Diagnostic discrimination of social network indicators in alcohol use disorder: Initial examination using high-resolution and brief assessments.

OBJECTIVE: Social network analysis (SNA) characterizes the structure and composition of a person's social relationships. Network features have been associated with alcohol consumption in observational studies, primarily of university undergraduates. No studies have investigated whether indicators from a person's social network can accurately identify the presence of alcohol use disorder (AUD), offering an indirect strategy for identifying AUD. METHOD: Two cross-sectional case-control designs examined the clinical utility of social network indicators for identifying individuals with AUD (cases) versus demographically matched drinkers without AUD (controls). Study 1 (N = 174) used high-resolution egocentric SNA assessment, whereas Study 2 (N = 189) used a brief assessment. RESULTS: In Study 1, significant differences between AUD+ participants and controls were present for network alcohol severity (i.e., heavy drinking days; d = 1.23) and frequency (d = 0.35), but not network structural features. Network alcohol severity exhibited very good classification of AUD+ individuals versus controls (area under the curve [AUC] = 0.80), whereas network frequency did not (AUC = 0.61). In Study 2, significant differences were present for network alcohol severity (d = 1.02), quantity (d = 0.74), and frequency (d = 0.43), and severity exhibited good differentiation (AUC = 0.76). CONCLUSIONS: Social network indicators of alcohol involvement robustly differentiated AUD+ individuals from matched controls, and the brief assessment performed almost as well as the high-resolution assessment. These findings provide proof-of-concept for severity-related SNA indicators as promising novel clinical assessments for AUD. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Using Measurement-Based Care as a Precision Medicine Strategy for Substance Use Disorders.

PURPOSE OF REVIEW: Precision medicine prioritizes characterization of individual patient parameters to optimize care and this review evaluates measurement-based care (MBC) as a strategy for doing so in the treatment of substance use disorders (SUD). Measurement-based care refers to the systematic use of validated assessments to inform diagnosis and treatment planning, with varying frequency of assessments. Despite the seemingly obvious grounds for the use of MBC in treating SUD, systematic implementation to date has been limited. Thus, the goal of this review is to evaluate efforts to date and to stimulate greater consideration of MBC models in addictions programs. RECENT FINDINGS: Data from two published randomized controlled trials and findings from pragmatic clinical research highlight the potential utility of MBC in the SUD treatment settings. Despite these findings, the existing literature indicates the high need for larger-scale clinical trials and quality improvement programs. Potential barriers to the implementation of MBC for SUD are outlined at the patient, provider, organization, and system levels, as well as the challenges associated with the use of MBC programs for clinical research. Critical thinking considerations and risk mitigation strategies are offered toward advancing MBC for SUD beyond the current nascent state. Collectively, the existing data confirm that MBC is a suitable and promising strategy for applying a precision medicine approach in SUD treatment, warranting further implementation efforts and scientific inquiry.

A high-resolution PheWAS approach to alcohol-related polygenic risk scores reveals mechanistic influences of alcohol reinforcing value and drinking motives.

AIMS: This study uses a high-resolution phenome-wide approach to evaluate the motivational mechanisms of polygenic risk scores (PRSs) that have been robustly associated with coarse alcohol phenotypes in large-scale studies. METHODS: In a community-based sample of 1534 Europeans, we examined genome-wide PRSs for the Alcohol Use Disorders Identification Test (AUDIT), drinks per week, alcohol use disorder (AUD), problematic alcohol use (PAU), and general addiction, in relation to 42 curated phenotypes. The curated phenotypes were in seven categories: alcohol consumption, alcohol reinforcing value, drinking motives, other addictive behaviors, commonly comorbid psychiatric syndromes, impulsivity, and personality traits. RESULTS: The PRS for each alcohol phenotype was validated via its within-sample association with the corresponding phenotype (adjusted R2s = 0.35-1.68%, Ps = 0.012-3.6 × 10-7) with the exception of AUD. All PRSs were positively associated with alcohol reinforcing value and drinking motives, with the strongest effects from AUDIT-consumption (adjusted R2s = 0.45-1.33%, Ps = 0.006-3.6 × 10-5) and drinks per week PRSs (adjusted R2s = 0.52-2.28%, Ps = 0.004-6.6 × 10-9). Furthermore, the PAU and drinks per week PRSs were positively associated with adverse childhood experiences (adjusted R2s = 0.6-0.7%, Ps = 0.0001-4.8 × 10-4). CONCLUSIONS: These results implicate alcohol reinforcing value and drinking motives as genetically-influenced mechanisms using PRSs for the first time. The findings also highlight the value of dissecting genetic influence on alcohol involvement through diverse phenotypic risk pathways but also the need for future studies with both phenotypic richness and larger samples.

Posttraumatic stress and delay discounting: a meta-analytic review.

Delay discounting-the extent to which individuals show a preference for smaller immediate rewards over larger delayed rewards-has been proposed as a transdiagnostic neurocognitive process across mental health conditions, but its examination in relation to posttraumatic stress disorder (PTSD) is comparatively recent. To assess the aggregated evidence for elevated delay discounting in relation to posttraumatic stress, we conducted a meta-analysis on existing empirical literature. Bibliographic searches identified 209 candidate articles, of which 13 articles with 14 independent effect sizes were eligible for meta-analysis, reflecting a combined sample size of N = 6897. Individual study designs included case-control (e.g. examination of differences in delay discounting between individuals with and without PTSD) and continuous association studies (e.g. relationship between posttraumatic stress symptom severity and delay discounting). In a combined analysis of all studies, the overall relationship was a small but statistically significant positive association between posttraumatic stress and delay discounting (r = .135, p < .0001). The same relationship was statistically significant for continuous association studies (r = .092, p = .027) and case-control designs (r = .179, p < .001). Evidence of publication bias was minimal. The included studies were limited in that many did not concurrently incorporate other psychiatric conditions in the analyses, leaving the specificity of the relationship to posttraumatic stress less clear. Nonetheless, these findings are broadly consistent with previous meta-analyses of delayed reward discounting in relation to other mental health conditions and provide further evidence for the transdiagnostic utility of this construct.

High-resolution examination of changes in drinking during the COVID-19 pandemic: Nine-wave findings from a longitudinal observational cohort study of community adults.

Few multi-wave longitudinal studies have examined changes in drinking across extended periods of the coronavirus 2019 (COVID-19) pandemic. Using multiple indicators over three years, the current study examined: a) overall drinking changes; b) sex, income, age, and pre-COVID drinking level as moderators of changes; and c) the clinical significance of the observed changes. Using a longitudinal observational cohort design with nonclinical adults from the general community (N = 1395), assessments were collected over nine waves, two pre-COVID (April 2019 and October 2019) and seven intra-COVID (April 2020-April 2022). Drinking was measured as percent drinking days, percent heavy drinking days, and the Alcohol Use Disorders Identification Test (AUDIT) score. Clinically significant changes were defined based on the World Health Organization risk levels. All indicators exhibited significant changes from pre-pandemic to intra-pandemic periods, with drinking changes comprising early pandemic increases followed by subsequent decreases and AUDIT scores consistently declining. Pre-pandemic drinking level substantially moderated all changes. Heavier drinkers exhibited larger decreases compared to other drinking groups. In terms of clinically important changes, ∼10% of pre-pandemic abstinent or low-risk drinkers transitioned to medium- or high-risk status during the pandemic. In contrast, 37.1% of medium-risk drinkers and 44.6% of high-risk drinkers exhibited clinically significant decreases during the intra-pandemic period. Collectively, these findings highlight the multifarious impacts of the pandemic on drinking over time, comprising both increases and decreases in drinking behaviour.

Mimicking superinfection exclusion disrupts alphavirus infection and transmission in the yellow fever mosquito Aedes aegypti.

Multiple viruses, including pathogenic viruses, bacteriophages, and even plant viruses, cause a phenomenon termed superinfection exclusion whereby a currently infected cell is resistant to secondary infection by the same or a closely related virus. In alphaviruses, this process is thought to be mediated, at least in part, by the viral protease (nsP2) which is responsible for processing the nonstructural polyproteins (P123 and P1234) into individual proteins (nsP1-nsP4), forming the viral replication complex. Taking a synthetic biology approach, we mimicked this naturally occurring phenomenon by generating a superinfection exclusion-like state in Aedes aegypti mosquitoes, rendering them refractory to alphavirus infection. By artificially expressing Sindbis virus (SINV) and chikungunya virus (CHIKV) nsP2 in mosquito cells and transgenic mosquitoes, we demonstrated a reduction in both SINV and CHIKV viral replication rates in cells following viral infection as well as reduced infection prevalence, viral titers, and transmission potential in mosquitoes.

Resting state functional connectivity as a predictor of brief intervention response in adults with alcohol use disorder: A preliminary study.

BACKGROUND: Brief interventions for alcohol use disorder (AUD) are generally efficacious, albeit with variability in response. Resting state functional connectivity (rsFC) may characterize neurobiological indicators that predict the response to brief interventions and is the focus of the current investigation. MATERIALS AND METHODS: Forty-six individuals with AUD (65.2% female) completed a resting state functional magnetic resonance imaging (fMRI) scan immediately followed by a brief intervention aimed at reducing alcohol consumption. Positive clinical response was defined as a reduction in alcohol consumption by at least one World Health Organization (WHO) risk drinking level at 3-month follow-up. rsFC was analyzed using seed-to-voxel analysis with seed regions from four networks: salience network, reward network, frontoparietal network, and default mode network. RESULTS: At baseline, responders had greater rsFC between the following seed regions in relation to voxel-based clusters than non-responders: (i) anterior cingulate cortex (ACC) in relation to left postcentral gyrus and right supramarginal gyrus (salience network); (ii) right posterior parietal cortex in relation to right ventral ACC (salience network); (iii) right interior frontal gyrus (IFG) pars opercularis in relation to right cerebellum and right occipital fusiform gyrus (frontoparietal); and (iv) right primary motor cortex in relation to left thalamus (default mode). Lower rsFC in responders vs. nonresponders was seen between the (i) right rostral prefrontal cortex in relation to left IFG pars triangularis (frontoparietal); (ii) right IFG pars triangularis in relation to right cerebellum (frontoparietal); (iii) right IFG pars triangularis in relation to right frontal eye fields and right angular gyrus (frontoparietal); and (iv) right nucleus accumbens in relation to right orbital frontal cortex and right insula (reward). CONCLUSIONS: Resting state functional connectivity in the frontoparietal, salience, and reward networks predicts the response to a brief intervention in individuals with AUD and could reflect greater receptivity or motivation for behavior change.

Leveraging related health phenotypes for polygenic prediction of impulsive choice, impulsive action, and impulsive personality traits in 1534 European ancestry community adults.

Impulsivity refers to a number of conceptually related phenotypes reflecting self-regulatory capacity that are considered promising endophenotypes for mental and physical health. Measures of impulsivity can be broadly grouped into three domains, namely, impulsive choice, impulsive action, and impulsive personality traits. In a community-based sample of ancestral Europeans (n = 1534), we conducted genome-wide association studies (GWASs) of impulsive choice (delay discounting), impulsive action (behavioral inhibition), and impulsive personality traits (UPPS-P), and evaluated 11 polygenic risk scores (PRSs) of phenotypes previously linked to self-regulation. Although there were no individual genome-wide significant hits, the neuroticism PRS was positively associated with negative urgency (adjusted R2 = 1.61%, p = 3.6 × 10-7 ) and the educational attainment PRS was inversely associated with delay discounting (adjusted R2 = 1.68%, p = 2.2 × 10-7 ). There was also evidence implicating PRSs of attention-deficit/hyperactivity disorder, externalizing, risk-taking, smoking cessation, smoking initiation, and body mass index with one or more impulsivity phenotypes (adjusted R2 s: 0.35%-1.07%; FDR adjusted ps = 0.05-0.0006). These significant associations between PRSs and impulsivity phenotypes are consistent with established genetic correlations. The combined PRS explained 0.91%-2.46% of the phenotypic variance for individual impulsivity measures, corresponding to 8.7%-32.5% of their reported single-nucleotide polymorphism (SNP)-based heritability, suggesting a non-negligible portion of the SNP-based heritability can be recovered by PRSs. These results support the predictive validity and utility of PRSs, even derived from related phenotypes, to inform the genetics of impulsivity phenotypes.

The Clinical Relevance of Impulsivity in Substance Use Disorder Treatment: Examining Within-Treatment Changes and Relationship to Psychiatric Symptoms and Cravings in a Large Inpatient Sample.

OBJECTIVE: Impulsivity is a multidimensional construct consistently associated with problematic substance use, but less is known about its relevance to clinical outcomes. The current study examined whether impulsivity changed over the course of addiction treatment and whether the changes were associated with changes in other clinical outcomes. METHOD: Participants were patients in a large inpatient addiction medicine program (N = 817; 71.40% male). Impulsivity was assessed using a self-report measure of delay discounting (i.e., overvaluation of smaller immediate rewards) and the UPPS-P Impulsive Behavior Scale, a self-report measure of impulsive personality traits. Outcomes were psychiatric symptoms including depression, anxiety, posttraumatic stress disorder, and drug cravings. RESULTS: Within-subjects analyses of variance revealed significant within-treatment changes in all UPPS-P subscales, all psychiatric indicators, and craving (ps < .005), but not delay discounting. Changes in all UPPS-P traits, except for sensation seeking, were significantly positively associated with changes in psychiatric symptoms and cravings over the course of treatment (ps < .01). CONCLUSIONS: These findings reveal that facets of impulsive personality change across addiction treatment and are generally related to positive changes in other clinically relevant outcomes. Evidence of change despite no explicit intervention targeting suggests that impulsive personality traits may be viable treatment targets in substance use disorder treatment.

Impacts of the COVID-19 public health restrictions on substance use, mental health, and psychosocial functioning among individuals with alcohol use disorder.

Background: The COVID-19 pandemic has been associated with major psychosocial disruptions and there is particular concern for individuals with substance use disorders.Objectives: This study characterized the psychosocial and experiential impacts of the pandemic on individuals seeking alcohol use disorder (AUD) recovery, including pandemic impacts on self-reported drinking, heavy drinking, tobacco, cannabis, and stimulant use.Methods: Participants were 125 AUD+ individuals (% males: 57.60; Mage = 49.11, SD = 12.13) reporting on substance use from January 1st-24th March, 2020 (pre-pandemic) and since the stay-at-home orders commenced, 24th March-June 28th 2020 (intra-pandemic). Within-subjects changes were examined and a latent profile analysis was performed to identify subgroups differentially impacted by the pandemic.Results: Large proportions reported psychosocial impacts of COVID-19, but drinking and other substance use did not reveal significant changes. Latent profile analyses revealed two subgroups: Profile 1 (n = 41/125), "Moderately Impacted") and Profile 2 (n = 84/125), "Severely Impacted"). Compared to the pre-pandemic period, the group that was moderately impacted by the pandemic exhibited significantly fewer heavy drinking days (p = .02) during the intra-pandemic period, but no other substance use changes. The group showing severe pandemic impacts did not exhibit changes in alcohol or other drug use but evidenced more severe anxiety and depression (ps < .001).Conclusions: We found heterogeneous subtypes of pandemic-related impacts in AUD recovery patients. There is need to provide psychosocial support to this particular population and further monitoring substance use and mental health.

Characterizing problematic internet use in a sample of heavy drinking emerging adults.

OBJECTIVE: Problematic internet use (PIU) is characterized by excessive or poorly controlled internet use resulting in impairment or distress. PIU is most prevalent during emerging adulthood, a period marked by an increase in psychiatric disorders, including substance use disorders (SUDs). In a sample of high-risk emerging adults, the aim of this study was to examine the relationship between PIU and quality of life (QoL), psychiatric disorders, and impulsivity. METHODS: Participants were a community sample of heavy drinking emerging adults in Hamilton, Ontario (N = 709). Measures included: PIU, QoL, eight psychiatric indicators, and three domains of impulsivity. All variables that were significantly associated with PIU were subsequently examined concurrently in structural equation models. RESULTS: PIU was negatively associated with physical QoL (ß = -0.27, p < .01) and social QoL (ß = -0.20, p < .01), but positively associated with environmental QoL (ß = 0.17, p < .01). For psychiatric conditions, PIU was positively associated with internalizing disorders (ß = 0.42, p < .01) but not SUD (ß = -0.01, p = .90). For impulsivity, PIU was positively associated with Lack of Perseverance (ß = 0.16, p < .01) and Negative Urgency (ß = 0.23, p < .01) but no other indicators. CONCLUSIONS: This study provides further evidence that PIU is associated with lower quality of life, selectively co-occurs with internalizing psychopathology, and is associated with certain impulsive traits. Lack of associations with SUD challenges conceptualizations of PIU as an alternative manifestation of externalizing psychopathology. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Public health guideline compliance and perceived government effectiveness during the COVID-19 pandemic in Canada: Findings from a longitudinal cohort study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has imposed enormous adversity worldwide. Public health guidelines have been a first line of defense but rely on compliance with evolving recommendations and restrictions. This study sought to characterize adherence to and perceptions of public health guidelines over a one-year timeframe during the pandemic. METHODS: Participants were 1435 community adults in Ontario who completed assessments at five time points (April 2020, July 2020, October 2020, January 2021, and April 2021; 92% retention). Participants were assessed for self-reported adherence to government protocols and perceptions of government response (importance, compliance, and effectiveness). Analyses used general linear mixed-effects modelling of overall changes by time and examined differences based on age and sex. FINDINGS: Over time, participants reported high or increasing behavioural engagement in public health guidelines, including physical distancing, restricting activity, and masking. In contrast, participants exhibited significant reductions in perceived importance and compliance, with evidence of more negative changes in younger participants. The largest changes were a substantial reduction in perceived government effectiveness, from predominantly positive perceptions to predominantly negative perceptions. INTERPRETATION: These results illuminate evolving trends in public health compliance and perceptions over the course of the pandemic in Canada, revealing the malleability of public perceptions of public health recommendations and government effectiveness. FUNDING: This research was funded by a grant from the Canadian Institutes of Health Research (CIHR). CIHR had no role in study design, data collection, data analysis, interpretation, or writing of the report.

Psychometric evaluation of the treatment entry questionnaire to assess extrinsic motivation for inpatient addiction treatment.

Introduction: Valid multi-faceted measurement of motivation for substance use disorder (SUD) treatment is needed to help inform treatment approaches and predict outcomes. This study examined evidence of validity for the Treatment Entry Questionnaire (TEQ-9). Methods: Data represented individuals entering inpatient SUD treatment (n = 1455). We used confirmatory factor analysis (CFA) to assess the three-factor structure of the TEQ-9 [identified (i.e., values/personally chooses treatment), introjected (i.e., internally controlled by guilt/shame) and external motivations (i.e., external pressure/demands)], and examined measurement invariance across gender, age, and ethno-racial identity. Correlation with readiness and confidence assessed convergent validity, while correlations with substance use problem severity and previous substance use treatment assessed meaningful group differences. Results: A three-factor structure was confirmed with all items loading significantly onto their respective factors (ps < 0.001). Each subscale demonstrated high internal consistency (Identified α = 0.90; Introjected α = 0.79; External α = 0.85). Each subscale demonstrated measurement invariance up to the scalar level across all sub-groups. Readiness, confidence, and substance use problem severity correlated as expected across various substances with the identified (rs = 0.098 - 0.262, ps < 0.05), and external (rs = -0.096 - -0.178, ps < 0.05) subscales. Additionally, the mean Identified subscale score was significantly higher among those who previously engaged in SUD treatment (p < 0.001). Findings for the Introjected subscale were more ambiguous. Conclusions: Findings provide evidence for factorial validity, measurement invariance, convergent validity and group differences of the TEQ-9 in a large clinically mixed inpatient SUD treatment population, providing further support of its clinical and research utility.

COVID-19 Vaccine Perceptions and Differences by Sex, Age, and Education in 1,367 Community Adults in Ontario.

Background: COVID-19 is a global pandemic and vaccination efforts may be impeded by vaccine hesitancy. The present study examined willingness to receive a COVID-19 vaccine, the associated reasons for willingness/unwillingness, and vaccine safety perceptions in a cross-sectional assessment of community adults in Ontario. Methods: One thousand three hundred sixty seven individuals (60.6% female, mean age = 37.5%) participated in this study between January 15, 2021 and February 15, 2021. Perceptions of vaccine safety and reasons for willingness/unwillingness to receive the COVID-19 vaccine were investigated using an online assessment. Perceptions were investigated in general and by age, sex and education using analysis of variance. Results: Overall, 82.8% of the sample reported they were willing to receive a COVID-19 vaccine and 17.2% reported they were unwilling. The three most common reasons for unwillingness were long-term side effects (65.5%), immediate side effects (60.5%), and lack of trust in the vaccine (55.2%). Vaccine willingness significantly differed by sex and education level, with female participants and those with less than a bachelor's degree being more likely to report unwillingness. Perception of COVID-19 vaccine safety was significantly lower (-10.3%) than vaccines in general and differed by age, sex and education, with females, older adults, and individuals with less than a bachelor's degree reporting lower perceived COVID-19 vaccine safety. Conclusion: In this sample of community adults, the COVID-19 vaccine hesitancy rate was less than one in five individuals, but with higher rates in population subgroups. Targeting public health messaging to females and individuals with less than bachelor's degree, and addressing concerns about long-term and immediate side effects may increase vaccine uptake.

Steep Discounting of Future Rewards as an Impulsivity Phenotype: A Concise Review.

This chapter provides an overview over the behavioral economic index of impulsivity known as delay discounting. Specifically, delay discounting refers to an individual's preference for smaller immediate rewards over a larger delayed rewards. The more precipitously an individual discounts future rewards, the more impulsive they are considered to be. First, the chapter reviews the nature of delay discounting as a psychological process and juxtaposes it with nominally similar processes, including other facets of impulsivity. Second, the chapter reviews the links between delay discounting and numerous health behaviors, including addiction, attention deficit/hyperactivity disorder, and obesity. Third, the determinants of individual variation in delay discounting are discussed, including both genetic and environmental contributions. Finally, the chapter evaluates delay discounting as a potentially modifiable risk factor and the status of clinical interventions designed to reduce delay discounting to address deficits in self-control in a variety of maladaptive behaviors.

Psychometric Validation of the Brief Alcohol Social Density Assessment in an Adult Community Sample.

BACKGROUND: Individuals' social networks exert a strong influence on alcohol use, but valid assessment of network drinking behavior is typically lengthy and high in participant burden. The aim of this study was to validate the Brief Alcohol Social Density Assessment (BASDA), an efficient measure of perceived alcohol use within a person's social network, in a sample of adult drinkers from the general community. Specifically, the convergent, criterion-related, incremental validity and internal validity were investigated by examining the BASDA in relation to other established measures of drinking motives, weekly drinking level, and severity of involvement. METHODS: Participants were 903 (56% female) adults who reported drinking in the last year and who completed the BASDA, the Drinking Motives Questionnaire, the Daily Drinking Questionnaire, and the Alcohol Use Disorders Identification Test (AUDIT). RESULTS: Significant positive correlations were found between the BASDA and drinking motives, drinking quantity, and the AUDIT (rs = 0.21 to 0.51, ps < 0.001), providing support for convergent validity. There was a significantly higher BASDA score for those scoring at or above an AUDIT cutoff for hazardous drinking (p < 0.001), providing support for criterion-related validity. Finally, beyond motives and covariates, the BASDA was significantly associated with total AUDIT score (ΔR2  = 0.09, p < 0.001), indicating its additive contribution and providing support for incremental validity. Confirmatory factor analysis revealed excellent fit, and all items significantly loaded onto a single factor (p < 0.0001), providing evidence of internal validity. The resulting alcohol social density latent variable was significantly and robustly associated with drinks per week and AUDIT total score. CONCLUSIONS: These findings provide further support for the BASDA as a valid and efficient measure of social network alcohol density for understanding social influences on alcohol misuse.

Improving feeding practices: current patterns, common constraints, and the design of interventions.

We propose a set of "best-practice complementary feeding behaviors," which were derived by combining principles of psychosocial care with current knowledge in nutritional sciences. We provide a theoretical rationale for assessing and describing complementary feeding practices in terms of what is fed, how food is prepared and given, who feeds the child, when food is fed (frequency and scheduling), and the feeding environment (where). We also discuss the significance of selected sociocultural determinants of these practices for the design of interventions. We then review 18 case studies in relation to these practices and their determinants. The exercise, in which we abstracted data from ethnographic reports, revealed areas of congruence and deviations from best-practice behaviors. The data on feeding practices are described with a common framework to facilitate comparison across sites. Key themes emerging from the studies include the significance of the larger family, the effects of competing maternal time demands, and the importance of parental perceptions and cultural constructs in affecting complementary feeding practices. Finally, we discuss the implications of the findings for future interventions.