Clozapine monitoring at a specialised psychiatric hospital: A retrospective chart review.

Background: Clozapine is the only Food and Drug Administration (FDA) and National Institute for Care and Excellence (NICE) approved drug for treatment-resistant schizophrenia (TRS). Its potentially life-threatening haematological side effects of neutropaenia and agranulocytosis mandate rigorous monitoring of neutrophil counts, presenting unique, Third-World population challenges. Aim: To describe the Clozapine white blood cell monitoring practice and outcomes in a local psychiatric hospital. Setting: At a specialist Psychiatry unit in Durban, KwaZulu-Natal, which follows a modified algorithm of the South African Standard Treatment Guidelines for Clozapine monitoring. Methods: A retrospective chart review composed of 120 patients on Clozapine treatment from 01 July 2018-31 December 2020. Demographic and clinical information was captured in a Redcap database. Descriptive statistics using categorical variables were used. Results: The study population was from a low socioeconomic background, with low levels of education and employment. A baseline neutrophil count was recorded in 58 files (48.3%). Clozapine was stopped in 6 out of the 120 patients due to 'neutropaenia' (absolute neutrophil counts ranging from 1.18 to 1.6); none developed agranulocytosis. Their duration of Clozapine treatment ranged from 2 weeks-15 years. Conclusion: Haematological monitoring frequency and documentation of patients receiving Clozapine were not in compliance with the hospital's adapted guidelines and may have resulted in the termination of treatment before true neutropaenia developed. Patients developed neutropaenia at low doses of Clozapine and after many years of treatment. Contribution: These results suggest local Clozapine monitoring guidelines should be more strictly adhered to.

A Meta-Analytic Review of the Effect of Antiretroviral Therapy on Neurocognitive Outcomes in Adults Living with HIV-1 in Low-and Middle-Income Countries.

HIV-associated neurocognitive impairment remains a challenge even in the era of antiretroviral therapy (ART). Over 90% of people living with HIV are in low- and middle-income countries. Hence, it is not surprising that such countries bear a considerable burden of comorbidities like HIV-associated neurocognitive impairment despite an overall increase in life expectancy. The literature suggests differences in patient characteristics, clinical profile, prevalent HIV subtypes, treatment choices, pharmacogenetics, and socioeconomic factors between low- and middle-income countries compared with high-income countries. Therefore, we aimed to evaluate the effect of ART on neurocognitive outcomes in low- and middle-income countries. A comprehensive search of five databases (PubMed, CINAHL, CENTRAL, PsychInfo, Google scholar) for studies published between 1996 to 2020 was performed to identify studies that reported neurocognitive outcomes in ART-treated and ART naïve HIV positive individuals. Two independent reviewers conducted study screening, data extraction, and evaluation of the risk of bias. Pooled effect size estimates (Hedges' g) and 95% CI were computed using random-effects models. Sensitivity analysis, subgroup analysis, meta-regression, and evaluation of publication bias were also conducted. Forty studies (24 cross-sectional, 13 longitudinal studies, and two randomized controlled trials) contributed to a series of meta-analyses. We found significant small to moderate effects of antiretroviral therapy for global cognition (Hedges' g observed = 0.30; 95% CI: 0.15, 0.44; k = 25; p = 0.0003; I2 = 92.1%; tau = 0.32; Q = 305.1), executive function (Hedges' g = 0.24, 95%CI: 0.02,0.46; p-0.04; k = 8; I2 = 37.5%; tau = 0.23; Q = 11.2), and speed of information processing (Hedges' g = 0.25, 95% CI: 0.05, 0.45; k = 9; p = 0.02; I2 = 86.4%; tau = 0.21; Q = 58.9). We found no significant ART effect on attention-working memory, learning and memory, motor function, and verbal fluency. No significant effect was seen with the duration of therapy, efavirenz use, and Central Penetrating Effectiveness (CPE) of antiretroviral therapy. Subgroup analyses identified study design (between-group and within-group; cross-sectional and longitudinal) and normative scores as significant sources of heterogeneity. Meta-regression analysis indicated that nadir CD4 modified the magnitude of ART's effect on cognitive outcomes. Age, gender, and country income-group were not significant moderators. Our findings provide systematic evidence that antiretroviral therapy improves neurocognitive outcomes in the domains of global cognition, executive function and speed of information processing, of people living with HIV in low- and middle-income countries, especially those with advanced immunosuppression. However, these findings are not definitive as they are limited by the probability of publication bias, high heterogeneity, and exclusion of significant confounders. Prospero registration number: CRD42020203791.

COVID-19 infection at a psychiatric hospital in KwaZulu-Natal, South Africa: Clinical service planning and challenges.

Background: South Africa had over 4 million cases of coronavirus disease 2019 (COVID-19) infections and more than 1 million COVID-19-related deaths. Despite the devastating psychological impact of the COVID-19 pandemic, there is little qualitative, critical evaluation of government mental health services in this resource-limited setting. Aim: The authors describe the clinical service plan and response to the COVID-19 pandemic at a government psychiatric hospital. Setting: KwaZulu-Natal, South Africa. Methods: A descriptive narrative overview of the specialised psychiatric hospital's clinical response (April 2020 - March 2021) to the COVID-19 pandemic was undertaken in the following domains: screening policy; testing and swabbing policy; staff training and monitoring; and restructuring the wards to accommodate mental health care users (MHCUs) with suspected cases of COVID-19. Results: The in-depth narrative reviews led to the introduction of staff training, routine COVID-19 reverse transcription polymerase chain reaction (RT-PCR) testing of all MHCUs, the creation of designated quarantine and isolation facilities and screening of physical health status of patients with COVID-19 prior to transfer being implemented to prevent an outbreak or increased morbidity or mortality. Conclusion: Implementing a service plan early which included staff training, screening and routine COVID-19 testing services for psychiatric admissions in a rapidly evolving environment with few additional resources was challenging. The absence of guidelines early in the pandemic that addressed the unique needs of a clinical psychiatric inpatient population is a noteworthy learning point. Contribution: The article highlights that the inpatient infrastructural requirements and clinical management protocols of acutely psychiatrically ill inpatients, in the context of infectious outbreaks, require dedicated task teams and bespoke policies.

The Impact of Antiretroviral Therapy on Neurocognitive Outcomes Among People Living with HIV in Low- and Middle-Income Countries (LMICs): A Systematic Review.

Low and middle-income countries (LMICs) are the epicenter of the HIV epidemic. The scale-up of antiretroviral therapy (ART) has reduced mortality, but HIV-associated neurocognitive impairment (HANI) remains prevalent, which impacts functional performance, medication adherence, and quality of life. We aimed to evaluate the effect of ART on neurocognitive outcomes among people living with HIV/AIDS in LMICs and to identify determinants of these outcomes. We searched electronic databases and reference lists for studies published between 1996 and 2019. Two reviewers screened the primary studies for inclusion and performed the critical appraisal. Results were synthesized using the 'Synthesis without meta-analysis' approach through simple vote counting. We identified 31 studies conducted across four regions (Africa, Asia, South America, and Eastern Europe). Nine studies were cross-sectional, 15 were prospective, and seven were randomized controlled trials. The majority of the articles showed improved neurocognitive performance with ART use but found no association with treatment duration, regimen, central penetrating effectiveness, and conventional biomarkers. Despite the lack of appropriate norms and not accounting for practice effect in most studies, the evidence suggests ART is useful in the treatment of HIV-associated neurocognitive impairment (HANI) but limited in addressing legacy effects, and peripheral, and central viral reservoirs. Improved early ART treatment programs, viral reservoir eradication strategies, and identification of novel biomarkers will be critical in efforts to minimize HIV-associated neurocognitive impairment. PROSPERO registration: CRD42020152908.

Neurocognitive functioning in MDR-TB patients with and without HIV in KwaZulu-Natal, South Africa.

OBJECTIVES: Optimising medication adherence is one of the essential factors in reversing the tide of a TB-HIV syndemic in sub-Saharan Africa, especially South Africa. Impairment in key neurocognitive domains may impair patients' ability to maintain adherence to treatment, but the level of cognition and its relationship to HIV status has not been examined in individuals with drug-resistant TB. We therefore investigated performance on several key neurocognitive domains in relationship to HIV status in a multidrug-resistant tuberculosis patients (MDR-TB) sample. METHODS: We enrolled microbiologically confirmed MDR-TB inpatients at a TB-specialist referral hospital in KwaZulu-Natal province, South Africa. We collected cross-sectional data on sociodemographic, clinical and neurocognitive function (e.g. attention, memory, executive functioning, language fluency, visual-spatial, eye-hand coordination). For the primary analysis, we excluded participants with major depressive episode/substance use disorder (MDE/SUD). We fitted adjusted Poisson regression models to explore the association between HIV and neurocognitive function. RESULTS: We enrolled 200 people with MDR-TB; 33 had MDE/SUD, and data of 167 were analysed (151 HIV+, 16 HIV-). The mean age of participants was 34.2 years; the majority were female (83%), and 53% had not completed secondary school. There was evidence of impaired neurocognitive functioning across all domains in both HIV+/- study participants. Based on the regression analyses, individuals with co-infection (MDR-TB/HIV+), as well as those who had longer duration of hospital stays experienced significantly lower cognitive performance in several domains. Poor cognitive performance was significantly related to older age and lower educational attainment. The presence of major depression or substance use disorders did not influence the significance of the findings. CONCLUSIONS: Adults with MDR-TB have significant neurocognitive impairment, especially if HIV positive. An integrated approach is necessary in the management of MDR-TB as cognitive health influences the ability to adhere to chronic treatment, clinical outcomes and functionality.

OBJECTIFS: L'optimisation de l'adhésion au traitement est l'un des facteurs essentiels pour inverser la tendance d'un syndrome TB-VIH en Afrique subsaharienne, en particulier en Afrique du Sud. Des déficiences dans des domaines neurocognitifs clés peuvent entraver la capacité des patients à maintenir l'adhésion au traitement, mais le niveau de cognition et sa relation avec le statut VIH n'ont pas été examinés chez les personnes atteintes de TB résistante aux médicaments. Nous avons donc étudié les performances de plusieurs domaines neurocognitifs clés en relation avec le statut VIH dans un échantillon de tuberculose multirésistante (TB-MDR). MÉTHODES: Nous avons recruté des patients hospitalisés pour une TB-MDR confirmée microbiologiquement dans un hôpital de référence spécialisé dans la TB dans la province du KwaZulu-Natal, en Afrique du Sud. Nous avons recueilli des données transversales sur les fonctions sociodémographiques, cliniques et neurocognitives (par exemple l'attention, la mémoire, le fonctionnement exécutif, la maîtrise du langage, la coordination visuelle-spatiale et œil-main). Pour l'analyse primaire, nous avons exclu les participants souffrant d'un épisode dépressif majeur ou d'un trouble lié à la consommation de substances (EDM/TCS). Nous avons appliqué des modèles de régression de Poisson ajustés pour explorer l'association entre le VIH et la fonction neurocognitive. RÉSULTATS: Nous avons recruté 200 personnes atteintes de TB-MDR, 33 d'entre elles étaient atteintes de EDM/TCS, les données des 167 autres ont été analysées (151 VIH-positives, 16 VIH-négatives). L'âge moyen des participants était de 34,2 ans; la majorité étaient des femmes (83%) et 53% n'avaient pas terminé leurs études secondaires. Les participants à l'étude VIH+ et VIH- présentaient des signes de dysfonctionnement neurocognitif dans tous les domaines. D'après les analyses de régression, les personnes coinfectées (TB-MDR/VIH), ainsi que celles qui ont été hospitalisées pendant une longue période, présentent des performances cognitives nettement inférieures dans plusieurs domaines. Les mauvaises performances cognitives étaient significativement liées à l'âge plus élevé et à un niveau d'éducation plus faible. La présence d'une dépression majeure ou de troubles liés à la consommation de substances n'a pas influencé la signification des résultats. CONCLUSIONS: Les adultes atteints de TB-MDR présentent une importante déficience neurocognitive, surtout s'ils sont VIH-positifs. Une approche intégrée est nécessaire dans la prise en charge de la TB-MDR car la santé cognitive influence la capacité d'adhésion à un traitement chronique, les résultats cliniques et la fonctionnalité.

Subjective and objective cognition 6-week post-coronary artery bypass graft surgery: A descriptive pilot study.

BACKGROUND: Coronary artery bypass graft (CABG) surgery has been found to be associated with post-operative cognitive decline. Despite the large and growing numbers being conducted in South Africa, the associated or ensuing cognitive symptoms or impairment have received little research attention. AIM: The aim of this pilot study was to describe the nature and extent of subjective cognitive complaints (SCCs) and objective cognitive impairments in patients 6-week post-CABG surgery in a clinical sample in KwaZulu-Natal (KZN) Province, South Africa. SETTING: A cross-sectional survey was conducted among outpatients attending their 6-week post-CABG surgical review at a cardiology clinic in a KZN provincial hospital. METHOD: Socio-demographic and clinical data were captured, with SCCs being determined by using standardised questions; cognition was assessed with the Montreal cognitive assessment (MoCA). RESULTS: The mean age of the sample (n = 28) was 58.72 years. The mean MoCA score was 23.96 (SD = 4.32); 60.71% (n = 17) screening positive (< 25/30) and more likely to be older, male, hypertensive and diabetic. A third (n = 9; 35.71%) reported at least one new SCC; their mean age was 55.36 years which was lower than those without subjective complaints (59.81). CONCLUSIONS: Subjective and objective cognitive impairments were evident in patients 6-week post-CABG surgery identifying a need for longitudinal cognitive screening both pre- and post- operatively in patients undergoing CABG surgery.

Neurocognitive Impairment Risk Among Individuals With Multiple Drug-Resistant Tuberculosis and Human Immunodeficiency Virus Coinfection: Implications for Systematic Linkage to and Retention of Care in Tuberculosis/Human Immunodeficiency Virus Treatment.

Although neurocognitive impairment (NCI) is a well-recognized challenge in human immunodeficiency virus (HIV), there is little evidence regarding it among individuals with multiple drug-resistant tuberculosis (MDR-TB) within HIV endemic sub-Saharan Africa. The extent of NCI risk, particularly HIV-associated neurocognitive disorders (HAND) risk, was investigated in 200 microbiologically confirmed inpatients with MDR-TB at a TB-specialist hospital in KwaZulu-Natal Province, South Africa. Within this population, the prevalence of HIV coinfection, major depressive episode, and substance use disorder was 89.50%, 10.50%, and 7.00%, respectively. After excluding individuals with major depressive episode/substance use disorder and monoinfection (i.e., MDR-TB without HIV), the prevalence of HAND risk was 43.5%. Older and low-income individuals had significantly greater odds of HAND risk, whereas those with family members/relatives who work(ed) in the health services had lower odds. The role of timely linkage to and retention of care in TB/HIV treatment to offset cognitive decline in MDR-TB/HIV coinfected individuals needs to be investigated further.

Major depression and household food insecurity among individuals with multidrug-resistant tuberculosis (MDR-TB) in South Africa.

PURPOSE: Household food insecurity in South Africa is a pervasive public health challenge. Although its link to chronic health conditions is well established, its relationship to mental illness, particularly major depression, is not well-understood. Despite KwaZulu-Natal Province being the epicenter of the drug-resistant tuberculosis (MDR-TB) epidemic, and having the largest share of poverty in South Africa, this relationship remains unexamined. This study investigated the association between major depressive episode (MDE) and household food insecurity among individuals with MDR-TB. METHODS: We enrolled and interviewed 141 newly admitted microbiologically confirmed MDR-TB inpatients at a specialized TB hospital in KwaZulu-Natal Province, South Africa. Logistic regression models were fitted to assess the relationship between MDE and household food insecurity, while accounting for socio-demographic status (e.g., age, gender, education, marital status, social grant status, income, and preference for living in one's community). RESULTS: The prevalence of MDE and household food insecurity was 11.35% and 21.01%, respectively. MDE was significantly associated with household food insecurity (aOR 4.63, 95% CI 1.17-18.38). Individuals who are female (aOR 6.29, 95% CI 1.13-35.03), young (aOR 8.86, 95% CI 1.69-46.34), have low educational attainment (aOR 6.19, 95% CI 1.70-22.59) and receive social grants (aOR 7.60, 95% CI 2.36-24.48) were most at risk of household food insecurity. CONCLUSIONS: MDE in individuals with MDR-TB was significantly associated with household food insecurity, independent of socio-economic status. Although MDR-TB is not exclusively a disease of the poor, individuals from socio-economically disadvantaged backgrounds (e.g., female, young adults, low education, and social grant recipients) were more likely to experience household food insecurity. Our study underscores the need to address the co-occurring cycles of food insecurity and untreated MDE in South Africa.

Depression, anxiety and stress symptoms in patients presenting with dyspepsia at a regional hospital in KwaZulu-Natal province.

BACKGROUND: Depression, anxiety and stress (DAS) have been shown to be co-morbid with dyspepsia. Local data on the factors associated with these co-morbidities could inform the role of psychiatric intervention in affected patients. AIM: The aim of this study was to describe the frequency of undiagnosed DAS and their associated protective and risk correlates in a sample of patients undergoing endoscopies for dyspepsia. SETTING: The study was conducted at a regional hospital's gastro-intestinal unit in KwaZulu-Natal province. METHOD: A cross-sectional survey was conducted on 201 in- and outpatients with symptoms of dyspepsia awaiting endoscopy. Information on DAS symptomatology (using the DASS-21 screening questionnaire, as well as socio-demographic and clinical data) were collected. ANALYSES: Following a descriptive analysis of the participants' socio-demographic and clinical details, linear regression models were fitted to identify potential risk and protective correlates linked to DAS symptomatology. RESULTS: The mean age of participants (N = 201) was 48.89 years, of whom approximately two-thirds (n = 133; 66.17%) were women, 97% (n = 195) were African and 64.68% (n = 130) resided in rural areas. Anxiety was the most prevalent symptom category (n = 149; 74.13%) versus depression (n = 96; 47.76%) and stress (n = 68; 33.83%) in each category of symptom (mild to extremely) severity. In the severe and extremely severe range, anxiety existed without co-morbid depression or stress in 61.19% of anxious patients. Alcohol use was significantly associated with all three symptom categories (p < 0.01). CONCLUSIONS: Given high frequencies of depression and anxiety in patients undergoing endoscopies for dyspepsia, screening for common mental disorders is essential.

A Nationwide Panel Study on Religious Involvement and Depression in South Africa: Evidence from the South African National Income Dynamics Study.

Panel data from the South African National Income Dynamics Study, a nationally representative sample of households (years 2008, 2010 and 2012), were used to examine the longitudinal association between religious involvement and depression risk. Approximately 89.6-91.8% identified themselves as religiously affiliated, while 88.0-90.3% perceived religion to be important in South Africa during the observed study periods. A short-term association between religious involvement and significant depressive symptomatology was not detected, but logistic regression models that accounted for the clustering of repeated observations within participants indicated that, over time, those with religious affiliations (aOR 0.85, 95% CI 0.76-0.96) were at a lower risk than those not affiliated. Furthermore, individuals who reported religious activity as being important (aOR 0.81; 95% CI 0.73-0.91) were at less risk of significant depressive symptomatology over time than those rating religious activity as not important. Our study points to the potentially important role of religious involvement as an emerging area of investigation toward improving mental health at a population level in resource-limited settings.

The Association Between Serum Mature and Precursor Brain-Derived Neurotrophic Factor and Neurocognitive Function in People With Human Immunodeficiency Virus: A Longitudinal Study.

Background: Despite antiretroviral therapy (ART), human immunodeficiency virus (HIV)-associated neurocognitive impairment persists. We investigated the association between serum levels of mature brain-derived neurotrophic factor (mBDNF), precursor brain-derived neurotrophic factor (proBDNF), and neurocognitive changes over time among adults with HIV in sub-Saharan Africa, seeking to elucidate the interplay between neurotrophic factors and neurocognitive outcomes post-ART. Methods: Utilizing data from the ACTG 5199 study in Johannesburg and Harare, serum mBDNF and proBDNF levels were measured via enzyme-linked immunosorbent assay. Neurocognitive performance was assessed at baseline and 24, 48, and 96 weeks using neuropsychological tests. The Friedman test and linear mixed-effects models were used to assess changes in mBDNF, proBDNF, and neurocognitive performance over time, accounting for individual variability and adjusting for multiple comparisons. Results: Among 155 participants, there were significant cognitive improvements (P < .001) and a rise in mBDNF levels from baseline to 96 weeks. The proBDNF levels initially remained stable (P = .57) but notably increased by 48 weeks (P = .04). Higher mBDNF levels were positively associated with enhanced neurocognitive performance at 48 weeks (ß = .16, P = .01) and 96 weeks (ß = .32, P < .001). Similarly, higher proBDNF levels were positively associated with neurocognitive performance at 96 weeks (ß = .25, P < .001). Conclusions: This study highlights the significant association between serum BDNF levels and neurocognitive improvement post-ART in adults with HIV. However, more research is needed to replicate these findings, establish causal relationships, and explore whether BDNF-enhancing activities can improve neurocognitive outcomes in people with HIV.

Risk factors and strategies for relapse prevention among individuals living with serious mental illness in South Africa: Qualitative inquiry from patients' and caregivers' perspectives.

INTRODUCTION: Relapse among individuals with serious mental illnesses in resource-limited contexts, including South Africa, is a significant concern. To date, the risks for relapse among this population is well documented, but little is known about prevention strategies to reduce its occurrence in these resource-limited settings. Therefore, this qualitative study explores the risk factors and strategies for relapse prevention from the patients' and caregivers' perspectives. METHODS: We conducted audio-recorded face-to-face in-depth interviews to capture the lived experience of relapse of inpatient study participants with serious mental illness (N = 24) at a public specialized psychiatry hospital in South Africa and their caregivers (N = 6). We conducted an inductive thematic analysis with two pre-specified themes (risk factors for relapse and strategies for prevention), with the codes devised from the data. RESULTS: Six sub-themes were identified from the analysis within the two pre-specified themes(Risk factors and strategies for relapse prevention): personal-related, family-related, and health system-related risk factors and strategies for preventing relapse, respectively. To highlight some essential findings, the importance of motivation for drug adherence, family involvement, and availability of anti-psychotic drugs in public health care were noted. More importantly, this study identified important cultural complexities where traditional healers play a significant role in some cultural understanding and treatment of mental illness, affecting medication adherence. CONCLUSION: This study calls for people-centered mental health care delivery in a public health system that listens to the voice of concern, including cultural challenges, and implements meaningful support that matters most to the patient and their family/caregivers.

The role of 'micro-decisions' in involuntary admissions decision-making for inpatient psychiatric care in general hospitals in South Africa.

While the ethics of involuntary admission for psychiatric inpatient care is widely contested, the practice is legally permissible across most jurisdictions. In many countries, laws governing the use of involuntary admission set out core criteria under which involuntary admission is permitted; these parameters broadly related to either risk of harm to self or others, need for treatment, or both. In South Africa, the use of involuntary admission is governed by the Mental Health Care Act no. 17 of 2002 (MHCA 2002), which sets out clear criteria to direct mental healthcare practitioners' decision-making and delineates a process by which decision-making should occur. However, recent research suggests that, in practice, the process of decision-making differs from the procedure prescribed in the MHCA 2002. To further explore how decision-making for involuntary admission occurs in practice, we interviewed 20 mental healthcare practitioners, all with extensive experience of making involuntary admission decisions, working in district, regional, and tertiary hospitals across five provinces. We also interviewed four mental health advocates to explore patient-centered insights. Our analysis suggests that the final decision to involuntarily admit individuals for a 72-h assessment period under the MHCA 2002 was preceded by a series of 'micro-decisions' made by a range of stakeholders: 1) the family's or police's decision to bring the individual into hospital, 2) a triage nurse's decision to prioritise the individual along a mental healthcare pathway in the emergency centre, and 3) a medical officer's decision to sedate the individual. Practitioners reported that the outcomes of each of these 'micro-decisions' informed aspects of their final decision to admit an individual involuntarily. Our analysis therefore suggests that the final decision to admit involuntarily cannot be understood in isolation because practitioners draw on a range of additional information, gleaned from these prior 'micro-decisions', to inform the final decision to admit.

Screen-based behaviour in children is more than meets the eye.

Increased screen time (ST) in children is quickly becoming a public health concern as children are now reliant on technology for social interaction and educational development. The eye-health community has paid considerable attention to this in the recent literature, documenting it as digital eye strain. Continual close eye work and a lack of outdoor play contribute to digital eye strain and today's myopia epidemic. This is a cause for concern for public health stakeholders insofar as it leads to sedentary, screen-based behaviour (SSB) in children. This results in a lack of physical activity and impacts both their bodies and their mental health. The potentially harmful effects of prolonged screen exposure on developing brains and bodies are likely to be unique and significant as physiological growth changes intersect with exponentially expanding e-platforms. While embracing the benefits of a highly digitalised world, we need to simultaneously mitigate the potential risks they pose to the health of growing children.

'Unheard,' 'uncared for' and 'unsupported': The mental health impact of Covid -19 on healthcare workers in KwaZulu-Natal Province, South Africa.

As a direct consequence of the Covid-19 pandemic, due to being exposed to chronic and multiple sources of psychological stress, healthcare workers constitute a vulnerable population. Despite the potential impact of Covid-19 on their psychological and physical health, insufficient attention has been given to their mental well-being. The primary objective of this study was to measure and understand this psychological impact on public sector doctors and nurses in KwaZulu-Natal Province, South Africa. The secondary objective was to ascertain their perceptions of psychosocial support, specific to Covid-19, within the workplace. This cross-sectional electronic survey was conducted from August to October 2020, following the first surge of the pandemic in the country, and included 312 participants. Depression, anxiety and stress symptoms were assessed with the Depression Anxiety and Stress Scale-21 item and post-traumatic stress was measured by the Impact of Events Scale-Revised version. Measures of employer support were assessed using an adapted closed-ended questionnaire. The participants' mean age was 36.6± 9.3 years with three quarters being male (n = 234, 75.0%) and predominantly (n = 214, 72.3%) medical doctors. Numbers of participants with depression, anxiety and stress were 121 (51.5%), 111 (47.2%) and 104 (44.3%) respectively, with 38 (16.2%), 50 (21.3%) and 38 (16.2%) in the combined severe/extremely severe range, respectively. On the Impact of Events Scale-Revised, 34 (13.7%) participants were in the severe range. Subjectively, 63.0% felt that their concerns were not 'heard', 75.1% did not feel 'cared for' and 81.1% and 74.0% did not feel 'physically' or 'psychologically' supported, respectively. High levels of depression, anxiety, stress and traumatic stress, combined with poor perceptions of employer support, highlight the need to identify and address the psychosocial support needs and expectations of healthcare workers for the duration of the pandemic, as well as for the mental health sequelae post-pandemic.

Neuropsychological functioning and cognitive reserve in newly HIV diagnosed antiretroviral-naïve South African adults from peri-urban and informal settlements.

Despite lower incidences of HIV-associated dementia due to antiretroviral therapy, neuropsychological impairment (NPI) remains a persistent challenge in sub-Saharan Africa. Improving cognitive reserve (CR) can mitigate NPI, but there are few investigations on neuropsychological (NP) performance, and its association with CR in newly diagnosed ART-naïve HIV-positive individuals to inform early treatment strategies. A comprehensive battery of tests were administered to assess various NP domains (International HIV Dementia Scale [for memory, motor speed, psychomotor speed], Digit Span Test [for attention], Action Fluency Test [for language] and Clock Drawing Test [for executive/visuospatial function]), and CR (using Cognitive Reserve Index Questionnaire) among 211 newly diagnosed ART-naïve HIV-positive participants from two clinics that serve peri-urban and informal settlement communities in KwaZulu-Natal, South Africa. Regression models were fitted to assess the association between NP performance and CR controlling for socioeconomic and clinical factors. Test results revealed high levels of impairment across NP domains: language (96.7%), memory and psychomotor speed (82.5%), concentration (17.5%), executive function (15.2%) and visuo-spatial function (3.3%). Low CR and educational attainment were the only factors consistently associated with poor NP performance based on regression. High levels of impairment were found in certain NP domains in a relatively young group of newly diagnosed ART-naïve HIV-positive individuals. Residents of peri-urban and informal settlements face multitude of complex challenges in South Africa. An early multilevel intervention targeting clinical- (e.g. CR) and structural-level challenges (e.g. access to education) is needed for mitigating HIV-associated NPI and promoting long-term healthy living.

Cognitive Reserve and Its Determinants in Newly HIV Diagnosed Antiretroviral-Naive Adults From Periurban and Informal Settlements: Evidence From an HIV Hyperendemic South African Setting.

BACKGROUND: Cognitive reserve (CR), the brain's capacity to resist pathology, plays an essential role in preserving the cognitive health of people living with HIV. Cognitive health differs by the HIV clinical stage, but there are few studies on CR in newly diagnosed antiretroviral treatment (ART)-naive HIV-positive adults to inform early intervention in sub-Saharan Africa. METHOD: We investigated the CR profile and its determinants among 211 newly diagnosed ART-naive HIV-positive participants from 2 clinics that serve periurban and informal settlement communities in KwaZulu-Natal, South Africa. CR domains in education, work, and leisure were assessed using the Cognitive Reserve Index questionnaire (CRIq). The CR determinants included major depression, substance use, CD4 count, history of head injury/medical comorbidity, in addition to sociodemographic status. Regression models were fitted to investigate relationships between the total/domain scores and their determinants. RESULTS: CRIq-Total scores were concentrated in the low-medium/medium functioning range with no individual in the extreme low or high CR functioning group. The determinants of CRIq-Total and CRIq-Education were older age, higher education attainment, and being employed. For the CRIq-Work domain, we found older age associated with lower CR. Major depression was only associated with lower CRIq-Leisure. CONCLUSION: ART scale-up will undoubtedly improve the longevity of individuals living with HIV, but we found high degree of suboptimal CR in a relatively young group of newly diagnosed ART-naive HIV-positive individuals from periurban and informal settlement communities. Early intervention focusing on increasing CR especially in socioeconomically vulnerable populations is needed to mitigate HIV-associated neurocognitive impairment and promote long-term healthy independent living.

The Role of Brain Derived Neurotrophic Factor in HIV-Associated Neurocognitive Disorder: From the Bench-Top to the Bedside.

Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) remains prevalent in the anti-retroviral (ART) era. While there is a complex interplay of many factors in the neuropathogenesis of HAND, decreased neurotrophic synthesis has been shown to contribute to synaptic degeneration which is a hallmark of HAND neuropathology. Brain derived neurotrophic factor (BDNF) is the most abundant and synaptic-promoting neurotrophic factor in the brain and plays a critical role in both learning and memory. Reduced BDNF levels can worsen neurocognitive impairment in HIV-positive individuals across several domains. In this paper, we review the evidence from pre-clinical and clinical studies showing the neuroprotective roles of BDNF against viral proteins, effect on co-morbid mental health disorders, altered human microbiome and ART in HAND management. Potential applications of BDNF modulation in pharmacotherapeutic, cognitive and behavioral interventions in HAND are also discussed. Finally, research gaps and future research direction are identified with the aim of helping researchers to direct efforts to make these BDNF driven interventions improve the quality of life of patients living with HAND.

Major Depression and Stigma among Individuals with Multidrug-Resistant Tuberculosis in South Africa.

Stigma is an important social determinant of health-seeking behavior; however, the nature and extent of its association with depression among people living with multidrug-resistant tuberculosis (MDR-TB) are not well-understood. We enrolled 200 microbiologically confirmed MDR-TB inpatients at a TB specialist hospital in KwaZulu-Natal Province, an area considered the epicenter for MDR-TB coinfection in South Africa. Four aspects of stigma and their association with major depression were assessed through individual interviews: 1) community and 2) patient perspectives toward TB, and 3) community and 4) patient perspectives toward HIV. A major depressive episode (MDE), HIV coinfection, and low income were significantly associated with greater stigma subscales. Based on an adjusted regression model, the MDE was the only factor independently associated with (all aspects of) stigma. These results indicate the potential utility of addressing stigma associated with the MDE as an important step in improving health-seeking behavior to promote adherence and retention in care.

The effectiveness of e-Interventions on reducing social isolation in older persons: A systematic review of systematic reviews.

As the older adult population group has been increasing in size, there has been evidence of growing social isolation and loneliness in their lives. The increased use of information communication technology and Internet-supported interventions has stimulated an interest in the benefits of e-Interventions for older people and specifically in having a role in increasing social networks and decreasing loneliness. A systematic review of e-Interventions to reduce loneliness in older people was conducted with the aim to synthesize high quality evidence on the effectiveness of e-Interventions to decrease social isolation/loneliness for older people living in community/residential care. A systematic search of 12 databases for reviews published between 2000-2017 was conducted using search term synonyms for older people, social isolation and interventions. Three independent researchers screened articles and two reviewers extracted data. The Revised-Assessment of Multiple Systematic Reviews was used to assess the quality of reviews. The final search identified 12 reviews, which included 22 unique primary research studies evaluating e-Interventions for social isolation or loneliness. The reviews were of moderate quality and the primary studies showed a lack of rigor. Loneliness was most frequently measured using the University California Los Angeles Loneliness Scale. Despite the limitations of the reviewed studies, there is inconsistent and weak evidence on using e-Interventions for loneliness in older people.