Treatment recommendations for the management of persistent pelvic pain: a systematic review of international clinical practice guidelines.

BACKGROUND: Females with persistent pelvic pain (PPP) report great variability in the treatments recommended to them despite the availability of clinical practice guidelines (CPGs) that aim to standardise care. A clear consensus for the best practice care for PPP is required. OBJECTIVE: To identify and summarise treatment recommendations across CPGs for the management of PPP, and appraise their quality. SEARCH STRATEGY: MEDLINE, CENTRAL, EMBASE, EmCare, SCOPUS, the Cochrane Database of Systematic Reviews, Web of Science Core Collection and relevant guideline databases were searched from their inception to June 2021. SELECTION CRITERIA: Included CPGs were those for the management of urogynaecological conditions in adult females published in English, of any publication date, and endorsed by a professional organisation or society. DATA COLLECTION AND ANALYSIS: We screened 1379 records and included 20 CPGs. CPG quality was assessed using The Appraisal of Guidelines for Research and Evaluation II (AGREE-II) tool. Descriptive synthesis compiled treatment recommendations across CPGs. MAIN RESULTS: The CPGs for seven conditions provided 270 individual recommendations. On quality appraisal, guidelines on average scored 'excellent' for the domains 'scope and purpose' (80.6%, SD = 13.3) and 'clarity and presentation' (74.4%, SD = 12.0); for other domains, average scores were satisfactory or poor. Four guidelines (for Endometriosis: NICE, RANZCOG and ESHRE; for polycystic ovary syndrome: Teede et al. 2018, International Evidence Based Guideline for the Assessment and Management of Polycystic Ovary Syndrome, Monash University, Melbourne, Australia) were deemed recommended for use. Recommendations were most frequent for pharmaceutical and surgical interventions. Recommendations were variable for psychological, physiotherapy and other conservative interventions. CONCLUSIONS: The quality of CPGs for PPP is generally poor. Several CPGs endorse the consideration of biopsychosocial elements of PPP. Yet most recommend pharmaceutical, surgical and other biomedical interventions.

Autoreactive T cell responses show proinflammatory polarization in diabetes but a regulatory phenotype in health.

According to the quality of response they mediate, autoreactive T cells recognizing islet beta cell peptides could represent both disease effectors in the development of type 1 diabetes (T1DM) and directors of tolerance in nondiabetic individuals or those undergoing preventative immunotherapy. A combination of the rarity of these cells, inadequate technology, and poorly defined epitopes, however, has hampered examination of this paradigm. We have identified a panel of naturally processed islet epitopes by direct elution from APCs bearing HLA-DR4. Employing these epitopes in a sensitive, novel cytokine enzyme-linked immunosorbent spot assay, we show that the quality of autoreactive T cells in patients with T1DM exhibits extreme polarization toward a proinflammatory Th1 phenotype. Furthermore, we demonstrate that rather than being unresponsive, the majority of nondiabetic, HLA-matched control subjects also manifest a response against islet peptides, but one that shows extreme T regulatory cell (Treg, IL-10-secreting) bias. We conclude that development of T1DM depends on the balance of autoreactive Th1 and Treg cells, which may be open to favorable manipulation by immune intervention.