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H E Paulus

Publications and source records attributed to H E Paulus.

At least 19 recordsLinked to original sources
PubMed2006

Development and validation of the revised Cedars-Sinai health-related quality of life for rheumatoid arthritis instrument.

OBJECTIVE: To improve accuracy and content coverage of the original 33-item Cedars-Sinai Health-Related Quality of Life for Rheumatoid Arthritis Instrument (CSHQ-RA). METHODS: A total of 312 RA patients from 55 sites were screened in a 24-week trial. Patients completed an expanded 48-item version of the CSHQ-RA, Medical Outcomes Study Short Form 36 (MOS SF-36), and Stanford Health Assessment Questionnaire (HAQ) Disability Index at 5 visits. The revised CSHQ-RA was created based on response frequencies and distributions, item-to-item correlation, factor and Rasch analysis, and input from experts. Psychometric evaluation included internal consistency, test-retest reliability, convergent and discriminant validity, and responsiveness. Minimum clinically important difference (MCID) was also measured. RESULTS: Response rates were 93% at baseline and 71% at 12 weeks. Eighty-one percent of respondents at baseline were women, mean +/- SD age was 52 +/- 12 years, and mean +/- SD duration of RA was 10.8 +/- 10.4 years. The revised CSHQ-RA included 36 items measuring 7 domains (4 original and 3 new). All Cronbach's alpha coefficients were >0.8, indicating good internal consistency. Test-retest reliability measured intraclass correlation coefficients, which ranged from 0.86 to 0.95. All 7 domains correlated significantly with the MOS SF-36 and HAQ, indicating good convergent validity. Analysis of variance of disability group scores showed good discriminant validity (P < 0.0001). The MCIDs ranged from 6.2 for social well-being to 14.8 for pain/discomfort. CONCLUSION: The revised CSHQ-RA was validated using a broader RA patient population. It captures 3 additional domains (social well-being, pain/discomfort, and fatigue), which allow for measuring all important aspects of health-related quality of life.

Arthritis, Rheumatoid↗
PubMed2006

Application of explicit process of care measurement to rheumatoid arthritis: Moving from evidence to practice.

OBJECTIVE: To construct quality measures with measurement validity and meaning for clinicians. METHODS: We conducted a prospective cohort study of rates of change in disease-modifying antirheumatic drug (DMARD) and/or systemic corticosteroid drug or dose for 568 patients with rheumatoid arthritis (RA) across 6,159 clinical encounters within 12 months to examine how changes in clinical specifications change adherence. RESULTS: Rates of DMARD change were sensitive to specifications regarding the intensity of disease activity (severe or moderate), duration of specified disease activity, and length of the observation period. Over 12 months, the proportions of 377 patients with severe disease activity observed for 1-month, 2-month, and 3-month time blocks who had a change in DMARD drug or dose were 36%, 57%, and 74%, respectively. Over 12 months, a change in DMARD drug or dose was observed for 44%, 50%, and 68% of 377 patients with severe disease within 3 months, 6 months, and 12 months, respectively, of the patient meeting criteria for severe disease activity. A change in DMARD drug or dose was observed for 21%, 23%, and 34% of 149 patients with moderate disease activity within 3, 6, and 12 months, respectively, of the patient meeting criteria for moderate disease activity. CONCLUSION: Rates of pharmacologic interventions for patients with moderate and severe RA disease activity vary substantially by intensity and duration of disease activity and by duration of period for observing change. Lack of precision in explicit process criteria could substantially mislead comparisons of quality of care across comparison groups.

Adrenal Cortex Hormones↗
PubMed2001

Management of rheumatoid arthritis: the historical context.

We review the historical highlights of the management of rheumatoid arthritis (RA). Studies of nonsteroidal antiinflammatory drugs, disease modifying antirheumatic drugs, and biological agents over 5 decades were evaluated and summarized. There is emphasis on drug therapy as it has developed and evolved from empirical relief of symptoms with salicylates to targeted intervention in the immunoinflammatory process with tumor necrosis factor inhibitors. A therapeutic paradigm has been proposed to rationalize the use of the available therapies. If one accepts the thesis that both the acute and chronic consequences of RA are due to persistent misdirected and inadequately controlled inflammation that causes tissue destruction and loss of function, then prolonged complete control of the abnormal inflammatory process is the fundamental first step in the management of all patients with RA. Unfortunately, even with the newest therapeutic options to treat RA, most patients achieve only partial suppression of inflammation and many lose therapeutic benefit after an initial good response. The management of persistent or recurrent rheumatoid inflammation and disability continues to be a challenge. It remains to be determined whether the future addition of more potent specific interventions in the immunoinflammatory process will be able to solve this problem without disarming host defenses against infections and tumors.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Relative contributions of the components of the American College of Rheumatology 20% criteria for improvement to responder status in patients with early seropositive rheumatoid arthritis.

OBJECTIVE: To evaluate factors that influence the responses defined by the American College of Rheumatology (ACR) 20% criteria for improvement in rheumatoid arthritis (RA). METHODS: ACR 20% and 50% response rates were calculated from data collected for the intervals 0-6, 0-12, and 0-24 months for 180 RA patients participating in the Western Consortium of Practicing Rheumatologists long-term observational study of early seropositive RA (mean +/- SD duration of RA at study entry 6.0 +/- 3.4 months). Analyzable cases were patients with paired data for tender and swollen joint counts plus at least 3 of the following criteria: physician's and patient's global assessments of disease activity and patient's score for pain (by visual analog scale), physical function score on the Health Assessment Questionnaire (HAQ), and levels of an acute-phase reactant. Response rates were then recalculated by 3 different methods: 1) using only cases with complete paired data for all criteria, 2) sequentially assuming no improvement in each of the 5 secondary criteria, and 3) substituting grip strength for HAQ scores. RESULTS: Using 464 paired observations for all analyzable cases, ACR 20% (50%) improvement rates were 52.6% (33.0%), compared with 55.6% (34.8%) for 365 paired observations from the cases with complete data. Decreases in ACR response rates when secondary criteria were sequentially set at "no improvement" ranged from 11.7% (pain at 0-6 months) to 1.2% (C-reactive protein at 0-12 months), but these were not statistically different by the kappa statistic. Overall numerical rankings of the relative contributions of the secondary criteria to the ACR 20% or 50% response rates were physician's global assessment, pain, HAQ, patient's global assessment, and acute-phase reactant. Only 7.8% of paired grip strength observations showed > or =20% improvement, compared with 71% of paired HAQ observations. CONCLUSION: The use of all "analyzable" cases (paired data for tender and swollen joint counts plus > or =3 of the 5 secondary criteria) increases the number of subjects and only slightly decreases the ACR response rate compared with analyses limited to cases with complete data. The contributions of the secondary criteria are not statistically different, supporting their equal weighting in the ACR definition of improvement. The ACR 20% response rates are higher when the HAQ, rather than grip strength, is used to measure physical function.

Adult↗
PubMed2000

Direct and indirect costs associated with the onset of seropositive rheumatoid arthritis. Western Consortium of Practicing Rheumatologists.

OBJECTIVE: To examine the direct and indirect costs of rheumatoid arthritis (RA) during the first year of disease. METHODS: As part of a longitudinal observational study, 150 patients with seropositive RA of 5.9 +/- 2.9 mo duration were recruited through the Western Consortium of Practicing Rheumatologists. Subjects completed questionnaires about health care services and resources utilized and about the number of days of usual activity lost as a result of RA during the 6 month period prior to enrolment. RESULTS: Study participants had active RA as evidenced by mean tender and swollen joint counts of 24.9 +/- 13.5 and 20.6 +/- 11.6, respectively, and moderate functional impairment reflected by a mean Health Assessment Questionnaire (HAQ) score of 1.24 +/- 0.7. The average total direct cost of RA was $200/month. Health care visits, medications, and radiographs accounted for 78% of the total direct cost, while expenditures for hospitalizations accounted for only 3.5% of the total. The average number of days of usual activity lost per month because of RA was 3.8 +/- 7.7, translating into an average indirect cost of $281/month. Of the 95 subjects who were gainfully employed prior to disease onset, 12 were disabled and 5 were on sick leave as a result of RA, corresponding to a work disability rate of 18%. Work disabled subjects reported significantly lower total household incomes and higher HAQ disability and global disease activity scores than subjects who continued working. CONCLUSION: In this group of patients with seropositive RA substantial costs, both direct and indirect, were incurred during the first year of disease.

Arthritis, Rheumatoid↗
PubMed2000

Progression of radiographic joint erosion during low dose corticosteroid treatment of rheumatoid arthritis.

OBJECTIVE: The reported prevention of joint damage during treatment with prednisolone 7.5 mg daily in patients with early rheumatoid arthritis (RA)3 may have important implications for management of RA. We evaluated this observation in another patient population. METHODS: Radiographic progression rates in paired hand radiographs were analyzed in 824 patients with RA who participated in a 3 year prospective, randomized clinical trial comparing the nonsteroidal antiinflammatory drugs (NSAID) etodolac (150 or 500 mg bid) and ibuprofen (600 mg qid). Disease modifying antirheumatic drugs (DMARD) were not permitted. Prednisone < or=5 mg daily was continued by 197 patients (mean dose 4.37 mg daily) who had started prednisone therapy at least 6 mo before study entry, but new prednisone starts were not allowed. Standardized hand/wrist radiographs were done yearly and at dropout; joint erosion and narrowing scores of 3 readers were averaged and progression rates were compared. RESULTS: Mean duration of RA was 3.6 years (range 1-7); patients' ages were 21-78 years; 71% were women. Among the 824 patients, those taking prednisone were more likely to have had previous DMARD, and at study entry had higher radiographic scores for joint erosion and joint space narrowing and slightly higher swollen joint counts, C-reactive protein values, and rheumatoid factor titers than those not taking prednisone. However, for the subgroup of 252 patients with RA duration of 12-24 months, prestudy radiographic scores were not different in those taking or not taking prednisone. The mean (+/-SD) monthly rate of increase in erosion scores was 0.228 +/-0.37 for the prednisone patients and 0.206+/-0.35 for patients not taking prednisone (p = 0.994 by ANCOVA). The subgroup with 12 to 24 months' disease duration at entry also showed no significant effect of prednisone treatment on erosion progression. CONCLUSION: Clinically indicated low dose prednisone did not prevent progressive radiographic damage in 197 NSAID treated patients whose physicians had initiated < or =5 mg daily before study entry. The risk/benefit ratio of chronic low dose prednisone in early RA remains uncertain.

Adrenal Cortex Hormones↗
PubMed1999

Equivalence of the acute phase reactants C-reactive protein, plasma viscosity, and Westergren erythrocyte sedimentation rate when used to calculate American College of Rheumatology 20% improvement criteria or the Disease Activity Score in patients with early rheumatoid arthritis. Western Consortium of Practicing Rheumatologists.

OBJECTIVE: In an additive cohort of patients with early rheumatoid arthritis (RA), to determine the effect of substituting one acute phase reactant for another on the number of patients satisfying the American College of Rheumatology (ACR) 20% preliminary criteria for improvement, and on calculated Disease Activity Scores (DAS). METHODS: A total of 251 patients with 6.4 months average disease duration had detailed clinical assessments at entry and 6, 12, and 24 months in a multicenter prospective longterm observational study. Matched erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and plasma viscosity (PV) assays were done at 366 time points. Disease modifying antirheumatic drugs were not started until after the baseline evaluation. RESULTS: After 6, 12, and 24 months, 50%, 53%, and 57% of patients were responders, as defined by the ACR 20% improvement criteria. The difference in response rates when ESR, CRP, or PV was used as the acute phase reactant ranged from 0.4% at 12 months to 3% at 24 months. Percentile distributions of the 366 matched CRP, ESR, and PV values were used to prepare a nomogram that can be used to calculate the other acute phase reactant values if the value of one is known. When the nomogram was used to impute ESR values from observed PV or CRP values, average DAS scores calculated with the actual ESR values were not different from average DAS scores calculated from the imputed ESR values. CONCLUSION: ESR, CRP, and PV are equally useful in calculating ACR 20% response rates in patients with active early RA. A nomogram can be used to impute ESR values from CRP or PV values; use of the imputed ESR values is as accurate as use of the actual ESR values to calculate average DAS.

Acute-Phase Reaction↗
PubMed1996

Early undifferentiated connective tissue disease. IV.Musculoskeletal manifestations in a large cohort of patients with undifferentiated connective tissue diseases compared with cohorts of patients with well-established connective tissue diseases: followup analyses in patients with unexplained polyarthritis and patients with rheumatoid arthritis at baseline.

OBJECTIVES: To examine the musculoskeletal manifestations in a large cohort of patients (n = 410) diagnosed with either a well-established connective tissue disease (CTD) (n = 197) or an early undifferentiated CTD (n = 213) with a symptom duration of <1 year. This study was aimed at determining the predictive value of demographic, clinical, and laboratory features on outcome in patients with unexplained polyarthritis (UPA) (from the early undifferentiated CTD cohort; n = 67) or rheumatoid arthritis (RA) (from the well-established CTD cohort; n = 57), over a 5-year followup period. METHODS: Patients from both cohorts were assessed at years 1, 3, and 5. At the study visits, clinical data were collected in a standardized manner, and sera were obtained and stored. A priori criteria were established for patient ascertainment and diagnosis over the duration of the study. Standard statistics were used for comparisons of baseline characteristics in patients diagnosed as having systemic lupus erythematosus, RA, undifferentiated CTD, and UPA at entry into the cohorts. Baseline features in patients with UPA were examined according to the different subsequent outcomes (RA, CTD, or undifferentiated CTD, remission [nonpersistent], or persistent or active UPA). Baseline features in patients with RA whose disease remained active versus those in whom remission was attained were also examined. Two multivariable analyses, classification trees and polychotomous logistic regression, were performed to predict disease outcomes over time. RESULTS: The overall rate of ascertainment for the 410 patients ranged from 90 % at year 1 to 71 % at year 5. Patients with established CTDs showed a tendency for more stable diagnoses than those with early undifferentiated CTDs (90-100% versus 45-70%). Consistent baseline predictors of persistent active disease among patients with RA, in both univariate and multivariable analyses, were higher joint counts for pain and tenderness and higher erythrocyte sedimentation rate (ESR). In approximately 20% of patients who were classified as having RA when they originally entered the cohort, the disease was in remission at 5 years. Twenty percent of the patients originally classified as having UPA developed RA over the duration of the study. These patients tended to be older and to have swelling of small joints at baseline. However, a consistent pattern of predictive variables could not be identified in the multivariable analyses, other than at year 1 (higher small joint counts for swelling and higher ESR). CONCLUSION: Baseline features (joint counts, and ESR) among RA patients were variously predictive of persistently active disease at years 1-5. Consistent baseline predictors of outcome among patients with UPA only emerged at year 1. Remission occurred in approximately 20% of RA patients, whereas a similar percentage of patients with UPA developed RA. These findings have implications with regard to treatment decisions in patients with early RA and/or UPA.

Adult↗
PubMed1996

History of combination therapy of rheumatoid arthritis.

Faced with continued active rheumatoid arthritis (RA) despite conventional treatments, clinicians have added and combined whatever drugs were available to them, attempting to increase the benefits and minimize the adverse effects of treatment. First, combined antimalarial and gold salts therapy was favorably compared with antimalarial therapy in a large series of patients reported in 1963, but was cautioned against in 1966 because of concern about increasing toxicity. This concern discouraged subsequent publication of clinical experiences with combination therapies until 1982, when major benefits were reported in 17 patients treated with cyclophosphamide, azathioprine, and hydroxychloroquine. This report opened the door to numerous abstracts and publications during the 1980s, describing anecdotal series and poorly controlled clinical trials with various combinations of disease modifying antirheumatic drugs (DMARD), mostly with favorable results. During the past 5 or 6 years, a few, large, well controlled, randomized, double blind clinical trials with a balanced design have been published, but conclusive evidence of benefit from combinations of DMARD was lacking. Recent abstracts have suggested that triple therapy with methotrexate (MTX), hydroxychloroquine, and sulfasalazine produces additive benefits, and that the addition of cyclosporine, in patients who are poorly controlled by MTX, is more effective than continuing MTX alone. Only a few of the many possible permutations and combinations of drugs and doses have been evaluated, and confirmatory studies have not been done. Combination therapy of RA is only now starting to evolve, with most major milestones yet to be achieved.

Antirheumatic Agents↗
PubMed1995

Guidelines for clinical trials in systemic sclerosis (scleroderma). I. Disease-modifying interventions. The American College of Rheumatology Committee on Design and Outcomes in Clinical Trials in Systemic Sclerosis.

OBJECTIVE: To develop guidelines for therapeutic trials designed to improve the overall course of systemic sclerosis (SSc), that is, to reduce the development of significant organ damage or death. METHODS: A committee developed general guidelines for patient inclusion and exclusion criteria, randomization, blinding of patients and physicians, controls, duration of the trial, investigator training, responses, samples size, study dropouts, statistical analyses, data management, and safety monitoring. Delphi and nominal group techniques were used. RESULTS: Briefly, patients with diffuse cutaneous SSc of less than 24 months' duration should be included because they are at greatest risk for the development of severe organ damage and death. Patients should be excluded if they have other connective tissue diseases, SSc-like illnesses related to exposures or ingestions, severe existing internal organ damage, an unacceptable risk of side effects, or concurrent therapies that might independently influence the outcome. Randomized, double-blind, placebo-controlled trials are preferred. The treatment and followup period must be long enough to permit observation of any disease modification, which is likely to require 18-36 months, unless an extraordinarily effective therapy is identified. Responses selected should be quantitative, consistently and accurately reflect activity of SSc in major target organs (not solely the skin), be sensitive to change, and be standardized, with limited variability. An example of a set of responses is given. Surrogate responses are desirable, but none have been validated as correlating with organ damage. CONCLUSION: Guidelines have been established for trials of disease-modifying interventions in SSc. These guidelines will need to be altered as additional information becomes available. Any given protocol will be individualized based on the nature of the intervention and objectives of the study. Nonetheless, each study team should develop a protocol that meets the spirit of these guidelines.

Clinical Protocols↗
PubMed1995

Innovative treatment approaches for rheumatoid arthritis. Combination therapy.

It is accepted that combination DMARD therapy is a useful tool in current rheumatological practice. However, well-designed, large, long-term, controlled clinical trials are needed to determine which combinations, dosage schedules, and sequences of administration are most beneficial and least toxic. Until we develop treatment regimens that reliably induce and sustain acceptable control of disease manifestations in all patients for the rest of their natural lifespan, daily oral prednisone will continue to be a troublesome component of 'bridge' therapy, as it becomes the sole surviving constant in complex regimens whose other components are eventually discontinued because of toxicity, lack of efficacy, or non-compliance. We have often seen patients in whom the replacement of a well-tolerated but presumable ineffective DMARD with another DMARD has led to worsening of disease, when the modest benefits of the discontinued DMARD were lost before the hoped for onset of benefit from its replacement became evident. Since the toxicity of combinations of DMARDs has not appeared to be excessive, one can reasonably add the second DMARD to the first, while carefully monitoring for adverse effects and planning ton continue the combination until increased benefit occurs. Subsequently, if the second DMARD is not tolerated, the partial benefit from the first has not been given up, and a longer duration of treatment with the initial DMARD is sometimes associated with satisfactory improvement. If better control of rheumatoid arthritis is evident after 3-6 months of treatment with the combination of DMARDs, one must still decide whether to stop the first DMARD, stop the second, or continue with the combination. In the absence of major toxicity, we are most likely to choose to continue the combination if the patient has had a good response, thus inadvertently embarking on prolonged combined DMARD therapy (Paulus, 1990). Of course, other drugs besides those discussed above are available to control different aspects of joint damage; they should be considered in any combination therapy. Drugs which potentially protect cartilage from damage, such as orgotein, glycosaminoglycan polysulphate (Arteparon), and Rumalon, may prove useful in rheumatoid arthritis; they have been studied in osteoarthritis, but there is evidence that they protect cartilage from breakdown by inflammation in some animal models. As one of the many goals of treatment in rheumatoid arthritis is to protect cartilage, these chondroprotective agents might also be considered as part of the combinations to be studied. The combination of modest clinical efficacy with minimal toxicity reported with minocycline treatment of rheumatoid arthritis make this another potentially interesting addition to combination therapy regimens (Tilley et al, 1995). It is also important to continue the development of so-called 'biological agents', such as interleukin-2 receptor antibodies, anti-CD4 antibodies, anti-TNF-alpha agents and anti-thymocyte globulin. Combinations which include such agents have not yet been evaluated, although is seems logical considering that these agents offer the possibility of precise intervention directed at specific steps of the immuno-inflammatory process; their combination may thus be more effective than the use of single agents alone. While we await results of well-designed studies of these newer agents in RA therapy, we should continue to consider creative ways of using drugs that are already available.

Antineoplastic Agents↗
PubMed1995

Clinical trial design for evaluating combination therapies.

Because the differences in efficacy between a disease-modifying antirheumatic drug (DMARD) combination and its constituent drugs are likely to be smaller than those between placebo and the single DMARDs, it has been difficult to prove that any combination of DMARDs has either additive or synergistic benefit. The discriminatory power of the study design can be enhanced by careful attention to the details of patient selection, study design and duration, and choices of primary outcome measures and analytical methods. Use of the American College of Rheumatology (ACR) 'core set' of outcome measures and the proposed ACR 'definition of improvement' for rheumatoid arthritis (RA) clinical trials, with intent-to-treat analysis, in a balanced, prospective, double-blind randomized clinical trial of 1-2 yr duration will optimize the chances of discriminating between the clinical benefit of the combination and its components if a real difference is present.

Antirheumatic Agents↗
PubMed1995

Rheumatoid arthritis. Outcome measures.

Rheumatologists have been pioneers in the development and use of clinical measures for outcome assessment. The Lansbury Index (1958) and the Empire Rheumatism Gold Trial (1960) used sophisticated double-blind pseudo-placebo-controlled trial designs and standardized prespecified clinical outcome measures to establish the clinical usefulness of a drug whose benefit did not become evident until it was administered for several months. Since these studies, other studies have establish the clinical and statistical groundwork for rheumatoid arthritis outcome measures. In 1980, the Health Assessment Questionnaire and the Arthritis Impact Measurement Scales were added. Future development of paradigms for the decision process in the clinical management of individual rheumatoid arthritis patients will no doubt incorporate standard outcome measures to provide the data upon which management decisions can be based.

Antirheumatic Agents↗