Survey of General Practitioner Perspectives on Endometriosis Diagnosis, Referrals, Management and Guidelines in New Zealand.

INTRODUCTION: There is a growing body of literature concerning endometriosis patients' perspectives on the healthcare system and endometriosis care in New Zealand. However, there is little research available on the perspectives of general practitioners (GPs) internationally, and none currently in New Zealand. The purpose of this study is to address New Zealand GPs' understanding of and approach to endometriosis diagnosis, referrals, management and guidelines. METHODS AND MATERIALS: An online, anonymous survey was shared with 869 GP clinics and completed by 185 New Zealand-based GPs regarding their awareness and application of the inaugural 2020 'Diagnosis and Management of Endometriosis in New Zealand' guidelines, their perception of their endometriosis knowledge, the diagnostic value they assign to symptoms, the treatments they recommend and the reasons they refer patients to specialist gynaecologists. Differences between groups were conducted using Chi-squared tests, and text answers were assessed thematically using inductive, semantic coding. RESULTS: All 185 GPs had gynaecology consults, and 73% had gynaecology consults every week. Despite 65% being aware of the 2020 guidelines, only 35% overall had read them. Only 52% of GPs considered themselves to know enough about endometriosis for their routine practice. The most common treatment to be considered first line was intrauterine contraceptive devices (IUDs; 96%), whereas the most common alternative treatment recommended was exercise (69%). The most common reason for referral to specialist care was the failure of all attempted treatments (84%). CONCLUSIONS: Many of the study's results align with current New Zealand and international endometriosis guidelines, particularly the prioritisation of progestin-only therapies, the reduced emphasis on surgical treatment as the first line and the low rates of alternative treatment recommendations. This study also highlights the need to improve awareness of inappropriate GP recommendations, including long-term treatment with prescription-only pain relief such as codeine and pregnancy for symptomatic relief. PATIENT OR PUBLIC CONTRIBUTION: Two of the authors involved in the design and conduct of the study, data interpretation and manuscript preparation have sought care for endometriosis. TRIAL REGISTRATION: NA.

USP50 suppresses alternative RecQ helicase use and deleterious DNA2 activity during replication.

Mammalian DNA replication relies on various DNA helicase and nuclease activities to ensure accurate genetic duplication, but how different helicase and nuclease activities are properly directed remains unclear. Here, we identify the ubiquitin-specific protease, USP50, as a chromatin-associated protein required to promote ongoing replication, fork restart, telomere maintenance, cellular survival following hydroxyurea or pyridostatin treatment, and suppression of DNA breaks near GC-rich sequences. We find that USP50 supports proper WRN-FEN1 localisation at or near stalled replication forks. Nascent DNA in cells lacking USP50 shows increased association of the DNA2 nuclease and RECQL4 and RECQL5 helicases and replication defects in cells lacking USP50, or FEN1 are driven by these proteins. Consequently, suppression of DNA2 or RECQL4/5 improves USP50-depleted cell resistance to agents inducing replicative stress and restores telomere stability. These data define an unexpected regulatory protein that promotes the balance of helicase and nuclease use at ongoing and stalled replication forks.

'I never see anyone like myself represented in discussions about endometriosis': priorities of LGBTQIA + endometriosis patients in New Zealand.

Limited information is available regarding the experiences and perspectives of LGBTQIA + patients internationally, and no literature exists for New Zealand. Twenty-eight LGBTQIA + endometriosis patients took part in asynchronous, online text-based discussions about their experiences navigating endometriosis diagnosis and management in Aotearoa New Zealand. Their qualitative responses were coded in an iterative thematic manner. The mean delay to diagnosis of this cohort was 10.2 ± 5.6 years from symptom onset, longer than previously reported delays in Aotearoa New Zealand. Participants shared a strong discomfort with the predominant focus of endometriosis management strategies on penetrative sex and pregnancy, and the sense they were dismissed if prioritising these functions was not their priority. Several potential improvements to current treatment and care for LGBTQIA + endometriosis patients were generally agreed upon by the cohort, including research to better understand a practice approach for managing the symptoms of transmasculine patients; expanding the management strategies for patients who are not prioritising fertility and penetrative sex; improving awareness of LGBTQIA + people and experiences amongst medical practitioners to reduce homophobia, transphobia, misogyny, misgendering and mistreatment in care; and the development of gender-neutral spaces for the support of patients who feel uncomfortable in cisgender women-centric endometriosis spaces.

A decade to wait: Update on the average delay to diagnosis for endometriosis in Aotearoa New Zealand.

Endometriosis is a common condition with varying delays from symptom onset to diagnosis reported internationally. In New Zealand, the previously accepted average delay to diagnosis was 8.6-8.7 years. An online survey completed by the largest cohort of self-reported New Zealand-confirmed endometriosis patients (n = 1024) for the collection of delay to diagnosis was conducted in September and October of 2023. The results revealed an average delay of 9.7 ± 7.1 years overall, with a significantly longer delay in the North Island than in the South. This study identifies potential factors for future research that may influence diagnostic delays in New Zealand.

Research priorities of endometriosis patients and supporters in Aotearoa New Zealand.

BACKGROUND: In New Zealand, an estimated 10% of women and people presumed female at birth have endometriosis, a disease characterised by the presence of tissue similar to the lining of the uterus, outside of the uterus. AIMS: The purpose of this study was to characterise the research priorities of New Zealand endometriosis patients and their support networks in alignment with an Australian study. This will allow researchers to be able to ensure their research aligns with closing research gaps prioritised by those who directly experience the impacts of the disease. METHODS AND MATERIALS: There were 1262 responses to an online Qualtrics survey advertised through Endometriosis New Zealand's social media accounts and mailing list to reach endometriosis patients and their support networks. RESULTS: Overall, the highest research priorities for surgically or radiologically confirmed endometriosis patients, clinically suspected endometriosis patients, chronic pelvic pain patients, and their parents, partners, family members and friends were the management and treatment of endometriosis, followed by understanding endometriosis' cause, and improved capacity to diagnose endometriosis earlier. The key differences between the priorities of symptomatic participants and supporters were that symptomatic participants placed a significantly higher priority on understanding the cause of endometriosis, and supporters placed a significantly higher priority on improving the diagnosis of endometriosis. CONCLUSIONS: There is alignment between the ranking of general research priority areas for endometriosis in Australasia, allowing for clear priorities for future research teams to structure their work around patient-centredness.

Visual attention patterns during a gaze following task in neurogenetic syndromes associated with unique profiles of autistic traits: Fragile X and Cornelia de Lange syndromes.

BACKGROUND: Gaze following difficulties are considered an early marker of autism, thought likely to cumulatively impact the development of social cognition, language and social skills. Subtle differences in gaze following abilities may contribute to the diverse range social and communicative autistic characteristics observed across people with genetic syndromes, such as Cornelia de Lange (CdLS) and fragile X (FXS) syndromes. AIMS: To compare profiles of 1) visual attention to the eye region at critical points of the attention direction process, 2) whether children follow the gaze cue to the object, and 3) participant looking time to the target object following the gaze cue between groups and conditions. MATERIALS AND METHODS: Children with CdLS (N = 11) and FXS (N = 8) and autistic (N = 22) and neurotypical (N = 15) children took part in a passive viewing paradigm adapted from Senju and Csibra (2008), in which videos of a central cue (ball/cartoon face/human face) directed attention towards one of two objects. Visual attention patterns were recorded via eye tracking technology. RESULTS: Neurotypical children were used as a reference group against which the autistic, CdLS and FXS groups were compared. Although autistic children looked at the eye region for significantly less time, they looked at the target object as frequently and for a similar duration as neurotypical children. Children with FXS looked at the target as frequently as neurotypical children but looked at it for comparatively less time. Both neurotypical children and children with CdLS frequently looked at the eye region, but children with CdLS were less likely to look at the target than neurotypical children. CONCLUSIONS: Findings provide preliminary evidence of unique patterns of visual attention and gaze following strategies in children with CdLS, children with FXS and autistic children. These unique gaze following patterns may underpin the distinct profiles of social and communication autistic traits observed between these groups.

USP50 suppresses alternative RecQ helicase use and deleterious DNA2 activity during replication.

Mammalian DNA replication employs several RecQ DNA helicases to orchestrate the faithful duplication of genetic information. Helicase function is often coupled to the activity of specific nucleases, but how helicase and nuclease activities are co-directed is unclear. Here we identify the inactive ubiquitin-specific protease, USP50, as a ubiquitin-binding and chromatin-associated protein required for ongoing replication, fork restart, telomere maintenance and cellular survival during replicative stress. USP50 supports WRN:FEN1 at stalled replication forks, suppresses MUS81-dependent fork collapse and restricts double-strand DNA breaks at GC-rich sequences. Surprisingly we find that cells depleted for USP50 and recovering from a replication block exhibit increased DNA2 and RECQL4 foci and that the defects in ongoing replication, poor fork restart and increased fork collapse seen in these cells are mediated by DNA2, RECQL4 and RECQL5. These data define a novel ubiquitin-dependent pathway that promotes the balance of helicase: nuclease use at ongoing and stalled replication forks.

What Role Does "Emotional Medicine" Play in Oncology Nursing?

The Susan D. Flynn Oncology Nursing Fellowship is an eight-week immersive experience that allows rising senior nursing students to gain clinical experience and promotes professional development in oncology nursing.

Dismissal informs the priorities of endometriosis patients in New Zealand.

Introduction: Endometriosis is a common condition with average delays to diagnosis in New Zealand of almost 9 years. Methods: In total, 50 endometriosis patients participated in anonymous, asynchronous, online group discussions about their priorities, and their experiences with the development of symptoms, seeking a diagnosis, and receiving appropriate treatment. Results: Higher subsidy of care was the top change endometriosis patients wanted, followed by more research funding. When asked to choose whether research should be focused on improving diagnosis or improving treatment methods, the results were evenly split. Within this cohort, patients highlighted that they did not know the difference between normal menstrual discomfort and pathological endometriotic pain. If, upon seeking help, medical practitioners classified their symptoms as "normal," these dismissals could instill doubt in patients, which made it more difficult for them to continue to seek a diagnosis and effective treatments. Patients who did not express dismissal had a significantly shorter delay from symptom onset to diagnosis of 4.6 ± 3.4 years vs. 9.0 ± 5.2 years. Conclusion: Doubt is a frequent experience for endometriosis patients in New Zealand, which was reinforced by some medical practitioners who were dismissive of their pain and thus prolonged the patient's delay to diagnosis.

The Comparative Invasiveness of Endometriotic Cell Lines to Breast and Endometrial Cancer Cell Lines.

Endometriosis is an invasive condition that affects 10% of women (and people assigned as female at birth) worldwide. The purpose of this study was to characterize the relative invasiveness of three available endometriotic cell lines (EEC12Z, iEc-ESCs, tHESCs) to cancer cell lines (MDA-MB-231, SW1353 and EM-E6/E7/TERT) and assess whether the relative invasiveness was consistent across different invasion assays. All cell lines were subjected to transwell, spheroid drop, and spheroid-gel invasion assays, and stained for vimentin, cytokeratin, E-Cadherin and N-Cadherin to assess changes in expression. In all assays, endometriotic cell lines showed comparable invasiveness to the cancer cell lines used in this study, with no significant differences in invasiveness identified. EEC12Z cells that had invaded within the assay periods showed declines in E-Cadherin expression compared to cells that had not invaded within the assay period, without significant changes in N-Cadherin expression, which may support the hypothesis that an epithelial-to-mesenchymal transition is an influence on the invasiveness shown by this peritoneal endometriosis cell line.