A cross sectional assessment of health status instruments in patients with rheumatoid arthritis participating in a clinical trial. Minocycline in Rheumatoid Arthritis Trial Group

OBJECTIVE: To (1) validate the Short-Form Health Survey (SF-36) as a generic functional health status measure in patients with rheumatoid arthritis (RA); and (2) assess correlations between the SF-36 and other outcome measures used in the Minocycline in Rheumatoid Arthritis (MIRA) Trial. METHODS: We conducted a cross sectional analysis of the final visit outcome measures from the 48 week, multicenter, placebo controlled, double blind MIRA trial. Multitrait scaling analyses assessed convergent and discriminant validity and internal consistency reliability of the SF-36 in the study patients. Responses to comparable items on the SF-36 and modified Health Assessment Questionnaire (M-HAQ) regarding physical functioning were compared and questions from both instruments were also compared to other RA outcome measures. RESULTS: In patients with RA, the SF-36 had high internal consistency and reliability, high discriminant and high convergent validity. Moderate correlations were observed (r = -0.46 to -0.61, p < 0.01 in each case) for comparable items on the SF-36 and M-HAQ regarding dressing, walking, and bending. Joint tenderness score correlations with items on the M-HAQ and SF-36, and joint tenderness score correlations with the SF-36 scales were higher than for joint swelling scores. Physician and patient global assessments were most highly correlated (r = 0.58 and 0.66; p < 0.01, respectively) with the SF-36 bodily pain item. CONCLUSION: The SF-36 is a valid instrument for this RA population. The SF-36 correlates with the M-HAQ and the physician and patient global assessments. The usefulness of the SF-36 in measuring change in RA clinical trials requires testing in longitudinal studies.     

Effect of social deprivation on disease severity and outcome in patients with rheumatoid arthritis

OBJECTIVE: Social deprivation is now recognised to have an important impact on morbidity and mortality. This study sought to ascertain the effect of deprivation, if any, on disease severity, functional disability, and outcome in rheumatoid patients in Glasgow. METHODS: 814 patients with rheumatoid arthritis (RA) were assessed for clinical, functional, and laboratory indices of disease activity. Deprivation categories for individual patients were determined using the Carstairs index. Five year follow up is available for 440 patients. RESULTS: The study population of RA patients live largely in the most deprived areas. Patients from deprived areas have significantly poorer function at outset and at five years as defined by the Health Assessment Questionnaire (HAQ) score. This is not attributable to differences in disease duration in patients from the most deprived regions or compliance with treatment. Furthermore, these patients do not achieve over five years the initial functional level of those living in the most advantaged localities. CONCLUSION: RA patients from deprived areas have poorer function, which is associated with greater need--medical, social, and paramedical. Strategies and resources for healthcare need to be adjusted according to this variation.     

Joint destruction after glucocorticoids are withdrawn in early rheumatoid arthritis. Arthritis and Rheumatism Council Low Dose Glucocorticoid Study Group

OBJECTIVE: Prednisolone reduced the progression of joint destruction over 2 yr in early, active rheumatoid arthritis. The response to discontinuation of prednisolone under double-blind conditions is now reported. METHODS: A randomized, double-blind, placebo-controlled trial of prednisolone 7.5 mg daily in addition to routine medication over 2 yr in 128 patients with early rheumatoid arthritis, using radiological progression (changes in the Larsen score) and the development of erosions as primary outcome measures. Study medication was blindly discontinued and follow-up maintained for a further year. Other assessments included disability, joint inflammation, pain and the acute-phase response. RESULTS: Similar results were obtained when all available radiographs were included for each year of assessment (maximum 114) and when only patients with radiographs at all time points were included (75 patients). In these 75, the mean progression in the prednisolone group was 0.21 Larsen units in year 1, 0.04 units in year 2 and 1.01 units in year 3 (P = 0.587, 0.913 and 0.039 for change within each year, respectively). The equivalent placebo group means were 2.34, 1.00 and 1.63 Larsen units (P = 0.001, 0.111 and 0.012; difference between groups: 2.13, 0.96 and 0.67 units, P = 0.082, 0.02 and 0.622). The percentage of hands which had erosions at each time point was: prednisolone group: 27.8, 29.2, 34.7 and 39.2; placebo group: 28.2, 48.7, 59.0 and 66.5. There was little evidence for a flare in clinical symptoms after discontinuation of prednisolone. CONCLUSION: Joint destruction resumed after discontinuation of prednisolone. This corroborates the previously reported therapeutic effect and challenges current concepts of disease pathogenesis.     

HLA-DQB1 polymorphism determines incidence, onset, and severity of collagen-induced arthritis in transgenic mice. Implications in human rheumatoid arthritis

Certain HLA-DR alleles have been associated with predisposition to human rheumatoid arthritis (RA). There is also evidence that certain HLA-DQ alleles may also be important in determining susceptibility to RA. We have previously demonstrated that mice transgenic for HLA-DQ8, a DQ allele associated with susceptibility to RA, develop severe arthritis after type II collagen immunization. To investigate the influence of polymorphic difference at the DQ loci on susceptibility to arthritis, we generated mice transgenic for HLA-DQ6, an allele associated with a nonsusceptible haplotype. The DQ6 mice were found to be resistant to collagen-induced arthritis. We also assessed the combined effect of an RA-susceptible and an RA nonassociated DQ allele by producing double-transgenic mice expressing DQ6 and DQ8 molecules, representing the more prevalent condition found in humans where heterozygosity at the DQ allele is common. The double-transgenic mice developed moderate CIA when immunized with CII when compared with the severe arthritis observed in DQ8 transgenic mice, much like RA patients bearing both susceptible and nonsusceptible HLA haplotypes. These studies support a role for HLA-DQ polymorphism in human RA.     

Relative predispositional effects and mode of inheritance of HLA-DRB1 alleles among community-based Caucasian females with rheumatoid arthritis

This review addresses two questions. First, why does clozapine apparently occupy low levels of dopamine D2 receptors in patients, in contrast to all other antipsychotic drugs which occupy 70-80% of brain dopamine D2 receptors? Second, what is the receptor basis of action of antipsychotic drugs which elicit low levels of Parkinsonism? Antipsychotic doses of clozapine occupy between 0% and 50% of D2 receptors, as measured in patients by a variety of radioligands. It has recently been found, however, that the percent occupancy of a receptor by a drug depends on the radioligand used to measure that receptor. Based on this new finding, this review concludes that clozapine clinically occupies high levels of D2 receptors in the absence of any radioligand. This occupancy is estimated to be of the order of 70-80% in the dopamine-rich region of the human striatum, and even higher in the limbic D2-containing regions which are low in endogenous synaptic dopamine. This conclusion arises from two different approaches. One approach is to relate the reported clozapine occupancies in the human striatum with the dissociation constants of the various radioligands at the D2 receptor. This relation extrapolates to approximately 70-80% occupancy by clozapine when clozapine competes with endogenous dopamine at the D2 receptor. The second approach is to calculate the D2 occupancy of each antipsychotic drug, using the average spinal fluid concentration and the correct dissociation constant of the antipsychotic, thereby revealing that all antipsychotic drugs, including clozapine, occupy approximately 70-80% of dopamine D2 receptors in the human striatum, and possibly higher in the limbic regions. As determined by the new dissociation constants, antipsychotic drugs which elicit Parkinsonism (trifluperazine, chlorpromazine, raclopride, haloperidol, fluphenazine, risperidone) bind more tightly than dopamine to D2, while those antipsychotic drugs which elicit little or no Parkinsonism (melperone, seroquel, perlapine, clozapine, remoxipride, molindone, sulpiride, olanzapine, sertindole) bind more loosely than dopamine to D2 receptors. Compared to the tightly bound antipsychotic drugs, the more loosely bound antipsychotics generally require higher clinical doses, require fewer days for clinical adjustment, but may dissociate from the D2 receptor more rapidly and could lead to clinical relapse somewhat earlier than that found with the traditional tightly bound antipsychotic drugs.     

Rheumatoid arthritis and hydroxyapatite-coated hip prostheses: five-year results. International ABG Study Group

Medium- and long-term results from cemented total hip arthroplasty (THA) in patients with rheumatoid arthritis (RA) show a higher incidence of infection and aseptic loosening when compared to other diagnoses. Early results using uncemented prostheses are variable. Hydroxyapatite (HA) coatings are thought to improve early osseointegration in uncemented THA. In a prospective, international, multicenter clinical study, 32 RA patients who received 33 uncemented HA-coated prostheses were followed up for a minimum of 5 years. Medium-term clinical results are excellent. No infection or aseptic loosening has been recorded. Excellent osseointegration was observed radiographically. Bone remodeling was consistent with mainly proximal to midstem stress transfer. We conclude that uncemented, proximally HA-coated prostheses are a promising alternative to cemented prostheses for RA patients.     

The prevalence and severity of rheumatoid arthritis in Oslo. Results from a county register and a population survey

The objective was (1) to examine the prevalence of rheumatoid arthritis (RA) by a county patient register, (2) to cross-validate the register findings by a postal population survey, and (3) to estimate prevalences of disease subsets according to age, sex, and levels of physical disability. The study was performed within a county setting in the city of Oslo with 356,486 inhabitants between 20 and 79 years of age. Prevalence estimates were calculated from a county patient register comprising 1333 patients with RA and a population survey of 10,000 inhabitants. The overall prevalence of RA between 20 and 79 years was 0.437 (95% CI 0.413, 0.461) after adjusting for the incompleteness of the register by a factor of 1.17. Prevalences exceeding 1.0% was only found among females over 60 years. The prevalence of RA with MHAQ scores > or = 1.5 and > or = 2.0 (range 1-4) was 0.225 (95% CI 0.209, 0.243) and 0.099 (0.088, 0.111) respectively. We conclude that RA is less frequent in the city of Oslo than stated in most of the literature. The prevalence of RA with physical disability levels assumed to be associated with increased mortality is less than half of the overall prevalence of 0.4-0.5%.     

The social environment and health in rheumatoid arthritis: marital quality predicts individual variability in pain severity

OBJECTIVE: To examine prospective relations between a wide array of measures of social functioning and pain, while controlling for disease duration and activity and functional grade. METHODS: As part of a larger study on health care utilization, longitudinal data were collected from 136 Dutch and 98 German outpatients on clinical status and pain. Social data included information on sexual handicap, spouse behavior, loneliness, daily emotional support, and the maintenance of pleasurable life domains. Pain severity was assessed at baseline and 12 months later with standard measures of pain and analyzed with hierarchical regressions. RESULTS: Social measures obtained at baseline were consistently associated with pain at followup. Depression was a moderate correlate of pain in the Dutch and German samples. The regressions revealed that patient reports of negative spouse behavior (such as avoidance and critical remarks) and baseline depression predicted worse pain outcome, and this association remained significant in analyses controlling for baseline pain. The level of formal education was a weak correlate of disability, emotional support, and pain. Daily emotional support and social life domains associated with positive affect had an indirect influence on outcome. The absence of strong rather than weak social ties was the component of the loneliness construct linked to pain. These associations between social prognostic factors and pain severity, however, were mediated by psychological functioning at baseline. CONCLUSION: The social environment was found to operate on the core health outcome, pain severity, via several pathways. Social functioning may be affected by rheumatoid arthritis (RA) progression, but it also appears to form a determinant of future health outcome. Not only the status of being married but also the quality of the relationship in terms of long-term stress and emotional support may be useful prognostic factors in RA.     

Helplessness and depression in rheumatoid arthritis.

Found that scores on a measure of helplessness mediated the relationship between severe, disabling rheumatoid arthritis (RA) and depression in 106 RA patients (aged 23–81 yrs). This association was independent of a previously demonstrated correlation between cognitive distortion and depression in RA patients. However, the association between disease severity and depression was mediated by Ss' views of their ability to control or cope with their disease. Both helplessness and cognitive distortion may be important factors in the development and treatment of depression among RA patients. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

AP-1 and NF-kappaB regulation in rheumatoid arthritis and murine collagen-induced arthritis

Mandibular distraction was performed on 14 children, between September 1991 and December 1997. Their average age was 6.9 years, ranging from 1.5 to 13.5 years. All patients had severe hypoplastic mandibles with retromandibulism. Seven of the children (50%) had respiratory distress due to obstruction of the upper airway before distraction. This resolved in every case. Five patients underwent unilateral and nine bilateral distraction. A total of 23 distractors were used, 15 were applied extraorally and 8 endorally. The average latency time after operation was 2.8 days, but for the past 2 years, distraction was started beginning with the operation. The distraction was increased twice daily for an average of 5.5 weeks, by 0.4 or 0.5 mm each time, depending on the distractor. Computed tomography and ultrasound were used to follow the ossification process in the distraction gap and to measure the lengthening achieved. Subsequent retention time averaged 2.4 weeks. The mandibles were elongated by up to 18 mm (average 9.3 mm) and the respiratory distress symptoms resolved in all patients. Several minor complications which are reported occurred. Six patients were followed up for periods between 3 and 7 years. During this time further growth of the distracted mandibles was recorded.     

The incidence and severity of rheumatoid arthritis, results from a county register in Oslo, Norway

OBJECTIVE: To examine the incidence of rheumatoid arthritis (RA) in the community of Oslo, Norway; and to link the incidence to measures of disease severity. METHODS: A register for RA in the county of Oslo was validated to be 85% complete for patients between 20 and 79 years of age. The incidence of RA was calculated from this register for patients with disease onset 1988-1993 (n=550). Data on health related quality of life [Modified Health Assessment Questionnaire (MHAQ), Arthritis Impact Measurement Scale 2 (AIMS2), pain, fatigue] were obtained from a postal survey (response rate 73%). RESULTS: The overall annual incidence of RA over a 6 year period was 25.7/100,000 (females 36.7, males 13.8). The incidence increased with age, from 7.8 in the age group 20-29 to 61.0 between 70 and 79 years. After 5 year followup a clinically important effect on physical function (MHAQ > 1.5) was seen in 38% of the patients, on social functioning (AIMS2 social > 4) in 50%, on mental distress (AIMS2 affect > 4) in 27%, on pain (VAS > 40 mm) in 35%, and on fatigue (VAS > 40 mm) in 41%. CONCLUSION: The incidence of RA was 25.7/100,000 in the population of Oslo. After 5 years, 40-50% had clinically important changes in health status. The annual disease incidence with clinically important effect on physical function after 5 years was 10/100,000 individuals at risk.     

Arthritis and perceptions of quality of life: An examination of positive and negative affect in rheumatoid arthritis patients.

The utility of measuring both positive and negative affective states for assessing rheumatoid arthritis (RA) patients was examined in 3 independent samples of male and female RA patients (Sample A: 179 women, 48 men; Sample B: 177 women, 24 men; Sample C: 134 women, 38 men). Confirmatory factor analyses of each sample indicated that positive and negative affect constituted separate, negatively correlated factors. The relations among disease variables, coping, and affects were consistent with a model in which coping mediates the relationship between disease variables and positive and negative affect. Patients with higher pain and limitation from RA had higher levels of maladaptive coping, and maladaptive coping was associated with lower positive affect and higher negative affect. Those RAs with higher activity limitation also reported less adaptive coping, which was associated with less positive affect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Groningen Activity Restriction Scale (GARS) in the evaluation of severity of rheumatoid arthritis]

The antiviral effect of amantadine (1-aminoadamantane) was tested in vitro as well as in vivo. Treatment of persistently Borna disease virus (BDV)-infected cell lines of different origin and for various length of time did not result in a general reduction of virus titer or clearance of virus from infected cells. In vivo, rats were treated with amantadine by daily oral application or by use of osmotic pumps, and in both cases treatment was started before infection. Neither route of application of the drug had any influence on the time of onset of disease, on antiviral antibody titers, on virus titer in the brain, on the severity of the inflammatory reaction in the brain, or on the severity of neurological symptoms. These experiments, although revealing negative results and obtained using a virus from a natural case of Borna disease grown after isolation in vitro for a long period of time, should caution from the general use of amantadine as a curative agent against BDV infection as has been implicated recently [Bode et al. (1997) Lancet 349:178-179].     

The role of risk factors for periodontal disease in patients with rheumatoid arthritis

This paper summarises the methods and some of the findings of a large cohort study of dementia and cognitive decline in subjects aged over 75 years in Cambridge, particularly regarding the incidence wave. From a sample of 1968 subjects previously studied in a prevalence study in 1985-1987, survivors were restudied at 2.4 years, in a two-stage design employing the Mini; Mental State Examination (MMSE) and the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX). High incidence rates of dementia were found, which rose steeply with age, particularly for Alzheimer's disease. New minimal dementia and milder cognitive impairment were also common. Cognitive decline on the MMSE showed a near normal, non-bimodal distribution. The sample has since been restudied at intervals for a total of up to 9 years to document longitudinal cognitive change. Brains have been obtained for post mortem neuropathological and molecular biological study, particularly of the early sequential changes associated with cognitive decline and dementia.     

Shared epitope homozygosity' is strongly associated with rheumatoid arthritis in Turkey. Istanbul Rheumatology Study Group

OBJECTIVE: Associations with HLA-DRB alleles, implicated in the aetiopathogenesis of rheumatoid arthritis (RA), are found to be different in various ethnic groups. This study aimed to investigate DRB1 alleles in RA patients in Turkey. METHODS: The DRB region of the MHC was screened by polymerase chain reaction/sequence-specific oligonucleotide (PCR/SSO) hybridizations in 101 seropositive RA patients and compared with 101 healthy controls. RESULTS: Significant differences were in the frequencies of DRB1*0404 (12 vs 1, P = 0.003, OR = 13.5), *0401 (19 vs 4, P = 0.001, OR = 5.6) and *0408 (5 vs 0, P = 0.06, OR = 11.6) between RA patients and controls. The shared epitope (SE) was present in 70.2% of RA patients compared to 31.6% of controls (P < 0.0001, OR = 5.1). A double dose of SE was considerably more frequent in the RA group (21 vs 1, P < 0.0001, OR = 26.5). CONCLUSION: These results support the reported positive association of RA with SE in seropositive patients in Turkey, and emphasize 'SE homozygosity' as the most strongly associated genetic susceptibility marker for RA.