Very recent onset rheumatoid arthritis: clinical and serological patient characteristics associated with radiographic progression over the first years of disease.

OBJECTIVES: Despite early recognition and disease modifying anti-rheumatic drug (DMARD) treatment, a sizable proportion of early rheumatoid arthritis (RA) patients show radiological progression. This study was performed to determine the frequency of erosive arthritis and the pace of radiological progression in an inception cohort of patients with very early RA (

The perception of rheumatoid arthritis core set measures by rheumatologists. Results of a survey.

OBJECTIVE: To investigate the perception of values of individual core set measures by rheumatologists, and how it differs across measures and across physicians. METHODS: We designed a survey in which 44 international expert rheumatologists explicitly marked positions on the scales of seven core-set measures that in their opinion corresponded to cut-points between remission, low, moderate and high disease activity. The measures comprised swollen and tender joint counts (SJC, TJC), CRP, ESR, patient and evaluator global assessments of activity (PGA, EGA), and the Health Assessment Questionnaire Disability Index (HAQ). RESULTS: The interpretation of measures across physicians was most consistent for ESR and PGA, while for CRP and joint counts there was most variation. Joint counts and CRP implied active disease at lower relative values (using normalized scales) than did PGA, EGA or ESR (P < 0.01 for most comparisons; Bonferroni-adjusted Wilcoxon signed rank test), and most physicians tended to tolerate higher numbers of tender joints than swollen joints to define similar levels of disease activity. Given these cut-points, more RA patients in a typical cross-sectional cohort would be regarded as being in remission according to joint counts (SJC, 35%; TJC, 55%) than to global scores (PGA, 18%; EGA, 9%), and fewer patients would be regarded as being in remission by physician-derived or laboratory measures than by patient-derived ones. CONCLUSION: These data give insights into the integrative process of activity evaluation and will be informative for future survey designs, studies using physician opinion as the gold standard for criterion validity of disease activity, and allow 'activity mapping' of values on different scales based on expert opinion.

[Activity-score based therapy in rheumatoid arthritis]. / Aktivitätsscore-basierte Therapieadaptation bei chronischer Polyarthritis.

Disease activity scores for rheumatoid arthritis have been developed and validated in recent years. They allow the longitudinal documentation of the effectiveness of treatment. Application of these scores in routine daily practice could significantly improve the effectiveness of therapy with relatively little effort. This review presents evidence for the benefits of the application disease activity scores in clinical routine.

Autoantibody profiling as early diagnostic and prognostic tool for rheumatoid arthritis.

BACKGROUND: Early treatment prevents progression of joint damage in rheumatoid arthritis (RA), but diagnosis in early disease is impeded by lack of appropriate diagnostic criteria. OBJECTIVE: To study the value of rheumatoid factor (RF), anti-cyclic citrullinated peptide autoantibodies (anti-CCP), and anti-RA33 autoantibodies for diagnosis of RA and prediction of outcome in patients with very early arthritis. METHODS: The prospective follow up inception cohort included 200 patients with very early (<3 months) inflammatory joint disease. Autoantibodies were measured at baseline and analysed in a tree based model which aimed at determining the added diagnostic value of testing for anti-CCP and anti-RA33 as compared with RF alone. RESULTS: RA was diagnosed in 102 patients, while 98 developed other inflammatory arthropathies. Receiver operator curve analysis showed an optimum cut off level for RF at 50 U/ml, above which anti-CCP and anti-RA33 had no additional diagnostic value. Remarkably, RF >or=50 U/ml and anti-CCP showed similar sensitivity and high specificity for RA, but overlapped considerably. Anti-RA33 was less specific and did not correlate with RF or anti-CCP. Among patients with RA, 72% showed at least one of these three autoantibodies, compared with 15% of non-RA patients. RF >or=50 U/ml and anti-CCP were predictors of erosive disease, whereas anti-RA33 was associated with mild disease. CONCLUSIONS: Stepwise autoantibody testing in early inflammatory joint disease, starting with RF, followed by anti-CCP (in patients with RF <50 U/ml), and finally anti-RA33, should be used as a sensitive and effective strategy for distinguishing patients with RA at high risk for poor outcome.

Attitudes to early rheumatoid arthritis: changing patterns. Results of a survey.

OBJECTIVE: To determine if rheumatologists have changed their views on diagnosis and treatment of early rheumatoid arthritis (RA). METHODS: Three consecutive questionnaires were sent out to international rheumatologists in 1997, 2000, and 2003. The following aspects of early RA were covered: definition; patient referral time; diagnostic means; follow up intervals; and treatment strategies. All initial participants who responded to at least one of the follow up surveys were included in the analysis. RESULTS: RA is now defined by a smaller number of affected joints (monarthritis: 9.8% respondents in 1997 v 17.4% in 2003), and shorter symptom duration (<3 months: 65.5% in 1997 v 85.8% in 2003). Early referrals (<6 weeks) increased (8.9% in 1997 v 17.4% in 2003). Serological test for diagnosis was mostly rheumatoid factor (100% in 2003), but anti-CCP was already used by 17.4% in 2003. Follow up of patients with early RA intensified (every 2 weeks: 16.1% in 1997 v 30.4% in 2003; every month: 47.8% in 2003 v 64.3% in 1997). Treatment with disease modifying antirheumatic drugs (DMARDs) mainly comprised methotrexate, sulfasalazine, and antimalarial drugs. Leflunomide was among the two favourite DMARDs of 10.9% in 2003, whereas no biological agent was so. In 2003, 46.7% respondents started treatment with DMARDs if RA was suspected (30.9% in 1997); no one waited for erosions to occur (7.3% in 1997). CONCLUSION: The data obtained in this study suggest that the concept of diagnosing and treating RA early is accepted by a large proportion of the rheumatological community.

Benefit of very early referral and very early therapy with disease-modifying anti-rheumatic drugs in patients with early rheumatoid arthritis.

OBJECTIVE: Delay of disease-modifying anti-rheumatic drug (DMARD) therapy is a major contributing factor for poor outcome in rheumatoid arthritis (RA). Although early therapy has been shown to be particularly effective, there is still uncertainty about the optimal time point of DMARD introduction. We wanted to test if a therapeutic window of opportunity may exist within the first few months of the disease. METHODS: In this case-control parallel-group study, 20 very early RA (VERA) patients with median disease duration of 3 months were age and gender matched to a group of 20 late early RA (LERA) patients with median disease duration of 12 months until first DMARD initiation. Follow-up time was 36 months. Primary outcome measures were the disease activity score (DAS28) and radiological joint destruction using the Larsen method. RESULTS: Already after 3 months of DMARD therapy we found a significant difference of improvement in favour of the VERA patients in the DAS28. This trend continued over the study period. At study end the DAS28 showed an improvement of 2.8+/-1.5 in the VERA vs 1.7+/-1.2 in the LERA group (P(c)<0.05). The Larsen scores showed a statistically significant retardation of progression in the VERA compared with the LERA. CONCLUSION: Our results indicate that there is a window of opportunity for highly successful treatment of RA in the first year, and especially within the first 3 months of therapy. Thus, early diagnosis and therapy may be the crucial step in achieving optimal control of disease progression and prognosis in RA.

The Austrian Early Arthritis Registry.

The Austrian Early Arthritis Registry (Austrian Early Arthritis Action, EAA) enrols and follows patients with inflammatory arthritis of very short (< 12 weeks) duration. Currently, data on 375 patients (almost 2000 individual follow-up examinations) have been entered into the EA database. Evaluations of data from 182 patients with a follow-up of at least one year are available. 65% of these patients have RA, as diagnosed using the ACR classification criteria in a cumulative fashion. Approximately 15% of these patients still have no established diagnosis and are being carried forward and observed as cases of "undifferentiated arthritis". In RA patients, the mean DAS 28 decreased significantly from an initial mean score of 5.5 (high disease activity) into the range of low disease activity. At the end of one year a DAS 28 of < 3.2 was observed in 52% of the RA patients. Radiological progression in these RA patients, who also received treatment very early, appears to be less severe than in other cohorts, although direct comparisons are impossible due to different methods of patient selection. In addition, the serological data from our cohort in cooperation with other study groups will allow development and validation of possible prediction algorithms for early arthritis patients which could improve the diagnostic and therapeutic approach to this patient group.

Practical progress in realisation of early diagnosis and treatment of patients with suspected rheumatoid arthritis: results from two matched questionnaires within three years.

BACKGROUND: Early diagnosis and treatment with disease modifying antirheumatic drugs (DMARDs) have been advocated for patients with rheumatoid arthritis (RA). This survey focuses on the individual definitions and treatment modalities of rheumatologists, and aims at determining the practical realisation of these concepts. METHODS: A questionnaire to be self completed was handed out at the EULAR Symposium 1997. The main issues dealt with were definition, referral time, diagnosis, follow up, and treatment of early RA. Of the 111 participants, who were from all continents and all age groups, 85 (77%) gave their name and address. In 2000, the same questionnaire was sent to these 85 primary respondents. Forty four questionnaires (52%) were returned, and their results were matched and further evaluated. RESULTS: The definition of early RA was heterogeneous, but two of three rheumatologists use the term "early" for symptoms shorter than three months. There was a drift towards acceptance of involvement of fewer affected joints. Serological tests obtained for early diagnosis were mostly rheumatoid factor and antinuclear antibodies, usually in combination (approximately 70%), while other tests (antikeratin antibodies, antiperinuclear factor, anti-RA33) were used rarely, but increasingly (21-25% all together). No significant change in the lag time of referral to the specialist of patients with suspected early RA was seen within these three years (<3 months for 50%, >6 months for 20%), while the proportion followed up during the first three months increased. At both times, every second rheumatologist started DMARD treatment only when the 1987 American College of Rheumatology (ACR) criteria were fulfilled. However, in 1997 about 10% were willing to wait for erosions before starting DMARDs, while none did so in 2000. Methotrexate, sulfasalazine, and antimalarial drugs were the most commonly prescribed DMARDs in early RA, with the first two of these still being in increasing use. CONCLUSION: The understanding of "early" rheumatoid arthritis is heterogeneous, but the vast majority of the rheumatologists surveyed regard symptom duration of <3 months as early. Rheumatoid factor was the most useful laboratory support in early diagnosis. Because there has been no shortening of referral time of patients with new RA within the past three years, and many rheumatologists start DMARDs only when the ACR criteria are fulfilled, it is concluded that guidelines for early referral, as well as for early (rheumatoid) arthritis, are needed.

Toward an understanding of violence: neurobehavioral aspects of unwarranted physical aggression: Aspen Neurobehavioral Conference consensus statement.

OBJECTIVE: Violence is a global problem that poses a major challenge to individuals and society. This document is a consensus statement on neurobehavioral aspects of violence as one approach to its understanding and control. BACKGROUND: This consensus group was convened under the auspices of the Aspen Neurobehavioral Conference, an annual consensus conference devoted to the understanding of issues related to mind and brain. The conference is supported by the Brain Injury Association and by individual philanthropic contributions. Participants were selected by conference organizers to represent leading opinion in neurology, neuropsychology, psychiatry, trauma surgery, nursing, evolutionary psychology, medical ethics, and law. METHODS: A literature review of the role of the brain in violent behavior was conducted and combined with expert opinion from the group. The major goal was to survey this field so as to identify major areas of interest that could be targeted for further research. Additional review was secured from the other attendees at the Aspen Neurobehavioral Conference. RESULTS: The group met in the spring of 1998 and 1999 for two 5-day sessions, between which individual assignments were carried out. The consensus statement was prepared after the second meeting, and agreement on the statement was reached by participants after final review of the document. CONCLUSIONS: Violence can result from brain dysfunction, although social and evolutionary factors also contribute. Study of the neurobehavioral aspects of violence, particularly frontal lobe dysfunction, altered serotonin metabolism, and the influence of heredity, promises to lead to a deeper understanding of the causes and solution of this urgent problem.

Lessons learned--15 years of the WHO-NCTB: a review.

Based on expert recommendations, the World Health Organization (WHO) recommended the Neurobehavioral Core Test Battery (NCTB) in 1983 to detect neurotoxicity in world-wide populations. The NCTB consists of 7 neurobehavioral tests (Digit Symbol, Digit Span, Benton visual memory test/recognition form, Santa Ana dexterity test, Simple Reaction Time, Pursuit Aiming II, and Profile of Mood States). Research with the NCTB provides the context for the results of a mini-symposium held in 1999 to discuss the lessons learned about using the NCTB in working populations. Speakers from Africa, Asia, Europe, and North America reviewed data from 94 studies using the NCTB, including 63 from China, 13 from Korea, 11 from Poland, three from South Africa, three from the USA, and one from Ecuador. Although a consensus was not sought in the symposium, the key lessons learned that emerged from the various presentations, were: * The NCTB is effective in testing adults with 12 or more years of formal education, but can not reliably test persons with less than 9 years of education. * People from cultures very different from those in Europe and North America (eg, aboriginal and African cultures) may not be tested effectively by the NCTB, although others such as at least some Asian populations, can be. To address this problem, the construct validity of the NCTB should be established in a wide range of countries. * The POMS measures of emotion proved to be very sensitive to neurotoxic exposures in several countries, but the POMS was the NCTB test most affected by cultural differences. The Digit Symbol or the Milan modification of that test was also highly sensitive to neurotoxic exposures. * Examiner drift following training to administer the NCTB is a significant problem in technically trained Examiners. Pursuit Aiming II is very difficult to score reliably.

An extended Glasgow Coma Scale (GCS-E) with enhanced sensitivity to mild brain injury.

OBJECTIVE: The Glasgow Coma Scale-Extended (GCS-E) was developed to flag mild cases of concussion (corresponding to Grades I and II concussion as defined by the American Academy of Neurology) at the time of first contact with the health care system. SUBJECTS AND SETTING: The GCS-E was applied to 561 consecutive admissions with GCS scores of 13 to 15 at two hospitals in South Africa and two in the United Kingdom (UK). RESULTS: The amnesia scale was readily learned and reliably applied by emergency department staff without affecting the standard scoring of the GCS itself. Among patients with an admitting GCS of 15, 27% in the UK and 31% in South Africa reported amnesia of some duration. CONCLUSIONS: Wide use of the GCS-E would hold mild traumatic brain injury cases in the treatment loop, improve access to counselling, rehabilitation services, and personal injury compensation, and reduce the "cognitive dissonance" between victims of mild traumatic brain injury and treating professionals.

Neuropsychological function in solvent-exposed South African paint makers.

Neuropsychological and neurological function were investigated in 228 organic solvent exposed paint manufacturing workers in two factories. Solvent exposure was expressed as both American Conference of Governmental Industrial Hygienists 1990 Threshold Limit Value equivalents and total hydrocarbon parts per million. The World Health Organization (WHO) neurobehavioral core test battery, the Neurobehavioural Evaluation System--2 (NES-2), and the UNISA Neuropsychological Assessment Procedure (UNAP) were used to measure outcomes, and a Vibratron II was used to measure peripheral vibration sensation. Exposures were generally below the Threshold Limit Value, and no exposure effect was found. Possible explanations for this finding are discussed, including low exposure, exposure, and outcome misclassification, together with inappropriateness, nonvalidity, and relative insensitivity of neuropsychological tests. Only age predicted Vibratron score. Some tests were clearly inappropriate for use in developing countries. Neuropsychological tests were sensitive to educational level, age, alcohol consumption, and cultural indicators. The WHO tests in particular showed good construct validity for neuropsychological functions and should be more formally validated for use in developing countries. Nevertheless, a major problem of cultural dependence is evident for all neuropsychological tests used in this study, and methods for bypassing this problem in less developed settings are discussed.

Luria in Uzbekistan: the vicissitudes of cross-cultural neuropsychology.

If the material conditions of culture shape cognitive structures, as Luria and Vygotsky argued, the "extraordinarily deep and rapid restructuring of historical forms" (Luria, 1971, 265) in the Soviet Republics that followed the Bolshevik revolution of 1917 provided a natural laboratory to determine whether processes of modernization changed traditional ways of thinking. This was the purpose of Luria's 1931 expedition to the Soviet Republic of Uzbekistan in central Asia. Luria's initial reports attracted vitriolic criticism because he had allegedly belittled "primitive" Uzbeki culture. The lasting importance of the Uzbek expedition is its emphasis on culture as a determinant of cognitive processes that remains valid to the present: in 1984, Gilbert replicated Luria's field studies in South Africa with near-identical results. Yet current neuropsychology has been slow to recognize the need for culturally sensitive assessment.

Health status among farm workers in the Western Cape--collateral evidence from a study of occupational hazards.

MOTIVATION: Farm workers are a marginalised occupational group whose poor living and working conditions may place them at increased risk for occupational and non-occupational morbidity and mortality. Research into the health status of farm workers has been neglected in the past. AIMS AND OBJECTIVES: As part of an investigation into the neurological and neurobehavioural effects of exposure to organophosphate insecticides, this study describes the demographics, life histories, risk factors for chronic illness and selected indicators of general health status among a group of farm workers in the Western Cape. STUDY DESIGN: Cross-sectional study conducted in the deciduous fruit farming industry in 1993. SUBJECTS: 164 pesticide applicators and 83 non-spraying controls (all men) from 73 farms, frequency matched for age and education. MEASUREMENTS: A structured questionnaire, venous blood sample for serum and erythrocyte cholinesterase, albumin, gamma glutamyl transferase and haemoglobin assessment, height and weight measurement. RESULTS: Most farm workers were children of farm workers and had lived and worked on farms for most of their lives. The study found substantial levels of illiteracy (21-44%, depending on the definition) and innumeracy (4%) and evidence of a significant morbidity burden: high levels of alcohol intake and ongoing reported application of the 'dop' system, high levels of head injury (70% of subjects) and evidence of substantial adult undernutrition. Protective equipment was relatively well distributed and used, although certain work activities (such as acting as a human marker) continue to pose substantial exposure hazards. There were no differences in respect of cholinesterase levels between spray applicators and controls, although past poisoning was reported by 9% of subjects. CONCLUSION: Farm workers appear to be a closed community with a high disease burden. Their health needs pose substantial challenges to the public health authorities.

Early arthritis therapy: rationale and current approach.

Rheumatoid arthritis (RA) is a disease that seriously affects patients' quality of life and may lead to disability or even premature death, despite the availability of effective treatments. Evidence suggests that delay of treatment may be the main contributing factor for poor outcome. Delay is caused primarily by the erroneous belief that the course of RA may be controlled in many cases by mild measures such as nonsteroidal antiinflammatory drugs, physiotherapy, and rest. While this may be true in a certain percentage of patients, many patients with RA progress to severe disability. To prevent progression of disease, early treatment of RA, particularly in patients at high risk, seems mandatory. Therefore, early arthritis clinics (EAC) have been established in a number of countries. We discuss the rationale for early intervention and our experiences in Austrian EAC.

Effects of long-term organophosphate exposures on neurological symptoms, vibration sense and tremor among South African farm workers.

OBJECTIVES: This study assessed the relationship between long-term exposure to organophosphate insecticides and neurological symptoms, vibration sense, and motor tremor after control for the effect of past poisoning and acute exposure. METHODS: This cross-sectional study included 164 pesticide applicators and 83 nonspraying reference workers on deciduous fruit farms. The workers were tested on the Vibratron II, on tests of dynamic and static tremor, and for a set of neurological and "dummy" symptoms. Exposure was derived with the use of a job-exposure matrix for pesticides in agriculture. RESULTS: Compared with nonapplicators, current applicators reported significantly more dizziness, sleepiness, and headache and had a higher overall neurological symptom score. This association remained statistically significant after multiple logistic regression analyses controlling for a range of confounders and effect modifiers [odds ratio (OR) 2.25, for current applicators having high neurological score, 95% confidence interval (95% CI) 1.15-4.39]. The average lifetime intensity of organophosphate exposure was nonsignificantly associated with both neurological (OR 1.98, 95% CI 0.49-7.94) and "dummy" symptoms (OR 2.37, 95% CI 0.54-10.35). Previous pesticide poisoning was significantly associated with the neurological scores (OR 4.08, 95% CI 1.48-11.22) but not with the "dummy" symptoms. Vibration sense outcomes were associated with age and height, but not with the organophosphate exposure measures. In the multiple linear regression modeling for tremor intensity in the dominant hand, recent organophosphate exposure in the past 10 days was a significant predictor (partial correlation coefficient = 0.04), but none of the long-term organophosphate exposure measures were significant. CONCLUSIONS: Strong evidence was found for an association between symptom outcomes and past organophosphate poisoning and between symptom outcomes and current spray activity. In contrast to symptoms, there was no association between either past poisoning or current spray activity and vibration sense or tremor outcome. Long-term organophosphate exposure did not appear to predict symptoms, vibration sense, or tremor outcome.

An investigation into neurologic and neurobehavioral effects of long-term agrichemical use among deciduous fruit farm workers in the Western Cape, South Africa.

Long-term exposure to organophosphates (OPs) in the absence of acute poisoning is increasingly suspected of causing chronic neurologic and neurobehavioral effects. A cross-sectional survey of 163 spray operators on deciduous fruit farms in the Western Cape, South Africa, and 84 nonspraying labororers was conducted in 1993 to investigate the relationship between long-term OP exposures and neurological and neurobehavioral outcomes. The study also sought to evaluate the performance of a set of neurobehavioral test batteries based on the information-processing theory of cognitive psychology, relative to the more established World Health Organization's Neurobehavioral Core Test Battery (WHO NCTB). These information-processing tests were designed for use in studies of subjects with little education, which are frequently conducted in developing countries in agriculture. They draw on experience from a previous South African study in which problems were encountered with a lack of cross-cultural validity of conventional test batteries. No evidence was found of a relationship between long-term OP exposure and loss of vibration sense. Small associations were found with the NCTB Pursuit-Aiming and Santa Ana (nondominant hand) subtests. The overall evidence of neurologic and neurobehavioral effects of long-term OP exposure was small; exposure misclassification may have contributed to this finding. Important confounders such as brain injury, alcohol consumption, and nutritional status were identified.

Critical psychology and the problem of mental health.

This paper reviews psychological treatment and mental health.

Neuropsychological assessment of organic solvent effects in South Africa: test selection, adaptation, scoring, and validation issues.

The neurobehavioral effects of organic solvent exposure were assessed in 68 South African workers in a paint manufacturing plant in which the maximum current combined solvent level in workplace air was 0.72 of the Threshold Limit Value. A 17-test battery was assembled from the WHO-NCTB, NES 2, and the University of South Africa Neuropsychological Assessment Procedure. Extensive modifications were made to some tests in the battery, using a guided learning rationale derived from the cross-cultural literature. In light of test correlations with demographic variables (age, education, and alcohol consumption), the construct and likely predictive validity of the tests in the battery are reviewed, and promising procedures identified. Finally, it is noted that in developing countries, the results of neuropsychological tests that have been well standardized in the West may be misleading unless the underlying validity issues that arise when a test developed in one culture is applied to another have been addressed.

A cross-sectional survey of neurobehavioral effects of chronic solvent exposure on workers in a paint manufacturing plant.

Neurobehavioral impairments in 84 workers with long-term exposure to organic solvents in a paint manufacturing plant were examined cross sectionally. The World Health Organization (WHO) Neurobehavioral Core Test Battery, the NES-2 computerized battery, and four additional South African tests were used. Exposure to solvents was determined by using company industrial hygiene data as well as from an industrial hygiene survey of current total solvent levels in air. Indexes for cumulative exposure and average lifetime intensity of exposure were calculated for groups of homogeneously exposed workers in each department. Exposure levels were below the AGGIH threshold limit values. Multiple linear regression revealed that education level, age, and alcohol consumption were strong predictors for several neurobehavioral test scores. After adjusting for potential confounding from this source, average lifetime intensity of solvent exposure was the most significant predictor of the NES-2 Continuous performance test (measuring sustained visual attention) score of the WHO Digit span backward test score (measuring attention span and double tracking). Pursuit aiming (measuring fine visuomotor tracking speed) was significantly associated with the cumulative exposure index, possibly indicating early neurotoxic effects.