GPRC5D-Targeted CAR T Cells for Myeloma.

BACKGROUND: B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapies have generated responses in patients with advanced myeloma, but relapses are common. G protein-coupled receptor, class C, group 5, member D (GPRC5D) has been identified as an immunotherapeutic target in multiple myeloma. Preclinical studies have shown the efficacy of GPRC5D-targeted CAR T cells, including activity in a BCMA antigen escape model. METHODS: In this phase 1 dose-escalation study, we administered a GPRC5D-targeted CAR T-cell therapy (MCARH109) at four dose levels to patients with heavily pretreated multiple myeloma, including patients with relapse after BCMA CAR T-cell therapy. RESULTS: A total of 17 patients were enrolled and received MCARH109 therapy. The maximum tolerated dose was identified at 150×106 CAR T cells. At the 450×106 CAR T-cell dose, 1 patient had grade 4 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS), and 2 patients had a grade 3 cerebellar disorder of unclear cause. No cerebellar disorder, ICANS of any grade, or cytokine release syndrome of grade 3 or higher occurred in the 12 patients who received doses of 25×106 to 150×106 cells. A response was reported in 71% of the patients in the entire cohort and in 58% of those who received doses of 25×106 to 150×106 cells. The patients who had a response included those who had received previous BCMA therapies; responses were observed in 7 of 10 such patients in the entire cohort and in 3 of 6 such patients who received 25×106 to 150×106 cells. CONCLUSIONS: The results of this study of a GPRC5D-targeted CAR T-cell therapy (MCARH109) confirm that GPRC5D is an active immunotherapeutic target in multiple myeloma. (Funded by Juno Therapeutics/Bristol Myers Squibb; ClinicalTrials.gov number, NCT04555551.).

Social marketing and mass media interventions to increase sexually transmissible infections (STIs) testing among young people: social marketing and visual design component analysis.

INTRODUCTION: Globally, sexually transmissible infections (STIs) continue to disproportionately affect young people. Regular STI testing is an important public health strategy but remains low among this age group. Raising awareness of testing is an essential step and requires effective interventions designed for young people. To inform the development of effective interventions that promote STI testing among young people, we conducted a systematic literature review to describe the social marketing and visual design components commonly found in STI testing interventions and explore associations of these components with intervention effectiveness. METHODS: We used a systemic review methodology to identify peer-reviewed articles that met pre-defined inclusion criteria. Social marketing and visual component analyses were conducted using structured data extraction tools and coding schemes, based on the eight key social marketing principles and 28 descriptive dimensions for visual analysis. RESULTS: 18 studies focusing on 13 separate interventions met the inclusion criteria. Most interventions used photograph-based images, using conventionally attractive actors, positioned centrally and making direct eye contact to engage the viewer. The majority of interventions featured text sparingly and drew on a range of tones (e.g. serious, humorous, positive, reassuring, empowering and informative) and three interventions used sexualised content. Four articles explicitly stated that the interventions was informed by social marketing principles, with two explicitly referencing all eight principles. Around half of the articles reported using a formal theoretical framework, but most were considered to have theoretical constructs implicit in interventions materials. Four articles provided detailed information regarding developmental consumer research or pre-testing. All articles suggested segmentation and development of materials specifically for young people. Explicit consideration of motivation and competition was lacking across all articles. This study found that there were some design elements common to interventions which were considered more effective. High social marketing complexity (where interventions met at least seven of the 11 criteria for complexity) seemed to be associated with more effective interventions. CONCLUSIONS: Our findings suggest that the incorporation of social marketing principles, could be more important for intervention effectiveness than specific elements of visual design. Effective and systematic use of social marketing principles may help to inform future evidence-informed and theoretically based interventions and should be employed within sexual health improvement efforts.

'Change creates change' - older female sex workers' experiences through the early COVID-19 pandemic.

COVID-19 and associated policy responses created unique social, economic and health risks for sex workers. Through semi-structured interviews we explored pre- and early COVID-19 experiences and work practices of ten cisgender female sex workers 50 years of age and older in Queensland, Australia, analysing the findings using a risk environment framework. Throughout early 2020, participants navigated a complex risk environment, managing economic needs, health and safety, occupational stigma and policing. Australia's policy responses altered the risks and opportunities available to participants. Half the participants continued sex work and half stopped sex work with some accessing economic support and withdrawing superannuation savings. Those who continued sex work drew on life and work experience to reassess changing health, stigma, and policing risks, and adapted their work strategies by increasing client screening and modifying services. Participants relied on information from peer networks and organisations to guide work practices but remained wary of contact tracing, police and the media. Decriminalisation of sex work and the strengthening of sex worker organisation and government partnerships are important in embedding equity in responses to ongoing and new public health threats.

Understanding access to healthcare for gender diverse young people: a critical review of the literature.

Gender diverse young people face well-documented physical, mental and sexual health disparities compared to the general population. Differential access to healthcare is a key driver of these inequities and literature highlights high unmet healthcare need among members of this group. Healthcare access has been described through a model that defines five dimensions of health services: approachability; acceptability; availability and accommodation; affordability; and appropriateness; and five abilities of health service consumers that interact with these dimensions: the abilities to perceive, seek, reach, pay and engage. This comprehensive literature review examined barriers to and facilitators of healthcare access among gender diverse young people using the lens provided by this model as it relates to dimensions of access at the health service level and/or the abilities of health service users. We advocate expansion of this model to incorporate demand- and supply-side barriers and facilitators of access, and important structural factors including the gender binary health system framework, intersectionality and stigma. Findings highlight the need for improvements to healthcare provider education and the participatory redesign of health services with a focus on intersectionality, individually-tailored service provision and healthcare that is responsive to the unique needs of gender diverse young people.

HIV Health literacy beyond the biomedical model: an innovative visual learning tool to highlight the psychosocial complexities of care.

The HIV care continuum represents a linear clinical pathway from testing to viral suppression; however, it does not capture the psychosocial complexities of contemporary HIV care. We developed an innovative and appealing visual learning resource to extend the scope of HIV health literacy beyond biomedical constructs. Based on the lived experiences of recently diagnosed people living with HIV in Queensland, the "Journeys through the HIV Care Continuum" Map presents the continuum as a complex journey incorporating challenges such as poor health literacy, health service access and stigma alongside facilitators to care, including emotional and peer support. Designed for audiences who may not access academic literature, the Map can be used to facilitate conversations between recently diagnosed people living with HIV and peer navigators, and as a learning tool for health professionals, carers and students. The Map highlights opportunities to support PLHIV in meaningful ways that will reduce stigma and promote care access.

Enduring stigma and precarity: A review of qualitative research examining the experiences of women living with HIV in high income countries over two decades.

The lived experience of HIV for women remains poorly understood. In particular, there has been little attention to the consequences for women living with HIV (WLHIV) of changing social, epidemiological, biomedical and policy contexts, or to the implications of long-term treatment and aging for the current generation of HIV-positive women. We reviewed qualitative research with WLHIV in selected high-income countries (Australia, Canada, New Zealand, the UK and the USA) to identify the most prevalent experiences of HIV for women and trends over time. Our synthesis highlights the relative consistency of experiences of a diverse sample of WLHIV, particularly the enduring prevalence of gendered HIV-related stigma, sociostructural barriers to healthcare and support, and negative encounters with health professionals. We also identified gaps in knowledge. Understanding women's experiences, particularly their changing needs and strategies for coping as they live long-term with HIV, is key to effective support and services for WLHIV.

Exploring the Social Impacts of the COVID-19 Pandemic on People Living with HIV (PLHIV): A Scoping Review.

Understanding the clinical impact of COVID-19 has been central to emerging research in the HIV field, but in focusing on the biomedical, researchers must not overlook the socially embedded nature of HIV and the potential social impacts of this new pandemic on PLHIV. We conducted a scoping review to explore emerging research examining the social impacts of COVID-19 on PLHIV in OECD countries over the first 12 months of the pandemic. Twenty articles were identified and included for review. Key themes included: impacts on HIV care access/telehealth; stress and mental health; social isolation and loneliness; food insecurity; changes to sexual behaviour; changes to substance use; impacts on income, education and employment; and racial and social inequality. Results from this review can help guide research into areas where it is needed to help minimise the negative social impacts of the COVID-19 pandemic.

Barriers to Accessing Sexual Health Services for Transgender and Male Sex Workers: A Systematic Qualitative Meta-summary.

Access to safe and effective sexual healthcare services for transgender and male sex workers (TMSW) is a human right. Globally, TMSW experience a higher prevalence of human immunodeficiency virus (HIV) and sexually transmitted infections than the general population or other sex workers, suggesting the existence of unique challenges for this group when accessing healthcare. A systematic database search identified 22 qualitative papers addressing barriers to accessing sexual healthcare services for TMSW. These papers were critically evaluated for adherence to best practice standards for qualitative research and research with sex workers. A coding process identified five themes. Stigma was the predominant barrier, and was divided into stigma related to sexuality, gender identity, HIV status, sex worker status, and internalised stigma. Other barriers were confidentiality concerns, sexual health literacy, fatalism, and structural barriers. Each of these themes were informed by the wider context of stigma. The literature presents a complex syndemic of social disadvantage and exclusion acting to produce and reinforce health disparities related to sexual health and access to screening and treatment for TMSW.

Sexual and reproductive health of women living with HIV in Muslim-majority countries: a systematic mixed studies review.

BACKGROUND: The number of women living with the human immunodeficiency virus (WLHIV) in Muslim-majority countries has increased significantly in the last decade. These women are often marginalized and face insecure sexual and reproductive health (SRH) needs and rights. However, little is known about the multi-faceted factors influencing these women's fertility, contraceptive, and perinatal decisions and sexual life. This systematic mixed studies review aimed to synthesize the empirical evidence on social, cultural, and structural factors influencing the SRH of WLHIV in Muslim-majority countries. METHODS: This review provides a synthesis of quantitative, qualitative and mixed-method research findings searched from PubMed, EMBASE, Scopus, CINAHL and Cochrane databases. We screened 3452 SRH studies involving WLHIV. The studies, published in English between 2008 and 2017, were from 20 Muslim-majority countries with increased numbers of WLHIV. The quality of eligible studies was appraised using a mixed-methods appraisal tool (MMAT) version 2011. Findings were thematically analysed by a hybrid deductive-inductive approach. Two independent reviewers were involved in the study selection, data extraction, quality appraisal, and data synthesis. RESULTS: We included 13 SRH-related studies involving 1748 WLHIV in eight Muslim-majority countries. Most of these studies explored fertility desire and sexual health, while only a small proportion related to contraceptive use and the perinatal-care experience. We identified that WLHIV faced neglect of their SRH rights. These rights were predominantly affected by the socio-cultural, religious and health-services context of the women's lives, which directed them to unsafe sex practices and stressful perinatal experiences. CONCLUSIONS: This study points to the need for SRH laws, policies, and interventions which stop WLHIV experiencing SRH discrimination violence and achieving their SRH rights.

Australian interdisciplinary healthcare providers' perspectives on the effects of broader pre-exposure prophylaxis (PrEP) access on uptake and service delivery: a qualitative study.

Background The addition of pre-exposure prophylaxis (PrEP) for HIV prevention to the Australian Government-subsidised Pharmaceutical Benefits Scheme (PBS) enables any doctor or nurse practitioner to prescribe it and has increased accessibility options. However, understanding of Australian healthcare providers' (HCP) knowledge and preparedness to prescribe PrEP remains limited. METHODS: Semistructured interviews, conducted before PBS listing (October 2016-April 2017), explored PrEP knowledge and prescription experiences of 51 multidisciplinary HCPs involved with the Queensland Pre-Exposure Prophylaxis Demonstration study. RESULTS: Thematic analysis revealed that participants viewed PrEP as a necessary HIV prevention option, but there was concern about confusing prevention messages and potential risk compensation. Clinical capacity, stigma, cultural norms, rural access and PrEP-associated costs were identified as barriers to access and uptake. Some of these barriers may be addressed by the PBS listing; nonetheless, there was strong specialist concern about the preparedness of general practitioners without sexual health experience to prescribe PrEP. Participants identified a need to educate all HCPs, implement multidisciplinary supply models and provide timely access to PrEP for vulnerable populations and those ineligible for Medicare (Australia's universal healthcare insurance system). CONCLUSIONS: Although PrEP listing on the PBS addressed structural barriers to access, this study highlights the role of nurses and other interdisciplinary healthcare workers in the provision of PrEP in addressing the sociocultural barriers that still affect the access of certain populations to HIV prevention measures. These findings will inform further professional training as PrEP is more widely accessed and requested outside specialist sexual health services. Future work is needed to ensure that the primary healthcare workforce is prepared to provide competent and safe access to PrEP across diverse locations and population groups.

Applying intersectionality theory in health promotion research and practice.

Health promotion researchers and practitioners are grappling with how to address growing health inequalities for population groups. In particular, critiques of dominant behaviour change approaches draw attention to the need to engage with social theories to better understand the social and relational drivers of health. Public health researchers are increasingly acknowledging intersectionality as an important theoretical approach, providing a framework for investigating health inequalities by highlighting intersections of individuals' multiple identities within social systems of power that compound and exacerbate experiences of ill health. This article provides an overview of the diverse ways public health researchers and practitioners have applied intersectionality theory to better understand and address health inequalities. We map three key applications of intersectionality theory in public health: as an epistemological approach, as a methodological approach, and as a tool for action and intervention. Drawing on this work, we argue that health promotion researchers and practitioners can enhance engagement with intersectionality theory to address important challenges within the field. Through this article, we aim to inspire the continued exploration of intersectionality and offer some insights into opportunities and challenges for doing so in health promotion.

How can HIV/STI testing services be more accessible and acceptable for gender and sexually diverse young people? A brief report exploring young people's perspectives in Queensland.

ISSUE ADDRESSED: Gender and sexually diverse young people (GSDYP) are an important target group for HIV/sexually transmitted infection (STI) prevention and there is an immediate need to explore ways to make testing interventions accessible and appropriate for this group. METHODS: We used a modified World Café workshop with 14 GSDYP in Brisbane Australia, to inform the development of a pilot community-based testing intervention. RESULTS: The workshop identified the key features of an ideal service, which would include multiple, accessible sites that offer holistic, affordable services and confidential care by respectful and knowledgeable providers. The service would allow young people to engage in decision-making processes, have a culturally inclusive, comfortable and friendly atmosphere, and provide free sexual and reproductive health technologies. CONCLUSION: When designing HIV/STI testing interventions for key groups, health promotion practitioners need to be cognisant of localised and nuanced expectations and ensure that services are tailored to the needs and experiences of the local population. SO WHAT?: This study provides insights into the needs and expectations of HIV/STI testing interventions for GSDYP in Australia, a key at-risk group whose perspectives are not adequately voiced in sexual health research and intervention design. SUMMARY: This study explores facilitators and current barriers to HIV/STI testing with a group of gender and sexually diverse young people in Brisbane, Australia. Outcomes provide insights into the needs and expectations of HIV/STI testing services for this group.

Factors affecting the decision to initiate antiretroviral therapy in the era of treatment-as-prevention: synthesis of evidence from qualitative research in high-income settings.

The emergence of treatment-as-prevention has made early initiation of antiretroviral treatment (ART) a "universal" policy. This review synthesizes qualitative research findings on barriers and facilitators of ART initiation in Organization for Economic Co-operation and Development (OECD) countries published since 2010. Ten articles describing seven research studies were included in the review. Findings confirmed ART initiation as a complicated process involving careful deliberation of the personal risks and benefits of treatment within the broader contexts of everyday life for people living with HIV (PLHIV). They also highlight interpersonal dynamics and concern for the public as increasingly important factors in shaping the decision to initiate treatment. The review provides valuable information for understanding treatment behaviour and maximizing treatment options brought forth by new biomedical advances.

Knowledge and awareness of HIV self-testing among Australian gay and bisexual men: a comparison of never, sub-optimal and optimal testers willingness to use.

This paper explores the willingness to use and pay for HIV Self-testing (HIVST) among Australian gay and bisexual men (GBM). Bivariate and univariate multinominal logistic regression of data from an online survey was performed. Thirty-one (13%) had never HIV tested and 41.9% (88) were testing sub-optimally by Australian guidelines. Half (58.4%, 136) had never heard of HIVST, however, 56.2% (131) reported willingness to use HIVST, with sub-optimal (OR=2.13; p < 0.01) and never-testers (OR=2.01; p < 0.10) significantly more likely to do so than optimal-testers. Most were confident (51.7%, 119) or somewhat confident (29.1%, 67) accessing support following a reactive result, however, never-testers were significantly less confident compared to previous testers (OR=3.47; p< 0.05). Less than a quarter (23.6%, 57) were willing to pay for a kit with AUD$15 (R2 = 0.9882) the estimated preferred price. This research confirms that HIVST is an important and accepted adjunct to established HIV testing modalities, particularly among sub-optimal and never-testers and that online (61.6%, 143) or clinic-based (61.6%, 143) dissemination are preferred. Research examining how best to disseminate HIVST in a range of safe and effective models needs to continue to ensure HIVST is part of a comprehensive strategy that facilitates usage and linkages to care.

'In the Islands people don't really talk about this stuff, so you go through life on your own': An arts-based study exploring intimate relationships with young people in Samoa.

This study explores conceptualisations and understandings of intimate relationships with young people in Samoa - an at-risk group experiencing high rates of intimate partner violence and alienation from sexual and relationship health promotion. Insights contribute to the immediate need to advance knowledge and practice around prevention with this group. An arts-based approach, which included a two-day interactive drama workshop coupled with follow-up, peer-led focus groups, was used to explore perceptions and understandings related to intimate relationships with 15 tertiary educated young people (nine female and six male) from across Samoa. Intersectionality informed the data collection and thematic analysis, examining participants' lived experiences and the ways multiple and intersecting identities interact within social and cultural systems to influence and inform these experiences. Outcomes highlight important tensions for young people, including the way in which age, gender, religion and sexuality interact with social hierarchies and power structures, socially prescribed gender norms, family structures and globalisation. This research provides insights that can inform the development of prevention strategies to address the root causes of intimate partner violence, building the knowledge and skills required for establishing intimate relationships free from violence with young people.

The Blind Men and the Elephant: Meta-Ethnography 30 Years On.

In the 30 years since its introduction, meta-ethnography has become a critical tool for synthesizing qualitative health research and providing a holistic understanding of complex health and social phenomena. Meta-ethnography has also been adapted to integrate a wider range of research methodologies, expanded to include a detailed taxonomy of research methods, and has led to the development of multiple other methods of synthesis. In this article, we describe the development of meta-ethnography, its unique research approaches, the innovations that have occurred since its inception, and potential future directions for the method. These include the need for consensus around the role of systematic database searches and critical appraisal, and a clearer path to action for clinicians interpreting qualitative research. Understanding and updating methods such as meta-ethnography will ensure that the exponentially developing field of qualitative research continues to have a meaningful and cumulative impact on complex issues of health and well-being.

HIV Testing in Men who have Sex with Men: A Follow-up Review of the Qualitative Literature since 2010.

The landscape of HIV testing has changed significantly in recent years following the rise in importance of the 'treatment as prevention' strategy and advancements in new HIV testing and prevention technologies. This review provides a synthesis of qualitative research findings published since 2010 on preferences and practices of men who have sex with men (MSM) surrounding HIV testing in high-income settings. MSM are one of the hardest groups to reach with standard or conventional HIV testing approaches. To develop innovative testing strategies for this particular group, a good understanding of their concerns, barriers and facilitators of accessing HIV testing is needed. This updated review provides valuable information for improving existing programs and designing new testing services for MSM.

Death, contagion and shame: The potential of cancer survivors' advocacy in Zambia.

Cancer has become a global health concern with marked differences in the incidence and mortality rates between developing and developed countries. Understanding the factors that shape uptake of preventative and screening services is the key. We use in-depth interviews with 13 Zambian urban-based female cancer survivors to explore the facilitators and barriers to screening, diagnosis and treatment, with a particular focus on cultural influences. We identified a central theme (i.e. a story told about cancer) in all of the interviews: 'cancer is a death sentence'. Most women referenced this theme to describe their own, their family members', or community members' reactions to their diagnosis, along with references to cancer as 'contagious' and 'a shameful illness'. We also identified a theme entitled 'survivors as advocates', within which women described engaging in advocacy work to challenge stigma, misconceptions and misinformation about cancer; and advocating early detection and diagnosis, compliance with medical treatment and the sharing of success stories. This analysis points to the need for survivors to be front and center of preventative efforts. Their personal experiences, legitimacy and connections in the community, and their enthusiasm in helping others should be fostered, particularly in low-resource settings.

Domain-specific and domain-general processes underlying metacognitive judgments.

Metacognition and self-awareness are commonly assumed to operate as global capacities. However, there have been few attempts to test this assumption across multiple cognitive domains and metacognitive evaluations. Here, we assessed the covariance between "online" metacognitive processes, as measured by decision confidence judgments in the domains of perception and memory, and error awareness in the domain of attention to action. Previous research investigating metacognition across task domains have not matched stimulus characteristics across tasks raising the possibility that any differences in metacognitive accuracy may be influenced by local task properties. The current experiment measured metacognition in perceptual, memorial and attention tasks that were closely matched for stimulus characteristics. We found that metacognitive accuracy across the three tasks was dissociated suggesting that domain specific networks support an individual's capacity for accurate metacognition. This finding was independent of objective performance, which was controlled using a staircase procedure. However, response times for metacognitive judgments and error awareness were associated suggesting that shared mechanisms determining how these meta-level evaluations unfold in time may underlie these different types of decision. In addition, the relationship between these laboratory measures of metacognition and reports of everyday functioning from participants and their significant others (informants) was investigated. We found that informant reports, but not self reports, predicted metacognitive accuracy on the perceptual task and participants who underreported cognitive difficulties relative to their informants also showed poorer metacognitive accuracy on the perceptual task. These results are discussed in the context of models of metacognitive regulation and neuropsychological evidence for dissociable metacognitive systems. The potential for the refinement of metacognitive assessment in clinical populations is also discussed.