A systematic review to determine use of the Endometriosis Health Profiles to measure quality of life outcomes in women with endometriosis.

BACKGROUND: The Endometriosis Health Profiles (EHPs), the EHP-30 and EHP-5, are patient-reported outcome measures that were developed to measure the health-related quality of life (HRQoL) of women living with endometriosis. Prior to their development, a systematic review was undertaken which identified that the HRQoL of women living with endometriosis was poorly understood, with only three medical and one surgical study identified. OBJECTIVE AND RATIONALE: The 20-year anniversary of the EHP-30 provided a timely opportunity to assess how the tools have been used and explore what the findings tell us about the impact of endometriosis and its associated treatments upon women's QoL. Applying robust systematic review methodology, following PRISMA guidelines, we sought to answer: How many studies have used the EHP and for what purpose?; What are the demographic characteristics and international context of the studies?; What is the methodological nature and quality of the studies?; Which interventions have been assessed and what are the reported EHP outcomes?; and Can the EHP outcomes of these interventions be analysed using a meta-analysis and, if so, what do the results show? SEARCH METHODS: The electronic databases MEDLINE, CINAHL, PsycINFO, PubMed, and Google Scholar were searched from the year the EHP was first published, in 2001 to 26 February 2020 using the search terms 'EHP30', 'EHP5', 'EHP-30', 'EHP-5', 'endometriosis health profile 30', and 'endometriosis health profile 5'. We updated the searches on 9 April 2021. All included studies were quality assessed using the Mixed Methods Appraisal Tool (MMAT). OUTCOMES: The review included 139 papers. In clinical intervention studies, the EHPs were deployed most frequently to measure the outcomes of medical (n = 35) and surgical (n = 21) treatment. The EHPs were also used in 13 other intervention studies, 29 non-interventional studies, 32 psychometric/cross cultural validation studies; six diagnostic studies, and in three other studies to measure outcomes in related conditions. They were mainly deployed in studies undertaken in Europe and North America. Overall, regardless of the nature of the intervention, most women reported improvements in HRQoL after treatment. Surgical interventions generally resulted in significant improvements for the longest amount of time. There was also evidence that when participants stopped taking medication their EHP scores worsened, perhaps reinforcing the temporary impact of medical treatment. Younger patients reported more negative impact upon their HRQoL. Further evidence using classical test theory to support the EHPs' robust psychometric properties, including acceptability, dimensionality, reliability, validity (including cross-cultural), and responsiveness, was demonstrated, particularly for the EHP-30. Strikingly, using anchor-based methods, EHP-30 responsiveness studies demonstrate the largest mean changes in the 'control and powerlessness' domain post-intervention, followed by 'pain'. MMAT outcomes indicated the quality of the papers was good, with the exception of five studies. A meta-analysis was not undertaken owing to the heterogeneity of the interventions and papers included in this review. WIDER IMPLICATIONS: Women with endometriosis face a lifetime of surgical and/or medical interventions to keep the condition under control. Less invasive treatments that can lead to improved longer term physical and psycho-social outcomes are needed. The EHPs are reliable, valid, acceptable, and responsive tools, but more assessment of EHP outcomes using modern psychometric methods and in the context of women from ethnically diverse backgrounds and in routine clinical care would be beneficial. Given the brevity of the EHP-5, it may be the most appropriate version to use in routine clinical practice, whereas the longer EHP-30, which provides more granularity, is more appropriate for research.

Using longitudinal qualitative research to explore the experience of receiving and using augmentative and alternative communication.

BACKGROUND: People who have communication difficulties may benefit from using augmentative and alternative communication (AAC). Understanding and measuring outcomes from the use of AAC is an important part of evaluating the impact of devices and services. Outcome measurement needs to reflect the changing nature of the impact of using AAC on an individual's ability to participate in activities of daily life. There is a limited understanding of the concepts that should inform the evaluation of outcomes from AAC device provision, nor how people's expectations from AAC may change over time. AIMS: To inform the development of a patient-reported outcome measure for AAC by understanding more about people's expectations from AAC and how these change over time. METHODS & PROCEDURES: A longitudinal qualitative research study was designed and carried out with seven participants over a period of 2 years. Participants were recruited from a regional specialist assessment service for AAC in the south-west of the UK. Four semi-structured interviews were carried out: (1) before assessment for AAC, (2) after assessment, (3) directly after provision of an AAC device and (4) between 6 and 12 months after provision. An original analytic method was used in this study that built on the principles of longitudinal interpretative phenomenology analysis, applied with a dialogic theoretical lens. This approach enabled the inclusion of a range of multimodal and embodied data collected to this study and allowed the research team to draw out salient themes across the cohort group while attending to the influence of time and context on experience. OUTCOMES & RESULTS: The results confirm and extend the three core concepts that were used to guide analysis: changes; contexts; future possibilities. The contextual and temporal influences on outcomes attainable from AAC for this cohort were also identified and illustrated through cross-case comparison. Deeper, analytic, and conceptual engagement with theory, which was then applied to analysis of the data, provided methodological rigour in the study. The results enhance our understanding of people's hopes and expectations from AAC and how these change over time. CONCLUSIONS & IMPLICATIONS: This qualitative longitudinal research study provides new insights into the journeys of people who experience communication disability, and the shifting nature of their sense of identity as they engage with, and learn from using, AAC. The study is significant as it attends to the dynamic nature of experience and how contextual and experiential factors influence people's hopes and expectations from AAC. The paper presents an original application of longitudinal qualitative research methodology with people who use AAC which can be further applied and tested in the field of communication disability research. WHAT THIS PAPER ADDS: What is already known on this subject We did not know the impact that time has on the concepts that have been identified to represent important outcomes from AAC. The existing concepts used to define outcomes from AAC were not adequately conceptualized to develop a patient-reported outcome measure. This study sought to extend our knowledge about outcomes from AAC. What this paper adds to the existing knowledge This study adds to the methodological toolkit available for qualitative inquiry in the field of communication disability research by presenting a longitudinal qualitative research methodology. It adds depth to our understanding of the concepts that underpin outcomes from AAC and highlights the dynamic nature of contexts and how this influences desired outcomes. What are the potential or actual clinical implications of this work? This longitudinal qualitative research study provides a broader perspective on the experience of getting AAC. It will enable clinicians to better navigate the contextual and transitionary factors that influence people's experience of acquiring AAC devices. The enhanced concepts described will also support clinical conversations that consider the wider facets of communication and what AAC can add to existing communicative tool kits beyond getting a message across.

Reproduction in life and death: should cancer patients with a poor prognosis be offered fertility preservation interventions?

In the context of a cancer diagnosis, fertility preservation interventions are used to mitigate the potential impact of gonadotoxic cancer treatment upon fertility. They provide patients with cancer the option to freeze their reproductive material to have their own biological child following treatment. The evidence suggests some clinicians are less likely to have fertility preservation discussions with patients who have an aggressive or metastatic cancer which has a poor prognosis. Although this is contrary to current policy recommendations, there is a lack of guidance relating to offering fertility preservation in the context of a poor prognosis to support clinicians. Controversy surrounds posthumous reproduction, and whether the wishes of the cancer patient, when living and deceased should take precedence over others' wellbeing. We consider the question of whether cancer patients with a poor prognosis should be offered FP from an ethics perspective. We structure the paper around key arguments to which multiple ethical principles might pertain, first establishing a central argument in favour of offering fertility preservation based on respect for autonomy, before exploring counterarguments. We conclude by proposing that a defeasible assumption should be adopted in favour of offering fertility preservation to all cancer patients who might benefit from it. It is important to recognise that patients could benefit from fertility preservation in many ways, and these are not limited to having a parenting experience. The burden of proof rests on the clinician in collaboration with their multi-disciplinary team, to show that there are good grounds for withholding the offer.

Formation of a conceptual framework during the development of a patient-reported outcome measure for early gastrointestinal recovery: phase I of the PRO-diGi study.

AIM: Patients admitted to hospital for abdominal surgery often experience gastrointestinal dysfunction. Many studies have reported outcomes following gastrointestinal dysfunction, yet there is no unified definition of recovery or a validated patient-reported outcome measure (PROM). The first stage of PROM development requires formation of a conceptual framework to identify key themes to patients. The aim of this study was to utilize semistructured interviews to identify core themes and concepts relevant to patients to facilitate development of a conceptual framework. METHOD: Adult patients admitted to hospital for major gastrointestinal, urological or gynaecological surgery, in an emergency or elective setting, were eligible to participate. Patients treated nonoperatively for small bowel obstruction were also eligible. Interviews were conducted by telephone, audio-recorded, transcribed, coded and analysed using NVivo software by two researchers and reviewed by lay members of the steering group. Interviews continued until data saturation was reached. Ethical approval was gained prior to interviews (21/WA/0231). RESULTS: Twenty nine interviews were completed (17 men, median age 64 years) across three specialties (20 gastrointestinal, six gynaecological, three urological). Two overarching themes of 'general recovery' and 'gastrointestinal symptoms' were identified. General recovery included three themes: 'life impact', 'mental impact', including anxiety, and 'physical impact', including fatigue. Gastrointestinal symptoms included three themes: 'abdominal symptoms' such as pain, 'diet and appetite' and 'expulsory function', such as stool frequency. A total of 18 gastrointestinal symptoms were identified during patient recovery-many of which lasted several weeks following discharge. CONCLUSION: This study reports a range of gastrointestinal and nongastrointestinal symptoms experienced by patients during early gastrointestinal recovery. Identified symptoms have been synthesized into a conceptual framework to enable development of a definitive PROM for early gastrointestinal recovery.

Accessing publicly funded donor insemination treatment in the UK: is funding information available on fertility clinic websites?

We sought to find out if information about public funding for regulated donor insemination (DI) was available on UK fertility clinic websites, and if so, what information was provided for same-sex couples and single women; and if the available information was easily readable. The 'Choose a fertility clinic' pages of the Human Fertilisation and Embryology Authority (HFEA) website were used to identify all licensed fertility clinics in the UK, and any available text on public funding for DI treatment was extracted. The Flesch reading ease scores were calculated to determine the readability of the extracted text. Of the 52 clinics included in the synthesis, 23 mentioned public funding, and for 16 of these, it was unclear whether public funding was available. Six of the 23 clinics mentioned public funding for same-sex couples, and two mentioned public funding for single women. The Flesch reading ease scores indicated that none of the text about funding for DI treatment on any of the clinic websites met the NHS-advised level of readability for health information. Fertility clinic websites should specify whether they offer publicly funded treatment, and to whom, as well as clearly stating the eligibility criteria, using suitably readable language to communicate this.

"I Assumed It Would Be Somebody Who Had a Stroke That Was Doing This": Views of Stroke Survivors, Caregivers, and Health Professionals on Tailoring a Relaxation and Mindfulness Intervention.

Stroke survivors and informal caregivers experience high levels of stress and anxiety, linked to heightened risk of secondary stroke in survivors. Relaxation and mindfulness could reduce stress and anxiety; being most effective when tailored to the target populations. Aims of the PPI include to: (1) consult on possible alterations to an existing relaxation and mindfulness intervention, delivered via YouTube/DVD and (2) discuss relevance and preference of prompts and cues designed to facilitate the daily practice of the intervention. Eleven UK PPI contributors were consulted during 2020: four stroke survivors (F = 2, M = 2), three caregivers (F = 1, M = 2), and four HCPs (F = 4) (range = 23-63 years). Contributors watched the existing intervention and provided feedback via online discussions. Transcripts were analysed using thematic analysis. Five themes were identified, highlighting several necessary alterations to the intervention: "Who represents the stroke population?"; "The paradox of age"; "Specifically selected language"; "Visual presentation of the intervention"; and the "Audio qualities". Contributors ranked the prompts and cues in order of preference with setting alarms and email alerts as the most popular. The PPI consultations resulted in several alterations enabling a revised version of the intervention. Including a PPI consultation at an early stage of the research improves the relevance and appropriateness of the research. The revised intervention is more representative of the stroke population thus more likely to be practised by survivors and caregivers, which will enhance the extent of effectiveness, reducing the risk of a secondary stroke.

The Unspoken Voice: Applying John Shotter's Dialogic Lens to Qualitative Data from People Who have Communication Difficulties.

As speech and language therapists, we explored theories of communication and voice that are familiar to our profession and found them an inadequate basis on which to generate deep and rich analysis of the qualitative data from people who have communication difficulties and who use augmentative and alternative communication. Expanding our conceptual toolkit to include the work of John Shotter allowed us to reconceptualise voice and where it is emergent in dialogue. Reimaging voice will inform clinical and research praxis with people who have communication difficulties as it allows practitioners to attend more closely to the complexity and nuance inherent in interactions with this population. Our proposition is exemplified with excerpts from a single participant who has communication difficulties to illustrate the value of dialogic theory in praxis. This article presents a provocation for the wider academy of qualitative health research; do we have the concepts and tools to develop meaning with people whose lived experiences may also be hard to voice in monologues?

The acceptability of cervical electrical impedance spectroscopy within a multi-modal preterm birth screening package: a mixed methods study.

BACKGROUND: Reducing the rate of preterm birth is a cornerstone of global efforts to address child mortality, however existing screening tests offer imperfect prediction. Cervical electrical impedance spectroscopy (EIS) is a novel technique to quantify the ripening changes which precede labour. Mid-trimester EIS measurements have been shown to accurately predict preterm birth in asymptomatic women. This study aimed to comprehensively evaluate the acceptability of cervical EIS to low and high-risk women as part of a package of screening tests performed during a larger prospective trial. METHODS: In this parallel convergent mixed methods study, 40 women completed questionnaires before and after screening tests (EIS, cervical length measurement and fetal fibronectin quantification). Quantitative outcomes were anxiety levels before and after screening (Spielberger State Trait Anxiety Inventory, STAI-6), pain (Short Form McGill Pain Questionnaire) and ratings of EIS device appearance and test acceptability (visual analogue scales). Twenty-one women (11 high-risk, 10 low-risk) also attended a semi-structured qualitative interview. Interviews were recorded and transcribed, then thematic analysis was performed. A convergence coding matrix was constructed to enable triangulation of quantitative and qualitative results. RESULTS: High risk women demonstrated a significant reduction in anxiety following screening (mean STAI-6 score 34.5 vs. 29.0, p = 0.002). A similar trend was observed among low-risk participants. Ratings of pain, EIS device appearance and procedural acceptability did not differ between groups. Mean pain ratings were low (visual analogue scale 0.97 and 1.01), comparing favourably to published evaluations of conventional screening tests. Qualitative analysis provided insight into both the physical consequences and emotional experiences of screening. Additional determinants of the screening experience included device design, pre-existing perspectives on intimate examination, attitudes to knowledge in pregnancy and interaction with clinical staff. Finally, a range of practical considerations regarding wider use of EIS were identified, with valuable complementary detail regarding acceptability for use in antenatal care. CONCLUSIONS: Cervical EIS is well tolerated and acceptable to both low and high-risk women when performed as part of a multi-modal screening package. These results provide useful insights to inform the design of future study and screening protocols.

A Systematic Review of Outcomes Following Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL).

Background: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) has increasingly become a significant concern for patients. Focus thus far has been on understanding pathogenesis and establishing treatment pathways. There has been less attention on the assessment of long-term treatment outcomes. The purpose of this study was to perform a systematic review to assess published data on treatment outcomes for BIA-ALCL. Methods: Using PRISMA guidelines, a systematic search of the literature was carried out from January 1997 to January 2021 using the Web of Science (PubMed) and Ovid Medline. Included in the review were any studies on the management and follow-up of patients, including disease status at a minimum of 18 months following treatment. Results: A total of 39 articles matched the inclusion criteria. However, 94% of patients were managed with explantation and capsulectomy. Then, 39% of patients had adjuvant chemotherapy, 19% radiotherapy, 6% autologous stem cell transplant, and 4% immunotherapy. The mean follow-up was 19 months (range 3-36 months), and 69% of patients were reported to be alive at 18 months. The mainstay of treatment was surgical - en bloc capsulectomy with adjuvant treatment for advanced disease. Conclusions: Robust survival data based on high-level evidence are challenging to establish in BIA-ALCL. Early diagnosis and en bloc capsulectomy with negative margins, whilst considering the need for adjuvant treatment, particularly targeted immune therapy in advanced disease represents the consistent forms of treatment. National databases, prospective studies, and treatment of patients in tertiary centres are all recommended to improve the quality of the research available in the management of BIA-ALCL.

A qualitative evidence synthesis of the experiences and perspectives of communicating using augmentative and alternative communication (AAC).

PURPOSE: This paper presents a review of the existing qualitative research literature concerning people's experience of communicating using augmentative and alternative communication (AAC). The aims of conducting this review were to find out more about the values and outcomes that are important to people about the AAC they use to support their communication. This review was conducted to provide a deeper understanding of these experiences to inform the development of a patient-reported outcome measure (PROM). MATERIALS AND METHODS: A qualitative evidence synthesis of existing qualitative research literature was undertaken to explore and appraise current knowledge about the experiences of people who use AAC. RESULTS: From 115 qualitative research reports 19 papers were identified that responded directly to the research question and aims of the review. Data were identified that could be organized within an a priori framework consisting of the constructs of values, outcomes, and context. CONCLUSION: The review has resulted in a deeper, analytical understanding of the experiences of people who require AAC. The results indicate a set of concepts that can be used to inform the development of a PROM. A PROM can be used to assist clinicians and researchers to better understand the perspectives of people who require AAC and evaluate interventions. The results also encourage professionals to reconsider the terminology and methods used when working alongside people who require AAC and to reflect on the multidimensional factors that influence people's experience of communication.IMPLICATIONS FOR REHABILITATIONPatient-reported outcome measures (PROMs) can be useful tools to support clinician-patient communication, facilitate shared decision making and establish priorities for rehabilitation.It can be difficult to engage people who have complex communication difficulties in decisions about the important outcomes to them from using augmentative and alternative communication (AAC).This qualitative evidence synthesis provides a deeper understanding of the experiences and perspectives of people who use AAC.The results will be used to inform the development of a PROM which can be used to facilitate shared decision-making, and evaluate AAC interventions from the perspective of the people who use these technologies.

Cancer, Fertility and Me: Developing and Testing a Novel Fertility Preservation Patient Decision Aid to Support Women at Risk of Losing Their Fertility Because of Cancer Treatment.

Background: Women with a new cancer diagnosis face complex decisions about interventions aiming to preserve their fertility. Decision aids are more effective in supporting decision making than traditional information provision. We describe the development and field testing of a novel patient decision aid designed to support women to make fertility preservation treatment decisions around cancer diagnosis. Methods: A prospective, mixed-method, three stage study involving: 1) co-development of the resource in collaboration with a multi-disciplinary group of key stakeholders including oncology and fertility healthcare professionals and patient partners (n=24), 2) alpha testing with a group of cancer patients who had faced a fertility preservation treatment decision in the past (n=11), and oncology and fertility healthcare professionals and stakeholders (n=14) and, 3) beta testing with women in routine care who had received a recent diagnosis of cancer and were facing a fertility preservation treatment decision (n=41) and their oncology and fertility healthcare professionals (n=3). Ten service users recruited from a closed Breast Cancer Now Facebook group and the support group Cancer and Fertility UK also provided feedback on CFM via an online survey. Results: A 60-page paper prototype of the Cancer, Fertility and Me patient decision aid was initially developed. Alpha testing of the resource found that overall, it was acceptable to cancer patients, healthcare professionals and key stakeholders and it was considered a useful resource to support fertility preservation treatment decision-making. However, the healthcare professionals felt that the length of the patient decision aid, and elements of its content may be a barrier to its use. Subsequently, the prototype was reduced to 40 pages. During beta testing of the shortened version in routine care, women who received the resource described its positive impact on their ability to make fertility preservation decisions and support them at a stressful time. However, practical difficulties emerged which impacted upon its wider dissemination in clinical practice and limited some elements of the evaluation planned. Discussion: Women receiving the decision aid within the cancer treatment pathway found it helped them engage with decisions about fertility preservation, and make better informed, values-based care plans with oncology and fertility teams. More work is needed to address access and implementation of this resource as part of routine oncology care pathways.

Deciphering the Immune Complexity in Esophageal Adenocarcinoma and Pre-Cancerous Lesions With Sequential Multiplex Immunohistochemistry and Sparse Subspace Clustering Approach.

Esophageal adenocarcinoma (EAC) develops from a chronic inflammatory environment across four stages: intestinal metaplasia, known as Barrett's esophagus, low- and high-grade dysplasia, and adenocarcinoma. Although the genomic characteristics of this progression have been well defined via large-scale DNA sequencing, the dynamics of various immune cell subsets and their spatial interactions in their tumor microenvironment remain unclear. Here, we applied a sequential multiplex immunohistochemistry (mIHC) platform with computational image analysis pipelines that allow for the detection of 10 biomarkers in one formalin-fixed paraffin-embedded (FFPE) tissue section. Using this platform and quantitative image analytics, we studied changes in the immune landscape during disease progression based on 40 normal and diseased areas from endoscopic mucosal resection specimens of chemotherapy treatment- naïve patients, including normal esophagus, metaplasia, low- and high-grade dysplasia, and adenocarcinoma. The results revealed a steady increase of FOXP3+ T regulatory cells and a CD163+ myelomonocytic cell subset. In parallel to the manual gating strategy applied for cell phenotyping, we also adopted a sparse subspace clustering (SSC) algorithm allowing the automated cell phenotyping of mIHC-based single-cell data. The algorithm successfully identified comparable cell types, along with significantly enriched FOXP3 T regulatory cells and CD163+ myelomonocytic cells as found in manual gating. In addition, SCC identified a new CSF1R+CD1C+ myeloid lineage, which not only was previously unknown in this disease but also increases with advancing disease stages. This study revealed immune dynamics in EAC progression and highlighted the potential application of a new multiplex imaging platform, combined with computational image analysis on routine clinical FFPE sections, to investigate complex immune populations in tumor ecosystems.

Exploring invisibility and epistemic injustice in Long Covid-A citizen science qualitative analysis of patient stories from an online Covid community.

BACKGROUND: In 2020, the long-lasting effects of the Covid-19 virus were not included in public messages of risks to public health. Long Covid emerged as a novel and enigmatic illness with a serious and life-changing impact. Long Covid is poorly explained by objective medical tests, leading to widespread disbelief and stigma associated with the condition. The aim of this organic research is to explore the physical and epistemic challenges of living with Long Covid. METHODS: Unlike any previous pandemic in history, online Covid communities and 'citizen science' have played a leading role in advancing our understanding of Long Covid. As patient-led research of this grassroots Covid community, a team approach to thematic analysis was undertaken of 66 patient stories submitted online to covid19-recovery.org at the beginning of the Covid-19 pandemic between April and September 2020. RESULTS: The overriding theme of the analysis highlights the complexities and challenges of living with Long Covid. Our distinct themes were identified: the life-changing impact of the condition, the importance of validation and how, for many, seeking alternatives was felt to be their only option. CONCLUSIONS: Long Covid does not easily fit into the dominant evidence-based practice and the biomedical model of health, which rely on objective indicators of the disease process. Patient testimonies are vital to understanding and treating Long Covid, yet patients are frequently disbelieved, and their testimonies are not taken seriously leading to stigma and epistemic injustice, which introduces a lack of trust into the therapeutic relationship. PATIENT CONTRIBUTION: The research was undertaken in partnership with our consumer representative(s) and all findings and subsequent recommendations have been coproduced.

Using an integrated competence model to evaluate a health visitor cascade training programme for the Family Resilience Assessment Instrument and Tool (FRAIT).

This paper reports on an evaluation of health visitor trainers' experience of a cascade training programme delivered in Wales, UK. Health visitors used Driscoll's model (What, So What, Now What) to organise their feedback and an integrated competence model developed by Weeks et al. was used to analyse the feedback via category analysis of free text. As well as feedback on the logistics of running the training, the evaluation allowed for cognitive and functional competence to be identified along with personal and meta competence. There was limited scope for identifying ethical competence in the Health Visitor cascade trainer feedback. Suggestions are made for how this may be addressed.

Are UK Policies and Practices for Regulated Donor Insemination Forcing Women to Find Unregulated Sperm Donors Online? A Perspective on the Available Evidence.

In recent years, there has been an increase in women obtaining donor sperm via unregulated websites and social media. In this article, we bring together the disparate evidence in this emerging field to consider whether restrictive UK policies and practices for regulated clinical donor insemination (DI) are a potential explanation for the growing use of the currently unregulated, online route to donor insemination. To this end, we examine the nature of the National Institute for Health and Care Excellence (NICE) guidelines, recent data provided by the Human Fertilisation and Embryology Authority (HFEA), and prior research on who uses online sperm donation and their reasons for doing so. In addition, we highlight why this issue is important by outlining some of the benefits and drawbacks of the unregulated route. We argue that, whilst there are many factors driving the unregulated route to DI, restrictive UK policies and practices for regulated DI might be one of these. We conclude that turning our attention to structural barriers, such as regulated DI policies and practices, is necessary to produce more definitive evidence of this potential issue, and that adopting a Reproductive Justice framework could lead to more equitable provision of regulated DI services.

Understanding the relationship between social determinants of health and maternal mortality: Scientific Impact Paper No. 67.

Within this document we use the terms pregnant woman and women's health. However, it is important to acknowledge that it is not only people who identify as women for whom it is necessary to access care. Obstetric and gynaecology services and delivery of care must therefore be appropriate, inclusive and sensitive to the needs of those individuals whose gender identity does not align with the sex they were assigned at birth.

A clinical study to optimise a sand fly biting protocol for use in a controlled human infection model of cutaneous leishmaniasis (the FLYBITE study).

Background: Leishmaniasis is a globally important yet neglected parasitic disease transmitted by phlebotomine sand flies. With new candidate vaccines in or near the clinic, a controlled human challenge model (CHIM) using natural sand fly challenge would provide a method for early evaluation of prophylactic efficacy. Methods : We evaluated the biting frequency and adverse effects resulting from exposure of human volunteers to bites of either Phlebotomus papatasi or P. duboscqi, two natural vectors of Leishmania major. 12 healthy participants were recruited (mean age 40.2 ± 11.8 years) with no history of significant travel to regions where L. major-transmitting sand flies are prevalent. Participants were assigned to either vector by 1:1 allocation and exposed to five female sand flies for 30 minutes in a custom biting chamber. Bite frequency was recorded to confirm a bloodmeal was taken. Participant responses and safety outcomes were monitored using a visual analogue scale (VAS), clinical examination, and blood biochemistry. Focus groups were subsequently conducted to explore participant acceptability. Results: All participants had at least one successful sand fly bite with none reporting any serious adverse events, with median VAS scores of 0-1/10 out to day 21 post-sand fly bite. Corresponding assessment of sand flies confirmed that for each participant at least 1/5 sand flies had successfully taken a bloodmeal (overall mean 3.67±1.03 bites per participant). There was no significant difference between P. papatasi and P. duboscqi in the number of bites resulting from 5 sand flies applied to human participants (3.3±0.81 vs 3.00±1.27 bites per participant; p=0.56) .  In the two focus groups (n=5 per group), themes relating to positive participant-reported experiences of being bitten and the overall study, were identified. Conclusions: These results validate a protocol for achieving successful sand fly bites in humans that is safe, well-tolerated and acceptable for participants. Clinicaltrials.gov registration: NCT03999970 (27/06/2019).

A Baby at All Costs? Exploring the Use and Provision of Unproven Adjuvant Treatments in the Context of IVF.

The year 2018 marked 40 years since the birth of Louise Brown, the first baby born as a result of pioneering in vitro fertilization (IVF) treatment. Since then, advances have seen a wide range of reproductive technologies emerge into clinical practice, including adjuvant treatments often referred to as IVF "add-ons." However, these "optional extras" have faced growing criticism, especially when they have often come at additional financial cost to the patient and have little evidence supporting their efficacy to improve pregnancy or birth rates. Despite this, according to the latest national patient survey by the Human Fertilisation and Embryology Authority, three quarters of patients who had fertility treatment in the United Kingdom in the past two years had at least one type of treatment add-on highlighting the growing demand for these interventions. This article uses a psychosocial perspective to consider the motivations behind patient and clinician behavior along with the wider societal and economic factors that may be impacting upon the increase in the use of adjuvant treatments in fertility clinics more widely. It suggests the reasons fertility patients use unproven "optional extras" are complex, with interpersonal, psychological, and social factors intertwining to generate an increase in the use of IVF add-ons.

Assessing public perception of a sand fly biting study on the pathway to a controlled human infection model for cutaneous leishmaniasis.

BACKGROUND: A controlled human infection model (CHIM) involves deliberate exposure of volunteers to pathogens to assess their response to new therapies at an early stage of development. We show here how we used public involvement to help shape the design of a CHIM to support future testing of candidate vaccines for the neglected tropical disease cutaneous leishmaniasis, a disease transmitted by the bite of infected sand flies in tropical regions. METHODS: We undertook a public involvement (PI) consultation exercise to inform development of a study to test the safety and effectiveness of a sand fly biting protocol using uninfected sand flies (FLYBITE: ClinicalTrials.gov ID NCT03999970 ) and a CHIM using Leishmania major-infected sand flies (LEISH_Challenge: ClinicalTrials.gov ID NCT04512742 ), both taking place in York, UK. We involved 10 members of the public including a patient research ambassador and a previous CHIM volunteer. The session took place at The University of York, UK and examined draft study volunteer-facing material and included the CHIM study design, potential adverse events and therapeutic interventions at study endpoints. A discussion of the scientific, ethical, humanitarian and economic basis for the project was presented to the participants to provoke discourse. An inductive, thematic analysis was used to identify the participants' key concerns. RESULTS: Themes were identified relating to i) quality of volunteer-facing written information, ii) improving study design, and iii) factors to motivate involvement in the research. Group participants responded positively to the overall study aims. Initial concerns were expressed about potential risks of study involvement, but further explanation of the science and mitigations of risk secured participant support. Participants provided advice and identified improved terminology to inform the volunteer-facing material. Lastly, treatment options were discussed, and excision of any cutaneous lesion was favoured over alternatives as a treatment. CONCLUSION: The consultation exercise provided invaluable information which led to improved study design and enhanced clarity in the volunteer-facing material. The session also reinforced the need to maintain public trust in scientific rigour prior to initiation of any study. The investigators hope that this description strengthens understanding of PI in clinical research, and encourages its use within other studies.

Our research team is designing a type of research study known as a controlled human infection model (CHIM). In CHIM studies, volunteers are exposed to infections on purpose and then studied to help understand diseases. Similar experiments, where humans are infected deliberately, have been used for hundreds of years to help test treatments. CHIM studies have already been used more recently to help test vaccines for diseases such as malaria.The disease leishmaniasis, a disease affecting millions each year, is spread by the bite of an infected sand fly in tropical countries. There are currently no vaccines for leishmaniasis that are available for use in humans. It is thought that by using CHIM studies, new vaccines might be tested and then approved more quickly. Scientific researchers have had many discussions about how useful CHIM studies are, especially in terms of the science behind them, the safety of volunteers and the ethics of these studies. Researchers also understand how important it is to involve the public in designing and carrying out research, especially studies involving humans, to get an independent point-of-view. We have therefore involved the public, in some parts of designing this research, in a group discussion. We also included a person who has already taken part in a different CHIM study. These discussions have had an important effect and have changed how we plan to carry out our future research studies. We also hope that this description will encourage other researchers to include the public when planning future research.