Alan T. Kaell

Reactive effects of diary self-assessment in chronic pain patients.

&NA; Several studies of experimental and acute clinical pain have indicated reactive effects of self‐assessment on pain intensity and tolerance. A recent study of chronic pain patients (vonBaeyer 1994), however, failed to show these effects. The present investigation sought to determine whether reactive effects can be produced in chronic pain patients by an intensive self‐assessment protocol. Using the methodology of ecological momentary assessment (EMA; Stone and Shiffman 1994), thirty‐five chronic rheumatoid arthritis patients completed diaries of pain and mood seven times a day for 1 wk. Eighteen patients were included in the final sample because they responded to at least half of the number of hourly prompts for each of the 7 days. Using repeated measures analysis of the daily means, no significant effects of time were found for any measures. Reactive effects that result in an average change in pain levels over time, therefore, do not appear to be produced by intensive self‐assessment in a naturalistic context. Results are discussed in terms of cognitive and behavioral theories of pain reactivity.

A naturalistic evaluation of cortisol secretion in persons with fibromyalgia and rheumatoid arthritis.

OBJECTIVE To compare cortisol levels, diurnal cycles of cortisol, and reactivity of cortisol to psychological stress in fibromyalgia (FM) and rheumatoid arthritis (RA) patients in their natural environment, and to examine the effect on results of accounting for differences among the groups in psychological stress and other lifestyle and psychosocial variables. METHODS Participants were 21 FM patients, 18 RA patients, and 22 healthy controls. Participants engaged in normal daily activities were signaled with a preprogrammed wristwatch alarm to complete a diary (assessing psychosocial- and lifestyle-related variables) or provide a saliva sample (for cortisol assessment). Participants were signaled to provide 6 diary reports and 6 saliva samples on each of two days. Reports of sleep quality and sleep duration were also made upon awakening. RESULTS FM and RA patients had higher average cortisol levels than controls; however, there were no differences between the groups in diurnal cycles of cortisol or reactivity to psychological stress. While the groups differed on stress measures, surprisingly, the patient groups reported less stress. Furthermore, statistically accounting for psychosocial- and lifestyle-related differences between the groups did not change the cortisol findings. CONCLUSION The results provide additional evidence of hypothalamic-pituitary-adrenal axis disturbance in FM and RA patients. While such elevations are consistent with other studies of chronically stressed groups, the elevations in cortisol in this study did not appear to be due to ongoing daily stress, and there was no evidence of disturbed cortisol reactivity to acute stressors.

RAPID3 (Routine Assessment of Patient Index Data) on an MDHAQ (Multidimensional Health Assessment Questionnaire): Agreement with DAS28 (Disease Activity Score) and CDAI (Clinical Disease Activity Index) activity categories, scored in five versus more than ninety seconds

To compare the Routine Assessment of Patient Index Data 3 (RAPID3) on a Multidimensional Health Assessment Questionnaire (MDHAQ) with the Disease Activity Score (DAS28), Clinical Disease Activity Index (CDAI), and individual core data set measures for correlations, agreement of activity levels, and time to score.

Dose-limiting toxicity of rifabutin in AIDS-related complex: syndrome of arthralgia/arthritis.

We studied the tolerance of humans to rifabutin, a rifamycin with antimycobacterial and in vitro anti-HIV activity. Sixteen subjects with AIDS-related complex were treated for 4–66 weeks with stepwise increasing oral doses of rifabutin from 300 to 2400 mg/day. The highest dose attained was twice that previously reported for humans. Serum and cerebrospinal fluid levels of drug were detected by high-pressure liquid chromatography. A reversible syndrome of arthritis/arthralgia, not previously described, was seen in most (nine out of 10) of those given doses exceeding 1050 mg/day. Uveitis and aphthous stomatitis developed at doses of approximately 1800 mg in two of those with joint manifestations. Typical manifestations of Reiters syndrome were not seen in any patient. An orange-tan skin pigmentation was almost universal. Other toxicities resembled those previously associated with rifampin. Serum levels did not approach those found to inhibit HIV significantly in vitro. No consistent antiviral or immunological effects were observed; even at the highest doses, rifabutin did not appear to inhibit cellular immunity. Rifabutin was well tolerated at daily doses blow 1 g.

Criteria for the diagnosis of fibromyalgia: validation of the modified 2010 preliminary American College of Rheumatology criteria and the development of alternative criteria.

To validate the 2011 modification of the 2010 American College of Rheumatology (ACR) preliminary criteria for the diagnosis of fibromyalgia (2011ModCr) and develop alternative criteria in a sample of patients with diverse pain disorders that are commonly seen in everyday practice by pain specialists, rheumatologists, and psychologists.

Structured writing about stressful events: exploring potential psychological mediators of positive health effects.

In a previous study, the authors found that structured writing about stressful events improved symptomatology in 112 patients with rheumatoid arthritis and asthma relative to patients who did not write (J. Smyth, A. Stone, A. Hurewitz, & A. Kaell, 1999). However, little is currently known about the pathways from the intervention to alterations in outcomes. In addition to measuring symptom outcomes after the intervention in the previous study, the authors monitored perceived stress, quality of sleep, affect, substance use, and medication use on a momentary basis for the 7 days prior to writing, during the 3 intervention days, and for the 14 days following the intervention (N = 105). These variables were tested in a secondary data analysis to determine whether they mediated the effects observed in the J. Smyth, A. Stone, et al. study. No evidence was found supporting mediation, and the mechanism underlying structured writing about stressful events remains unknown.

Nurse practitioners can effectively deliver pain coping skills training to osteoarthritis patients with chronic pain: A randomized, controlled trial

Summary A multisite, randomized, controlled trial showed that nurse practitioners can effectively deliver pain coping skills training to osteoarthritis patients with chronic pain. ABSTRACT A multisite, randomized, controlled clinical effectiveness trial was conducted for osteoarthritis patients with chronic pain of the knee or hip. Adult health nurse practitioners provided a 10‐session intervention, pain coping skills training (PCST), in patients’ doctors’ offices (N = 129 patients); the control group received usual care (N = 127 patients). Primary outcomes assessed at baseline, posttreatment, 6‐month follow‐up, and 12‐month follow‐up were: pain intensity, physical functioning, psychological distress, self‐efficacy, catastrophizing, use of coping strategies, and quality of life. Secondary measures included fatigue, social functioning, health satisfaction, and use of pain medication. Methods favoring external validity, consistent with pragmatic, effectiveness research, were utilized. Primary ITT and secondary per‐protocol analyses were conducted. Attrition was within the expected range: 11% at posttreatment and 29% at 12‐month follow‐up; rates did not differ between groups. Omnibus ITT analyses across all assessment points indicated significant improvement for the PCST group compared with the control group for pain intensity, physical functioning, psychological distress, use of pain coping strategies, and self‐efficacy, as well as fatigue, satisfaction with health, and reduced use of pain medication. Treatment effects were robust to covariates (demographics and clinical sites). Trends in the outcomes across the assessments were examined. All outcomes, except for self‐efficacy, were maintained through the 12‐month follow‐up; effects for self‐efficacy degraded over time. Per‐protocol analyses did not yield greater effect sizes. Comparisons of PCST patients who were more vs less treatment adherent suggested greater effectiveness for patients with high adherence. Results support the effectiveness of nurse practitioner delivery of PCST for chronic osteoarthritis pain.

Distress and disease status among patients with rheumatoid arthritis: Roles of coping styles and perceived responses from support providers

Previous research has shown that social support can have a beneficial impact on coping processes and psychological adjustment in patients with rheumatoid arthritis (RA). The association of individual coping styles and perceived responses from others to one’s pain episodes with patients’ distress and disease status over time was investigated. The sample consisted of 42 middle-aged patients with RA who were predominantly White (98%), female (64%), and married (88%). Participants completed surveys and their rheumatologist completed clinical assessments of patient disease status at 2 time points over a 9-month period. Although punishing responses from others (e.g., getting irritated or angry when the patient is in pain) were perceived as relatively infrequent, they were associated with a patient coping style of focusing on and venting of negative emotion as well as elevated negative affect (NA). Findings also indicated that those who perceived punishing responses from close others and coped by venting negative emotions reported increased NA over time and were rated by their rheumatologist as having more severe RA disease status over time. Implications for psychosocial intervention and directions for future research are discussed.

Occurrence of antibodies to Borrelia burgdorferi in patients with nonspirochetal subacute bacterial endocarditis

Lyme disease, a consideration in the differential diagnosis of patients with fever and musculoskeletal symptoms [1], is often established serologically by detecting antibodies to the causative organism, Borrelia burgdorferi [2-12]. False-positive Lyme test results are well recognized in patients with other spirochetal infections (for example, syphilis [6]), viral diseases (for example, Epstein-Barr virus mononucleosis and parvovirus [3, 5]), and sarcoidosis [3]. We previously described [1] four patients with nonspecific musculoskeletal manifestations who were initially thought to have Lyme borreliosis based on positive results of serum tests for B. burgdorferi but in whom test results from blood cultures confirmed nonspirochetal subacute bacterial endocarditis. These patients all resided in an area where B. burgdorferi infection was endemic. To determine the frequency and specificity of antibodies to B. burgdorferi (as measured by ELISA) in patients with endocarditis, we studied patients who resided in an area devoid of B. burgdorferi-infected ticks. We also assessed whether increased levels of antibodies to B. burgdorferi in patients with endocarditis were attributable to rheumatoid factor often present in patients with endocarditis. Methods All patients had nonspirochetal, subacute bacterial endocarditis (proven by blood culture) diagnosed at Cornell Medical Center between 1979 and 1981. All resided in areas not endemic for Lyme borreliosis. No patient had a history of deer tick bite or erythema migrans rash. These patients with endocarditis were diagnosed before the advent of Lyme serologic tests, and none had their illness attributed to Lyme disease. Sera obtained from these patients during their endocarditis illness were stored at 40C. Anti-B. burgdorferi antibodies were detected by ELISA using sonicated, whole B31 strain as previously described [13]. A convenience sample of frozen sera collected between 1989 and 1990 from asymptomatic persons residing in Suffolk County, New York, were used as negative controls (n = 30); this baseline control value was 1.8 0.6 units. Sera were rated positive if they were more than 4.0 units (>3 SD above the mean of the controls). In the figures, data are reported as the ratio of the sample optical density to the negative cut-off value of 4.0 units. Immunoblotting was done with these sera using the laboratory-adapted B31 strain of B. burgdorferi as previously described [13]. Spirochetes were sonicated in phosphate-buffered saline containing 1 mol/L p-methyl sulfinylfluoride and were then concentrated and boiled in 2.5% sodium dodecyl sulfate/2.5% -mercaptoethanol for 3 minutes. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transfer to nitrocellulose (0.2 pore size; Hoeffer, San Francisco, California) were done according to standard methods [14]. Samples for specific IgG were incubated at a 1:200 dilution of sera, and samples for specific IgM and IgA were incubated at a 1:50 dilution. Bound antibodies were detected with a 1:5000 dilution of goat anti-human -, -, or -specific IgG conjugated to alkaline phosphatase and were developed with BICIP-Substrate System (5-bromo-4-chloro-3-indole phosphate, nitroblue tetrazolium; Kirkegaard and Perry Laboratories, Gaithersburg, Maryland). Reactions were stopped by rinsing the blots in distilled water. Immunoblots were interpreted to be diagnostic of Lyme disease according to published criteria [15] (that is, positive immunoblots have distinct 41-kd bands and at least four other defined bands). IgM rheumatoid factor was quantified by a solid-phase radioimmunoassay using iodine 125-labeled F (Ab)2 anti- reagents to detect IgM rheumatoid factor bound to solid-phase, adsorbed, heat-aggregated human IgG, as previously described [16]. A positive result was defined as more than 2.2% binding, a value 2 SD above the mean (10 normal controls had a mean = 1.8% 0.2 SD). Values are reported in the figures as the ratio of the sample percentage binding to the negative control cut-off binding of 2.2%. Rheumatoid factor was also measured in two additional groups. IgM rheumatoid factor was measured by latex agglutination (Behring) in a convenience sample of frozen sera collected between 1991 and 1992 at the Stony Brook Lyme Center from 15 patients with seropositive Lyme disease who met criteria for Lyme disease established by the Centers for Disease Control and Prevention [17]. In addition, consecutive sera were collected from 20 patients with rheumatoid arthritis who were positive for rheumatoid factor and were treated in a private rheumatology office practice in Suffolk County between August 1991 and January 1992. Sera were tested for antibodies to B. burgdorferi by ELISA. All patients with rheumatoid arthritis fulfilled at least four of seven disease criteria of the American College of Rheumatology [18] and were positive for IgM rheumatoid factor using a latex agglutination test. None had coincident bacterial infection. All resided in Suffolk County, New York, an area endemic for Lyme disease, but none had a history of an erythema migrans rash. Statistical Analyses Values are presented as mean SE. Comparisons between dichotomous values were done using chi-square analysis with the Yates correction. For continuous measures, t-tests and Pearson correlations were used. Results Thirteen of 30 patients with subacute bacterial endocarditis (43%) had a positive ELISA result (> 4 units) for B. burgdorferi, whereas 3 of the 30 controls (10%) had ELISA values greater than 4.0 units (P < 0.01). The mean of the B. burgdorferi antibody-positive sera was 7.52 units in the patients with endocarditis (range, 4.2 to 19.8 units). The mean of the normal controls was 1.8 units (range, 0.1 to 10 units). The causative organisms in the 30 patients with endocarditis included a broad spectrum of streptococci in addition to five Staphylococcus aureus isolates and one isolate each of Staphylococcus epidermidis and Lactobacillus casei. No preponderance of any one organism was noted in patients with endocarditis who were either positive or negative for B. burgdorferi antibody. Immunoblot analysis of 22 of the 30 sera are shown in Figure 1. Positive Lyme sera are positioned in lanes 1 and 24 (lane 24 is serum from a previously reported patient with both endocarditis and Lyme disease [1]). The three normal control sera from patients with increased antibodies for B. burgdorferi (using immunoblot tests) showed only isolated 41-kd reactivity (data not shown). Of the 13 patients with endocarditis who had positive ELISA results for B. burgdorferi antibodies, 1 (lane 19) had high antibody levels (19.8 units), and the immunoblot of this serum showed multiple bands, including a strong 41-kd band consistent with, but not diagnostic of, previous exposure to B. burgdorferi [15]. Five of the remaining 12 patients (42%) had 60-to 67-kd reactivity (Figure 1; lanes 7, 18, 19, 22, and 23). An additional dark 41-kd reactivity line, seen in almost all seropositive Lyme patients, was not seen. The weak anti-41-kd reactivity seen in many of the sera from patients with endocarditis is indistinguishable from the faint anti-41-kd bands seen in sera from normal patients [13]. Seven of 12 patients had positive ELISA results (mean, 7.86 units), yet 3 (43%) of these had no strong bands on immunoblots. These three immunoblots, despite positive ELISA results, were indistinguishable from normal negative controls. Overall, 12 of 30 (40%) patients with endocarditis who had increased antibodies to B. burgdorferi, as measured by ELISA, were falsely positive. This represents a specificity of only 60% (95% CI, 42% to 78%). Of our 30 patients with endocarditis, sufficient sera were available from 13 patients to measure IgM rheumatoid factor. Eleven of the 13 patients (85%) tested positive for quantitative IgM rheumatoid factor, but the titers varied widely. Figure 2 shows the comparison between normalized levels of IgM rheumatoid factor in the endocarditis groups positive (n = 5) and negative (n = 8) for B. burgdorferi antibody. Although the mean levels of IgM rheumatoid factor were slightly higher in the group seropositive for antibody to B. burgdorferi (n = 5; mean, 5.6 1.15 units) than in the seronegative group (n = 8; mean, 3.96 0.90 units), the differences were not statistically significant (P > 0.2). No correlation was found between the IgM rheumatoid factor level and the B. burgdorferi antibody level for both groups combined (R = 0.2; P > 0.2). Figure 1. Immunoblot analysis of sera from 23 of 30 patients with nonspirochetal bacterial endocarditis who reside in nonendemic areas for Lyme disease. Borrelia B. burgdorferi B. burgdorferi B. burgdorferi Figure 2. Relation between IgM rheumatoid factor and B. burgdorferi antibody levels in 13 patients with endocarditis. Borrelia B. burgdorferi P Both IgM rheumatoid factor and B. burgdorferi antibodies were also measured in two control groups (Figure 3). Of 15 patients who met criteria for Lyme disease established by the Centers for Disease Control and Prevention and had antibodies to B. burgdorferi, none had a positive rheumatoid factor (Figure 3, left). Conversely, in 20 patients with rheumatoid arthritis who were positive for rheumatoid factor, only one had increased levels of B. burgdorferi antibodies using ELISA (Figure 3, right). An immunoblot of this patients sera showed reactivity to the 31-, 41-, 56-, 58-, and 66-kd bands of B. burgdorferi consistent with previous infection (data not shown). Figure 3. Relation between IgM rheumatoid factor and B. burgdorferi antibody levels. Left. Right. Borrelia Discussion The diagnosis of noncutaneous Lyme borreliosis is based on the serologic confirmation of previous exposure to B. burgdorferi plus clinical manifestations suggestive of Lyme borreliosis [1, 2, 19]. Such manifestations are defined by the Centers for Disease Control and Prevention for the purpose of detecting patients with Lyme borreliosis (

Single momentary assessments are not reliable outcomes for clinical trials

Patient reported outcomes (PROs) play an essential role in clinical trials, though questions have been raised about the accuracy of PROs using long recall periods. This paper examines the utility of a PRO employing a single momentary assessment of pain in a sample of community rheumatology patients. We explore the accuracy and reliability of a single assessment versus the average of multiple assessments taken over 1-week, which is considered a common outcome reporting period. A secondary analysis of 128 patients who monitored their pain intensity with momentary data collections several times a day for a week and 3 months later for another week allowed a comparison of randomly-selected single momentary assessments with the average of many assessments from the week. Results from cross-sectional analyses of the first week were that levels of pain measured by single points were not significantly different than the week average in 4 of 5 analyses, but these single-point assessments had much higher variance. Correlations of single-point and week averages were below 0.70. Longitudinal analysis of change scores across 3 months also demonstrated considerable unreliability of single-point measures, thus the statistical power generated by single-point assessments was considerably less than the more reliable week average. Our conclusion is that single momentary assessments, at least for representing an outcome over a period of a week, are not ideal measures. We discuss alternative measurement strategies for efficiently collecting PRO data for a 1-week period using end-of-day diaries or 7-day recall measures.