Relationship between physical activity and hip pain in persons with and without cam or pincer morphology: a population-based case-control study.

OBJECTIVES: The purpose of the study was to determine if physical activity (PA) is a risk factor for persistent or recurrent hip pain in young and middle-aged persons with and without radiographic findings of cam or pincer morphology (CPM). METHODS: A population sample of persons aged 20-49 with (cases) and without (controls) hip pain in Metro Vancouver, Canada, was selected through random digit dialing (RDD). Self-reported PA was expressed as average energy expenditure (MET-hours) per year, over lifetime. CPM was defined as alpha angle >55°, lateral centre edge angle (LCE) >40°, or positive cross-over sign. RESULTS: Data were obtained for 500 subjects, 269 cases and 231 controls. Prevalence of radiographic CPM was 49% in the cases and 44% in the controls. In a logistic regression model adjusted for age, gender and CPM, total lifetime PA, including occupational, domestic and recreational activities, was significantly associated with hip pain (Odds ratio (OR) 1.30 per 1000 MET-hours, 95% CI 1.15-1.38). The effect of total PA was observed in those with CPM (1.44, 1.17-1.78) and without CPM (1.23, 1.04-1.45). For domestic activities, the association was seen only in those with CPM (significant interaction). When PA was categorized into quartiles, higher levels of PA were associated with a greater risk of pain. CONCLUSIONS: PA, as measured by average energy expenditure over lifetime is a risk factor for hip pain in young and middle-aged persons. For some activities, the risk is likely increased in persons with radiographic evidence of CPM.

The validity of a non-radiologist reader in identifying cam and pincer femoroacetabular impingement (FAI) using plain radiography.

The purpose of this study was to evaluate the validity and reliability of a radiographic diagnosis of femoroacetabular impingement (FAI) by a non-radiologist. Symptomatic FAI is prevalent and thought to be a cause of hip osteoarthritis. However, the diagnosis is often delayed by 1-2 years, in large part because radiographic findings are often subtle and clinicians have been unaware of their significance. The purpose of this study was to evaluate the validity of a radiographic diagnosis of FAI by a non-radiologist. A population-based sample of 701 subjects was recruited in Vancouver, Canada. For the current study, 50 subjects were selected-40 randomly from the population sample and 10 from an orthopedic practice with confirmed FAI. An anterior-posterior pelvis and bilateral Dunn radiographs were acquired and read by a fellowship-trained musculoskeletal radiologist and a third-year medical student who received basic training in radiographic signs of FAI. Three radiographic signs were evaluated: the lateral center edge angle, alpha angle and crossover sign. Validity was assessed using sensitivity and specificity, Bland-Altman limits of agreement and kappa. The sample contained 65% women (n = 31), was 62% Caucasian and 38% Chinese and had a mean age of 38.3 years. For correctly diagnosing FAI, the non-radiologist reader had a sensitivity of 0.83 and specificity of 0.87. Intra-rater κ value was 0.72, and prevalence-adjusted bias-adjusted κ was 0.76. This study provides evidence that a non-radiologist can accurately and reliably identify FAI on plain films.

The relationship between subchondral sclerosis detected with MRI and cartilage loss in a cohort of subjects with knee pain: the knee osteoarthritis progression (KOAP) study.

PURPOSE: To assess the association between subchondral sclerosis detected at baseline with MRI and cartilage loss over time in the same region of the knee in a cohort of subjects with knee pain. METHODS: 163 subjects with knee pain participated in a longitudinal study to assess knee osteoarthritis progression (KOAP). Subjects received baseline knee radiographs as well as baseline and 3-year follow-up MRI examinations. Baseline subchondral sclerosis and bone marrow lesions (BMLs) were scored semiquantitatively on MRI in each region from 0 to 3. Cartilage morphology at baseline and follow-up was scored semiquantitatively from 0 to 4. The association between baseline subchondral sclerosis and cartilage loss in the same region of the knee was evaluated using logistic regression, adjusting the results for age, gender, body mass index, and the presence of concomitant BMLs. RESULTS: The prevalence of subchondral sclerosis detected by MRI in the regions of the knee varied between 1.6% (trochlea) and 17% (medial tibia). The occurrence of cartilage loss over time in regions varied between 6% (lateral tibia) and 13.1% (medial femur). The prevalence of radiographically-detected subchondral sclerosis in compartments varied from 2.9% (patellofemoral) to 14.2% (medial tibiofemoral). In logistic regression models, there were no significant associations between baseline subchondral sclerosis detected by MRI and cartilage loss in the same region of the knee. CONCLUSION: Baseline subchondral sclerosis as detected by MRI did not increase the risk of cartilage loss over time.

Natural history of cartilage damage and osteoarthritis progression on magnetic resonance imaging in a population-based cohort with knee pain.

OBJECTIVES: To determine the natural history of cartilage damage and of osteoarthritis (OA) progression using magnetic resonance imaging (MRI); to evaluate whether OA progression varies by stage of disease. METHODS: A population-based cohort with knee pain was assessed clinically, with X-ray (Kellgren-Lawrence [KL] grading) and MRI. Cartilage was graded 0-3 on six joint surfaces. Frequency of cartilage damage change was determined for each joint site. Progression of OA was defined as a worsening of MRI cartilage damage by ≥1 grade in at least two joint sites or ≥2 grades in at least one joint site. The association of KL grade with OA progression was evaluated using parametric lifetime regression analysis. RESULTS: 163 subjects were assessed at baseline and follow-up (mean 3.2 years). KL grade ≥2 was present in 39.4% at baseline. An increase in cartilage damage by ≥1 grade was seen in 8.0-14.1% of subjects at different joint sites. OA progression on MRI was present in 15.5%. Baseline KL grade was a significant predictor of OA progression with hazard ratio (HR) of 6.5 (95% confidence interval [CI] 1.4-30.7), 6.1 (95% CI 1.3-28.9), and 9.2 (95% CI 1.9-44.9) for KL grades 1, 2 and ≥3, respectively. CONCLUSION: A low OA progression rate was seen over 3 years in this population-based symptomatic cohort. Radiographic severity, including KL grade 1, was a significant predictor of OA progression. Future interventions aimed at reducing progression will need to target not only radiographic OA, but also those with early abnormalities suggestive of pre-radiographic OA.

The association of magnetic resonance imaging (MRI)-detected structural pathology of the knee with crepitus in a population-based cohort with knee pain: the MoDEKO study.

Osteoarthritis (OA) is the most common arthropathy of the knee joint(1). Symptoms reported by patients and signs noted during physical examination guide clinicians in identifying subjects with knee OA(2-4). Pain is one of the most important symptoms reported by subjects with knee OA(2,3). Although very common, pain is a non-specific symptom, related to pathology in several structures within the knee joint, and includes synovitis(5), subchondral bone marrow lesions(6), and joint effusion(7). Further, pain is a subjective symptom that cannot be directly measured or assessed during physical examination. Crepitus or crepitation in association with arthritis is defined as a crackling or grinding sound on joint movement with a sensation in the joint. Crepitus may occur with or without pain and is a common finding during physical examination in subjects with knee OA(2-4,8,9). It is not known whether crepitus is related to pathology in various structures within the knee. The aim of our study was to determine the cross-sectional associations of structural pathologies within the knee with crepitus in a population-based cohort with knee pain, using magnetic resonance imaging (MRI). Subjects with knee pain were recruited as a random population sample, with crepitus assessed in each compartment of the knee using a validated and standardized approach during physical examination(10). MRI of the knee was performed to assess cartilage morphology, meniscal morphology, osteophytes, cruciate ligaments, and collateral ligaments. For both compartment-specific and whole-knee analyses, a multiple logistic regression analysis was performed to assess the associations of MRI-detected structural pathology with crepitus, adjusting for potential confounders. Variables were selected by backwards elimination within each compartment and in the overall knee models, and only statistically significant variables remained in the "selected" models; remaining variables in these models are adjusted for each other. An increased risk for compartment-specific crepitus was associated with osteophytes at the patellofemoral (PF) and lateral tibiofemoral (LTF) joints. Crepitus was associated with osteophytes and medial collateral ligament (MCL) pathology at the medial tibiofemoral (MTF) compartment, but cartilage damage was negatively associated with crepitus at this compartment. In the selected whole-knee model, only meniscal tears were associated with an increased risk for general crepitus. Thus, it seems that crepitus may be associated with pathology in several internal structures.

Influence of lifetime hip joint force on the risk of self-reported hip osteoarthritis: a community-based cohort study.

OBJECTIVE: To investigate the influence of cumulative lifetime hip joint force on the risk of self-reported medically-diagnosed hip osteoarthritis (OA). DESIGN: Prospective cohort. SETTING: General population. PARTICIPANTS: Members of Canadian Association of Retired Persons, community-dwelling. MAIN OUTCOME: Health-professional diagnosed hip OA, self-reported. METHODS: Exposure data on lifetime physical activity type (occupational, household, sport) and dose (frequency, intensity, duration) was collected in 2005. Subjects were ranked in terms of a 'cumulative peak force index' (CFPI), a measure of lifetime mechanical hip joint force. Multivariable survival analyses were performed to obtain adjusted effects for mean lifetime exposure and during 5-year age periods. RESULTS: Of 2918 subjects aged 45-85, 176 (6.03%) developed hip OA during the 2-year follow up (43 men, 133 women). The highest quintile of mean lifetime hip CPFI (HR 2.32; 95% CI 1.31-4.12), and high hip force in three age periods (35-39, 40-44, 45-49) were independently associated with hip OA. Previous hip injury was an approximate five-fold risk for development of hip OA across all models. In analysis by activity domain (occupation, sport, household), there was a trend (non-significant) for the highest quintile of occupational force, but not sport or household, to be associated with hip OA. CONCLUSIONS: A newly proposed measure of lifetime mechanical hip force was used to estimate the risk of self-reported, medically-diagnosed hip OA. While there are important limitations, this prospective study suggests that lifelong physical activity is generally safe. Very high levels of lifetime force from all domains combined, and in particular from occupational forces, may be important in the etiology of hip OA.

Not all "quality-adjusted life years" are equal.

BACKGROUND: There is evidence that utility elicitation methods used in the calculation of quality-adjusted life years (QALYs) yield different results. It is not clear how these differences impact economic evaluations. METHODS: Using a mathematical model incorporating data on efficacy, costs, and utility values, we simulated the experiences of 100,000 hypothetical rheumatoid arthritis patients over 10 years (50,000 exposed to infliximab plus methotrexate [MTX] and 50,000 exposed to MTX alone). QALYs, were derived from the Health Utilities Index 2 and 3 (HUI2 and HUI3), the Short Form 6-D (SF-6D), and the Euroqol 5-D (EQ-5D). Incremental cost-utility ratios were determined using each instrument to calculate QALYs and the results were compared using cost-effectiveness acceptability curves. RESULTS: Using the different utility measurement methods, the mean difference in QALYs between the infliximab plus MTX and MTX groups ranged from a high of 1.95 QALYs (95% CI=1.93-1.97) using the HUI3 to 0.89 QALYs (95% CI=0.88-0.91) using the SF-6D. Adopting the commonly cited value of society's willingness to pay for a QALY of $50,000, 91% of the simulations favored the cost utility of infliximab plus MTX when using the HUI3 to calculate QALYs. However, when using the EQ-5D, HUI2, or the SF-6D utility values to calculate QALYS, the proportion of simulations that favored the cost utility of infliximab were 63%, 45%, and 12%, respectively. CONCLUSION: Depending on the method for determining utility values used in the calculation of QALYs, very different incremental cost-utility ratios are generated.

A reappraisal of the United Kingdom epidemic of fatal asthma. Can general mortality data implicate a therapeutic agent?

The 1960s epidemic of asthma deaths that affected young persons in England and Wales, as well as in other countries, was attributed to the effect of newly available pressurized aerosols containing sympathomimetic bronchodilators. The subsequent decision to ban the nonprescription sale of these agents in the United Kingdom represented a unique use of national and international mortality data. The application of such data for decisions about therapeutic agents has implications for the current rise of asthma deaths in New Zealand, for the recent United States regulatory action regarding the nonprescription sale of aerosolized bronchodilators, and for the appraisal of adverse reactions to other pharmaceutical substances. This article is concerned with the quality of the scientific evidence used to implicate bronchodilators in the 1960s epidemic, and also with the strengths and weaknesses of the ecologic studies on which the implication depended. After concluding that the causal link between asthma deaths and bronchodilators was not supported by satisfactory scientific evidence, we present new data and an alternative diagnostic-exchange hypothesis that may, in part, help explain the original association.

A controlled study of diffuse idiopathic skeletal hyperostosis. Clinical features and functional status.

Diffuse idiopathic skeletal hyperostosis (DISH) is a common but little-studied disorder in the elderly that is infrequently recognized by physicians. Its prevalence in adults over 40 years of age is estimated at 3.8% for men and 2.6% for women. The present case-control study evaluated the history of pain and stiffness, radicular pain and enthesitis, physical findings on the musculoskeletal examination, and level of physical and psychologic disability in 130 persons: 56 patients with DISH, 43 control patients with spondylosis of the lumbar spine, and 31 healthy control patients. DISH patients were more likely to report a past history of upper extremity pain, medial epicondylitis of the elbow, enthesitis of the patella or heel, or dysphagia than spondylosis patients. They had more extremity and spinal stiffness and pain than healthy controls. DISH patients weighed more at a young age and their body mass index was greater at the time of the clinical evaluation than either spondylosis or healthy control patients. On musculoskeletal examination, DISH patients had a greater reduction in neck rotation and thoracic movements than either spondylosis patients or healthy controls, and had a greater reduction in lumbar movement than healthy controls. DISH patients had similar levels of spinal disability and physical disability overall, as measured by standardized indices, as spondylosis patients. No differences were found among the 3 groups of patients for the laboratory tests evaluated. DISH is clearly a distinct disorder with signs and symptoms that distinguish it from other causes of spinal complaint and from healthy individuals. It has the potential to cause major disability. Future studies need to address the natural history of DISH, pursue pathogenic mechanisms, and evaluate treatment modalities.

Incidence, prevalence, and evidence. Scientific problems in epidemiologic statistics for the occurrence of cancer.

Major changes in policy for health, nutrition, and industrial safety have been proposed because of the "epidemic of apprehension" produced by statistics for the occurrence rates of cancer. The statistical information, however, contains gross violations of epidemiologic principles and scientific standards for credible evidence. The calculations often depend on an improper linkage of numerators and denominators; and the calculated rates, assembled from reports of overtly detected cases of cancer, represent neither incidence nor prevalence. Many of the secular or regional changes in rates are due to corresponding changes in the availability and dissemination of diagnostic technology, but the technologic changes have not been adequately evaluated or investigated. Improvements will require drastically altered approaches to the use of death certificates, tumor registries, and clues from necropsy data.

The overdiagnosis of fibromyalgia syndrome.

PURPOSE: As fibromyalgia syndrome (FM) has gained greater acceptance and awareness in both the medical and the lay community, the possibility of overdiagnosis exists. Diffuse body pain in a woman is likely to suggest this diagnosis. We report the diagnosis of FM in 11 female patients whose primary cause for musculoskeletal symptoms was spondyloarthritis rather than only FM. PATIENTS AND METHODS: Of a total of 321 new rheumatology referrals in a 1-year period, 35 (11%) were diagnosed with FM. A further 11 (3%) were referred with either a previous diagnosis of FM or a presumed diagnosis of FM in whom the musculoskeletal syndrome could be attributed to previously unrecognized spondyloarthropathy. RESULTS: The 11 female patients had mostly experienced musculoskeletal symptoms for prolonged periods of time ranging from 1 to 40 years. Symptoms included prominent spinal pain involving at least 2 locations in the spine (n = 10), night pain that disturbed sleep (n = 10), and prolonged morning stiffness (n = 9). A previous history of enthesopathy, or history in the patient or first-degree relative of one of the seronegative associated diseases, such as psoriasis or ulcerative colitis, occurred in nine patients. Most patients had already undergone extensive investigations by various specialists in musculoskeletal medicine, but spondyloarthritis had only infrequently been considered a diagnostic possibility. CONCLUSION: Spondyloarthropathy in women may present subtly and have considerable overlap in symptomalogy with FM. A diagnosis of spondyloarthropathy should be considered in women with an ill-defined pain syndrome with prominent spinal pain and associated enthesopathy, or history or family history of seronegative-associated disease. It is possible that a primary diagnosis of FM is being made too freely, without consideration of other diagnoses, in the setting of ill-defined musculoskeletal pain.

Adult Still's disease.

The clinical and laboratory features in six patients with adult Still's disease are presented and compared with those in 52 other cases gathered from the literature. Although there is no pathognomonic abnormality, the condition can be readily recognized by the striking constellation of clinical and laboratory abnormalities. The typical rash occurs in 90 per cent of the cases, arthritis in 88 per cent, a fever with temperatures of 40 degrees C or more in 83 per cent and leukocytosis of 18,000 cells/mm3 or more in 67 per cent. One or more ot the following are frequently found: lymphadenopathy (48 per cent), splenomegaly (45 per cent), pleuritis or pneumonitis (31 per cent) and pericarditis (26 per cent). The initial therapy of choice is high doses of nonsteroidal anti-inflammatory drugs. This is not an uncommon disease, as was once thought, and awareness of it will avoid unnecessary diagnostic procedures and delay in initiating therapy.

Tuberculosis of the sacroiliac joint: clinical features, outcome, and evaluation of closed needle biopsy in 11 consecutive cases.

Sacroiliac joint (SIJ) involvement has been reported in up to 9.7 percent of patients with skeletal tuberculosis. Lack of awareness of this now uncommon form of infection often leads to diagnostic delay and increased morbidity. Eleven consecutive cases of SIJ tuberculosis are reported; clinical and radiologic features, diagnosis, treatment, and outcome are discussed. Buttock pain was the presenting complaint in all patients. However, radicular pain in the lower back (seven patients) or lower limb (10 patients) was common and in one patient precipitated an unnecessary surgical intervention. SIJ tuberculosis is frequently an isolated phenomenon. Therefore, direct sampling of the SIJ is necessary to establish the diagnosis. The recently described technique of closed needle biopsy of the SIJ was employed in all 11 patients and established the diagnosis in nine of the 11.

Diagnosis and treatment of ossification of the posterior longitudinal ligament of the spine: report of eight cases and literature review.

PURPOSE: Ossification of the posterior longitudinal ligament (OPLL) is a common, well-recognized cause of spinal stenosis and myelopathy in Japan. Although also common in whites, especially among the elderly, it has received little scientific attention. We wish to increase awareness of this important cause of myelopathy, and to determine if the clinical characteristics of OPLL are similar in non-Japanese and Japanese patients. PATIENTS AND METHODS: The clinical and radiologic features of eight cases of OPLL are presented. These cases combined with 73 non-Japanese cases gathered from the English literature are contrasted with 2,125 Japanese cases of OPLL. RESULTS: Similarities among non-Japanese and Japanese cases included: (1) male predominance; (2) peak age at onset of symptoms in the sixth decade; (3) clinical presentation, which ranged from asymptomatic to quadriplegia, with progressive or acute onset of neurologic deterioration; (4) greater than 95% localization to the cervical spine, spastic quadriparesis being the most common neurologic presentation; (5) an association with several rheumatic conditions including diffuse idiopathic skeletal hyperostosis (DISH), spondylosis, and ankylosing spondylitis; and (6) neurologic improvement with either conservative or surgical treatment in a significant proportion of patients. Differences between the two groups were minimal and included a higher mean age at onset (although onset in both groups occurred within the sixth decade) and a greater proportion of patients with DISH and with the continuous type of OPLL in the non-Japanese group. CONCLUSION: The clinical characteristics of OPLL are similar in Japanese and non-Japanese patient populations. Increased awareness of this condition, which has potentially devastating neurologic complications, will favorably influence diagnosis, treatment, and outcome.

A controlled study of the long-term prognosis of adult Still's disease.

PURPOSE: To assess the long-term prognosis of patients with adult Still's disease for physical and psychological disability, pain, social functioning, social support, medication use, formal education, occupation, time lost from work, and family income, and to contrast these results with those of same-sex sibling controls. PATIENTS AND METHODS: Patients were recruited from medical center-based cohorts in Pittsburgh and Eastern Canada and from a national survey of rheumatologists. Patients and same-sex sibling controls completed the Health Assessment Questionnaire for physical disability, the psychological and social function domains of the Arthritis Impact Measurement Scales, and the Interpersonal Skills Evaluation List questionnaire for social support, and replied to questions on medication use, formal education, occupation, time lost from work, and family income. RESULTS: One hundred four of 111 eligible adult Still's patients (94%) provided data. They identified 86 same-sex sibling controls, of whom 60 (70%) participated. The mean duration of adult Still's disease was 10 years. Approximately half of patients continued to require medication even 10 years after diagnosis. Patients had significantly higher levels of pain, physical disability, and psychological disability when compared with the controls. However, the levels of pain and physical disability were low compared to patients with other rheumatic diseases. Educational achievement, occupational prestige, social functioning and support, time lost from work, and family income were similar for both patients and controls. CONCLUSIONS: Despite causing disability, pain, and, in many, the need for long-term medication, patients with adult Still's disease are resilient. The disease did not interfere with educational attainment, occupational prestige, social functioning and support, time lost from work, or family income.

Rheumatic diseases in North America's indigenous peoples.

OBJECTIVES: There are at least 3 million North American Indians and Eskimos in North America. The epidemiology of rheumatic diseases in Native North Americans differs from that described for the remainder of the North American population. An enhanced understanding of rheumatic diseases in these indigenous people may provide valuable clues to the cause of these disorders and improve rheumatologic care. METHODS: The world literature was searched for all reports of rheumatic diseases in North American Indians and Eskimos. The reports were reviewed and the findings summarized by disease process. RESULTS: Many Native American groups have high prevalence rates of rheumatoid arthritis (RA), systemic lupus erythematosus, connective tissue diseases, and spondyloarthropathies. There appears to be a correlation between the pattern of rheumatic diseases in Native North Americans and the patterns of migration and ancestry. In general, Amerind Indians have increased rates of RA and connective tissue disease, while Na-Dene Indians and Eskimos have high rates of spondyloarthropathies. The RA seen in Native Americans is generally severe, seropositive, with an early age of onset, and frequent extraarticular manifestations. Many Native American groups have very high frequencies of the RA shared epitope. The majority of Native American and Eskimo groups also have high frequencies of HLA-B27, and some of the world's highest prevalence rates of spondyloarthropathies are described in these groups. Although some groups show a marked tendency to develop either Reiter's syndrome or ankylosing spondylitis, psoriatic and enteropathic arthritis are rare. CONCLUSIONS: The excess rheumatic disease seen in this population is most likely genetic in origin. Because of the combination of high rates of rheumatic disease and relative genetic homogeneity, Native North Americans represent a singular opportunity to study genetic contributions to rheumatic disease. For clinicians, the index of suspicion for rheumatic diseases in North American Indians and Eskimos should be high, and the severe disease and sometimes atypical presentations kept in mind.

The pathogenesis and prognosis of lupus nephritis: information from repeat renal biopsy.

Of an inception cohort of 87 patients with lupus nephritis who underwent a renal biopsy, 42 underwent second biopsies a median of 25 months later. From first to second biopsy, focal and diffuse proliferative nephritis (World Health Organization classes III and IV) became less frequent, and mesangial hypercellularity (class II) and a membranous pattern (class V) increased. The National Institutes of Health activity index and mesangial and subendothelial deposits declined while the chronicity index, a tubulointerstitial index, and subepithelial deposits increased. The biopsy improvement in urinary protein excretion was best explained by decreases in the activity index score and the amount of subendothelial deposits. A decrease in the amount of subendothelial deposits tended to predict an improvement in the serum creatinine level from first to second biopsy. With follow-up from second biopsy in excess of 7 years, the best predictors of long-term outcome were the ultrastructural variables mesangial, subendothelial and subepithelial deposits. When the change in biopsy predictors from first to second biopsy was evaluated, a decrease in the amount of mesangial or subendothelial deposits was best at predicting a lower risk of renal impairment, renal insufficiency, and mortality. The results confirm the importance of immune complex deposition as measured by electron microscopy in the pathogenesis of lupus nephritis and suggest that control of this process may alter renal function and prognosis.

Comprehensive radiographic evaluation of diffuse idiopathic skeletal hyperostosis: development and interrater reliability of a scoring system.

OBJECTIVE: To develop a scoring system for radiographic findings in diffuse idiopathic skeletal hyperostosis (DISH) and to test interrater reliability. MATERIALS AND METHODS: Fifty-five DISH patients and 35 spondylosis patients underwent two views (anteroposterior and lateral) of the cervical, thoracic, and lumbar spine, lateral views of both ankles, knees, and elbows, and anteroposterior views of the pelvis and shoulders. Two raters reviewed and scored the x-rays. Interrater reliability was assessed with the alpha statistic (alpha) for categorical variables and with the intraclass correlation coefficient (ICC) for continuous variables. RESULTS: The agreement was similar for the three spinal segments (alpha = 0.44 to 0.71). The lower extremity agreement ranged from 0.28 to 0.76, with higher agreement at the knee (alpha > or = 0.46) and the ankle (alpha > or = 0.56) than at the pelvis (ICC < or = 0.58). The agreement at the shoulders and elbows ranged from 0.50 to 0.75. The agreement between the readers was higher with summary measurements than with single (site-by-site) measurements: for each spinal segment, the ICC was 0.83 or greater; for the lower extremity, the ICC = 0.79; and for the upper extremity, the ICC = 0.68. CONCLUSION: We have described a comprehensive scoring system to assess the spinal and peripheral involvement of DISH.

Aberrant cellular localization of rubella viral genome in patients with adult Still's disease--a pilot study.

The rubella virus (RV) genome was detected using polymerase chain amplification techniques in several peripheral blood cell populations in patients with adult Still's disease (ASD) and normal controls (NC), including mononuclear cells (PBMC), B-cells, T-cells, monocyte/macrophages, and polymorphonuclear leukocytes (PMN). Five of 6 ASD patients and 3 of 6 NC subjects had detectable RV genome. Viral genomic load was significantly higher in ASD than in NC subjects (4.4 fold higher, p = 0.03). Interestingly, a differential cellular distribution of viral genome was observed between ASD and NC individuals. RV genome was detected more frequently in the PBMCs of ASD (5 of 6) patients compared to 2 of 6 NC. The viral genome was more localized to the PMN compartment equally in ASD and in NC subjects. On further cellular analysis, RV genome was detected in B-cells and macrophages but not T-cells in one patient. Existence of a differential viral genomic reservoir between ASD and NC suggests that this may play a role in the pathogenesis of disease manifestations and may reflect the inability to clear latent virus.

Randomized discontinuation trials: utility and efficiency.

The randomized discontinuation trial (RDT) is a two-phase trial. In phase I all patients are openly treated with the medication being evaluated. In phase II, those who have responded are randomly assigned to continue the same treatment or switch to placebo. Usually, non-compliers and "adverse reactors" identified in phase I are excluded from phase II. To investigate the value of this design, we reviewed the advantages and limitations of discontinuation studies, and compared the RDT design to the classic randomized clinical trial design in terms of clinical utility and efficiency (sample size). A computer model was used to study the efficiency of the two designs under a broad range of assumptions. The RDT design is particularly useful in studying the effect of long-term, non-curative therapies, especially when the clinically important effect is relatively small, and the use of placebo should be minimized for ethical or feasibility reasons. However, its use is limited if the objective of an investigation is to estimate the magnitude of absolute treatment effects and toxic effects in the source population, or to evaluate a potentially curative treatment. Our results indicate that selecting responders prior to randomization has a very strong effect on the relative efficiency of the trial. Further improvement may be achieved by excluding non-compliers and adverse reactors. Under the assumptions tested in our model, the sample size required in phase II of an RDT was only 20-50% of that in a classic trial.