Widespread Pain With Nociplastic Features is an Independent Predictor of Low Physical Activity in People with Multiple Sclerosis.

Exploring the relationship between underlying pain mechanisms and physical activity could inform interventions to optimize physical activity in persons with multiple sclerosis (PwMS). This cross-sectional nationwide survey examined whether pain phenotype is a significant predictor of self-reported physical activity in PwMS. The study included 938 persons with a self-reported diagnosis of MS (93% reported neurologist-diagnosed MS) who completed surveys of demographic, clinical information, pain intensity, indicators of underlying pain mechanisms (Fibromyalgia Survey Criteria and painDETECT), and physical activity (Godin Leisure-Time Exercise Questionnaire). Responses were used to categorize pain phenotypes as widespread pain with nociplastic features (WPNF), neuropathic, nociceptive, or mixed (neuropathic/WPNF). Following current physical activity guidelines, self-reported physical activity was categorized as active or insufficiently active/sedentary. Applying multivariable logistic regression, participants with no chronic pain had 2.30 higher odds of being physically active when compared to participants with chronic mixed pain. Similarly, participants with neuropathic and nociceptive pain had, respectively, 1.90 and 1.66 higher odds of being physically active compared to individuals with mixed pain. Higher scores on the fibromyalgia survey criteria (operationalized in this study as an indicator of WPNF) were a significant independent predictor of insufficient physical activity (OR = .93, P < .01). Findings indicate that experience and phenotype of chronic pain, in particular WPNF, are associated with physical inactivity in PwMS. This suggests that assessing pain phenotype may be important to identify individuals at risk of inadequate physical activity and may guide the tailoring of behavioral therapeutic approaches to help PwMS achieve the recommended level of physical activity. PERSPECTIVE: This study examines the association between pain mechanism and physical activity in multiple sclerosis. These findings highlight the possibility that a basic screening for pain mechanism could offer clinically useful information without requiring extensive neurobiological phenotyping and may inform the development of behavioral interventions to enhance physical activity in multiple sclerosis.

Mind the Mood: Momentary Depression and Anxiety Moderate the Correspondence Between Subjective and Objective Cognitive Functioning in Fibromyalgia.

OBJECTIVE: Subjective cognitive dysfunction (SCD) affects 55-75% of individuals with fibromyalgia (FM), but those reporting cognitive difficulties often lack corresponding objective deficits. Symptoms of depression and anxiety are prevalent in FM and may account for part of this discrepancy. This study was undertaken to investigate whether momentary (within-day, across 7 days) changes in mood moderate the relationship between within-the-moment SCD and mental processing speed performance. METHODS: A total of 50 individuals with FM (mean age 44.8 years, mean education 15.7 years, 88% female, 86% White) completed momentary assessments of subjective cognitive functioning, depressive and anxious symptoms, and a test of processing speed. Assessments were completed 5 times per day for 8 consecutive days on a study-specific smartphone application. RESULTS: Momentary ratings of SCD were positively associated with mean reaction time (P < 0.001) and variability of processing speed (P = 0.02). Depressive symptoms moderated the relationship between SCD and processing speed, with lower correspondence when depressive symptoms were higher (P = 0.03). A similar moderating effect was demonstrated for both depression (P = 0.02) and anxiety (P = 0.03) on the association between SCD and variability in processing speed performance. CONCLUSION: Individuals with FM may have more accurate self-perception of momentary changes in mental processing speed during periods of less pronounced mood symptoms based on their corresponding objective processing speed performance. However, during moments of heightened depression and anxiety, we found increasingly less correspondence between SCD and objective performance, suggesting that psychological symptoms may play an important role in self-perception of cognitive dysfunction in FM as it relates to mental processing speed.

Trajectories of medication use and polypharmacy among children with cerebral palsy.

BACKGROUND: Children with cerebral palsy (CP) may have chronic exposure to polypharmacy to address several medical needs, but there is little research on the topic to inform surveillance methods and clinical practice. OBJECTIVE: To identify the trajectories of medication number and pediatric polypharmacy (≥2 concurrent medications) exposure over 3.5 years among children with CP. METHODS: This cohort study used commercial claims from January 1, 2015, to December 31, 2018 (4-year period). Children with CP, aged 5-18 years by January 1, 2016, and with continuous health plan enrollment for all 4 years, were included and categorized as with or without co-occurring neurological/ RESULTS: Of the 1,252 children with CP, 600 were in the CP only cohort (mean [SD]; age, 11.4 [4.1] years; 46.0% female) and 652 were in the CP + NDDs cohort (age, 11.9 [4.1] years; 41.3% female; 32.7% had ≥2 of the NDDs). For the primary GBTM, 3 trajectory groups were identified for CP only: on average, no prescribed medications (69.7% of the cohort), 1 medication/month (24.8%), and 4 medications/month (5.5%). Five trajectory groups were identified for CP + NDDs: 0 (22.4%), 1 (25.6%), 2 (25.2%), 4 (18.4%), and 6 (8.4%) prescribed medications/month. For the secondary GBTM, 3 trajectory groups were identified for CP only: 80.5% were characterized as negligible probability of polypharmacy exposure, 10.8% as low probability, and 8.7% as high probability. Five trajectory groups were identified for CP + NDDs: 37.9% as negligible probability of polypharmacy exposure, 32.8% as constantly high probability, and 29.2% as changing probability (eg, increasing/decreasing). CONCLUSIONS: Children with CP are chronically exposed to differing levels of polypharmacy. Findings can help establish polypharmacy surveillance practices. Studies need to determine if polypharmaceutical strategies are balanced to optimize health and development for children with CP. DISCLOSURES: Dr Whitney is supported by the University of Michigan Office of Health Equity and Inclusion Diversity Fund. The funding source had no role in the design or conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.

International, multidisciplinary Delphi consensus recommendations on non-pharmacological interventions for fibromyalgia.

OBJECTIVES: To develop evidence-based expert recommendations for non-pharmacological treatments for pain, fatigue, sleep problems, and depression in fibromyalgia. METHODS: An international, multidisciplinary Delphi exercise was conducted. Authors of EULAR and the Canadian Fibromyalgia Guidelines Group, members of the American Pain Society and clinicians with expertise in fibromyalgia were invited. Participants were asked to select non-pharmacological interventions that could be offered for specific fibromyalgia symptoms and to classify them as either core or adjunctive treatments. An evidence summary was provided to aid the decision making. Items receiving >70% votes were accepted, those receiving <30% votes were rejected and those obtaining 30-70% votes were recirculated for up to two additional rounds. RESULTS: Seventeen experts participated (Europe (n = 10), North America (n = 6), and Israel (n = 1)) in the Delphi exercise and completed all three rounds. Aerobic exercise, education, sleep hygiene and cognitive behavioural therapy were recommended as core treatments for all symptoms. Mind-body exercises were recommended as core interventions for pain, fatigue and sleep problems. Mindfulness was voted core treatment for depression, and adjunctive treatment for other symptoms. Other interventions, namely music, relaxation, hot bath, and local heat were voted as adjunctive treatments, varying between symptoms. CONCLUSIONS: This study provided evidence-based expert consensus recommendations on non-pharmacological treatments for fibromyalgia that may be used to individualise treatments in clinical practice targeting the diverse symptoms associated with fibromyalgia.

Within-day rhythms of pain and cognitive function in people with and without fibromyalgia: synchronous or syncopated?

ABSTRACT: Cognitive dysfunction is a common fibromyalgia (FM) symptom and can impact on the daily lives of those affected. We investigated whether within-day pain intensity ratings were associated with contemporaneous objective and subjective measures of cognitive function and whether within-day increases in pain intensity preceded increases in cognitive dysfunction or vice versa. Inclusion of a non-FM group allowed us to examine whether effects were specific to FM. Fifty people with FM and 50 non-FM controls provided 7 days of data. Cognitive tests (processing speed and working memory) and ecological momentary assessments (pain intensity and self-reported cognitive functioning) were conducted ×5/day. Three-level multilevel models examined contemporaneous and within-day 1-lag pain intensity-cognitive functioning associations. Interaction terms assessed possible moderating effects of FM status. Momentary increase in pain was associated with increased self-reported cognitive dysfunction, more strongly so for those with FM (B = 0.27, 95% confidence interval 0.22-0.32; non-FM B = 0.17, 95% confidence interval 0.10-0.23). For the FM group, higher pain was associated with longer processing speed; for the non-FM group, higher pain was associated with shorter processing speed. Pain increase did not precede change in subjective or objective cognitive function in the FM group, but reduction in working memory preceded increase in pain intensity. This finding warrants further research attention and, if replicated, could hold prognostic and/or therapeutic potential.

The effect of COVID-19 public health restrictions on the health of people with musculoskeletal conditions and symptoms: the CONTAIN study.

OBJECTIVE: To quantify the change in quality of life, disease-specific indicators, health and lifestyle before and during the COVID-19 pandemic among people with musculoskeletal diagnoses and symptoms. METHODS: We undertook an additional follow-up of two existing UK registers involving people with axial spondyloarthritis (axSpA) or psoriatic arthritis (PsA) and participants in a trial in the UK who had regional pain and were identified at high risk of developing chronic widespread pain. Participants completed the study questionnaire between July and December 2020, throughout which time there were public health restrictions in place. RESULTS: The number of people taking part in the study was 1054 (596 axSpA, 162 PsA, 296 regional pain). In comparison with their previous (pre-pandemic) assessment, there was an age-adjusted significant, small decrease in quality of life measured by EQ-5D [-0.020 (95% CI -0.030, -0.009)] overall and across all population groups examined. This was primarily related to poorer mental health and pain. There was a small increase in fibromyalgia symptoms, but a small decrease in sleep problems. There was a small deterioration in axSpA disease activity, and disease-specific quality of life and anxiety in PsA participants. Predictors of poor quality of life were similar pre- and during the pandemic. The effect of lockdown on activity differed according to age, gender and deprivation. CONCLUSION: Important lessons include focusing on addressing anxiety and providing enhanced support for self-management in the absence of normal health care being available, and awareness that all population groups are likely to be affected.

Obstructive sleep apnea and fractures in children and adolescents.

STUDY OBJECTIVES: To examine, among girls and boys, associations between site-specific extremity fracture and sleep apnea diagnosis or treatment. METHODS: A cross-sectional analysis of claims data from 2016 to 2018 for children aged 2-18 years. Children with sleep apnea, continuous positive airway pressure, adenotonsillectomy, and fracture were identified using International Classification of Diseases, 10th Revision, Current Procedural Terminology, and Healthcare Common Procedure Coding System codes. We examined sex-stratified associations between site-specific fracture, sleep apnea, and sleep apnea treatment. RESULTS: Among 2,327,104 children, 9,547 (0.41%) had sleep apnea and nearly 61% were treated. Girls with sleep apnea, treated or untreated, had increased odds of lower, but not upper, extremity fracture compared to those without sleep apnea (treated 1.56, 95% confidence interval 1.11, 2.21; untreated odds ratio 1.63, 95% confidence interval 1.09, 2.44). Only boys untreated for sleep apnea had increased odds of lower extremity fracture in comparison to those without a diagnosis of sleep apnea (odds ratio 1.65, 95% confidence interval 1.20, 2.27). Interestingly, boys treated for sleep apnea but not those untreated, in comparison to boys without sleep apnea, had different (reduced) odds of upper extremity fracture (odds ratio 0.74, 95% confidence interval 0.59, 0.95). CONCLUSIONS: These large datasets provide evidence that both boys and girls with untreated sleep apnea have higher odds of lower extremity fractures. However, treatment for sleep apnea was associated with improved odds of lower extremity fracture only in boys. Upper extremity data were less clear. These data are cross-sectional and cannot show causality, but they suggest that treatment for sleep apnea may lower risk for extremity fractures in boys. CITATION: Matlen LB, Whitney DG, Whibley D, Jansen EC, Chervin RD, Dunietz GL. Obstructive sleep apnea and fractures in children and adolescents. J Clin Sleep Med. 2021;17(9):1853-1858.

Characterizing chronic pain phenotypes in multiple sclerosis: a nationwide survey study.

ABSTRACT: Chronic pain is highly prevalent in multiple sclerosis (MS). Pain heterogeneity may contribute to poor treatment outcomes. The aim of this study was to characterize pain phenotypes distributions in persons with MS and compare pain phenotypes in terms of pain intensity, frequency of chronic overlapping pain conditions, and use and analgesic effects of different classes of pain medications. Data were collected through a national web-based survey with measures of neuropathic (painDETECT) and nociplastic pain (Fibromyalgia Survey Criteria), chronic overlapping pain conditions, and pain medication use and pain relief. In a sample of N = 842 adults with chronic pain and MS, the largest proportion (41%) showed evidence of nociceptive pain, 27% had mixed neuropathic/nociplastic pain, 23% had nociplastic pain, and 9% had neuropathic pain. Nociplastic pain was associated with significantly higher pain intensity and frequency of chronic overlapping pain conditions. Across all pain types, high frequency of pain medication use along with poor-modest pain relief was reported. Cannabis use for pain was more common, and pain relief ratings were higher among those with nociplastic pain, relative to nociceptive pain. Although NSAID use was highest among those with nociplastic pain (80%), pain relief ratings for NSAIDs were highest among those with nociceptive pain. These findings underscore the need for multidimensional assessment of pain in MS with greater emphasis on the identification of pain phenotype. An improved characterization of pain as a multifaceted condition in MS could inform therapeutic approaches.

The Role of Environmental Distractions in the Experience of Fibrofog in Real-World Settings.

OBJECTIVE: Perceived cognitive dysfunction in people with fibromyalgia (FM), "fibrofog," is commonly reported and has been demonstrated in neurocognitive testing. Distractibility and inattention have been implicated as potential contributors to fibrofog, but the role of environmental distractions has not been explored. In this study, ambulatory assessment methods were used to examine whether FM is related to more environmental distractions and to examine the impact of distractions on subjective and objective cognitive functioning. METHODS: Fifty people with FM and 50 age-, sex-, and education-matched controls without FM completed 8 consecutive days of ambulatory assessments. Five times per day, participants reported perceived cognitive functioning and environmental distractions and completed validated tests of processing speed and working memory. RESULTS: The FM group reported distractions in a higher proportion of the ambulatory cognitive testing sessions (40.5%) compared with the group without FM (29.8%; P < 0.001) and more often reported multiple simultaneous distractions. For both groups, sound was the most common distraction. The group with FM reported more distractions caused by light, and the group without FM reported more social distractions. Group differences in subjective and objective cognitive functioning were not augmented during distraction relative to during periods of no distraction. There were no group differences in within-person changes in cognitive functioning as a function of distraction. CONCLUSION: The group with FM reported more distractions than the group without FM; both groups reported poorer processing speed when distracted, and the effects of distraction on test performance did not differ significantly by group. Findings suggest that sensitivity to environmental distractions may play a role in the experience of cognitive dysfunction in FM.

Fibrofog in Daily Life: An Examination of Ambulatory Subjective and Objective Cognitive Function in Fibromyalgia.

OBJECTIVE: Perceived cognitive dysfunction in fibromyalgia (FM), "fibrofog," is common. Prior laboratory-based studies have limited our understanding of cognitive function in FM in daily life. The objective of this study was to explore levels of subjective and objective cognitive functioning and the association between subjective and objective aspects of cognition in people with and without FM in the lived environment. METHODS: Participants (n = 50 adults with FM; n = 50 adults without FM, matched for age, sex, and education) completed baseline measures of subjective and objective cognitive functioning (NIH Toolbox). They also completed ecological momentary assessments of cognitive clarity and speed and tests of processing speed and working memory, via a smart phone app, 5×/day for 8 days. RESULTS: On baseline objective measures, the FM group demonstrated poorer cognitive functioning across 3 NIH Toolbox tests. There were no strong correlations between subjective and objective cognitive functioning in both the FM and control groups. In the lived environment, the FM group demonstrated poorer subjective cognition and objective working memory; groups did not differ on processing speed. Momentary ratings of subjective cognitive dysfunction were significantly related to changes in objective processing speed but not working memory, with no group differences. CONCLUSION: Findings indicate worse laboratory-based and ambulatory subjective and objective cognitive function for those individuals with FM compared to those without FM. Similar associations between measures of subjective and objective cognitive functioning for the groups suggest that people with FM are not overstating cognitive difficulties. Future research examining contributors to ambulatory fibrofog is warranted.

The effect of low-trauma fracture on one-year mortality rate among privately insured adults with and without neurodevelopmental disabilities.

BACKGROUND: Individuals with neurodevelopmental disabilities (NDDs) have poor development and preservation of skeletal health throughout the lifespan, and are especially vulnerable to low-trauma fracture and post-fracture health complications. However, no studies have examined if adults with NDDs have greater post-fracture mortality risk compared to adults without NDDs. The purpose of this study was to determine whether adults with NDDs have greater 12-month mortality rates following a low-trauma fracture compared to adults without NDDs. METHODS: Data from 2011 to 2017 was leveraged from Optum Clinformatics® Data Mart; a nationwide claims database from a single private payer in the U.S. Data were extracted from adults (18+ years) with and without NDDs that sustained a low-trauma fracture between 01/01/2012-12/31/2016, as well as pre-fracture chronic diseases (i.e., cardiovascular diseases, cerebrovascular diseases, diabetes, chronic obstructive pulmonary diseases, cancer). Mortality rate was estimated for adults with and without NDDs, and the mortality rate ratio (RR) and 95% confidence interval (CI) was calculated. Cox regression was used to estimate hazard ratio (HR) and 95% CI for 1-, 3-, 6-, and 12-month post-fracture mortality rates between adults with and without NDDs after adjusting for age, sex, race, U.S. region, and pre-fracture chronic diseases. RESULTS: Mean age (SD) at baseline was 56.7 (20.6) for adults with NDDs (n = 3749; 45.2% men) and 63.9 (19.2) for adults without NDDs (n = 585,910; 34.4% men). During the 12-month follow-up period, 182 adults with NDDs (mean age [SD] = 69.8 [14.7]; 46.2% men) and 25,456 adults without NDDs (mean age [SD] = 78.9 [9.8]; 38.3% men) died. Crude mortality rate was not different between adults with and without NDDs for any time points (e.g., 12-months: 5.40 vs. 4.96 per 100 person years; RR = 1.09; 95% CI = 0.94-1.26); however, it was greater for adults with intellectual disabilities compared to adults without NDDs (RR = 1.46; 95% CI = 1.23-1.79). After adjustments, adults with NDDs had greater post-fracture mortality rates for 3-, 6-, and 12-month time points (e.g., 12-months: HR = 1.46; 95% CI = 1.27-1.69). When stratified by the type of NDD, adults with intellectual disabilities and adults with autism spectrum disorders, but not adults with cerebral palsy, had greater 12-month post-fracture mortality risk. When stratified by fracture location, lower extremities were associated with greater crude mortality rate (RR = 1.69; 95% CI = 1.22-2.35) and adjusted mortality risk (HR = 2.41; 95% CI = 1.73-3.35), while upper extremities were associated with greater adjusted mortality risk (HR = 1.76; 95% CI = 1.23-2.50) for adults with vs. without NDDs. CONCLUSIONS: Among privately insured adults with NDDs, low-trauma fracture is associated with greater mortality risk within 1 year of the fracture event, even after adjusting for pre-fracture chronic diseases. Study findings suggest the need for earlier fracture prevention strategies and improved post-fracture healthcare management.

Maintained physical activity and physiotherapy in the management of distal arm pain: a randomised controlled trial.

Objectives: The epidemiology of distal arm pain and back pain are similar. However, management differs considerably: for back pain, rest is discouraged, whereas patients with distal arm pain are commonly advised to rest and referred to physiotherapy. We hypothesised that remaining active would reduce long-term disability and that fast-track physiotherapy would be superior to physiotherapy after time on a waiting list. Methods: Adults referred to community-based physiotherapy with distal arm pain were randomised to: advice to remain active while awaiting physiotherapy (typically delivered after 6-8 weeks); advice to rest while awaiting physiotherapy, or immediate treatment. Intention-to-treat analysis determined whether the probability of recovery at 26 weeks was greater among the active advice group, compared with those advised to rest and/or among those receiving immediate versus usually timed physiotherapy. Results: 538 of 1663 patients invited between February 2012 and February 2014 were randomised (active=178; rest=182; immediate physiotherapy=178). 81% provided primary outcome data, and complete recovery was reported by 60 (44%), 46 (32%) and 53 (35%). Those advised to rest experienced a lower probability of recovery (OR: 0.54; 95% CI 0.32 to 0.90) versus advice to remain active. However, there was no benefit of immediate physiotherapy (0.64; 95% CI 0.39 to 1.07). Conclusions: Among patients awaiting physiotherapy for distal arm pain, advice to remain active results in better 26-week functional outcome, compared with advice to rest. Also, immediate physiotherapy confers no additional benefit in terms of disability, compared with physiotherapy delivered after 6-8 weeks waiting time. These findings question current guidance for the management of distal arm pain.

Fatigue is associated with excess mortality in the general population: results from the EPIC-Norfolk study.

BACKGROUND: Significant fatigue is a frequent reason for seeking medical advice in the general population. Patients, however, commonly feel their complaint is ignored. This situation may be because clinicians perceive fatigue to be benign, unrelated to traditional biomedical outcomes such as premature mortality. The present study aimed to investigate whether an association between significant fatigue and mortality actually exists, and, if so, to identify potential mechanisms of this association. METHODS: A population-based cohort of 18,101 men and women aged 40-79 years who completed a measure of fatigue (Short Form 36 vitality domain, SF36-VT) in addition to providing information on possible confounding factors (age, sex, body mass index, marital status, smoking, education level, alcohol consumption, social class, depression, bodily pain, diabetes, use of ß blockers, physical activity and diet) and mechanisms (haemoglobin, C-reactive protein and thyroid function) were followed up prospectively for up to 20 years. Mortality from all causes, cancer and cardiovascular disease was ascertained using death certification linkage with the UK Office of National Statistics. RESULTS: During 300,322 person years of follow-up (mean 16.6 years), 4397 deaths occurred. After adjusting for confounders, the hazard ratio (HR) for all-cause mortality was 1.40 (95 % confidence interval [CI] 1.25-1.56) for those reporting the highest fatigue (bottom SF36-VT quartile) compared with those reporting the lowest fatigue (top SF36-VT quartile). This significant association was specifically observed for those deaths related to cardiovascular disease (HR 1.45, 95 % CI 1.18-1.78) but not cancer (HR 1.09, 95 % CI 0.90-1.32). Of the considered mechanisms, thyroid function was most notable for attenuating this association. The risk of all-cause mortality, however, remained significant even after considering all putative confounders and mechanisms (HR 1.26, 95 % CI 1.10-1.45). CONCLUSIONS: High levels of fatigue are associated with excess mortality in the general population. This commonly dismissed symptom demands greater evaluation and should not automatically be considered benign.

Management of Widespread Pain and Fibromyalgia.

Specialists' views of fibromyalgia (FM) are typically colored by their experiences of the selected, complex cases that they are regularly called to evaluate. At a population level, it is crucial to recognize that education which promotes patient empowerment and non-pharmacological interventions which support self-management are very effective. The temptation, for both physician and patient, to first reach for pharmacological interventions should be resisted until such holistic approaches are explored. In particular, a strong evidence base supports graded exercise and cognitive behavioral therapies, but such treatments must be intelligently "prescribed." As reflected by the recent ACR criteria, FM is a highly heterogeneous disorder and is not simply a disorder of pain. For some patients, co-occurring symptoms, such as fatigue, can be equally as impactful and so management strategies should be sufficiently versatile to target those dimensions which are considered priorities at the level of the individual patient. In those patients who do require pharmacological support, patients should not be led to expect significant gains in isolation. The importance of self-management requires emphasis at each and every tier of management. It is true that advances in our understanding of neurobiology have greatly informed the selection of adjunctive drug classes which may provide benefit (as well as those which do not-as is the case of opioids). However, further unpicking of pathogenesis is still required if the FM landscape is to move further towards drug-led management.