Clinical profiling of specific diagnostic subgroups of women with chronic pelvic pain

IntroductionChronic pelvic pain (CPP) is a common condition affecting up to 26.6% of women, with many suffering for several years before diagnosis and/or treatment. Its clinical presentation is varied and there are frequently comorbid conditions both within and outside the pelvis. We aim to explore whether specific subgroups of women with CPP report different clinical symptoms and differing impact of pain on their quality of life (QoL).MethodsThe study is part of the Translational Research in Pelvic Pain (TRiPP) project which is a cross-sectional observational cohort study. The study includes 769 female participants of reproductive age who completed an extensive set of questions derived from standardised WERF EPHect questionnaires. Within this population we defined a control group (reporting no pelvic pain, no bladder pain syndrome, and no endometriosis diagnosis, N = 230) and four pain groups: endometriosis-associated pain (EAP, N = 237), interstitial cystitis/bladder pain syndrome (BPS, N = 72), comorbid endometriosis-associated pain and BPS (EABP, N = 120), and pelvic pain only (PP, N = 127).ResultsClinical profiles of women with CPP (13–50 years old) show variability of clinical symptoms. The EAP and EABP groups scored higher than the PP group (p < 0.001) on the pain intensity scales for non-cyclical pelvic pain and higher than both the BPS and PP groups (p < 0.001) on the dysmenorrhoea scale. The EABP group also had significantly higher scores for dyspareunia (p < 0.001), even though more than 50% of sexually active participants in each pain group reported interrupting and/or avoiding sexual intercourse due to pain in the last 12 months. Scores for the QoL questionnaire (SF-36) reveal that CPP patients had significantly lower QoL across all SF-36 subscales (p < 0.001). Significant effects were also observed between the pain groups for pain interference with their work (p < 0.001) and daily lives (p < 0.001), with the EABP suffering more compared to the EAP and PP groups (p < 0.001).DiscussionOur results demonstrate the negative impact that chronic pain has on CPP patients' QoL and reveal an increased negative impact of pain on the comorbid EABP group. Furthermore, it demonstrates the importance of dyspareunia in women with CPP. Overall, our results demonstrate the need for further exploration of interventions targeting QoL more broadly and suggest that novel approaches to classifying women with CPP are needed

Clinical profiling of specific diagnostic subgroups of women with chronic pelvic pain

Introduction: Chronic pelvic pain (CPP) is a common condition affecting up to 26.6% of women, with many suffering for several years before diagnosis and/or treatment. Its clinical presentation is varied and there are frequently comorbid conditions both within and outside the pelvis. We aim to explore whether specific subgroups of women with CPP report different clinical symptoms and differing impact of pain on their quality of life (QoL). Methods: The study is part of the Translational Research in Pelvic Pain (TRiPP) project which is a cross-sectional observational cohort study. The study includes 769 female participants of reproductive age who completed an extensive set of questions derived from standardised WERF EPHect questionnaires. Within this population we defined a control group (reporting no pelvic pain, no bladder pain syndrome, and no endometriosis diagnosis, N = 230) and four pain groups: endometriosis-associated pain (EAP, N = 237), interstitial cystitis/bladder pain syndrome (BPS, N = 72), comorbid endometriosis-associated pain and BPS (EABP, N = 120), and pelvic pain only (PP, N = 127). Results: Clinical profiles of women with CPP (13–50 years old) show variability of clinical symptoms. The EAP and EABP groups scored higher than the PP group (p p p p p p p  Discussion: Our results demonstrate the negative impact that chronic pain has on CPP patients' QoL and reveal an increased negative impact of pain on the comorbid EABP group. Furthermore, it demonstrates the importance of dyspareunia in women with CPP. Overall, our results demonstrate the need for further exploration of interventions targeting QoL more broadly and suggest that novel approaches to classifying women with CPP are needed

Safety of growth hormone replacement in survivors of cancer and intracranial and pituitary tumours: a consensus statement

Growth hormone (GH) has been used for over 35 years, and its safety and efficacy has been studied extensively. Experimental studies showing the permissive role of GH/insulin-like growth factor 1 (IGF-I) in carcinogenesis have raised concerns regarding the safety of GH replacement in children and adults who have received treatment for cancer and those with intracranial and pituitary tumours. A consensus statement was produced to guide decision-making on GH replacement in children and adult survivors of cancer, in those treated for intracranial and pituitary tumours and in patients with increased cancer risk. With the support of the European Society of Endocrinology, the Growth Hormone Research Society convened a Workshop, where 55 international key opinion leaders representing 10 professional societies were invited to participate. This consensus statement utilized: (1) a critical review paper produced before the Workshop, (2) five plenary talks, (3) evidence-based comments from four breakout groups, and (4) discussions during report-back sessions. Current evidence reviewed from the proceedings from the Workshop does not support an association between GH replacement and primary tumour or cancer recurrence. The effect of GH replacement on secondary neoplasia risk is minor compared to host- and tumour treatment-related factors. There is no evidence for an association between GH replacement and increased mortality from cancer amongst GH-deficient childhood cancer survivors. Patients with pituitary tumour or craniopharyngioma remnants receiving GH replacement do not need to be treated or monitored differently than those not receiving GH. GH replacement might be considered in GH-deficient adult cancer survivors in remission after careful individual risk/benefit analysis. In children with cancer predisposition syndromes, GH treatment is generally contraindicated but may be considered cautiously in select patients

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Comorbid chronic pain and opioid misuse in youth: Knowns, unknowns, and implications for behavioral treatment

Chronic pain and opioid misuse are both common in pediatric populations and associated with a range of negative adverse outcomes that may persist into adulthood. While the association between chronic pain, opioid prescribing, and opioid-related adverse consequences is reasonably well established in adults, the relation in pediatric patients is not well understood and the long-term impact of opioid exposure during childhood is yet to be fully revealed. The present review draws from the available literature on chronic and acute pediatric pain prevalence and treatment, opioid misuse, and adolescent substance use to address knowns and unknowns of co-morbid pediatric chronic pain and opioid misuse. Additionally, gaps in knowledge regarding the prevalence and etiology of co-occurring chronic pain and opioid misuse in youth are identified. Hypothesized, modifiable risk factors associated with both pediatric pain and opioid misuse are considered. Due to a lack of empirically supported integrated treatments for co-morbid chronic pain and opioid misuse in youth, this review examines the evidence base and best practices from both the chronic pain and opioid treatment literature to guide treatment recommendations for these co-morbid conditions in youth. Recommendations are then provided to promote screening and mitigate risk of chronic pain and opioid misuse across a range of pediatric settings. Lastly, a comprehensive agenda to prevent and treat chronic pain and opioid misuse in adolescents and young adults is discussed

Exploring Comorbidities in Adolescent and Young Adults with Hypermobile Ehlers–Danlos Syndrome with and without a Surgical History: A Preliminary Investigation

Ehlers–Danlos Syndrome (EDS) is a rare disease affecting the skin, joints, vasculature, and internal organs. Approximately 85% of those affected are categorized as the hypermobile type (hEDS), which is associated with numerous medical and psychiatric comorbidities, including chronic pain. Additionally, approximately 71% of patients with hEDS undergo at least one surgical procedure; however, indicators for surgery and pain outcomes after surgery are poorly understood. This preliminary study used a medical chart review to identify the frequency and nature of comorbidities in a cohort of adolescents and young adult patients with hEDS and a surgical history compared to those without a surgical history. Results showed that patients diagnosed with hEDS who underwent surgery reported significantly more comorbidities (e.g., CRPS, IBS, Fibromyalgia, POTS, hypothyroidism, etc.) than those who did not have surgery. Seventy percent of individuals who presented for surgery fell within the categories of orthopedic, gastrointestinal, or laparoscopic/endometriosis-related surgeries. Identifying patients with hEDS who are at risk for needing surgery will help identify the mechanisms contributing to risk factors for poor surgical outcomes. The results of this study may be instructive in the management and care of hEDS patients undergoing surgery

Table2_Quantitative sensory testing in a magnetic resonance environment: considerations for thermal sensitivity and patient safety.docx

IntroductionQuantitative sensory testing (QST) is often used to understand the perceptual basis of acute and chronic conditions, including pain. As the need grows for developing a mechanistic understanding of neurological pathways underlying perception in the basic and clinical sciences, there is a greater need to adapt techniques such as QST to the magnetic resonance (MR) environment. No studies have yet evaluated the impact of the MR environment on the perception of thermal stimuli. This study aimed to evaluate the differences in temperature sensitivity outside an MR environment and during an MRI scanning session. We hypothesized that there would be a difference in how participants reported their pain sensitivity between the two environments.MethodsHealthy participants underwent thermal QST outside the MR scanning environment, where they were asked to rate the temperature of a noxious stimulus at which they perceived their pain to be 7/10, using a Likert scale ranging from 0 to 10. Participants repeated this procedure inside a 3.0 T MRI approximately 30 min later. We repeated our investigation in a clinical cohort of participants with a chronic pain condition.ResultsThere were statistically significant changes of 1.1°C in thermal sensitivity between environments. This increase in pain threshold was found in healthy participants and replicated in the clinical cohort.DiscussionFindings can be applied toward improving MR safety, the resolution of brain pathways underlying pain mechanisms, and to more broadly comment on the impact of the MR environment on investigations that integrate perception-influenced processes.</p

Table1_Quantitative sensory testing in a magnetic resonance environment: considerations for thermal sensitivity and patient safety.docx

IntroductionQuantitative sensory testing (QST) is often used to understand the perceptual basis of acute and chronic conditions, including pain. As the need grows for developing a mechanistic understanding of neurological pathways underlying perception in the basic and clinical sciences, there is a greater need to adapt techniques such as QST to the magnetic resonance (MR) environment. No studies have yet evaluated the impact of the MR environment on the perception of thermal stimuli. This study aimed to evaluate the differences in temperature sensitivity outside an MR environment and during an MRI scanning session. We hypothesized that there would be a difference in how participants reported their pain sensitivity between the two environments.MethodsHealthy participants underwent thermal QST outside the MR scanning environment, where they were asked to rate the temperature of a noxious stimulus at which they perceived their pain to be 7/10, using a Likert scale ranging from 0 to 10. Participants repeated this procedure inside a 3.0 T MRI approximately 30 min later. We repeated our investigation in a clinical cohort of participants with a chronic pain condition.ResultsThere were statistically significant changes of 1.1°C in thermal sensitivity between environments. This increase in pain threshold was found in healthy participants and replicated in the clinical cohort.DiscussionFindings can be applied toward improving MR safety, the resolution of brain pathways underlying pain mechanisms, and to more broadly comment on the impact of the MR environment on investigations that integrate perception-influenced processes.</p

Stressful experiences impact clinical symptoms in people with endometriosis

Endometriosis is a chronic condition that affects ~10% of women globally. Its symptoms include chronic pelvic pain, heavy periods and tiredness/fatigue, which have been associated with poorer quality of life and mental health. We aim to explore the impact of the COVID-19 pandemic on pain and fatigue symptoms and their interactions with the impact on mental health in people with endometriosis. This global cross-sectional online survey study collected data from 4717 adults with self-reported surgical/radiological diagnosis of endometriosis between May and June 2020. The survey included questions on the current status and changes of endometriosis symptoms (pelvic pain, tiredness/fatigue, and bleeding patterns), mental health, pain catastrophising, and the impact of the COVID-19 pandemic on the respondents’ lives. Compared to 6 months earlier, Respondents reported a marked worsening of their endometriosis symptoms (endometriosis-associated pain (39.3%; 95% CI: 37.7, 40.5), tiredness/fatigue (49.9%; 95% CI: 48.4, 51.2) and bleeding patterns (39.6%; 95% CI: 38.2, 41)) and mental health (38.6%; 95% CI: 37.2, 39.9). Those with a pre-existing mental health diagnosis (38.8%) were more likely to report their symptoms worsening. Worsening of pain and tiredness/fatigue was significantly correlated with worsening of mental health (P