preparados (PIJP) is a program that aims to prevent tobacco and other substance use among Latino youth by promoting positive parenting. Although the trial used CBPR approaches, attendance was inconsistent. In the present study, factors associated with attendance and nonattendance and recommendations to maximize participation were explored in 12 brief feedback discussions (BFDs) with participants and in 10 in-depth interviews (IDIs) with facilitators who delivered PIJP. Content analysis guided two pairs of researchers, who independently coded emerging themes and categories (κ = .86 for BFDs and .73 for IDIs). Data from BFDs and IDIs were merged and interpreted together. We grouped factors that positively affected participation into three categories: individual and family (e.g., motivation), program (e.g., offering food and childcare and having facilitators who are trusted), and research (e.g., having incentives). Barriers to participation were grouped into four categories: individual and family (e.g., family conflicts), sociocultural (e.g., community and cultural beliefs), program (e.g., fixed schedules), and research (e.g., recruitment procedures). Participants provided recommendations to address all types of barriers. Although PIJP used CBPR, complete satisfaction of community needs is difficult. Effective community programs must address participants' needs and preferences.

Safety, tolerability, and immunogenicity of an adult pneumococcal conjugate vaccine, V116 (STRIDE-3): a randomised, double-blind, active comparator controlled, international phase 3 trial.

BACKGROUND: The same pneumococcal conjugate vaccines (PCVs) have been used in adults and children in many settings. Differences in the epidemiology of pneumococcal disease between populations necessitates an adult-specific PCV. We aimed to assess the safety, tolerability, and immunogenicity of V116, an investigational 21-valent PCV designed for adults. METHODS: This randomised, double-blind, active comparator controlled, international phase 3 trial enrolled adults with or without stable chronic medical conditions at 112 clinical sites in 11 countries or territories. Random assignment was performed using a central electronic interactive response technology system. Cohort 1 (≥50 years) was stratified by age (50-64, 65-74, 75-84, and ≥85 years) and randomised 1:1 to receive one intramuscular dose of V116, or the active comparator, PCV20. Cohort 2 (18-49 years) was randomised 2:1 to receive one intramuscular dose of V116 or PCV20. Pneumococcal serotype-specific opsonophagocytic activity (OPA) and IgG responses were measured before (day 1) and after vaccination (day 30). Four primary immunogenicity outcomes were assessed per-protocol. First, in cohort 1, non-inferiority of V116 to PCV20 was tested using serotype-specific OPA geometric mean titres (GMT) ratios for serotypes common to both vaccines; the lower bound of the 95% CI had to be greater than 0·5 for non-inferiority. Second, superiority of V116 to PCV20 was tested for OPA GMT ratios for the serotypes unique to V116; the lower bound of the 95% CI had to be greater than 2·0 for superiority. Third, superiority of V116 to PCV20 was evaluated by the proportions of participants with a four-fold or greater rise from day 1 to day 30 for serotypes unique to V116; the lower bound of the 95% CI of the differences in proportions (V116 - PCV20) had to be greater than 10% for superiority. Finally, in cohort 2, immunobridging was assessed for all 21 serotypes in V116 for adults aged 18-49 years to 50-64 years; the lower bound of the 95% CI for the OPA GMTs had to be greater than 0·5 for non-inferiority. The safety analysis included all randomly assigned participants who received study vaccine. The primary safety outcome was the proportion of participants with solicited injection site and solicited systemic adverse events until day 5 and vaccine-related serious adverse events up to 6 months after vaccination. This trial is registered at ClinicalTrials.gov (NCT05425732). FINDINGS: Between July 13, and Nov 22, 2022, 2754 individuals were screened and 2663 participants were randomly assigned. 2656 individuals were vaccinated (1179 in V116 cohort 1; 1177 in PCV20 cohort 1; 200 in V116 cohort 2; and 100 in PCV20 cohort 2). V116 met non-inferiority criteria compared with PCV20 for the ten serotypes common to both vaccines at day 30 in cohort 1 (p<0·0001 for each common serotype). V116 met superiority criteria compared with PCV20 in cohort 1 for ten of the 11 serotypes unique to V116 at day 30 (OPA GMT ratio: p<0·0001 for all unique serotypes except 15C, which was p=0·41; four-fold or greater rise in OPA from day 1-30: p<0·0001 for all serotypes except 15C, which was p=0·67). Immune responses in V116 participants aged 18-49 years were non-inferior compared with V116 participants aged 50-64 years for all V116 serotypes (p<0·0001 for all V116 serotypes). In cohort 1, 685 (58·2%) of participants in V116, and 778 (66·2%) of participants in PCV20 reported one or more adverse event. In cohort 2, 164 (82·0%) participants in V116 and 79 participants (79·0%) in PCV20 reported one or more adverse event. Six deaths were reported, all in cohort 1, none of which were considered vaccine-related (in V116: one due to sepsis, one due to cerebrovascular accident, one due to myocardial infarction, and one due to hepatic cirrhosis and hepatic encephalopathy; in PCV20: one due to cardiac arrest and one due to abdominal abscess). There were no vaccine-related serious adverse events. INTERPRETATION: V116 was non-inferior to PCV20 for the ten serotypes common to both vaccines and superior to PCV20 for all serotypes unique to V116, except for 15C. Immune responses successfully immunobridged between younger and older adults for all serotypes in V116. V116 was generally well tolerated with safety profile similar to PCV20. FUNDING: Merck Sharp & Dohme, subsidiary of Merck & Co, Rahway, NJ, USA (MSD).

A mixed-methods evaluation of the ¡Vamos por Más! parenting program implementation in Chile.

INTRODUCTION AND AIMS: Substance use is a significant global concern. Strengthening parenting in families with adolescents has been shown to reduce substance use initiation. The ¡Vamos por Más! (¡VxM!) program is a positive-parenting program developed in Chile to improve family relations and reduce adolescent substance use that combines in-person school workshops, multimedia messaging and personalized support. This manuscript reports a mixed-methods evaluation of the pilot implementation of the ¡VxM! program utilizing the Consolidated Framework for Implementation Research and Proctor's taxonomy for process outcomes. METHODS: An explanatory sequential design was used. Quantitative methods evaluated program use, acceptability, appropriateness, and fidelity, and were followed by qualitative focus groups (FGs) to assess the implementation process and understand these outcomes. Thirteen FGs stratified by school and role, including school leaders, program facilitators, participants, and researchers, were conducted. RESULTS: The program was implemented in three schools, reaching 253 families with in-person workshops (40.5% of potential participants), 257 parents who viewed on average 72.1% of sent multimedia messages, and 2 families who used the personalized support (0.3%). Overall, the program was viewed as acceptable and appropriate by participants and implementers due to the high quality of program materials, targeted content, and activities. Implementation differed by schools. Key implementation factors were the outer context, inner school setting, and implementation processes. CONCLUSIONS: This comprehensive evaluation, including both intervention implementers and participants, identified implementation facilitators, barriers, and outcomes. Future ¡VxM! implementations should alter program components of schools with lower engagement to improve program implementation and outcomes.

Safety, Tolerability, Bioavailability, and Biological Activity of Inhaled Interferon-α2b in Healthy Adults: The IN2COVID Phase I Randomized Trial.

BACKGROUND AND OBJECTIVES: Interferons have been identified as a potential treatment alternative for coronavirus disease 2019. This study assessed the safety, tolerability, bioavailability, and biological activity of inhaled interferon-α2b (IFN)-α2b in healthy adults. METHODS: A double-blind, randomized, phase I clinical trial was conducted with two cohorts of healthy subjects aged 18-50 years. The first cohort received 2.5 MIU of inhaled IFN-α2b twice daily for 10 days (n = 6) or placebo (n = 3); the second cohort received 5.0 MIU of inhaled IFN-α2b in a similar scheme (n = 6) or placebo (n = 3). The first two doses were administered in an emergency department, then participants completed their treatment at home. Safety was measured through vital signs, new symptoms, and laboratory tests. Tolerability was measured as participants' treatment acceptability. Bioavailability and biological activity were measured from serum IFNα concentrations and real-time quantitative polymerase chain reaction of interferon-induced genes in blood before and after treatments. RESULTS: Exposure to inhaled IFN-α2b at 2.5-MIU or 5-MIU doses did not produce statistically significant changes in participant vital signs, or elicit new symptoms, and standard hematological and biochemical blood measurements were comparable to those recorded in individuals who received placebo. A total of 58 adverse events were observed. All were mild or moderate and did not require medical care. All participants reported very high tolerability towards a twice-daily nebulized treatment for 10 days (98.0, 97.0, and 97.0 in the placebo, 2.5-MIU, and 5-MIU groups, respectively, on a 0- to 100-mm visual analog scale). A dose-dependent mild increase in serum IFN-α concentrations and an increase in serum RNA expression of IFN-induced genes were observed 11 days after treatment (p < 0.05 for all between-group comparisons). CONCLUSIONS: Inhaled IFN-α2b was preliminarily safe and well tolerated, and induced systemic biological activity in healthy subjects. CLINICAL TRIAL REGISTRATION: The trial was registered in ClinicalTrials.gov (NCT04988217), 3 August, 2021.

Interferon ß-1a ring prophylaxis to reduce household transmission of SARS-CoV-2: a cluster randomised clinical trial.

Background: Accumulating evidence indicates that an early, robust type 1 interferon (IFN) response to SARS-CoV-2 is important in determining COVID-19 outcomes, with an inadequate IFN response associated with disease severity. Our objective was to examine the prophylactic potential of IFN administration to limit viral transmission. Methods: A cluster randomised open label clinical trial was undertaken to determine the effects of pegylated IFNß-1a administration on SARS-CoV-2 household transmission between December 3rd, 2020 and June 29th, 2021. Index cases were identified from databases of confirmed SARS-CoV-2 individuals in Santiago, Chile. Households were cluster randomised (stratified by household size and age of index cases) to receive 3 doses of 125 µg subcutaneous pegylated IFNß-1a (172 households, 607 participants), or standard care (169 households, 565 participants). The statistical team was blinded to treatment assignment until the analysis plan was finalised. Analyses were undertaken to determine effects of treatment on viral shedding and viral transmission. Safety analyses included incidence and severity of adverse events in all treatment eligible participants in the standard care arm, or in the treatment arm with at least one dose administered. Clinicaltrials.gov identifier: NCT04552379. Findings: 5154 index cases were assessed for eligibility, 1372 index cases invited to participate, and 341 index cases and their household contacts (n = 831) enrolled. 1172 participants in 341 households underwent randomisation, with 607 assigned to receive IFNß-1a and 565 to standard care. Based on intention to treat (ITT) and per protocol (PP) analyses for the primary endpoints, IFNß-1a treatment did not affect duration of viral shedding in index cases (absolute risk reduction = -0.2%, 95% CI = -8.46% to 8.06%) and transmission of SARS-CoV-2 to household contacts (absolute risk reduction = 3.87%, 95% CI = -3.6% to 11.3%). Treatment with IFNß-1a resulted in significantly more treatment-related adverse events, but no increase in overall adverse events or serious adverse events. Interpretation: Based upon the primary analyses, IFNß-1a treatment did not affect duration of viral shedding or the probability of SARS-CoV-2 transmission to uninfected contacts within a household. Funding: Biogen PTY Ltd. Supply of interferon as 'Plegridy (peginterferon beta-1a).' The study was substantially funded by BHP Holdings Pty Ltd.