Theo de Boo

Cognitive behaviour therapy for chronic fatigue syndrome: a multicentre randomised controlled trial

BACKGROUND Cognitive behaviour therapy (CBT) seems a promising treatment for chronic fatigue syndrome (CFS), but the applicability of this treatment outside specialised settings has been questioned. We compared CBT with guided support groups and the natural course in a randomised trial at three centres. METHODS Of 476 patients diagnosed with CFS, 278 were eligible and willing to take part. 93 were randomly assigned CBT (administered by 13 therapists recently trained in this technique for CFS), 94 were assigned the support-group approach, and 91 the control natural course. Multidimensional assessments were done at baseline, 8 months, and 14 months. The primary outcome variables were fatigue severity (on the checklist individual strength) and functional impairment (on the sickness impact profile) at 8 and 14 months. Data were analysed by intention to treat. FINDINGS 241 patients had complete data (83 CBT, 80 support groups, 78 natural course) at 8 months. At 14 months CBT was significantly more effective than both control conditions for fatigue severity (CBT vs support groups 5.8 [2.2-9.4]; CBT vs natural course 5.6 [2.1-9.0]) and for functional impairment (CBT vs support groups 263 [38-488]; CBT vs natural course 222 [3-441]). Support groups were not more effective for CFS patients than the natural course. Among the CBT group, clinically significant improvement was seen in fatigue severity for 20 of 58 (35%), in Karnofsky performance status for 28 of 57 (49%), and self-rated improvement for 29 of 58 (50%). Prognostic factors for outcome after CBT were a higher sense of control predicting more improvement, and a passive activity pattern and focusing on bodily symptoms predicting less improvement. INTERPRETATION CBT was more effective than guided support groups and the natural course in a multicentre trial with many therapists. Our study showed a lower proportion of patients with improvement than CBT trials with a few highly skilled therapists.

Effect of folic or folinic acid supplementation on the toxicity and efficacy of methotrexate in rheumatoid arthritis: a forty-eight week, multicenter, randomized, double-blind, placebo-controlled study

OBJECTIVE To study the effect of folates on discontinuation of methotrexate (MTX) as single-drug antirheumatic treatment due to toxicity, to determine which type of adverse events are reduced, to study the effects on the efficacy of MTX, and to compare folic with folinic acid supplementation in a 48-week, randomized, double-blind, placebo-controlled trial. METHODS Patients with active RA (n = 434) were randomly assigned to receive MTX plus either placebo, folic acid (1 mg/day), or folinic acid (2.5 mg/week). The initial MTX dosage was 7.5 mg/week; dosage increases were allowed up to a maximum of 25 mg/week for insufficient responses. Folate dosages were doubled once the dosage of MTX reached 15 mg/week. The primary end point was MTX withdrawal because of adverse events. Secondary end points were the MTX dosage and parameters of efficacy and toxicity of MTX. RESULTS Toxicity-related discontinuation of MTX occurred in 38% of the placebo group, 17% of the folic acid group, and 12% of the folinic acid group. These between-group differences were explained by a decreased incidence of elevated liver enzyme levels in the folate supplementation groups. No between-group differences were found in the frequency of other adverse events or in the duration of adverse events. Parameters of disease activity improved equally in all groups. Mean dosages of MTX at the end of the study were lower in the placebo group (14.5 mg/week) than in the folic and folinic acid groups (18.0 and 16.4 mg/week, respectively). CONCLUSION Both folate supplementation regimens reduced the incidence of elevated liver enzyme levels during MTX therapy, and as a consequence, MTX was discontinued less frequently in these patients. Folates seem to have no effect on the incidence, severity, and duration of other adverse events, including gastrointestinal and mucosal side effects. Slightly higher dosages of MTX were prescribed to obtain similar improvement in disease activity in the folate supplementation groups.

Pain and reduced mobility in complex regional pain syndrome I: outcome of a prospective randomised controlled clinical trial of adjuvant physical therapy versus occupational therapy

There are no adequate comparative studies on physical therapy (PT) versus occupational therapy (OT) in patients with complex regional pain syndrome I (CRPS I). Therefore, we conducted a prospective randomised clinical trial to assess their effectiveness. The outcomes regarding reducing pain and normalising active range of motion (AROM) are discussed. Included in the study were 135 patients who had been suffering from CRPS I of one upper extremity for less than one year. They were randomly assigned to one of three groups: PT, OT, or control (social work, CT). Measurements were taken at base-line (t0), after 6 weeks, and after 3, 6 and 12 months (t1 to t4). Pain was measured on four visual analogue scales (VAS) and the McGill Pain Questionnaire, Dutch Language Version (MPQ-DLV). The AROM was recorded relative to the contralateral side. Explorative statistical evaluations were performed (Wilcoxon; alpha=0.05). PT and to a lesser extent OT, resulted in more rapid improvement in the VAS scores than CT, especially for the VAS during or after effort (P<0.05 at t1 to t3). PT was superior to CT and OT according to the MPQ-DLV particularly at t4. Improvement on the MPQ-DLV over the year was significantly greater for PT than for OT and CT (P<0.05). PT -and to a lesser degree OT- led to better results than CT for the AROM of the wrist, fingers and thumb at t1 to t3 (most-times P<0.05 for PT), but the improvements over the year were not significantly different. Our results indicated that PT, and to a lesser extent OT, were helpful for reducing pain and improving active mobility in patients with CRPS I of less than one year duration, localised in one upper extremity.

The C677T mutation in the methylenetetrahydrofolate reductase gene: A genetic risk factor for methotrexate-related elevation of liver enzymes in rheumatoid arthritis patients

OBJECTIVE To study the possible relationship between the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and the toxicity and efficacy of treatment with methotrexate (MTX) in patients with rheumatoid arthritis (RA). METHODS Genotype analysis of the MTHFR gene was done in 236 patients who started MTX treatment with (n = 157) or without (n = 79) folic or folinic acid supplementation. Outcomes were parameters of efficacy of MTX treatment, patient withdrawal due to adverse events, discontinuation of MTX treatment because of elevated liver enzyme levels, and the total occurrence of elevated liver enzyme levels during the study. Multivariate logistic regression analysis was used to study the relationship between the presence of the MTHFR C677T mutation and toxicity outcomes of MTX treatment. RESULTS Forty-eight percent of the patients showed the homozygous (T/T) or heterozygous (T/C) mutation. The presence of the C677CT or C677TT genotypes was associated with an increased risk of discontinuing MTX treatment because of adverse events (relative risk 2.01; 95% confidence interval 1.09, 3.70), mainly due to an increased risk of elevated liver enzyme levels (relative risk 2.38; 95% confidence interval 1.06, 5.34). Efficacy parameters were not significantly different between the patients with and those without the mutation. CONCLUSION The C677T mutation is the first identified genetic risk factor for elevated alanine aminotransferase values during MTX treatment in patients with RA. We postulate that the incidence of clinically important elevation of liver enzyme levels during MTX treatment is mediated by homocysteine metabolism. Supplementation with folic or folinic acid reduced the risk of toxicity-related discontinuation of MTX treatment both in patients with and in patients without the mutation.

Adjuvant physical therapy versus occupational therapy in patients with reflex sympathetic dystrophy/complex regional pain syndrome type I

OBJECTIVE To investigate the effectiveness and cost of physical therapy (PT) or occupational therapy (OT) in patients with reflex sympathetic dystrophy (RSD). DESIGN Prospective randomized controlled trial, with 1 year follow-up. SETTING Two university hospitals. PATIENTS One hundred thirty-five patients who had been suffering from RSD of one upper extremity for less than 1 year. INTERVENTIONS Patients were assigned to PT, OT, or a control group (social work). MAIN OUTCOME MEASURES Improvement in impairment level sumscore (ISS) over 1 year (Students t test). A difference of 5 ISS points between the groups was defined as being clinically relevant. Furthermore, severity of disability and handicap was measured and tested exploratively (Wilcoxon; alpha = .05), and cost-effectiveness of the groups was calculated. RESULTS PT and, to a lesser extent, OT resulted in a significant and also more rapid improvement in the ISS as compared with controls (6 and 4 ISS points, respectively). On a disability level, a positive trend was found in favor of OT. On a handicap level, no differences were found between the groups. PT had an advantage over OT regarding the cost-effectiveness ratio. CONCLUSION In different ways PT and OT each contribute to the recovery from RSD of the upper extremity.

Circulating soluble tumor necrosis factor receptors, interleukin‐2 receptors, tumor necrosis factor α, and interleukin‐6 levels in rheumatoid arthritis.

Objective. To assess whether circulating concentrations of soluble tumor necrosis factor receptors (sTNFR; p55 and p75), soluble interleukin-2 receptors (sIL-2R), tumor necrosis factor α (TNFα), and interleukin-6 (IL-6) reflect clinical response and whether changes are dependent on the drug used in rheumatoid arthritis (RA) patients taking methotrexate (MTX) or azathioprine (AZA). Methods. These cytokines and soluble receptors were assessed in 20 control subjects and serially for up to 48 weeks in 61 RA patients, by bioassay (IL-6) and immunoassays (sTNFR, sIL-2R, TNFα, and IL-6). Results. Concentrations of p55 and p75, sIL-2R, and TNFα (but not IL-6) were significantly higher in RA patients than in controls. Significant decreases in sIL-2R and p55 concentrations were associated with clinical improvement and were observed in patients treated with MTX, but not AZA. Both treatments induced decreases in IL-6 concentrations, but circulating AZA (or its metabolites) appears to interfere with the measurement of IL-6 bioactivity. TNFα and p75 levels did not show significant changes. Conclusion. Measurement of circulating sIL-2R, p55, and IL-6 may be useful in the evaluation of RA disease activity and response to therapy. Interference by circulating levels of drugs must be ruled out when bioassays are used to evaluate cytokine levels.

Doppler ultrasound scanning in the detection of renal artery stenosis in hypertensive patients

The diagnostic accuracy of Doppler ultrasound in the detection of renal arterial disease has been assessed in a prospective study of 61 hypertensive patients. The findings of Doppler ultrasound were compared with the results of renal angiography. In 15 patients (24.5%) no accurate Doppler signs could be obtained and the Doppler ultrasound examination was considered a technical failure. Of the remaining 46 patients, 24 had renal artery stenosis. Nine of the stenoses were not detected by Doppler ultrasound and in three patients a false positive diagnosis of renal artery stenosis was made. The sensitivity of Doppler ultrasound was 62.5%, the specificity 86.4% and the overall diagnostic accuracy was 73.9%. By comparing the 15 patients in whom Doppler ultrasound failed with the 46 in whom it was successful, age appeared to be higher and creatinine clearance lower in the failure group. By comparing the 34 patients with true positive and true negative results with the 12 patients with false results, no significant differences were found. In a multivariate analysis, higher age showed a significant relation to failure of Doppler ultrasound. Doppler ultrasound has limited value in the screening of hypertensive patients for renal artery stenosis.

The Radboud skills questionnaire: construction and reliability in patients with reflex sympathetic dystrophy of one upper extremity

Purpose: To construct a questionnaire to measure skills in which notably both hands are active, which is suitable for patients with a disease of one or both hands and to research its response stability and possible improvements. Method: Using the Dutch elaboration of the ICIDH and then experts in a Delphi round, the questionnaire was constructed. Thereafter, test-retest and inter-observer reliability was examined. Fifty-four patients with RSD in one upper extremity and a normal contralateral extremity participated in the study, the first twenty to evaluate the construction of the questionnaire and the others to test reliability. Results: The constructed Radboud skills questionnaire was reliable in terms of response stability (median coefficients of variation 2.2% to 6.6%). Correlations between categories of items were fair to good. Conclusions: A useful questionnaire was constructed to map alterations in the level of disability in patients with a disease of one hand or both hands.PURPOSE To construct a questionnaire to measure skills in which notably both hands are active, which is suitable for patients with a disease of one or both hands and to research its response stability and possible improvements. METHOD Using the Dutch elaboration of the ICIDH and then experts in a Delphi round, the questionnaire was constructed. Thereafter, test-retest and inter-observer reliability was examined. Fifty-four patients with RSD in one upper extremity and a normal contralateral extremity participated in the study, the first twenty to evaluate the construction of the questionnaire and the others to test reliability. RESULTS The constructed Radboud skills questionnaire was reliable in terms of response stability (median coefficients of variation 2.2% to 6.6%). Correlations between categories of items were fair to good. CONCLUSIONS A useful questionnaire was constructed to map alterations in the level of disability in patients with a disease of one hand or both hands.

Reliability and normal values for measuring the skin temperature of the hand with an infrared tympanic thermometer: A pilot study

Recording asymmetry in skin temperature between symmetric body areas is useful in monitoring diseases that alter skin temperature. This pilot study checked the reported high reliability of recording skin temperature of the hands with an infrared tympanic thermometer, provided insight into the relationship between dorsal and palmar temperature differences, and assessed the agreement between these data and normative data obtained from thermograms. Using an infrared tympanic thermometer, two independent assessors measured the temperature of 13 asymptomatic, right-handed subjects (mean age, 30 years; range, 21 to 44 years). Both test-retest and interobserver reliabilities were high. Skin temperature of the hand differed with the site where it was measured; differences between sites changed over time. The mean absolute differences in skin temperature between dorsal and palmar aspects of the hands were 0.30 degrees C and 0.25 degrees C, respectively. These data match normative values reported in the literature for infrared thermograms.

Hemodynamic effects of isometric exercise and mental arithmetic in hypertension treated with selective and nonselective β‐blockade

Hypertensive patients have an unfavorable pressor response to exogenous epinephrine during nonselective β‐blockade. We studied hemodynamics during epinephrine release induced by handgrip exercise and mental arithmetic to examine the clinical relevance of this phenomenon. Twenty‐two hypertensive patients were examined in a double‐blind crossover experiment with placebo, propranolol (240 mg daily), placebo‐washout, and metoprolol (300 mg daily). Changes induced by stress tests for systolic and diastolic blood pressure, heart rate (HR), and forearm blood flow (FBF) were of the same order on both β‐blockers. Rises in HR and FBF were equally reduced by both drugs. Neither handgrip exercise nor mental arithmetic induced significant differences in reaction during selective and nonselective β‐blockade.