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K Eberhardt

Publications and source records attributed to K Eberhardt.

At least 37 records · Page 2Linked to original sources
PubMed1999

Economic consequences of the progression of rheumatoid arthritis in Sweden.

OBJECTIVE: To develop a simulation model for analysis of the cost-effectiveness of treatments that affect the progression of rheumatoid arthritis (RA). METHODS: The Markov model was developed on the basis of a Swedish cohort of 116 patients with early RA who were followed up for 5 years. The majority of patients had American College of Rheumatology (ACR) functional class II disease, and Markov states indicating disease severity were defined based on Health Assessment Questionnaire (HAQ) scores. Costs were calculated from data on resource utilization and patients' work capacity. Utilities (preference weights for health states) were assessed using the EQ-5D (EuroQol) questionnaire. Hypothetical treatment interventions were simulated to illustrate the model. RESULTS: The cohort distribution among the 6 Markov states clearly showed the progression of the disease over 5 years of followup. Costs increased with increasing severity of the Markov states, and total costs over 5 years were higher for patients who were in more severe Markov states at diagnosis. Utilities correlated well with the Markov states, and the EQ-5D was able to discriminate between patients with different HAQ scores within ACR functional class II. CONCLUSION: The Markov model was able to assess disease progression and costs in RA. The model can therefore be a useful tool in calculating the cost-effectiveness of different interventions aimed at changing the progression of the disease.

Arthritis, Rheumatoid↗
PubMed1999

Mortality in rheumatoid arthritis patients with disease onset in the 1980s.

OBJECTIVE: Several previous studies have shown increased mortality in rheumatoid arthritis (RA) patients. This study investigated if this was true also for patients with disease onset in the 1980s. PATIENTS AND METHODS: The study group comprised 183 patients (67 men and 116 women) with definite RA participating in an ongoing prospective study. Mean age at onset of disease was 51 years, and mean duration of joint symptoms at inclusion was 11 months. The patients were included between 1985-89. Seventy five per cent of the patients were rheumatoid factor (RF) positive, 85% carried the shared epitope, and 90% became erosive. By 1 September 1997 the number and causes of death, obtained from the death certificates, were recorded. Standardised mortality ratio (SMR) was calculated, comparing the observed number of deaths in the cohort with the expected number of deaths in the general population in the same area, age and sex matched. The predictive values of demographics, genotype, RF status, and clinical data at baseline were estimated using the Cox proportional hazards regression model. RESULTS: Eighteen patients (11 men and 7 women) had died compared with 20 expected deaths. SMR with 95% confidence intervals was 87 (53, 136). There was no significant increase in the number of deaths at any time during follow up for either sex. RA was not the main cause of death in any of the cases. By reading the patient charts two cases were found where RA or its treatment could have contributed to death. No RA related variable contributed significantly to an increased risk of death. CONCLUSION: There was no increased mortality during the first 8-13 years of disease in this group of patients who developed RA in the 1980s.

Adult↗
PubMed1999

Nucleotide sequences specific for nonnominal immunoglobulin allotypes in rheumatoid arthritis patients and in normal individuals and their expression in synovial tissue of rheumatoid arthritis patients.

The production of antibodies against nonnominal immunoglobulin allotypes in rheumatoid arthritis (RA) patients suggests that the immune system of these patients has been exposed to such foreign allotypes. The presence of nonnominal allotypes is, however, a genetic enigma. We searched for nucleotide sequences specific for nonnominal G3mg and G3mb copies in individuals homozygous for these alleles. Using a sensitive and specific nested polymerase chain reaction (PCR) method with genomic DNA from blood of 18 RA patients and 5 normal controls, we found G3mg sequences in 18 of 18 tested G3mb homozygous persons. The allele specificity of the PCR fragments was confirmed by sequencing and RFLP analysis. The PCR products contained genomic nonspliced parts of the nonnominal sequences. An analysis of cDNA from inflammatory tissue of 5 RA patients detected nonnominal G3mb sequences in 1 of 3 tested G3mg homozygotes and G3mg sequences in 2 of 2 tested G3mb homozygotes. The cDNA-derived PCR products contained sequences from normally spliced nonnominal Ig fragments. The results also showed that the nonnominal Ig sequences were present in very low copy numbers, lower than the Mendelian 1-2 copies per cell. The origin of such a low copy number of Ig gene fragments may be explained by a virus-mediated capture and transfer mechanism of Ig gene fragments generated by the normal Ig switch-associated gene excision process.

Arthritis, Rheumatoid↗
PubMed1999

Preliminary core set of domains and reporting requirements for longitudinal observational studies in rheumatology.

Observational and longitudinal observational studies (LOS) provide essential information about the course and outcome of rheumatic disorders that cannot be provided by randomized controlled trials, and they constitute the major clinical scientific communication in rheumatology. There has been no consensus as to the full and appropriate content of LOS. This report defines a core set of domains and reporting requirements for LOS. At the 1998 OMERACT IV Conference a consensus process evaluated the literature of rheumatology in light of the constructs, variables, and outcomes of rheumatology by using introductory lectures, nominal groups, and plenary sessions. The result of this process was to identify 5 "core" domains that should be included in every LOS: Health Status, Disease Process, Damage, Mortality, and Toxicity/Adverse Reactions. Two additional domains, Work Disability and Costs, were recognized as important, but need not be used in all LOS. Eleven subdomains were identified that divided the domains into convenient clinical and conceptual units. A set of reporting requirements was also determined. The core recommendations, which follow on the WHO ICIDH-2 outline, are not disease-specific; the substitution of different "disease process" and "damage" measures make them suitable for many rheumatic disorders. The core set is intended to serve as a core for LOS in almost all rheumatic conditions.

Decision Making↗
PubMed1998

[Treatment of stage IIIB loco-regionally advanced non-small-cell bronchial carcinomas with radiation and interferon-beta. Preliminary results of a phase II study].

BACKGROUND: In-vitro and in-vivo studies demonstrated the radiosensitizing effect of interferon beta on malignant tumor tissue as well as simultaneously a radioprotective effect on normal lung tissue. In this phase II study the outcome of combining radiotherapy with interferon beta in patients with advanced non-small cell lung cancer was evaluated. PATIENTS AND METHOD: From February 1994 until November 1996 14 patients with non-small cell lung cancer, stage IIIB were treated with locoregional radiation up to 59.4 Gy, with daily doses of 1.8 Gy and 5 fractions per week. Five million units of interferon beta (Fiblaferon) were given intravenously immediately preceding radiotherapy on the first 3 days of week 1, 3 and 5. RESULTS: Four of 14 patients (28.6%) showed complete response and 7 patients (50%) partial response, resulting in an overall response rate of 78.6%. After a mean follow-up time of 23.3 months the 1-, 2- and 3-year survival rates were 56.3%, 37.5% and 37.5%, respectively. The median survival time was 13 months. Three of 14 patients (21.4%) suffered from 7 Grade-3 acute side effects and 2 patients (14.3%) from 1 Grade-3 late toxicity in each case. One further patient, whose right lung was resected 3 months after completion of radiotherapy, developed as a consequence of this operation 2 Grade-4 complications. CONCLUSION: Considering the toxicity and the preliminary results of combining irradiation and interferon beta in the treatment of locally advanced non-small cell lung cancer it seems, that this procedure is worth to be tested in a phase III study.

Adult↗
PubMed1998

Clinical course and remission rate in patients with early rheumatoid arthritis: relationship to outcome after 5 years.

OBJECTIVE: To investigate the clinical course in early rheumatoid arthritis (RA) patients followed prospectively, to relate course to outcome after 5 yr, and to try to identify prognostic features. METHODS: A total of 183 patients with definite RA and a mean disease duration of 11 months were included. Of these, 75% were rheumatoid factor (RF) positive; 85% carried the shared epitope, 32% on both alleles. Most patients were assessed every 6 months. Disability was evaluated with the Health Assessment Questionnaire (HAQ) and radiographic findings according to Larsen. Remission was defined in two ways: with the American Rheumatism Association (ARA) criteria and as 'no arthritis at least at one follow-up visit'. RESULTS: Twenty per cent achieved ARA-defined remission periods of at least 6 months duration; 21 were spontaneous and 18 drug induced. Average length of remission was 20.5 months. The remission periods constituted 7% of follow-up for all patients. Another 36% achieved remission according to the second definition. All 56% were considered to have a relapsing-remitting disease pattern, in contrast to the remaining 44% with a persistent disease pattern. More patients with persistent disease were treated with disease-modifying anti-rheumatic drugs (DMARDs) and had also received a larger number of different drugs. Outcome after 5 yr regarding disability, joint inflammation and joint damage was worse for patients with persistent disease. Neither ARA-defined remission nor disease pattern could be accurately predicted. CONCLUSIONS: Long-term ARA-defined remission was rare, constituting 7% of follow-up for the entire cohort. For those 20% achieving remission, this period represented 34% of their follow-up. A total of 56% had a relapsing-remitting disease pattern and 44% had a persistent disease pattern. This classification had prognostic implications with persistency being a bad prognostic sign.

Adult↗
PubMed1998

Effect of rheumatoid arthritis on work status and social and leisure time activities in patients followed 8 years from onset.

OBJECTIVE: To evaluate the development of handicap in patients with rheumatoid arthritis (RA) followed 8 years from onset. METHODS: The study group consisted of 106 patients participating in a prospective early RA study. The mean duration of joint symptoms at inclusion was one year. The patients were assessed at least once annually. Disability was measured with the Health Assessment Questionnaire (HAQ) and emotional distress with a self-administered test (Symptom Checklist). Work status and different social measures were registered. A structured interview regarding work capacity, leisure time, and social activities was performed about 8 years after disease onset. RESULTS: Compared to study start, disease activity had decreased, emotional distress was unchanged, disability had increased somewhat, and radiographic changes had increased markedly. The prevalence of work disability at the end of the study was 37%. The majority of patients that eventually got disability pension had stopped working the first year after onset. Seventy-eight percent of the patients who continued to work had to adjust their work conditions to stay employed. The 3 most important predictors for work disability were higher HAQ at study start, lower educational level, and older age. Three-quarters of the patients had to alter leisure time activities and half of them were not satisfied with their recreation. Many patients experienced difficulties in their roles as spouse and parent. Higher levels of emotional distress were associated with these handicaps. CONCLUSION: In this cohort of patients with RA we found a high frequency of different types of handicaps at an early stage. Slightly more than 1/3 were work disabled. The majority had stopped working during the first year. Patients perceived handicaps in terms of changed leisure time activities, and difficulties performing different social roles were frequent. Patients with these handicaps felt more emotional distress.

Adolescent↗
PubMed1997

Tissue-derived macromolecules and markers of inflammation in serum in early rheumatoid arthritis: relationship to development of joint destruction in hands and feet.

We have previously shown that serum concentrations of cartilage oligomeric matrix protein (COMP) are increased early in rheumatoid arthritis (RA) patients who subsequently develop advanced large-joint destruction. A prognostic value for joint damage of serum concentrations of hyaluronan (HA) is also suggested by previous studies. In contrast, serum concentrations of bone sialoprotein (BSP) have not been useful for identifying patients with progressive large-joint destruction. In the present study, we have examined the hypothesis that serum concentrations of these tissue-derived markers are of prognostic value in RA for the development of radiographically detectable joint damage in hands and feet. Serum concentrations of COMP, HA and BSP were quantified in samples obtained from 62 patients within the first year after onset of RA and were related to the development of radiographically detectable damage in these joints after 5 yr. Neither the serum concentrations of COMP nor of BSP at inclusion predicted joint damage in hands and feet after 5 yr, and the concentration of these proteins did not change over the 5 yr period. However, the serum concentration of HA at inclusion correlated with the radiographic score at the 5 yr follow-up (r = 0.425, P < 0.01), but was not a better predictor in this respect than the erythrocyte sedimentation rate or C-reactive protein levels at inclusion. Thus, serum concentrations of the three studied tissue-derived macromolecules were in this study not useful for identifying patients prone to small-joint destruction.

Adult↗
PubMed1997

Regulation of protein A synthesis by the sar and agr loci of Staphylococcus aureus.

The synthesis of protein A in Staphylococcus aureus is regulated by global regulatory loci such as sar and agr. Phenotypic data indicate that both sar and agr suppress protein A synthesis; like agr, sar also regulates protein A production at the transcriptional level. To determine the genetic requirement of sar in protein A suppression, we transformed shuttle plasmids containing various sar fragments into a sar mutant. Our results indicated that the 560-bp sarA transcript, or, more probably, the SarA protein (13.5 kDa), is sufficient for suppressing protein A gene transcription when introduced on a multicopy plasmid or as a single copy in the chromosome. Immunoblot analysis with a chicken anti-protein A antibody also confirmed the reduction in protein A expression in these sar mutant clones. Complementation studies revealed that the transcription of the protein A gene can be suppressed in a sar mutant background by a plasmid containing RNAIII. Surprisingly, in agr deletion mutant clones and in clones derived from the agr-sar double mutant, protein A gene transcription can also be suppressed by plasmids containing the sarA transcript plus additional upstream sequence but not the sarA transcript alone. These data suggest that the sar locus can down-modulate protein A gene transcription via both RNAIII-dependent and RNAIII-independent pathways. Consistent with the hypothesis of an RNAIII-independent pathway is an additional genetic requirement for protein A suppression in the agr deletion mutant RN6911 as well as the isogenic double sar-agr mutant, whereas in the sar mutant background, the sarA transcript encoding the SarA protein alone is sufficient. These data suggested that both sar and agr are coregulators of protein A synthesis in S. aureus.

Base Sequence↗
PubMed1996

Development of radiographic damage during the first 5-6 yr of rheumatoid arthritis. A prospective follow-up study of a Swedish cohort.

The objective of this study was to describe the development of radiographic damage in patients with RA and to search for predictors of radiographic progression over 5 yr. One hundred and thirteen patients, 75 female and 38 male, mean age 53 yr, with definite RA and mean disease duration of 11.4 months, were followed prospectively for 5 yr at an out-patient clinic. Radiographs of the hands and feet were performed annually, and evaluated according to Larsen. The predictive value of demographic, clinical and laboratory variables at study start was evaluated. A stepwise logistic regression model was applied. We found that radiological joint damage occurred early and was significantly progressive during the 5 study years. The rate of progression was most prominent during the first 2 yr. At study start, 53% of the patients had no detectable erosions, but only 11% remained non-erosive. Twenty-six per cent of the patients with the initial presence of erosions did not progress substantially and needed no aggressive therapy. High joint damage progression during the first year, female gender and high baseline ESR could predict 57% of the patients with high total radiographic progression. Age, disease duration, rheumatoid factor, genetic factors, active joint count and the presence of erosions at study start had no predictive value.

Antirheumatic Agents↗
PubMed1996

Associations of HLA-DRB and -DQB genes with two and five year outcome in rheumatoid arthritis.

OBJECTIVE: To evaluate the clinical usefulness of genomic HLA typing during the first five years of established rheumatoid arthritis (RA). METHODS: The HLA-DRB and -DQB alleles were determined by restriction length polymorphisms and polymerase chain reaction amplification with sequence specific primers in 99 Swedish patients with RA. Clinical features after two and five years disease duration were related to the genetic pattern. Seventy four patients were seropositive, 25 had nodules, 90 developed erosions, and 15 required joint replacements. Twelve patients were in remission after five years. Disability was assessed by health assessment questionnaire, and radiographic damage in hands and feet by the Larsen method. RESULTS: Eighty seven per cent of the patients carried the conserved third hypervariable region sequence (HVR3), 32% had DRB1*04 on one allele, and 26% had DRB1*04 on both alleles (all frequencies significantly greater than in controls). Frequencies of DRB1*04 associated DQB*0301 and *0302 were normal. Patients carrying DRB1*04 on both alleles tended to have more radiographic changes after two years, but this difference had diminished after five years. Disability did not vary with regard to the genotype. Homozygous HVR3 patients had about three times greater risk of undergoing joint replacement. Homozygosity for HVR3 and presence of DQB*0302 both tended to be associated with erosive disease. CONCLUSIONS: We confirmed a strong association of disease with the presence of the shared epitope on one or two alleles. However, genotype was not strongly associated with disease severity after two and five years disease duration, and thus the value of genomic typing to select patients for early aggressive therapy is questionable.

Adult↗
PubMed1995

Autologous bone marrow transplantation for first remission acute myeloblastic leukemia in patients older than 50 years: a retrospective analysis of the European Bone Marrow Transplant Group.

High-dose chemotherapy, with or without radiotherapy, followed by autologous stem-cell rescue is used increasingly for the intensification of first remission in acute myeloblastic leukemia (AML). However, these treatments have been limited to young patients due to the increased risks of regimen-related toxicities and mortality with age. Several investigators have recently published the upper age limit for autologous bone marrow transplant (ABMT) in AML because of encouraging results. The results of ABMT for AML were studied in 111 patients > or = 50 years of age intensified in first remission. Median age at transplant was 53 years (range, 50 to 63 years). Fifty patients were conditioned with total body irradiation and 61 with polychemotherapy: 23 with busulfancyclophosphamide, 11 with the University College Hospital (UCH; London, UK) regimen, 6 with BAVC, and 21 with various other treatments. Marrow was purged in only 11 cases. Results were compared with 786 ABMTs performed for AML in patients between 16 and 49 years of age (median, 35 years). For AML in first remission, the probability of leukemia-free survival (LFS) at 4 years was 34% +/- 5% for patients aged 50 years or more and 43% +/- 2% for patients less than 50 years of age (P = .004), with a survival probability of 35% +/- 6% and 48% +/- 2%, respectively (P = .004). The probability of relapse was not significantly different between the two groups (52% +/- 7% v 50% +/- 2%), but transplant-related mortality was significantly higher in the older age group (28% +/- 5% v 14% +/- 2%; P < .0001) and mainly due to infectious complications. In a multivariate analysis, age less than 50 years was a favorable risk factor for LFS, treatment-related mortality (TRM), and survival but not for relapse incidence. These data suggest that ABMT should be considered in older AML patients.

Acute Disease↗
PubMed1995

Hip involvement in early rheumatoid arthritis.

OBJECTIVE: To study early hip involvement in rheumatoid arthritis (RA) and to evaluate the usefulness of ultrasonography in the detection of hip joint synovitis in RA. METHODS: Study I: The number of hip joint replacements was recorded in a cohort of 113 patients with RA of at least five years disease duration followed from an early stage. Study II: Ultrasonography was evaluated as a method to identify hip joint synovitis in 76 patients with RA of shorter disease duration, by relating it to radiograms and clinical findings. RESULTS: Study I: Twenty one hip joint replacements were performed in 15 of the 113 patients. The median disease duration at the time of first arthroplasty was 48 (range 10-76) months; the annual incidence was approximately constant between two and six years. High disease activity at the start of the study was predictive of requirement for hip prosthesis. Study II: Hip ultrasonography was pathological in 13 of the 76 patients studied, bilaterally in nine. Hip joint synovitis could not be confirmed on clinical grounds only as seven of the patients with positive ultrasonographic findings were asymptomatic, and the remaining six patients had only mild symptoms of hip involvement. Also, six of the 63 patients with normal ultrasonography had mild symptoms. There was no difference regarding demographic, clinical, and laboratory findings in patients with and without hip synovitis. CONCLUSIONS: Early hip joint destruction giving symptoms mostly at a very late stage is frequent in RA. Ultrasonography rather than signs or symptoms could identify patients with hip joint involvement and provide a rationale for early treatment.

Adult↗
PubMed1994

[Bilateral multiple pulmonary coin lesions--adenoid cystic carcinoma of the lung with 14-year follow-up].

The authors report on an adenoid cystic carcinoma (ACC) of the lung that had been discovered by chance 14 years before the death of the patient and that had at first been interpreted morphologically as a metastatic lung or as a bronchioalveolar carcinoma. The patient remained without any complaints for 13 years. Diagnosis of ACC became possible only by means of a renewed peripheral lung biopsy. An extrapulmonary primary tumour was excluded by postmortem examination. The disease pattern and the special course of the ACC are described.

Adult↗
PubMed1994

[Consequences of early-stage rheumatoid arthritis].

The consequences of early rheumatoid arthritis were studied in a series of patients treated at University Hospital, Lund, during the period 1985-1989. Mean disease duration at enrollment was 12 months. Most of the patients have now been followed prospectively for five years, during which time disease activity and pain have increased markedly. Ability to perform the activities of daily living (ADL) was well maintained, and the level of psychological distress fairly low. Radiographic changes in the hands and feet increased markedly, hand deformity being a common sign of severe disease; and only about ten per cent of the patients remained non-erosive. Another subgroup of ten per cent of the patients manifested rapidly progressive disease, resulting in destruction of larger joints, particularly hip joints, necessitating joint replacement in one or both hips. Eighteen per cent of the patients were in remission at 5-year follow-up. At 2-year follow-up, there was a high (37 per cent) prevalence of work disability, most patients who had had to stop work having done so in the first year. Physically demanding work and difficulties in performing ADL at presentation were the best predictors of subsequent work disability. The disease had a pronounced effect on life style, ability to cope with shopping, housework, leisure activities and social activities being adversely affected in more than half the patients.

Activities of Daily Living↗
PubMed1993

Psychological reactions in patients with early rheumatoid arthritis.

We report the interaction of RA and psychological factors over 2 years in a group of 89 patients with newly established disease. Short-time outcome regarding physical features was fairly good. Disease activity decreased, and disability evaluated by HAQ remained at a low level. Psychological distress as measured by the depression and anxiety subscales of SCL 90 (Symptom Check List) was not very pronounced and not related to disease state factors. A slight decrease of anxiety was recorded after 2 years. A new adjustment test was applied. It contained 13 items focused mainly on negative illness effects such as loss of independence, feelings of guilt, and change of social and leisure time activities. Three factors (regret of lost life values, dysphoric mood, and acceptance) explained 48% of the variance of the 13 items. The validity of the test was acceptable. The patients' degree of adjustment changed slowly or not at all during the 2 years.

Adaptation, Psychological↗