Epilepsy Treatment Complacency in Patients, Caregivers, and Health Care Professionals.

OBJECTIVE: To explore the perspectives of adult patients with epilepsy, caregivers, and health care professionals (HCPs) on treatment for seizures and treatment decisions, we developed and administered the STEP Survey (Seize the Truth of Epilepsy Perceptions). METHODS: Participants were recruited from online panel M3 and by Rare Patient Voice and completed the self-administered online STEP Survey. Analysis of variance and chi-square tests were used for group comparisons. RESULTS: The STEP Survey was completed by 400 adult patients, 201 caregivers, and 258 HCPs. Patients estimated reporting 45% of their seizures to their HCP, whereas caregivers estimated 83% and HCPs estimated 73% were reported. The most common reason for not reporting seizures was that the seizures were not serious enough to mention (patients 57%; caregivers 66%). A minority of patients (25%) and caregivers (30%) were very or extremely likely to ask their HCP about changing antiseizure medication (ASM) in the next 12 months. The HCP was most frequently selected by patients, caregivers, and HCPs as the person who initiates discussion of changing ASMs (patients 73%/caregivers 66%/HCPs 75%) and increasing ASM dosage (patients 77%/caregivers 68%/HCPs 81%). A majority of patients (65%) and caregivers (68%) somewhat or strongly agreed that they do not change ASMs due to fear of getting worse. HCPs perceive this fear less often, stating that 50% of their patients feel afraid when a second ASM was added. CONCLUSIONS: Improved reporting of all seizures, discussion of treatment changes, and the impact of fear on treatment decisions provide opportunities to reduce complacency and optimize patient outcomes.

Severe cutaneous adverse reaction associated with antiseizure medications: Diagnosis, management, and prevention.

Severe cutaneous adverse reactions (SCARs) are potentially life-threatening, with considerable morbidity and mortality. They are nonimmediate hypersensitivity reactions that occur in specifically predisposed patients with delayed T-cell-mediated hypersensitivity reaction. Antiseizure medications (ASMs) are among the drugs that can induce SCAR. Increased awareness of SCAR among clinicians treating patients with ASMs is critically important for early recognition of symptoms, prompt identification and removal of the causal drug, and early intervention to reduce SCAR-related acute and long-term morbidity and mortality. The diagnosis, management, and prevention of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) are reviewed, along with the current understanding of the pathomechanisms and role of genetics in SCAR development. Supportive care and immunomodulating treatments for SCAR are discussed.

Poor sleep quality and exaggerated salivary cortisol reactivity to the cold pressor task predict greater acute pain severity in a non-clinical sample.

Poor sleep is often independently associated with greater pain sensitivity and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis (e.g., greater basal cortisol and exaggerated stress-induced cortisol reactivity). However, the interactions among sleep, pain, and the HPA axis have not been adequately evaluated. In this study, 40 healthy adults provided self-report regarding perceived sleep quality over the past month prior to completion of an acute noxious physical stressor (i.e., cold pressor task; CPT). Following the CPT, they reported on the severity of pain experienced. Salivary cortisol was sampled before, immediately following, and during recovery from CPT. Using bootstrapped confidence intervals with a bias correction, results showed that poor sleep quality was significantly associated with greater reports of CPT-induced pain severity and greater cortisol reactivity (i.e., increase from baseline). Furthermore, greater cortisol reactivity to the CPT was found to significantly mediate the relationship between poor sleep and pain severity.

Experimental pain ratings and reactivity of cortisol and soluble tumor necrosis factor-α receptor II following a trial of hypnosis: results of a randomized controlled pilot study.

OBJECTIVE: Current evidence supports the efficacy of hypnosis for reducing the pain associated with experimental stimulation and various acute and chronic conditions; however, the mechanisms explaining how hypnosis exerts its effects remain less clear. The hypothalamic-pituitary-adrenal (HPA) axis and pro-inflammatory cytokines represent potential targets for investigation given their purported roles in the perpetuation of painful conditions; yet, no clinical trials have thus far examined the influence of hypnosis on these mechanisms. DESIGN: Healthy participants, highly susceptible to the effects of hypnosis, were randomized to either a hypnosis intervention or a no-intervention control. Using a cold pressor task, assessments of pain intensity and pain unpleasantness were collected prior to the intervention (Pre) and following the intervention (Post) along with pain-provoked changes in salivary cortisol and the soluble tumor necrosis factor-α receptor II (sTNFαRII). RESULTS: Compared with the no-intervention control, data analyses revealed that hypnosis significantly reduced pain intensity and pain unpleasantness. Hypnosis was not significantly associated with suppression of cortisol or sTNFαRII reactivity to acute pain from Pre to Post; however, the effect sizes for these associations were medium-sized. CONCLUSIONS: Overall, the findings from this randomized controlled pilot study support the importance of a future large-scale study on the effects of hypnosis for modulating pain-related changes of the HPA axis and pro-inflammatory cytokines.

Salivary cortisol and soluble tumor necrosis factor-α receptor II responses to multiple experimental modalities of acute pain.

The present study compared cortisol and soluble tumor necrosis factor-α receptor II (sTNFαRII) responses provoked by cold pressor, hot water, ischemic, and neutral water (i.e., room temperature) modalities. Oral fluid samples were collected before, immediately after, and during recovery to assess physiological responses. From baseline, the cold pressor, but not hot water or ischemic modalities, produced a significant time-dependent elevation in cortisol, whereas cortisol significantly decreased for the neutral water task. When compared to baseline, the cold pressor, hot water, and ischemic modalities were associated with decreased sTNFαRII responses over time. The sTNFαRII response to neutral water initially decreased but returned to approximate baseline levels. Pain ratings were positively associated with cortisol increase from baseline and the overall cortisol response was negatively associated with the overall sTNFαRII response.

Enhanced cortisol increase upon awakening is associated with greater pain ratings but not salivary cortisol or soluble tumor necrosis factor-α receptor II responses to acute pain.

OBJECTIVES: The cortisol awakening response (CAR) is related to psychosocial factors and health in potentially significant ways, suggesting that it may be a distinctive marker of hypothalamic-pituitary-adrenal axis function and dysfunction. This study sought to expand upon previous work that examined the association between CAR and ratings of laboratory-evoked acute pain stimulation. In addition to evoked pain ratings, this study also tested whether CAR was prospectively related with salivary cortisol and soluble tumor necrosis factor-α receptor II responses to acute pain stimulation. METHODS: This study included 36 healthy, pain-free volunteers of both sexes recruited through posted study flyers. Prior to completion of laboratory pain testing, salivary cortisol samples were obtained at home over the course of a single morning according to the following time frame: upon awakening, and 15, 30, and 60 minute after awakening. After collection of saliva, study participants brought their home saliva samples to the laboratory for assay and subsequently completed acute experimental pain testing procedures. RESULTS: Cluster analysis of CAR revealed two distinct groups with similar patterns of cortisol response to awakening; increased and flattened. Relative to flattened CAR, increased CAR was associated with greater ratings of pain intensity and unpleasantness. Salivary cortisol was significantly increased and soluble tumor necrosis factor-α receptor II significantly decreased after pain testing, but neither of these responses differed as a function of increased versus flattened CAR. DISCUSSION: CAR may be a marker for stress sensitivity and/or the anticipation of impending stress, which could explain why the increased CAR cohort reported greater acute pain ratings.

Ethnic Group Differences in the Outcomes of Multidisciplinary Pain Treatment.

OBJECTIVES: The aim of this prospective investigation was to evaluate ethnic group differences in pain-related outcomes following multidisciplinary chronic pain treatment. A prospective pre- and post-treatment assessment design was employed to investigate the effects of ethnicity on changes in pain-related variables following completion of a multidisciplinary pain treatment program. METHODS: One hundred fifty five chronic pain patients participating in a multidisciplinary pain treatment program completed measures of pain and mood both prior to and following the four-week treatment. Primary outcome variables included pain severity, pain-related interference, and depressive symptoms. RESULTS: Baseline differences between African-Americans and Whites were observed for depressive symptoms, but not for pain severity or pain-related interference. Following multidisciplinary pain treatment, both White and African-American patients displayed post-treatment reductions in depressive symptoms and pain-related interference. However, White patients also reported reduced pain severity while African-Americans did not. CONCLUSIONS: The treatment approach used in the present study appeared to be less effective in reducing self-reported pain severity in African-American versus White patients, though both groups benefited in terms of reduced depressive symptoms and pain-related interference. Moreover, the observation that improvements in functioning occurred without reductions in pain severity in African-American patients suggests that differences may exist in treatment processes as a function of ethnic group, and will consequently be an important area for future research.

Subjective sleep quality and ethnicity are interactively related to standard and situation-specific measures of pain catastrophizing.

OBJECTIVE: Sleep quality and ethnicity are related to a host of general health outcomes including the experience of pain, yet it remains unclear whether poor sleep quality and ethnicity might interactively affect pain catastrophizing and laboratory-evoked acute pain reports. The current study examined the cross-sectional associations of subjective sleep quality, ethnicity, and their interaction with pain catastrophizing and pain reports. DESIGN: Healthy (N = 149), ethnically diverse (58% Caucasian American, 23% Asian American, 19% African American) young adults were subjected to a cold pressor task (CPT). Prior to CPT, participants completed the Pittsburgh Sleep Quality Index and a standard version of the Pain Catastrophizing Scale (PCS). Following CPT, participants completed a situation-specific version of the PCS. RESULTS: Adjusted analyses revealed a significant sleep quality by ethnicity interaction for standard catastrophizing reports. Particularly, African Americans with poor overall sleep quality reported the greatest level of catastrophizing on the standard PCS relative to their Caucasian American and Asian American counterparts. Furthermore, African Americans with poorer sleep efficiency reported greater catastrophizing on the situation-specific PCS compared with Caucasian American and Asian Americans. Catastrophizing was significantly correlated with pain reports. CONCLUSIONS: These results suggest that African Americans with poorer sleep quality may be at greater risk for catastrophizing, a known contributor to more intense pain and increased pain-related emotional distress. Whether interventions that improve the sleep quality of ethnic minorities affect pain catastrophizing is in need of investigation.

Ethnicity, catastrophizing, and qualities of the pain experience.

OBJECTIVE: It is generally well established that catastrophizing exerts a potent influence on individuals' experience of pain and accompanying emotional distress. Further, preliminary evidence has shown that meaningful differences among various pain relevant outcomes (e.g., pain ratings, endogenous pain inhibitory processes) can be attributed to individuals' ethnic background. The mechanisms that might explain ethnic differences in pain outcomes are unclear, and it remains to be fully established whether the relation between ethnicity and pain response may be indirectly affected by pain catastrophizing. DESIGN: In the current study, we examined differences in pain responses by ethnicity among healthy, young adults (N=62), and attempted to determine whether such an ethnicity-pain relation was mediated by catastrophizing using the standard Pain Catastrophizing Scale (PCS) and a modified version of the PCS reflecting situational catastrophizing during a cold pressor task. RESULTS: Results showed that pain responses varied by ethnicity, as did reported catastrophizing. Catastrophizing mediated the relation between ethnicity and affective and sensory pain responses. CONCLUSIONS: To better explicate our findings, we described the context in which these findings occurred following a "who, what, where, when, and why" approach. This approach provides an efficient description of how our findings align with previous research, while identifying future research that should clarify the theoretical underpinnings of catastrophizing and pain and also inform clinical intervention.

Ethnicity moderates the influence of perceived social status on subjective sleep quality.

It has long been recognized that socioeconomic status (SES) influences health and health-related behaviors, and it has been suggested that the adverse impact of low SES on health may be partly mediated by poor sleep quality. The relation between sleep and objective and subjective measures of SES has only been explored in a preliminary manner, providing indirect evidence that associations between SES and health might be explained, in part, by disrupted sleep. However, it remains unclear whether low SES directly affects sleep quality or whether the SES-sleep quality relation varies as a function of ethnicity given robust ethnic disparities across SES-related factors. This study examined the relation between perceived social status (i.e., individuals' perception of their socioeconomic standing) and subjective sleep quality among 149 college students, and examined the moderating effect of ethnicity to determine whether the magnitude or direction of association differed among Caucasian, Asian, and African Americans. Using hierarchical regressions and a dummy-coded ethnicity variable, results demonstrated significant moderation (ΔR2 = 0.04, p = .02), such that both Asian (p = .04) and African Americans (p = .02) were significantly different from Caucasian Americans. Lower perceived social status was related to greater impairment in sleep quality for Asian Americans (ß = -.37, p < .01) and African Americans (ß = -.51, p < .01), but not Caucasian Americans (ß = -.02, p = .87). These findings provide initial support for the negative impact of low perceived social status on sleep quality for specific subgroups of ethnic minorities.

Pain catastrophizing mediates the relationship between self-reported strenuous exercise involvement and pain ratings: moderating role of anxiety sensitivity.

OBJECTIVE: To investigate the cross-sectional associations among self-reported weekly strenuous exercise bouts, anxiety sensitivity, and their interaction with pain catastrophizing and pain responses to the cold pressor task (CPT) in healthy, ethnically diverse young adults (n = 79). Exercise involvement has been shown to have hypoalgesic effects and cognitive factors may partially explain this effect. Particularly, alterations in pain catastrophizing have been found to mediate the positive pain outcomes of multidisciplinary treatments incorporating exercise. Further, recent evidence suggests that exercise involvement and anxiety sensitivity may act together, as interacting factors, to exert an effect on catastrophizing and pain outcomes; however, further research is needed to clarify the nature of this interaction. METHODS: Before the CPT, participants were asked to complete the Godin Leisure-Time Exercise Questionnaire, the Beck Depression Inventory, and the Anxiety Sensitivity Index. After the CPT, participants completed a modified version of the Pain Catastrophizing Scale and the Short Form-McGill Pain Questionnaire. RESULTS: At a high level of anxiety sensitivity, controlling for depressive symptoms, CPT immersion time, and sex differences, a bias-corrected (BC), bootstrapped confidence interval revealed that pain catastrophizing significantly mediated the relationship between self-reported weekly strenuous exercise bouts and pain response (95% BC Confidence Interval = -9.558, -0.800 with 1000 resamples). At intermediate and low levels of anxiety sensitivity, no significant mediation effects were found. CONCLUSIONS: These findings support that, for pain catastrophizing to mediate the strenuous exercise-pain response relation, individuals must possess a high level of anxiety sensitivity.

Associations between catastrophizing and endogenous pain-inhibitory processes: sex differences.

UNLABELLED: Pain catastrophizing is among the most robust predictors of pain outcomes, and a disruption in endogenous pain-inhibitory systems is 1 potential mechanism that may account for increased pain among individuals who report higher pain catastrophizing. Pain catastrophizing may negatively influence diffuse noxious inhibitory controls (DNIC), a measure of endogenous pain inhibition, through complex anatomical circuitry linking cortical responses to pain with processes that modulate pain. The current study examined whether DNIC mediated the relationship between catastrophizing and pain among 35 healthy young adults and examined the moderating effects of sex to determine whether the magnitude or direction of associations differed among men and women. DNIC was assessed using pressure pain thresholds on the forearm before and during a cold pressor task. Using bias-corrected bootstrapped confidence intervals, results showed that diminished DNIC was a significant partial mediator of the relation between greater pain-related catastrophizing and more severe pain ratings. Participant sex moderated these associations; higher catastrophizing predicted lower DNIC for men and women, however, the effect of catastrophizing on pain ratings was partially mediated by DNIC for women only. These findings further support the primary role of pain catastrophizing in modulation of pain outcomes. PERSPECTIVE: These findings support the hypothesis that the heightened pain reported by individuals higher in pain catastrophizing may be related to a disruption in the endogenous modulation of pain, operationalized by assessing DNIC. Whether interventions that reduce pain catastrophizing affect pain outcomes via effects on DNIC is in need of investigation.

Association of catastrophizing with interleukin-6 responses to acute pain.

Catastrophizing exerts its deleterious effects on pain via multiple pathways, and some researchers have reported that high levels of catastrophizing are associated with enhanced physiological reactivity to painful stimulation. In this project, 42 generally healthy adults underwent a series of psychophysical pain testing procedures assessing responses to noxious mechanical, heat, and cold stimuli. Pain catastrophizing cognitions were assessed prior to and then immediately after the various pain induction procedures. Blood samples were taken at baseline and then at several time points from the end of the procedures to 1h post-testing. Samples were assayed for serum levels of cortisol and interleukin-6 (IL-6). Both cortisol and IL-6 increased from baseline during the post-testing period (p's<.05), with cortisol returning to baseline by 1h post-testing and IL-6 remaining elevated. Pain catastrophizing, measured immediately after the pain procedures, was unrelated to cortisol reactivity, but was strongly related to IL-6 reactivity (p<.01), with higher levels of catastrophizing predicting greater IL-6 reactivity. In multivariate analyses, the relationship between catastrophizing and IL-6 reactivity was independent of pain ratings. Collectively, these findings suggest that cognitive and emotional responses during the experience of pain can shape pro-inflammatory immune system responses to noxious stimulation. This pathway may represent one important mechanism by which catastrophizing and other psychosocial factors shape the experience of both acute and chronic pain in a variety of settings.

Catastrophizing, pain, and social adjustment in scleroderma: relationships with educational level.

OBJECTIVES: Low educational attainment is related to numerous adverse health outcomes, and some evidence suggests that psychosocial variables may mediate education's effects. Moreover, the relationship between psychosocial functioning and health-related outcomes may be moderated by educational level, with individuals lower in formal education being more susceptible to the deleterious effects of negative cognitive and affective states. The present study sought to characterize such interrelationships between educational level and pain-related catastrophizing. METHODS: We investigated the association of self-reported educational level with pain and social disability, we evaluated catastrophizing's potential mediating role in those associations, and we also investigated education as a moderator of catastrophizing's effects on pain and social disability in a sample of patients with scleroderma, a frequently painful autoimmune disorder. RESULTS: First, education-related differences in pain report were accounted for by catastrophizing and depression. Second, after controlling for demographic factors, disease severity, and depressive symptoms, education moderated the relationship between catastrophizing, pain affect, and social function. Specifically, catastrophizing was more highly associated with greater reporting of affective pain among those with less formal education. In addition, catastrophizing inversely correlated with social disruption among individuals with less formal education. DISCUSSION: Collectively, study findings support multiple models of interaction between education and pain-related cognitive/affective functioning, though in both mediational and moderational analyses, lower levels of formal education act as a risk factor for adverse pain-related outcomes.

Cognitive-Behavioral self-help for chronic pain.

Cognitive behavioral self-help is a potentially cost-saving method of delivering evidence-based treatment to a wide range of chronic pain patients. This article provides a rationale for self-help and focuses on the effectiveness of self-help in the management of chronic pain, which typically includes some degree of lay leader or professional facilitation. The evidence for these treatments is generally positive (e.g., reductions in pain and pain-related disability) across such illnesses as arthritis, back pain, headache, and temporomandibular joint disorders. When implementing self-help, professionals need to consider individual differences in suitability for using a self-management treatment and evaluate the outcome in the context of a stepped care approach. This article uses three case examples to illustrate the use of cognitive behavioral self-help delivered in the care of scleroderma patients.

Pain and wound healing in surgical patients.

BACKGROUND: Human and animal laboratory studies have shown that stress delays healing of standardized punch biopsy wounds. PURPOSE: This 5-week prospective study of 17 women who underwent elective gastric bypass surgery addressed the association between postsurgical pain intensity and subsequent healing of a standard 2.0-mm punch biopsy wound. METHODS: Participants were assessed 1 week before surgery, within 3 hr before surgery, 1 to 3 days postsurgery, and at weekly intervals for 4 weeks following surgery. RESULTS: Patient ratings of greater acute postsurgical pain, averaged over Days 1 and 2 postsurgery, and greater persistent postsurgical pain, averaged over 4 weekly postsurgery pain ratings, were significantly associated with subsequent delayed healing of the punch biopsy wound. Presence of depressive symptoms on the day of surgery, pre-existing persistent pain, and medical complications following initial discharge from the hospital were not related to wound healing. Depressive symptoms on the day of surgery and pre-existing persistent pain did predict persistent postsurgical pain intensity. CONCLUSIONS: These findings extend the previous laboratory models of wound healing to a surgical population, providing the first evidence that pain plays an important role in postsurgery wound healing, a key variable in postsurgical recovery.

Psychotic motivation and the paradox of current research on serious mental illness and rates of violence.

Persuasive empirical support exists for a positive association between serious mental illness (SMI) and rates of violence; a great deal of support is also present for the clinical impression that psychotic symptoms sometimes motivate "symptom-consistent" violence. We propose that the issue of the motivation for violence in the SMI population can be considered independently of the issue of the association between SMI and violence rates. We review much of the current literature on the association between SMI and violence in a framework that emphasizes motivational influences unique to the SMI population. We conclude that the contribution of psychotic motivation to rates of violence in the SMI population is a major research issue. Furthermore, we believe that recognition of the independence of motivational influences and violence rates, and consideration of the impact of treatment on violence, may help explain the paradox of current research: Delusions and hallucinations may motivate violent behavior, but this psychotic motivation may not be reflected in the actual rate of violence.

Psychologic factors in scleroderma.

CB interventions have been shown to reduce pain and improve psychosocial functioning in patients who have chronic illnesses, particularly chronically painful rheumatologic syndromes. These interventions are typically administered by specially trained professionals and are conducted during weekly individual or group sessions. When focused on pain and chronic illness, these interventions seem to have, at best, small effects on depression. Data from the headache literature and recent data about patients who have dental/facial pain indicate that minimal-contact CB therapy, the combination of some professional contact with audiotaped and written materials, may reduce pain in many patients, but the impact on functioning is less clear. Future studies should examine the impact of CB interventions on pain, depression, concerns about disfigurement, and physical and psychosocial functioning in scleroderma. Such knowledge is necessary for the optimal care of persons who have this debilitating illness. Although complicated, the advent of disease-specific interventions that are administered by way of the Internet may prove particularly useful in a rare illness, such as scleroderma. Psychologic factors with demonstrated relevance to scleroderma include pain, depression, and distress about disfigurement, physical function, and social function. Although these dimensions of quality of life are interrelated, pain, depression, and distress about disfigurement are common and may respond to psychologic interventions.

Psychoneuroimmunology: psychological influences on immune function and health.

This review focuses on human psychoneuroimmunology studies published in the past decade. Issues discussed include the routes through which psychological factors influence immune function, how a stressor's duration may influence the changes observed, individual difference variables, the ability of interventions to modulate immune function, and the health consequences of psychosocially mediated immune dysregulation. The importance of negative affect and supportive personal relationships are highlighted. Recent data suggest that immune dysregulation may be one core mechanism for a spectrum of conditions associated with aging, including cardiovascular disease, osteoporosis, arthritis, Type 2 diabetes, certain cancers, and frailty and functional decline; production of proinflammatory cytokines that influence these and other conditions can be stimulated directly by negative emotions and indirectly by prolonged infection.

Depressive symptoms and lymphocyte proliferation in older adults.

In an 18-month prospective study, community-dwelling older adults, including both spousal caregivers of dementia patients and noncaregiving controls, were examined. Participants were selected on the basis of the presence or absence of chronic depressive symptoms that exceeded a cutoff score for clinically relevant depressive symptoms on a self-report symptom measure. Compared with nondepressed older adults, those with chronic, mild depressive symptoms had poorer T cell responses to 2 mitogens from baseline to follow-up. Additionally, among individuals with depressive symptoms, older age was associated with the poorest blastogenic response to the mitogens at follow-up. These findings extend the association between depression and immune function to community-dwelling older adults with chronic, mild depressive symptoms.