Hemolytic disease of the fetus and newborn mediated by anti-Dia in a U.S. hospital.

Dia is one of the most clinically significant low-prevalence antigens in the Diego blood group system, since antibodies to Dia have, albeit rarely, been implicated in hemolytic transfusion reactions and hemolytic disease of the fetus and newborn (HDFN). Given the geographical association, most anti-Dia HDFN cases have been reported in Japan, China, and Poland. We describe a case of HDFN in a neonate born to a 36-year-old G4P2012 woman of self-identified Hispanic ethnicity and of South American descent with multiple negative antibody detection tests in a U.S. hospital. Upon delivery, a cord blood direct antiglobulin test was positive (3+ reactivity), and neonatal bilirubin levels were moderately elevated, but phototherapy and transfusion were not required. This case highlights a rare, unexpected cause of HDFN in the United States secondary to anti-Dia, given the near-universal absence of this antigen and antibody in most U.S. patient populations. The case also demonstrates the need for awareness of antibodies to antigens that are considered "low-prevalence" in most populations but that might be encountered more frequently in specific racial or ethnic groups and may require more extensive testing.

Effectiveness of Remission Induction Strategies for Early Rheumatoid Arthritis: a Systematic Literature Review.

PURPOSE OF REVIEW: To review the effectiveness of remission induction strategies compared to single csDMARD-initiating strategies according to current guidelines in early RA. RECENT FINDINGS: Twenty-nine studies, heterogeneous on, e.g., specific treatment strategy and remission outcome used, were identified. Using DAS28-remission over 12 months, 13 (76%) of 17 remission induction strategies showed significantly more patients achieving remission. Pooled relative "risk" was 1.73 [95%CI 1.59-1.88] for bDMARD-based remission induction strategies and 1.20 [95%CI 1.03-1.40] for combination csDMARD-based remission induction strategies compared to single csDMARD-initiating strategies. When additional glucocorticoid "bridging therapy" was used in single csDMARD-initiating strategies, the higher proportion patients achieving remission in remission induction strategies was no longer statistically significant (pooled RR 1.06 [95%CI 0.83-1.35]). For other remission outcomes, results were in line with above. Remission induction strategies are more effective in achieving remission compared to single csDMARD-initiating strategies, possibly more so in bDMARD-based induction strategies. However, compared to single csDMARD-initiating strategies with glucocorticoids, induction strategies may not be more effective.

Most children with eosinophilic esophagitis have a favorable outcome as young adults.

The disease progression of eosinophilic esophagitis (EoE) from childhood into adulthood is unclear. To determine the clinical outcome of patients who were diagnosed with EoE as children, and who now are young adults. Children (<18 years old) diagnosed with EoE were enrolled in a prospective registry on demographics, presenting symptoms, and endoscopic/histologic findings. Subjects who now are adults (≥18 years old) were identified, and a structured telephone interview was conducted to obtain follow-up data on symptom prevalence (dysphagia to solids and liquids, nausea/vomiting, abdominal pain, and heartburn/regurgitation), food impaction, medication usage, health-care utilization, and resolution of atopy/food allergies. A favorable outcome was defined if EoE symptoms were resolved or improved by subjects' assessment. Unfavorable outcomes was defined as symptoms same or worse. Clinical variables that predicted a favorable outcome as an adult were examined. Mayo Dysphagia Scale (MDQ-30: scored 0-100) was administered to validate the outcome assessment. Mantel-Haenszel odds ratio and unpaired t-test were used. Fifty-eight subjects (64% male) who met study criteria were enrolled. Mean age at diagnosis was 12 years (range 4-17) and mean duration of follow-up was 8.3 years (2-16). As children, the most common presenting symptoms were abdominal pain (54%), dysphagia (33%), and vomiting (24%). As young adults, 47 subjects (81%) had a favorable outcome. Total MDQ-30 scores were 4.6 (0-30) and 14.1 (0-50) in subjects with favorable outcome and unfavorable outcome, respectively (P = 0.015). Two-thirds of subjects did not use steroids or proton pump inhibitors in the preceeding 12 months. Male children with EoE were four times more likely to have a favorable outcome as young adults compared with female children. Females were more likely to report nausea/vomiting as young adults (odds ratio 3.23, CI 0.97-10.60). Of all presenting symptoms in EoE children, dysphagia was the most likely to persist into adulthood (odds ratio 6.29, CI 1.85-21.38). Eighty one percent of EoE children had a favorable outcome as young adults. Most patients with symptom resolution did not require any form of steroid therapy or seek healthcare.

Assessment of disease activity in patients with rheumatoid arthritis using optical spectral transmission measurements, a non-invasive imaging technique.

OBJECTIVES: In rheumatoid arthritis (RA), treat-to-target strategies require instruments for valid detection of joint inflammation. Therefore, imaging modalities are increasingly used in clinical practice. Optical spectral transmission (OST) measurements are non-invasive and fast and may therefore have benefits over existing imaging modalities. We tested whether OST could measure disease activity validly in patients with RA. METHODS: In 59 patients with RA and 10 patients with arthralgia, OST, joint counts, Disease Activity Score (DAS) 28 and ultrasonography (US) were performed. Additionally, MRI was performed in patients with DAS28<2.6. We developed and validated within the same cohort an algorithm for detection of joint inflammation by OST with US as reference. RESULTS: At the joint level, OST and US performed similarly inproximal interphalangeal-joints (area under the receiver-operating curve (AUC) of 0.79, p<0.0001) andmetacarpophalangeal joints (AUC 0.78, p<0.0001). Performance was less similar in wrists (AUC 0.62, p=0.006). On the patient level, OST correlated moderately with clinical examination (DAS28 r=0.42, p=0.001), and US scores (r=0.64, p<0.0001). Furthermore, in patients with subclinical and low disease activity, there was a correlation between OST and MRI synovitis score (RAMRIS (Rheumatoid Arthritis MRI Scoring) synovitis), r=0.52, p=0.005. CONCLUSIONS: In this pilot study, OST performed moderately in the detection of joint inflammation in patients with RA. Further studies are needed to determine the diagnostic performance in a new cohort of patients with RA.

Economic evaluation of a tight-control treatment strategy using an imaging device (handscan) for monitoring joint inflammation in early rheumatoid arthritis.

OBJECTIVES: To evaluate the cost-effectiveness of a tight-control treatment strategy using the handscan (TCHS) compared to using only clinical assessments (TC) and compared to a general non-tight-control treatment strategy (usual care; UC) in early rheumatoid arthritis (RA). METHODS: Data from 299 early RA patients from the CAMERA trial were used. Clinical outcomes were extrapolated to Quality Adjusted Life Years (QALYs) and costs using a Markov model. Costs and QALYs were compared between the TC and UC treatment strategy arm of the CAMERA trial and a simulated tight-control treatment strategy using the handscan (TCHS). Incremental Cost-Effectiveness Ratios (ICERs) were calculated and several scenario analyses performed. All analyses were performed probabilistically to obtain confidence intervals and costs-effectiveness planes and acceptability curves. RESULTS: In TCHS, €4,660 (95% CI -€11,516 to €2,045) was saved and 0.06 (95% CI 0.01 to 0.11) QALYs were gained when compared to UC, with an ICER of €77,670 saved per QALY gained. Ninety-one percent (91%) of simulations resulted in less costs and more QALYs. TCHS resulted in comparable costs or even limited savings €642 (95% CI -€6,903 to €5,601)) and comparable QALYs to TC. In all scenario analyses, TCHS and TC were found to be cost effective as compared to UC. CONCLUSIONS: A tight-control treatment strategy is highly cost-effective compared to a non-tight-control approach in early RA. Using the handscan as a monitoring device might facilitate implementation of tight-control treatment strategy at comparable costs and with comparable effects. This approach should be investigated further.

The separate impact of tight control schemes and disease activity on quality of life in patients with early rheumatoid arthritis: results from the CAMERA trials.

OBJECTIVES: To examine in patients with early rheumatoid arthritis (RA) whether quality of life (QoL), independently of disease activity, is affected by tight control treatment strategy schemes. METHODS: In the Computer Assisted Management in Early RA (CAMERA) trials, patients with early RA, disease duration <1 year, no prior use of DMARDs) had been randomised to a methotrexate (MTX)-based tight control strategy or usual care (CAMERA study) or to 10 mg/d prednisone or placebo both added from start to a MTX-based tight control strategy (CAMERA-II study). In either study, randomisation to the more intensive strategy resulted in lower disease activity. To assess QoL, the 'Influence of Rheumatic Diseases on General Health and Lifestyle' questionnaire (IRGL) was used. Baseline and 1- and/or 2-year measurements were analysed with regression analyses with the IRGL (sub)scales as outcome variables and treatment strategy and disease activity assessing 28 joints (DAS28) as independent variables, correcting for baseline values of each scale and possible confounders (gender, age, rheumatoid factor status). RESULTS: There was no clear association between either of the treatment strategies and QoL, but a decrease in DAS28 was associated with improvement in the majority of QoL (sub)scales. CONCLUSIONS: No independent effect of the specific tight control strategies schemes on QoL was found, while there was a clear disease activity related effect. Thus frequent outpatient visits or the inclusion of prednisone in a tight control strategy did not negatively influence QoL.

Identifying factors hampering physical activity in longstanding rheumatoid arthritis: what is the role of glucocorticoid therapy?

OBJECTIVES: To identify factors hampering the level of physical activity in longstanding rheumatoid arthritis (RA) patients, and to evaluate the effects of glucocorticoid therapy on physical activity. METHODS: Patient characteristics, disease characteristics and cardiovascular parameters were recorded in 170 patients, who participated in a study about glucose metabolism in longstanding RA treated with or without glucocorticoids. Disease activity scores (DAS28) were calculated and x-rays of hands and feet were taken and scored according to the Sharp van der Heijde score (SHS). Participants completed the health assessment questionnaire and short questionnaire to assess health-enhancing physical activity (SQUASH), which reflect physical disability and physical activity, respectively. Adherence rates to recommendations on physical activity were calculated, and patients were categorised as fully adhering, insufficiently adhering (adherence on less than the recommended number of days per week) or inactive (adherence on none of the days). RESULTS: Forty-four percent of the patients showed adherence to the recommended minimum level of physical activity, and 22% were classified as inactive. Higher DAS28 and SHS, glucocorticoid therapy, and presence of cardiovascular risk factors were associated with lower total SQUASH physical activity scores univariately. In a multivariate model, higher age, higher body mass index (BMI), higher DAS28, and higher SHS negatively influenced the score significantly; cardiovascular risk factors and glucocorticoid therapy were no longer significantly influencing physical activity. CONCLUSIONS: Physical activity in longstanding RA is hampered by higher age, higher BMI, higher disease activity, and more radiographic joint damage. Glucocorticoid therapy was not identified as independent risk factor in multivariate analyses.

Incidence of Antibiotic Exposure for Suspected and Proven Neonatal Early-Onset Sepsis between 2019 and 2021: A Retrospective, Multicentre Study.

Management of suspected early-onset sepsis (EOS) is undergoing continuous evolution aiming to limit antibiotic overtreatment, yet current data on the level of overtreatment are only available for a select number of countries. This study aimed to determine antibiotic initiation and continuation rates for suspected EOS, along with the incidence of culture-proven EOS in The Netherlands. In this retrospective study from 2019 to 2021, data were collected from 15 Dutch hospitals, comprising 13 regional hospitals equipped with Level I-II facilities and 2 academic hospitals equipped with Level IV facilities. Data included birth rates, number of neonates started on antibiotics for suspected EOS, number of neonates that continued treatment beyond 48 h and number of neonates with culture-proven EOS. Additionally, blood culture results were documented. Data were analysed both collectively and separately for regional and academic hospitals. A total of 103,492 live-born neonates were included. In 4755 neonates (4.6%, 95% CI 4.5-4.7), antibiotic therapy was started for suspected EOS, and in 2399 neonates (2.3%, 95% CI 2.2-2.4), antibiotic treatment was continued beyond 48 h. Incidence of culture-proven EOS was 1.1 cases per 1000 live births (0.11%, 95% CI 0.09-0.14). Overall, for each culture-proven EOS case, 40.6 neonates were started on antibiotics and in 21.7 neonates therapy was continued. Large variations in treatment rates were observed across all hospitals, with the number of neonates initiated and continued on antibiotics per culture-proven EOS case varying from 4 to 90 and from 4 to 56, respectively. The high number of antibiotic prescriptions compared to the EOS incidence and wide variety in clinical practice among hospitals in The Netherlands underscore both the need and potential for a novel approach to the management of neonates with suspected EOS.

EULAR evidence-based and consensus-based recommendations on the management of medium to high-dose glucocorticoid therapy in rheumatic diseases.

To develop recommendations for the management of medium to high-dose (ie, >7.5 mg but ≤100 mg prednisone equivalent daily) systemic glucocorticoid (GC) therapy in rheumatic diseases. A multidisciplinary EULAR task force was formed, including rheumatic patients. After discussing the results of a general initial search on risks of GC therapy, each participant contributed 10 propositions on key clinical topics concerning the safe use of medium to high-dose GCs. The final recommendations were selected via a Delphi consensus approach. A systematic literature search of PubMed, EMBASE and Cochrane Library was used to identify evidence concerning each of the propositions. The strength of recommendation was given according to research evidence, clinical expertise and patient preference. The 10 propositions regarded patient education and informing general practitioners, preventive measures for osteoporosis, optimal GC starting dosages, risk-benefit ratio of GC treatment, GC sparing therapy, screening for comorbidity, and monitoring for adverse effects. In general, evidence supporting the recommendations proved to be surprisingly weak. One of the recommendations was rejected, because of conflicting literature data. Nine final recommendations for the management of medium to high-dose systemic GC therapy in rheumatic diseases were selected and evaluated with their strengths of recommendations. Robust evidence was often lacking; a research agenda was created.

Are changes in bone mineral density different between groups of early rheumatoid arthritis patients treated according to a tight control strategy with or without prednisone if osteoporosis prophylaxis is applied?

UNLABELLED: Addition of 10 mg prednisone daily to a methotrexate-based tight control strategy does not lead to bone loss in early rheumatoid arthritis (RA) patients receiving preventive treatment for osteoporosis. A small increase in lumbar bone mineral density (BMD) during the first year of treatment was recorded, regardless of use of glucocorticoids. INTRODUCTION: This study aims to describe effects on BMD of treatment according to EULAR guidelines with a methotrexate-based tight control strategy including 10 mg prednisone daily versus the same strategy without prednisone in early RA patients who received preventive therapy for osteoporosis. METHODS: Early RA patients were included in the CAMERA-II trial: a randomized, placebo-controlled, double-blind 2-year trial, in which effects of addition of 10 mg prednisone daily to a methotrexate-based tight control strategy were studied. All patients received calcium, vitamin D and bisphosphonates. Disease activity was assessed every 4 weeks. Radiographs of hands and feet and dual-energy X-ray absorptiometry of lumbar spine and left hip were performed at baseline and after 1 and 2 years of treatment. RESULTS: BMD increased significantly over time in both treatment groups at the lumbar spine with a mean of 2.6% during the first year (p<0.001), but not at the hip; at none of the time points did BMD differ significantly between the prednisone and placebo group. Higher age and lower weight at baseline and higher disease activity scores during the trial, but not glucocorticoid therapy, were associated with lower BMD at both the lumbar spine and the hip in mixed-model analyses. CONCLUSION: Addition of 10 mg prednisone daily to a methotrexate-based tight control strategy does not lead to bone loss in early RA patients on bisphosphonates. A small increase in lumbar BMD during the first year of treatment was found, regardless of use of glucocorticoids.

Calibration of FRAX ® 3.1 to the Dutch population with data on the epidemiology of hip fractures.

UNLABELLED: The FRAX tool has been calibrated to the entire Dutch population, using nationwide (hip) fracture incidence rates and mortality statistics from the Netherlands. Data used for the Dutch model are described in this paper. INTRODUCTION: Risk communication and decision making about whether or not to treat with anti-osteoporotic drugs with the use of T-scores are often unclear for patients. The recently developed FRAX models use easily obtainable clinical risk factors to estimate an individual's 10-year probability of a major osteoporotic fracture and hip fracture that is useful for risk communication and subsequent decision making in clinical practice. As of July 1, 2010, the tool has been calibrated to the total Dutch population. This paper describes the data used to develop the current Dutch FRAX model and illustrates its features compared to other countries. METHODS: Age- and sex-stratified hip fracture incidence rates (LMR database) and mortality rates (Dutch national mortality statistics) for 2004 and 2005 were extracted from Dutch nationwide databases (patients aged 50+ years). For other major fractures, Dutch incidence rates were imputed, using Swedish ratios for hip to osteoporotic fracture (upper arm, wrist, hip, and clinically symptomatic vertebral) probabilities (age- and gender-stratified). The FRAX tool takes into account age, sex, body mass index (BMI), presence of clinical risk factors, and bone mineral density (BMD). RESULTS: Fracture incidence rates increased with increasing age: for hip fracture, incidence rates were lowest among Dutch patients aged 50-54 years (per 10,000 inhabitants: 2.3 for men, 2.1 for women) and highest among the oldest subjects (95-99 years; 169 of 10,000 for men, 267 of 10,000 for women). Ten-year probability of hip or major osteoporotic fracture was increased in patients with a clinical risk factor, lower BMI, female gender, a higher age, and a decreased BMD T-score. Parental hip fracture accounted for the greatest increase in 10-year fracture probability. CONCLUSION: The Dutch FRAX tool is the first fracture prediction model that has been calibrated to the total Dutch population, using nationwide incidence rates for hip fracture and mortality rates. It is based on the original FRAX methodology, which has been externally validated in several independent cohorts. Despite some limitations, the strengths make the Dutch FRAX tool a good candidate for implementation into clinical practice.

Early clinical response to treatment predicts 5-year outcome in RA patients: follow-up results from the CAMERA study.

OBJECTIVE: To investigate the long-term effects of the tight control (TC) and conventional (CT) methotrexate-based strategies of the Computer Assisted Management in Early Rheumatoid Arthritis trial in early rheumatoid arthritis and evaluate the predictive value of an early response to treatment. METHODS: Clinical and radiographic 5-year outcome was compared between initial strategies. Patients were classified according to the EULAR response criteria. The prognostic value of early response to treatment in addition to established predictors was analysed by multiple linear regression analyses. RESULTS: 5 years of data were available for 205 of 299 patients, with no indication for selective drop-out. At 5 years there was no longer any significant difference for clinical and radiographic outcomes between treatment strategies applied during the first 2 years. Good-responders had a mean disease activity score of 2.39 (1.2) and median yearly radiographic progression rate of 0.6 (0.0 to 2.2) at 5 years; significantly lower (both p<0.02) when compared to moderate- and non-responders. Multiple regression analysis showed that early response to treatment is an independent predictor of 5-year outcome, irrespective of treatment strategy. CONCLUSIONS: The difference in disease activity between treatment strategies disappeared over the years. Good-response to treatment independently predicts significantly better 5-year clinical and radiographic outcome. The TC principle probably should be continued in the long-term.

Glucose tolerance, insulin sensitivity and ß-cell function in patients with rheumatoid arthritis treated with or without low-to-medium dose glucocorticoids.

OBJECTIVES: To compare glucose tolerance and parameters of insulin sensitivity and ß-cell function between chronic glucocorticoid (GC)-using and GC-naive patients with rheumatoid arthritis (RA). METHODS: Frequently sampled 75 g oral glucose tolerance tests were performed in 58 chronic GC-using and 82 GC-naive patients with RA with established disease, with no known type 2 diabetes mellitus (T2DM), and 50 control subjects of comparable age with normal glucose tolerance. The associations between cumulative GC dose and disease characteristics and glucose tolerance state, insulin sensitivity and ß-cell function were tested using multivariate linear and logistic regression models, correcting for patient characteristics. RESULTS: Glucose tolerance state, insulin sensitivity and ß-cell function did not differ between the two RA populations; de novo T2DM was detected in 11% and impaired glucose metabolism in 35% of patients with RA. In patients with RA, cumulative GC dose was associated with T2DM, which seemed mostly driven by the effects of cumulative GC dose on insulin resistance; however, the association decreased when corrected for current disease activity. Patients with RA had decreased insulin sensitivity and impaired ß-cell function compared with controls, and multivariate regression analyses showed a negative association between the presence of RA and insulin sensitivity. CONCLUSIONS: GC-using and GC-naive patients with RA had comparable metabolic parameters, and had decreased insulin sensitivity and ß-cell function as compared with healthy controls. Although cumulative GC dose was shown to have a negative impact on glucose tolerance state and insulin sensitivity, confounding by indication remains the main challenge in this cross-sectional analysis.

Glucocorticoids in rheumatoid arthritis: lessons from the Utrecht study.

The lessons from the Utrecht study on glucocorticoid therapy in early rheumatoid arthritis and of the spin-off and follow-up studies are reviewed. The data indicate that: glucocorticoids are DMARDs, the joint-sparing effect is predominantly on erosions, glucocorticoids do not influence the percentage of patients developing erosive disease, and the gain in joint-sparing effect persists after the stop of treatment. Further lessons are that the size of the joint-sparing effect and the (presumed) size of the symptomatic effect of glucocorticoids depend on co-therapies. Additional DMARDs must be added to glucocorticoids for maximum effect on radiographic progression. Finally, low-dose glucocorticoids are safer than often thought.

Glucocorticoids in rheumatology: indications and routes of administration.

This paper in short reviews general indications, doses and routes of administration of glucocorticoid therapy in rheumatology. It presents greater detail concerning intralesional and intra-articular glucocorticoid injections.

Adverse events of intravenous glucocorticoid pulse therapy in inflammatory diseases: a meta-analysis.

OBJECTIVES: To systematically analyse the literature on reported adverse events (AEs) of intravenous pulse glucocorticoids (GCs) (≥ 250 mg prednisone equivalent) for inflammatory diseases. METHODS: A literature search was done using PubMed, Embase, and Cochrane databases. Studies were selected by two reviewers (NAMS and ND). Available data on the prevalence of GC-related AEs in patients with inflammatory diseases were retrieved. RESULTS: In only 8 studies (344 patients), 4 placebo-controlled and 4 not placebo-controlled studies, intravenous pulse GC-related AEs had been documented (in total 323 AEs), with an AE rate of 35/100 patient-years. In the 4 placebo-controlled studies among RA and systemic sclerosis patients, most of the odds ratios of individual AEs were not statistically significant, except for flushing, heart rhythm disorder, disturbance of taste, lower respiratory infection, and headache. In the 4 not placebo-controlled studies increased diastolic blood pressure was most frequent, followed by flushing and diabetes mellitus. Adverse events seen in more than 15% of patients of all included studies were increased blood pressure, flushing, headache, disturbance of taste, tachycardia and hyperglycemia. CONCLUSIONS: GC pulse therapy results in a high AE rate, i.e. 35/100 patient-years. Cardiovascular AEs are most frequently reported in the literature. Furthermore, flushing had the highest odds ratio in the placebo-controlled studies and also a high event rate in the not placebo-controlled studies.

Toward safer treatment with glucocorticoids: via patient and rheumatologist perspectives to recommendations on monitoring for adverse events.

Glucocorticoids (GCs) play an important role in the treatment of rheumatic diseases, but adverse events (AEs) are common, particularly at high doses. By identifying perspectives of patients and rheumatologists on GC therapy reasons for concerns about GC therapy and resistance to this treatment were evaluated. Both patients and rheumatologists expressed concerns about AEs like osteoporosis, diabetes and cardiovascular diseases. These concerns and the fact that many GC-related AEs are - at least in part - preventable or treatable, underline the importance of identification of AEs. The EULAR Task Force on Glucocorticoids developed recommendations for monitoring of AEs during low-dose GC therapy in daily practice and clinical trials, which were based on literature, perspectives of patients and rheumatologists and issues such as clinical relevance. Safe treatment with low-dose GCs in daily practice can be enhanced with use of a limited set of recommendations. In clinical trials, monitoring of a more comprehensive set of AEs is recommended, because this will also contribute to the identification of the relevant AE-profile of GC therapy.

Lack of understanding in fibromyalgia and rheumatoid arthritis: the Illness Invalidation Inventory (3*I).

BACKGROUND: Patients with rheumatic diseases may face 'discounting' (denying and patronising) or 'lack of understanding' because of having symptoms without external clinical signs, but instruments to assess such invalidation experiences are lacking. OBJECTIVES: To develop and evaluate the Illness Invalidation Inventory (3*I), to compare invalidation experiences of two groups of patients who differ in visual signs and laboratory findings-rheumatoid arthritis (RA) and fibromyalgia-and to examine the association of invalidation with health status. METHODS: A questionnaire (eight items with respect to five sources: spouse, family, medical professionals, work environment and social services) was constructed. It was completed by 142 patients with RA and 167 patients with fibromyalgia. RESULTS: Principal axis factoring with oblimin rotation yielded two factors with high internal consistency (α>0.70): 'discounting' (five items) and 'lack of understanding' (three items). Patients with fibromyalgia experienced significantly more discounting and lack of understanding from their family, medical professionals, colleagues and social services than did patients with RA. Both patient groups experienced more invalidation from social services, colleagues and family than from medical professionals and spouses. More discounting and lack of understanding correlated with poorer mental well-being and social functioning in both patient groups. Discounting correlated with more physical disability and pain in patients with RA. CONCLUSIONS: The 3*I is a brief, reliable instrument for assessing patients' perceptions of invalidation from different sources, which differ between patient groups and are associated with health status. Future validation research should clarify the clinical impact of invalidation on treatment adherence and outcome.

Adverse events and factors associated with toxicity in patients with early rheumatoid arthritis treated with methotrexate tight control therapy: the CAMERA study.

OBJECTIVE: To evaluate toxicity profiles in patients with rheumatoid arthritis (RA) treated either according to an intensive or a conventional treatment strategy approach with methotrexate (MTX) and to study factors associated with MTX-related toxicity. METHODS: Data were used from the Computer-Assisted Management in Early Rheumatoid Arthritis (CAMERA) study, in which clinical efficacy of an intensive treatment strategy with MTX was more beneficial than a conventional treatment strategy approach. In this study, data on adverse events (AEs) were compared between the two strategy groups. Logistic regression analyses were used to identify possible associations between factors assessed at baseline and withdrawal due to MTX-related AEs or liver toxicity at follow-up. RESULTS: Although significantly more patients in the intensive strategy group experienced MTX-related AEs than in the conventional strategy group, all recorded AEs were relatively mild. A higher body mass index (BMI) was significantly associated with withdrawal due to MTX-related AEs in the multiple regression analyses (odds ratio=1.207, 95% confidence interval 1.02 to 1.44, p=0.033). There was a trend towards an association between diminished creatinine clearance and MTX withdrawal. For liver toxicity, increased serum liver enzymes at baseline were associated with liver toxicity during follow-up. CONCLUSION: Although the occurrence of AEs in the intensive strategy group was higher than in the conventional strategy group, the previously observed clinical efficacy of an intensive treatment strategy seems to outweigh the observed toxicity profiles. When starting MTX, attention should be given to patients with a high BMI and those with increased levels of liver enzymes and decreased renal function.