Symptom tracking in endometriosis using digital technologies: Knowns, unknowns, and future prospects.

Endometriosis is a common chronic pain condition with no known cure and limited treatment options. Digital technologies, ranging from smartphone apps to wearable sensors, have shown potential toward facilitating chronic pain assessment and management; however, to date, many of these tools have not been specifically deployed or evaluated in patients with endometriosis-associated pain. Informed by previous studies in related chronic pain conditions, we discuss how digital technologies may be used in endometriosis to facilitate objective, continuous, and holistic symptom tracking. We postulate that these pervasive and increasingly affordable technologies present promising opportunities toward developing decision-support tools assisting healthcare professionals and empowering patients with endometriosis to make better-informed choices about symptom management.

Self-management strategies to consider to combat endometriosis symptoms during the COVID-19 pandemic.

The care of patients with endometriosis has been complicated by the coronavirus disease 2019 (COVID-19) pandemic. Medical and allied healthcare appointments and surgeries are being temporarily postponed. Mandatory self-isolation has created new obstacles for individuals with endometriosis seeking pain relief and improvement in their quality of life. Anxieties may be heightened by concerns over whether endometriosis may be an underlying condition that could predispose to severe COVID-19 infection and what constitutes an appropriate indication for presentation for urgent treatment in the epidemic. Furthermore, the restrictions imposed due to COVID-19 can impose negative psychological effects, which patients with endometriosis may be more prone to already. In combination with medical therapies, or as an alternative, we encourage patients to consider self-management strategies to combat endometriosis symptoms during the COVID-19 pandemic. These self-management strategies are divided into problem-focused and emotion-focused strategies, with the former aiming to change the environment to alleviate pain, and the latter address the psychology of living with endometriosis. We put forward this guidance, which is based on evidence and expert opinion, for healthcare providers to utilize during their consultations with patients via telephone or video. Patients may also independently use this article as an educational resource. The strategies discussed are not exclusively restricted to consideration during the COVID-19 pandemic. Most have been researched before this period of time and all will continue to be a part of the biopsychological approach to endometriosis long after COVID-19 restrictions are lifted.

A two-arm parallel double-blind randomised controlled pilot trial of the efficacy of Omega-3 polyunsaturated fatty acids for the treatment of women with endometriosis-associated pain (PurFECT1).

BACKGROUND: Endometriosis is defined by the presence of endometrial-like tissue (lesions) outside the uterus, commonly on the pelvic peritoneum. It affects 6-10% of women and is associated with debilitating pelvic pain. Current management options are often unsatisfactory. Omega-3 polyunsaturated fatty acids (O-PUFA) have the potential to reduce the painful symptoms associated with endometriosis, reduce lesion size, preserve the patient's ability to conceive, and have minimal side effects. We performed a two-arm, parallel double-blinded randomised controlled trial to inform the planning of a future multicentre randomised controlled trial to evaluate the efficacy of O-PUFA for endometriosis-associated pain. OBJECTIVES: The primary objectives of the trial were to assess recruitment and retention rates. The secondary objectives were to determine the acceptability to women of the proposed methods of recruitment, randomisation, treatments and questionnaires, to estimate the variability in the proposed primary endpoints to inform the sample size calculation and to refine the research methodology for the future definitive trial. METHODS: We recruited women with endometriosis from June 2016 to June 2017 and randomised them to eight weeks of treatment with O-PUFA or olive oil. Pain scores and quality of life questionnaires were collected at baseline and eight weeks. We calculated the proportion of eligible women randomised, and of randomised participants who were followed up to eight weeks. Acceptability questionnaires were used to evaluate women's experiences of the trial. RESULTS: The proportion of eligible participants who were randomised was 45.2% (33/73) and 81.8% (27/33) completed the study. The majority of participants described their overall trial experience favourably and there were no adverse events in either group. CONCLUSION: Our pilot trial supports the feasibility of a future larger trial to definitively evaluate the efficacy of O-PUFA for endometriosis-associated pain. TRIAL REGISTRATION: The trial was registered on the ISRCTN registry (registration number ISRCTN44202346).

Chronic pelvic pain in women: an embedded qualitative study to evaluate the perceived benefits of the meridian balance method electro-acupuncture treatment, health consultation and National Health Service standard care.

INTRODUCTION: Chronic pelvic pain (CPP) - defined as intermittent or constant pain in the lower abdomen or pelvis of at least 6 months' duration, not occurring exclusively with menstruation or intercourse and not associated with pregnancy - is estimated to affect 6-27% of women worldwide. In the United Kingdom, over 1 million women suffer from CPP, which has been highlighted as a key area of unmet need. Current medical treatments for CPP are often associated with unacceptable side effects. A specific style of acupuncture, the meridian balance method electro-acupuncture (BMEA) and traditional Chinese medicine health consultation (TCM HC (BMEA + TCM HC = BMEA treatment)), may be effective for CPP in women. AIM: Three focus group discussions and semi-structured telephone interviews were embedded in a randomised controlled feasibility trial to gain in-depth description of the perceived benefits of the participants' respective interventions. METHODS: Women with CPP were randomised into the BMEA treatment, TCM HC or National Health Service standard care (NHS SC). Focus group discussions were recorded, transcribed and analysed thematically. Semi-structured telephone interviews were conducted post focus group discussions. FINDINGS: A total of 30 women were randomised into BMEA treatment, TCM HC or NHS SC. A total of 11 participants attended the three focus group discussions. Thematic analysis of focus group discussions showed: a perceived pain reduction, enhanced sleep, energy level and sense of well-being in the BMEA treatment and TCM HC groups; a dislike for the adverse effects of medications, frustration at the lack of effective treatment, heavy reliance on medications and services that are helpful, in the NHS SC group. Semi-structured telephone interviews showed that the methodology was acceptable to the participants. CONCLUSION: The embedded focus group discussions captured the rich and complex narratives of the participants and provided insights into the perceived benefits of the BMEA treatment, TCM HC and NHS SC interventions.

The impact of meridian balance method electro-acupuncture treatment on chronic pelvic pain in women: a three-armed randomised controlled feasibility study using a mixed-methods approach.

INTRODUCTION: Chronic pelvic pain (CPP) is estimated to affect 6%-27% of women worldwide. In the United Kingdom, over 1 million women suffer from CPP and it has been highlighted as a key area of unmet need. Standard treatments are associated with unacceptable side effects. The meridian balance method electro-acupuncture (BMEA), and traditional Chinese medicine health consultation (TCM HC) (BMEA + TCM HC = BMEA treatment) may be an effective adjunct to standard treatment. AIM: The aim of our study was to evaluate the feasibility of a future trial, to determine the effectiveness of the BMEA treatment for CPP in women. The primary objectives were to determine recruitment and retention rates. The secondary objectives were to assess the effectiveness of the BMEA treatment and acceptability of the study's methodology. METHODS: Women with CPP were randomised into BMEA treatment (group 1), TCM HC alone (group 2) (each intervention administered twice weekly for 4 weeks) or National Health Service standard care (NHS SC, group 3). Primary outcomes were assessed by the proportion of eligible participants randomised, and the proportion of randomised participants who returned follow-up questionnaires. Interventions were assessed by validated pain/physical/emotional functioning questionnaires at baseline (0), 4, 8 and 12 weeks. Focus groups and semi-structured telephone interviews were embedded in the study. RESULTS: A total of 30 women (51% of those referred) were randomised over 8 months. Retention rates were 80% (95% confidence interval (CI): 74-96), 53% (95% CI: 36-70) and 87% (95% CI: 63-90), in groups 1, 2, and 3, respectively. Qualitative data suggested a favourable trial experience in groups 1 and 3. DISCUSSION: Group 2 retention rate was problematic and has implications for our next trial. CONCLUSION: Our study suggests that a future trial to determine the effectiveness of BMEA treatment for women with CPP is feasible but with modifications to the study design.

A pilot randomised double blind controlled trial of the efficacy of purified fatty acids for the treatment of women with endometriosis-associated pain (PurFECT): study protocol.

BACKGROUND: Endometriosis affects 6-10% of women and is associated with debilitating pelvic pain. It costs the UK > £2.8 billion per year in loss of productivity. Endometriosis can be managed by surgical excision or medically by ovarian suppression. However, ~ 75% symptoms recur after surgery and available medical treatments have undesirable side effects and are contraceptive. Omega-3 purified fatty acids (PUFA) have been shown in animal models to reduce factors that are thought to lead to endometriosis-associated pain, have minimal side effects, and no effects on fertility. This paper presents a protocol for a two-arm, pilot parallel randomised controlled trial (RCT) which aims to inform the planning of a future multicentre trial to evaluate the efficacy of Omega-3 PUFA in the management of endometriosis-associated pain in women. METHODS: The study will recruit women with endometriosis over a 12-month period in the National Health Service (NHS) Lothian, UK, and randomise them to 8 weeks of treatment with Omega-3 PUFA or comparator (olive oil). The primary objective is to assess recruitment and retention rates. The secondary objectives are to determine the effectiveness/acceptability to participants of the proposed methods of recruitment/randomisation/treatments/questionnaires, to inform the sample size calculation and to refine the research methodology for a future large randomised controlled trial. Response to treatment will be monitored by pain scores and questionnaires assessing physical and emotional function compared at baseline and 8 weeks. DISCUSSION: We recognise that there may be potential difficulties in mounting a large randomised controlled trial for endometriosis to assess Omega-3 PUFA because they are a dietary supplement readily available over the counter and already used by women with endometriosis. We have therefore designed this pilot study to assess practical feasibility and following the 'Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials' recommendations for the design of chronic pain trials. TRIAL REGISTRATION: ISRCTN44202346.

Pharmaceutical treatments to prevent recurrence of endometriosis following surgery: a model-based economic evaluation.

OBJECTIVE: Conduct an economic evaluation based on best currently available evidence comparing alternative treatments levonorgestrel-releasing intrauterine system, depot-medroxyprogesterone acetate, combined oral contraceptive pill (COCP) and 'no treatment' to prevent recurrence of endometriosis after conservative surgery in primary care, and to inform the design of a planned trial-based economic evaluation. METHODS: We developed a state transition (Markov) model with a 36-month follow-up. The model structure was informed by a pragmatic review and clinical experts. The economic evaluation adopted a UK National Health Service perspective and was based on an outcome of incremental cost per quality-adjusted life year (QALY). As available data were limited, intentionally wide distributions were assigned around model inputs, and the average costs and outcome of the probabilistic sensitivity analyses were reported. RESULTS: On average, all strategies were more expensive and generated fewer QALYs compared to no treatment. However, uncertainty attributing to the transition probabilities affected the results. Inputs relating to effectiveness, changes in treatment and the time at which the change is made were the main causes of uncertainty, illustrating areas where robust and specific data collection is required. CONCLUSIONS: There is currently no evidence to support any treatment being recommended to prevent the recurrence of endometriosis following conservative surgery. The study highlights the importance of developing decision models at the outset of a trial to identify data requirements to conduct a robust post-trial analysis.

The BMEA study: the impact of meridian balanced method electroacupuncture on women with chronic pelvic pain-a three-arm randomised controlled pilot study using a mixed-methods approach.

INTRODUCTION: Chronic pelvic pain (CPP) affects 3-4% of women worldwide. Proven treatments for CPP are limited and unsatisfactory. The meridian balance method (BM) electroacupuncture (EA) treatment (BMEA + Traditional Chinese Medicine Health Consultation (TCM HC) may be effective for CPP. Previous EA studies have demonstrated an analgesic effect. Large-scale studies on acupuncture for other chronic pain conditions suggest that patient-healthcare provider interaction might play a role in pain reduction. We propose a pilot study to explore the effectiveness of the meridian BMEA treatment in managing women with CPP to inform a future large randomised controlled trial. METHODS AND ANALYSIS: A 3-armed randomised controlled pilot study is proposed with an aim to recruit 30 women with CPP in National Health Service (NHS) Lothian. Randomisation will be to BMEA treatment, TCM HC or standard care (SC). Validated pain, physical and emotional functioning questionnaires will be administered to all participants at weeks 0, 4, 8 and 12. Focus group discussions will be conducted when week 12 questionnaires are completed. The primary objective is to determine, recruitment and retention rates. The secondary objectives are to assess the effectiveness and acceptability of the proposed methods of recruitment, randomisation, interventions and assessment tools. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Scotland Research Ethics Committee (REC 14/SS/1022). Data will be published in peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: NCT02295111.

Effects of gefitinib, an epidermal growth factor receptor inhibitor, on human placental cell growth.

OBJECTIVE: Placenta has the highest expression of epidermal growth factor (EGF) receptor of all tissues, a cell signaling pathway promoting survival and growth. Therefore, EGF receptor inhibition could potentially treat ectopic pregnancy. We undertook preclinical studies to examine whether gefitinib (orally available EGF receptor inhibitor) with or without methotrexate inhibits placental cell growth. METHODS: Gefitinib and methotrexate were added to placental cells and their ability inhibit cell growth, block EGF receptor signaling, and induce apoptosis (programmed cell death) was examined. They were also administered to two animal mouse models to examine their effects on placental tissue in vivo. RESULTS: Epidermal growth factor receptor was highly expressed in placental tissue from ectopic pregnancies. Combining gefitinib with methotrexate potently inhibited growth of placental cells, including placental cell lines (JEG3, BeWo cells) and cells isolated from first-trimester placenta. These drugs were additive in blocking EGF receptor signaling and inducing apoptosis. Gefitinib and methotrexate administered together were more potent in decreasing the volume of human placental cells xenografted subcutaneously onto mice compared with either alone. By day 19 after xenografting, mean (± standard error of the mean), xenograft volumes were: 821 (± 68) mm after gefitinib treatment, 901 (± 204) mm after methotrexate treatment, and 345 (±137) mm after both drugs were given (P<.01 for both comparisons of single therapy compared with combination therapy). Combining these agents doubled rates of fetal resorption in pregnant mice compared with each drug alone. CONCLUSION: Combining gefitinib with methotrexate potently inhibits placental cell growth in vitro and in mouse models. The combination may have potential in treating ectopic pregnancies.