Baseline measures for women with mesh complications accessing a pain service (as part of the London Complex Mesh Centre).

Introduction: Pelvic mesh was first used for stress urinary incontinence in 1998 following which its usage rapidly expanded to include treatment of pelvic organ prolapse. Numerous complications relating to mesh insertion soon became apparent, culminating in the Independent Medicines and Medical Devices Safety: First Do No Harm Report published by Baroness Cumberlege in 2020. Following this report, the UCLH London Complex Mesh Centre funded by NHS England, was one of a small number of specialist centres set up for mesh-injured women. The Pelvic Pain service of the Pain Management Centre at UCLH provides a service for patients attending the London Complex Mesh Centre. The aim of our study was to distinguish the differing needs of mesh-injured women from those with chronic pelvic pain by comparing patient-reported outcome measures between these two cohorts. Methods: Distribution of data was calculated using the D'Agostino-Pearson normality test. Mann-Whitney tests were used to ascertain statistical difference between the two cohorts. Ethnicity was compared between groups using Fisher's exact test. Quantile regression models were used to assess whether differences in medians between groups remained after adjustment for age and ethnicity. Statistical significance was set at p < .05. Results: Patients with mesh were significantly older than those with chronic pelvic pain and were more likely to be of white ethnicity. After adjustment for age and ethnicity, analysis revealed that bladder interference, sex interference and DAPOS A were significantly higher amongst mesh-injured women, whereas GP and hospital admissions were significantly lower. Discussion: Our data shows the importance of mesh-injured women having access to pain management services with pathways of care integrated within women's and mental health services. It is essential that these programmes include support to discuss ways of returning to sexual relationships and have models to address anxiety such as graded exposure and psychological input.

ESHRE guideline: endometriosis.

STUDY QUESTION: How should endometriosis be diagnosed and managed based on the best available evidence from published literature? SUMMARY ANSWER: The current guideline provides 109 recommendations on diagnosis, treatments for pain and infertility, management of disease recurrence, asymptomatic or extrapelvic disease, endometriosis in adolescents and postmenopausal women, prevention and the association with cancer. WHAT IS KNOWN ALREADY: Endometriosis is a chronic condition with a plethora of presentations in terms of not only the occurrence of lesions, but also the presence of signs and symptoms. The most important symptoms include pain and infertility. STUDY DESIGN SIZE DURATION: The guideline was developed according to the structured methodology for development of ESHRE guidelines. After formulation of key questions by a group of experts, literature searches and assessments were performed. Papers published up to 1 December 2020 and written in English were included in the literature review. PARTICIPANTS/MATERIALS SETTING METHODS: Based on the collected evidence, recommendations were formulated and discussed within specialist subgroups and then presented to the core guideline development group (GDG) until consensus was reached. A stakeholder review was organized after finalization of the draft. The final version was approved by the GDG and the ESHRE Executive Committee. MAIN RESULTS AND THE ROLE OF CHANCE: This guideline aims to help clinicians to apply best care for women with endometriosis. Although studies mostly focus on women of reproductive age, the guideline also addresses endometriosis in adolescents and postmenopausal women. The guideline outlines the diagnostic process for endometriosis, which challenges laparoscopy and histology as gold standard diagnostic tests. The options for treatment of endometriosis-associated pain symptoms include analgesics, medical treatments and surgery. Non-pharmacological treatments are also discussed. For management of endometriosis-associated infertility, surgical treatment and/or medically assisted reproduction are feasible. While most of the more recent studies confirm previous ESHRE recommendations, there are five topics in which significant changes to recommendations were required and changes in clinical practice are to be expected. LIMITATIONS REASONS FOR CAUTION: The guideline describes different management options but, based on existing evidence, no firm recommendations could be formulated on the most appropriate treatments. Also, for specific clinical issues, such as asymptomatic endometriosis or extrapelvic endometriosis, the evidence is too scarce to make evidence-based recommendations. WIDER IMPLICATIONS OF THE FINDINGS: The guideline provides clinicians with clear advice on best practice in endometriosis care, based on the best evidence currently available. In addition, a list of research recommendations is provided to stimulate further studies in endometriosis. STUDY FUNDING/COMPETING INTERESTS: The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with the literature searches and with the dissemination of the guideline. The guideline group members did not receive payments. C.M.B. reports grants from Bayer Healthcare and the European Commission; Participation on a Data Safety Monitoring Board or Advisory Board with ObsEva (Data Safety Monitoring Group) and Myovant (Scientific Advisory Group). A.B. reports grants from FEMaLE executive board member and European Commission Horizon 2020 grant; consulting fees from Ethicon Endo Surgery, Medtronic; honoraria for lectures from Ethicon; and support for meeting attendance from Gedeon Richter; A.H. reports grants from MRC, NIHR, CSO, Roche Diagnostics, Astra Zeneca, Ferring; Consulting fees from Roche Diagnostics, Nordic Pharma, Chugai and Benevolent Al Bio Limited all paid to the institution; a pending patent on Serum endometriosis biomarker; he is also Chair of TSC for STOP-OHSS and CERM trials. O.H. reports consulting fees and speaker's fees from Gedeon Richter and Bayer AG; support for attending meetings from Gedeon-Richter, and leadership roles at the Finnish Society for Obstetrics and Gynecology and the Nordic federation of the societies of obstetrics and gynecology. L.K. reports consulting fees from Gedeon Richter, AstraZeneca, Novartis, Dr KADE/Besins, Palleos Healthcare, Roche, Mithra; honoraria for lectures from Gedeon Richter, AstraZeneca, Novartis, Dr KADE/Besins, Palleos Healthcare, Roche, Mithra; support for attending meetings from Gedeon Richter, AstraZeneca, Novartis, Dr KADE/Besins, Palleos Healthcare, Roche, Mithra; he also has a leadership role in the German Society of Gynecological Endocrinology (DGGEF). M.K. reports grants from French Foundation for Medical Research (FRM), Australian Ministry of Health, Medical Research Future Fund and French National Cancer Institute; support for meeting attendance from European Society for Gynaecological Endoscopy (ESGE), European Congress on Endometriosis (EEC) and ESHRE; She is an advisory Board Member, FEMaLe Project (Finding Endometriosis Using Machine Learning), Scientific Committee Chair for the French Foundation for Research on Endometriosis and Scientific Committee Chair for the ComPaRe-Endometriosis cohort. A.N. reports grants from Merck SA and Ferring; speaker fees from Merck SA and Ferring; support for meeting attendance from Merck SA; Participation on a Data Safety Monitoring Board or Advisory Board with Nordic Pharma and Merck SA; she also is a board member of medical advisory board, Endometriosis Society, the Netherlands (patients advocacy group) and an executive board member of the World Endometriosis Society. E.S. reports grants from National Institute for Health Research UK, Rosetrees Trust, Barts and the London Charity; Royalties from De Gruyter (book editor); consulting fees from Hologic; speakers fees from Hologic, Johnson & Johnson, Medtronic, Intuitive, Olympus and Karl Storz; Participation in the Medicines for Women's Health Expert Advisory Group with Medicines and Healthcare Products Regulatory Agency (MHRA); he is also Ambassador for the World Endometriosis Society. C.T. reports grants from Merck SA; Consulting fees from Gedeon Richter, Nordic Pharma and Merck SA; speaker fees from Merck SA, all paid to the institution; and support for meeting attendance from Ferring, Gedeon Richter and Merck SA. The other authors have no conflicts of interest to declare. DISCLAIMER: This guideline represents the views of ESHRE, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a consensus between the relevant ESHRE stakeholders has been obtained. Adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not replace the need for application of clinical judgement to each individual presentation, nor variations based on locality and facility type. ESHRE makes no warranty, express or implied, regarding the clinical practice guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose (Full disclaimer available at www.eshre.eu/guidelines.).

Basal Cell Carcinoma of Prostate With MSMB-NCOA4 Fusion and a Probable Basal Cell Carcinoma In Situ: Case Report.

Basal cell carcinomas of prostate (BCCP) are very rare. Most arise in the transition zone and thus are associated with lower urinary tract symptoms and rarely associated with elevated prostate-specific antigen (PSA). These features make diagnosis/early diagnosis difficult because of the routine protocols followed. Basal cell carcinomas have distinctive histopathological, immunohistochemical, and to some extent also different molecular characteristics. Basal cell carcinoma in situ (BCCIS) is a nonexistent histological lesion as per the current literature, but here is an attempt to describe it through this case.A 74-year-old man presented with hematuria and previous diagnosis of prostatic hyperplasia. Based on this history, he underwent a prostatectomy ad modum Freyer. Pathological examination surprisingly revealed a diffusely infiltrative tumor with nonacinar adenocarcinoma morphology and many glandular structures probably representing BCCIS. Tumor was diagnosed as BCCP. Patient presented with metastasis to the abdominal wall 8 months postprostatectomy.BCCP is an aggressive type of prostate cancer, which might be challenging to diagnose based on routine protocols. This results in delayed diagnosis and treatment and thus poor prognosis. Furthermore, patients with this subtype of prostate cancer need appropriately designed, and maybe a totally different follow-up regimen as PSA is of no use for BCCP patients. Finally, diagnosis of BCCIS, if agreed upon its existence needs to be studied in larger cohorts as a precursor lesion.

'ReConnect': a model for working with persistent pain patients on improving sexual relationships.

INTRODUCTION: Many individuals with persistent pain experience difficulties with sexual function which are exacerbated by avoidance and anxiety. Due to embarrassment or shame, sexual activity may not be identified as a goal for pain management programmes (PMPs). In addition, clinicians can feel that they lack skills and confidence in addressing these issues. METHODS: We sought to develop a biopsychosocial model for helping patients return to sexual activity and manage relationships in the context of pain management, known as 'ReConnect'. The model amalgamates well-established methods from pain management and sex therapy to guide multidisciplinary team members. ReConnect comprises three components: (1) 'cognitive and myth-busting', (2) 'sensations and feelings' and (3) 'action-experimentation'. We collected self-report data from 281 women and 92 men from our specialist PMP for chronic abdomino-pelvic. pain, including questions measuring interference with and avoidance of sex due to pain, and the Multi-dimensional Sexuality Questionnaire (MSQ) to measure anxiety about sexual activity. RESULTS: The results show statistically significant improvements for anxiety, avoidance of sex and sexual interference. Using the ReConnect model to structure clinical work, pain management clinicians reported increased confidence in addressing sexual activity goals. CONCLUSION: By using the ReConnect model is a framework for clinicians to use to support sexual activity goals. It has demonstrated improvements in clinical outcomes such as anxiety around sex and interference of pain in sexual activity. We encourage its application in pain management services in both one-to-one and group sessions, as a method for encouraging pain patients to address this important area of life which can be adversely affected by pain.

The application of psychologically informed practice: observations of experienced physiotherapists working with people with chronic pain.

OBJECTIVES: Psychologically informed practice (PIP) is advocated for physiotherapists to help people with chronic pain. There is little research observing how PIP is delivered in clinical practice. This study describes behaviours and techniques used by experienced physiotherapists working with groups of people with chronic pain. SETTING AND PARTICIPANTS: Experienced physiotherapists (n=4) were observed working with groups of people with chronic pain in out-patient pain management, and physiotherapy departments, in a large UK city centre teaching hospital. DESIGN: We observed the clinical behaviours and interpersonal skills of experienced psychologically informed physiotherapists, enriched by their accounts of intentions. The physiotherapists were audio and video recorded delivering group movement sessions. Recordings were reviewed with the physiotherapists for elaboration of intentions, then thematically analysed for comparison with defined CBT competencies. RESULTS: Four themes representing physiotherapist intentions when working with people with chronic pain were identified; building a therapeutic alliance, reducing perceived threat, reconceptualising beliefs and somatic experience, and fostering self-efficacy. The physiotherapists also reflected on challenges including engaging patients in self-management, encouraging activity and reinforcing rather than correcting movement. Considerable overlap existed between the observed behaviours in this study and existing CBT competencies. CONCLUSIONS: This paper complements current recommendations for delivering psychologically informed physiotherapy by providing examples of these skills being used in clinical practice. Further research supporting the development of training for, and mentoring of, physiotherapists, to promote competence and confidence in delivering psychologically informed interventions is recommended.

Trigger Point Manual Therapy for the Treatment of Chronic Noncancer Pain in Adults: A Systematic Review and Meta-analysis.

OBJECTIVE: To determine the effectiveness of trigger point manual therapy (TPMT) for reducing chronic noncancer pain and associated problems in adults, by analyzing all relevant randomized controlled trials (RCTs). DATA SOURCES: We searched databases and clinical trials registers from their inception to May 2017. STUDY SELECTION: We included RCTs in any language that recruited patients older than 18, with pain of 3 months' duration or more. We assessed pain, function, and patient-reported improvement as outcomes. DATA EXTRACTION: Two authors independently extracted and verified data. Meta-analysis was completed where possible, otherwise data were synthesized narratively. DATA SYNTHESIS: We combined all data using a random-effects model and assessed the quality of evidence using GRADE. A total of 19 trials (involving 1047 participants) met inclusion criteria, representing TPMT treatment of musculoskeletal, pelvic, and facial pain. No effect was found for short-term pain relief (mean standardized difference -0.53; 95% confidence interval [CI], -1.08 to 0.02). One small study showed a longer-term benefit for pain (mean standardized difference -2.00; 95% CI, -3.40 to -0.60) but with low confidence in the effect. Significant gains emerged for function (mean standardized difference -0.77; 95% CI, -1.27 to -0.26) and in patient global response (odds ratio 3.79; 95% CI, 1.86-7.71) from 4 studies, but not for health-related quality of life. CONCLUSIONS: Evidence for TPMT for chronic noncancer pain is weak and it cannot currently be recommended.

Automatic characterization of dynamics in Absence Epilepsy.

Dynamics of the spike-wave paroxysms in Childhood Absence Epilepsy (CAE) are automatically characterized using novel approaches. Features are extracted from scalograms formed by Continuous Wavelet Transform (CWT). Detection algorithms are designed to identify an estimate of the temporal development of frequencies in the paroxysms. A database of 106 paroxysms from 26 patients was analyzed. The database is large compared to other known studies in the field of dynamics in CAE. CWT is more efficient than the widely used Fourier transform due to CWTs ability to recognize smaller discontinuities and variations. The use of scalograms and the detection algorithms result in a potentially usable clinical tool for dividing CAE patients into subsets. Differences between the grouped paroxysms may turn out to be useful from a clinical perspective as a prognostic indicator or when adjusting drug treatment.

The Na+/H+ exchanger NHE1, but not the Na+, HCO3(-) cotransporter NBCn1, regulates motility of MCF7 breast cancer cells expressing constitutively active ErbB2.

We and others have shown central roles of the Na(+)/H(+) exchanger NHE1 in cell motility. The aim of this study was to determine the roles of NHE1 and of the Na(+), HCO(3)(-) cotransporter NBCn1 in motility of serum-starved MCF-7 breast cancer cells expressing constitutively active ErbB2 (ΔNErbB2). ΔNErbB2 expression elicited NBCn1 upregulation, Ser(703)-phosphorylation of NHE1, and NHE1-inhibitor (EIPA)-sensitive pericellular acidification, in conjunction with increased expression of ß1 integrin and ERM proteins. Active ERM proteins and NHE1 colocalized strongly to invadopodial rosettes, the diameter of which was increased by ΔNErbB2. Adhesion and migration on collagen-I were augmented by ΔNErbB2, unaffected by the NBC inhibitor S0859, and further stimulated by EIPA in a manner potentiated by PI3K-Akt-inhibition. These findings demonstrate that NHE1 inhibition can enhance cancer cell motility, adding an important facet to the understanding of NHE1 in cancer.