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The primary aim of this study was to evaluate activity rhythms in fibromyalgia syndrome (FMS) and their association with FMS-related symptoms. We hypothesized that stronger and more consistent activity rhythms would be associated with reduced symptom severity and presentation in FMS. Two hundred ninety-two patients with FMS (mean age = 45.1 ± 11.1; 272 women) provided a 7-day actigraphy recording and responses to questionnaires addressing degree of pain, fatigue, mood, and physical impairment. Using a simple cosine model, we extracted Amplitude (activity range), Phi (time at maximum), Mesor (mean activity), and their variabilities (across days) from each participant's actigraphy. The clinical and actigraphic measures were operationally independent. There was a significant canonical relationship between activity rhythm parameters and clinical FMS measures (r = 0.376, R = 0.14, P < 0.001). The set of Mesor, Amplitude, and Phi activity parameters remained associated with clinical measures when controlled statistically for both demographics and activity variability (P < 0.001). Each activity parameter provided unique discrimination of the clinical set by multivariate test (P = 0.003, 0.018, and 0.007 for Amplitude, Phi, and Mesor, respectively). These results revealed that better pain, fatigue, mood, physical impairment, and sleep outcomes were associated with higher activity range and more rhythmicity (Amplitude), increased mean activity (Mesor), and with earlier timing of peak activity (Phi). Exploratory analyses revealed significantly worse sleep for individuals with low Amplitude and more delayed Phi.

Chronic pain produces major functional disability and quality-of-life impairment. Monitoring of health-related quality of life (HRQoL) outcomes in chronic pain patients during treatment is of great importance. Nevertheless, monitoring individual chronic pain patients remains a challenge due to the lack of a validated and efficient HRQoL assessment instrument. The Treatment Outcomes in Pain Survey (TOPS) is a validated HRQoL tool with sufficient accuracy and sensitivity to monitor the overall pain experience of individual patients while receiving multidisciplinary chronic pain management. However, the amount of time required to complete the TOPS questionnaire limits routine clinical utility and patient compliance. The full 14 TOPS scales are not needed to monitor routine clinical outcomes. Therefore, we developed and initially validated a shortened and restructured instrument, the S-TOPS, for individual patient monitoring in multidisciplinary chronic pain treatment. The reliability and validity of the S-TOPS were analyzed using data from 964 chronic pain patients who were treated in a single interdisciplinary pain clinic and completed >1 TOPS. The 7 scales of the S-TOPS have excellent construct validity, high reliabilities, and improved sensitivity to change for monitoring individual patient outcomes. Patients accepted the S-TOPS well, finding it brief enough for routine repeated administration.

Investigating dose-dependent effects of placebo analgesia (PA) in laboratory subjects undergoing pain testing, we evaluated 2 hypotheses: (1) greater expectancy for relief produces greater PA, and (2) cued expectancy for relief triggered by a predictive cue leads to more enhanced analgesia than does passive expectancy (no predictive cue). We used conditioning procedures in which 84 subjects experienced reduced stimulation intensity following the application of purported analgesic creams to the 2 experimental fingers, while the control finger received the same levels of stimulation as in the baseline block. The dose of placebos was manipulated by creating 2 levels of expectations for relief. The form of expectation (cued vs uncued) was also manipulated by a predictive cue specifying the next finger to be stimulated. Subjective reports and psychophysiological responses served as critical indicators for evaluating impacts of the placebo manipulation on subsequent pain processing. The dose-dependent PA was unambiguously demonstrated by the predicted ordering of the 3 fingers (ie, manipulated expectation levels) in terms of both response sensitivity and average response magnitude, in mixed-effects analysis of 3 outcome indicators (evoked potential, skin conductance response, pain report). Greater expectation for relief led to both (1) greater reductions in the average dependent variable slope (response sensitivity) as a function of stimulus intensity, and (2) greater reductions in average response magnitude. Unexpectedly, uncued expectation led to a slightly larger PA than did cued expectation. The study provided clear evidence that PA can occur in a "dose"-dependent manner, mediated by the levels of expectancy for pain relief.

The defense response theory implies that individuals should respond to increasing levels of painful stimulation with correlated increases in affectively mediated psychophysiological responses. This paper employs structural equation modeling to infer the latent processes responsible for correlated growth in the pain report, evoked potential amplitudes, pupil dilation, and skin conductance of 92 normal volunteers who experienced 144 trials of three levels of increasingly painful electrical stimulation. The analysis assumed a two-level model of latent growth as a function of stimulus level. The first level of analysis formulated a nonlinear growth model for each response measure, and allowed intercorrelations among the parameters of these models across individuals. The second level of analysis posited latent process factors to account for these intercorrelations. The best-fitting parsimonious model suggests that two latent processes account for the correlations. One of these latent factors, the activation threshold, determines the initial threshold response, while the other, the response gradient, indicates the magnitude of the coherent increase in response with stimulus level. Collectively, these two second-order factors define the defense response, a broad construct comprising both subjective pain evaluation and physiological mechanisms.

The distinctive features of individual patients, here termed individual differences, are inescapable aspects of day-to-day patient pain management, but classically designed research studies ignore such differences. This paper introduces statistical pattern visualization methodology for the study of complex individual differences in clinical settings. We demonstrate the application of such methods in patients undergoing bone marrow transplantation (BMT) and suffering severe oral mucositis as a consequence of the aggressive BMT preparative regimen. Oral mucositis produces severe pain and patients often require parenteral opioid medication for several weeks. Unfortunately, the opioid can cause side-effects that limit drug use for pain control. Patients differ in severity and duration of oral mucositis, analgesic response to opioids, and side-effects. We identified and classified individual differences in patterns of drug use, pain control and side-effects in 33 BMT patients who received opioid drug via patient-controlled analgesia (PCA) systems for 7 days or more. These systems allowed bolus dosing and also provided a basic level of analgesic protection through continuous drug infusion. Continuous infusion levels increased or decreased in response to patient bolus self-administration. We employed statistical smoothing (moving average) techniques to remove random variation from the individual data sets and created three-way (trivariate) plots of change over time in drug use, pain and an opioid side-effect (impairment of concentration). The patterns apparent in these plots indicated that 24.2% of patients used PCA optimally (increases in drug use associated with reductions in pain and little or no side-effect), an additional 30.3% manifested a potentially optimal pattern limited by side-effect that worsened with dosing, and 36.4% used PCA suboptimally (modest pain control plus side-effects). In addition, for each subject we created a summary measure for the simultaneous change in three variables: the distance of each day's trivariate score from the origin of a three dimensional plot. This summary measure correlated significantly with the changing severity of patients' oral mucositis over time (r = 0.502). This study demonstrates how interactive graphic techniques can provide a basis for examining changes over time among multiple, correlated variables associated with a single individual. It illustrates the application of such techniques and demonstrates that individual subject data sets merit examination in cases where clinical data reflect human performance.

Background Propofol and alfentanil frequently are administered together for intravenous sedation. This study investigated pharmacokinetic and pharmacodynamic interactions between propofol and alfentanil, at sedative concentrations, with specific regard to effects on ventilation, analgesia, sedation, and nausea. Methods Ten male volunteers underwent steady-state infusions on 3 separate days consisting of propofol alone, alfentanil alone, or a combination of the two. Target plasma concentrations for propofol were 150, 300, and 600 ng/ml for 1 h at each concentration; for alfentanil it was 40 ng/ml for 3 h. Assessment included serial measurements of (1) ventilatory function (minute ventilation, carbon dioxide production, end-tidal carbon dioxide, ventilatory response to rebreathing 7% CO2); (2) analgesia (subjective pain report in response to graded finger shock and evoked potential amplitude); (3) sedation (subjective rating, observer scores, and digit symbol substitution test); (4) nausea (visual analog scale, 0-100 mm). Results During combination treatment, propofol plasma concentration was 22% greater than during propofol alone using replicate infusion schemes (P < 0.009). End-tidal carbon dioxide was unchanged by propofol, and increased equally by alfentanil and alfentanil/propofol combined (delta end-tidal carbon dioxide 7.5 and 6.2 mmHg, respectively). Analgesia with propofol/alfentanil combined was greater than with alfentanil alone. (Pain report decreased 50% by PA vs. 28% for alfentanil, P < 0.05). Sedation was greater with propofol/alfentanil combined than with alfentanil or propofol alone (digit symbol substitution test 30 for propofol/alfentanil combined vs. 57 for alfentanil, and 46 for propofol, P < 0.05). Nausea occurred in 50% of subjects during alfentanil, but in none during propofol/alfentanil combination treatment. Conclusions The combination of propofol and alfentanil produced greater sedation and analgesia than that with either drug alone. Propofol offset the emetic effects of alfentanil. Equivalent depression of the carbon dioxide response curve, and elevation of end-tidal carbon dioxide occurred with propofol/alfentanil combined and alfentanil.

Few controlled clinical trials of psychological interventions for cancer pain relief exist in spite of frequent support for their importance as adjuncts to medical treatment. This study compared oral mucositis pain levels in 4 groups of cancer patients receiving bone marrow transplants (BMT): (1) treatment as usual control, (2) therapist support, (3) relaxation and imagery training, and (4) training in a package of cognitive-behavioral coping skills which included relaxation and imagery. A total of 94 patients completed the study which involved two training sessions prior to treatment and twice a week 'booster' sessions during the first 5 weeks of treatment. Results confirmed our hypothesis that patients who received either relaxation and imagery alone or patients who received the package of cognitive-behavioral coping skills would report less pain than patients in the other 2 groups. The hypothesis that the cognitive-behavioral skills package would have an additive effect beyond relaxation and imagery alone was not confirmed. Average visual analogue scale (VAS) report of pain within the therapist support group was not significantly lower than the control group (P = 0.103) nor significantly higher than the training groups. Patient reports of relative helpfulness of the interventions for managing pain and nausea matched the results of VAS reports. From these results, we conclude that relaxation and imagery training reduces cancer treatment-related pain; adding cognitive-behavioral skills to the relaxation with imagery does not, on average, further improve pain relief.

Pre-transplant conditioning regimens for bone marrow transplantation often cause oral mucositis and severe pain. We evaluated the agreement of self- and parent reports of daily oral mucositis pain in children between the ages of 6 and 16 years. Child patients were asked to report their pain on visual analog scales (VAS) daily for 20 days following their transplants. Daily VAS ratings were also obtained from one of the parents. The analysis sample consisted of ten children aged 7–9, nine children aged 10–12, eight children aged 13–16, and their parents. We modeled individual child and parent reports as quadratic functions of the number of days post transplant. Empirical Bayes/restricted maximum-likelihood estimates were obtained of individual coefficients, treated as random effects, and age group coefficients, treated as fixed effects. Parents exhibited higher average pain curves than their children in each of the three age groups. The middle age group reported the highest average pain. Average within-person error variances representing unreliability were 692.2, 461.9, and 303.9 for young, middle, and old children, respectively; for parents, the corresponding error variances were 375.1, 413.3, and 252.4. These results challenge the presumption that children tend to over-report pain but are consistent with the contention that younger children may be less reliable reporters than adolescents and adults.

Few controlled clinical trials have tested the efficacy of psychological techniques for reducing cancer pain or post-chemotherapy nausea and emesis. In this study, 67 bone marrow transplant patients with hematological malignancies were randomly assigned to one of four groups prior to beginning transplantation conditioning: (1) hypnosis training (HYP); (2) cognitive behavioral coping skills training (CB); (3) therapist contact control (TC); or (4) treatment as usual (TAU; no treatment control). Patients completed measures of physical functioning (Sickness Impact Profile; SIP) and psychological functioning (Brief Symptom Inventory; BSI), which were used as covariates in the analyses. Biodemographic variables included gender, age and a risk variable based on diagnosis and number of remissions or relapses. Patients in the HYP, CB and TC groups met with a clinical psychologist for two pre-transplant training sessions and ten in-hospital "booster" sessions during the course of transplantation. Forty-five patients completed the study and provided all covariate data, and 80% of the time series outcome data. Analyses of the principal study variables indicated that hypnosis was effective in reducing reported oral pain for patients undergoing marrow transplantation. Risk, SIP, and BSI pre-transplant were found to be effective predictors of inpatient physical symptoms. Nausea, emesis and opioid use did not differ significantly between the treatment groups. The cognitive behavioral intervention, as applied in this study, was not effective in reducing the symptoms measured.

Background.Individual differences in treatment responses to health-related quality-of-life interventions arise ubiquitously and prominently in clinical trials. These differences do not reflect error, but instead represent patterns of response that vary reliably across patients. Individual difference