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Objective To examine the impact of educational materials for chronic overlapping pain conditions (COPCs), the feasibility of delivering materials online, and to explore its impact on self-reported self-management applications at 3-month follow-up. Design Prospective cohort study Setting Online Subjects Individuals from a university-wide active research repository with ≥1 coded diagnostic COPC by ICD-9/10 in the medical record. Methods We determined the number of COPCs per participant as indicated by diagnostic codes in the medical record. Consenting participants completed self-report questionnaires and read educational materials. We assessed content awareness and knowledge pre- and post-exposure to education. Comprehension was assessed via embedded questions in reading materials in real time. Participants then completed assessments regarding concept retention, self-management engagement, and pain-related symptoms at 3-months. Results N = 216 individuals enrolled, with 181 (84%) completing both timepoints. Results indicated that participants understood materials. Knowledge and understanding of COPCs increased significantly after education and was retained at 3-months. Patient characteristics suggested the number of diagnosed COPCs was inversely related to age. Symptoms or self-management application did not change significantly over the 3-month period. Conclusions The educational materials facilitated teaching of key pain concepts in self-management programs, which translated easily into an electronic format. Education alone may not elicit self-management engagement or symptom reduction in this population; however, conclusions are limited by the study's uncontrolled design. Education is likely an important and meaningful first step in comprehensive COPC self-management. [ABSTRACT FROM AUTHOR]

A response from author of the article "Bruton's tyrosine kinase promotes persistence of mature anti-insulin B cells" that was published in a previous issue is presented.

Objective: The goal of this study was to examine the cost-effectiveness of fulvestrant 500 mg for the treatment of first progression or recurrence of advanced breast cancer in postmenopausal patients compared with generic nonsteroidal aromatase inhibitors (anastrozole and letrozole) in the United Kingdom. Methods: A cost-utility model based on a time-instate approach was used. Clinical effectiveness estimates used in the model were derived from a network meta-analysis for overall survival and serious adverse events. Overall survival was extrapolated by using a Weibull distribution, and progression-free survival (PFS) estimates were derived from a simultaneous network meta-analysis and extrapolation of PFS curves by using the log-normal distribution. Data on resource use, costs, and utilities were based on various sources, including expert opinion and published data. To explore uncertainty, 1-way and probability sensitivity analyses were conducted. The study was conducted from the perspective of the UK National Health Service, and costs are reported in 2010/2011 British pounds. Results: The base case incremental cost-effectiveness ratio (ICER) for fulvestrant 500 mg versus letrozole was £34,528, with incremental costs of £14,383 and an incremental quality-adjusted life-year (QALY) of 0.417. Extended dominance occurred for anastrozole because the ICER for anastrozole versus letrozole was higher than the ICER for fulvestrant 500 mg versus anastrozole. Based on the probability sensitivity analyses, the probability that fulvestrant 500 mg was the most cost-effective treatment option was 3%, 20%, and 53% at a willingness-to-pay threshold of £20,000, £30,000, and £40,000 per QALY, respectively. According to the 1-way sensitivity analyses, the PFS estimates were the key drivers of the model results. Conclusions: Although fulvestrant 500 mg was found not to be a cost-effective option at a standard UK threshold of £20,000 to £30,000 per QALY, it may be relevant to apply a higher threshold due to the poor prognosis of patients with advanced breast cancer and the limited number of hormonal treatment options available for this stage of treatment. Certain subgroups may also benefit from fulvestrant as a treatment option; however, limited data are currently available to identify these subgroups. (Clin Ther. 2013;35:246-260) © 2013 Elsevier HS Journals, Inc. All rights reserved [ABSTRACT FROM AUTHOR]

Abstract: Objectives: A chronic illness such as fibromyalgia can interfere with daily activities and goals by limiting available resources, including time and energy. This leads to competition between goals, known as goal conflict. The purpose of this study was to determine if goal conflict increases symptoms in women with fibromyalgia and whether symptoms lead to perceptions of goal conflict. Methods: Women with fibromyalgia (N=27) recorded their pain, emotional distress, and fatigue each morning and evening for five consecutive days. Each evening, they listed that day''s goals, rating goals on their level of conflict. Goal conflict was also rated by independent raters, and a difference score reflected goal conflict discrepancy. Results: On days with higher goal conflict, pain increased more from morning to evening (γ=1.71, 95% confidence interval=0.32–3.09, P<.05). On days with higher morning emotional distress, goal conflict was overestimated (γ=0.075, 95% confidence interval=0.035–0.116, P<.05). Women who had a higher symptom burden also typically overestimated their goal conflict relative to those with fewer symptoms (P<.05 for all). Conclusions: Goal pursuit may deplete psychological and physical resources in this vulnerable population, resulting in higher pain. Conversely, emotional distress may affect perception of goal conflict, resulting in less ambitious goal pursuit. Understanding the dynamic relationship between goal conflict and fibromyalgia symptoms may lead to more effective management of limited resources and pursuit of daily goals with fibromyalgia. [Copyright &y& Elsevier]

Aim: To test the hypothesis that rheumatoid arthritis (RA) influenced levels of salivary biomarkers of periodontal disease. Methods: Medical assessments, periodontal examinations and pain ratings were obtained from 35 RA, 35 chronic periodontitis and 35 age- and gender-matched healthy controls in a cross-sectional, case-controlled study. Unstimulated whole saliva samples were analysed for interleukin-1β (IL-1β), matrix metalloproteinase-8 (MMP-8) and tumour necrosis factor-a (TNF-α) concentrations. Results: The arthritis and healthy groups had significantly less oral disease than the periodontitis group (P<0.0001), with the arthritis group having significantly more sites bleeding on probing (BOP) than matched controls (P=0.012). Salivary levels of MMP-8 and IL-1β were significantly elevated in the periodontal disease group (P<0.002), and IL-1β was the only biomarker with significantly higher levels in the arthritis group compared with controls (P=0.002). Arthritis patients receiving anti-TNF-α antibody therapy had significantly lower IL-1β and TNF-α levels compared with arthritis patients not on anti-TNF-α therapy (P=0.016, 0.024) and healthy controls (P<0.001, P=0.011), respectively. Conclusion: RA patients have higher levels of periodontal inflammation than healthy controls, i.e., an increased BOP. Systemic inflammation appears to influence levels of select salivary biomarkers of periodontal disease, and anti-TNF-α antibody-based disease-modifying therapy significantly lowers salivary IL-1β and TNF-α levels in RA. [ABSTRACT FROM AUTHOR]

The use of opioids for the treatment of chronic pain has increased dramatically over the past decade. Whether these drugs provide considerable benefits in terms of pain reduction and improved function to balance the risks associated with their use, however, is unclear. Of particular importance to clinicians treating chronic musculoskeletal pain is opioid-induced hyperalgesia, the activation of pronociceptive pathways by exogenous opioids that results in central sensitization to pain. This phenomenon results in an increase in pain sensitivity and can potentially exacerbate pre-existing pain. Opioids also have powerful positive effects on the reward and reinforcing circuits of the brain that might lead to continued drug use, even if there is no abuse or misuse. The societal risk of increased opioid prescription is associated with increased nonmedical use, serious adverse events and death. Patients with chronic musculoskeletal pain should avoid the long-term use of opioids unless the benefits are determined to outweigh risks, in which case, the use of chronic opioids should be regularly re-evaluated. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Sleep disturbances are common in patients with fibromyalgia (FM). The objective of this analysis was to evaluate the effects of pregabalin on sleep in patients with FM. Methods: Analyses were based on two randomized, double-blind, placebo-controlled trials of pregabalin (300mg, 450mg, and 600mg daily) in adult FM patients. Sleep outcomes included the Medical Outcomes Study (MOS) Sleep Scale and a daily diary assessment of sleep quality. Treatment effects were evaluated using analysis of covariance. Clinically important differences (CID) in the Sleep Quality Diary and MOS Sleep Disturbance scores were estimated using mixed-effects models of changes in scores as a function of patients’ global impressions of change. Mediation modeling was used to quantify the direct treatment effects on sleep in contrast to indirect influence of the treatment on sleep via pain. Results: A total of 748 and 745 patients were randomized in the respective studies. Patients were predominantly Caucasian females, average age 48–50 years, on average had FM for 9–10 years, and experienced moderate to severe baseline pain. Pregabalin significantly improved the Sleep Quality Diary (P <0.001), MOS Sleep Disturbance (P <0.01), MOS Quantity of Sleep (P <0.003), and MOS Sleep Problems Index scores (P <0.02) relative to placebo. Treatment effects for the 450mg and 600mg groups exceeded the estimated CID thresholds of 0.83 and 7.9 for the Sleep Quality Diary and MOS Sleep Disturbance scores, respectively. Mediation models indicated that 43–80% of the benefits on sleep (versus placebo) were direct effects of pregabalin, with the remainder resulting from an indirect effect of treatment via pain relief. Conclusions: These data demonstrate improvement in FM-related sleep dysfunction with pregabalin therapy. The majority of this benefit was a direct effect of pregabalin on the patients’ insomnia, while the remainder occurred through the drug’s analgesic activity. [Copyright &y& Elsevier]

Fibromyalgia is a prevalent disorder that is characterized by widespread pain along with numerous other symptoms, including fatigue, poor sleep, mood disorders, and stiffness. Previous guidelines for the management of fibromyalgia recommended an approach that integrates pharmacologic and nonpharmacologic therapies selected according to the symptoms experienced by individual patients. However, they offered no recommendations for a system of patient assessment that would provide a basis for individualized treatment selection. We present a simple, rapid and easily remembered system for symptom quantitation and pharmacologic management of fibromyalgia that combines visual analogue scale symptom scores from a modified form of the disease-neutral Fibromyalgia Impact Questionnaire, with a review of medications that can be used to treat the individual symptoms. This symptom-based approach is amenable to caring for patients with fibromyalgia in a busy clinical practice. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The objective of this study was to elicit and assess important symptom domains and the impact of fibromyalgia on patients’ quality of life and functioning from a patient''s perspective. The intention was to collect this information as part of an overall effort to overcome shortcomings of existing outcome measures in fibromyalgia. Methods: This was a qualitative study in which six focus group sessions with 48 women diagnosed with fibromyalgia were conducted to elicit concepts and ideas to assess the impact of fibromyalgia on their lives. Results: The focus groups conducted with fibromyalgia patients identified symptom domains that had the greatest impact on their quality of life including pain, sleep disturbance, fatigue, depression, anxiety, and cognitive impairment. Fibromyalgia had a substantial negative impact on social and occupational function. Patients reported disrupted relationships with family and friends, social isolation, reduced activities of daily living and leisure activities, avoidance of physical activity, and loss of career or inability to advance in careers or education. Conclusion: The findings from the focus groups revealed that fibromyalgia has a substantial negative impact on patients’ lives. Practice implications: A comprehensive assessment of the multiple symptoms domains associated with fibromyalgia and the impact of fibromyalgia on multidimensional aspects of function should be a routine part of the care of fibromyalgia patients. [Copyright &y& Elsevier]

Abstract: Objective: To determine whether previously described sleep stage dynamics, reflecting the mean duration of specific sleep stages, may have clinical utility in a sample of patients with fibromyalgia syndrome (FMS) and controls. Methods: Women with FMS (n =15, screened to exclude other sleep disorders) and age-matched women in good health (n =15) were studied with nocturnal polysomnography, multiple sleep latency tests, 2-week pain diaries, and a measure of current pain intensity. Results: The FMS subjects, in comparison to controls, did not show differences in several common polysomnographic measures, except for increased numbers of stage shifts (126±27 vs. 107±22, p =.042). Mean durations for episodes of total sleep, stage 1 sleep, stage 3/4 sleep, and rapid eye movement sleep failed to distinguish FMS and control subjects (Wilcoxon rank sum tests, p >.10 for each), but those for stage 2 sleep were shorter in the FMS subjects (p =.006), possibly because transitions to stage 3/4 sleep occurred more quickly (p =.036). Shorter stage 2 sleep durations predicted higher pain diary scores (Spearman rho =−.56, p =.0014) and current pain intensity (rho =−.71, p <0.0001). Conclusions: Sleep stage dynamic, and, more specifically, shorter durations of sleep stage 2 periods, distinguish FMS and control female subjects and may predict pain levels experienced in FMS. Analysis of the lengths of individual sleep stages, in addition to the usual sleep stage amounts and percentages listed in standard polysomnogram reports, may have clinical utility. [Copyright &y& Elsevier]

Abstract: This was a multicenter, double-blind (DB), placebo-controlled, randomized discontinuation trial to evaluate the efficacy of pregabalin monotherapy for durability of effect on fibromyalgia (FM) pain. The trial included a 6-week open-label (OL) pregabalin-treatment period followed by 26-week DB treatment with placebo or pregabalin. Adults with FM and ⩾40-mm score on 100-mm pain visual analog scale (VAS) were eligible. During OL weeks 1–3, patients received escalating dosages of pregabalin to determine their optimal dosages. During OL weeks 4–6, patients received their optimal fixed dosages (300, 450, 600mg/d). To be randomized, patients must have had ⩾50% decrease in pain VAS and a self-rating of “much” or “very much” improved on Patient Global Impression of Change (PGIC) at the end of OL. Double-blind treatment was with placebo or the patient’s optimal fixed dosage of pregabalin. Primary outcome was time to loss of therapeutic response (LTR), defined as <30% reduction in pain (from OL baseline) or worsening of FM. A total of 1051 patients entered OL; 287 were randomized to placebo, 279 to pregabalin. Time to LTR was longer for pregabalin versus placebo (P <.0001). Kaplan–Meier estimates of time-to-event showed half the placebo group had LTR by Day 19; half the pregabalin group still had not lost response by trial end. At the end of DB, 174 (61%) placebo patients met LTR criteria versus 90 (32%) pregabalin patients. Pregabalin was well tolerated, though 178 (17%) discontinued during OL for treatment-related adverse events (AE), and more pregabalin than placebo patients discontinued for AEs during DB. In those who respond, pregabalin demonstrated durability of effect for relieving FM pain. [Copyright &y& Elsevier]

Objective. To assess symptoms of anxiety and depression in a large cohort of fibromyalgia patients and to determine the impact of these symptoms on response of pain to pregabalin treatment. Design. Patients completed the Hospital Anxiety and Depression Scale at the baseline visit in a randomized, controlled trial of pregabalin for treatment of fibromyalgia. Mean anxiety and depression subscale scores were calculated, and proportions of patients by symptom severity were determined. The difference between the proportion of patients reporting anxiety and depression at baseline was tested using McNemar’s test. Baseline anxiety and depression were evaluated as covariates by including them—as interaction terms with treatment—in anancova model. A path analysis evaluated the association between improvements in anxiety and depression and pain relief. Results. In total, 529 patients were enrolled. Significantly more patients reported anxiety symptoms (71%) than depressive symptoms (56%) ( P < 0.0001). Improvement in pain symptoms with pregabalin compared with placebo did not depend linearly on baseline anxiety or depression scores. By path analysis, 75% of the pain reduction was not explained by improvements in anxiety and depressive symptoms. Conclusions. Anxiety symptoms were more common than depressive symptoms in this cohort. Our results suggest patients with fibromyalgia should be routinely assessed for the presence of both anxiety and depression. The pain treatment effect of pregabalin did not depend on baseline anxiety or depressive symptoms, suggesting pregabalin improves pain in patients with or without these symptoms. Much of the pain reduction appears to be independent of improvements in anxiety or mood symptoms. [ABSTRACT FROM AUTHOR]

Syndromes characterized by pain, fatigue, mood disorder, cognitive dysfunction, and sleep disturbance have been referred to as stress-related somatic disorders by virtue of the observation that onset and exacerbation of symptoms occur with stress. These syndromes include but are not limited to fibromyalgia, chronic fatigue syndrome, temporomandibular disorder, and irritable bowel syndrome. As with most chronic illnesses, genetic susceptibility and lifetime environmental exposures play a role in creating vulnerability to disease. Cumulative lifetime stress has been associated with a number of physiologic changes in the brain and body that reflect dysregulated hormonal and autonomic activity. Exposure to the stressor of violence is likely to create a state of vulnerability for the stress-related somatic syndromes and also to contribute to symptom expression and severity. Understanding the relationship between violence, stress, and somatic syndromes will help in clarifying the consequences of violence exposure to long-term health and health-related quality of life. [ABSTRACT FROM AUTHOR]

The authors present a reply to comments on their article on the Coatomer Protein Complex Subunit Alpha (COPA) syndrome and the importance of considering a genetic etiology in evaluating patients with interstitial lung disease (ILD). They state that alternative etiologies should be considered before an Interstitial Pneumonia with Autoimmune Features (IPAF) classification on a patient. Also noted is their advocacy for multidisciplinary team care for the patients to ensure the best diagnosis.

The objective of this study was to evaluate and compare the basal circadian and pulsatile architecture of the HPA axis in groups of patients with FMS, CFS, or both syndromes with individually matched control groups. Forty patients with either FMS (n=13), FMS and CFS (n=12), or CFS (n=15) were matched by age (18–65), sex, and menstrual status to healthy controls. Subjects were excluded if they met criteria for major Axis I psychiatric disorders by structured clinical interview (SCID). Subjects were admitted to the General Clinical Research Center where meals and activities were standardized. Blood was collected from an intravenous line every 10 min over 24 h for analysis of ACTH and cortisol. Samples were evaluable for ACTH in 36 subject pairs and for cortisol in 37 subject pairs. There was a significant delay in the rate of decline from acrophase to nadir for cortisol levels in patients with FMS (P<.01). Elevation of cortisol in the late evening quiescent period was evident in half of the FMS patients compared with their control group, while cortisol levels were numerically, but not significantly, lower in the overnight period in patients with CFS compared with their control group. Pulsatility analyses did not reveal statistically significant differences between patient and control groups. We conclude that the pattern of differences for basal circadian architecture of HPA axis hormones differs between patients with FMS and CFS compared to their matched control groups. The abnormalities in FMS patients are consistent with loss of HPA axis resiliency. [Copyright &y& Elsevier]

: BackgroundNephrogenic fibrosing dermopathy is a newly recognized cutaneous fibrosing disorder marked by the acute onset of induration involving the upper and lower limbs in patients with acute or chronic renal failure. The etiology, pathogenesis, associated clinical conditions (other than renal failure), and ultimate course have not been defined in the few cases studied. Presently, there is no effective treatment, and the condition persists in most patients.: MethodsClinical and histopathologic data on 13 patients from our institution with the diagnosis of nephrogenic fibrosing dermopathy were reviewed. Several clinical and laboratory parameters were examined to see if any were consistently associated with the disease. Biopsy specimens were analyzed to determine if there was a pattern to the evolution of fibrosis in these patients.: ResultsAll 13 patients had renal failure before disease onset: 8 were undergoing chronic hemodialysis, 2 were undergoing chronic peritoneal dialysis, and 3 with acute renal failure had never undergone dialysis before the development of dermopathy. Most patients had other serious underlying medical conditions. Many patients were taking erythropoietin, cyclosporine, or both before the onset of disease. In transplant patients, no histocompatibility antigens were found to be associated with the disease. There were various laboratory abnormalities, but none were consistently associated with the condition. In skin biopsy specimens taken 7 to 180 days after disease onset, there were histopathologic changes suggestive of a tissue reaction to injury, as well as the development of smooth muscle actin–positive myofibroblasts.: ConclusionNephrogenic fibrosing dermopathy is a novel cutaneous fibrosing disorder that is distinguished from other sclerosing or fibrosing skin disorders by distinctive clinical and histopathologic findings occurring in the setting of renal failure. There were no additional clinical risk factors or laboratory findings common to the 13 patients studied, other than renal failure. The resemblance to a tissue injury reaction and the presence of myofibroblasts in the tissue specimens suggest that fibrogenic cytokines may be involved in the evolution of the disease. [Copyright &y& Elsevier]

Objectives: To summarize the current status of the hypothalamic pituitary adrenal [HPA] axis in the fibromyalgia syndrome [FMS]. Findings: Attention has been focused on the HPA axis in FMS because there is a perceived association of the onset of this disorder with physiologically stressful situations. The medical literature strongly supports some kind of dsyfunction in the HPA system in FMS, but when studies have compared FMS with healthy normal controls, the actual patterns of HPA axis abnormalities have been suprisingly variable. It is possible that some of this variability may relate to a variable balance between the two receptors for corticotropin-releasing hormone which exhibit opposite influences on the stress management system when activated. Conclusions: The roles of the psychological stress response systems, including the HPA axis, remain uncertain in FMS because there has been so much variability of the findings from controlled studies. Part of the problem may be that pain is the defining symptom in the classification of FMS while the HPA axis may relate more to fatigue and psychological distress. [ABSTRACT FROM PUBLISHER]

The article focuses on the role of the hypothalamic-pituitary-adrenal (HPA) axis and the hypothalamic-pituitary-gonadal (HPG) axis in the increased susceptibility of women to rheumatic disease. The hypothalamus produces releasing hormones that act on the pituitary gland. Hormones of the anterior pituitary act to stimulate synthesis of the end-hormones that have direct effects on target tissues. Both autoimmune inflammatory rheumatic diseases and non-inflammatory rheumatic pain syndromes disproportionately affect women and contribute significantly to disability. The HPA axis is generally considered to play a pivotal role in the coordinated physiologic response to physical and psychological stress. Activation of the HPA axis involves a complex array of biochemical events occurring principally among the hypothalamus, anterior pituitary, and adrenal cortex. Activation of the HPA axis begins with the release of the corticotropin-releasing hormone (CRH) peptide into the hrpophyseal portal plexus. Stimulation of specific receptors for CRH on the corticotroph cells on the anterior pituitary causes the release of adrenocorticotropic hormone into the systemic circulation, subsequently affecting glucocorticoid release from the adrenal cortex.

Gonadotropin-releasing hormone (GnRH) is known to possess dirct immunomodulatory effects. We have previously demonstrated that the administration of GnRH analogues modulates the expression of murine lupus independently of effects on gonadal steroids. We speculate that GnRH exerts direct actions at the level of the immune cells. GnRH receptors have been identified on lymphocytes. Because GnRH and GnRH receptor (GnRH-R) expression varies with the estrous cycle at the levels of the hypothalamus and pituitary, we speculated that similar cyclicity might be demonstrable in lymphoid tissue. In this report, we used competitive reverse transcription PCR to quantitate the expression of GnRH and GnRH-R mRNA in lymphoid organs throughout the estrous cycle in mice. We demonstrate that the pattern of expression of GnRH-R mRNA in spleen agrees closely with the pattern in the pituitaries of the same mice and the pattern previously reported in the rat pituitary, with significantly increased levels of expression seen on the afternoon of proestrus compared to the morning of metestrus. A similar pattern is seen with GnRH-R mRNA expression in the thymus. Furthermore, we show that the expression of GnRH mRNA in both thymus and spleen agrees closely with the pattern of expression of its receptor, with significantly increased levels of expression seen on the afternoon of proestrus compared to the morning of metestrus. Additional in vitro studies demonstrate that both GnRH and estradiol significantly increase the expression of GnRH-R mRNA in immune cells. These findings support an active role for GnRH in the immune system. [ABSTRACT FROM AUTHOR]

Objectives Pain may decrease well-being in older adults by limiting social and leisure activities. However, some activities can exacerbate pain. We hypothesized that autonomously motivated goal engagement could ameliorate negative effects of pain on goal engagement and amplify positive effects of goal engagement on eudemonic well-being (EWB). Methods Midlife and older women (N = 200) were oversampled for chronic pain. Daily diaries (n = 10,697) including goal lists and ratings, pain, and EWB were completed for 7 days every 3 months for 2 years. Results Pain was not a correlate of goal engagement. More engagement was associated with higher EWB when motivation was autonomous. However, more goal engagement correlated with lower EWB the next day and, when not autonomously motivated, higher pain. Discussion Goal engagement can benefit people with or without physical pain, but the motivation behind goal engagement is equally if not more important. Goals motivated by autonomous sources increase EWB and may protect against maladaptive patterns of activity associated with pain. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion In the randomized Scleroderma: Cyclophosphamide or Transplantation (SCOT) trial, myeloablation, followed by hematopoietic stem cell transplantation (HSCT), led to the normalization of systemic sclerosis (SSc) peripheral blood cell (PBC) gene expression signature at the 26‐month visit. Herein, we examined long‐term molecular changes ensuing 54 months after randomization for individuals receiving an HSCT or 12 months of intravenous cyclophosphamide (CYC).Global PBC transcript studies were performed in study participants at pretreatment baseline and at 38 months and 54 months after randomization, as well as in healthy controls using Illumina HT‐12 arrays.Thirty (HSCT = 19 and CYC = 11) participants had 38‐month samples available, and 26 (HSCT = 16 and CYC = 11) had 54‐month samples available. In the paired comparison to baseline, a significant down‐regulation of interferon modules and an up‐regulation of cytotoxic/natural killer module were observed at the 38‐month and 54‐month visits in the HSCT arm, indicating a long‐term normalization of baseline SSc gene expression signature. No differentially expressed modules were detected in the CYC arm. In comparison to samples from healthy controls, 38‐month visit samples in the HSCT arm showed an up‐regulation of B cell and plasmablast modules and a down‐regulation of myeloid and inflammation modules. Importantly, 54‐month HSCT samples did not show any differentially expressed modules compared to healthy control samples, suggesting completion of immune reconstitution. Participants in the CYC arm continued to show an SSc transcript signature in comparison to controls at both time points.Paralleling the observed clinical benefit, HSCT leads to durable long‐term normalization of the molecular signature in SSc, with completion of immune resetting to 54 months after HSCT. [ABSTRACT FROM AUTHOR]

Background: Disturbed sleep is prevalent in older adulthood and particularly among women. Greater psychological well-being (PWB) is associated with better sleep, but intraindividual variability in PWB has not been examined.Purpose: The current study examined whether mean levels and variability in PWB were associated with sleep disturbances in midlife and older women.Methods: Participants (N = 189) completed up to seven daily diaries and an end of the week assessment every 3 months for nine waves. Participants answered questions about their nightly sleep disturbances and reported their PWB using Ryff's six dimensions of PWB.Results: Regression models indicated that greater variability in one aspect of PWB, positive relations with others, was related to greater sleep disturbance even after adjusting for mean levels of well-being. Greater variability in environmental mastery, purpose in life, and self-acceptance were also associated with sleep disturbance, but these associations were no longer significant after adjusting for mean levels of well-being.Conclusions: Results suggest that fluctuations in positive relations with others are related to sleep in adult women above and beyond mean levels of well-being. Results highlight the importance of considering variability in addition to mean levels of PWB. [ABSTRACT FROM AUTHOR]

Objective Disparities in pregnancy outcomes among women with SLE remain understudied, with few available racially diverse datasets. We sought to identify disparities between Black and White women in pregnancy outcomes within academic institutions in the United States. Methods Using the Common Data Model electronic medical record (EMR)-based datasets within the Carolinas Collaborative, we identified women with pregnancy delivery data (2014–2019) and ≥1 SLE International Classification of Diseases 9 or 10 code (ICD9/10) code. From this dataset, we identified four cohorts of SLE pregnancies, three based on EMR-based algorithms and one confirmed with chart review. We compared the pregnancy outcomes identified in each of these cohorts for Black and White women. Results Of 172 pregnancies in women with ≥1 SLE ICD9/10 code, 49% had confirmed SLE. Adverse pregnancy outcomes occurred in 40% of pregnancies in women with ≥1 ICD9/10 SLE code and 52% of pregnancies with confirmed SLE. SLE was frequently over-diagnosed in women who were White, resulting in 40–75% lower rates of adverse pregnancy outcomes in EMR-derived vs confirmed SLE cohorts. Over-diagnosis was less common for Black women with pregnancy outcomes 12–20% lower in EMR-derived vs confirmed SLE cohorts. Black women had higher rates of adverse pregnancy outcomes than White women in the EMR-derived, but not the confirmed cohorts. Conclusion EMR-derived cohorts of pregnancies in women who are Black, but not White, provided accurate estimations of pregnancy outcomes. The data from the confirmed SLE pregnancies suggest that all women with SLE, regardless of race, referred to academic centres remain at very high risk for adverse pregnancy outcome. [ABSTRACT FROM AUTHOR]

Background: Pain interferes with people's daily lives and often limits the extent to which they can pursue goals and engage in activities that promote well-being. However, people vary in how much interference they experience at a given level of pain.Purpose: The present study tested how optimism affects and is affected by pain interference and goal-directed activity among older women.Methods: Every 3 months for 2 years, community-dwelling middle- and older-age women (N = 199) completed online daily diaries at home for a 7 day period, in which they reported their daily pain, pain interference, and goal-directed activity. Optimism was measured at the start and end of the study. Multilevel models tested the between- and within-person relationships among pain, optimism, and pain interference or goal-directed activity. Linear regression predicted change in optimism over 2 years from pain interference and goal-directed activity.Results: Pain best predicted pain interference and optimism best predicted goal-directed activity. There were subtle interactions between optimism and pain-predicting interference and goal-directed activity. Accumulated goal-directed activity and pain interference across the study predicted longitudinal changes in optimism, with higher activity and lower pain interference predicting increased optimism over 2 years.Conclusions: Optimism may play a protective role in disruptions caused by pain on a day-to-day basis, leading to increased goal-directed activity and possibly decreased pain interference. In turn, less interference and more goal-directed activity feed forward into increased optimism, resulting in a virtuous cycle that enhances optimism and well-being among older women. [ABSTRACT FROM AUTHOR]

The article explains why rheumatologists and other rheumatology health professionals view fibromyalgia syndrome (FMS) as difficult to manage. Many rheumatologists have little formal training in neurobiology or pain management. Also many rheumatologists view themselves as clinical immunologists rather than specialists in musculoskeletal medicine. Furthermore, primary care physicians are uncomfortable with diagnosis and management of myofascial pain or FMS.

Although profibrotic cytokines, such as IL-17A and TGF-β1, have been implicated in the pathogenesis of interstitial lung disease (ILD), the interactions between gut dysbiosis, gonadotrophic hormones and molecular mediators of profibrotic cytokine expression, such as the phosphorylation of STAT3, have not been defined. Here, through chromatin immunoprecipitation sequencing (ChIP-seq) analysis of primary human CD4+ T cells, we show that regions within the STAT3 locus are significantly enriched for binding by the transcription factor estrogen receptor alpha (ERa). Using the murine model of bleomycin-induced pulmonary fibrosis, we found significantly increased regulatory T cells compared to Th17 cells in the female lung. The genetic absence of ESR1 or ovariectomy in mice significantly increased pSTAT3 and IL-17A expression in pulmonary CD4+ T cells, which was reduced after the repletion of female hormones. Remarkably, there was no significant reduction in lung fibrosis under either condition, suggesting that factors outside of ovarian hormones also contribute. An assessment of lung fibrosis among menstruating females in different rearing environments revealed that environments favoring gut dysbiosis augment fibrosis. Furthermore, hormone repletion following ovariectomy further augmented lung fibrosis, suggesting pathologic interactions between gonadal hormones and gut microbiota in relation to lung fibrosis severity. An analysis of female sarcoidosis patients revealed a significant reduction in pSTAT3 and IL-17A levels and a concomitant increase in TGF-β1 levels in CD4+ T cells compared to male sarcoidosis patients. These studies reveal that estrogen is profibrotic in females and that gut dysbiosis in menstruating females augments lung fibrosis severity, supporting a critical interaction between gonadal hormones and gut flora in lung fibrosis pathogenesis. [ABSTRACT FROM AUTHOR]

Fibromyalgia is characterized by widespread pain, fatigue, sleep disturbances and other symptoms, and has a substantial socioeconomic impact. Current biomedical and psychosocial treatments are unsatisfactory for many patients, and treatment progress has been hindered by the lack of a clear understanding of the pathogenesis of fibromyalgia. We present here a model of fibromyalgia that integrates current psychosocial and neurophysiological observations. We propose that an imbalance in emotion regulation, reflected by an overactive 'threat' system and underactive 'soothing' system, might keep the 'salience network' (also known as the midcingulo-insular network) in continuous alert mode, and this hyperactivation, in conjunction with other mechanisms, contributes to fibromyalgia. This proposed integrative model, which we term the Fibromyalgia: Imbalance of Threat and Soothing Systems (FITSS) model, should be viewed as a working hypothesis with limited supporting evidence available. We hope, however, that this model will shed new light on existing psychosocial and biological observations, and inspire future research to address the many gaps in our knowledge about fibromyalgia, ultimately stimulating the development of novel therapeutic interventions. [ABSTRACT FROM AUTHOR]

Objectives Transcutaneous electrical nerve stimulation (TENS) is a nonpharmacological intervention that provides an electrical current through the skin to produce analgesia. The primary purpose of this study is to examine if the addition of TENS to routine physical therapy improves movement-evoked pain in individuals with fibromyalgia in a physical therapy clinical setting. Methods Fibromyalgia TENS in Physical Therapy Study is a phase III embedded pragmatic clinical trial funded through the National Institutes of Health Helping to End Addiction Long-Term Initiative. This trial will utilize a randomized cluster design that includes more than 110 physical therapists in 24 to 30 physical therapy clinics within 6 health care systems and 7 states. Clinics will be randomized to TENS or No-TENS, stratified by health care system and clinic size. The plan is to enroll 600 participants, with all participants completing physical therapy as prescribed by their physical therapist. Participants at TENS clinics will utilize TENS for a minimum of 2-hour per day while at the physical therapy clinic and at home when active. The primary outcome is reduction in movement-evoked pain from baseline to day 60 on an 11-point numeric rating scale when participants sit and stand 5 times (Sit and Stand Test). Secondary outcomes include resting pain and fatigue, pain interference, fibromyalgia disease activity, movement-evoked fatigue, multidimensional assessment of fatigue, rapid assessment of physical activity, patient global impression of change, and common data elements shared across studies supported through the Helping to End Addiction Long-Term Initiative. Impact The findings from this study will provide effectiveness data on TENS for individuals with fibromyalgia for health care policymakers, clinicians, and insurers. Data from this study will also inform future pragmatic trials for nonpharmacological interventions and chronic musculoskeletal pain conditions. [ABSTRACT FROM AUTHOR]

Editorial. Asserts that since the mechanism of action of aspirin and anti-inflammatory medications is the inhibition of the cyclooxygenase enzymes, their adverse-event and efficacy profiles may change when they are used in combination. Research conducted by Catella-Lawson et al in this issue; The important distinctions among the mechanisms of action of aspirin, nonsteroidal antinflammatory drugs, COX-2 inhibitors, and acetaminophen; View that the choice of therapeutic agent should be based on the preference of the patient.

Fibromyalgia (FM) is a chronic pain disorder characterized by chronic widespread musculoskeletal pain (CWP), resting pain, movement-evoked pain (MEP), and other somatic symptoms that interfere with daily functioning and quality of life. In clinical studies, this symptomology is assessed, while preclinical models of CWP are limited to nociceptive assays. The aim of the study was to investigate the human-to-model translatability of clinical behavioral assessments for spontaneous (or resting) pain and MEP in a preclinical model of CWP. For preclinical measures, the acidic saline model of FM was used to induce widespread muscle pain in adult female mice. Two intramuscular injections of acidic or neutral pH saline were administered following baseline measures, 5 days apart. An array of adapted evoked and spontaneous pain measures and functional assays were assessed for 3 weeks. A novel paradigm for MEP assessment showed increased spontaneous pain following activity. For clinical measures, resting and movement-evoked pain and function were assessed in adult women with FM. Moreover, we assessed correlations between the preclinical model of CWP and in women with fibromyalgia to examine whether similar relationships between pain assays that comprise resting and MEP existed in both settings. For both preclinical and clinical outcomes, MEP was significantly associated with mechanical pain sensitivity. Preclinically, it is imperative to expand how the field assesses spontaneous pain and MEP when studying multi-symptom disorders like FM. Targeted pain assessments to match those performed clinically is an important aspect of improving preclinical to clinical translatability of animal models. [ABSTRACT FROM AUTHOR]

Interstitial lung disease (ILD) represents a significant cause of morbidity and mortality in systemic sclerosis (SSc). The purpose of this study was to examine recirculating lymphocytes from SSc patients for potential biomarkers of interstitial lung disease (ILD). Peripheral blood mononuclear cells (PBMCs) were isolated from patients with SSc and healthy controls enrolled in the Vanderbilt University Myositis and Scleroderma Treatment Initiative Center cohort between 9/2017–6/2019. Clinical phenotyping was performed by chart abstraction. Immunophenotyping was performed using both mass cytometry and fluorescence cytometry combined with t-distributed stochastic neighbor embedding analysis and traditional biaxial gating. This study included 34 patients with SSc-ILD, 14 patients without SSc-ILD, and 25 healthy controls. CD21lo/neg cells are significantly increased in SSc-ILD but not in SSc without ILD (15.4 ± 13.3% vs. 5.8 ± 0.9%, p = 0.002) or healthy controls (5.0 ± 0.5%, p < 0.0001). While CD21lo/neg B cells can be identified from a single biaxial gate, tSNE analysis reveals that the biaxial gate is comprised of multiple distinct subsets, all of which are increased in SSc-ILD. CD21lo/neg cells in both healthy controls and SSc-ILD are predominantly tBET positive and do not have intracellular CD21. Immunohistochemistry staining demonstrated that CD21lo/neg B cells diffusely infiltrate the lung parenchyma of an SSc-ILD patient. Additional work is needed to validate this biomarker in larger cohorts and longitudinal studies and to understand the role of these cells in SSc-ILD. [ABSTRACT FROM AUTHOR]

The hypothalamic-pituitary-adrenal (HPA) axis is crucial in coping with stress and maintaining homeostasis. Hormones produced by the HPA axis exhibit both complex univariate longitudinal profiles and complex relationships among different hormones. Consequently, modeling these multivariate longitudinal hormone profiles is a challenging task. In this article, we propose a bivariate hierarchical state space model, in which each hormone profile is modeled by a hierarchical state space model, with both population-average and subject-specific components. The bivariate model is constructed by concatenating the univariate models based on the hypothesized relationship. Because of the flexible framework of state space form, the resultant models not only can handle complex individual profiles, but also can incorporate complex relationships between two hormones, including both concurrent and feedback relationship. Estimation and inference are based on marginal likelihood and posterior means and variances. Computationally efficient Kalman filtering and smoothing algorithms are used for implementation. Application of the proposed method to a study of chronic fatigue syndrome and fibromyalgia reveals that the relationships between adrenocorticotropic hormone and cortisol in the patient group are weaker than in healthy controls. Supplementary materials for this article are available online. [ABSTRACT FROM AUTHOR]

Abstract: A dynamic systems model was used to generate parameters describing a phenotype of Hypothalamic–Pituitary–Adrenal (HPA) behavior in a sample of 36 patients with chronic fatigue syndrome (CFS) and/or fibromyalgia (FM) and 36 case-matched healthy controls. Altered neuroendocrine function, particularly in relation to somatic symptoms and poor sleep quality, may contribute to the pathophysiology of these disorders. Blood plasma was assayed for cortisol and ACTH every 10min for 24h. The dynamic model was specified with an ordinary differential equation using three parameters: (1) ACTH-adrenal signaling, (2) inhibitory feedback, and (3) non-ACTH influences. The model was “personalized” by estimating an individualized set of parameters from each participant’s data. Day and nighttime parameters were assessed separately. Two nocturnal parameters (ACTH-adrenal signaling and inhibitory feedback) significantly differentiated the two patient subgroups (“fatigue-predominant” patients with CFS only versus “pain-predominant” patients with FM and comorbid chronic fatigue) from controls (all p’s<.05), whereas daytime parameters and diurnal/nocturnal slopes did not. The same nocturnal parameters were significantly associated with somatic symptoms among patients (p’s<.05). There was a significantly different pattern of association between nocturnal non-ACTH influences and sleep quality among patients versus controls (p <.05). Although speculative, the finding that patient somatic symptoms decreased when more cortisol was produced per unit ACTH, is consistent with cortisol’s anti-inflammatory and sleep-modulatory effects. Patients’ HPA systems may compensate by promoting more rapid or sustained cortisol production. Mapping “behavioral phenotypes” of stress–arousal systems onto symptom clusters may help disentangle the pathophysiology of complex disorders with frequent comorbidity. [Copyright &y& Elsevier]

Abstract: Ability to self-regulate varies and self-regulatory strength is a limited source that can be depleted or fatigued. Research on the impact of individual differences on self-regulatory capacity is still scarce, and this study aimed to examine whether personality factors such as dispositional optimism, conscientiousness, and self-consciousness can impact or buffer self-regulatory fatigue. Participants were patients diagnosed with chronic multi-symptom illnesses (N =50), or pain free matched controls (N =50), randomly assigned to either a high or low self-regulation task, followed by a persistence task. Higher optimism predicted longer persistence (p =.04), and there was a trend towards the same effect for conscientiousness (p =.08). The optimism by self-regulation interaction was significant (p =.01), but rather than persisting despite self-regulatory effort, optimists persisted longer only when not experiencing self-regulatory fatigue. The effects of optimism were stronger for controls than patients. There was also a trend towards a similar conscientiousness by self-regulation interaction (p =.06). These results suggest that the well-established positive impact of optimism and conscientiousness on engagement and persistence may be diminished or reversed in the presence of self-regulatory effort or fatigue, adding an important new chapter to the self-regulation, personality, and pain literature. [ABSTRACT FROM AUTHOR]

Abstract: Chronic pain conditions such as fibromyalgia (FM) and temporomandibular disorders (TMDs) are accompanied by complex interactions of cognitive, emotional, and physiological disturbances. Such conditions are complicated and draining to live with, and successful adaptation may depend on ability to self-regulate. Self-regulation involves capacity to exercise control and guide or alter reactions and behavior, abilities essential for human adjustment. Research indicates that self-regulatory strength is a limited source that can be depleted or fatigued, however, and the current study aimed to show that patients with FM and TMD are vulnerable to self-regulatory fatigue as a consequence of their condition. Patients (N =50) and pain-free matched controls (N =50) were exposed to an experimental self-regulation task followed by a persistence task. Patients displayed significantly less capacity to persist on the subsequent task compared with controls. In fact, patients exposed to low self-regulatory effort displayed similar low persistence to patients and controls exposed to high self-regulatory effort, indicating that patients with chronic pain conditions may be suffering from chronic self-regulatory fatigue. Baseline heart rate variability, blood glucose, and cortisol predicted persistence, more so for controls than for patients, and more so in the low vs. high self-regulation condition. Impact of chronic pain conditions on self-regulatory effort was mediated by pain, but not by any other factors. The current study suggests that patients with chronic pain conditions likely suffer from chronic self-regulatory fatigue, and underlines the importance of taking self-regulatory capacity into account when aiming to understand and treat these complex conditions. [Copyright &y& Elsevier]

The article evaluates the effectiveness of fibromyalgia (FM) therapies. It identifies and prioritizes the key clinically relevant and important domains impacted by FM that should be evaluated by outcome assessment instruments used in FM clinical trials. A conceptual framework for measuring patient-reported outcomes is proposed.

Focuses on a study which examined the expression, function, and regulation of the cyclooxygenase (COX)-2 gene in gastric parietal cells. Discussion on the role of COX-1 and COX-2 in the generation of prostaglandins; Materials and methodology; Explanation on the function of COX-2 in gastric pathophysiology; Analysis and discussion.

Abstract: We previously showed that 1 month of transcutaneous electrical nerve stimulation (TENS) reduces movement-evoked pain and fatigue in women with fibromyalgia (FM). Using data from this study (Fibromyalgia Activity Study with TENS [FAST]), we performed a responder analysis to identify predictors of clinical improvement in pain and fatigue with TENS, validated these models using receiver operator characteristic, and determined number needed to treat and number needed to harm. Participants were randomly assigned to active-TENS (2-125 Hz; highest-tolerable intensity), placebo-TENS, or no-TENS for 1 month. At the end of the randomized phase, placebo-TENS and no-TENS groups received active-TENS for 1 month. The predictor model was developed using data from the randomized phase for the active-TENS group (n = 103) and validated using data from placebo-TENS and no-TENS groups after active-TENS for 1 month (n = 155). Participant characteristics, initial response to TENS for pain and fatigue, sleep, psychological factors, and function were screened for association with changes in pain or fatigue using a logistic regression model. Predictors of clinical improvement in pain were initial response to pain and widespread pain index (area under the curve was 0.80; 95% confidence interval: 0.73-0.87). Predictors of clinical improvement in fatigue were marital status, sleep impairment, and initial response to TENS (area under the curve was 0.67; 95% confidence interval: 0.58-0.75). Number needed to treat for pain and fatigue ranged between 3.3 and 5.3. Number needed to harm ranged from 20 to 100 for minor TENS-related adverse events. The response to an initial 30-minute TENS treatment predicts who responds to longer-term TENS use in women with FM, making this a clinically useful procedure. Number needed to treat and number needed to harm suggest that TENS is effective and safe for managing pain and fatigue in FM. [ABSTRACT FROM AUTHOR]

Objective: To provide a large‐scale assessment of serum protein dysregulation in diffuse cutaneous systemic sclerosis (dcSSc) and to investigate serum protein correlates of SSc fibrotic features. Methods: We investigated serum protein profiles of 66 participants with dcSSc at baseline who were enrolled in the Scleroderma: Cyclophosphamide or Transplant Trial and 66 age‐ and sex‐matched healthy control subjects. A panel of 230 proteins, including several cytokines and chemokines, was investigated. Whole blood gene expression profiling in concomitantly collected samples was performed. Results: Among the participants with dcSSc, the mean disease duration was 2.3 years. All had interstitial lung disease (ILD), and none were being treated with immunosuppressive agents at baseline. Ninety proteins were differentially expressed in participants with dcSSc compared to healthy control subjects. Similar to previous global skin transcript results, hepatic fibrosis, granulocyte and agranulocyte adhesion, and diapedesis were the top overrepresented pathways. Eighteen proteins correlated with the modified Rodnan skin thickness score (MRSS). Soluble epidermal growth factor receptor was significantly down‐regulated in dcSSc and showed the strongest negative correlation with the MRSS, being predictive of the score's course over time, whereas α1‐antichymotrypsin was significantly up‐regulated in dcSSc and showed the strongest positive correlation with the MRSS. Furthermore, higher levels of cancer antigen 15‐3 correlated with more severe ILD, based on findings of reduced forced vital capacity and higher scores of disease activity on high‐resolution computed tomography. Only 14 genes showed significant differential expression in the same direction in serum protein and whole blood RNA gene expression analyses. Conclusion: Diffuse cutaneous SSc has a distinct serum protein profile with prominent dysregulation of proteins related to fibrosis and immune cell adhesion/diapedesis. The differential expression for most serum proteins in SSc is likely to originate outside the peripheral blood cells. [ABSTRACT FROM AUTHOR]

Objective: Fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS) are complicated medical disorders, with little known etiologies. The purpose of this research is to characterize FMS and CFS by studying the variations in cortisol secretion patterns, timings, amplitudes, the number of underlying pulses, as well as infusion and clearance rates of cortisol. Methods: Using a physiological state-space model with plausible constraints, we estimate the hormonal secretory events and the physiological system parameters (i.e., infusion and clearance rates). Results: Our results show that the clearance rate of cortisol is lower in FMS patients as compared to their matched healthy individuals based on a simplified cortisol secretion model. Moreover, the number, magnitude, and energy of hormonal secretory events are lower in FMS patients. During early morning hours, the magnitude and energy of the hormonal secretory events are higher in CFS patients. Conclusion: Due to lower cortisol clearance rate, there is a higher accumulation of cortisol in FMS patients as compared to their matched healthy subjects. As the FMS patient accumulates higher cortisol residues, internal inhibitory feedback regulates the hormonal secretory events. Therefore, the FMS patients show a lower number, magnitude, and energy of hormonal secretory events. Though CFS patients have the same number of secretory events, they secrete lower quantities during early morning hours. When we compare the results for CFS patients against FMS patients, we observe different cortisol alteration patterns. Significance: Characterizing CFS and FMS based on the cortisol alteration will help us to develop novel methods for treating these disorders. [ABSTRACT FROM AUTHOR]

Thus, we are surprised with Clauw et al.'s statement that we claim that "psychological stress is the sole cause of fibromyalgia" or that "adverse childhood events ... are key drivers in the development of fibromyalgia"[1]. 1:STN:280:DC%2BC1c3hs1agtg%3D%3D. 10.1002/ejp.1003. 28146315 5 Ellingsen D-M. A picture is worth a thousand words: linking fibromyalgia pain widespreadness from digital pain drawings with pain catastrophizing and brain cross-network connectivity. [Extracted from the article]

Reply to 'Imbalance of threat and soothing systems in fibromyalgia: rephrasing an established mechanistic model? 5741296 6 Grayston R. A systematic review and meta-analysis of the prevalence of small fiber pathology in fibromyalgia: implications for a new paradigm in fibromyalgia etiopathogenesis. The pathophysiology of fibromyalgia is too complex for a unidimensional view, which Martínez-Lavín seems to recognize when stating elsewhere[4] that fibromyalgia "cannot be explained by the prevailing linear-reductionist medical paradigm". [Extracted from the article]

Prostaglandins (PG) are pleiotropic bioactive lipids involved in the control of many physiological processes, including key roles in regulating inflammation. This links PG to the modulation of the quality and magnitude of immune responses. T cells, as a core part of the immune system, respond readily to inflammatory cues from their environment, and express a diverse array of PG receptors that contribute to their function and phenotype. Here we put in context our knowledge about how PG affect T cell biology, and review advances that bring light into how specific T cell functions that have been newly discovered are modulated through PG. We will also comment on drugs that target PG metabolism and sensing, their effect on T cell function during disease, and we will finally discuss how we can design new approaches that modulate PG in order to maximize desired therapeutic T cell effects. [ABSTRACT FROM AUTHOR]

Objective: Fibromyalgia (FM) is characterized by pain and fatigue, particularly during physical activity. Transcutaneous electrical nerve stimulation (TENS) activates endogenous pain inhibitory mechanisms. This study was undertaken to investigate if using TENS during activity would improve movement‐evoked pain and other patient‐reported outcomes in women with FM. Methods: Participants were randomly assigned to receive active TENS (n = 103), placebo TENS (n = 99), or no TENS (n = 99) and instructed to use it at home during activity 2 hours each day for 4 weeks. TENS was applied to the lumbar and cervicothoracic regions using a modulated frequency (2–125 Hz) at the highest tolerable intensity. Participants rated movement‐evoked pain (primary outcome measure) and fatigue on an 11‐point scale before and during application of TENS. The primary outcome measure and secondary patient‐reported outcomes were assessed at baseline (time of randomization) and at 4 weeks. Results: After 4 weeks, a greater reduction in movement‐evoked pain was reported in the active TENS group versus the placebo TENS group (group mean difference –1.0 [95% confidence interval –1.8, –0.2]; P = 0.008) and versus the no TENS group (group mean difference –1.8 [95% confidence interval –2.6, –1.0]; P < 0.0001). A reduction in movement‐evoked fatigue was also reported in the active TENS group versus the placebo TENS group (group mean difference –1.4 [95% confidence interval –2.4, –0.4]; P = 0.001) and versus the no TENS group (group mean difference –1.9 [95% confidence interval –2.9, –0.9]; P = <0.0001). A greater percentage of the patients in the active TENS group reported improvement on the global impression of change compared to the placebo TENS group (70% versus 31%; P < 0.0001) and the no TENS group (9%; P < 0.0001). There were no TENS‐related serious adverse events, and <5% of participants experienced minor adverse events from TENS. Conclusion: Among women who had FM and were on a stable medication regimen, 4 weeks of active TENS use compared to placebo TENS or no TENS resulted in a significant improvement in movement‐evoked pain and other clinical outcomes. Further research is needed to examine effectiveness in a real‐world setting to establish the clinical importance of these findings. [ABSTRACT FROM AUTHOR]

This study examined whether depression and anxiety differentially relate to fatigue, sleep disturbance, pain catastrophizing, fear of movement, and pain severity in women with fibromyalgia. Baseline data from the Fibromyalgia Activity Study with Transcutaneous Electrical Nerve Stimulation were analyzed. Of 191 participants, 50 percent reported high anxiety and/or depression (17% high anxiety, 9% high depression, and 24% both). Fatigue and sleep impairment were associated with high depression (p < 0.05). Pain severity, pain catastrophizing, and fear of movement were associated with high anxiety and high depression (p < 0.05). Possible implications for underlying mechanisms and the need for targeted treatments are discussed. [ABSTRACT FROM AUTHOR]

Background: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating condition carrying substantial psychosocial burden. Psychological treatment for IC/BPS is little studied, and there are barriers to its use in clinical management. Whether psychological treatments benefit patients with IC/BPS is unclear and we do not know whether such treatments would meet patient needs. Aims: Incorporating patient-reported needs and acknowledging diversity in pain experiences can inform patient-centered interventions for IC/BPS. This project characterized the experience of living with IC/BPS and patient perceptions of needs in its treatment, with the goal of informing patient-centered treatment for IC/BPS. Methods: Using both quantitative and qualitative methods, 27 females with IC/BPS participated in a focus group and completed validated self-report assessments evaluating urinary symptoms, pain, and emotional functioning. Focus groups were audio recorded and transcribed and then coded and analyzed using an iterative inductive/deductive approach. Linear regression models evaluated the relationship between psychological functioning and symptom severity. Results: We conducted six focus groups between August and December 2017. Five major themes emerged from qualitative analysis: managing physical symptoms, emotional symptoms, impact on daily life and socio-contextual factors, responding to illness, and addressing needs in treatment. The physiological and emotional consequences of IC/BPS were reported, highlighting their impact on interpersonal relationships and challenges in obtaining appropriate treatment for IC/BPS. Quantitative analysis showed that depression levels were significantly associated with worsened IC/BPS symptomology, after controlling for known confounding factors. Conclusion: Individuals with IC/BPS could benefit from tailored psychological interventions focusing on pain management, emotion regulation, communications skills, along with sexual dysfunction and intimacy fears. [ABSTRACT FROM AUTHOR]