A Research Report submitted to the Faculty of Health Sciences, University of the Witwatersrand, in partial fulfilment of the requirements for the Degree of Master of Science in Medicine (Pharmaceutical Affairs) Johannesburg, 2016 / Background The World Health Organization (WHO) defines medicines regulation as the “promotion and protection of public health by ensuring the safety, efficacy and quality of drugs, and the appropriateness and accuracy of product information” (1). Medicines regulation is a key function in the realisation of the right to essential medicines. However, a satisfactory level of harmonization of regulatory activities has not been achieved in the Southern African Development Community (SADC) region as yet. Objectives The study evaluated the current status of medicines regulatory harmonization within the SADC region, as well as explored perceived barriers to regulatory harmonization and potential strategies to address these. Methods A cross-sectional exploratory study design with qualitative techniques, as well as an inductive approach was used. In-depth, semi-structured, face-to-face interviews with interviewees from the SADC Secretariat, the African Medicines Harmonization (AMRH) Initiative and the Southern Africa Regional Programme on Access to Medicines and Diagnostics (SARPAM) was used, involving secondary formal qualitative approaches to identify the emergent themes, was utilised initially. A questionnaire was formulated and adapted using secondary data collected from the face-to-face interviews, then piloted. Questionnaires were sent to senior members of all 15 regulatory authorities belonging to SADC, including registrars and deputy registrars. Theoretical and analytical codes were identified from repeated ideas, concepts or elements. Codes were grouped into concepts, and then into categories. Trend analysis was conducted, involving an in-depth analysis of patterns. Results Barriers to regulatory harmonization in the SADC region perceived by participants included i) deficiencies in governance and leadership within the SADC Secretariat, ii) human resource and technical capacity constraints, iii) limited financial resources, iv) lack of political will within SADC governments, v) lack of intra-SADC relationships, vi) risk-benefit analysis differences in assessment of applications and bias according to local population needs, as well as vii) different guidance documents and legal frameworks among member countries. Strategies identified to address these included i) using other harmonization initiatives as models, ii) application format harmonization and African Union (AU) Model Law adoption, iii) redirecting focus of harmonization to information sharing and technical matter rather than complex legislative frameworks, iv) regulator initiatives of harmonization instead of SADC secretariat reliance, v) World Bank Agreement adoption, vi) human resource capacity development and vii) convergence of guidelines instead of complete harmonization of all regulatory requirements. Conclusions The findings in this study suggest that it may be necessary to redirect the focus of harmonization to more readily achievable activities and aim for convergence of guidelines. Regulatory harmonization is possible if barriers to it are addressed. / MT2016

Den här studien grundar sig i en kvalitativ textanalys ur ett retoriskt och semiotiskt perspektiv. Syftet med denna undersökning var att se om det finns några skillnader i budskapen i kriskommunikationen som rör Covid-19 på World Health Organizations Instagram- och TikTokkonto samt att se om det finns några retoriska argument i dessa inlägg. Uppsatsen vill även ta reda på hur WHO förstärker budskapen som kommuniceras. De teoretiska utgångspunkterna för denna studie är kriskommunikation och krisretorik. I den tidigare forskningen som denna uppsats utgått ifrån beskrivs framgångsrik kriskommunikation ur ett retoriskt perspektiv. Ett av framgångskoncepten ur en retorisk synvinkel var att bygga sin kriskommunikation med hjälp av pathos. I resultatet för denna undersökning framkom det att budskapen skiljer sig men inte avsevärt mycket mellan plattformarna men att på Instagram byggs kommunikationen mera på logos och på TikTok mera på pathos. Resultatet visade även att WHO på Instagram använder sig av piktogram och bilder för att förstärka budskapet.

Magister Public Health - MPH / Sub Saharan Africa (SSA) single-handedly accounted for approximately two thirds (196 000) of the world maternal deaths. High maternal deaths have been attributed to high prevalence of HIV and low uptake of Antenatal Care (ANC). This made World Health Organization (WHO) to recommend integration of Prevention of Mother to Child Transmission of HIV (PMTCT) services into ANC to improve accessibility and utilization. According to Zambia Ministry of Health (MoH), every pregnant woman should have her ANC registration in the first trimester and achieve eight visits by delivery time. With the extra need of PMTCT services in the women living with HIV, early and regular ANC attendance is emphasized. However, in Zambia, there is limited information on ANC uptake and its associated factors among women living with HIV. / 2023

Philosophiae Doctor - PhD / The incidence of Diffuse large B cell Lymphoma has been increasing lately at an alarming rate especially, in developing countries like Sudan. The standard therapy in Sudan is based solely on the R-CHOP chemotherapy regimen, yet it has been noticed that Diffuse Large B cell Lymphoma prognosis remains unfavorable. The late diagnosis and the consequent side-effects of the therapy directly affected the disease’s poor outcome. There is a scarcity of scientific publications regarding DLBCL in Sudan, but the increased burden necessitates the need for further research.

The World Health Organization estimates that there are 285 million people suffering from visual impairment worldwide. The top two causes of uncorrectable vision loss are glaucoma and age-related macular degeneration (AMD), with 112 million people anticipated to be impacted by glaucoma by 2040 and nearly 15% of U.S. adults aged 43-86 predicted to be diagnosed with AMD over the next 15 years. To slow the progression of these ophthalmic diseases, the most valuable preventive action is timely detection and treatment by an ophthalmologist. However, over 50% of glaucoma cases go undetected due to lack of timely assessment by a medical expert. This thesis seeks to transform artificial intelligence (AI) into a trustworthy partner to clinicians, aiding in expediting diagnostic screening for obvious cases and serving as corroboration/a ‘second opinion’ in ambiguous cases. In order to develop AI algorithms that can be trusted as team-mates in the clinic, the AI must be robust to data collected at various sites/from various patient populations, its decision-making mechanisms must be explainable, and to benefit the broadest population (for whom expensive imaging equipment and/or specialist time may not be available), it must be portable. This thesis addresses these three challenges (1) by developing and evaluating robust deep learning (DL) algorithms for detection of glaucoma and AMD from data collected at multiple sites or using multiple imaging modalities, (2) by making AI interpretable, through: (a) comparison of image concepts used by DL systems for decision-making with image regions fixated upon by human experts during glaucoma diagnosis, and (b) through odds ratio ranking of clinical biomarkers most indicative of AMD risk used by both experts and AI, and (3) by enhancing theimage quality of data collected via a portable OCT device using deep-learning based super-resolution generative adversarial network (GAN) approaches. The resulting robust deep learning algorithms achieve accuracy as high as 95% at detection of glaucoma and AMD from optical coherence tomography (OCT) and OCT angiography images/volumes. The interpretable AI-concept/expert-eye-movement comparison showed the importance of three OCT-report sub-regions used by both AI and human experts for glaucoma detection. The pipeline described here for evaluating AI robustness and validating interpretable image concepts used by deep learning systems in conjunction with expert eye movements has the potential to help standardize the acceptance of new AI tools for use in the clinic. Furthermore, the eye movement collection protocols introduced in this thesis may also help to train current medical residents and fellows regarding key features employed by expert specialists for accurate and efficient eye disease diagnosis. The odds ratio ranking of AMD biomarkers distinguished the top two clinical features (choroidal neovascularization and geographic atrophy) most indicative of AMD risk that are agreed upon by both AI and experts. Lastly, GAN-based super-resolution of portable OCT images boosted performance of downstream deep learning systems for AMD detection, facilitating future work toward embedding AI algorithms within portable OCT systems, in order for a larger population to gain access to potentially sight-saving technology. By enhancing AI robustness, interpretability, and portability, this work paves the way for ophthalmologist-AI teams to achieve augmented performance compared to human experts or AI alone, leading to expedited eye disease detection, treatment, and thus better patient outcomes.

Background: Common mental illnesses are a major public health challenge. Two common mental illnesses, depression and anxiety, were respectively ranked the second and eighth major causes of disability in 2019. However, the mental health treatment gap in low- and middle-income countries (LMICs) is higher than 90%. Systematic reviews suggest that integrated models delivered by primary health or lay providers are effective at reducing symptoms and improving quality of life among those with mental illnesses in LMICs. However, integrated models have not been widely implemented in routine primary care and community settings, beyond researcher-controlled pilot studies in LMICs. This integrated learning experience (ILE) contributes to key gaps in global mental health and implementation research by outlining implementation strategies (the ‘how’) and components of integrated models (the ‘what’) for people living with common mental illnesses in Latin America, a region composed of LMICs and selected high income countries (HICs) widely known for being early adopters of integrated models. Given current literature gaps, this study also provides an applied example of the assessment of contextual implementation factors and the selection of implementation strategies for integrated models for common mental illnesses in Guatemala, a LMIC in Central America where the burden due to common mental illnesses is high and the implementation of integrated models is low. Methods: First, we conducted a scoping review to map and summarize the existing literature on integrated service models for common mental illnesses in primary care and community settings in Latin America. Second, we conducted a multi-methods assessment of the local context prior to selecting the implementation strategies for a collaborative care program for Maya T’zutujil young adults living with common mental illnesses in a rural municipal health district in Sololá, a rural department in Guatemala. We used data collected through the public health system to develop behavior-over-time (BOT) graphs outlining the number of primary care visits for common mental illnesses over time (2018-2022). We followed the Practical, Robust Implementation and Sustainability Model (PRISM) framework to conduct qualitative semi-structured interviews. Participants represented Ministry of Health coordinators and providers; community youth leaders with lived experience; and community providers. We performed matrix-based thematic analysis of interview transcripts. Third, we used group model building (GMB), a participatory systems thinking approach to inform the selection of implementation strategies for a primary care, community-based collaborative care program for common mental illnesses in rural Guatemala. Results: First, our scoping review included 33 publications conducted in 6 countries (Belize, Brazil, Chile, Colombia, Mexico, Peru) about 18 programs commonly addressing depression (N=14, 77.78%). Four studies were experimental. The most and least common components were ‘team-based care’ (N=14, 77.78%) and ‘family/user engagement’ (N=1, 5.55%). The most and least common Expert Recommendations for Implementing Change (ERIC) categories were ‘supporting clinicians’ (N=17, 94.44%), mainly through task-sharing, and ‘changing infrastructure’ (N=4, 22.22%). We found wide heterogeneity across studies about combinations of components and implementation strategies. Second, our multi-methods assessment showed that less than 1% of the total number of public health visits corresponded to common mental illnesses in the study health district. A collaborative care program could help to increase the number of visits. To enhance fit to the study health district, the program would need to ensure the users’ right to privacy and engage community providers (e.g. Maya providers, religious leaders) and Maya explanatory models of mental health. Infrastructural elements at the municipal health district, such as the availability of psychotropic medications, would need to be met to ensure the program’s implementation and sustainability. Third, we identified two health-district subsystems influencing the implementation of public primary mental health services. At the community-level, we identified four subsystems. We identified 32 distinct implementation strategies representing the nine ERIC categories. Conclusion: This ILE indicates the need for additional studies focused on the participatory design and evaluation of implementation strategies that go beyond the provider-level (supply side of implementation) and focus on the community-level (demand side of implementation). Our results and methodologies may be utilized by researchers and implementers seeking to integrate mental health services in Guatemala and other LMICs.

People with psychosocial disabilities and mental health conditions are commonly exposed to human rights violations within the mental health care system and the general community. The negative consequences of such violations have been widely documented but attempts to change the status quo have met with little success. The present dissertation aims to challenge this situation and advance the human rights-based global agenda for mental health by promoting a change within the mental health care system and the general community. Chapter 2 is a scoping review that comprehensively examines the literature on interventions that apply a human rights-based approach to promote the rights of persons with psychosocial disabilities and mental health conditions in health settings and the general community. Chapter 3 is an empirical paper that evaluates the psychometric properties of three instruments that can be used to assess the effect of future interventions aiming to promote the rights of persons with psychosocial disabilities and mental health conditions. Chapter 4 is an empirical paper that assesses the efficacy of the WHO QualityRights e-training, a new intervention to promote the human rights of persons with psychosocial disabilities and mental health conditions. The scoping review indicated that there is a growing body of literature on interventions that apply a human rights-based approach to promote the rights of people with psychosocial disabilities and mental health conditions. However, many of the studies evaluating these interventions are currently low-quality and there is urgent need for additional and methodologically robust research on this topic. Additionally, our findings showed that worldwide there are many promising practices and interventions that are currently unexamined or insufficiently evaluated. The psychometric analyses in Chapter 3 indicated that the three instruments developed to assess the knowledge about the rights of persons with mental health conditions and psychosocial disabilities (WHO QualityRights Knowledge), the attitudes towards them and their role as rights holders (WHO QualityRights Attitudes), and mental health professionals’ practices related to substitute decision-making and coercion (WHO QualityRights Practices) are sufficiently valid and reliable and could be used in future research. Finally, the data analyzed in Chapter 4 demonstrated that the WHO QualityRights e-training, compared with a placebo intervention, is effective in improving mental health professionals’ knowledge about human rights and attitudes towards people with psychosocial disabilities and mental health conditions and their role as rights-holders. Furthermore, these improvements are maintained over time. The WHO QualityRights e-training was also effective in reducing self-reported practices related to substitute-decision making and restraint both at 3 and 6 months. Given the impact that human rights violations have on the health and wellbeing of persons with psychosocial disabilities and mental health conditions, more efforts are needed to develop new interventions and carry out methodologically strong research in this area. This dissertation is a right step in this direction.

(1) Background: Low rates of hepatitis C virus (HCV) diagnosis and sub-optimal linkage to care constitute barriers toward eliminating the infection. In 2012/2013, we showed that HCV screening in primary care detects unknown cases. However, hepatitis C patients may not receive further diagnostics and therapy because they drop out during the referral pathway to secondary care. Thus, we used an existing network of primary care physicians and a practice of gastroenterology to investigate the pathway from screening to therapy. (2) Methods: HCV screening was prospectively included in a routine check-up of primary care physicians who cooperated regularly with a private gastroenterology practice. Anti-HCV-positive patients were referred for further specialized diagnostics and treatment if indicated. (3) Results: Seventeen primary care practices screened 1875 patients. Twelve individuals were anti-HCV-positive (0.6%), six of them reported previous antiviral HCV therapy, and one untreated patient was HCV-RNA-positive (0.05% of the population). None of the 12 anti-HCV-positive cases showed up at the private gastroenterology practice. Further clinical details of the pathway from screening to therapy could not be analyzed. (4) Conclusions: The linkage between primary and secondary care appears to be problematic in the HCV setting even among cooperating partners, but robust conclusions require larger datasets.

Linkage to care presents one obstacle toward eliminating HCV, and the current two-step pathway (anti-HCV, followed by HCV-RNA testing) results in the loss of patients. HCV screening was tested in the primary care setting with the fingerstick Xpert HCV viral load point-of-care assay to analyze the practicability of immediate diagnosis. Anti-HCV (Cobas) and HCV-RNA (Cobas Amplicor version 2.0, only performed if anti-HCV was positive) were analyzed centrally as the gold standard. The Xpert assay was performed by 10 primary care private practices. In total, 622 patients were recruited. Five individuals (0.8%) were anti-HCV positive, and one was HCV-RNA positive. The Xpert test was valid in 546/622 (87.8%) patients. It was negative in 544 and positive in 2 cases, both of whom were anti-HCV negative. The HCV-RNA PCR and the Xpert test were both negative in 4/5 anti-HCV-positive cases, and the individual with HCV-RNA 4.5 × 106 IU/mL was not detected by the Xpert test. Primary care physicians rated the Xpert test practicability as bad, satisfactory, or good in 6%, 13%, and 81%, respectively, though 14/29 (48%) bad test ratings were assigned by a single practice. Despite adequate acceptance, interpretability and diagnostic performance in primary care settings should be further evaluated before its use in HCV screening can be recommended.

Background: Autism and other neurodevelopmental disorders (NDD) are common in low- and middle-income countries (LMIC). However, services to address the needs of this group in LMIC are almost non-existent. The World Health Organization (WHO) developed the Caregiver Skills Training (CST) programme to be suitable for delivery in diverse global contexts. Ethiopia, the country of focus in this study, has a largely rural population and a lack of specialist service providers. Additional contextual challenges, including poverty, low literacy, limited access to healthcare and a lack of specialist child mental health services, may undermine the delivery of CST in this setting. This thesis, therefore, seeks to explore the acceptability and feasibility of non-specialist delivery of the WHO-CST from the perspective of providers and caregivers in rural Ethiopia. Methods: In Chapter one, a general literature review of neurodevelopmental disability and caregiver skills training is presented, with a focus on sub-Saharan Africa, to help contextualise the main qualitative study, outlined in chapter two. In-depth interviews were conducted with caregivers (n=19) who were all participants in two rural pilot studies of the WHO-CST programme. In addition, three focus group interviews were conducted with non-specialist facilitators (n=8), who facilitated the CST programme in two rural pilot tests. Data were analysed using the framework approach. Results: Findings were mapped onto the three framework themes created for this analysis: 1) Programme content: caregivers and facilitators uniformly indicated that the adapted programme addressed a need and was relevant for their context; caregivers emphasised how the programme helped them understand their child's problems and improve their skills to support their children; facilitators highlighted having acquired new knowledge and skills relating to NDD; 2) Programme facilitation: caregiver responses suggested that programme facilitation by non-specialists was acceptable; non-specialist facilitators emphasised the importance of support and supervision for the facilitators and simplification and modification of some concepts, such as the concept of play, and 3) CST training approach and delivery: participants indicated that the training modalities, including home visits and group training, were acceptable and feasible in the local context. Conclusions: This study suggested that, with some contextually appropriate modifications of programme content and delivery and continuing supervision of facilitators, the WHO-CST programme facilitated by non-specialists would be acceptable and feasible in rural Ethiopia. Results from this study may be useful to fine-tune the implementation of non-specialist delivery of the CST programme in Ethiopia, as well as other LMIC.