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  1. Article ; Online: Understanding Uganda's early adoption of novel differentiated HIV treatment services: a qualitative exploration of drivers of policy uptake.

    Zakumumpa, Henry / Kwiringira, Japheth / Katureebe, Cordelia / Spicer, Neil

    BMC health services research

    2023  Volume 23, Issue 1, Page(s) 343

    Abstract: Background: Although differentiated service delivery (DSD) for HIV treatment was endorsed by the WHO in its landmark 2016 guidelines to lessen patients' need to frequently visit clinics and hence to reduce unnecessary burdens on health systems, uptake ... ...

    Abstract Background: Although differentiated service delivery (DSD) for HIV treatment was endorsed by the WHO in its landmark 2016 guidelines to lessen patients' need to frequently visit clinics and hence to reduce unnecessary burdens on health systems, uptake has been uneven globally. This paper is prompted by the HIV Policy Lab's annual report of 2022 which reveals substantial variations in programmatic uptake of differentiated HIV treatment services across the globe. We use Uganda as a case study of an 'early adopter' to explore the drivers of programmatic uptake of novel differentiated HIV treatment services.
    Methods: We conducted a qualitative case-study in Uganda. In-depth interviews were held with national-level HIV program managers (n = 18), district health team members (n = 24), HIV clinic managers (n = 36) and five focus groups with recipients of HIV care (60 participants) supplemented with documentary reviews. Our thematic analysis of the qualitative data was guided by the Consolidated Framework for Implementation Research (CFIR)'s five domains (inner context, outer setting, individuals, process of implementation).
    Results: Our analysis reveals that drivers of Uganda's 'early adoption' of DSD include: having a decades-old HIV treatment intervention implementation history; receiving substantial external donor support in policy uptake; the imperatives of having a high HIV burden; accelerated uptake of select DSD models owing to Covid-19 'lockdown' restrictions; and Uganda's participation in clinical trials underpinning WHO guidance on DSD. The identified processes of implementation entailed policy adoption of DSD (such as the role of local Technical Working Groups in domesticating global guidelines, disseminating national DSD implementation guidelines) and implementation strategies (high-level health ministry buy-in, protracted patient engagement to enhance model uptake, devising metrics for measuring DSD uptake progress) for promoting programmatic adoption.
    Conclusion: Our analysis suggests early adoption derives from Uganda's decades-old HIV intervention implementation experience, the imperative of having a high HIV burden which prompted innovations in HIV treatment delivery as well as outer context factors such as receiving substantial external assistance in policy uptake. Our case study of Uganda offers implementation research lessons on pragmatic strategies for promoting programmatic uptake of differentiated treatment HIV services in other countries with a high HIV burden.
    MeSH term(s) Humans ; Uganda ; COVID-19 ; Ambulatory Care Facilities ; Policy ; HIV Infections/drug therapy
    Language English
    Publishing date 2023-04-05
    Publishing country England
    Document type Journal Article
    ZDB-ID 2050434-2
    ISSN 1472-6963 ; 1472-6963
    ISSN (online) 1472-6963
    ISSN 1472-6963
    DOI 10.1186/s12913-023-09313-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Understanding Uganda’s early adoption of novel differentiated HIV treatment services

    Henry Zakumumpa / Japheth Kwiringira / Cordelia Katureebe / Neil Spicer

    BMC Health Services Research, Vol 23, Iss 1, Pp 1-

    a qualitative exploration of drivers of policy uptake

    2023  Volume 14

    Abstract: Abstract Background Although differentiated service delivery (DSD) for HIV treatment was endorsed by the WHO in its landmark 2016 guidelines to lessen patients’ need to frequently visit clinics and hence to reduce unnecessary burdens on health systems, ... ...

    Abstract Abstract Background Although differentiated service delivery (DSD) for HIV treatment was endorsed by the WHO in its landmark 2016 guidelines to lessen patients’ need to frequently visit clinics and hence to reduce unnecessary burdens on health systems, uptake has been uneven globally. This paper is prompted by the HIV Policy Lab’s annual report of 2022 which reveals substantial variations in programmatic uptake of differentiated HIV treatment services across the globe. We use Uganda as a case study of an ‘early adopter’ to explore the drivers of programmatic uptake of novel differentiated HIV treatment services. Methods We conducted a qualitative case-study in Uganda. In-depth interviews were held with national-level HIV program managers (n = 18), district health team members (n = 24), HIV clinic managers (n = 36) and five focus groups with recipients of HIV care (60 participants) supplemented with documentary reviews. Our thematic analysis of the qualitative data was guided by the Consolidated Framework for Implementation Research (CFIR)’s five domains (inner context, outer setting, individuals, process of implementation). Results Our analysis reveals that drivers of Uganda’s ‘early adoption’ of DSD include: having a decades-old HIV treatment intervention implementation history; receiving substantial external donor support in policy uptake; the imperatives of having a high HIV burden; accelerated uptake of select DSD models owing to Covid-19 ‘lockdown’ restrictions; and Uganda’s participation in clinical trials underpinning WHO guidance on DSD. The identified processes of implementation entailed policy adoption of DSD (such as the role of local Technical Working Groups in domesticating global guidelines, disseminating national DSD implementation guidelines) and implementation strategies (high-level health ministry buy-in, protracted patient engagement to enhance model uptake, devising metrics for measuring DSD uptake progress) for promoting programmatic adoption. Conclusion Our analysis suggests early adoption ...
    Keywords Antiretroviral therapy ; HIV treatment ; Differentiated service delivery ; DSD ; Case study ; Health policy and systems ; Public aspects of medicine ; RA1-1270
    Subject code 360
    Language English
    Publishing date 2023-04-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Is Internalised Homonegativity associated with HIV testing and HIV risk behaviours of men who have sex with men: a multilevel cross-sectional study of sub-Saharan African countries.

    Kalu, Ngozi / Ross, Michael W / Taegtmeyer, Miriam / Spicer, Neil / Adebajo, Sylvia / Owolabi, Rotimi / Lamontagne, Erik / Howell, Sean / Neuman, Melissa

    BMJ open

    2024  Volume 14, Issue 1, Page(s) e074791

    Abstract: Objectives: This study assessed the associations of Internalised Homonegativity (IH) with HIV testing and risk behaviours of adult men who have sex with men (MSM) in sub-Saharan Africa (SSA) and effect modification by the legal climate.: Design: We ... ...

    Abstract Objectives: This study assessed the associations of Internalised Homonegativity (IH) with HIV testing and risk behaviours of adult men who have sex with men (MSM) in sub-Saharan Africa (SSA) and effect modification by the legal climate.
    Design: We used data from the cross-sectional 2019 Global Lesbian, Gay, Bisexual, Transgender and Intersex (LGBTI+) Internet survey study.
    Setting and participants: Overall, the 2019 Global LGBTI Internet Survey collected data from 46 SSA countries. In this secondary analysis, we included data from 3191 MSM in 44 SSA countries as there were no eligible MSM responses in the 2 countries excluded.
    Outcome measures: Our response variables were self-reported binary indicators of ever tested for HIV, recently tested in the past 6 months (from those who reported ever testing), transactional sex (paying for and being paid for sex in the past 12 months), and unprotected anal sex (that is without a condom or pre-exposure prohylaxis (PrEP)) with a non-steady partner (in the past 3 months).
    Results: Our findings showed high levels of IH (range 1-7) in MSM across SSA (mean (SD)=5.3 (1.36)). We found that MSM with higher IH levels were more likely to have ever (adjusted OR (aOR) 1.18, 95% CI 1.03 to 1.35) and recently tested (aOR 1.19, 95% CI 1.07 to 1.32) but no evidence of an association with paying for sex (aOR 1.00, 95% CI 0.89 to 1.12), selling sex (aOR 1.06, 95% CI 0.95 to 1.20) and unprotected sex (aOR 0.99, 95% CI 0.89 to 1.09). However, we observed that a favourable legal climate modifies the associations of IH and paying for sex (aOR 0.75, 95% CI 0.60 to 0.94). Increasing levels of IH had a negative association with paying for sex in countries where same-sex relationships are legal. We found no associations of IH with unprotected anal sex in the population surveyed.
    Conclusions: We confirm that IH is widespread across SSA but in countries that legalise same-sex relationships, MSM were less likely to engage in transactional sex compared with those in countries where homosexuality is criminalised.
    MeSH term(s) Male ; Adult ; Female ; Humans ; Homosexuality, Male ; Cross-Sectional Studies ; HIV Infections/diagnosis ; HIV Infections/epidemiology ; Sexual and Gender Minorities ; Sexual Behavior ; Surveys and Questionnaires ; Risk-Taking ; HIV Testing
    Language English
    Publishing date 2024-01-29
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2599832-8
    ISSN 2044-6055 ; 2044-6055
    ISSN (online) 2044-6055
    ISSN 2044-6055
    DOI 10.1136/bmjopen-2023-074791
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Dispensing antiretrovirals during Covid-19 lockdown: re-discovering community-based ART delivery models in Uganda.

    Zakumumpa, Henry / Tumwine, Christopher / Milliam, Kiconco / Spicer, Neil

    BMC health services research

    2021  Volume 21, Issue 1, Page(s) 692

    Abstract: Background: The notion of health-system resilience has received little empirical attention in the current literature on the Covid-19 response. We set out to explore health-system resilience at the sub-national level in Uganda with regard to strategies ... ...

    Abstract Background: The notion of health-system resilience has received little empirical attention in the current literature on the Covid-19 response. We set out to explore health-system resilience at the sub-national level in Uganda with regard to strategies for dispensing antiretrovirals during Covid-19 lockdown.
    Methods: We conducted a qualitative case-study of eight districts purposively selected from Eastern and Western Uganda. Between June and September 2020, we conducted qualitative interviews with district health team leaders (n = 9), ART clinic managers (n = 36), representatives of PEPFAR implementing organizations (n = 6).In addition, six focus group discussions were held with recipients of HIV care (48 participants). Qualitative data were analyzed using thematic approach.
    Results: Five broad strategies for distributing antiretrovirals during 'lockdown' emerged in our analysis: accelerating home-based delivery of antiretrovirals,; extending multi-month dispensing from three to six months for stable patients; leveraging the Community Drug Distribution Points (CDDPs) model for ART refill pick-ups at outreach sites in the community; increasing reliance on health information systems, including geospatial technologies, to support ART refill distribution in unmapped rural settings. District health teams reported leveraging Covid-19 outbreak response funding to deliver ART refills to homesteads in rural communities.
    Conclusion: While Covid-19 'lockdown' restrictions undoubtedly impeded access to facility-based HIV services, they revived interest by providers and demand by patients for community-based ART delivery models in case-study districts in Uganda.
    MeSH term(s) COVID-19 ; Communicable Disease Control ; Delivery of Health Care ; HIV Infections/drug therapy ; HIV Infections/epidemiology ; Humans ; SARS-CoV-2 ; Uganda
    Language English
    Publishing date 2021-07-13
    Publishing country England
    Document type Journal Article
    ZDB-ID 2050434-2
    ISSN 1472-6963 ; 1472-6963
    ISSN (online) 1472-6963
    ISSN 1472-6963
    DOI 10.1186/s12913-021-06607-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: What are the challenges for antibiotic stewardship at the community level? An analysis of the drivers of antibiotic provision by informal healthcare providers in rural India.

    Gautham, Meenakshi / Spicer, Neil / Chatterjee, Soumyadip / Goodman, Catherine

    Social science & medicine (1982)

    2021  Volume 275, Page(s) 113813

    Abstract: In many low- and middle-income countries, providers without formal training are an important source of antibiotics, but may provide these inappropriately, contributing to the rising burden of drug resistant infections. Informal providers (IPs) who ... ...

    Abstract In many low- and middle-income countries, providers without formal training are an important source of antibiotics, but may provide these inappropriately, contributing to the rising burden of drug resistant infections. Informal providers (IPs) who practise allopathic medicine are part of India's pluralistic health system legacy. They outnumber formal providers but operate in a policy environment of unclear legitimacy, creating unique challenges for antibiotic stewardship. Using a systems approach we analysed the multiple intrinsic (provider specific) and extrinsic (community, health and regulatory system and pharmaceutical industry) drivers of antibiotic provision by IPs in rural West Bengal, to inform the design of community stewardship interventions. We surveyed 291 IPs in randomly selected village clusters in two contrasting districts and conducted in-depth interviews with 30 IPs and 17 key informants including pharmaceutical sales representatives, managers and wholesalers/retailers; medically qualified private and public doctors and health and regulatory officials. Eight focus group discussions were conducted with community members. We found a mosaic or bricolage of informal practices conducted by IPs, qualified doctors and industry stakeholders that sustained private enterprise and supplemented the weak public health sector. IPs' intrinsic drivers included misconceptions about the therapeutic necessity of antibiotics, and direct and indirect economic benefits, though antibiotics were not the most profitable category of drug sales. Private doctors were a key source of IPs' learning, often in exchange for referrals. IPs constituted a substantial market for local and global pharmaceutical companies that adopted aggressive business strategies to exploit less-saturated rural markets. Paradoxically, the top-down nature of regulations produced a regulatory impasse wherein regulators were reluctant to enforce heavy sanctions for illegal sales, fearing an adverse impact on rural healthcare, but could not implement enabling strategies to improve antibiotic provision due to legal barriers. We discuss the implications for a multi-stakeholder antibiotic stewardship strategy in this setting.
    MeSH term(s) Anti-Bacterial Agents/therapeutic use ; Antimicrobial Stewardship ; Health Personnel ; Humans ; India ; Rural Population
    Chemical Substances Anti-Bacterial Agents
    Language English
    Publishing date 2021-03-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 4766-1
    ISSN 1873-5347 ; 0037-7856 ; 0277-9536
    ISSN (online) 1873-5347
    ISSN 0037-7856 ; 0277-9536
    DOI 10.1016/j.socscimed.2021.113813
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: National health governance, science and the media: drivers of COVID-19 responses in Germany, Sweden and the UK in 2020.

    Hanson, Claudia / Luedtke, Susanne / Spicer, Neil / Stilhoff Sörensen, Jens / Mayhew, Susannah / Mounier-Jack, Sandra

    BMJ global health

    2022  Volume 6, Issue 12

    Abstract: The COVID-19 pandemic is an unprecedented global crisis in which governments had to act in a situation of rapid change and substantial uncertainty. The governments of Germany, Sweden and the UK have taken different paths allowing learning for future ... ...

    Abstract The COVID-19 pandemic is an unprecedented global crisis in which governments had to act in a situation of rapid change and substantial uncertainty. The governments of Germany, Sweden and the UK have taken different paths allowing learning for future pandemic preparedness. To help inform discussions on preparedness, inspired by resilience frameworks, this paper reviews governance structures, and the role of science and the media in the COVID-19 response of Germany, Sweden and the UK in 2020. We mapped legitimacy, interdependence, knowledge generation and the capacity to deal with uncertainty.Our analysis revealed stark differences which were linked to pre-existing governing structures, the traditional role of academia, experience of crisis management and the communication of uncertainty-all of which impacted on how much people trusted their government. Germany leveraged diversity and inclusiveness, a 'patchwork quilt', for which it was heavily criticised during the second wave. The Swedish approach avoided plurality and largely excluded academia, while in the UK's academia played an important role in knowledge generation and in forcing the government to review its strategies. However, the vivant debate left the public with confusing and rapidly changing public health messages. Uncertainty and the lack of evidence on how best to manage the COVID-19 pandemic-the main feature during the first wave-was only communicated explicitly in Germany. All country governments lost trust of their populations during the epidemic due to a mix of communication and transparency failures, and increased questioning of government legitimacy and technical capacity by the public.
    MeSH term(s) COVID-19 ; Germany/epidemiology ; Humans ; Pandemics/prevention & control ; SARS-CoV-2 ; Sweden/epidemiology ; United Kingdom/epidemiology
    Language English
    Publishing date 2022-05-17
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ISSN 2059-7908
    ISSN 2059-7908
    DOI 10.1136/bmjgh-2021-006691
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: 'It's far too complicated': why fragmentation persists in global health.

    Spicer, Neil / Agyepong, Irene / Ottersen, Trygye / Jahn, Albrecht / Ooms, Gorik

    Globalization and health

    2020  Volume 16, Issue 1, Page(s) 60

    Abstract: Background: Despite many efforts to achieve better coordination, fragmentation is an enduring feature of the global health landscape that undermines the effectiveness of health programmes and threatens the attainment of the health-related Sustainable ... ...

    Abstract Background: Despite many efforts to achieve better coordination, fragmentation is an enduring feature of the global health landscape that undermines the effectiveness of health programmes and threatens the attainment of the health-related Sustainable Development Goals. In this paper we identify and describe the multiple causes of fragmentation in development assistant for health at the global level. The study is of particular relevance since the emergence of new global health problems such as COVID-19 heightens the need for global health actors to work in coordinated ways. Our study is part of the Lancet Commission on Synergies between Universal Health Coverage, Health Security and Health Promotion.
    Methods: We used a mixed methods approach. This consisted of a non-systematic literature review of published papers in scientific journals, reports, books and websites. We also carried out twenty semi-structured expert interviews with individuals from bilateral and multilateral organisations, governments and academic and research institutions between April 2019 and December 2019.
    Results: We identified five distinct yet interconnected sets of factors causing fragmentation: proliferation of global health actors; problems of global leadership; divergent interests; problems of accountability; problems of power relations. We explain why global health actors struggle to harmonise their approaches and priorities, fail to align their work with low- and middle-income countries' needs and why they continue to embrace funding instruments that create fragmentation.
    Conclusions: Many global actors are genuinely committed to addressing the problems of fragmentation, despite their complexity and interconnected nature. This paper aims to raise awareness and understanding of the causes of fragmentation and to help guide actors' efforts in addressing the problems and moving to more synergistic approaches.
    MeSH term(s) COVID-19 ; Coronavirus Infections/epidemiology ; Global Health ; Humans ; International Cooperation ; Pandemics ; Pneumonia, Viral/epidemiology
    Keywords covid19
    Language English
    Publishing date 2020-07-09
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ISSN 1744-8603
    ISSN (online) 1744-8603
    DOI 10.1186/s12992-020-00592-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Professional advice for primary healthcare workers in Ethiopia: a social network analysis.

    Sabot, Kate / Blanchet, Karl / Berhanu, Della / Spicer, Neil / Schellenberg, Joanna

    BMC health services research

    2020  Volume 20, Issue 1, Page(s) 551

    Abstract: Background: In an era of increasingly competitive funding, governments and donors will be looking for creative ways to extend and maximise resources. One such means can include building upon professional advice networks to more efficiently introduce, ... ...

    Abstract Background: In an era of increasingly competitive funding, governments and donors will be looking for creative ways to extend and maximise resources. One such means can include building upon professional advice networks to more efficiently introduce, scale up, or change programmes and healthcare provider practices. This cross-sectional, mixed-methods, observational study compared professional advice networks of healthcare workers in eight primary healthcare units across four regions of Ethiopia. Primary healthcare units include a health centre and typically five satellite health posts.
    Methods: One hundred sixty staff at eight primary healthcare units were interviewed using a structured tool. Quantitative data captured the frequency of healthcare worker advice seeking and giving on providing antenatal, childbirth, postnatal and newborn care. Network and actor-level metrics were calculated including density (ratio of ties between actors to all possible ties), centrality (number of ties incident to an actor), distance (average number of steps between actors) and size (number of actors within the network). Following quantitative network analyses, 20 qualitative interviews were conducted with network study participants from four primary healthcare units. Qualitative interviews aimed to interpret and explain network properties observed. Data were entered, analysed or visualised using Excel 6.0, UCINET 6.0, Netdraw, Adobe InDesign and MaxQDA10 software packages.
    Results: The following average network level metrics were observed: density .26 (SD.11), degree centrality .45 (SD.08), distance 1.94 (SD.26), number of ties 95.63 (SD 35.46), size of network 20.25 (SD 3.65). Advice networks for antenatal or maternity care were more utilised than advice networks for post-natal or newborn care. Advice networks were typically limited to primary healthcare unit staff, but not necessarily to supervisors. In seeking advice, a colleague's level of training and knowledge were valued over experience. Advice exchange primarily took place in person or over the phone rather than over email or online fora. There were few barriers to seeking advice.
    Conclusion: Informal, inter-and intra-cadre advice networks existed. Fellow primary healthcare unit staff were preferred, particularly midwives, but networks were not limited to the primary healthcare unit. Additional research is needed to associate network properties with outcomes and pilot network interventions with central actors.
    MeSH term(s) Attitude of Health Personnel ; Cross-Sectional Studies ; Ethiopia ; Female ; Health Personnel ; Humans ; Infant, Newborn ; Male ; Maternal Health Services ; Midwifery ; Parturition ; Pregnancy ; Primary Health Care ; Professional Practice ; Social Network Analysis ; Social Networking
    Language English
    Publishing date 2020-06-17
    Publishing country England
    Document type Journal Article ; Observational Study
    ISSN 1472-6963
    ISSN (online) 1472-6963
    DOI 10.1186/s12913-020-05367-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Understanding implementation barriers in the national scale-up of differentiated ART delivery in Uganda.

    Zakumumpa, Henry / Rujumba, Joseph / Kwiringira, Japheth / Katureebe, Cordelia / Spicer, Neil

    BMC health services research

    2020  Volume 20, Issue 1, Page(s) 222

    Abstract: Background: Although Differentiated Service Delivery (DSD) for anti-retroviral therapy (ART) has been rolled-out nationally in several countries since World Health Organization (WHO)'s landmark 2016 guidelines, there is little research evaluating post- ... ...

    Abstract Background: Although Differentiated Service Delivery (DSD) for anti-retroviral therapy (ART) has been rolled-out nationally in several countries since World Health Organization (WHO)'s landmark 2016 guidelines, there is little research evaluating post-implementation outcomes. The objective of this study was to explore patients' and HIV service managers' perspectives on barriers to implementation of Differentiated ART service delivery in Uganda.
    Methods: We employed a qualitative descriptive design involving 124 participants. Between April and June 2019 we conducted 76 qualitative interviews with national-level HIV program managers (n = 18), District Health Team leaders (n = 24), representatives of PEPFAR implementing organizations (11), ART clinic in-charges (23) in six purposively selected Uganda districts with a high HIV burden (Kampala, Luwero, Wakiso, Mbale, Budadiri, Bulambuli). Six focus group discussions (48 participants) were held with patients enrolled in DSD models in case-study districts. Data were analyzed by thematic approach as guided by a multi-level analytical framework: Individual-level factors; Health-system factors; Community factors; and Context.
    Results: Our data shows that multiple barriers have been encountered in DSD implementation. Individual-level: Individualized stigma and a fear of detachment from health facilities by stable patients enrolled in community-based models were reported as bottlenecks. Socio-economic status was reported to have an influence on patient selection of DSD models. Health-system: Insufficient training of health workers in DSD delivery and supply chain barriers to multi-month ART dispensing were identified as constraints. Patients perceived current selection of DSD models to be provider-intensive and not sufficiently patient-centred. Community: Community-level stigma and insufficient funding to providers to fully operationalize community drug pick-up points were identified as limitations.
    Context: Frequent changes in physical addresses among urban clients were reported to impede the running of patient groups of rotating ART refill pick-ups.
    Conclusion: This is one of the first multi-stakeholder evaluations of national DSD implementation in Uganda since initial roll-out in 2017. Multi-level interventions are needed to accelerate further DSD implementation in Uganda from demand-side (addressing HIV-related stigma, community engagement) and supply-side dimensions (strengthening ART supply chain capacities, increasing funding for community models and further DSD program design to improve patient-centeredness).
    MeSH term(s) Ambulatory Care Facilities ; Anti-Retroviral Agents/therapeutic use ; Attitude of Health Personnel ; Attitude to Health ; Delivery of Health Care/methods ; Focus Groups ; Government Programs ; HIV Infections/drug therapy ; Health Care Surveys ; Health Personnel ; Humans ; Interviews as Topic ; Patient-Centered Care ; Professional Competence ; Qualitative Research ; Social Stigma ; Uganda
    Chemical Substances Anti-Retroviral Agents
    Language English
    Publishing date 2020-03-17
    Publishing country England
    Document type Journal Article
    ISSN 1472-6963
    ISSN (online) 1472-6963
    DOI 10.1186/s12913-020-5069-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Biophysical Survey of Small-Molecule β-Catenin Inhibitors: A Cautionary Tale.

    McCoy, Michael A / Spicer, Dominique / Wells, Neil / Hoogewijs, Kurt / Fiedler, Marc / Baud, Matthias G J

    Journal of medicinal chemistry

    2022  Volume 65, Issue 10, Page(s) 7246–7261

    Abstract: The canonical Wingless-related integration site signaling pathway plays a critical role in human physiology, and its dysregulation can lead to an array of diseases. β-Catenin is a multifunctional protein within this pathway and an attractive yet ... ...

    Abstract The canonical Wingless-related integration site signaling pathway plays a critical role in human physiology, and its dysregulation can lead to an array of diseases. β-Catenin is a multifunctional protein within this pathway and an attractive yet challenging therapeutic target, most notably in oncology. This has stimulated the search for potent small-molecule inhibitors binding directly to the β-catenin surface to inhibit its protein-protein interactions and downstream signaling. Here, we provide an account of the claimed (and some putative) small-molecule ligands of β-catenin from the literature. Through in silico analysis, we show that most of these molecules contain promiscuous chemical substructures notorious for interfering with screening assays. Finally, and in line with this analysis, we demonstrate using orthogonal biophysical techniques that none of the examined small molecules bind at the surface of β-catenin. While shedding doubts on their reported mode of action, this study also reaffirms β-catenin as a prominent target in drug discovery.
    MeSH term(s) Animals ; Biophysical Phenomena ; Drug Discovery ; Humans ; Small Molecule Libraries/chemistry ; Small Molecule Libraries/pharmacology ; Wnt Signaling Pathway ; beta Catenin
    Chemical Substances Small Molecule Libraries ; beta Catenin
    Language English
    Publishing date 2022-05-17
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/acs.jmedchem.2c00228
    Database MEDical Literature Analysis and Retrieval System OnLINE

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