'Building bridges': reflections and recommendations for co-producing health research.

BACKGROUND: Co-produced research is when all stakeholders, including experts by experience and researchers, work together to conceptualise, design, deliver and disseminate research to enhance understanding and knowledge. This type of participatory inquiry is being increasingly used across health research; however, it continues to be a complex area to navigate given existing institutional structures. MAIN BODY: We collaborated across three independent co-produced research studies to share insights, reflections, and knowledge of our work in the fields of HIV, mental health, and disability research. We co-designed and delivered a three-hour online workshop at a conference to share these reflections using the metaphor of 'building bridges' to describe our co-production journey. We generated key principles of co-production from our different experiences working in each individual research project as well as together across the three projects. Our principles are to: (1) be kind, have fun and learn from each other; (2) share power (as much as you can with people); (3) connect with people you know and don't know; (4) remain connected; and (5) use clear and simple language. CONCLUSION: We recommend that co-produced research needs additional funding, resource, and flexibility to remain impactful and ethical. Co-produced research teams need to be mindful of traditional power structures and ensure that the process is transparent, fair, and ethical. Addressing equality, diversity, and inclusion of traditionally underrepresented groups in research is essential as are the skills, expertise, and experiences of all members of the co-production team.

Co-produced research occurs when a range of people, including researchers and people with lived experience of a topic work together on all stages of a piece of research, from design to publication, to improve understanding of a topic. This methodology has become increasingly popular in the field of health research, however ­ it can be difficult to undertake because of how health institutions are structured. As a team, we examined three co-produced studies (focusing on HIV, mental health, and disability research) to share our insights and reflections. We then shared these reflections through a co-designed online workshop at a conference. We used the metaphor of 'building bridges' to describe our teamwork. From our experiences on these studies, we came up with five key suggestions for co-production in research: (1) be kind, have fun and learn from each other; (2) share power as much as possible with everyone; (3) connect with people you know and those you don't; (4) stay connected; (5) use clear and simple language. To achieve ethical and impactful co-produced research, we suggest that it needs more funding, resources, and flexibility. Teams who are conducting co-produced research must be fair and clear about how they do so, and ensure that everyone, especially groups who are often unheard, get a chance to be part of research so that everyone's skills and experiences are equally considered.

Barriers and facilitators to HIV Pre-Exposure Prophylaxis (PrEP) in Specialist Sexual Health Services in the United Kingdom: A systematic review using the PrEP Care Continuum.

OBJECTIVES: HIV pre-exposure prophylaxis (PrEP) delivery in the UK is inequitable; over 95% of PrEP users were men who have sex with men (MSM) despite making up less than 50% of new HIV diagnoses. We conducted a systematic review to identify modifiable barriers and facilitators to PrEP delivery in the UK among underserved populations. METHODS: We searched bibliographic/conference databases using the terms HIV, PrEP, barriers, facilitators, underserved populations, and UK. Modifiable factors were mapped along the PrEP Care Continuum (PCC) to identify targets for interventions. RESULTS: In total, 44 studies were eligible: 29 quantitative, 12 qualitative and three mixed-methods studies. Over half (n = 24 [54.5%]) exclusively recruited MSM, whereas 11 were in mixed populations (all included MSM as a sub-population) and the other nine were in other underserved populations (gender and ethnicity minorities, women, and people who inject drugs). Of the 15 modifiable factors identified, two-thirds were at the PrEP contemplation and PrEParation steps of the PCC. The most reported barriers were lack of PrEP awareness (n = 16), knowledge (n = 19), willingness (n = 16), and access to a PrEP provider (n = 16), whereas the more reported facilitators were prior HIV testing (n = 8), agency and self-care (n = 8). All but three identified factors were at the patient rather than provider or structural level. CONCLUSIONS: This review highlights that the bulk of the scientific literature focuses on MSM and on patient-level factors. Future research needs to ensure underserved populations are included and prioritized (e.g. ethnicity and gender minorities, people who inject drugs) and provider and structural factors are investigated.

Caregiver perceptions and experiences of paediatric emergency department attendance during the COVID-19 pandemic: A mixed-methods study.

BACKGROUND: During the early stages of the COVID-19 pandemic, concerns were raised about reduced attendance at hospitals, particularly in paediatric emergency departments, which could result in preventable poorer outcomes and late presentations among children requiring emergency care. We aimed to investigate the impact of COVID-19 on health-seeking behaviour and decision-making processes of caregivers presenting to paediatric emergency services at a National Health Service (NHS) Trust in London. MATERIALS AND METHODS: We conducted a mixed-methods study (survey and semi-structured interviews) across two hospital sites between November-December 2020. Data from each study were collected concurrently followed by data comparison. RESULTS: Overall, 100 caregivers participated in our study; 80 completed the survey only, two completed the interview only and 18 completed both. Our quantitative study found that almost two-thirds (63%, n = 62) of caregivers attended the department within two days of their child becoming ill. Our qualitative study identified three major themes which were underpinned by concepts of trust, safety and uncertainty and were assessed in relation to the temporal nature of the pandemic and the caregivers' journey to care. We found most caregivers balanced their concerns of COVID-19 and a perceived "overwhelmed" NHS by speaking to trusted sources, predominantly general practitioners (GPs). CONCLUSION: Caregivers have adapted their health-seeking behaviour throughout the pandemic as new information and guidance have been released. We identified several factors affecting decisions to attend; some existed before the pandemic (e.g., concerns for child's health) whilst others were due to the pandemic (e.g., perceived risks of transmission when accessing healthcare services). We recommend trusted medical professionals, particularly GPs, continue to provide reassurance to caregivers to seek emergency paediatric care when required. Communicating the hospital safety procedures and the importance of early intervention to caregivers could additionally provide reassurance to those concerned about the risks of accessing the hospital environment.

Impact of daily, oral pre-exposure prophylaxis on the risk of bacterial sexually transmitted infections among cisgender women: a systematic review and narrative synthesis.

Background: There are concerns that the use of pre-exposure prophylaxis (PrEP) may result in an increased incidence of sexually transmitted infections (STIs). Evidence for this is mixed and has mostly been based on reviews focussed on gay and bisexual men and transgender women, while none have summarised evidence in cisgender women. Methods: We conducted a systematic review to explore whether daily, oral PrEP use is associated with changes in bacterial STI occurrence (diagnoses or self-reported) and/or risk among HIV seronegative cisgender women (ciswomen). The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tool. Results: We included 11 full text articles in a narrative synthesis, with the studies published between 2012 and 2021. The studies were mostly based in Africa (n=7, 63.6%) and reported on 3168 ciswomen using PrEP aged 16-56 years. Studies had marked differences in variables, including measurements and definitions (e.g., STI type) and limited data available looking specifically at ciswomen, principally in studies with both male and female participants. The limited evidence suggests that PrEP use is not associated with increased STI rates in ciswomen generally; however, adolescent girls and young women in Sub Saharan Africa have a higher prevalence of bacterial STIs prior to PrEP initiation, compared to adult ciswomen and female sex workers. Conclusions: We suggest future PrEP research make efforts to include ciswomen as study participants and report stratified results by gender identity to provide adequate data to inform guidelines for PrEP implementation. PROSPERO registration: CRD42019130438.

Influence of Material Deprivation on Clinical Outcomes Among People Living with HIV in High-Income Countries: A Systematic Review and Meta-analysis.

Despite developments in HIV treatment and care, disparities persist with some not fully benefiting from improvements in the HIV care continuum. We conducted a systematic review to explore associations between social determinants and HIV treatment outcomes (viral suppression and treatment adherence) in high-income countries. A random effects meta-analysis was performed where there were consistent measurements of exposures. We identified 83 observational studies eligible for inclusion. Social determinants linked to material deprivation were identified as education, employment, food security, housing, income, poverty/deprivation, socioeconomic status/position, and social class; however, their measurement and definition varied across studies. Our review suggests a social gradient of health persists in the HIV care continuum; people living with HIV who reported material deprivation were less likely to be virologically suppressed or adherent to antiretrovirals. Future research should use an ecosocial approach to explore these interactions across the lifecourse to help propose a causal pathway.

RESUMEN: A pesar de los avances en el tratamiento y la atención al VIH, ciertas desigualdades persisten en estas áreas. Como resultado, algunas personas que viven con el VIH no se benefician plenamente de las mejoras en la atención del VIH a todos los niveles. Realizamos una revisión sistemática para explorar las asociaciones entre los determinantes sociales de la salud y los resultados del tratamiento del VIH (supresión viral y tratamiento de adherencia) en países de ingresos altos. Completamos un metaanálisis siguiendo un modelo de efectos aleatorios e incluyendo medidas consistentes de exposiciones. Identificamos 83 estudios observacionales elegibles para inclusión. Los determinantes sociales vinculados a las circunstancias materiales (privación) se identificaron como educación, empleo, seguridad alimentaria, vivienda, ingresos, pobreza / privación, situación / posición socioeconómica y clase social; sin embargo, su medición y definición variaron entre los estudios. Nuestro estudio sugiere que un gradiente de salud social persiste en la atención sanitaria del VIH a todos los niveles; las personas que viven con el VIH que declaran privación material tenían menos probabilidades de alcanzar la supresión viral o de ser adherente a los antirretrovirales. Futuras investigaciones deberían utilizar un enfoque ecosocial para explorar estas interacciones a lo largo del curso de la vida para ayudar a proponer una vía causal.

A qualitative exploration of participant and investigator perspectives from the TRED-HF trial.

AIMS: We explored the experiences and motivations of participants and staff who took part in the TRED-HF trial (Therapy withdrawal in REcovered Dilated cardiomyopathy). METHODS AND RESULTS: We conducted a qualitative study, using semi-structured interviews, with participants (n = 12) and the research team (n = 4) from the TRED-HF trial. Interviews were carried out in 2019 and were audio-recorded and transcribed. Data were managed using NVivo and analysed using framework analysis. A patient representative provided guidance on the interpretation of findings and presentation of themes to ensure these remained meaningful, and an accurate representation, to those living with dilated cardiomyopathy. Three key themes emerged from the data: (i) perception of health; (ii) experiences and relationships with healthcare services and researchers; and (iii) perception of risk. Study participants held differing perceptions of their health; some did not consider themselves to have a heart condition or disagreed with the medical term 'heart failure'. Relationships between participants, research staff, and clinical management teams influenced participants' experiences and decision making during the trial, including following clinical advice. There were differences in participants' perceptions of risk and their decisions to take heart failure medication after the trial was completed. Although the original TRED-HF trial did not provide the results many had hoped for, a strong motivator for taking part was the opportunity to withdraw medication in a safely monitored environment which had been previously considered by some participants before. Investigators acknowledged that the insights gained from the study can now be used to support evidence-based conversations with patients. CONCLUSIONS: For people whose dilated cardiomyopathy is in remission, decisions to continue, reduce, or stop their medication are influenced by perceptions of personal health, perceive risk and the important of work, employment, recreation, relationships, and long-term plans. The unique relationship between patient and cardiologist provides opportunities to promote honest discussion about adherence to medication and personalized long-term management.

Harlequin syndrome in a young girl: An opportunity to rethink the terminology.

Harlequin syndrome is a rare disorder of the autonomic nervous system, presenting as unilateral reduced flushing and sweating of the face induced by exercise, stress, or heat. It is caused by a cervical sympathetic deficit located at the preganglionic or postganglionic level on the non-flushing side. We present a case of an 8 year old with harlequin syndrome and review the other dermatological conditions for which the term "harlequin" is part of the nomenclature.

Usability and Acceptability of Home-based Self-testing for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibodies for Population Surveillance.

BACKGROUND: This study assesses acceptability and usability of home-based self-testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies using lateral flow immunoassays (LFIA). METHODS: We carried out public involvement and pilot testing in 315 volunteers to improve usability. Feedback was obtained through online discussions, questionnaires, observations, and interviews of people who tried the test at home. This informed the design of a nationally representative survey of adults in England using two LFIAs (LFIA1 and LFIA2) which were sent to 10 600 and 3800 participants, respectively, who provided further feedback. RESULTS: Public involvement and pilot testing showed high levels of acceptability, but limitations with the usability of kits. Most people reported completing the test; however, they identified difficulties with practical aspects of the kit, particularly the lancet and pipette, a need for clearer instructions and more guidance on interpretation of results. In the national study, 99.3% (8693/8754) of LFIA1 and 98.4% (2911/2957) of LFIA2 respondents attempted the test and 97.5% and 97.8% of respondents completed it, respectively. Most found the instructions easy to understand, but some reported difficulties using the pipette (LFIA1: 17.7%) and applying the blood drop to the cassette (LFIA2: 31.3%). Most respondents obtained a valid result (LFIA1: 91.5%; LFIA2: 94.4%). Overall there was substantial concordance between participant and clinician interpreted results (kappa: LFIA1 0.72; LFIA2 0.89). CONCLUSIONS: Impactful public involvement is feasible in a rapid response setting. Home self-testing with LFIAs can be used with a high degree of acceptability and usability by adults, making them a good option for use in seroprevalence surveys.

Patient data-sharing for immigration enforcement: a qualitative study of healthcare providers in England.

AIM: To explore healthcare providers' perceptions and experiences of the implications of a patient data-sharing agreement between National Health Service (NHS) Digital and the Home Office on access to NHS services and quality of care received by migrant patients in England. DESIGN: A qualitative study using semi-structured interviews, thematic analysis and constant-comparison approach. PARTICIPANTS: Eleven healthcare providers and one non-clinical volunteer working in community or hospital-based settings who had experience of migrants accessing NHS England services. Interviews were carried out in 2018. SETTING: England. RESULTS: Awareness and understanding of the patient data-sharing agreement varied among participants, who associated this with a perceived lack of transparency by the government. Participants provided insight into how they thought the data-sharing agreement was negatively influencing migrants' health-seeking behaviour, their relationship with clinicians and the safety and quality of their care. They referred to the policy as a challenge to their core ethical principles, explicitly patient confidentiality and trust, which varied depending on their clinical specialty. CONCLUSIONS: A perceived lack of transparency during the policy development process can result in suspicion or mistrust towards government among the health workforce, patients and public, which is underpinned by a notion of power or control. The patient data-sharing agreement was considered a threat to some of the core principles of the NHS and its implementation as adversely affecting healthcare access and patient safety. Future policy development should involve a range of stakeholders including civil society, healthcare professionals and ethicists, and include more meaningful assessments of the impact on healthcare and public health.

Dermal CD14(+) Dendritic Cell and Macrophage Infection by Dengue Virus Is Stimulated by Interleukin-4.

Dengue virus (DENV) is responsible for the most prevalent arthropod-borne viral infection in humans. Events decisive for disease development occur in the skin after virus inoculation by the mosquito. Yet, the role of human dermis-resident immune cells in dengue infection and disease remains elusive. Here we investigated how dermal dendritic cells (dDCs) and macrophages (dMs) react to DENV and impact on immunopathology. We show that both CD1c(+) and CD14(+) dDC subsets were infected, but viral load greatly increased in CD14(+) dDCs upon IL-4 stimulation, which correlated with upregulation of virus-binding lectins Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Nonintegrin (DC-SIGN/CD209) and mannose receptor (CD206). IL-4 also enhanced T-cell activation by dDCs, which was further increased upon dengue infection. dMs purified from digested dermis were initially poorly infected but actively replicated the virus and produced TNF-α upon lectin upregulation in response to IL-4. DC-SIGN(+) cells are abundant in inflammatory skin with scabies infection or Th2-type dermatitis, suggesting that skin reactions to mosquito bites heighten the risk of infection and subsequent immunopathology. Our data identify dDCs and dMs as primary arbovirus target cells in humans and suggest that dDCs initiate a potent virus-directed T-cell response, whereas dMs fuel the inflammatory cascade characteristic of dengue fever.

Are patients with coeliac disease seeking alternative therapies to a gluten-free diet?

BACKGROUND & AIMS: The cornerstone of treatment for coeliac disease is a gluten-free diet (GFD). However, adherence to a GFD is variable. Recently investigators have been reporting their preliminary findings using novel therapies. In addition, there is a growing interest in the use of complementary or alternative medicine (CAM) in gastrointestinal illnesses. These observations suggest that patients with coeliac disease may be dissatisfied with a GFD and possibly are seeking/using alternative therapies for their disease. Our aim was to assess the satisfaction levels of adults with coeliac disease towards a GFD, their use of oral CAM and views regarding novel therapies. METHODS: 310 patients with coeliac disease completed a questionnaire survey while attending their out-patient appointment. The control group comprised 477 individuals. RESULTS: Over 40% of patients with coeliac disease were dissatisfied with a GFD. The frequency of CAM use in patients with coeliac disease was 21.6% (67/310) vs 27% in the control group (129/477), p=0.09. All patients expressed an interest in novel therapies, with a vaccine being the first choice in 42% of patients, 35% and 23% for anti- zonulin and peptidases, respectively. Universally, patients placed genetically modified wheat as the lowest preference. CONCLUSIONS: A large proportion of patients with coeliac disease are dissatisfied with a GFD. Coeliac patients are not taking CAM any more than controls, suggesting they do not view CAM as an alternative to a GFD. However, all the patients in this survey were keen to consider novel therapies, with a vaccine being the most preferred option.