Optimal hepatitis C treatment adherence patterns and sustained virologic response among people who inject drugs: The HERO study.

BACKGROUND & AIMS: Direct-acting antivirals (DAAs) are highly effective for treating HCV infection even among people who inject drugs (PWID). Yet, little is known about patients' adherence patterns and their association with sustained virologic response (SVR) rates. We aimed to summarize various adherence patterns and determine their associations with SVR. METHODS: Electronic blister packs were used to measure daily adherence to once-a-day sofosbuvir/velpatasvir during the 12-week treatment period among active PWIDs. Blister pack data were available for 496 participants who initiated DAAs for whom SVR status was known. Adherence was summarized in multiple patterns, such as total adherent days, consecutive missed days, and early discontinuations. Thresholds for adherence patterns associated with >90% SVR rates were also determined. RESULTS: The overall SVR rate was 92.7%, with a median adherence rate of 75%. All adherence patterns indicating greater adherence were significantly associated with achieving SVR. Participant groups with ≥50% (>42/84) adherent days or <26 consecutive missed days achieved an SVR rate of >90%. Greater total adherent days during 9-12 weeks and no early discontinuation were significantly associated with higher SVR rates only in those with <50% adherence. Participants with first month discontinuation and ≥2 weeks of treatment interruption had low SVR rates, 25% and 85%, respectively. However, greater adherent days were significantly associated with SVR (adjusted odds ratio 1.10; 95% CI 1.04-1.16; p <0.001) even among participants with ≥14 consecutive missed days. CONCLUSIONS: High SVR rates can be achieved in the PWID population despite suboptimal adherence. Encouraging patients to take as much medication as possible, with <2 weeks consecutive missed days and without early discontinuation, was found to be important for achieving SVR. IMPACT AND IMPLICATIONS: People who inject drugs can be cured of HCV in >90% of cases, even with relatively low adherence to direct-acting antivirals, but early discontinuations and long treatment interruptions can significantly reduce the likelihood of achieving cure. Clinicians should encourage people who inject drugs who are living with HCV to adhere daily to direct-acting antivirals as consistently as possible, but if any days are interrupted, to continue and complete treatment. These results from the HERO study are important for patients living with HCV, clinicians, experts writing clinical guidelines, and payers. CLINICAL TRIAL NUMBER: NCT02824640.

Risk, resilience and family relationships among at-risk Ethiopian immigrant youth in Israel: A focus group investigation.

Despite the pivotal role that parents play in their adolescent children's lives, intervention programs aimed at at-risk, immigrant youth have often neglected the role of the parents. Informed by an ecological perspective, the current study explored how the intersecting experiences of parents and adolescents in the Ethiopian immigrant community in Israel inform adolescent risk and resilience. A sample of 55 parents and adolescent children, who were involved in a program serving at-risk families, and eight service providers participated in five focus groups. Grounded theory analyses of transcripts provided insights into family processes in which the experience of disenfranchisement of parents (due to societal and familial processes) transacts with feelings of isolation and withdrawal of their adolescent children. We documented five issues that reinforced this core pattern: Stigma and discrimination, cultural and language differences between parents and youth, disempowerment in interactions with authorities, parental role strain, and negative influence of the neighborhood. We also documented three resilience processes that counter this pattern (community cohesion, cultural socialization and ethnic and cultural pride, and vigilant parental monitoring). Results suggest a need for family-based intervention programs that can counter reinforcing cycles of disenfranchisement and build on families' resilience resources.

Cultural accommodation of internet-based interventions for substance use and related disorders: a proposed comprehensive framework based on a pilot study and a literature review.

Despite the low utilization rates of substance use and related disorders services, and the ability of internet-based interventions for substance use and related disorders (IBIS) to address challenges related to service engagement, limited attention has been placed on the processes for the accommodation of these interventions to diverse cultural settings. This study aimed to develop a framework for the cultural accommodation of IBIS across populations based on a pilot study and a literature review. A pilot study of cultural accommodation of an existing internet intervention for alcohol use was carried out in Israel, which involved focus groups and daily online surveys of prospective consumers (N = 24) as well as interviews with experts (N = 7) in the substance abuse treatment field. Thematic analysis revealed a range of themes that relate to the general Israeli culture and the specific Israeli drinking subculture, identified as needing to be addressed in the process of intervention accommodation. A comprehensive framework for cultural accommodation of IBIS is suggested, consisting of five stages: Technical and cultural feasibility; Engagement of target group; Identification of accommodation variables, Accommodation, and evaluation of the accommodated intervention. In addition, the framework consists of four dimensions of accommodation: Barriers and facilitators; Audio-visual materials and language; Mechanisms of change; Intersectional factors. We suggest that the proposed framework may serve as a guide for the cultural accommodation of existing internet-based interventions for substance use and related disorders across a range of cultural and geographical settings, thus augmenting the ecological validity of internet-based interventions for substance use and related disorders, expanding cross-cultural intervention research, and reducing health disparities worldwide.

Secreted metabolome of porcine blastocysts encapsulated within in vitro 3D alginate hydrogel culture systems undergoing morphological changes provides insights into specific mechanisms involved in the initiation of porcine conceptus elongation.

CONTEXT: The exact mechanisms regulating the initiation of porcine conceptus elongation are not known due to the complexity of the uterine environment. AIMS: To identify contributing factors for initiation of conceptus elongation in vitro , this study evaluated differential metabolite abundance within media following culture of blastocysts within unmodified alginate (ALG) or Arg-Gly-Asp (RGD)-modified alginate hydrogel culture systems. METHODS: Blastocysts were harvested from pregnant gilts, encapsulated within ALG or RGD or as non-encapsulated control blastocysts (CONT), and cultured. At the termination of 96h culture, media were separated into blastocyst media groups: non-encapsulated control blastocysts (CONT); ALG and RGD blastocysts with no morphological change (ALG- and RGD-); ALG and RGD blastocysts with morphological changes (ALG+ and RGD+) and evaluated for non-targeted metabolomic profiling by liquid chromatography (LC)-mass spectrometry (MS) techniques and gas chromatography-(GC-MS). KEY RESULTS: Analysis of variance identified 280 (LC-MS) and 1 (GC-MS) compounds that differed (P <0.05), of which 134 (LC-MS) and 1 (GC-MS) were annotated. Metabolites abundance between ALG+ vs ALG-, RGD+ vs RGD-, and RGD+ vs ALG+ were further investigated to identify potential differences in metabolic processes during the initiation of elongation. CONCLUSIONS: This study identified changes in phospholipid, glycosphingolipid, lipid signalling, and amino acid metabolic processes as potential RGD-independent mechanisms of elongation and identified changes in lysophosphatidylcholine and sphingolipid secretions during RGD-mediated elongation. IMPLICATIONS: These results illustrate changes in phospholipid and sphingolipid metabolic processes and secretions may act as mediators of the RGD-integrin adhesion that promotes porcine conceptus elongation.

Impact of new country, discrimination, and acculturation-related factors on depression and anxiety among ex-Soviet Jewish migrants: data from a population-based cross-national comparison study.

Migration, displacement, and flight are major worldwide phenomena and typically pose challenges to mental health. Therefore, migrants' mental health, and the factors which may predict it, have become an important research subject. The present population-based cross-national comparison study explores symptoms of depression, anxiety, and somatization, as well as quality-of-life in samples of ex-Soviet Jewish migrants settling in three new countries: Germany, Austria and Israel, as well as in a sample of non-migrant ex-Soviet Jews in their country of origin, Russia. In the current study, we investigate the relationship of perceived xenophobiа and antisemitism, acculturation attitudes, ethnic and national identity, as well as affiliation with Jewish religion and culture to the psychological well-being of these migrants. Furthermore, we consider xenophobic and antisemitic attitudes as well as the acculturation orientation of the new countries' societies, assessed in the native control samples. Our data suggest that attitudes of the new country's society matter for the mental health of this migrant group. We conclude that the level of distress among ex-Soviet Jewish migrants seems to depend, among other factors, on the characteristics of the new country and/or specific interactions of the migrant population with the society they are settling in.

Mechanisms regulating the initiation of porcine conceptus elongation.

Significant increases in litter size within commercial swine production over the past decades have led to increases in preweaning piglet mortality due to increase within-litter birthweight variation, typically due to mortality of the smallest littermate piglets. Therefore, identifying mechanisms to reduce variation in placental development and subsequent fetal growth are critical to normalizing birthweight variation and improving piglet survivability in high-producing commercial pigs. A major contributing factor to induction of within-litter variation occurs during the peri-implantation period as the pig blastocyst elongates from spherical to filamentous morphology in a short period of time and rapidly begins superficial implantation. During this period, there is significant within-litter variation in the timing and extent of elongation among littermates. As a result, delays and deficiencies in conceptus elongation not only contribute directly to early embryonic mortality, but also influence subsequent within-litter birthweight variation. This study will highlight key aspects of conceptus elongation and provide some recent evidence pertaining to specific mechanisms from -omics studies (i.e., metabolomics of the uterine environment and transcriptomics of the conceptus) that may specifically regulate the initiation of conceptus elongation to identify potential factors to reduce within-litter variation and improve piglet survivability.

Access to medical care and its association with physical injury in adolescents: a cross-national analysis.

BACKGROUND: Strong variations in injury rates have been documented cross-nationally. Historically, these have been attributed to contextual determinants, both social and physical. We explored an alternative, yet understudied, explanation for variations in adolescent injury reporting-that varying access to medical care is, in part, responsible for cross-national differences. METHODS: Age-specific and gender-specific rates of medically treated injury (any, serious, by type) were estimated by country using the 2013/2014 Health Behaviour in School-aged Children study (n=209 223). Available indicators of access to medical care included: (1) the Healthcare Access and Quality Index (HAQ; 39 countries); (2) the Universal Health Service Coverage Index (UHC; 37 countries) and (3) hospitals per 100 000 (30 countries) then physicians per 100 000 (36 countries). Ecological analyses were used to relate injury rates and indicators of access to medical care, and the proportion of between-country variation in reported injuries attributable to each indicator. RESULTS: Adolescent injury risks were substantial and varied by country and sociodemographically. There was little correlation observed between national level injury rates and the HAQ and UHC indices, but modest associations between serious injury and physicians and hospitals per 100 000. Individual indicators explained up to 9.1% of the total intercountry variation in medically treated injuries and 24.6% of the variation in serious injuries. CONCLUSIONS: Cross-national variations in reported adolescent serious injury may, in part, be attributable to national differences in access to healthcare services. Interpretation of cross-national patterns of injury and their potential aetiology should therefore consider access to medical care as a plausible explanation.

Gender Differences in Bullying Reflect Societal Gender Inequality: A Multilevel Study With Adolescents in 46 Countries.

PURPOSE: Social patterns in bullying show consistent gender differences in adolescent perpetration and victimization with large cross-national variations. Previous research shows associations between societal gender inequality and gender differences in some violent behaviors in adolescents. Therefore, there is a need to go beyond individual associations and use a more social ecological perspective when examining gender differences in bullying behaviors. The aim of the present study was twofold: (1) to explore cross-national gender differences in bullying behaviors and (2) to examine whether national-level gender inequality relates to gender differences in adolescent bullying behaviors. METHODS: Traditional bullying and cyberbullying were measured in 11-year-olds to 15-year-olds in the 2017/18 Health Behaviour in School-aged Children study (n = 200,423). We linked individual data to national gender inequality (Gender Inequality Index, 2018) in 46 countries and tested their association using mixed-effects (multilevel) logistic regression models. RESULTS: Large cross-national variations were observed in gender differences in bullying. Boys had higher odds of perpetrating both traditional and cyberbullying and victimization by traditional bullying than girls. Greater gender inequality at country level was associated with heightened gender differences in traditional bullying. In contrast, lower gender inequality was associated with larger gender differences for cyber victimization. DISCUSSION: Societal gender inequality relates to adolescents' involvement in bullying and gendered patterns in bullying. Public health policy should target societal factors that have an impact on young people's behavior.

Global analysis of differential gene expression within the porcine conceptus transcriptome as it transitions through spherical, ovoid, and tubular morphologies during the initiation of elongation.

This study aimed to identify transcriptome differences between distinct or transitional stage spherical, ovoid, and tubular porcine blastocysts throughout the initiation of elongation. We performed a global transcriptome analysis of differential gene expression using RNA-Seq with high temporal resolution between spherical, ovoid, and tubular stage blastocysts at specific sequential stages of development from litters containing conceptus populations of distinct or transitional blastocysts. After RNA-Seq analysis, significant differentially expressed genes (DEGs) and pathways were identified between distinct morphologies or sequential development stages. Overall, 1898 significant DEGs were identified between distinct spherical and ovoid morphologies, with 311 total DEGs between developmental stages throughout this first morphological transition, while 15 were identified between distinct ovoid and tubular, with eight total throughout these second morphological transition developmental stages. The high quantity of DEGs and pathways between conceptus stages throughout the spherical to ovoid transition suggests the importance of gene regulation during this first morphological transition for initiating elongation. Further, extensive DEG coverage of known elongation signaling pathways was illustrated from spherical to ovoid, and regulation of lipid signaling and membrane/ECM remodeling across these early conceptus stages were implicated as essential to this process, providing novel insights into potential mechanisms governing this rapid morphological change.

Positive and negative social contacts with immigrants from different groups: Investigating the role of group appraisal and opportunity for contact using network analysis.

What can enhance positive inter-group contacts in a world of mass immigration is a subject high on the theoretical and practical agenda. However, there is a lack of research examining how contacts with different immigrant groups are related to characteristics of the group, as perceived by the receiving society. Using Threat-Benefit Theory (Tartakovsky & Walsh, 2016a, 2016b, 2019, 2020), the present study examines how different domains of positive and negative appraisal of a specific immigrant group may relate to contacts with group members. Using a representative sample of 1600 adults in the majority of the Jewish population in Israel, we applied network analysis to examine relationships between threat-benefit appraisal, opportunities for contact and levels of positive and negative contacts with four immigrant groups: diaspora immigrants from Ethiopia, Western countries and the former Soviet Union and asylum seekers. Levels of contact were related to particular domains of appraisal, which differed across immigrant groups. However, opportunities for contact had a stronger association with contact than the appraisal. Results point to a theoretical need to develop nuanced models related to inter-group contact, which consider particular characteristics of the immigrant group as perceived by the local population.

The role of psychologists in international migration research: Complementing other expertise and an interdisciplinary way forward.

This research note addresses the current and potential future role of psychologists in the study of international migration. We review ways in which psychologists have contributed to the study of migration, as well as ways in which psychological scholarship could be integrated with work from other social science fields. Broadly, we discuss four major contributions that psychology brings to the study of international migration-studying migrants' internal psychological experiences, incorporating a developmental perspective, conducting experimental studies, and integrating across levels of analysis. Given the position of psychology as a 'hub science' connecting more traditional social sciences with health and medical sciences, we argue for a more prominent role for psychologists within the study of international migration. Such a role is intended to complement the roles of other social scientists and to create a more interdisciplinary way forward for the field of migration studies. The research note concludes with an agenda for further scholarship on migration.

Localised release of matrix metallopeptidase 8 in fatal cerebral malaria.

OBJECTIVE: Cerebral malaria (CM) is a complication of Plasmodium falciparum malaria, in which progressive brain swelling is associated with sequestration of parasites and impaired barrier function of the cerebral microvascular endothelium. To test the hypothesis that localised release of matrix metallopeptidase 8 (MMP8) within the retina is implicated in microvascular leak in CM, we examined its expression and association with extravascular fibrinogen leak in a case-control study of post-mortem retinal samples from 13 Malawian children who met the clinical case definition of CM during life. Cases were seven children who were found on post-mortem examination to have 'true-CM' (parasite sequestration in brain blood vessels), whilst controls were six children who had alternative causes of death ('faux-CM', no parasite sequestration in blood vessels). METHODS: We used immunofluorescence microscopy and independent scoring, by two assessors blinded to the CM status, to assess MMP8 expression, extravascular fibrinogen as an indicator of vascular leak and their co-localisation in the retinal microvasculature. RESULTS: In 'true-CM' subjects, MMP8 staining was invariably associated with sequestered parasites and a median of 88% (IQR = 74-91%) of capillaries showed MMP8 staining, compared with 14% (IQR = 3.8-24%) in 'faux-CM' (P-value = 0.001). 41% (IQR = 28-49%) of capillaries in 'true-CM' subjects showed co-localisation of extravascular fibrinogen leak and MMP8 staining, compared with 1.8% of capillaries in 'faux-CM' (IQR = 0-3.9%, P-value = 0.01). Vascular leak was rare in the absence of MMP8 staining. CONCLUSION: Matrix metallopeptidase 8 was extensively expressed in retinal capillaries of Malawian children with malarial retinopathy and strongly associated with vascular leak. Our findings implicate MMP8 as a cause of the vascular endothelial barrier disruption in CM, which may precipitate fatal brain swelling.

Mental Health in Adolescents with a Migration Background in 29 European Countries: The Buffering Role of Social Capital.

Previous research is inconclusive as to whether having an immigration background acts as a risk factor for poor mental health in adolescents, and furthermore, what contribution the social context in which adolescents grow up may make. To address these questions, the current study uses an integrative resilience framework to investigate the association between immigration background and adolescent mental health, and the moderating role of social capital at the individual, the school, and the national level. The study uses data gathered from nationally representative samples of adolescents aged 11, 13, and 15 years (Ngirls = 63,425 (52.1%); Mage = 13.57, SD = 1.64) from 29 countries participating in the 2017/18 Health Behaviour in School-aged Children (HBSC) study. Data analysis reveals that first- and second-generation immigrants reported higher levels of life dissatisfaction and psychosomatic symptoms than their native peers, and that this association varied across schools and countries. In addition, social capital was found to moderate the association between immigration background and adolescent mental health. Individual-level social support from peers and family and national-level trust protected against poor mental health in adolescents with an immigration background, while the opposite was true for individual-level teacher support. Supportive teacher-student relationships were found to provide more protection against poor mental health for native adolescents than for immigrant adolescents. Our findings indicate the importance of taking an ecological approach to design interventions to reduce the negative effects of having an immigration background on adolescent mental health.

Personal Value Preferences, Threat-Benefit Appraisal of Immigrants and Levels of Social Contact: Looking Through the Lens of the Stereotype Content Model.

The study examines a model proposing relationships between personal values, positive (i.e., benefits) and negative (i.e., threats) appraisal of immigrants, and social contact. Based on a values-attitudes-behavior paradigm, the study extends previous work on personal values and attitudes to immigrants by examining not only negative but also positive appraisal and their connection with social contact with immigrants. Using a representative sample of 1,600 adults in the majority population in Israel, results showed that higher preference for anxiety-avoidance values (self-enhancement and conservation) was related to higher levels of perceived threat and lower levels of benefit, while higher preference for anxiety-free values (self-transcendence and openness to change) was related to higher levels of perceived benefits and lower levels of threat. Greater opportunities for contact and perceived benefits and lower levels of threats were related to more social contact. The model showed good fit across the total sample, and across four diverse immigrant groups in Israel (diaspora immigrants from the Former Soviet Union, Ethiopia and Western countries, and asylum seekers). In line with a Stereotype Content Model, which suggests that group-specific stereotypes are related to social structural characteristics of the group, associations between variables differed by group. Results strengthen a theoretical conceptualization that posits an indirect relationship between personal value preferences and behavior through group appraisal. They highlight the importance of comprehensive conceptualizations including both positive and negative appraisal of immigrants, which take into account the way different groups may be appraised by the majority population.

Smoking behavior and symptoms of depression and anxiety among young adult backpackers: Results from a short longitudinal study.

Levels of smoking and smoking initiation have been found to increase during the transition to adulthood. Symptoms of depression and anxiety may both precede or follow smoking behavior, yet there is equivocal evidence regarding the direction of this relationship. The aim of the current study was to examine the direction of this relationship in a group of young adult backpackers who traveled to social environments which are permissive of smoking. The current study involved a quasi-experimental design examining 199 (52% men, mean age 24.27, SD = 1.05 years at time 1) young adults, before, during and following a backpacking experience of at least six months. Regression analyses was used to examine the association between smoking and symptoms of depression and anxiety over time. Relative to smoking levels before the journey, a significant transient increase in smoking was found during the journey. The increase in smoking during the journey predicted increases in both depressive and anxiety symptoms following the journey. The reverse direction models were not significant. Our study suggests that social contexts which are permissive of smoking, such as backpacking, increase young adult smoking behavior. Mood symptoms did not contribute to the observed increase in smoking behavior but, inversely, increases in smoking contributed to heightened mood symptoms. Additional longitudinal studies are needed to explore the role that smoking behavior plays in young adults' mental health.

Optimizing Hepatitis C Virus (HCV) Treatment in a US Colocated HCV/Opioid Agonist Therapy Program.

BACKGROUND: A minority of patients with opioid use disorder are treated for hepatitis C virus infection (HCV). While colocated HCV and opioid agonist therapy (OAT) along with harm reduction can facilitate prevention and cascade to cure, there are few real-world examples of such embedded care models in the United States in the direct-acting antiviral (DAA) era. METHODS: We conducted a retrospective chart review to determine sustained virologic response (SVR) and reinfection rates during the first 5-year period of DAA availability among individuals tested and treated on-site at Rhode Island's only nonprofit methadone maintenance program. RESULTS: Of 275 who initiated DAAs, the mean age (range) was 43 (22-71) years, 34.5% were female, 57.5% had genotype 1a, 23.3% had cirrhosis, and 92% were Medicaid recipients. SVR was 85.0% (232/273), while modified intent-to-treat SVR was 93.2% (232/249); 17 patients did not achieve SVR, 2 awaited SVR 12 weeks post-end-of-treatment, and 24 were lost to follow-up. Thirty reinfections were identified over 375.5 person-years of follow-up (rate, 7.99/100 person-years). The median time to first reinfection (interquartile range) was 128 (85.25-202.5) days. Before July 1, 2018, 72 patients accessed DAAs over 3.7 years; after Medicaid DAA restrictions were lifted, 109 patients accessed DAAs over 1.3 years. The Prior Authorization (PA) process requires many steps, differing across 11 RI insurers, taking 45-120 minutes per patient. CONCLUSIONS: DAA treatment was effective among a marginalized population in an urban colocated OAT/HCV program. Removing DAA restrictions facilitates treatment initiation. The PA process remains a modifiable barrier to expanding capacity in the United States.

"What's a normal weight?" - Origin and receiving country influences on weight-status assessment among 1.5 and 2nd generation immigrant adolescents in Europe.

Many adolescents struggle with adequately assessing their weight-status, often leading to unnecessary weight-related interventions or preventing necessary ones. The prevalence of weight-status over- and underestimation differs considerably cross-nationally, suggesting that individual weight-status assessment is informed by cross-nationally differing standards of evaluation. For adolescents with a migration background, this brings up the possibility of a simultaneous influence of origin- and receiving country standards. The current study examines the magnitude of both influences using data from the 2014 Health Behaviour in School-Aged Children study. The cross-national design of the study enabled us to aggregate weight-evaluation standards for 41, primarily European, countries. Subsequently, we identified a sample of 8 124 adolescents with a migration background whose origin as well as receiving country participated in the study. Among those adolescents, we assessed the effects of origin and receiving country weight-evaluation standards using cross-classified multilevel regression analyses. Descriptive analyses revealed considerable differences in weight-evaluation standards between the countries. Regression analyses showed that both origin- and receiving country weight-evaluation standards were significantly associated cross-sectionally with weight-status assessment among the immigrant adolescents, with a stronger impact of receiving country standards. Results illustrate the context-sensitivity of adolescent weight-status assessment and reinforce the theoretical notion that immigrant adolescent development is not only informed by factors pertaining to their receiving country but also, albeit to a lesser extent, by those pertaining to their origin country.

A Modifiable Barrier to Hepatitis C Virus Elimination in Rhode Island: The Prior Authorization Process for Direct-Acting Antiviral Agents.

Hepatitis C virus (HCV) is disproportionately prevalent among different groups of marginalized populations in Rhode Island (RI). Although direct-acting antiviral (DAA) agents are safe and cure HCV, RI payers limit access to these life-saving medications using prior authorizations (PAs). We assessed RI DAA-specific PA criteria. The authors reviewed payers' websites and/or called payers to obtain, describe, and analyze DAA PA forms, and approval and appeal processes. While some information was consistently required, we observed substantial differences among payers' requirements. All PA forms require at least one piece of data that is clinically superfluous for DAA prescription. These include post-treatment laboratory results, prescriber requirements, documentation of co-treatment of substance use disorders, and repeat diagnostic tests. Post-approval barriers also exist; DAA PAs are time-limited, and DAAs can only be obtained from preferred pharmacies. The PA process requires many steps, differing across RI payers, taking 45-120 minutes per patient. To achieve HCV elimination, DAA PA forms and processes should be standardized, streamlined, and ultimately removed.