Small Steps, Big Vision: using multi-stage qualitative research to develop a grab-and-go guide to support utilisation of the Ambitions for Palliative and End of Life Care framework.

BACKGROUND: The Ambitions for Palliative and End of Life Care is a national framework for local action in England co-produced by over 30 partners; little research has been conducted on how the Framework is received and used. This study sought to examine and support how people understand, interpret, and implement the Framework. METHODS: A multi-stage qualitative methodology involving four stages of data collection: (1) case study interviews, (2) focus groups, (3) interactive workshops, and (4) Evidence Cafés. From initial interviews, ongoing thematic data analysis informed the design and focus of subsequent stages as part of a process of knowledge transfer. RESULTS: A practical resource to support service provision and development was produced; a grab-and-go guide called "Small Steps, Big Visions". It focuses on the eight foundations in the Ambitions Framework, with additional guidance on collaboration and partnership working, and sharing learning. Each foundation is presented with a 'what' (definition), 'ask' (prompt questions), and 'examples in action' (drawn from case studies). CONCLUSIONS: Research can contribute to policy implementation to advance palliative and end of life care. The engagement and input of those responsible for implementation is key.

Can storytelling of women's lived experience enhance empathy in medical students? A pilot intervention study.

PURPOSE: This pilot study aimed to investigate the acceptability and efficacy of a patient storytelling intervention (live and recorded) on empathy levels of medical students. MATERIALS AND METHODS: Medical students participated in a storytelling intervention that had three components: listening to live or recorded stories from women with abnormal uterine bleeding, reflective writing, and a debriefing session. Empathy scores of students pre- and post-intervention were measured using the Jefferson Scale of Empathy-student version (JSE-S). Students also completed a feedback survey. Descriptive and inferential statistics were used to analyse quantitative data and content analysis was used for text comments. RESULTS: Both live and recorded storytelling interventions had positive effects on student's empathy scores post intervention. Overall, students were satisfied with the intervention and reported that it improved their understanding of life experiences of women. Suggestions were made for an in-person storytelling session and interactive discussion after listening to each story. CONCLUSION: A storytelling intervention has the potential to improve medical students' empathy and understanding of lived experience of women with health conditions. This could be valuable when student-patient interactions are limited in healthcare settings, or to enable stories of small numbers of patient volunteers to reach students.

Increasing incidence of endometrial cancer in Aotearoa New Zealand: Health professionals' perspective.

BACKGROUND: The incidence of endometrial cancer is globally increasing. Aotearoa New Zealand is no exception with a 59% increase in cases over that last ten years. AIMS: We report a sub-set of themes which pertain to provider reflections of rising endometrioid-type endometrial cancer incidence in individuals with high weight. MATERIALS AND METHODS: Fifteen semi-structured interviews with healthcare professionals experienced in providing care to women with endometrial cancer were audio-recorded and transcribed. Interviews were analysed using reflexive thematic analysis. RESULTS: Two main themes emerged: (1) concerns for the future; and (2) impact on fertility and treatment options. Healthcare professionals discussed rising incidence in younger people and a need for increased awareness about the association of excess weight as a risk factor for developing the disease. The concern extended to workforce and equipment shortfalls of meeting the needs of individuals with higher weight, which subsequently influenced treatment options, health outcomes and survivorship. CONCLUSIONS: Rising incidence of endometrial cancer in individuals with high weight presents multiple chances for inequitable access and health outcomes over the care continuum for endometrial cancer. Action is required to address incidence, awareness, access to equitable and inclusive treatment, and survivorship.

Non-invasive tests for endometriosis are here; how reliable are they, and what should we do with the results?

A reliable non-invasive biomarker for endometriosis is highly likely in the coming years. In the lead-up to this, clinicians need to be aware of commercially available tests as they become accessible, be aware of the level of evidence to support them and be prepared to counsel and manage patients who present with the results of such tests. One such test gaining popularity in Europe was developed using a machine-based learning algorithm to analyse thousands of microRNAs based on a 200-patient cohort with suspected endometriosis in France. We explore the background science for this commercially available test; outline the questions that remain to be answered; and caution against its use outside of a research setting.

Transcriptomic identification of differentially expressed genes in Levonorgestrel resistant endometrial cancer cell lines.

Endometrial cancer (EC) is the most common gynecologic malignancy in the world and incidence is steadily increasing. The Levonorgestrel Intrauterine System (LNG-IUS) is an alternative conservative treatment for early-stage EC, however, Levonorgestrel (LNG) resistance occurs for 1 in 3 people. This study aimed to present potential LNG resistance mechanisms and identify differentially expressed genes (DEGs) in EC cell lines. Two LNG resistant cell lines were developed through long term culture in LNG (MFE296R and MFE319R ). Whole transcriptome sequencing was carried out on triplicate RNA samples. EdgeR v3.32.1 was used to identify differentially DEGs. Blast2go V6.0 (BioBam software) was used for functional annotation and analysis of genomic datasets. Protein interactions were investigated using the STRING database, including the identification of genes with high levels of interaction (HUB genes). Select DEGs and HUB genes were validated by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Fifteen DEGs were identified according to FDR < 0.05 and logFC < 2. Protein analysis identified six HUB genes with a degree of connectivity > 10. Relative mRNA expression of MAOA, MAOB, THRSP, CD80, NDP, LINC01474, DUSP2 and CXCL8 was significantly upregulated in both LNGR cell lines. Relative protein expression of GNAO1 and MAOA were significantly upregulated in both LNGR cell lines. This research identified novel markers of resistance in LNGR cell lines. We discussed potential mechanisms of LNG resistance including dedifferentiation and immunostimulation. The next step for this research is to validate these findings further in both translational and clinical settings.

Ambitions for palliative and end of life care: mapping examples of use of the framework across England.

BACKGROUND: Since 2015, the Ambitions for Palliative and End of Life Care: a national framework for local action has provided guidance for care within England and beyond. Relaunched in 2021, the Framework sets out six Ambitions which, collectively, provide a vision to improve how death, dying and bereavement are experienced and managed. However, to date, there has been no central evaluation of how the Framework and its Ambitions have been implemented within service development and provision. To address this evidence gap, we investigated understanding and use of the Framework. METHODS: An online questionnaire survey was conducted to identify where the Framework has been used; examples of how it has been used; which Ambitions are being addressed; which foundations are being used; understanding of the utility of the Framework; and understanding of the opportunities and challenges involved in its use. The survey was open between 30 November 2021-31 January 2022, promoted via email, social media, professional newsletter and snowball sampling. Survey responses were analysed both descriptively, using frequency and cross-tabulations, and exploratively, using content and thematic analysis. RESULTS: 45 respondents submitted data; 86% were from England. Findings indicate that the Framework is particularly relevant to service commissioning and development across wider palliative and end of life care, with most respondents reporting a focus on Ambition 1 (Each person is seen as an individual) and Ambition 3 (Maximising comfort and wellbeing). Ambition 6 (Each community is prepared to help) was least likely to be prioritised, despite people welcoming the focus on community in national guidance. Of the Framework foundations, 'Education and training' was seen as most necessary to develop and/or sustain reported services. The provision of a shared language and collaborative work across sectors and partners were also deemed important. However, there is some indication that the Framework must give more prioritisation to carer and/or bereavement support, have greater scope to enhance shared practice and mutual learning, and be more easily accessible to non-NHS partners. CONCLUSIONS: The survey generated valuable summary level evidence on uptake of the Framework across England, offering important insights into current and past work, the factors impacting on this work and the implications for future development of the Framework. Our findings suggest considerable positive potential of the Framework to generate local action as intended, although difficulties remain concerning the mechanisms and resources necessary to enact this action. They also offer a valuable steer for research to further understand the issues raised, as well as scope for additional policy and implementation activity.

Retrospective review of endometriosis surgery at Te Whatu Ora - Capital and Coast.

INTRODUCTION: Endometriosis is an under-researched disease, with Aotearoa-specific data severely lacking. Current estimates of parameters such as rates of endometriosis diagnosis, indication for surgery and sites of disease are based on international data. There is currently no published data on endometriosis surgeries in Aotearoa New Zealand. AIMS: We aimed to describe the laparoscopic surgeries conducted for suspected endometriosis at Te Whatu Ora - Capital and Coast, including the prevalence of endometriosis in this cohort, indication for surgery, symptoms experienced, endometriosis stage and sites involved, number of repeat laparoscopies, and prevalence of endometriosis at repeat surgery. MATERIALS AND METHODS: To conduct this retrospective cross-sectional study, data were extracted from Te Whatu Ora - Capital and Coast systems to identify all records indicating surgery for suspected endometriosis during 2018 and 2019. Variables investigated included age, ethnicity, endometriosis diagnosis (International Classification of Diseases-10 Clinical Modification coding), stage of endometriosis, histological report and endometriosis symptoms (pain and/or fertility). RESULTS: There were 436 surgeries for suspected endometriosis performed during 2018 and 2019, and endometriosis was diagnosed in 68.3% of these surgeries. Pacific and Asian people were under-represented in the study cohort compared to the demographics of the hospital catchment area (Pacific: 3.0% vs 8.4%, Asian: 9.9% vs 12.9%). The most common indication for surgery was pain. There were 76 surgeries performed for suspected recurrence of endometriosis, and endometriosis was identified in 55.6% of these. CONCLUSIONS: Endometriosis surgeries in this hospital in Aotearoa show similar presentations and surgical findings to international data. Our findings highlight areas requiring more research in an Aotearoa-specific context.

A promising future for endometriosis diagnosis and therapy: extracellular vesicles - a systematic review.

Endometriosis is a chronic, inflammatory gynaecological disease that can have severe negative impacts on quality of life and fertility, placing burden on patients and the healthcare system. Due to the heterogeneous nature of endometriosis, and the lack of correlation between symptom and surgical disease severity, diagnosis and treatment remain a significant clinical challenge. Extracellular vesicles (EVs) are biologically active particles containing molecular cargo involved in intercellular communication, that can be exploited for diagnostic and therapeutic purposes.We systematically reviewed studies exploring EVs and their role in endometriosis, specifically addressing diagnostic and therapeutic potential and current understanding of pathophysiology. Five databases (Pubmed, Embase, Medline, Web of Science, Google Scholar) were searched for keywords 'endometriosis' and either 'extracellular vesicles' or 'exosomes'.There were 28 studies included in the review. Endometrium derived EVs contribute to the development of endometriosis. EVs derived from endometriosis lesions contribute to angiogenesis, immunomodulation and fibrosis. Such EVs can be detected in blood, with early data demonstrating utility in diagnosis and recurrence detection. EV isolation techniques varied between studies and only eight of twenty-eight studies fully characterised EVs according to current recommended standards. Reporting/type of endometriosis was limited across studies. Varied patient population, type of sample and isolation techniques created bias and difficulty in comparing studies.EVs hold promise for improving care for symptomatic patients who have never had surgery, as well as those with recurrent symptoms after previous surgery. We encourage further EV research in endometriosis with the inclusion of rigorous reporting of both the patient population and technical methodology used, with the ultimate goal of achieving clinical utility for diagnosis, prognosis and eventually treatment.

Circulating cell-free DNA undergoes significant decline in yield after prolonged storage time in both plasma and purified form.

OBJECTIVES: Circulating DNA (cirDNA) is generally purified from plasma that has been biobanked for variable lengths of time. In long-term experiments or clinical trials, the plasma can be stored frozen for up to several years. Therefore, it is crucial to determine the stability of cirDNA to ensure confidence in sample quality upon analysis. Our main objective was to determine the effect of storage for up to 2 years on cirDNA yield and fragmentation. METHODS: We stored frozen EDTA plasma and purified cirDNA from 10 healthy female donors, then quantified cirDNA yield at baseline, and at regular intervals for up to 2 years, by qPCR and Qubit. We also compared cirDNA levels in non-haemolysed and haemolysed blood samples after 16 months of storage and tested the effect of varying DNA extraction protocol parameters. RESULTS: Storage up to two years caused an annual cirDNA yield decline of 25.5% when stored as plasma and 23% when stored as purified DNA, with short fragments lost more rapidly than long fragments. Additionally, cirDNA yield was impacted by plasma input and cirDNA elution volumes, but not by haemolysis. CONCLUSIONS: The design of long-term cirDNA-based studies and clinical trials should factor in the deterioration of cirDNA during storage.

Barriers to seeking consultation for abnormal uterine bleeding: systematic review of qualitative research.

BACKGROUND: Although Abnormal Uterine Bleeding (AUB) can have serious medical consequences and significantly impacts daily life, the overall trend is that most women do not seek care for these symptoms. The objective of this review was to synthesise factors impeding women's access care for AUB. METHODS: Systematic literature review of qualitative studies (interview and focus group) regarding the lived in experiences of women with abnormal menstrual symptoms, followed by a thematic analysis of these studies. We screened CINAHL, SCOPUS, ProQuest, OVID and Pubmed for qualitative studies. Studies were assessed using the Clinical Appraisal Skills Programme checklist and thematic synthesis was used to develop themes from the findings of the studies. RESULTS: The review yielded 12 studies that satisfied the inclusion criteria. Three themes were developed that described barriers for women seeking care for AUB: health literacy (understanding of normal periods, role of cervical Pap smears and lack of access to appropriate information), taboo/normalisation (fear and embarrassment of symptoms, prioritising others) and health care provider (lack of accessible and trusted female GPs and poor experiences with GPs). CONCLUSIONS: For 20 years women have consistently reported poor experiences in accessing care for AUB. The findings from our review indicate that drivers to impeding access are multiple; therefore any approaches to improve access will need to be multi-level - from comprising local sociocultural considerations to improved GP training.

Designing Effective Digital Advertisements to Prevent Online Consumption of Child Sexual Exploitation Material.

The necessity of developing effective and innovative primary prevention strategies is a pressing objective in stemming the harm caused by the production and consumption of child sexual exploitation material (CSEM). Digital media interventions - including search engine advertisements - hold promise as prevention tools to deflect potential users away from CSEM and redirect them to therapeutic services. This study aimed to establish an evidence base for effective advertising in this context by creating mock-up helpline advertisements and testing them in focus groups and interviews with staff and clients of New Zealand's major treatment service providers for harmful sexual behavior. Prior to testing these advertisements in situ (on online platforms), this paper reports on a foundational creative and qualitative investigation of effective advertisements - what imagery, text, and design features are most likely to succeed in diverting people away from seeking CSEM and encouraging them to reach out to a helpline? The findings of this study offer deeper understanding of the mindset, emotions, and barriers to reaching out that are experienced by onset CSEM users, as well as suitability of certain imagery and text for advertising in this context, and thereby contribute to strengthening primary prevention efforts in combatting CSEM consumption.

Reflection on the current status of endometrial cancer in New Zealand.

Incidence of endometrial cancer is increasing rapidly in the developed world and is the most common gynaecological cancer in Australia and New Zealand. In line with obesity rates, the landscape and average age of women diagnosed with endometrial cancer are changing. There is still unmet need in early diagnosis, directed treatment, management of comorbidities and prevention strategies. This opinion piece aims to reflect on the current status of endometrial cancer in New Zealand in parallel to Australia, drawing out areas for future research and discussion.

"I'm not getting paid to give you a TED talk on how my trans body works". Experiences of hysterectomy gender affirming surgery: A qualitative study.

OBJECTIVE: To explore the experiences of care surrounding hysterectomy as part of gender affirming surgery. METHODS: An in-depth reflexive thematic analysis from accounts by 10 out of 12 people was undertaken. Experiences were then mapped to the surgery journey as a template for developing system responsiveness. RESULTS: No one person's experience of the procedure was affirmed across the entire surgery journey. Transgender health literacy was central to inclusive practice as it mediated bodily autonomy being upheld. The physical care environment influenced the experience, for example, the waiting room was marginalizing (intimidating), with a gendered clinic name and toilets. Some participants took a female support person/partner so that "people looking would assume that I was there supporting her, not the other way around." Communication misalignments were evident around information provided/understood about fertility and ovarian preservation. Participants were also placed in the position of both receiving care and providing education: "I also shouldn't have to be going in there for treatment, and then being expected to educate the medical professional that's meant to be helping me… I'm not getting paid to give you a TED talk on how my trans body works." The experiences mapped across the surgery journey highlighted multiple levels of service provision development needed to foster inclusive practice, for example, from workforce education to healthcare policy. CONCLUSION: Healthcare for transgender people can be unsafe and inequitable. Increasing transgender health responsiveness across the surgery journey will facilitate better alignments in communication and uphold bodily autonomy, leading to safer and inclusive practice.

Comparison of cervicovaginal fluid extracellular vesicles isolated from paired cervical brushes and vaginal swabs.

Endometriosis is a common gynaecological condition, with a long diagnostic delay. Surgery is required to confirm a diagnosis, highlighting the need for a non-invasive biomarker. Extracellular vesicles (EVs) may have a role in endometriosis pathogenesis, yet there is limited EV biomarker literature available. This study aimed to investigate the feasibility of isolating cervico-vaginal fluid EVs sampled using cervical brushes and vaginal swabs and to compare these methods. After providing informed consent, patients undergoing surgery for suspected endometriosis had cervical brush and vaginal swab samples collected under general anaesthetic. Isolated EVs were characterised through negative stain transmission electron microscopy (TEM), Western blotting (TSG101, CD63, Calnexin, ApoB, Albumin), tunable resistive pulse sensing (TRPS), microBCA assays and RT-qPCR of miRNAs. PCR was performed on samples prior to EV isolation to assess bacteria present in samples. Cervical brush and vaginal swab EVs were intact vesicles with limited co-isolated contaminants. Cervical brushes had higher concentrations of particles compared to match vaginal swabs, although both samples had low concentrations. Protein and miRNA yield were similar between matched samples. PCR demonstrated only a small amount DNA within samples was bacterial (>0.5%). Cervico-vaginal fluids EVs were successfully isolated from cervical brushes and vaginal swabs, demonstrating a new method of sampling reproductive EVs. EV yield from both sample types was low. Similar protein and miRNA levels suggest either sampling method may be suitable for biomarker studies.

Investigational drugs for the treatment of dysmenorrhea.

INTRODUCTION: Dysmenorrhea is the most common cause of gynecological pain among women that has considerable impact on quality of life and psychosocial wellbeing. Non-steroidal anti-inflammatory drugs (NSAIDs) and hormonal therapies are most commonly used to treat dysmenorrhea. However, given these drugs are often associated with bothersome side effects and are less effective when there is an underlying cause contributing to dysmenorrhea (e.g. endometriosis), a patient-centered approach to managing dysmenorrhea is important. Various new drugs are currently being investigated for the treatment of primary and secondary dysmenorrhea. AREAS COVERED: This review provides an updated overview on new therapeutic targets and investigational drugs for the treatment of primary and secondary dysmenorrhea. The authors describe the clinical development and implications of these drugs. EXPERT OPINION: Among the investigative drugs discussed in this review, anti-inflammatories show the most promising results for the treatment of dysmenorrhea. However, given some trials have considerable methodological limitations, many drugs cannot be currently recommended. Research focused on understanding the mechanisms involved in menstruation and its associated symptoms will be important to identify new therapeutic targets for dysmenorrhea. Further robust clinical trials are required to better understand the efficacy and safety of investigational drugs for treating primary and secondary dysmenorrhea.

Development of a long term, ex vivo, patient-derived explant model of endometrial cancer.

Incidence of endometrial cancer (EC) is rising in the developed world. The current standard of care, hysterectomy, is often infeasible for younger patients and those with high body mass index. There are limited non-surgical treatment options and a lack of biologically relevant research models to investigate novel alternatives to surgery for EC. The aim of the present study was to develop a long-term, patient-derived explant (PDE) model of early-stage EC and demonstrate its use for investigating predictive biomarkers for a current non-surgical treatment option, the levonorgestrel intra-uterine system (LNG-IUS). Fresh tumour specimens were obtained from patients with early-stage endometrioid EC. Tumours were cut into explants, cultured on media-soaked gelatin sponges for up to 21 days and treated with LNG. Formalin-fixed, paraffin embedded (FFPE) blocks were generated for each explant after 21 days in culture. Tumour architecture and integrity were assessed by haematoxylin and eosin (H&E) and immunohistochemistry (IHC). IHC was additionally performed for the expression of five candidate biomarkers of LNG resistance. The developed ex vivo PDE model is capable of culturing explants from early-stage EC tumours long-term (21 Days). This model can complement existing models and may serve as a tool to validate results obtained in higher-throughput in vitro studies. Our study provides the foundation to validate the extent to which EC PDEs reflect patient response in future research.

Providing high-quality end-of-life care universally.

The National End of Life Care Programme was launched in November 2004, and has been instrumental in delivering the Department of Health's (2008) End-of-Life Care Strategy and the National Institute of Health and Clinical Excellence's (2011) Quality Standard for End of Life Care for Adults. End-of-life care now sits within NHS Improving Quality. In this article we discuss an overview of the programme's successes, challenges and priorities for the future.

Reflections on access to care for heavy menstrual bleeding: Past, present, and in times of the COVID-19 pandemic.

The symptom of heavy menstrual bleeding (HMB) affects at least a quarter of reproductive-age menstruators. However, given the variance in diagnosing the underlying causes, barriers, and inequity in access to care for HMB, and therefore reporting of HMB, this figure is likely to be a gross underestimate. HMB can have a detrimental impact on quality of life. From the limited reports available it is estimated that around 50%-80% of people with HMB do not seek care for this debilitating symptom, and for those that do, it may take years until the first treatment action. Almost half of those with HMB believe their condition is unworthy of treatment, that there is no treatment available, or that it is "normal". The term "medical gaslighting" has recently been used to describe how healthcare professionals disregard people's symptoms. This has the ensuing effect of negatively compounding self-doubt and embarrassment around menstrual bleeding, creating a cycle of diminished experience inhibiting further seeking of care. There is a scarcity of intervention studies informing increased access to care. Multilevel approaches are needed to increase access to care and support for those with HMB. During the COVID-19 global pandemic, barriers to care access and support for HMB have been exacerbated and, given the significant pressures that this pandemic has placed on healthcare services worldwide, it will take many years to recover. In the meantime, it is crucial to ensure that medically "benign" conditions such as the symptom of HMB are not overlooked.

Exploring health professionals' viewpoint of provision of nutrition advice for women with endometrial cancer.

AIMS: The aim of this study was to explore barriers and facilitators to delivery and uptake of nutrition advice to women diagnosed with endometrial cancer from a health professionals' viewpoint. METHODS: Fifteen semi-structured interviews with health professionals with experience in providing healthcare to women diagnosed with endometrial cancer were audio-recorded and transcribed. Interviews were analysed using reflexive thematic analysis. Topics included high weight as a risk factor for endometrial cancer, nutrition information sources, and barriers and facilitators to delivering nutrition advice in clinical care. RESULTS: Four themes were identified. The first three exist as barriers to women receiving nutrition advice-how to navigate conversations about high weight, access to limited resourcing and health professionals feeling powerless to overcome system influences. The fourth theme identified a community approach need to facilitate a supportive environment and share knowledge. CONCLUSIONS: This study, through the lens of health professionals, highlights barriers to the delivery and uptake of nutrition advice at the patient, community and system levels. Enhancing survivorship for women after the diagnosis of endometrial cancer may be enabled by further understanding of how to overcome barriers and promote facilitators. Communication and partnership with women are imperative to achieving this.