Measuring sexual behavior stigma among cisgender men who have sex with men: an assessment of cross-country measurement invariance.

Objectives: Globally, cisgender men who have sex with men experience sexual stigma, but limited investigation of cross-population scale performance hinder comparisons. As measurement invariance is a necessary but seldom-established criterion of valid cross-cultural comparisons, we assessed invariance in scales of stigma related to sexual behavior across 9 countries. Methods: This secondary analysis used data collected from adult (mean age=29.6, standard deviation=12.5) cisgender men who have sex with men (n=8,669) in studies from 6 West African, 2 Southern African, and 1 North American country from 2012-2016. A common item set assessed 2 sexual behavior stigma domains. A sequential process was used to test the factor structure and measurement invariance, which included multigroup confirmatory factor analyses (CFA). Individual countries, items, living with HIV, and disclosure were explored as possible sources of noninvariance. Results: Goodness-of-fit statistics indicated adequate fit of the same 2-factor model in 7 of the 9 countries. The chi2 difference test comparing a constrained and unconstrained 7-country model in which loadings and thresholds were freely estimated was significant (p<0.001), indicating metric and scalar noninvariance, but removing the US provided evidence of invariance and freeing certain items led to a finding of partial invariance. Sexuality disclosure exhibited a direct relationship with select stigma items in several countries. Conclusions: Our findings point to the utility of the two stigma scale dimensions in making cross-country comparisons, but also to the necessity of assessing invariance with explicit attention to several factors including differential disclosure of sexuality across contexts to ensure valid comparisons.

Does perceived caregiver HIV stigma and depression increase adolescent neuro-behavioral difficulties? A mediation analysis in the Asenze Cohort.

People living with HIV (PLWH) often experience HIV related stigma that is, in turn, associated with several negative health outcomes including depression, harmful drinking, and intimate partner violence. Despite knowledge of these proximal impacts of HIV stigma on PLWH, less is known about the impact that Caregivers living with HIV's perception of stigma has on the health and behavior of adolescents in their care. Utilizing data from adolescents and their primary caregivers from the population-based Asenze cohort study in KwaZulu-Natal, South Africa, we conducted a path analysis to determine if caregiver depression [operationalized as mental health functioning] is a mediator of the hypothesized association between caregiver HIV stigma and adolescent neurodevelopmental behavior including internalizing and externalizing behaviors. Results suggest good model fit and a statistically significant relationship between caregiver HIV stigma and caregiver mental health functioning. However, neither the direct nor indirect (including potential mediator caregiver mental health functioning) effect of HIV stigma on adolescent behavioral difficulties was statistically significant. This paper builds on previous research demonstrating the relationship between HIV stigma and depression, highlighting the need for continued study of underlying mechanisms that impact the stigma and health of PLWH and others important to them such as their children.

HIV status and substance use disorder treatment need and utilization among adults in the United States, 2015-2019: Implications for healthcare service provision and integration.

INTRODUCTION: Substance use disorders (SUD) are associated with HIV acquisition and care disruptions. Most research focuses on clinical samples; however, we used a nationally representative, community-based sample to estimate SUD treatment need and utilization by HIV status. METHODS: We included participants from the 2015-2019 National Survey on Drug Use and Health aged 18 and older who met past-year DSM-IV SUD criteria (n = 22,166). Participants self-reported whether a healthcare professional ever told them they had HIV or AIDS [i.e., people with HIV (PWH), non-PWH, HIV status unknown]. Outcomes included past-year: 1) any SUD treatment use; 2) any specialty SUD treatment use; and 3) perceived SUD treatment need. Survey weighted multivariable logistic regression models estimated the likelihood of each outcome by HIV status, adjusting for age, sex, race/ethnicity, education, survey year, health insurance status, and household income. RESULTS: Overall, 0.5 % were PWH and 0.8 % had an HIV unknown status. Any past-year SUD treatment utilization was low across all groups (10.3 % non-PWH, 24.2 % PWH, and 17.3 % HIV status unknown respondents). Specialty SUD treatment utilization was reported by 7.2 % of non-PWH, 17.8 % PWH, and 10.9 % HIV status unknown respondents. Perceived treatment need was reported by 4.9 % of non-PWH, 12.4 % of PWH, and 3.7 % of HIV status unknown respondents. In adjusted models, PWH were more likely than non-PWH to report any past-year SUD treatment utilization (aOR = 2.06; 95 % CI = 1.08-3.94) or past-year specialty SUD treatment utilization (aOR = 2.07; 95 % CI = 1.07-4.01). Among those with a drug use disorder other than cannabis, respondents with HIV-unknown status were less likely than HIV-negative individuals to report past-year perceived treatment need (aOR = 0.39; 95 % CI = 0.20-0.77). CONCLUSIONS: Despite high SUD treatment need among PWH, more than three quarters of PWH with SUD reported no past-year treatment. Compared to non-PWH, PWH had higher treatment utilization and higher specialty treatment utilization, but SUD treatment was low across all groups. As SUD is associated with adverse HIV outcomes, our findings highlight the need for the integration of SUD treatment with HIV testing and care. Increasing access to SUD treatment could help reduce negative SUD-related outcomes along the HIV care continuum.

PTHrP intracrine actions divergently influence breast cancer growth through p27 and LIFR.

The role of parathyroid hormone (PTH)-related protein (PTHrP) in breast cancer remains controversial, with reports of PTHrP inhibiting or promoting primary tumor growth in preclinical studies. Here, we provide insight into these conflicting findings by assessing the role of specific biological domains of PTHrP in tumor progression through stable expression of PTHrP (-36-139aa) or truncated forms with deletion of the nuclear localization sequence (NLS) alone or in combination with the C-terminus. Although the full-length PTHrP molecule (-36-139aa) did not alter tumorigenesis, PTHrP lacking the NLS alone accelerated primary tumor growth by downregulating p27, while PTHrP lacking the NLS and C-terminus repressed tumor growth through p27 induction driven by the tumor suppressor leukemia inhibitory factor receptor (LIFR). Induction of p27 by PTHrP lacking the NLS and C-terminus persisted in bone disseminated cells, but did not prevent metastatic outgrowth, in contrast to the primary tumor site. These data suggest that the PTHrP NLS functions as a tumor suppressor, while the PTHrP C-terminus may act as an oncogenic switch to promote tumor progression through differential regulation of p27 signaling.

Task Sharing and Remote Delivery of Brief Interpersonal Counseling for Venezuelan Migrants and Refugees Living in Peru during the COVID-19 Pandemic: A Mixed-Methods Pilot Study.

Refugees and migrants experience an elevated risk for mental health problems and face significant barriers to receiving services. Interpersonal counseling (IPC-3) is a three-session intervention that can be delivered by non-specialists to provide psychological support and facilitate referrals for individuals in need of specialized care. We piloted IPC-3 delivered remotely by eight Venezuelan refugee and migrant women living in Peru. These counselors provided IPC-3 to Venezuelan refugee and migrant clients in Peru (n = 32) who reported psychological distress. Clients completed assessments of mental health symptoms at baseline and one-month post-intervention. A subset of clients (n = 15) and providers (n = 8) completed post-implementation qualitative interviews. Results showed that IPC-3 filled a gap in the system of mental health care for refugees and migrants in Peru. Some adaptations were made to IPC-3 to promote its relevance to the population and context. Non-specialist providers developed the skills and confidence to provide IPC-3 competently. Clients displayed large reductions in symptoms of depression (d = 1.1), anxiety (d = 1.4), post-traumatic stress (d = 1.0), and functional impairment (d = 0.8). Remote delivery of IPC-3 by non-specialists appears to be a feasible, acceptable, and appropriate strategy to address gaps and improve efficiency within the mental health system and warrants testing in a fully powered effectiveness study.

Leveraging a Digitized Mental Wellness (DIGImw) Program to Provide Mental Health Care for Internally Displaced People.

A local insurgency has displaced many people in the northern Mozambican province of Cabo Delgado. The authors' global team (comprising members from Brazil, Mozambique, South Africa, and the United States) has been scaling up mental health services across the neighboring province of Nampula, Mozambique, now host to >200,000 displaced people. The authors describe how mental health services can be expanded by leveraging digital technology and task-shifting (i.e., having nonspecialists deliver mental health care) to address the mental health needs of displaced people. These methods can serve as a model for other researchers and clinicians aiming to address mental health needs arising from humanitarian disasters in low-resource settings.

Effectiveness of trauma-focused cognitive behavioral therapy compared to psychosocial counseling in reducing HIV risk behaviors, substance use, and mental health problems among orphans and vulnerable children in Zambia: a community-based randomized controlled trial.

Orphans and vulnerable children (OVC) in sub-Saharan Africa are at high risk for HIV infection and transmission. HIV prevention and treatment efforts with OVC are hindered by mental health and substance use problems. This randomized controlled trial compared a mental health intervention, Trauma Focused Cognitive Behavioral Therapy (TF-CBT), to an enhanced version of an existing HIV Psychosocial Counseling (PC+) program among 610 adolescents who met PEPFAR criteria for OVC and had HIV risk behaviors in Lusaka, Zambia. Outcomes included HIV risk behaviors (e.g., risky sexual behaviors), mental health (internalizing symptoms, externalizing behaviors, PTSD) and substance use. At 12-month follow-up, there were significant within group reductions in both groups for all outcomes, with the only significant between group difference being for substance use, in which OVC who received TF-CBT had significantly greater reductions than OVC who received PC+. In a subgroup analysis of OVC with high levels of PTSD symptoms, TF-CBT was superior to PC + in reducing internalizing symptoms, functional impairment, and substance use. Findings support TF-CBT for reducing substance use among OVC. Subgroup analysis results suggest that a robust intervention such as TF-CBT is warranted for OVC with significant mental and behavioral health comorbidities. The similar performance of TF-CBT and PC + in the overall sample for risky sexual behavior and mild mental health problems indicates that enhancing existing psychosocial programs, such as PC, with standard implementation factors like having a defined training and supervision schedule (as was done to create PC+) may improve the efficacy of HIV risk reduction efforts.Clinical Trials Number: NCT02054780.

Efficacy and moderators of efficacy of cognitive behavioural therapies with a trauma focus in children and adolescents: an individual participant data meta-analysis of randomised trials.

BACKGROUND: Existing clinical trials of cognitive behavioural therapies with a trauma focus (CBTs-TF) are underpowered to examine key variables that might moderate treatment effects. We aimed to determine the efficacy of CBTs-TF for young people, relative to passive and active control conditions, and elucidate putative individual-level and treatment-level moderators. METHODS: This was an individual participant data meta-analysis of published and unpublished randomised studies in young people aged 6-18 years exposed to trauma. We included studies identified by the latest UK National Institute of Health and Care Excellence guidelines (completed on Jan 29, 2018) and updated their search. The search strategy included database searches restricted to publications between Jan 1, 2018, and Nov 12, 2019; grey literature search of trial registries ClinicalTrials.gov and ISRCTN; preprint archives PsyArXiv and bioRxiv; and use of social media and emails to key authors to identify any unpublished datasets. The primary outcome was post-traumatic stress symptoms after treatment (<1 month after the final session). Predominantly, one-stage random-effects models were fitted. This study is registered with PROSPERO, CRD42019151954. FINDINGS: We identified 38 studies; 25 studies provided individual participant data, comprising 1686 young people (mean age 13·65 years [SD 3·01]), with 802 receiving CBTs-TF and 884 a control condition. The risk-of-bias assessment indicated five studies as low risk and 20 studies with some concerns. Participants who received CBTs-TF had lower mean post-traumatic stress symptoms after treatment than those who received the control conditions, after adjusting for post-traumatic stress symptoms before treatment (b=-13·17, 95% CI -17·84 to -8·50, p<0·001, τ2=103·72). Moderation analysis indicated that this effect of CBTs-TF on post-traumatic stress symptoms post-treatment increased by 0·15 units (b=-0·15, 95% CI -0·29 to -0·01, p=0·041, τ2=0·03) for each unit increase in pre-treatment post-traumatic stress symptoms. INTERPRETATION: This is the first individual participant data meta-analysis of young people exposed to trauma. Our findings support CBTs-TF as the first-line treatment, irrespective of age, gender, trauma characteristics, or carer involvement in treatment, with particular benefits for those with higher initial distress. FUNDING: Swiss National Science Foundation.

Evaluation of the Early Adolescent Skills for Emotions (EASE) intervention in Lebanon: A randomized controlled trial.

BACKGROUND: There is a need for scalable evidence-based psychological interventions for young adolescents experiencing high levels of psychological distress in humanitarian settings and low- and middle-income countries. Poor mental health during adolescence presents a serious public health concern as it is a known predictor of persistent mental disorders in adulthood. This study evaluates the effectiveness of a new group-based intervention developed by the World Health Organization (Early Adolescent Skills for Emotions; EASE), implemented by non-specialists, to reduce young adolescents' psychological distress among mostly Syrian refugees in Lebanon. METHODS: We conducted a two-arm, single-blind, individually randomized group treatment trial. Adolescents aged 10 to 14 years who screened positive for psychological distress using the Pediatric Symptom Checklist (PSC) were randomly allocated to EASE or enhanced treatment as usual (ETAU) (1:1.6). ETAU consisted of a single scripted psycho-education home-visit session with the adolescent and their caregivers. EASE consists of seven group sessions with adolescents and three sessions with caregivers. The primary outcome was adolescent-reported psychological distress as measured with the PSC (internalizing, externalizing, and attentional symptoms). Secondary outcomes included depression, posttraumatic stress, well-being, functioning, and caregivers' parenting and distress. All outcomes were assessed at baseline, endline, and 3 months (primary time point) and 12 months follow-up. RESULTS: Due to the COVID-19 pandemic and other adversities in Lebanon at the time of this research, the study was prematurely terminated, resulting in an under-powered trial sample (n = 198 enrolled compared to n = 445 targeted). We screened 604 children for eligibility. The 198 enrolled adolescents were assigned to EASE (n = 80) and ETAU (n = 118), with retention rates between 76.1 and 88.4% across all timepoints. Intent-to-treat analyses demonstrated no between-group differences on any of the outcome measures between the EASE and ETAU. We did observe a significant improvement on the primary outcome equally in the EASE and ETAU groups (-0.90, 95% CI: -3.6, 1.8; p = .52), - a trend that was sustained at three months follow-up. Sub-group analyses, for those with higher depression symptoms at baseline, showed ETAU outperformed EASE on reducing depression symptoms (difference in mean change = 2.7, 95% CI: 0.1, 5.3; p = .04; d = 0.59) and internalizing problems (difference in mean change 1.0, 95% CI: 0.08, 1.9; p = .03; d = 0.56) . CONCLUSION: No conclusions can be drawn about the comparative effectiveness of the intervention given that the sample was underpowered as a result of early termination. Both EASE and single session psycho-education home visits resulted in meaningful improvements in reducing psychological distress. We did not identify any indications in the data suggesting that EASE was more effective than a single session family intervention in the context of the COVID-19 pandemic and other crises in Lebanon. Fully powered research is needed to evaluate the effectiveness of EASE.

Alcohol and other drug use patterns and services in an integrated refugee settlement in Northern Zambia: a formative research study.

BACKGROUND: Evidence on patterns of alcohol and other drug (AOD) use and how to effectively deliver services to address AOD use in humanitarian settings is limited. This study aimed to qualitatively explore the patterns of AOD use among Congolese refugees in Mantapala Refugee Settlement and members of the surrounding host community and identify potential appropriate intervention and implementation approaches to address AOD use disorders among conflict-affected populations. METHODS: Fifty free listing interviews, 25 key informant interviews, and four focus group discussions were conducted among refugees, host community members, humanitarian implementing agency staff, and refugee incentive workers. These participants were selected based on their knowledge of AOD use and related problems in the settlement and the surrounding host community in northern Zambia. RESULTS: Cannabis and home-brewed alcohol were the substances that were perceived to be most commonly used and have the greatest impact on the community. Participants reported that self-medication, boredom, and relief of daily stressors associated with lack of housing, safety, and employment were reasons that people used AODs. Participants recommended that programming include components to address the underlying causes of AOD use, such as livelihood activities. Stigma due to the criminalization of and societal ideals and religious beliefs regarding AOD use was identified as a substantial barrier to accessing and seeking treatment. CONCLUSIONS: Our study's findings indicate the need for services to address AOD use in Mantapala Refugee Settlement. Interventions should consider the social and structural determinants of AOD use.

Re-Evaluating the Role of PTHrP in Breast Cancer.

Parathyroid-hormone-related protein (PTHrP) is a protein with a long history of association with bone metastatic cancers. The paracrine signaling of PTHrP through the parathyroid hormone receptor (PTHR1) facilitates tumor-induced bone destruction, and PTHrP is known as the primary driver of humoral hypercalcemia of malignancy. In addition to paracrine signaling, PTHrP is capable of intracrine signaling independent of PTHR1 binding, which is essential for cytokine-like functions in normal physiological conditions in a variety of tissue types. Pre-clinical and clinical studies evaluating the role of PTHrP in breast cancer have yielded contradictory conclusions, in some cases indicating the protein is tumor suppressive, and in other studies, pro-growth. This review discusses the possible molecular basis for the disharmonious prognostic indications of these studies and highlights the implications of the paracrine, intracrine, and nuclear functions of the protein. This review also examines the current understanding of the functional domains of PTHrP and re-evaluates their role in the unique context of the breast cancer environment. This review will expand on the current understanding of PTHrP by attempting to reconcile the functional domains of the protein with its intracrine signaling in cancer.

HIV stigma and disclosure of alcohol use to physicians: examining the mediating role of depression among persons living with HIV.

Alcohol use among persons living with HIV (PWH) can lead to poor disease outcomes. Disclosure of alcohol consumption to physicians is critical to inform HIV care. HIV stigma is associated with poor care engagement, and this relationship is partially mediated by depression. However, less is known about how HIV stigma and depression affect reporting of alcohol use to care providers. We used baseline data from an HIV intervention trial of 330 adult PWH in Baltimore, MD. We fit a path model to examine whether HIV stigma was associated with increased depression symptoms and whether higher levels of depression were, in turn, associated with underreporting of alcohol use to physicians. Among PWH reporting past 6-month alcohol use (n = 182, 55%), 64% met symptom criteria for probable depression, 58% met criteria for hazardous drinking, and 10% reported not disclosing alcohol use to their physician. HIV stigma was associated with higher levels of depression (ß = 0.99, p < .0001); depression was associated with a lower likelihood of alcohol disclosure (ß = -0.04, p < .0001); and depression mediated the indirect pathway from stigma to alcohol disclosure (ß = -0.04, p < .01). Methods to augment or strengthen alcohol self-report may be useful in HIV care, particularly among PWH experiencing HIV stigma and depression.

Efficacy of alcohol reduction interventions among people with HIV as evaluated by self-report and a phosphatidylethanol (PEth) outcome: protocol for a systematic review and individual participant data meta-analysis.

INTRODUCTION: Unhealthy alcohol use is associated with a range of adverse outcomes among people with HIV (PWH). Testing the efficacy and promoting the availability of effective interventions to address unhealthy alcohol use among PWH is thus a priority. Alcohol use outcomes in intervention studies are often measured by self-report alone, which can lead to spurious results due to information biases (eg, social desirability). Measuring alcohol outcomes objectively through biomarkers, such as phosphatidylethanol (PEth), in addition to self-report has potential to improve the validity of intervention studies. This protocol outlines the methods for a systematic review and individual participant data meta-analysis that will estimate the efficacy of interventions to reduce alcohol use as measured by a combined categorical self-report/PEth variable among PWH and compare these estimates to those generated when alcohol is measured by self-report or PEth alone. METHODS AND ANALYSIS: We will include randomised controlled trials that: (A) tested an alcohol intervention (behavioural and/or pharmacological), (B) enrolled participants 15 years or older with HIV; (C) included both PEth and self-report measurements, (D) completed data collection by 31 August 2023. We will contact principal investigators of eligible studies to inquire about their willingness to contribute data. The primary outcome variable will be a combined self-report/PEth alcohol categorical variable. Secondary outcomes will include PEth alone, self-report alone and HIV viral suppression. We will use a two-step meta-analysis and random effects modelling to estimate pooled treatment effects; I2 will be calculated to evaluate heterogeneity. Secondary and sensitivity analyses will explore treatment effects in adjusted models and within subgroups. Funnel plots will be used to explore publication bias. ETHICS AND DISSEMINATION: The study will be conducted with deidentified data from completed randomised controlled trials and will be considered exempt from additional ethical approval. Results will be disseminated through peer-reviewed publications and international scientific meetings. PROSPERO REGISTRATION NUMBER: CRD42022373640.

Psychosocial and pharmacologic interventions to reduce harmful alcohol use in low- and middle-income countries.

BACKGROUND: Harmful alcohol use is defined as unhealthy alcohol use that results in adverse physical, psychological, social, or societal consequences and is among the leading risk factors for disease, disability and premature mortality globally. The burden of harmful alcohol use is increasing in low- and middle-income countries (LMICs) and there remains a large unmet need for indicated prevention and treatment interventions to reduce harmful alcohol use in these settings. Evidence regarding which interventions are effective and feasible for addressing harmful and other patterns of unhealthy alcohol use in LMICs is limited, which contributes to this gap in services. OBJECTIVES: To assess the efficacy and safety of psychosocial and pharmacologic treatment and indicated prevention interventions compared with control conditions (wait list, placebo, no treatment, standard care, or active control condition) aimed at reducing harmful alcohol use in LMICs. SEARCH METHODS: We searched for randomized controlled trials (RCTs) indexed in the Cochrane Drugs and Alcohol Group (CDAG) Specialized Register, the Cochrane Clinical Register of Controlled Trials (CENTRAL) in the Cochrane Library, PubMed, Embase, PsycINFO, CINAHL, and the Latin American and Caribbean Health Sciences Literature (LILACS) through 12 December 2021. We searched clinicaltrials.gov, the World Health Organization International Clinical Trials Registry Platform, Web of Science, and Opengrey database to identify unpublished or ongoing studies. We searched the reference lists of included studies and relevant review articles for eligible studies. SELECTION CRITERIA: All RCTs comparing an indicated prevention or treatment intervention (pharmacologic or psychosocial) versus a control condition for people with harmful alcohol use in LMICs were included. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 66 RCTs with 17,626 participants. Sixty-two of these trials contributed to the meta-analysis. Sixty-three studies were conducted in middle-income countries (MICs), and the remaining three studies were conducted in low-income countries (LICs). Twenty-five trials exclusively enrolled participants with alcohol use disorder. The remaining 51 trials enrolled participants with harmful alcohol use, some of which included both cases of alcohol use disorder and people reporting hazardous alcohol use patterns that did not meet criteria for disorder. Fifty-two RCTs assessed the efficacy of psychosocial interventions; 27 were brief interventions primarily based on motivational interviewing and were compared to brief advice, information, or assessment only. We are uncertain whether a reduction in harmful alcohol use is attributable to brief interventions given the high levels of heterogeneity among included studies (Studies reporting continuous outcomes: Tau² = 0.15, Q =139.64, df =16, P<.001, I² = 89%, 3913 participants, 17 trials, very low certainty; Studies reporting dichotomous outcomes: Tau²=0.18, Q=58.26, df=3, P<.001, I² =95%, 1349 participants, 4 trials, very low certainty). The other types of psychosocial interventions included a range of therapeutic approaches such as behavioral risk reduction, cognitive-behavioral therapy, contingency management, rational emotive therapy, and relapse prevention. These interventions were most commonly compared to usual care involving varying combinations of psychoeducation, counseling, and pharmacotherapy. We are uncertain whether a reduction in harmful alcohol use is attributable to psychosocial treatments due to high levels of heterogeneity among included studies (Heterogeneity: Tau² = 1.15; Q = 444.32, df = 11, P<.001; I²=98%, 2106 participants, 12 trials, very low certainty). Eight trials compared combined pharmacologic and psychosocial interventions with placebo, psychosocial intervention alone, or another pharmacologic treatment. The active pharmacologic study conditions included disulfiram, naltrexone, ondansetron, or topiramate. The psychosocial components of these interventions included counseling, encouragement to attend Alcoholics Anonymous, motivational interviewing, brief cognitive-behavioral therapy, or other psychotherapy (not specified). Analysis of studies comparing a combined pharmacologic and psychosocial intervention to psychosocial intervention alone found that the combined approach may be associated with a greater reduction in harmful alcohol use (standardized mean difference (standardized mean difference (SMD))=-0.43, 95% confidence interval (CI): -0.61 to -0.24; 475 participants; 4 trials; low certainty). Four trials compared pharmacologic intervention alone with placebo and three with another pharmacotherapy. Drugs assessed were: acamprosate, amitriptyline, baclofen disulfiram, gabapentin, mirtazapine, and naltrexone. None of these trials evaluated the primary clinical outcome of interest, harmful alcohol use.   Thirty-one trials reported rates of retention in the intervention. Meta-analyses revealed that rates of retention between study conditions did not differ in any of the comparisons (pharmacologic risk ratio (RR) = 1.13, 95% CI: 0.89 to 1.44, 247 participants, 3 trials, low certainty; pharmacologic in addition to psychosocial intervention: RR = 1.15, 95% CI: 0.95 to 1.40, 363 participants, 3 trials, moderate certainty). Due to high levels of heterogeneity, we did not calculate pooled estimates comparing retention in brief (Heterogeneity: Tau² = 0.00; Q = 172.59, df = 11, P<.001; I2 = 94%; 5380 participants; 12 trials, very low certainty) or other psychosocial interventions (Heterogeneity: Tau² = 0.01; Q = 34.07, df = 8, P<.001; I2 = 77%; 1664 participants; 9 trials, very low certainty). Two pharmacologic trials and three combined pharmacologic and psychosocial trials reported on side effects. These studies found more side effects attributable to amitriptyline relative to mirtazapine, naltrexone and topiramate relative to placebo, yet no differences in side effects between placebo and either acamprosate or ondansetron. Across all intervention types there was substantial risk of bias. Primary threats to validity included lack of blinding and differential/high rates of attrition. AUTHORS' CONCLUSIONS: In LMICs there is low-certainty evidence supporting the efficacy of combined psychosocial and pharmacologic interventions on reducing harmful alcohol use relative to psychosocial interventions alone. There is insufficient evidence to determine the efficacy of pharmacologic or psychosocial interventions on reducing harmful alcohol use largely due to the substantial heterogeneity in outcomes, comparisons, and interventions that precluded pooling of these data in meta-analyses. The majority of studies are brief interventions, primarily among men, and using measures that have not been validated in the target population. Confidence in these results is reduced by the risk of bias and significant heterogeneity among studies as well as the heterogeneity of results on different outcome measures within studies. More evidence on the efficacy of pharmacologic interventions, specific types of psychosocial interventions are needed to increase the certainty of these results.

Testing a Screening, Brief Intervention, and Referral to Treatment Intervention Approach for Addressing Unhealthy Alcohol and Other Drug Use in Humanitarian Settings: Protocol of the Ukuundapwa Chapamo Randomised Controlled Trial.

Refugees and other displaced persons are exposed to many risk factors for unhealthy alcohol and other drug (AOD) use and concomitant mental health problems. Evidence-based services for AOD use and mental health comorbidities are rarely available in humanitarian settings. In high income countries, screening, brief intervention and referral to treatment (SBIRT) systems can provide appropriate care for AOD use but have rarely been used in low- and middle-income countries and to our knowledge never tested in a humanitarian setting. This paper describes the protocol for a randomised controlled trial to compare the effectiveness of an SBIRT system featuring the Common Elements Treatment Approach (CETA) to treatment as usual in reducing unhealthy AOD use and mental health comorbidities among refugees from the Democratic Republic of the Congo and host community members in an integrated settlement in northern Zambia. The trial is an individually randomised, single-blind, parallel design with outcomes assessed at 6-months (primary) and 12-months post-baseline. Participants are Congolese refugees and Zambians in the host community, 15 years of age or older with unhealthy alcohol use. Outcomes are: unhealthy alcohol use (primary), other drug use, depression, anxiety and traumatic stress. The trial will explore SBIRT acceptability, appropriateness, cost-effectiveness, feasibility, and reach.

Telemedicine for unhealthy alcohol use in adults living with HIV in Alabama using common elements treatment approach: A hybrid clinical efficacy-implementation trial protocol.

Background: Unhealthy alcohol use is an unaddressed barrier to achieving and maintaining control of the human immunodeficiency virus (HIV) epidemic. Integrated screening, treatment of common behavioral and mental health comorbidities, and telemedicine can improve alcohol treatment and HIV clinical and quality of life outcomes for rural and underserved populations. Objective: In a randomized controlled clinical trial, we will evaluate the effectiveness and implementation of telephone-delivered Common Elements Treatment Approach (T-CETA), a transdiagnostic cognitive behavioral therapy protocol, on unhealthy alcohol use, HIV, other substance use and mental health outcomes among predominantly rural adults with HIV receiving care at community clinics in Alabama. Methods: Adults with HIV receiving care at four selected community clinics in Alabama will receive a telephone-delivered alcohol brief intervention (BI), and then be assigned at random (stratified by clinic and sex) to no further intervention or T-CETA. Participants will be recruited after screening positively for unhealthy alcohol use or when referred by a provider. The target sample size is 308. The primary outcome will be change in the Alcohol Use Disorder Identification Test (AUDIT) at six- and 12-months post-enrollment. Additional outcomes include HIV (retention in care and viral suppression), patient-reported mental health (anxiety, depression, posttraumatic stress), and quality of life. A range of implementation measures be evaluated including T-CETA provider and client acceptability, feasibility, cost and cost-effectiveness. Conclusions: This trial will inform alcohol treatment within HIV care programs, including the need to consider comorbidities, and the potential impact of alcohol interventions on HIV and quality of life outcomes.

Feasibility randomised controlled trial of the Early Adolescent Skills for Emotions psychological intervention with young adolescents in Lebanon.

BACKGROUND: Globally, there is a vast mental health treatment gap, whereby the majority of adolescents living in low- and middle-income countries requiring mental health services, do not have access to adequate care. To improve access, the World Health Organization (WHO) developed a range of interventions, designed to be low-cost and delivered by non-specialists. We conducted a two-arm, individually randomised group treatment feasibility trial of a new WHO group intervention for young adolescents with emotional distress ('Early Adolescent Skills for Emotions'; EASE) in Lebanon. METHOD: The aim of this study was to determine the feasibility of the intervention and study procedures. Adolescents aged 10 to 14 years were eligible to take part if they scored above a validated cut-off on the Child Psychosocial Distress Screener. Participants were randomized to EASE or enhanced treatment as usual (ETAU) control using a 1:1 ratio. EASE consisted of seven group sessions with adolescents and three sessions with caregivers. ETAU consisted of a single brief psychoeducation home visit. Child and caregiver outcomes were measured by blind assessors at baseline, endline (8 weeks post-randomisation), and three month follow-up (20 weeks post-randomisation), with the primary outcome measure being child psychological symptoms on the Pediatric Symptom Checklist. Qualitative interviews were conducted with adolescents (n = 13), caregivers (n = 17), facilitators (n = 6), trainers (n = 3), and outreach staff (n = 1) at endline to assess barriers and facilitators related to the feasibility and delivery of EASE and study procedures. RESULTS: Of 154 adolescents screened, 67 (43%) were eligible, completed baseline, and were randomized. Sixty adolescents (90%) completed endline assessments (31 EASE, 29 ETAU), and fifty-nine (88%) completed three-month assessments (29 EASE, 30 ETAU). Qualitatively, participants provided overall positive feedback about the intervention. Several challenges and suggestions for improvement were raised around logistics, intervention content, and acceptability of assessment measures. Implementation data highlighted challenges with intervention uptake and attendance. Outcome measures generally had strong psychometric properties (range: α = 0.77 to α = 87), however did not demonstrate change over time in either group. CONCLUSIONS: The EASE intervention and study procedures are acceptable and feasible for implementation with vulnerable adolescents in Lebanon, however several improvements are necessary prior to full-scale evaluation. TRIAL REGISTRATION: #ISRCTN60799626, retrospectively registered on 04/10/2022.

Alcohol-focused and transdiagnostic treatments for unhealthy alcohol use among adults with HIV in Zambia: A 3-arm randomized controlled trial.

BACKGROUND: Clinical and quality of life outcomes in people living with human immunodeficiency virus (PLWH) are undermined by unhealthy alcohol use (UAU), which is highly prevalent in this population and is often complicated by mental health (MH) or other substance use (SU) comorbidity. In sub-Saharan Africa, evidence-based and implementable treatment options for people with HIV and UAU are needed. METHODS: We are conducting a hybrid clinical effectiveness-implementation trial at three public-sector HIV clinics in Lusaka, Zambia. Adults with HIV, who report UAU, and have suboptimal HIV clinical outcomes, will be randomized to one of three arms: an alcohol-focused brief intervention (BI), the BI with additional referral to a transdiagnostic cognitive behavioral therapy (Common Elements Treatment Approach [CETA]), or standard of care. The BI and CETA will be provided by HIV peer counselors, a common cadre of lay health worker in Zambia. Clinical outcomes will include HIV viral suppression, alcohol use, assessed by audio computer-assisted self-interview (ACASI) and direct alcohol biomarkers, Phophatidylethanol and Ethyl glucuronide, and comorbid MH and other SU. A range of implementation outcomes including cost effectiveness will also be analyzed. CONCLUSION: Hybrid and 3-arm trial design features facilitate the integrated evaluation of both brief, highly implementable, and more intensive, less implementable, treatment options for UAU among PLWH in sub-Saharan Africa. Use of ACASI and alcohol biomarkers will strengthen understanding of treatment effects.