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T Pincus

Publications and source records attributed to T Pincus.

At least 19 recordsLinked to original sources
PubMed2006

Work disability in early rheumatoid arthritis: higher rates but better clinical status in Finland compared with the US.

OBJECTIVE: To analyse and compare work disability attributed to rheumatoid arthritis in two cohorts of patients with early disease: one in the US and the other in Finland. PATIENTS AND METHODS: Two cohorts of patients who were working and aged <65 years at the time of their first symptom of rheumatoid arthritis were studied: 269 patients in Nashville, TN, USA (median age 46 years, 72.5% females), and 364 patients from Jyväskylä, Finland, (median age 47.1 years, 70.9% females). The cohorts were analysed and compared for measures of clinical status and work disability status over a median (interquartile range) of 38.9 months in Nashville and 48.4 months in Jyväskylä. RESULTS: The probability of working at 36 months was 0.89 (0.84-0.92) for patients from Nashville and 0.84 (0.80-0.88) for patients from Jyväskylä (p = 0.02). These rates were lower than in earlier decades. Patients from Jyväskylä had significantly higher rates of work disability (p = 0.02) than those from Nashville, but better scores for self-report physical function (p<0.001), pain (p<0.001) and global status (p<0.001) at last observation. The likelihood of being disabled from work was 2.6-fold higher in Jyväskylä compared to Nashville (95% confidence interval 1.44 to 4.59, p = 0.001), after adjustment for demographic and disease-specific variables. CONCLUSION: Rates of work disability in both early rheumatoid arthritis cohorts were improved from earlier decades, but differed significantly in two different social systems. Higher work disability rates with better clinical status was seen in the Finnish early rheumatoid arthritis cohort than in the US cohort.

Adult↗
PubMed2006

Are American College of Rheumatology 50% response criteria superior to 20% criteria in distinguishing active aggressive treatment in rheumatoid arthritis clinical trials reported since 1997? A meta-analysis of discriminant capacities.

OBJECTIVE: To carry out a meta-analysis designed to compare the discriminant capacities of American College of Rheumatology 50% (ACR50) with 20% (ACR20) responses in clinical trials on rheumatoid arthritis reported after 1997 and to analyse whether ACR50 can be as informative as ACR20 in distinguishing active from control treatments in more recent trials. METHODS: Clinical trials on rheumatoid arthritis reported since 1997 were identified, which included aggressive combinations of disease-modifying antirheumatic drugs and glucocorticoids, as well as powerful new agents-leflunomide, etanercept, infliximab, anakinra, adalimumab, abatacept, tacrolimus and rituximab. A meta-analysis of ACR20 compared with ACR50 responses for 21 clinical trials was carried out on differences in proportions of responders for active and control treatments and corresponding odds ratios (ORs). RESULTS: In all but one clinical trial on rheumatoid arthritis published since 1997 with data available on ACR20 and ACR50, more than 50% of patients who were ACR20 responders among those randomised to active treatment were also ACR50 responders. This phenomenon was seen for control groups in 38% of trials, many of which included treatment with methotrexate. A meta-analysis of the clinical trials indicated a slight advantage to ACR50 for quantifying treatment comparisons, not significant for differences in proportions but significant for ORs. CONCLUSION: ACR20 and ACR50 seem to be similar in distinguishing active from control treatments in clinical trials on rheumatoid arthritis reported since 1997. As ACR50 represents a considerably stronger clinical response, ACR50 may be a preferred end point for contemporary clinical trials on rheumatoid arthritis.

Antirheumatic Agents↗
PubMed2005

Declines in number of tender and swollen joints in patients with rheumatoid arthritis seen in standard care in 1985 versus 2001: possible considerations for revision of inclusion criteria for clinical trials.

OBJECTIVE: To analyse tender and swollen joint counts in three cohorts of patients with rheumatoid arthritis (RA), with a focus on the proportions of patients who had fewer than 6-12 tender or swollen joints, as possible evidence based information toward more generalisable inclusion criteria for current and future RA clinical trials. METHODS: Tender and swollen joint counts were analysed in three cohorts of patients with RA: 125 in 1985, 138 in 2000, and 232 with early RA in 2001. RESULTS: The median numbers of tender joints were 11, 2, and 4 in 1985, 2000, and in early RA in 2001, respectively. The median numbers of swollen joints were 12, 6, and 5 in 1985, 2000, and 2001, respectively. The numbers of tender joints among 28 assessed were >or=12, >or=6, >or=4, and >or=3 in 47%, 80%, 85%, and 90% of patients in 1985; 20%, 37%, 44%, and 49% in 2000; and 17%, 37%, 50%, and 58% in early RA in 2001. The numbers of swollen joints among 28 assessed were >or=12, >or=6, >or=4, and >or=3 in 51%, 78%, 86%, and 90% of patients in 1985; 20%, 50%, 64%, and 67% in 2000; and 14%, 46%, 58%, and 72% in 2001. The number of patients with >or=6 tender or swollen joints in 1985 was greater than the number with >or=3 joints in 2000 and in early RA in 2001. CONCLUSION: Contemporary cohorts of patients seen in standard care have smaller numbers of tender and swollen joints than in previous times. These findings suggest that revision of inclusion criteria for numbers of tender and swollen joints in contemporary RA clinical trials might improve generalisability.

Adult↗
PubMed2005

Most visits of most patients with rheumatoid arthritis to most rheumatologists do not include a formal quantitative joint count.

OBJECTIVE: To ask rheumatologists about the likelihood of performing a formal joint count at each visit of a patient with rheumatoid arthritis (RA) in standard clinical care. METHOD: Direct query of rheumatologists at an international meeting of about 600 rheumatologists from 17 European countries. RESULTS: Overall, 14% of rheumatologists reported performing a formal joint count at each visit of each patient, and 44% of rheumatologists reported performing a formal joint count at more than 50% of visits of patients with RA. Therefore, 56% of rheumatologists reported performing a joint count at fewer than 50% of visits, including 45% at fewer than 25% of visits. One in eight rheumatologists (13%) reported never performing a formal joint count. CONCLUSION: Although the joint count remains the most specific measure for RA, most visits of most patients with RA to most rheumatologists do not include a formal quantitative joint count.

Arthritis, Rheumatoid↗
PubMed2004

Long term safety of methotrexate in routine clinical care: discontinuation is unusual and rarely the result of laboratory abnormalities.

OBJECTIVE: To analyse patients with rheumatoid arthritis, treated with methotrexate in a weekly academic rheumatology clinic over 13 years, for continuation of courses and reasons for discontinuation. METHODS: All 248 patients with an analysable longitudinal course who took methotrexate in standard care between 1990 and 2003 were studied. Continuation of courses was analysed using life tables. All abnormal and severely abnormal values for aspartate aminotransferase (AST) >40 U/l, >80 U/l, albumin <35 g/l, <30 g/l, white blood cell (WBC) count <4.0 x 10(9)/l, <3.0 x 10(9)/l, and platelet count <150 x 10(9)/l, <100 x 10(9)/l, were identified. Responses of the clinician and subsequent laboratory values were reviewed. RESULTS: Over 1007 person-years, the probability of continuing methotrexate over five years was 79% (95% confidence interval, 72% to 84%). Severe laboratory abnormalities occurred in 2.9 per 100 person-years, specifically 0.9 for AST >80 U/l, 1.1 for albumin <30 g/l, 0.7 for WBC <3.0 x 10(9)/l, and 0.3 for platelets <100 x 10(9)/l. No severe laboratory abnormality progressed to further severity or clinical disease. Permanent discontinuations of methotrexate occurred in 46 patients (19%), 26 (10% of all patients) for adverse effects, 15 (32.6%) for inefficacy; only two discontinuations resulted from laboratory abnormalities, both of WBC, possibly from other sources. CONCLUSIONS: Methotrexate was associated with a high rate of continuation, and few clinically significant laboratory abnormalities. Discontinuation primarily reflected clinical rather than laboratory findings. Vigilance for methotrexate toxicity is required but methotrexate appears among the safest treatments for rheumatoid arthritis.

Antirheumatic Agents↗
PubMed2004

Patient Preference for Placebo, Acetaminophen (paracetamol) or Celecoxib Efficacy Studies (PACES): two randomised, double blind, placebo controlled, crossover clinical trials in patients with knee or hip osteoarthritis.

BACKGROUND: Acetaminophen (paracetamol) is recommended as the initial pharmacological treatment for knee or hip osteoarthritis. However, survey and clinical trial data indicate greater efficacy for non-steroidal anti-inflammatory drugs and cyclo-oxygenase-2 specific inhibitors. DESIGN: Two randomised, double blind, placebo controlled, crossover multicentre clinical trials, Patient Preference for Placebo, Acetaminophen or Celecoxib Efficacy Studies (PACES). PATIENTS: Osteoarthritis of knee or hip. INTERVENTION: "Wash out" of treatment; randomisation; 6 weeks of celecoxib 200 mg/day, acetaminophen 1000 mg four times a day, or placebo; second "wash out;" crossover to 6 weeks of second treatment. MEASUREMENTS: Western Ontario McMaster Osteoarthritis Index (WOMAC), visual analogue pain scale, patient preference between two treatments. RESULTS: Celecoxib was more efficacious than acetaminophen in both periods in both studies; WOMAC and pain scale scores differed at p<0.05 in period II and both periods combined of PACES-a and in periods I and II and both periods combined in PACES-b, but not in period I of PACES-a. Acetaminophen was more efficacious than placebo, generally p<0.05 in PACES-b, and >0.05 in PACES-a. Patient preferences were 53% celecoxib v 24% acetaminophen in PACES-a (p<0.001) and 50% v 32% in PACES-b (p = 0.009); 37% acetaminophen v 28% placebo in PACES-a (p = 0.340) and 48% v 24% in PACES-b (p = 0.007). No clinically or statistically significant differences were seen in adverse events or tolerability among the three treatment groups. CONCLUSIONS: Greater efficacy was seen for celecoxib v acetaminophen v placebo, while adverse events and tolerability were similar. Variation in results and statistical significance in the two different trials are of interest.

Acetaminophen↗
PubMed2004

Should contemporary rheumatoid arthritis clinical trials be more like standard patient care and vice versa?

The information used by rheumatologists when delivering care to patients with rheumatoid arthritis (RA) is derived mainly from two sources: randomised controlled clinical trials and experience in clinical care. However, these two sources differ significantly because (a) the extensive inclusion and exclusion criteria result in clinical trial participants being recruited from only a minority of patients seen in standard clinical care; (b) assessments in clinical trials are conducted according to standard quantitative measures and indices, while standard clinical care of most patients with RA is generally conducted empirically, without collection of any quantitative data other than laboratory tests to estimate prognosis and document change in status; and (c) although baseline databases of various clinical trials (and observational studies) are 60-90% identical in content, they are not standardised and therefore not amenable to direct comparisons. Strategies to promote similarities between clinical trials and standard clinical care in patients with RA may include: more generalised inclusion criteria; incorporation of quantitative measurement into standard care, easily accomplished by asking each patient to complete a simple questionnaire at each visit to a rheumatologist; and consensus among rheumatologists for databases with standard content and format in clinical care and research involving patients with RA.

Antirheumatic Agents↗
PubMed2003

An index of the three core data set patient questionnaire measures distinguishes efficacy of active treatment from that of placebo as effectively as the American College of Rheumatology 20% response criteria (ACR20) or the Disease Activity Score (DAS) in a rheumatoid arthritis clinical trial.

OBJECTIVE: To evaluate the capacity of a pooled index of only the 3 patient self-report questionnaire measures among the 7 American College of Rheumatology (ACR) core data set (Core Data Set) measures to distinguish efficacy of active treatment of rheumatoid arthritis (RA) with leflunomide or methotrexate versus placebo in a randomized, controlled clinical trial, and to compare the results with those obtained using the ACR 20% response criteria (ACR20), Disease Activity Score (DAS), and other pooled indices. METHODS: The 7 ACR Core Data Set measures of 1) joint swelling, 2) joint tenderness, 3) physician global assessment, 4) erythrocyte sedimentation rate (ESR), 5) functional disability, 6) pain, and 7) patient global assessment were combined into the following 5 pooled indices: "All Core Data Set" (all 7 measures), "Assessor Only" (measures 1-3), "Assessor + ESR" (measures 1-4), "Patient Only" (measures 5-7), and "Patient + ESR" (measures 4-7). The capacity of each of these 5 indices to detect differences between active treatment and placebo treatment was compared with that of the ACR20 and the DAS using 4 different analytic methods, each of which presented advantages and limitations. Agreement of the indices with one another and with the ACR20 and the DAS was analyzed according to pairwise kappa statistics and Z scores in multivariate logistic regression models. RESULTS: Each of the 5 indices, including "Patient Only," had a similar capacity to detect greater efficacy of leflunomide and methotrexate versus placebo in this clinical trial, according to each of 4 methods, at similar levels of statistical and clinical significance. CONCLUSION: A pooled index of patient self-report questionnaire Core Data Set measures appears to be as informative as ACR20 responses, DAS scores, and pooled indices of all and assessor-derived Core Data Set measures for distinguishing between active treatment and placebo treatment in this RA clinical trial.

Antirheumatic Agents↗
PubMed2002

Evidence from clinical trials and long-term observational studies that disease-modifying anti-rheumatic drugs slow radiographic progression in rheumatoid arthritis: updating a 1983 review.

Earlier reports, including a comprehensive 1983 review, had indicated that slowing of radiographic progression was relatively unusual in treatment of rheumatoid arthritis (RA) using traditional disease modifying anti-rheumatic drugs. However, in recent years, slowing of radiographic progression has been documented in a number of clinical trials, as well as long-term observational studies, with use of (in alphabetical order) adalimumab, anakinra, corticosteroids, cyclophosphamide, cyclosporin, etanercept, gold salts, infliximab, leflunomide, methotrexate and sulphasalazine. At this time, disease modification is a realistic goal in the clinical care of patients with RA. Documentation of improved long-term outcomes requires long-term observational data over 5-20 yr to supplement data from randomized controlled clinical trials over 6-24 months.

Antirheumatic Agents↗
PubMed2001

A genomewide screen in multiplex rheumatoid arthritis families suggests genetic overlap with other autoimmune diseases.

Rheumatoid arthritis (RA) is an autoimmune/inflammatory disorder with a complex genetic component. We report the first major genomewide screen of multiplex families with RA gathered in the United States. The North American Rheumatoid Arthritis Consortium, using well-defined clinical criteria, has collected 257 families containing 301 affected sibling pairs with RA. A genome screen for allele sharing was performed, using 379 microsatellite markers. A nonparametric analysis using SIBPAL confirmed linkage of the HLA locus to RA (P < .00005), with lambdaHLA = 1.79. However, the analysis also revealed a number of non-HLA loci on chromosomes 1 (D1S235), 4 (D4S1647), 12 (D12S373), 16 (D16S403), and 17 (D17S1301), with evidence for linkage at a significance level of P<.005. Analysis of X-linked markers using the MLOD method from ASPEX also suggests linkage to the telomeric marker DXS6807. Stratifying the families into white or seropositive subgroups revealed some additional markers that showed improvement in significance over the full data set. Several of the regions that showed evidence for nominal significance (P < .05) in our data set had previously been implicated in RA (D16S516 and D17S1301) or in other diseases of an autoimmune nature, including systemic lupus erythematosus (D1S235), inflammatory bowel disease (D4S1647, D5S1462, and D16S516), multiple sclerosis (D12S1052), and ankylosing spondylitis (D16S516). Therefore, genes in the HLA complex play a major role in RA susceptibility, but several other regions also contribute significantly to overall genetic risk.

Alleles↗
PubMed2001

A randomized, double-blind, crossover clinical trial of diclofenac plus misoprostol versus acetaminophen in patients with osteoarthritis of the hip or knee.

OBJECTIVE: To perform a randomized, double-blind, crossover clinical trial of diclofenac + misoprostol versus acetaminophen in ambulatory patients with osteoarthritis of the hip or knee. METHODS: Patients in 12 ambulatory care settings were eligible if they were age >40 years and if they had Kellgren/Lawrence radiographic grade 2-4 osteoarthritis of the knee or hip and a score of > or =30 mm on a 100-mm visual analog pain scale. Patients were randomized to one of two groups, 75 mg diclofenac + 200 microg misoprostol twice daily or 1,000 mg acetaminophen 4 times daily (each for 6 weeks), and were then crossed over to the other treatment for 6 weeks. A placebo was included in each treatment regimen to enable double blinding. The primary outcome measures were the Western Ontario and McMaster Universities Osteoarthritis Index and the visual analog pain scale of the Multidimensional Health Assessment Questionnaire. Safety was assessed using a standard form to review adverse events. RESULTS: We enrolled 227 patients, of whom 218 provided data for the first treatment period and 181 provided data for both treatment periods. Significantly higher levels of improvement in the primary outcomes were seen for diclofenac + misoprostol than for acetaminophen (P < 0.001). Adverse events were more common when patients took diclofenac + misoprostol (P = 0.046). Diclofenac + misoprostol was rated as "better" or "much better" by 57% of the 174 patients who provided such ratings for both treatment periods, while acetaminophen was rated as "better" or "much better" by 20% of these patients, and 22% reported no difference (P < 0.001). Differences favoring diclofenac + misoprostol over acetaminophen were greater in patients with more severe osteoarthritis according to baseline pain scores, radiographs, or number of involved joints. CONCLUSION: Patients with osteoarthritis of the hip or knee had significantly greater improvements in pain scores over 6 weeks with diclofenac + misoprostol than with acetaminophen, although patients with mild osteoarthritis had similar improvements with both drugs. Acetaminophen was associated with fewer adverse events.

Acetaminophen↗
PubMed2001

Clinical evidence for osteoarthritis as an inflammatory disease.

Osteoarthritis (OA) is not a simple consequence of "wear and tear" or aging--the presence of cytokines suggests a role for inflammation. OA is polyarticular in most patients, with metabolic and differential risk factors for prevalence and severity. Odds ratios for the prevalence of OA according to formal education levels are similar to those seen for dysregulatory diseases such as hypertension, diabetes, and rheumatoid arthritis. Clinical survey data indicate significant patient preference for nonsteroidal anti-inflammatory drugs (NSAIDs) compared with acetaminophen. A recent crossover clinical trial indicated significantly greater efficacy of the NSAID, diclofenac/misoprostol, versus acetaminophen for most patients with OA.

Acetaminophen↗