The early clinical recognition of juvenile-onset ankylosing spondylitis and its differentiation from juvenile rheumatoid arthritis

Objective. To determine which early clinical data differentiate juvenile-onset ankylosing spondylitis (AS) from juvenile rheumatoid arthritis (JRA). Methods. Medical records of 35 patients with juvenile-onset AS and 75 with JRA (excluding type II pauciarticular JRA), all of whom had disease onset at age ≤16 years, disease duration of ≤2½ years at the initial visit to the rheumatology clinic, and followup of ≥ 10 years, were analyzed retrospectively with regard to features of disease found 6 months, 12 months, and 10 years after onset. Results. At 6 months, various features appeared more frequently in the juvenile-onset AS group than in the JRA group, i.e., pauciarthritis (54.3% versus 30.7%; P = 0.03, odds ratio [OR] = 2.7), enthesopathy (82.9% versus 0%; P < 0.0001, OR = 321.4), tarsal disease (71.4% versus 1.3%; P < 0.0001, OR = 185.0), and lumbar/sacroiliac symptoms (11.4% versus 0%; P = 0.02, OR = 11.9). At 12 months, the features found more frequently among juvenile-onset AS patients than JRA patients were enthesopathy (88.6% versus 4.0%; P < 0.0001, OR = 186.0), tarsal disease (85.7% versus 10.7%; P < 0.0001, OR = 50.3), and knee disease (100.0% versus 82.7%; P = 0.04, OR = 8.0). Involvement of the upper extremities (especially the hands) was found in significantly fewer juvenile-onset AS patients compared with the JRA group. Definite involvement of the spine and sacroiliitis in juvenile-onset AS occurred after a mean ± SD of 7.3 ± 2.0 years. Conclusion. Regardless of axial disease, enthes opathy and tarsal disease in children who have arthritis of the lower, but not of the upper extremities differentiate juvenile-onset AS from JRA within 1 year of symptoms. The discriminative value of these parameters approaches that of axial disease (the gold standard) throughout the followup period.     

Reduction in long-term disability in patients with rheumatoid arthritis by disease-modifying antirheumatic drug–based treatment strategies

Objective. Therapeutic strategies for rheumatoid arthritis (RA) have been evolving from the traditional “pyramid” approach toward one based upon early and sustained use of disease-modifying antirheumatic drugs (DMARDs), in the hope of improving long-term health outcomes. However, few data to have been presented to document the effects of this approach. We sought to directly assess associations between consistent DMARD use and long-term functional outcomes. Methods. We studied 2,888 RA patients who were followed up prospectively for up to 20 years (average 9 years) at 8 databank centers. The independent variable was the proportion of patient encounters that resulted in treatment with ⩾1 DMARD (hydroxychloroquine, sulfasalazine, auranofin, intramuscular gold, D-penicillamine, methotrexate, and/or azathioprine). The dependent variable was each patient's last recorded Disability Index value from the Health Assessment Questionnaire (HAQ). Results. Increased DMARD use was strongly associated with better long-term Disability Index values (P < 0.0001). The association was strengthened when restricted to more seriously affected (rheumatoid factor (RF)–positive) patients. The magnitude of the effect, unadjusted, was a difference of 0.53 HAQ Disability units (scale 0–3) between 100% DMARD use and 0%. Correlation coefficients ranged up to 0.26. Effects were similar for all disease duration periods (0–4, 5–9, 10–14, 15–19, and 20+ years). “Control” correlations, with variables computed to represent the proportion of time in which patients were taking either nonsteroidal antiinflammatory drugs or prednisone, failed to show positive associations. A multiple linear regression model, which controlled for age, disease duration, sex, RF positivity, proportion of visits under a prednisone regimen, and initial disability level, included the proportion of time in which patients were taking DMARDs (P < 0.0001), with a model R² of 0.54. These results were obtained despite an adverse selection bias in which more severely affected individuals were given DMARDs more frequently, and despite absence of data on drug use early in the disease course of many patients. Thus, these results, which suggest up to a 30% reduction in longterm disability with consistent DMARD use, are most likely conservative. Conclusion. An association between consistent DMARD use and improvement in long-term functional outcomes in RA is supported by these data.     

Cross‐cultural adaptation and validation of the Malay health assessment questionnaire for use in rheumatoid arthritis

Objective: To validate the Malay version of the Health Assessment Questionnaire (Malay‐HAQ) for use in Malay‐speaking rheumatoid arthritis (RA) patients in the Malaysian setting. The HAQ – Disability Index has been validated in several languages, but not in Malay. Methods: The original HAQ was modified and translated into Malay by two translators, one of whom was aware of the objectives of the Questionnaire and the other as a lay translator. Two sets of Malay‐HAQ were distributed to RA patients during their routine follow‐up visits; one set to be completed immediately and another set to be completed 2 weeks later. A total of 61 patients completed the two sets of Malay‐HAQ. The data collected was analysed using SPSS V. 11.0. Reliability of the data was evaluated using the test‐retest method and internal consistency was assessed by Cronbach's alpha. Result: The study showed that the Malay‐HAQ is feasible and reliable. The Spearman's correlation coefficient ranged from 0.65 to 0.82, while the internal consistency was 0.88–0.92. Conclusion: The Malay‐HAQ is a sensitive, reliable and valid instrument for the measurement of functional status in RA patients in a Malay setting.     

Primary juvenile fibromyalgia. Psychological adjustment,family functioning,coping, and functional disability

Objectives. 1) To determine the importance of psychological adjustment and family functioning in primary juvenile fibromyalgia by assessing these factors in children with fibromyalgia and in their parents, compared with children with juvenile rheumatoid arthritis (JRA) and with pain-free control children and their parents. 2) To examine which of these factors predict functional disability. Methods. Fifteen children in each of the 3 study groups, and their parents, completed self-report questionnaires and pain diaries. A medical evaluation of each child was performed, including assessment of tender points by palpation and by dolorimetry. Results. All children in the fibromyalgia group met the Yunus and Masi criteria for fibromyalgia, and 11 met the American College of Rheumatology criteria. There were almost no significant group differences in the children's or parents' psychological adjustment, ratings of family functioning, or coping strategies. Significant group differences in functional disability, pain, fatigue, tender point threshold, and control point tolerance were found. A number of the psychological adjustment, pain, fatigue, and coping variables were significantly associated with functional disability. Conclusion. The notion that fibromyalgia is a psychogenic condition is not supported by these results. Fibromyalgia is associated with disability of a magnitude comparable to that of other chronic pain conditions. Disability among children with fibromyalgia or JRA is a function of the children's psychological adjustment and physical state, and of the parents' physical state and method of coping with pain.     

Impaired functional status in primary Sjögren's syndrome

Objective

Several studies have demonstrated that primary Sjögren's syndrome (SS) is associated with reduced productivity; however, the impact of primary SS on daily function is not fully understood. This study aims to assess the physical function of primary SS patients and determine the relationship between the functional impairment experienced by primary SS patients and disease activity, patient‐reported symptoms, and quality of life.

Methods

Sixty‐nine primary SS patients from a specialist clinical service were assessed for their functional ability (Improved Health Assessment Questionnaire [HAQ]), dryness, pain, and overall primary SS–related symptom burden; systemic disease activity; levels of fatigue, daytime somnolence, anxiety, and depression symptoms; quality of life; and systemic inflammation (erythrocyte sedimentation rate, C‐reactive protein [CRP] level). Data were compared to 69 healthy volunteers matched for age and sex.

Results

Primary SS patients experienced greater functional impairment than controls (Improved HAQ total scores: mean ± SD 24 ± 25 for primary SS versus 9 ± 19 for controls; P = 0.0002) across all domains of activity. In primary SS, functional impairment was significantly associated with physical fatigue (P < 0.0001, R² = 0.3), pain (P < 0.0001, R² = 0.3), depression (P < 0.0001, R² = 0.3), total symptom burden (P < 0.0001, R² = 0.3), systemic disease activity (P = 0.002, R² = 0.15), quality of life (P < 0.0001, R² = 0.3), dryness (P = 0.002, R² = 0.12), daytime somnolence (P = 0.02, R² = 0.08), anxiety score (P = 0.03, R² = 0.07), and CRP level (P = 0.04, R² = 0.06). Only CRP level is independently associated with functional impairment (β = 0.38, P = 0.025).

Conclusion

Primary SS patients experience significant functional disability compared to age‐matched healthy controls. Impaired function is associated with reduced quality of life and symptoms such as pain, fatigue, and depression, as well as disease activity, illustrating the importance of optimal management of all aspects of the disease.     

The value of the health assessment questionnaire and special patient-generated scales to demonstrate change in systemic sclerosis patients over time

Objective. To determine the validity and usefulness of a modified Health Assessment Questionnaire (HAQ) for measurement of disease status and changes in disease status over time in patients with systemic sclerosis (SSc). Methods. Since 1985,1,250 patients attending the University of Pittsburgh Scleroderma Clinic have completed a modified HAQ annually. In addition to the standard HAQ questions about disability, the questionnaire includes visual analog scales (VAS) to evaluate SSc organ system symptoms, Raynaud's phenomenon, gastrointestinal (GI) tract and lung involvement, pain, and overall disease severity. In this study, the disability index (DI) (from the HAQ) and the VAS scores (on a 0–3 scale) were compared with various clinical and laboratory features recorded within 3 months of administration of the HAQ and VAS, using t-tests and Spearman's correlation tests. Results. The HAQ DI correlated directly with skin involvement, scleroderma heart or kidney disease, tendon friction rubs, hand contractures, and proximal muscle strength. Over time, the DI correlated with changes in skin score and was a good predictor of survival. There was a significant improvement in the DI during a 2-year time period in patients treated with D-penicillamine. The VAS for digital ulcers, GI symptoms, and lung symptoms correlated very closely with subjective and objective findings for these organ systems. The presence of new digital ulcers or improvement in digital ulcers showed significant associations with the Vascular scale, new GI symptoms or improvement in GI symptoms and institution of H₂-blockers showed appropriate strong correlations with the GI scale, and changes in the forced vital capacity had an excellent correlation with the Lung scale (r = 0.58, P < 0.001). By Cox regression analysis, the HAQ DI was one of the best predictors of survival. Conclusion. These data provide convincing evidence that a self-administered questionnaire is an accurate and inexpensive tool to measure disease status changes in SSc. Prospective studies with the HAQ administered at regular intervals, as in controlled trials, should be performed to further assess the benefits and limitations of this instrument.     

Aberrant IgG galactosylation precedes disease onset,correlates with disease activity,and is prevalent in autoantibodies in rheumatoid arthritis

Objective

To examine the association between aberrant IgG galactosylation and disease parameters in rheumatoid arthritis (RA).

Methods

Analysis of N‐glycan in serum samples from multiple cohorts was performed. The IgG N‐glycan content and the timing of N‐glycan aberrancy relative to disease onset were compared in healthy subjects and in patients with RA. Correlations between aberrant galactosylation and disease activity were assessed in the RA cohorts. The impact of disease activity, sex, age, anti–cyclic citrullinated peptide (anti‐CCP) antibody titer, disease duration, and C‐reactive protein level on aberrant galactosylation was determined using multivariate analysis. The N‐glycan content was also compared between epitope affinity–purified autoantibodies and the remaining IgG repertoire in RA patients.

Results

Our results confirm the aberrant galactosylation of IgG in RA patients as compared with healthy controls (mean ± SD 1.36 ± 0.43 versus 1.01 ± 0.23; P < 0.0001). We observed a significant correlation between levels of aberrant IgG galactosylation and disease activity (Spearman's ρ = 0.37, P < 0.0001). This correlation was higher in women (Spearman's ρ = 0.60, P < 0.0001) than in men (Spearman's ρ = 0.16, P = 0.10). Further, aberrant IgG galactosylation substantially predated the onset of arthritis and the diagnosis of RA (3.5 years) and resided selectively in the anticitrullinated antigen fraction.

Conclusion

Our findings identify aberrant IgG galactosylation as a dysregulated component of the humoral immune response in RA that begins prior to disease onset, associates with disease activity in a sex‐specific manner, and resides preferentially in autoantibodies.

     

Disability and patient’s appraisal of general health contribute to depressed mood in rheumatoid arthritis in a large clinical study in Japan

Abstract

The aim of this study was to evaluate the factors responsible for depressed mood in rheumatoid arthritis (RA). Clinical and laboratory measures were collected from 4558 RA patients enrolled in a large clinical cohort study for RA conducted at the Institute of Rheumatology, Tokyo Women’s Medical University (IORRA study). A two-question depressed screening included in the U.S. Preventive Services Task Force recommendation were utilized to identify “depressed patients.” A total of 1875 (41.1%) were identified as “depressed patients” who presented with symptoms suggestive of depression. Patient’s Visual Analog Scale (VAS) for general health (43.3?mm vs 24.6?mm, P < 0.0001) and pain (40.9?mm vs 23.8?mm, P < 0.0001) and the disability index scores measured by the Health Association Questionnaire (HAQ) (0.986 vs 0.574, P < 0.0001) were significantly higher in depressed patients than in nondepressed patients. The presence of three or more comorbidities (odds ratio [OR] 2.157, P < 0.0001), infection (OR 1.754, P < 0.0001), and joint surgery (OR 1.878, P < 0.0001) were significantly correlated with depressed mood in RA. The results of the Generalized Linear Model analysis showed that HAQ disability index (P < 0.0001) and patient’s VAS for general health (P < 0.0001) were also strongly and significantly associated to the response variable “probability of depressed patients.’ Patient appraisal of poor general health and greater disability were associated with depressed mood in RA.     

Validation of a rheumatoid arthritis health‐related quality of life instrument,the CSHQ‐RA

Objective

To test the validity and reliability of a newly developed disease‐specific multidimensional quality of life instrument: the Cedars‐Sinai Health‐Related Quality of Life Instrument (CSHQ‐RA).

Methods

A total of 350 rheumatoid arthritis (RA) patients were asked to complete the CSHQ‐RA at 2 time points (4 weeks apart). Patients also completed the Medical Outcomes Study Short Form 36 (SF‐36) and the Stanford Health Assessment Questionnaire (HAQ) Disability Index (DI) at the second time point. Construct validity was tested, using Pearson's correlations, by comparing subscale scores on the CSHQ‐RA to those obtained from the mental component summary (MCS) and physical component summary (PCS) of the SF‐36. HAQ DI scores were used to assess the discriminant validity of the CSHQ‐RA. Intraclass correlation coefficients (ICCs) were used to assess test–retest reliability.

Results

Response rates for the first and second survey were 83% (291) and 93% (276), respectively; 84% of respondents were women, and mean age was 57 years. Mean scores ± SDs on instruments were: HAQ 0.73 ± 0.69; MCS 49 ± 12; and PCS 33 ± 11. Pearson's correlations between the CSHQ‐RA subscale scores and the SF‐36 scores ranged from 0.55 to 0.76 (P < 0.001). Analysis of variance indicate that scores on the CSHQ‐RA discriminated between levels of physical disability as measured by the HAQ (P < 0.001). Test–retest reliability was demonstrated in the instrument's subscale scores (ICC 0.70–0.90).

Conclusion

These results support the construct validity, discriminant validity, and reliability of the CSHQ‐RA as a measure that captures the impact of RA on patients' health‐related quality of life.

     

Adrenocorticotropic hormone response to hypoglycemic stress was preserved by a single bedtime 3-mg dose of prednisolone in patients with rheumatoid arthritis

Abstract

We have studied the effect of low-dose prednisolone administered before sleep on the hypothalamic–pituitary–adrenal axis and the symptoms of patients with rheumatoid arthritis (RA). Plasma adrenocorticotropic hormone (ACTH) and serum cortisol levels were measured in the basal state and after hypoglycemic stress induced by the insulin tolerance test in 21 patients receiving prednisolone at 3–5?mg daily. The patient's global assessment of their disease activity scores on a 100-mm visual analogue scale (VAS) and self-reporting of their functional status using the health assessment questionnaire (HAQ) were evaluated. While both the cortisol and the ACTH responses were impaired dose-dependently in patients treated with prednisolone, the ACTH response was maintained in patients treated with a single daily 3-mg dose of prednisolone before sleep. There was an inverse correlation between the extent of the ACTH response and disease activity as revealed by the VAS (r = 0.521, P < 0.05). There was also a weak correlation between VAS and the self-rating depression scale (SDS) (r = 0.443), especially when only patients with an HAQ score > 10 were included in order to exclude any possible contribution of the limitations in the activities of daily living to the SDS score (r = 0.859, P < 0.05). These results suggest that a single daily low dose (3?mg) of prednisolone administered before sleep maintains the ACTH response in RA patients, and patients with a good ACTH response appear to be less depressed and have milder symptoms.     

Functional and work outcomes improve in patients with rheumatoid arthritis who receive targeted,comprehensive occupational therapy

Objective

Work disability is a serious consequence of rheumatoid arthritis (RA). We conducted a 6‐month, prospective randomized controlled trial comparing assessments of function, work, coping, and disease activity in employed patients with RA receiving occupational therapy intervention versus usual care.

Methods

Employed patients with RA with increased perceived work disability risk were identified by the RA Work Instability Scale (WIS; score ≥10). Patients were stratified into medium‐ (score ≥10 and <17) and high‐risk (≥17) groups, then randomized into occupational therapy or usual care groups. Assessments were conducted at baseline and 6 months. The primary outcome was the Canadian Occupational Performance Measure (COPM), a standardized patient self‐report of function. Other outcomes included the disability index (DI) of the Health Assessment Questionnaire (HAQ); Disease Activity Score in 28 joints (DAS28); RA WIS; EuroQol Index; visual analog scales (VAS) for pain, work satisfaction, and work performance; and days missed/month. Independent sample t‐tests and Mann‐Whitney U tests were used.

Results

We recruited 32 employed patients with RA. At baseline the groups were well matched. At 6 months the improvement in the occupational therapy group was significantly greater than that in the usual care group for all functional outcomes (COPM performance P < 0.001, COPM satisfaction P < 0.001, HAQ DI P = 0.02) and most work outcomes (RA WIS [P = 0.04], VAS work satisfaction [P < 0.001], VAS work performance [P = 0.01]). Additionally, Arthritis Helplessness Index (P = 0.02), Arthritis Impact Measurement Scales II pain subscale (P = 0.03), VAS pain (P = 0.007), EuroQol Index (P = 0.02), EuroQol global (P = 0.02), and DAS28 (P = 0.03) scores significantly improved.

Conclusion

Targeted, comprehensive occupational therapy intervention improves functional and work‐related outcomes in employed RA patients at risk of work disability.     

The Nottingham health profile in rheumatoid arthritis: correlation with other health status measurements and clinical variables

Objective The overall effect of rheumatoid arthritis (RA) on general health status has drawn attention in recent years. The aim of this study was to determine the clinical relevance of the Nottingham Health Profile (NHP) in RA patients and the relationship between conventional clinical measures, the Health Assessment Questionnaire (HAQ), and the Beck Depression Inventory (BDI)Method One hundred RA patients (mean age 48.9±12.1 years, mean disease duration 101.3±85.5 months) were included in the study. Quality of life, health status, and psychological mood of the patients were assessed using NHP, HAQ, and BDI. The Ritchie Articular Index (RAI), visual analog scale, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor, and modified Larsen Scale were used to assess clinical, laboratory, and radiological changes.Results All subgroups of the NHP significantly correlated to VAS, RAI, BDI, and HAQ scores (P<0.001). Except in the social isolation subgroup, there were significant correlations with ESR (P<0.05, P<0.001, and P<0.0001, respectively). There were no correlations between CRP levels and health status measures (P>0.05).Conclusion The NHP reflects the clinical and psychological status of RA patients and can be used as a sensitive health status measure for clinical evaluation.     

Marital status and the progression of functional disability in patients with rheumatoid arthritis

Objective. To determine if marital status is associated with differences in rates of progression of functional disability in patients with rheumatoid arthritis (RA). Methods. A community cohort of 282 persons with RA was followed prospectively for up to 9.5 years. The progression of functional disability over time was determined using the Health Assessment Questionnaire Disability Index, which was completed by study participants every 6 months. Results. At study entry, the Disability Index was 1.1 ± 0.8 (mean ± 1 SD) (possible range 0–3) among the 188 married participants and 1.3 ± 0.9 among the 94 unmarried participants. Over time, the rate of progression of functional disability was generally higher among unmarried participants. However, the extent of this difference varied somewhat over the disease course, with rates of progression higher among unmarried than among married participants during years 5–7 and years 17–29 of RA. Overall estimated rates of progression, adjusted for the effects of other sociodemographic factors, were 0.03 Disability Index units per year in unmarried participants and 0.01 Disability Index units per year in married participants (P < 0.0001). Conclusion. Marriage, possibly reflecting the influence of social support, is associated with a lower rate of progression of functional disability in persons with RA.     

Asthma Severity,Psychiatric Morbidity,and Quality of Life: Correlation with Inhaled Corticosteroid Dose

Objectives.?Psychiatric phenomena in asthma has been debated for some time. Inhaled corticosteroids (ICS) are a significant part of treatment. We attempted to quantify the prevalence of psychiatric morbidity relative to asthma severity, quality of life (QOL), and ICS dose. Data Sources.?Fifty asthmatic patients (18 ≥ X ≤ 75 years) on ICS, attending an urban clinic had asthma and ICS dose stratified by symptom severity and preparation potency. Peak flow and forced expiratory volume in 1 second (FEV₁) were measured. Patients completed general QOL and disease-specific QOL questionnaires, along with psychiatric rating scales. Results.?Patients (n = 50) clustered in the 40–59 year range (n = 27, 54%) and were predominantly female (n = 44, 88%) Hispanics (n = 30, 60%), with mild-moderate asthma (n = 18, 36%) and on low-dose ICS (n = 22, 44%). FEV₁ ranged from 32 to 123 (mean 76.98, SE 3.01). Peak flow ranged from 210 to 590 (mean 407.83, SE 13.24). Prevalence of anxiety and depressive symptoms were higher than expected (Kendall's tau-c, n = 50, P < .01). Independently, high ICS dose and asthma severity correlated directly with all measures of psychiatric morbidity (Pearson's r 0.781, P < .01). High ICS dose correlated inversely with SF-36 Mental Component Scale (Pearson's r 0.681, P < .01) and directly with FEV₁ and peak flow when age/sex adjusted (Spearman's rho: 0.660, P < .001). Conclusions.?Psychiatric morbidity is more prevalent in this population and impacts negatively on QOL. Use of high-dose ICS benefited pulmonary function and “physical” QOL, yet may have negatively affected patients' mental well-being. Longitudinal follow-up, extension of sample size, and better study control would allow closer approximation of possible negative associations with ICS.     

The Disability Index of the Health Assessment Questionnaire is a predictor and correlate of outcome in the high‐dose versus low‐dose penicillamine in systemic sclerosis trial

Objective

To explore the clinical implications of a score of ≥1.0 on the Disability Index of the Health Assessment Questionnaire (HAQ DI) at the first patient visit, and to examine the implications of improvement in HAQ DI score over 2 years in a cohort of systemic sclerosis (SSc) patients with diffuse cutaneous scleroderma.

Methods

SSc skin and visceral involvement was assessed in 134 SSc patients with diffuse scleroderma (mean ± SD disease duration of 10 ± 4 months) when they entered a multicenter drug trial and again 2 years later. Mortality and the occurrence of scleroderma renal crisis were assessed for a mean ± SD of 4.0 ± 1.1 years. Logistic and linear regression analyses were used to examine the relationship of the baseline HAQ DI score to morbidity, mortality, and visceral involvement, as well as the relationship of changes in the HAQ DI score to changes in physical examination, laboratory, and functional variables over 2 years.

Results

A baseline HAQ DI score of ≥1.0 was predictive of mortality (odds ratio 3.22, 95% confidence interval 1.097–9.468) over 4 years. Multivariate linear regression demonstrated that a model which included the erythrocyte sedimentation rate at baseline (P = 0.005) and changes at 2 years in the swollen joint count (P = 0.002), total skin score (P = 0.005), and white blood cell count (P = 0.005) best explained the change in HAQ DI score over 2 years (R² = 0.528). The HAQ DI score and total skin score at baseline were highly correlated (correlation coefficient 0.368), as were changes in the HAQ DI score and the total skin score over 2 years (correlation coefficient 0.492). Although the HAQ DI score was heavily influenced by hand dysfunction at baseline and at 2 years, improvement (reduction) in the HAQ DI score over 2 years was related to factors other than hand dysfunction.

Conclusion

A baseline HAQ DI score of ≥1.0 predicted mortality over 4 years. Improvement in the HAQ DI score in these patients with diffuse scleroderma was associated with improvement in skin thickening, hand function, oral aperture, lung function, signs of arthritis, serum creatinine level, and the investigator's global assessment of improvement. The HAQ DI is a self‐administered questionnaire that SSc patients can complete easily and rapidly and that gives the practicing physician important information about prognosis, patient status, and changes in disease course over time.

     

Development and psychometric evaluation of the Benzodiazepine Craving Questionnaire

Aim To assess the scalability, reliability and validity of a newly constructed self‐report questionnaire on craving for benzodiazepines (BZs), the Benzodiazepine Craving Questionnaire (BCQ). Setting and participants The BCQ was administered once to a sample of 113 long‐term and 80 former long‐term general practice BZ users participating in a large BZ reduction trial in general practice. Measurements (1) Unidimensionality of the BCQ was tested by means of the Rasch model. (2) The Rasch‐homogeneous BCQ items were assessed for subject and item discriminability. (3) Discriminative and construct validity were assessed. Findings The BCQ met the requirements for Rasch homogeneity, i.e. BZ craving as assessed by the scale can be regarded as a unidimensional construct. Subject and item discriminability were good. Construct validity was modest. Highest significant associations were found with POMS depression (Kendall's tau‐c = 0.15) and Dutch Shortened MMPI negativism (Kendall's tau‐c = 0.14). Discriminative validity was satisfactory. Highest discriminative power was found for a subset of eight items (Mann–Whitney U Z = ? 3.6, P = 0.000). The first signs of craving are represented by the acknowledgement of expectations of positive outcome, whereas high craving is characterized by direct intention to use. Conclusions The BCQ proved to be a reliable and psychometrically sound self‐report instrument to assess BZ craving in a general practice sample of long‐term BZ users.     

Development and initial validation of a self‐assessed lupus organ damage instrument

Objective

The Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) is a validated instrument for assessing organ damage in systemic lupus erythematosus (SLE). Trained physicians must complete it, thus limiting utility where this is impossible.

Methods

We developed and pilot tested a self‐assessed organ damage instrument, the Lupus Damage Index Questionnaire (LDIQ), in 37 SLE subjects and 7 physicians. After refinement, 569 English‐speaking SLE subjects and 14 rheumatologists from 11 international SLE clinics participated in validation. Subjects and physicians completed the instruments separately. We calculated sensitivity, specificity, Spearman's correlations, and agreement using the SDI as the gold standard. Six hundred five SLE participants in the community‐based National Data Bank for Rheumatic Diseases (NDB) study completed the LDIQ and we assessed correlations with outcome and disability measures.

Results

The mean LDIQ score was 3.3 (range 0–16) and the mean SDI score was 1.5 (range 0–9). The LDIQ had a moderately high correlation with the SDI (Spearman's r = 0.50, P < 0.001). Specificities of individual LDIQ items were >80%, except for neuropathy. Sensitivities were variable and lowest for damage, with <1% prevalence. Agreement between the SDI and LDIQ was >85% for all but neuropathy, reduced renal function, deforming arthritis, and alopecia. In the NDB, the LDIQ correlated well with the comorbidity index (r = 0.45), the Short Form 36 physical component scale (r = 0.43), the Medical Research Council dyspnea scale (r = 0.40), disability (r = 0.37), and the Systemic Lupus Erythematosus Activity Questionnaire score (r = 0.37).

Conclusion

The metric properties of the LDIQ are good compared with the SDI. It has construct validity and correlations with health assessments similar to the SDI. The LDIQ should allow expansion of SLE research. Its ultimate value will be determined in longitudinal studies.     

Disability and patient’s appraisal of general health contribute to depressed mood in rheumatoid arthritis in a large clinical study in Japan

The aim of this study was to evaluate the factors responsible for depressed mood in rheumatoid arthritis (RA). Clinical and laboratory measures were collected from 4558 RA patients enrolled in a large clinical cohort study for RA conducted at the Institute of Rheumatology, Tokyo Women's Medical University (IORRA study). A two-question depressed screening included in the U.S. Preventive Services Task Force recommendation were utilized to identify “depressed patients.” A total of 1875 (41.1%) were identified as “depressed patients” who presented with symptoms suggestive of depression. Patient's Visual Analog Scale (VAS) for general health (43.3 mm vs 24.6 mm, P < 0.0001) and pain (40.9 mm vs 23.8 mm, P < 0.0001) and the disability index scores measured by the Health Association Questionnaire (HAQ) (0.986 vs 0.574, P < 0.0001) were significantly higher in depressed patients than in nondepressed patients. The presence of three or more comorbidities (odds ratio [OR] 2.157, P < 0.0001), infection (OR 1.754, P < 0.0001), and joint surgery (OR 1.878, P < 0.0001) were significantly correlated with depressed mood in RA. The results of the Generalized Linear Model analysis showed that HAQ disability index (P < 0.0001) and patient's VAS for general health (P < 0.0001) were also strongly and significantly associated to the response variable “probability of depressed patients.” Patient appraisal of poor general health and greater disability were associated with depressed mood in RA.     

Coronary artery injection technique: A quantitative in vivo investigation using modern catheters

To date, there have been no quantitative in vivo assessments of contrast volumes and injection rates using modern high flow catheters during coronary angiography. Contrast volumes (n = 554), injection durations (n = 563), and injection rates (n = 498) were collected during 88 cardiac catheterizations. With increasing cathetersize (6, 7, and 8 French), injection volume increased (P < 0.0001), duration decreased (P < 0.0001), and rate increased (P < 0.0001). Compared with injections into the right coronary artery, left coronary artery injections were larger (7.1 ± 0.1 cc vs. 4.8 ± 0.1 cc, p < 0.0001), longer (3.6 ± 0.05 sec vs 3.0 ± 0.07 sec, P < 0.0001) and faster (2.1 ± 0.04 cc/sec vs. 1.7 ± 0.06 cc/sec, P < 0.0001). Patients with a significant stenosis in the left main or proximal right coronary artery received less contrast (P < 0.0001) more slowly (P < 0.0001) over a similar duration of injection (P = NS). When collaterals arose from the injected artery, angiographers injected more contrast (P < 0.001) over a longer period (P < 0.0001) more slowly (P < 0.0001). Catheter size and the injected vessel's location and anatomy significantly affect coronary catheterization injection technique. Cathet. Cardiovasc. Diagn. 44:34-39, 1998. © 1998 Wiley-Liss, Inc.     

Do determinants of platelet function co-segregate with genetic markers of type 1 diabetes mellitus?: Analysis of platelet and fibrinolytic parameters in families with type 1 diabetes mellitus

This study examined the significance of selected parameters of primary haemostasis to discriminate between relatives of children with insulin-dependent diabetes mellitus (IDDM). Platelet function, including markers of spontaneous and agonist-induced platelet activation (CD62), platelet consumption (microparticles) and clumping (aggregates), as well as selected parameters of the fibrinolytic system (t-PA and PAI-1), were studied in IDDM children (n = 45), their parents (n = 65), siblings (n = 17) and unrelated healthy controls (n = 51). The fraction of activated platelets circulating in whole blood amounted to 4.3±2.1% in IDDM children, and significantly exceeded the level found in parents (1.3±0.7%, P < 0.002), siblings (1.2±1.0%, P < 0.002), and controls (1.2±0.6%, P < 0.002). Furthermore, an enhanced formation of platelet microparticles was observed in the IDDM group, both in resting platelets and also when platelets were stimulated with thrombin. Significantly decreased total PAI-1 occurred in IDDM children (P < 0.02 versus parents); also slightly lowered active PAI-1 and t-PA antigen were noticed in IDDM subjects compared to other groups, however, the differences were not statistically significant. To assess dissimilarities between the groups of subjects we applied the forward stepwise model of discriminant function analysis, which included platelet flow cytometry parameters. The best separation and the highest discrepancy (expressed as the so called squared Mahalanobis distances, d_M) was revealed between controls and IDDM patients (P ? 0.0001) and between controls and parents (P ? 0.0001). The values of d_M found between IDDM children and their siblings (P < 0.001), as well as parents (P < 0.01), were of much lower significance. The finding that the control group, representing unrelated subjects, remains particularly well separated from the other groups, more or less clustered together, implies the possible involvement of genetic factor(s) which might potentially affect platelet activation and reactivity. In addition, the distinguished distribution of HLA DQAI⁵² and HLA DQBI⁵⁷ genotypes in the groups further validates the suspicion that the altered platelet function and response in diabetes might be associated with some independent genetic factor(s), and is not likely to result from HLA DQAI⁵² and HLA DQBI⁵⁷ impact.