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The aims of this study were to: (1) estimate the prevalence of chronic pain (CP) and high impact chronic pain (HICP) in a community sample of children and adolescents; and (2) compare groups (those without CP, those with CP but no HICP, and those with HICP) with respect to demographic variables, pain variables, and physical, psychological, and school-related function. One thousand one hundred and fifteen children and adolescents participated (56% girls; age: ߂= 11.67; SD = 2.47; range = 8 to 18 years). The prevalence of CP and HICP was 46% and 5%, respectively, and was higher in girls and increased with age. Participants with HICP reported greater pain intensity and higher pain frequency than those with CP but no HICP. In addition, participants with HICP reported lower mobility, greater fatigue, worst sleep quality, more anxiety and depression symptoms, worst cognitive function, missing more school days, and worse perceived school performance. HICP is a prevalent condition in children and adolescents and is associated with many negative consequences. Stakeholders must be aware of this and ensure that treatment programs are available to reduce the individual and societal impact of HICP in young individuals. PERSPECTIVE: : This article provides information on CP and HICP prevalence and impact in children and adolescents. By better understanding the nature and score of these conditions, we will be able to develop more effective early interventions to help this population and thereby reduce their long-term negative impact.

The 0 to 10 numeric rating scale (NRS) of pain intensity is a standard outcome in randomized controlled trials (RCTs) of pain treatments. For individuals taking analgesics, there may be a disparity between “observed” pain intensity (the NRS, irrespective of concurrent analgesic use), and “underlying” pain intensity (what the NRS would be had concurrent analgesics not been taken). Using a contemporary causal inference framework, we compare analytic methods that can potentially account for concurrent analgesic use, first in statistical simulations, and second in analyses of real (non-simulated) data from an RCT of lumbar epidural steroid injections (LESI). The default analytic method was ignoring analgesic use, which is the most common approach in pain RCTs. Compared to ignoring analgesic use and other analytic methods, simulations showed that a quantitative pain and analgesia composite outcome based on adding 1.5 points to observed pain intensity for those who were taking an analgesic (the QPAC1.5) optimized power and minimized bias. Analyses of real RCT data supported the results of the simulations, showing greater power with analysis of the QPAC1.5 as compared to ignoring analgesic use and most other methods examined. We propose alternative methods that should be considered in the analysis of pain RCTs.

TK2d is an ultrarare autosomal recessive mitochondrial DNA depletion syndrome. Nucleoside therapy improves or stabilizes disease across key outcomes including survival, ambulation, and requirement for mechanical ventilation. However, little is known about the effects of nucleoside therapy treatment of TK2d from the patient's perspective. This study sought to address this knowledge gap. Participants with TK2d and/or their parents/caregivers completed online surveys with standardized health measures and interviews. During interviews, participants rated and described TK2d's impact on 13 quality of life domains, changes since starting nucleoside therapy, and if they would recommend nucleoside therapy. Twenty-five individuals participated (17 adults with TK2d, 4 parent-participant pairs, 4 parents of children with TK2d). Adult participants with TK2d had clinically meaningfully worse scores than the general population on global physical and mental health, physical function, pain interference, fatigue, anxiety, and social function. Children's mobility and pain interference were significantly worse than the general pediatric population. Physical domains most affected by TK2d were: mobility (84%), fatigue (60%), respiratory function (56%), and hospitalizations (55%). Psychosocial domains most affected were: impact on family members (39%), mood (36%), and social life (28%). Most (77%) treated patients reported improvement; whereas, 67% in the untreated group reported worsening. All participants would recommend nucleoside therapy. In summary, TK2d has significant negative impacts on most areas of life and function. Measures of fatigue, sleep, swallowing/eating, speaking, and mood, should be considered as outcomes in clinical trials and research studies. Nucleoside therapy appears to provide meaningful improvements across many health domains affected by TK2d. SYNOPSIS: The consequences of having TK2d are devastating for both those with the disorder and their families; however, nucleoside therapy appears to provide meaningful improvements across many health domains affected by TK2d.

Measures of pain intensity (eg, numeric rating scales [NRS]) are widely used in clinical research and practice. While these measures have evidence for validity and reliability, poor standardization of instructions, and response options limits precision of pain assessment, allows for inconsistency in interpretation, and presents a challenge for comparison and aggregation of study results. Despite these pitfalls, the 0 to 10 NRS remains the most commonly used primary outcome measure in clinical trials of pain treatments and is the core measure recommended by regulatory agencies. The purpose of this study was to describe the first phase in the development of a pain intensity measure that is easily interpretable, psychometrically sound, and that adheres to FDA qualification processes. The Analgesic, Anesthetic, and Addiction Clinical Trial, Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership conducted concept elicitation interviews (N = 44; 22 with acute pain; 22 with chronic pain) to understand the patient perspective on rating pain intensity and to identify actionable suggestions for improved clarity and meaningfulness of instructions, recall periods, and response options. This article summarizes interview findings, describes how patient input and FDA feedback informed preliminary candidate measures, and provides an overview of the FDA qualification process. PERSPECTIVE: Concept elicitation interviews informed the development of content-valid candidate measures of acute and chronic pain intensity for planned use in clinical trials of pain treatments, and comprise the initial stage in FDA clinical outcome assessment qualification. Measures will subsequently be evaluated through cognitive interviews and a series of psychometric studies.

Chronic pain is a multidimensional experience and pain treatments targeting psychosocial factors reduce pain and improve function. These treatments often overlook the sociocultural factors that influence pain and the psychological factors associated with function in people with chronic pain. Although preliminary findings suggest that cultural background may influence pain and function via their effects on beliefs and coping, no previous study has directly tested if the country of origin moderates the associations between these psychological factors and pain and function. This study sought to address this knowledge gap. Five hundred sixty-one adults with chronic pain, born and living in the USA (n = 273) or Portugal (n = 288), completed measures of pain, function, pain-related beliefs, and coping. Between-country similarities were found in the endorsement of beliefs related to disability, pain control, and emotion, and in asking for assistance, task persistence, and coping self-statement responses. Portuguese participants reported greater endorsement of harm, medication, solicitude, and medical cure beliefs, more frequent use of relaxation and support seeking, and less frequent use of guarding, resting, and exercising/stretching. In both countries, disability and harm beliefs and guarding responses were associated with worse outcomes; pain control and task persistence were associated with better outcomes. Six country-related small effect-size moderation effects emerged, such that task persistence and guarding are stronger predictors of pain and function in adults from the USA, but pain control, disability, emotion, and medication beliefs are more important in adults from Portugal. Some modifications may be needed when adapting multidisciplinary treatments from one country to another. Perspective: This article examines the similarities and differences in beliefs and coping endorsed by adults with chronic pain from 2 countries, and the potential moderation effects of country on the associations between these variables and pain and function. The findings suggest that some modifications may be needed when culturally customizing psychological pain treatments.

Objective To describe pain intensity and interference in people with progressive multiple sclerosis (MS), compare these with people with relapsing-remitting multiple sclerosis (RRMS), and identify common and unique factors associated with pain intensity in people with progressive MS and RRMS. Design Observational, cross-sectional analysis using baseline data from a longitudinal survey on quality of life in participants with MS. Setting Community. Participants A total of 573 adults with MS (N=573; progressive MS, n=142; RRMS, n=431). Interventions Not applicable. Main Outcome Measures Average pain intensity was measured by an 11-point numeric rating scale, and pain interference was measured by the Patient-Reported Outcomes Measurement Information System Pain Interference Short Form. Results Participants with progressive MS reported moderate average pain intensity (3.22±2.50) and elevated pain interference (T score of 55.55±9.13). They did not differ significantly from those with RRMS in average pain intensity or pain interference. Common factors associated with higher average pain intensity were more severe disability, lower education level, unemployment, and current smoking. In those with progressive MS, older age was associated with lower average pain intensity. Conclusions Pain intensity and interference are similar across MS types. In addition to assessing and treating pain, it is important to screen for modifiable pain-related factors, such as smoking cessation, in this population.

Pain catastrophizing has been recognized as an important and consistent psychosocial predictor of nearly every key pain-related outcome. The purpose of this study was to develop a new measure of pain catastrophizing using modern psychometric methodology. People with chronic pain (N = 795) responded to thirty items. Data were analyzed using item response theory, including assessment of differential item functioning and reliability. Sensitivity to change and validity were examined using data collected from patients undergoing spinal fusion surgery (n = 184) and participating in an ongoing longitudinal aging with a disability survey study (n = 1,388). The final 24-item bank had no items with significant local dependence, misfit, or differential item functioning. Results provided strong evidence of reliability and validity. Six- and 2-item short forms were developed for use when computer adaptive testing is not feasible or desirable. The item bank was named the University of Washington Concerns About Pain scale because the term "catastrophizing" was considered stigmatizing by people with chronic pain. Guidance for score interpretation was developed with extensive feedback from individuals with chronic pain. The Concerns About Pain item bank, short forms, and user manuals are free and publicly available to all users and can be accessed online at https://uwcorr.washington.edu/measures/. PERSPECTIVE: This article presents the development of the University of Washington Concerns About Pain scale, the first item response theory-based item bank of pain catastrophizing. The measure is intended for clinicians interested in improving outcomes of patients with chronic pain and for researchers who study impact of and treatment interventions aimed at reducing pain catastrophizing.

The estimated probability of progressing from phase 3 analgesic clinical trials to regulatory approval is approximately 57%, suggesting that a considerable number of treatments with phase 2 trial results deemed sufficiently successful to progress to phase 3 do not yield positive phase 3 results. Deficiencies in the quality of clinical trial conduct could account for some of this failure. An Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials meeting was convened to identify potential areas for improvement in trial conduct in order to improve assay sensitivity (ie, ability of trials to detect a true treatment effect). We present recommendations based on presentations and discussions at the meeting, literature reviews, and iterative revisions of this article. The recommendations relate to the following areas: 1) study design (ie, to promote feasibility), 2) site selection and staff training, 3) participant selection and training, 4) treatment adherence, 5) data collection, and 6) data and study monitoring. Implementation of these recommendations may improve the quality of clinical trial data and thus the validity and assay sensitivity of clinical trials. Future research regarding the effects of these strategies will help identify the most efficient use of resources for conducting high quality clinical trials. PERSPECTIVE: Every effort should be made to optimize the quality of clinical trial data. This manuscript discusses considerations to improve conduct of pain clinical trials based on research in multiple medical fields and the expert consensus of pain researchers and stakeholders from academia, regulatory agencies, and industry.

Ultramarathon runners commonly endure musculoskeletal pain during endurance events. However, the effect of pain coping skills on performance has not been examined.A prospective observational study during three 250 km (155 mi), 6 stage ultramarathons was conducted. Finish line surveys were completed after each of the four 40 km (25 mi) and one 80 km (50 mi) stages of racing. Variables gathered included pain intensity, pain coping strategy use, pain interference, finishing position (quintile), and successful race completion.A total of 204 participants (age 41.4±10.3 y; 73% male) reported average pain intensity of 3.9 (±2.0 SD) and worst pain intensity of 5.3 (±2.3) on a 0 to 10 scale. They used greater adaptive pain coping strategies (3.0±1.3) relative to maladaptive strategies (1.3±1.1). Worst pain and pain interference increased over each stage of the race for all runners (P0.001), with worst pain being significantly different by finishing status (P=0.02). Although all runners endured increased pain and interference, the nonfinishers (28 [14%]) had significantly greater differences in changes in pain intensity (P0.01) and pain interference (P0.001). Maladaptive pain coping strategies were more common in nonfinishers; with each 1-point increase (0-6 scale), there was a 3 times increase in odds of not finishing the race.Although increased pain intensity and pain interference was found in all multistage ultramarathon runners, successful event completion was significantly associated with less maladaptive pain coping. Training in coping with pain may be a beneficial part of ultramarathon preparation.

Background Sleep problems are common for individuals living with physical disabilities and chronic pain. However, the factors that influence the relationship between pain and sleep problems in these populations remain unknown. Objective The aim of this study was to increase our understanding of the physical, emotional and cognitive factors associated with sleep disturbance in individuals with chronic health conditions often associated with physical disabilities. Methods Participants were recruited from a database of individuals with a variety of chronic health conditions, including multiple sclerosis, spinal cord injury, back pain, osteoarthritis, and amputations. To participate in the study, they needed to report having a chronic pain problem. Participants completed an online survey using REDCap assessing average pain intensity (Numerical Rating Scale-11), pain extent (number of painful body areas), sleep disturbance (PROMIS Sleep Disturbance), depression (PROMIS Emotional Distress-Depression) and catastrophizing (Coping Strategies Questionnaire). A total of 455 participants (Mage = 58.9; SD = 11.4), of which 292 (64%) were women, provided complete data. We performed a series of four regression analyses. Results After controlling for age and sex, the predictors explained an additional 7–16% of the variance in sleep disturbance. The final model with all of the predictors explained 22%. Conclusions Consistent with the study hypothesis, all the variables examined made significant and independent contributions to the variance in sleep disturbance. The findings provide additional evidence that physical, emotional and cognitive factors all play a role in the sleep quality of individuals with chronic health conditions often associated with physical disabilities.

That certain psychological factors are negatively associated with function in patients with chronic pain is well established. However, few studies have evaluated these factors in individuals with chronic pain from the general population. The aims of this study were to: 1) evaluate the unique associations between catastrophizing and perceived solicitous responses and psychological function, physical function, and insomnia severity in individuals with neuropathic pain, osteoarthritis, or spinal pain in the general population; and 2) determine if diagnosis moderates the associations found. Five hundred fifty-one individuals from the general population underwent examinations with a physician and physiotherapist, and a total of 334 individuals were diagnosed with either neuropathic pain (n = 34), osteoarthritis (n = 78), or spinal pain (n = 222). Results showed that catastrophizing was significantly associated with reduced psychological and physical function, explaining 24% and 2% of the variance respectively, whereas catastrophizing as well as perceived solicitous responding were significantly and uniquely associated with insomnia severity, explaining 8% of the variance. Perceived solicitous responding was significantly negatively associated with insomnia severity. Moderator analyses indicated that: 1) the association between catastrophizing and psychological function was greater among individuals with spinal pain and neuropathic pain than those with osteoarthritis, and 2) the association between catastrophizing and insomnia was greater among individuals with spinal pain and osteoarthritis than those with neuropathic pain. No statistically significant interactions including perceived solicitous responses were found. The findings support earlier findings of an association between catastrophizing and function among individuals with chronic pain in the general population, and suggest that diagnosis may serve a moderating role in some of these associations. Perspective When examining persons with pain in the general population, catastrophizing is associated with several aspects of function, and diagnosis serves as a moderator for these associations. The replication of these associations in the general population support their reliability and generalizability.

Background In individuals with multiple sclerosis (MS) comorbidities and quality of life (QOL) may be affected by tobacco use. Objective To evaluate the associations between smoking status, in particular quit attempts, and comorbidities among individuals with MS. Methods We used a web-based survey to obtain cross-sectional data from 335 individuals with MS who were members of the Gateway Chapter of the National MS Society email registry. We then examined the associations between smoking variables (current use, frequency, and quit attempts) and comorbidities. Results The prevalence of participants who ever smoked was 50%, which is greater than that reported for the general population; 20% were current smokers. Migraine headaches were associated with current use and everyday smoking, and those with recent failed quit attempts had a higher prevalence of depression than those who were current smokers but who did not attempt to quit or had successfully quit in the past year. Conclusion Given the associations between smoking and comorbidities in individuals with MS, health care providers should both (1) assess smoking history and quit attempts, and (2) encourage individuals with MS who smoke to become non-smokers and refer for treatment, as indicated. In order to increase the chances that individuals will be successful in becoming non-smokers, clinicians would do well to also assess and treat depression in their patients who smoke and are also depressed.

Objectives To determine if resilience is uniquely associated with functional outcomes (satisfaction with social roles, physical functioning, and quality of life) in individuals with physical disabilities, after controlling for measures of psychological health (depression and anxiety) and symptom severity (pain, fatigue, and sleep disturbance); and to examine the potential moderating effect of sex, age, and diagnosis on the hypothesized associations between resilience and function. Design Cross-sectional survey study. Setting Surveys were mailed (81% response rate) to a community sample of 1949 individuals with multiple sclerosis, muscular dystrophy, postpoliomyelitis syndrome, or spinal cord injury. Participants were recruited through the Internet or print advertisement (28%), a registry of previous research participants who indicated interest in future studies (21%), a departmental registry of individuals interested in research (19%), disability-specific registries (18%), word of mouth (10%), or other sources (3%). Participants Convenience sample of community-dwelling adults aging with physical disabilities (N=1574), with a mean Connor-Davidson Resilience Scale (10 items) score of 29. Interventions Not applicable. Main Outcome Measures Patient-Reported Outcomes Measurement Information System measures of Satisfaction with Social Roles and Activities and Physical Functioning, the World Health Organization's brief Older People's Quality of Life Questionnaire, and the Connor-Davidson Resilience Scale (10 items). Results After controlling for age, age squared, sex, diagnosis, psychological health, and symptom severity, resilience was significantly and positively associated with satisfaction with social roles (β=.17, P P P >.05). For every 1-point increase in scores of resilience, there was an increase of .50 in the quality of life score and .20 in the satisfaction with social roles score. Sex also moderated the association between resilience and satisfaction with social roles (F 1,1453 =4.09, P =.043). Conclusions The findings extend past research, providing further evidence indicating that resilience plays a unique role in nonphysical functional outcomes among individuals with physical disabilities.

Objectives (1) To determine if resilience exhibits similar stability across time as depression, fatigue, and sleep quality; and (2) to determine if changes in resilience over a period of 1 year are associated with changes in depression, fatigue, sleep quality, and physical function over the same time period. Design Observational longitudinal survey study with measures administered 2 times, 1 year apart. Setting Community-based population sample. Participants Adults with physical disabilities (N=893). Interventions Not applicable. Main Outcome Measures Primary outcomes were measures of resilience (Connor-Davidson Resilience Scale), depression (Patient Health Questionnaire-9), fatigue (Patient-Reported Outcomes Measurement Information System [PROMIS] Fatigue Short Form), sleep quality (PROMIS Sleep Disturbance), and physical function (8-item PROMIS Physical Functioning). Results Resilience ( r =.71, P r =.71, P r =.79, P r =.68, P 1,885 =70.23; P R 2 =.54) and fatigue (F 1,885 =25.66; P R 2 =.64), and an increase in resilience was associated with improved sleep quality (F 1,885 =30.76; P R 2 =.48) and physical function (F 1,885 =16.90; P R 2 =.86) over a period of 1 year, while controlling for age, sex, and diagnosis. Conclusions Resilience exhibits similar test-retest stability as other important domains that are often treatment targets. Changes in resilience were associated with changes in depression, fatigue, sleep quality, and physical functioning over the course of 1 year. Further longitudinal and experimental research is warranted to investigate the potential causal effect of changes in resilience on quality of life in individuals with physical disabilities.

Available online This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal .

Objective To determine whether baseline levels of pain, fatigue, sleep disturbance, and physical activity measured at the initial assessment predicted the development of or improvement of depression 3.5 years later, while controlling for sex, age, and disease severity. Design Observational, longitudinal survey study. Setting A community-based population sample. Participants Adults with multiple sclerosis (MS) (N=489). Interventions Not applicable. Main Outcome Measure Primary outcome was classification of depression group measured using a Patient Health Questionnaire-9 cutoff score ≥10, indicating probable major depression. Results Fatigue severity (odds ratio, 1.19; 95% confidence interval, 1.12–1.26; P P =.001) predicted probable major depression 3.5 years later among those not depressed at the initial assessment. An effect of age (odds ratio, .96; 95% confidence interval, .92–.99; P =.008) was found among those who developed depression, indicating that younger adults were more likely to develop depression. Pain, fatigue, sleep, and physical activity at baseline were not significantly associated with recovery from depression among those depressed at the initial assessment. Conclusions Fatigue and sleep may contribute to the development of depression. Clinical trial research targeting these variables to determine their influence on depression is warranted.

Background Adults with long-term disability are living longer and may experience accelerated aging. More information is needed to understand the incidence of chronic comorbid medical conditions in this population. Objective To examine the incidence, prevalence, age of onset and predictors of five chronic conditions in a sample of adults with long-term physical disability. Methods Longitudinal self-report surveys were mailed to 1594 adults with multiple sclerosis, muscular dystrophy, post-polio syndrome or spinal cord injury twice, 3.5 years apart. Survey questions assessed demographics (date of birth, sex, income, disability type, height/weight), self-reported diagnosis of coronary heart disease, hypertension, arthritis, diabetes and cancer, and health behaviors (alcohol use, smoking, physical activity). Results Over the course of the study, the most commonly reported new onset chronic comorbid medical condition was arthritis (percent incidence = 14%), followed by hypertension (9%) and cancer (7%). Report of a new condition was greatest in adults aged between 56 and 65 years, and risk factors included greater BMI, waist circumference, and the presence of another chronic comorbid medical condition at baseline. Conclusions Chronic comorbid medical conditions are prevalent in persons with long-term physical disability. Midlife appears to be the period of greatest risk for onset of a new condition, and risk for incidence increases in the presence of other chronic comorbid medical conditions. Modifiable risk factors include BMI and waist circumference. Future research should explore whether changes in modifiable factors at midlife or earlier (e.g., diet, exercise) would help prevent or delay onset of comorbid conditions in this population.

Purposes To (1) determine the frequency and severity of hot flashes, (2) examine the associations between hot flash frequency and severity and quality of life, and (3) identify the predictors of hot flash activity in breast cancer survivors. Methods The study used a cross-sectional design and mailed survey of 253 breast cancer survivors recruited from a cancer wellness clinic. Participants provided information regarding cancer history, hot flashes, pain intensity, sleep problems, physical functioning, and psychological functioning. Results About half of the survivors reported at least one hot flash in the past 24 h (45%) or past week (52%). The average frequency of hot flashes was 1.9 in the past 24 h and 1.8 in the past week. Hot flash severity was usually mild or asymptomatic. However, participants with hot flashes reported significantly more sleep problems and higher pain severity than those reporting no hot flashes. Moreover, the severity of hot flashes was associated with more sleep problems, higher pain severity, and more psychological dysfunction. History of hormonal suppression therapy and younger age predicted hot flash activity in the study sample. Conclusions In breast cancer survivors, hot flashes are common and are associated with unpleasant symptoms and poor quality of life. Research is needed to determine if treatments that reduce the frequency and severity of hot flashes in breast cancer survivors also result in improvements in symptoms such as sleep problems, pain, and psychological dysfunction.

Catastrophizing is associated with negative outcomes in chronic pain and illness. The communal coping model (CCM) and cognitive behavioral (CB) formulations provide differing accounts of the function of catastrophizing in these contexts. In the present study we examined predictions from CCM and CB theoretical models in a sample of 116 patients with chronic fatigue to test 1) whether patient-reported solicitous responses from significant others mediate the relationship of catastrophizing with patient-reported pain and fatigue behaviors, as predicted by the CCM; and 2) whether pain and fatigue behaviors mediate the relationship of catastrophizing with solicitous responses, consistent with a CB model. This work is a secondary data analysis in which the strength of the indirect (ie, mediating) effects among study variables was examined. Consistent with CB models, pain and fatigue behaviors were associated with catastrophizing and solicitous responses, and there was a significant indirect effect of catastrophizing on solicitous responses through pain and fatigue behaviors. Results were inconsistent with the CCM; catastrophizing was not significantly associated with solicitous responses, nor did solicitous responses mediate the relationship between catastrophizing and pain or fatigue behaviors. These findings highlight the importance of behavioral expressions of pain and fatigue in understanding the relationship of catastrophizing to solicitous responses in chronic fatigue. Perspective This study of chronic fatigue patients tested CB and CCMs of catastrophizing, pain, and fatigue behaviors, and solicitous responses by significant others. Results were more consistent with CB formulations, which highlighted the importance of behavioral expressions of pain and fatigue in understanding the relationship of catastrophizing to solicitous responses.

Successful management of problems related to the hands and upper extremities begins with a comprehensive assessment of the pain experience and related factors. Pain intensity is the domain most commonly assessed, and pain relief is often the primary goal of treatment. Because pain is a private and subjective experience, self-report is considered the gold standard of pain measurement. This article describes and discusses the strengths and weaknesses of the most commonly used self-report scales used to measure hand pain intensity, and gives recommendations to help clinicians select from among the various options for measuring the intensity of hand pain.

The effective separation of trivalent actinides and lanthanides is capable of reducing the long term radiation hazard associated with used nuclear fuel. This class of separation exploits the tendency of ligands containing large and polarizable soft donor atoms to preferentially bind to the trivalent actinides instead of the lanthanides. Among the soft donors, nitrogen and sulfur based ligands have received the most attention with sulfur donors generally having greater selectivity for the actinides. Herein, the speciation, mechanism, and selectivity for the extraction of lanthanides and actinides from aqueous media into an organic phase by various sulfur containing extractants is reviewed.

Objectives To describe the protocol of a randomized controlled trial to evaluate the effectiveness and mechanisms of three behavioral interventions. Methods Participants will include up to 343 Veterans with chronic pain due to a broad range of etiologies, randomly assigned to one of three 8-week manualized in-person group treatments: (1) Hypnosis (HYP), (2) Mindfulness Meditation (MM), or (3) Education Control (EDU). Projected outcomes The primary aim of the study is to compare the effectiveness of HYP and MM to EDU on average pain intensity measured pre- and post-treatment. Additional study aims will explore the effectiveness of HYP and MM compared to EDU on secondary outcomes (i.e., pain interference, sleep, depression, anxiety and PTSD), and the maintenance of effects at 3- and 6-months post-treatment. Participants will have electroencephalogram (EEG) assessments at pre- and post-treatment to determine if the power of specific brain oscillations moderate the effectiveness of HYP and MM (Study Aim 2) and examine brain oscillations as possible mediators of treatment effects (exploratory aim). Additional planned exploratory analyses will be performed to identify possible treatment mediators (i.e., pain acceptance, catastrophizing, mindfulness) and moderators (e.g., hypnotizability, treatment expectations, pain type, cognitive function). Setting The study treatments will be administered at a large Veterans Affairs Medical Center in the northwest United States. The treatments will be integrated within clinical infrastructure and delivered by licensed and credentialed health care professionals.

Objective To investigate the prevalence of and risk factors for falling among individuals aging with multiple sclerosis (MS), muscular dystrophy (MD), postpolio syndrome (PPS), and spinal cord injury (SCI). Design Cross-sectional survey data from 2009 to 2010 were analyzed. We used forward logistic regression models to examine whether risk factors such as age, sex, mobility level, years since diagnosis, vision, balance, weakness, number of comorbid conditions, and physical activity could distinguish participants who reported falling from those who did not. Setting Surveys were mailed to community-dwelling individuals who had 1 of 4 diagnoses (MS, MD, PPS, or SCI). The survey response rate was 91%. Participants A convenience sample of community-dwelling individuals (N=1862; age, 18–94y) with MS, MD, PPS, or SCI in the United States. Interventions Not applicable. Main Outcome Measure Self-reported fall within the last 6 months. Results Fall prevalence for people with MS (54%), MD (70%), PPS (55%), and SCI (40%). Across all 4 groups, fall rates peaked in middle age (45–64y) and among people with moderate mobility limitations. Seven risk factors differentiated participants who fell from those who did not: mobility level, imbalance, age, curvilinear age (age 2 ), number of comorbid conditions, duration of diagnosis, and sex. The models differed across diagnostic groups. Conclusions People aging with long-term physical disabilities experience unique challenges that affect their risk of falls. A better understanding of the frequency, severity, and risk factors of falls across diagnostic groups is needed to design and implement customized, effective fall prevention and management programs for these individuals.

Rational and background Traditional Thai massage (TTM) is an alternative medicine treatment used for pain relief. The purpose of this paper is to provide a systematic review of the research about the effects of TTM on pain intensity and other important outcomes in individuals with chronic pain. Methods We performed a systematic review of the controlled trials of the effects of TTM, using the keywords “Traditional Thai massage” or “Thai massage” with the keyword “Chronic pain.” Results Six research articles met the inclusion criteria. All of the studies found a pre- to post-treatment pain reductions, varying from 25% to 80% and was also associated with improvements in disability, perceived muscle tension, flexibility and anxiety. Summary The TTM benefits of pain reduction appear to maintain for up to 15 weeks. Additional research is needed to identify the moderators, mediators and to determine the long-term benefits of TTM relative to control conditions.

Objective To examine the additive effect of age on disability for adults with spinal cord injury (SCI). Design Prospective cohort study. Setting SCI Model Systems. Participants Individuals with SCI (median age at injury, 32y; range, 6–88y) with a discharge motor FIM score and at least 1 follow-up motor FIM score who also provided measures of other covariates (N=1660). Of the total sample, 79% were men, 72% were white, 16% had incomplete paraplegia, 33% had complete paraplegia, 30% had incomplete tetraplegia, and 21% had complete tetraplegia. Interventions Not applicable. Main Outcome Measures The primary study outcome was the motor subscale of the FIM. A mixed-models approach was used to examine the additive effect of age on disability for individuals with SCI. Results When controlling for motor FIM at discharge from rehabilitation, level and severity of injury, age at injury, sex, race, and the age × time interaction were not significant ( P =.07). Age at the time of SCI was significantly associated with motor FIM (F 1,238 =22.49, P P =.03, P =.02) and age × time-square ( P =.01, P =.006) models. Trajectory of motor FIM scores is moderated slightly by age at the time of injury. The older participants were at the time of injury, the greater the curvature and the more rapid decline were found in later years. Conclusions These findings indicate that age moderately influences disability for some individuals with SCI: the older the age at the time of injury, the greater the influence age has on disability. The findings serve as an important empirical foundation for the evaluation and development of interventions designed to augment accelerated aging experienced by individuals with SCI.

To (1) evaluate the effects of a single session of four non-pharmacological pain interventions, relative to a sham tDCS procedure, on pain and electroencephalogram- (EEG-) assessed brain oscillations, and (2) determine the extent to which procedure-related changes in pain intensity are associated with changes in brain oscillations.30 individuals with spinal cord injury and chronic pain were given an EEG and administered measures of pain before and after five procedures (hypnosis, meditation, transcranial direct current stimulation [tDCS], neurofeedback, and a control sham tDCS procedure).Each procedure was associated with a different pattern of changes in brain activity, and all active procedures were significantly different from the control procedure in at least three bandwidths. Very weak and mostly non-significant associations were found between changes in EEG-assessed brain activity and pain.Different non-pharmacological pain treatments have distinctive effects on brain oscillation patterns. However, changes in EEG-assessed brain oscillations are not significantly associated with changes in pain, and therefore such changes do not appear useful for explaining the benefits of these treatments.The results provide new findings regarding the unique effects of four non-pharmacological treatments on pain and brain activity.

The neptunyl ion is very toxic and has the potential to be highly mobile in the environment. In an effort to understand how its interactions with biological surfaces may affect its movement in the environment, we investigated neptunyl interactions with Bacillus subtilis endospores and their exudates. The exudates were dominated by dipicolinic acid. Spectrophotometric investigations of the chemical form of neptunyl in exudate solutions are consistent with the formation of 1:1 neptunyl–dipicolinate complexes. Using neptunyl–endospore adsorption data and spectrophotometric measurements of neptunyl–dipicolinate complexes, we determined thermodynamic stability constants for both species. Neptunyl adsorption onto the endospore surface decreased with an increasing pH, which corresponds to increasing aqueous complexation of neptunyl by dipicolinate. Adsorption was also highly ionic strength dependent with adsorption increasing as ionic strength decreased. With stability constants determined in this work, we compared controls on neptunyl partitioning in a simulated system with B . subtilis endospores, vegetative cells, and generic natural organic matter. Neptunyl complexation by B . subtilis endospore exudates exerted the greatest biological control in the simulated systems.

A growing body of research indicates that chronic pain is a significant problem for many persons with chronic, slowly progressive neuromuscular disease (NMD).1–16 However, it is still not clear how much pain intensity factors in to the negative bio-psychosocial and physical consequences of chronic pain in the setting of slowly progressive NMD. Pain intensity is one of the most common dimensions assessed by clinicians and researchers who treat and study pain. Reduction in global pain intensity is also the standard by which most pain treatments are judged. However, although average pain intensity is an important pain domain, other pain domains are also potentially important (eg, pain frequency, duration, location, and quality) as factors that could contribute to patient dysfunction, especially in individuals with chronic pain.17 Unfortunately, research is lacking regarding the relative importance of these additional domains for understanding adjustment to pain. The research that has been conducted on this topic in other pain populations suggests that pain site may contribute to adjustment to chronic pain over and above the effects of global pain intensity. For example, Marshall and colleagues18 found that the intensity of back pain in patients with amputation explained a significant amount of variance in interference in daily activities beyond the pain associated with limb amputation. Similarly, there is some preliminary evidence that pain in the low back and arms is more strongly associated with patient functioning than pain in other body locations in a sample of patients with a variety of chronic pain problems (Tan G, Jensen MP, unpublished data, 2011). Nonetheless, research in this area is sparse, and it is not known whether these preliminary findings replicate in other samples of patients with chronic pain, including those with NMD. If these findings do replicate across different chronic pain populations, then clinicians should assess both pain intensity and its location(s) to better understand the potential impact that the pain might have on a specific patient. Moreover, if low back pain or pain in the extremities is more closely linked to a patient’s quality of life than pain at other sites, then treatments that address pain at these sites may be more important to patients with chronic pain than treatments that address pain at other sites (eg, the head or torso). Thus, research in this area could help inform the work of clinicians and scientists who are developing new pain treatments for individuals with specific pain conditions. However, the authors are not aware of any research that has studied the relative importance of pain site to patient functioning in individuals with slowly progressive NMD. Pain extent is a separate and distinct domain from intensity and refers to the overall number of body areas with pain. Research suggests that this pain domain may also be important to patient functioning. For example, Tait and colleagues19 found a significant association between pain extent and the tendency of patients to report greater complaints of weakness, fatigue, and depression. Similarly, Toomey and colleagues20 reported that patients with more pain sites were more likely to report pain as having a greater negative impact in their functioning. Turp and colleagues21 found that pain extent, along with pain intensity, was a significant predictor of pain-related disability in a sample of female patients with chronic facial pain. Patients with pain at multiple sites have shown a reduced level of health-related functioning, are more likely to have difficulties with mobility regardless of physical impairments than those with no pain or localized pain, and have worse prognosis for future work ability.22–24 In a series of studies, Kamaleri and colleagues25 reported significant associations between pain extent and functioning in patients with musculoskeletal pain. They found a strong and linear association between increasing number of pain sites and decreasing functional ability; a strong relationship with decreasing psychological health, sleep quality, and overall health; and future work disability after a 14-year period.25,26 As with research on the importance of specific pain sites to patient functioning, it is unclear if these findings regarding pain extent replicate in other populations of individuals with chronic pain, including persons with slowly progressive NMD. Most published studies on these issues have been conducted with low back patients receiving treatment at secondary and tertiary care facilities. Thus, these findings may not generalize to other populations of patients with pain.27 Further delineating the relative importance of pain site and extent in relation to patient functioning is particularly important in patients with NMD, because research indicates they typically experience pain in more than one location.5 Given what previous studies have found in other pain populations, the authors hypothesize that pain extent would be negatively associated with psychological functioning and positively associated with pain interference, whereas pain intensity in specific pain sites would show stronger associations with measures of patient functioning than pain at other sites. More specifically, one would expect that pain in the low back and arms might evidence stronger associations with pain interference and psychological functioning than pain at other sites.

Background Depression is common among people with multiple sclerosis (MS), and research shows that individuals, including individuals with MS, who are more physically active report lower rates of depression. However, little is known about the relative importance of level of physical activity (e.g., moderate versus vigorous) in relationship to depression, or the role that age might play in this relationship among people with MS. The current study sought to (1) clarify the associations between moderate and vigorous physical activity and depression in a sample of individuals with MS, (2) determine the associations between age and physical activity, and (3) test for the potential moderating influence of age on the associations between physical activity and depression. Objective/hypothesis Cross-sectional survey. Methods 112 individuals with MS completed a survey assessing demographic variables, amount of moderate and vigorous physical activity, and depression. Results There was a gradual decrease in the amount of moderate and vigorous physical activity as age increased, but this decrease was not statistically significant. Moderate physical activity was significantly (negatively) associated with depression across all age cohorts. Time spent in vigorous physical activity was significantly (negatively) associated with depression among the middle-aged but not younger or older participants who are physically active. Conclusions The findings support a link between moderate physical activity and depression and, for middle-aged individuals, vigorous physical activity and depression in persons with MS. The findings indicate that research examining the impact of activity enhancing treatments on depression in individuals with MS is warranted.

Assessing burden of disease is a complex process involving identifying the physical, psychological, and socioeconomic aspects that make up the totality of disease burden on patients, families, and caregivers, and society as a whole, with chronic pain affecting all of these aspects. It is the job of the physiatrist to identify disability and promote interventions to minimize it, including facilitating access to appropriate treatment for chronic pain, and ultimately easing disease burden. Chronic pain causes significant psychosocial dysfunction for patients with neuromuscular disease and contributes substantially to the overall disease burden. There are many psychosocial factors closely associated with pain and dysfunction in patients with neuromuscular disease, most notably a perception of inadequate psychosocial support. The assessment of children with neuromuscular disorders must include the parents or guardians as well, given that chronic pain in a child will affect the entire family.

Background Body mass index (BMI) and waist circumference (WC) are well-understood in the general population, but are not adequately understood among persons with disabilities. Objective To describe and compare BMI and WC among individuals with muscular dystrophy (MD), multiple sclerosis (MS), post-polio syndrome (PPS), and spinal cord injury (SCI). BMI scores were also compared to normative data of the U.S. population, with consideration for age, sex, and mobility limitations. Methods Persons with MD (n = 339), MS (n = 597), PPS (n = 443), and SCI (n = 488) completed postal surveys that included self-reported BMI and WC data. NHANES data were used to compare the current sample with a representative US sample. Results Participants with PPS had higher BMI than participants with MD, MS, and SCI. In addition, participants with MS had significantly higher BMI relative to participants with SCI. BMI was significantly positively associated with age, years since diagnosis, mobility, and interactions of some of these factors. Relative to the general population, BMI was lower in MD, MS, and SCI across age groups, as well as in men with PPS and women ages 60-74 years with PPS. No significant differences were identified between MD, MS, PPS, and SCI in WC. Conclusions The presence of group differences in BMI and absence of group differences in WC suggests that BMI may not accurately represent health risk in SCI, MD, and possibly MS, because of biasing elements of the conditions, such as changes in body composition and mobility limitations.

Plutonium can enter the body through different routes and remains there for decades; however its specific biochemical interactions are poorly defined. We, for the first time, have studied plutonium-binding proteins using a metalloproteomic approach with rat PC12 cells. A combination of immobilized metal ion chromatography, 2D gel electrophoresis, and mass spectrometry was employed to analyze potential plutonium-binding proteins. Our results show that several proteins from PC12 cells show affinity towards Pu(4+)-NTA (plutonium bound to nitrilotriacetic acid). Proteins from seven different spots in the 2D gel were identified. In contrast to the previously known plutonium-binding proteins transferrin and ferritin, which bind ferric ions, most identified proteins in our experiment are known to bind calcium, magnesium, or divalent transition metal ions. The identified plutonium interacting proteins also have functional roles in downregulation of apoptosis and other pro-proliferative processes. MetaCore™ analysis based on this group of proteins produced a pathway with a statistically significant association with development of neoplastic diseases.

Pain beliefs as indexed by the Survey of Pain Attitudes (SOPA) have been consistently shown to predict pain adjustment outcomes in Western populations. However, its utility in non-Western populations is unclear.We evaluated the construct and predictive validity of the Chinese version of the 14-item SOPA (ChSOPA-14) in a sample of Chinese patients with chronic pain.A total of 208 Chinese patients with chronic musculoskeletal pain completed the ChSOPA-14, the Chronic Pain Grade questionnaire, the Pain Catastrophizing Scale, the Center for Epidemiological Studies-Depression Scale, and measures of sociodemographic characteristics.Except Medical Cure, all ChSOPA-14 scales were significantly correlated with validity criterion measures (all P0.05) in expected directions. The present Chinese sample scored the highest on the Medical Cure scale (mean=2.98, standard deviation [SD]=1.05) but the lowest on the Disability scale (mean=1.75, SD=1.67). Results of hierarchical multiple regression analyses showed that the ChSOPA-14 scales predicted concurrent depression (F(7,177)=14.51, P0.001) and pain disability (F(7,180)=8.77, P0.001). Pain Control (stdβ [standardized beta coefficient]=-0.13; 95% confidence interval [CI]: -3.41, -0.13; P0.05) and Emotion (stdβ=29; 95% CI: 1.76, 5.02; P0.001) emerged as significant independent predictors of concurrent depression whereas Disability (stdβ=0.19; 95% CI: 1.33, 7.88; P0.01), Emotion (stdβ=16; 95% CI: 0.08, 7.59; P0.05), and Solicitude (stdβ=-0.14; 95% CI: -7.05, -0.04; P0.05) significantly associated with concurrent disability.The findings offer preliminary evidence for the construct and concurrent predictive validity of the ChSOPA-14. This makes available a suitable instrument for chronic pain in the Chinese population and will facilitate future cross-cultural research on pain beliefs.

Global ratings of treatment satisfaction and improvement can provide an opportunity for patients to aggregate multiple aspects of their treatment into a single measure of its perceived benefits and disadvantages. Although such measures have been recommended for chronic pain clinical trials, only limited data are available that address the hypothesis that they reflect multiple aspects of patients’ treatment experience. Our objective was to identify the factors that make independent contributions to ratings of treatment satisfaction. We analyzed data from 5 open-label clinical trials of lidocaine patch 5% in osteoarthritis knee pain and chronic low back pain that were 2 to 12 weeks in duration. A total of 383 patients completed the Patient Global Assessment of Treatment Satisfaction scale and measures of pain, interference with physical and emotional functioning, sleep interference, and adverse events. The results of multivariate analyses indicated that improvements in measures of pain intensity, pain relief, and interference with physical functioning each made independent contributions to treatment satisfaction in both groups of patients. Improvements in interference with emotional functioning and sleep and the presence and severity of adverse events were not associated with satisfaction. Perspective Measures of treatment satisfaction can reflect different aspects of the patient’s treatment response, including improvements in pain and physical functioning. Increased understanding of such global measures may facilitate development of clinical trial outcomes that allow patients to evaluate with minimal burden those aspects of the treatment experience they consider personally meaningful.

Objective A recently published instrument (PRECIS) was designed to assist investigative teams in understanding the various design decisions that need to be made regarding pragmatic vs. explanatory trials. Our team used this instrument during an investigators' meeting to organize our discussion regarding the design of a planned trial and to determine the extent of consensus among the study investigators. Study Design and Setting The study was descriptive in nature and occurred during an investigator meeting. After reading and reviewing the 10 PRECIS criteria, the team made quantitative judgments of the planned study regarding each PRECIS criteria to reflect initial, ideal, and final study design perceptions. Results Data indicated that the final study design was more explanatory in nature than the preliminary plan. Evidence of consensus was obtained. Conclusion The investigative team found that applying PRECIS principles were useful for (1) detailing points of discussion related to trial design, (2) making revisions to the design to be consistent with the project goals, and (3) achieving consensus. We believe our experiences with PRECIS may prove valuable for trial researchers in much the same way that case reports can provide valuable insights for clinicians.

The potential benefits of combining pain education (PE) with clinical hypnosis (CH) has not yet been investigated in individuals with chronic pain. A total of 100 patients with chronic nonspecific low back pain were randomized to receive either: 1) PE alone, or 2) PE with CH. Outcomes were collected by a blinded assessor at 2 weeks and 3 months after randomization. The primary outcomes were average pain intensity, worst pain intensity (both assessed with 11-point numeric rating scales), and disability (24-item Roland Morris Disability Questionnaire) at 2 weeks. At 2 weeks, participants who received PE with CH reported lower worst pain intensity (mean difference = 1.35 points, 95% confidence interval [CI] = .32–2.37) and disability (mean difference = 2.34 points, 95% CI = .06–4.61), but not average pain intensity (mean difference = .67 point, 95% CI = −.27 to 1.62), relative to participants who received PE alone. PE with CH participants also reported more global perceived benefits at 2 weeks (mean difference = −1.98 points, 95% CI = −3.21 to −.75). At 3 months, participants who received PE with CH reported lower worst pain intensity (mean difference = 1.32 points, 95% CI = .29–2.34) and catastrophizing (mean difference = 5.30 points, 95% CI = 1.20–9.41). No adverse effects in either treatment condition were reported. To our knowledge, this is the first trial showing that additional use of hypnosis with PE results in improved outcomes over PE alone in patients with chronic nonspecific low back pain. Perspective This study provides evidence supporting the efficacy of another treatment option for teaching patients to self-manage chronic low back pain that has a relatively low cost and that can be offered in groups.

Research generally indicates that providers demonstrate modest insight into their clinical decision processes. In a previous study utilizing virtual human (VH) technology, we found that patient demographic characteristics and facial expressions of pain were statistically significant predictors of many nurses' pain-related decisions. The current study examined the correspondence between the statistically identified and self-reported influences of contextual information on pain-related decisions. Fifty-four nurses viewed vignettes containing a video of a VH patient and text describing a postsurgical context. VH sex, race, age, and facial expression varied across vignettes. Participants made pain-assessment and treatment decisions on visual analogue scales. Participants subsequently indicated the information they relied on when making decisions. None of the participants reported using VH sex, race, or age in their decision process. Statistical modeling indicated that 28 to 54% of participants (depending on the decision) used VH demographic cues. 76% of participants demonstrated concordance between their reported and actual use of the VH facial expression cue. Vital signs, text-based clinical summary, and VH movement were also reported as influential factors. These data suggest that biases may be prominent in practitioner decision-making about pain, but that providers have minimal awareness of and/or a lack of willingness to acknowledge this bias. Perspective The current study highlights the complexity of provider decision-making about pain management. The VH technology could be used in future research and education applications aimed at improving the care of all persons in pain.

Understanding the complex trajectories of disability and aging requires a biopsychosocial approach that considers disability in the broader context of later adulthood. Although disability service researchers and gerontologists have many shared interests and a similar mission, the fields are relatively new to one another and have had little historical interaction. The purpose of this article is to increase and improve collaboration among investigators in these fields by providing some background in social gerontology to the disability researcher, and by applying key theories in aging to the issue of growing older with physical disability. The article discusses particular problem areas for older adults, including social support, and also discusses the parallel paradoxes of aging and disability.