South African Medical Research Council (SAMRC) Repository
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Expert appraisal of criteria for assessing gaming disorder: An international Delphi study
Get PDFBackground and aims: Following the recognition of 'internet gaming disorder' (IGD) as a condition requiring further study by the DSM-5, 'gaming disorder' (GD) was officially included as a diagnostic entity by the World Health Organization (WHO) in the 11th revision of the International Classification of Diseases (ICD-11). However, the proposed diagnostic criteria for gaming disorder remain the subject of debate, and there has been no systematic attempt to integrate the views of different groups of experts. To achieve a more systematic agreement on this new disorder, this study employed the Delphi expert consensus method to obtain expert agreement on the diagnostic validity, clinical utility and prognostic value of the DSM-5 criteria and ICD-11 clinical guidelines for GD.
Methods: A total of 29 international experts with clinical and/or research experience in GD completed three iterative rounds of a Delphi survey. Experts rated proposed criteria in progressive rounds until a pre-determined level of agreement was achieved.
Results: For DSM-5 IGD criteria, there was an agreement both that a subset had high diagnostic validity, clinical utility and prognostic value and that some (e.g. tolerance, deception) had low diagnostic validity, clinical utility and prognostic value. Crucially, some DSM-5 criteria (e.g. escapism/mood regulation, tolerance) were regarded as incapable of distinguishing between problematic and non-problematic gaming. In contrast, ICD-11 diagnostic guidelines for GD (except for the criterion relating to diminished non-gaming interests) were judged as presenting high diagnostic validity, clinical utility and prognostic value.
Conclusions: This Delphi survey provides a foundation for identifying the most diagnostically valid and clinically useful criteria for GD. There was expert agreement that some DSM-5 criteria were not clinically relevant and may pathologize non-problematic patterns of gaming, whereas ICD-11 diagnostic guidelines are likely to diagnose GD adequately and avoid pathologizing
Brief psychotherapy administered by nonspecialised health workers to address risky substance use in patients with multidrugresistant tuberculosis: A feasibility and acceptability study
No full textBackground: Only 55% of multidrug-resistant tuberculosis (MDR-TB) cases worldwide complete treatment, with problem substance use a risk for default and treatment failure. Nevertheless, there is little research on psychotherapeutic interventions for reducing substance use amongst MDR-TB patients, in general, and on their delivery by non-specialist health workers in particular.
Objectives: To explore the feasibility and acceptability of a non-specialist health worker-delivered 4-session brief motivational interviewing and relapse prevention (MI-RP) intervention for problem substance use and to obtain preliminary data on the effects of this intervention on substance use severity, depressive symptoms, psychological distress and functional impairment at 3 months after hospital discharge.
Methods: Between December 2015 and October 2016, consenting MDR-TB patients admitted to Brewelskloof Hospital who screened at moderate to severe risk for substance-related problems on the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) were enrolled, and a baseline questionnaire administered. In the 4 weeks prior to planned discharge, trained counsellors delivered the MI-RP intervention. The baseline questionnaire was re-administered 3 months post-discharge and qualitative interviews were conducted with a randomly selected sample of participants (n = 10).
Results: Sixty patients were screened: 40 (66%) met inclusion criteria of which 39 (98%) were enrolled. Of the enrolled patients, 26 (67%) completed the counselling sessions and the final assessment. Qualitative interviews revealed participants' perceptions of the value of the intervention. From baseline to follow-up, patients reported reductions in substance use severity, symptoms of depression, distress and functional impairment.
Conclusion: In this feasibility study, participant retention in the study was moderate. We found preliminary evidence supporting the benefits of the intervention for reducing substance use and symptoms of psychological distress, supported by qualitative reports of patient experiences. Randomised studies are needed to demonstrate efficacy of this intervention before considering potential for wider implementation
Identification and profiling of a novel diazaspiro[3.4]octane chemical series active against multiple stages of the human malaria parasite plasmodium falciparum and optimization efforts
No full textA novel diazaspiro[3.4]octane series was identified from a Plasmodium falciparum whole-cell high-throughput screening campaign. Hits displayed activity against multiple stages of the parasite lifecycle, which together with a novel sp3-rich scaffold provided an attractive starting point for a hit-to-lead medicinal chemistry optimization and biological profiling program. Structure-activity-relationship studies led to the identification of compounds that showed low nanomolar asexual blood-stage activity (<50 nM) together with strong gametocyte sterilizing properties that translated to transmission-blocking activity in the standard membrane feeding assay. Mechanistic studies through resistance selection with one of the analogues followed by whole-genome sequencing implicated the P. falciparum cyclic amine resistance locus in the mode of resistance.The University of Cape Town, South African Medical Research Council, and South African Research Chairs Initiative of the Department of Science and Innovation, administered through the South African National Research Foundation are gratefully acknowledged for support (K.C. UID: 64767; L.-M.B. UID: 84627; L.L.K. UID: 64763)
"Your health - who do you trust?"
No full textHosted Professor Glenda Gray from the South African Medical Research Council shared her medical expertise and data-driven insights on the Covid-19 vaccine
Knowledge and attitudes towards maternal immunization: Perspectives from pregnant and non-pregnant mothers, their partners, mothers, healthcare providers, community and leaders in a selected urban setting in South Africa
No full textBackground: Maternal immunization has prevented millions of child deaths globally; nevertheless, incomplete vaccination remains a public health concern in South Africa, where almost half of child deaths occur during neonatal period. This study explored the knowledge and attitudes inhibiting vaccine acceptancy during pregnancy.
Methods: Key informant and semi-structured interviews were conducted with pregnant women receiving antenatal care at community clinics, antenatal care staff, women enrolled in maternal immunization trials, community leaders and non-pregnant women residing in Soweto. Focus Group Discussions were also held with the mothers and husbands/partners of the pregnant women (n = 55).
Results: The study established good knowledge, a positive attitude and high acceptability of maternal immunization among pregnant women, non-pregnant women, antenatal staff as well as church and community leaders. Men were the least positive about maternal immunization. Aside from antenatal staff, there was poor knowledge regarding the types of vaccinations administered and the health benefits of immunization across all the study groups. Reasons adduced for poor knowledge about the types of vaccinations include lack of communication on maternal immunization during antenatal sessions or clinic visits and power dynamics that tend to exist between healthcare workers and patients.
Conclusion: Ensuring that healthcare workers provide useful information on immunization during antenatal visits as well as include men in education sessions regarding the benefit of vaccination may increase patients' confidence and immunization uptake
Gene therapy for lysosomal storage disorders: Ongoing studies and clinical development
No full textRare monogenic disorders such as lysosomal diseases have been at the forefront in the development of novel treatments where therapeutic options are either limited or unavailable. The increasing number of successful pre-clinical and clinical studies in the last decade demonstrates that gene therapy represents a feasible option to address the unmet medical need of these patients. This article provides a comprehensive overview of the current state of the field, reviewing the most used viral gene delivery vectors in the context of lysosomal storage disorders, a selection of relevant pre-clinical studies and ongoing clinical trials within recent years
A review of systems biology research of anxiety disorders
No full textThe development of "omic" technologies and deep phenotyping may facilitate a systems biology approach to understanding anxiety disorders. Systems biology approaches incorporate data from multiple modalities (e.g., genomic, neuroimaging) with functional analyses (e.g., animal and tissue culture models) and mathematical modeling (e.g., machine learning) to investigate pathological biophysical networks at various scales. Here we review: i) the neurobiology of anxiety disorders; ii) how systems biology approaches have advanced this work; and iii) the clinical implications and future directions of this research. Systems biology approaches have provided an improved functional understanding of candidate biomarkers and have suggested future potential for refining the diagnosis, prognosis, and treatment of anxiety disorders. The systems biology approach for anxiety disorders is, however, in its infancy and in some instances is characterized by insufficient power and replication. The studies reviewed here represent important steps to further untangling the pathophysiology of anxiety disorders.This study received financial support from the Research Council of Norway (grant 276082), the South African Medical Research Council, the David and Elaine Potter Foundation, and the South African National Research Fund
RBBP6 interactome: RBBP6 isoform 3/DWNN and Nek6 interaction is critical for cell cycle regulation and may play a role in carcinogenesis
No full textRBBP6 is a multidomain protein, with four splice variants translated into four functional isoforms. RBBP6 isoform 1 has been reported to interact with TP53 and pRb as well as with proteins that regulate transcriptional response to tumorigenesis such as HDM2, ZBTB38, YBX1 and NEK6. Experimental validation of isoforms 2 and 4 is yet to be conducted. The third isoform, consisting of only the DWNN domain and a short unordered c terminus, has been shown to be down-regulated in several human cancers and demonstrated as a regulator of G2/M cell cycle arrest. A number of studies have supported the role of DWNN in cell cycle regulation, however, its mechanism in these processes remains obscure. Posttranslational modification of DWNN could be critical for its function and this study was formulated to understand how the DWNN regulates the cell cycle. Our study identified 12 cell cycle-related proteins interacting with DWNN using various bioinformatics tools. We also identified 10 ubiquitin ligases that interact with DWNN.
The most relevant interacting partner, the cell cycle regulator Nek6, has been reported to interact with DWNN during the cell cycle. It was therefore critical to interrogate the interaction between Nek6 and DWNN by homology modelling and docking. The DWNN mutants had a reduced affinity for NEK6 with at least one of the mutants having changes that affect at least one phosphorylation site. It is likely that NEK6 promotes cell proliferation by phosphorylating DWNN. This work suggests that DWNN co-regulates RNA splicing, ubiquitination, and cell cycle control. DWNN may therefore, be targeted for novel anticancer therapies through cell cycle regulation.We thank the South African Medical Research Council (SAMRC) and the National Research Foundation (NRF) for funding this project
What does social support sound like? Challenges and opportunities for using passive episodic audio collection to assess the social environment
No full textBackground: The social environment, comprised of social support, social burden, and quality of interactions, influences a range of health outcomes, including mental health. Passive audio data collection on mobile phones (e.g., episodic recording of the auditory environment without requiring any active input from the phone user) enables new opportunities to understand the social environment. We evaluated the use of passive audio collection on mobile phones as a window into the social environment while conducting a study of mental health among adolescent and young mothers in Nepal.
Methods: We enrolled 23 adolescent and young mothers who first participated in qualitative interviews to describe their social support and identify sounds potentially associated with that support. Then, episodic recordings were collected for 2 weeks from the mothers using an app to record 30 s of audio every 15 min from 4 A.M. to 9 P.M. Audio data were processed and classified using a pretrained model. Each classification category was accompanied by an estimated accuracy score. Manual validation of the machine-predicted speech and non-speech categories was done for accuracy.
Results: In qualitative interviews, mothers described a range of positive and negative social interactions and the sounds that accompanied these. Potential positive sounds included adult speech and laughter, infant babbling and laughter, and sounds from baby toys. Sounds characterizing negative stimuli included yelling, crying, screaming by adults and crying by infants. Sounds associated with social isolation included silence and TV or radio noises. Speech comprised 43% of all passively recorded audio clips (n = 7,725). Manual validation showed a 23% false positive rate and 62% false-negative rate for speech, demonstrating potential underestimation of speech exposure. Other common sounds were music and vehicular noises.
Conclusions: Passively capturing audio has the potential to improve understanding of the social environment. However, a pre-trained model had the limited accuracy for identifying speech and lacked categories allowing distinction between positive and negative social interactions. To improve the contribution of passive audio collection to understanding the social environment, future work should improve the accuracy of audio categorization, code for constellations of sounds, and combine audio with other smartphone data collection such as location and activity
