Subcortical volumes across the lifespan: data from 18,605 healthy individuals aged 3-90 years

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.Education and Child Studie

Integration of mental health counselling into chronic disease services at the primary health care level: Formative research on dedicated versus designated strategies in the Western Cape, South Africa

Objective: To explore health care providers’ views on the acceptability and feasibility of two models for integrating facility-based counsellor delivered mental health counselling into chronic disease care, and how such an approach could be improved in South Africa. Methods: Fourteen focus group discussions and 25 in-depth individual interviews were conducted with 109 health care workers and facility managers from 24 primary health clinics in the Western Cape, South Africa. Results: Findings suggested that despite recent efforts to integrate mental health counselling into chronic disease services for common mental disorders, there remains limited availability of psychosocial and psychological counselling. Feedback on the two models of integration suggested equipoise and the potential of a hybrid approach where these approaches may be tailored to the specific needs and available resources of each facility. Participants identified constraints within the health system and broader social context that require consideration for integrating mental health counselling into chronic disease care. Conclusion: Although study participants unanimously agreed that counselling for common mental disorders should be integrated into chronic disease services, they had differing views on the type of model that should be adopted. There is a need for further testing of the two models and aspects of the health service that may require strengthening to implement any such model

Gender Moderates Results of a Randomized Clinical Trial for the Khanya Intervention for Substance Use and ART Adherence in HIV Care in South Africa

Little is known about gender effects of alcohol and drug use (AOD) among people living with HIV (PLWH) in resource-limited settings. Using multilevel models, we tested whether gender moderated the effect of Khanya, a cognitive-behavioral therapy-based intervention addressing antiretroviral (ART) adherence and AOD reduction. We enrolled 61 participants from HIV care and examined outcomes at 3- and 6-months compared to enhanced treatment as usual (ETAU). Gender significantly moderated the effect of Khanya on ART adherence (measured using electronically-monitored and biomarker-confirmed adherence), such that women in Khanya had significantly lower ART adherence compared to men in Khanya; no gender differences were found for AOD outcomes. Exploratory trajectory analyses showed men in Khanya and both genders in ETAU had significant reductions in at least one AOD outcome; women in Khanya did not. More research is needed to understand whether a gender lens can support behavioral interventions for PLWH with AOD. Trial registry ClinicalTrials.gov identifier: NCT03529409. Trial registered on May 18, 2018

White-matter damage in clade C HIV-positive subjects: A diffusion tensor imaging study

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Patient preferences for the integration of mental health counseling and chronic disease care in South Africa

Purpose: To describe patient perceptions of the acceptability of integrating mental health counseling within primary care facilities in the Western Cape province of South Africa and their preferences for the way in which this care is delivered. Patients and methods: Qualitative interviews with 30 purposively selected patients receiving treatment for HIV or diabetes within primary care facilities who screened positive for depression using the Center for Epidemiological Studies Depression Scale or hazardous alcohol use through the Alcohol Use Disorders Identification Test. Results: Participants articulated high levels of unmet need for mental health services and strong associations between poor mental health and the challenges of living with a chronic disease. Consequently, they considered it acceptable to offer screening and mental health counseling within the context of chronic disease care. They thought counseling would be highly relevant if it helped patients develop adaptive strategies for coping with stress and negative emotions. Irrespective of chronic disease, patients indicated a preference for lay counselors rather than existing clinicians as potential delivery agents, supporting a task-shared approach to mental health counseling delivery in primary care settings. Some expressed concern about the feasibility of using lay counselors already present in facilities to deliver this service, suggesting that additional counselors might be needed. Conclusion: Findings demonstrate a need for mental health counseling within the context of chronic disease care in South Africa. Task-shared approaches, using lay counselors, seem acceptable to patients – provided counselors are selected to ensure they possess the qualities associated with effective counselors. Findings have informed the design of a task-shared mental health program that is responsive to the preferences of patients with chronic diseases

Associations Between Patterns of Alcohol Use and Viral Load Suppression Amongst Women Living with HIV in South Africa

This study aimed to identify alcohol use patterns associated with viral non-suppression among women living with HIV (WLWH) and the extent to which adherence mediated these relationships. Baseline data on covariates, alcohol consumption, ART adherence, and viral load were collected from 608 WLWH on ART living in the Western Cape, South Africa. We defined three consumption patterns: no/light drinking (drinking ≤ 1/week and ≤ 4 drinks/occasion), occasional heavy episodic drinking (HED) (drinking > 1 and ≤ 2/week and ≥ 5 drinks/occasion) and frequent HED (drinking ≥ 3 times/week and ≥ 5 drinks/occasion). In multivariable analyses, occasional HED (OR 3.07, 95% CI 1.78–5.30) and frequent HED (OR 7.11, 95% CI 4.24–11.92) were associated with suboptimal adherence. Frequent HED was associated with viral non-suppression (OR 2.08, 95% CI 1.30–3.28). Suboptimal adherence partially mediated the relationship between frequent HED and viral non-suppression. Findings suggest a direct relationship between frequency of HED and viral suppression. Given the mediating effects of adherence on this relationship, alcohol interventions should be tailored to frequency of HED while also addressing adherence

Project Khanya: results from a pilot randomized type 1 hybrid effectiveness-implementation trial of a peer-delivered behavioural intervention for ART adherence and substance use in HIV care in South Africa

Introduction: South Africa (SA) has the highest number of people living with HIV (PLWH) globally, and a significant burden of alcohol and other drug use (AOD). Although integrating AOD treatment into HIV care may improve antiretroviral therapy (ART) adherence, this is not typically routine practice in SA or other low-resource settings. Identifying interventions that are feasible and acceptable for implementation is critical to improve HIV and AOD outcomes. Methods: A pilot randomized hybrid type 1 effectiveness-implementation trial (N = 61) was conducted to evaluate the feasibility and acceptability of Khanya, a task-shared, peer-delivered behavioral intervention to improve ART adherence and reduce AOD in HIV care in SA. Khanya was compared to enhanced treatment as usual (ETAU), a facilitated referral to on-site AOD treatment. Implementation outcomes, defined by Proctor’s model, included feasibility, acceptability, appropriateness and fidelity. Primary pilot effectiveness outcomes were ART adherence at post-treatment (three months) measured via real-time electronic adherence monitoring, and AOD measured using biomarker and self-report assessments over six months. Data collection was conducted from August 2018 to April 2020. Results and discussion: Ninety-one percent of participants (n = 56) were retained at six months. The intervention was highly feasible, acceptable, appropriate and delivered with fidelity (>90% of components delivered as intended by the peer). There was a significant treatment-by-time interaction for ART adherence (estimate = −0.287 [95% CI = −0.507, −0.066]), revealing a 6.4 percentage point increase in ART adherence in Khanya, and a 22.3 percentage point decline in ETAU. Both groups evidenced significant reductions in alcohol use measured using phosphatidylethanol (PEth) (F(2,101) = 4.16, p = 0.01), significantly decreased likelihood of self-reported moderate or severe AOD (F(2,104) = 7.02, p = 0.001), and significant declines in alcohol use quantity on the timeline follow-back (F(2,102) = 21.53, p < 0.001). Among individuals using drugs and alcohol, there was a greater reduction in alcohol use quantity in Khanya compared to ETAU over six months (F(2,31) = 3.28, p = 0.05). Conclusions: Results of this pilot trial provide initial evidence of the feasibility and acceptability of the Khanya intervention for improving adherence in an underserved group at high risk for ongoing ART non-adherence and HIV transmission. Implementation results suggest that peers may be a potential strategy to extend task-sharing models for behavioral health in resource-limited, global settings

Study protocol: an observational study of distress, immune function and persistent pain in HIV

Introduction: Many people with HIV report both distress and pain. The relationship between distress and pain is bidirectional, but the mechanisms by which distress exacerbates pain are unclear. The inflammatory response to challenge (inflammatory reactivity, IR) may be a partial mediator, given that neuroimmune interactions provide a substrate for IR to also influence neurological reactivity and, thus, pain-related neural signalling. This prospective, observational, case–control study will characterise the relationships between distress, IR, pain-related signalling as captured by induced secondary hyperalgesia (SH), and pain, in people with HIV who report persistent pain (PP) (cases) or no pain (controls). Methods and analysis: One hundred people with suppressed HIV, reporting either PP or no pain, will be assessed two or four times over 6 months. The primary outcomes are distress (Hopkins 25-item symptom checklist), IR (multiplex assay after LPS challenge), and PP (Brief Pain Inventory), assessed at the baseline timepoint, although each will also be assessed at follow-up time points. Induced SH will be assessed in a subsample of 60 participants (baseline timepoint only). To test the hypothesis that IR partly mediates the relationship between distress and pain, mediation analysis will use the baseline data from the PP group to estimate direct and indirect contributions of distress and IR to pain. To test the hypothesis that IR is positively associated with SH, data from the subsample will be analysed with generalised mixed effects models to estimate the association between IR and group membership, with SH as the dependent variable. Ethics and dissemination: Information obtained from this study will be published in peer-reviewed journals and presented at scientific meetings. The study has been approved by the Human Research Ethics Committee of the University of Cape Town (approval number: 764/2019) and the City of Cape Town (ref: 24699). Trial registration number NCT04757987.Victoria J Madden, Ncumisa Msolo, Luyanduthando Mqadi, Maia Lesosky, Gillian J Bedwell, Mark R Hutchinson, Jonathan Grant Peter, Romy Parker, Andrew Schrepf, Robert R Edwards, John A Josk

Community health worker-delivered counselling for common mental disorders among chronic disease patients in South Africa: A feasibility study

Objectives: To examine the feasibility and acceptability of integrating a 'designated' approach to community health worker (CHW)-delivered mental health counselling (where existing CHWs deliver counselling in addition to usual duties) and a 'dedicated' approach (where additional CHWs have the sole responsibility of delivering mental health counselling) into chronic disease care. Design: A feasibility test of a designated and dedicated approach to CHW-delivered counselling and qualitative interviews of CHWs delivering the counselling. Setting: Four primary healthcare clinics in the Western Cape, South Africa allocated to either a designated or dedicated approach and stratified by urban/rural status. Participants: Forty chronic disease patients (20 with HIV, 20 with diabetes) reporting hazardous alcohol use or depression. Interviews: with seven CHWs. Intervention Three sessions of structured mental health counselling. Main outcome measures: We assessed feasibility by examining the proportion of patients who were willing to be screened, met inclusion criteria, provided consent, completed counselling and were retained in the study. Acceptability of these delivery approaches was assessed through qualitative interviews of CHWs. Results: Regardless of approach, a fair proportion (67%) of eligible patients were willing to receive mental health counselling. Patients who screened positive for depression were more likely to be interested in counselling than those with hazardous alcohol only. Retention in counselling (85%) and the study (90%) was good and did not differ by approach. Both dedicated and designated CHWs viewed the counselling package as highly acceptable but requested additional training and support to facilitate implementation. Conclusions: Dedicated and designated approaches to CHW-delivered mental health counselling were matched in terms of their feasibility and acceptability. A comparative efficacy trial of these approaches is justified, with some adjustments to the training and implementation protocols to provide further support to CHWs

Greater male than female variability in regional brain structure across the lifespan

For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders