A prototype low-cost secondary standard calorimeter for reference dosimetry with ultra-high pulse dose rates.

OBJECTIVES: Ultra-high pulse dose rate modalities present significant dosimetry challenges for ionisation chambers due to significant ion recombination. Conversely, calorimeters are ideally suited to measure high dose, short duration dose deliveries and this work describes a simple calorimeter as an alternative dosemeter for use in the clinic. METHODS: Calorimeters were constructed featuring a disc-shaped core and single sensing thermistor encased in a 3D-printed body shaped like a Roos ionisation chamber. The thermistor forms one arm of a DC Wheatstone bridge, connected to a standard DMM. The bridge-out-of-balance voltage was calibrated in terms of temperature. A graphite-core calorimeter was calibrated in terms of absorbed dose to water (J/kg) in Co-60 and conventional 6, 10 and 15 MV X-rays. Similarly, an aluminium-core calorimeter was calibrated in a conventional 20 MeV electron beam and tested in a research high dose per pulse 6 MeV electron beam. RESULTS: Calorimeters were successfully calibrated in terms of absorbed dose to water in conventional radiotherapy beams at approximately 5 Gy/min with an estimated uncertainty of ±2-2.5% (k = 2), and performed similarly in a 6 MeV electron beam delivering approximately 180 Gy/s. CONCLUSIONS: A simple, low-cost calorimeter traceably calibrated to existing primary standards of absorbed dose could be used as a secondary standard for dosimetry for ultra-high pulse dose rates in the clinic. ADVANCES IN KNOWLEDGE: Secondary standard calorimeters for routine measurements are not available commercially; this work presents the basis of a simple, low-cost solution for reference dosimetry for ultra-high pulse dose rate beams.

Multi-institutional dosimetric delivery assessment of intracranial stereotactic radiosurgery on different treatment platforms.

BACKGROUND AND PURPOSE: Assessment of dosimetric accuracy of radiosurgery on different treatment platforms. MATERIAL AND METHODS: Thirty-three single fraction treatment plans were assessed at thirty centres using an anthropomorphic head phantom with target and brainstem structures. The target being a single irregular shaped target, ~8 cc, 10 mm from the brainstem. The phantom was "immobilised", scanned, planned and treated following the local protocols. EBT-XD films and alanine pellets were used to measure absolute dose, inside both the target and the brainstem, and compared with TPS predicted dose distributions. RESULTS: PTV alanine measurements from gantry-based linacs showed a median percentage difference to the TPS of 0.65%. Cyberknife (CK) had the highest median difference of 2.3% in comparison to the other platforms. GammaKnife (GK) showed the smallest median of 0.3%. Similar trends were observed in the OAR with alanine measurements showing median percentage differences of1.1%, 2.0% and 0.4%, for gantry-based linacs, CK and GK respectively. All platforms showed comparable gamma passing rates between axial and sagittal films. CONCLUSIONS: This comparison has highlighted the dosimetric variation between measured and TPS calculated dose for each delivery platform. The results suggest that clinically acceptable agreement with the predicted dose distributions is achievable by all treatment delivery systems.

Correction to: PANLAR consensus statement on biosimilars.

The two co-authors of the mentioned above article were incorrect. The correct are authors should have been "P. A. Beltrán" instead of "P. A. B. Roa" and "J. F. Diaz-Coto" instead of "L. Diaz Soto".

PANLAR consensus statement on biosimilars.

INTRODUCTION: Biologics have improved the treatment of rheumatic diseases, resulting in better outcomes. However, their high cost limits access for many patients in both North America and Latin America. Following patent expiration for biologicals, the availability of biosimilars, which typically are less expensive due to lower development costs, provides additional treatment options for patients with rheumatic diseases. The availability of biosimilars in North American and Latin American countries is evolving, with differing regulations and clinical indications. OBJECTIVE: The objective of the study was to present the consensus statement on biosimilars in rheumatology developed by Pan American League of Associations for Rheumatology (PANLAR). METHODS: Using a modified Delphi process approach, the following topics were addressed: regulation, efficacy and safety, extrapolation of indications, interchangeability, automatic substitution, pharmacovigilance, risk management, naming, traceability, registries, economic aspects, and biomimics. Consensus was achieved when there was agreement among 80% or more of the panel members. Three Delphi rounds were conducted to reach consensus. Questionnaires were sent electronically to panel members and comments about each question were solicited. RESULTS: Eight recommendations were formulated regarding regulation, pharmacovigilance, risk management, naming, traceability, registries, economic aspects, and biomimics. CONCLUSION: The recommendations highlighted that, after receiving regulatory approval, pharmacovigilance is a fundamental strategy to ensure safety of all medications. Registries should be employed to monitor use of biosimilars and to identify potential adverse effects. The price of biosimilars should be significantly lower than that of reference products to enhance patient access. Biomimics are not biosimilars and, if they are to be marketed, they must first be evaluated and approved according to established regulatory pathways for novel biopharmaceuticals. KEY POINTS: • Biologics have improved the treatment of rheumatic diseases. • Their high cost limits access for many patients in both North America and Latin America. • Biosimilars typically are less expensive, providing additional treatment options for patients with rheumatic diseases. • PANLAR presents its consensus on biosimilars in rheumatology.

Hot joints: myth or reality? A thermographic joint assessment of inflammatory arthritis patients.

Rheumatoid arthritis is a common inflammatory disease that causes destruction of joints. Accurate recognition of active disease has significant implications in determining appropriate treatment; however, there is significant inter-rater variability in clinical joint assessment. This study aimed to assess the utility of thermographic imaging in the evaluation of inflammatory arthritis activity as an adjunct to clinical assessment. This was a cross-sectional study of 79 subjects recruited from the University of Alberta Outpatient Rheumatology clinic comparing the hand joints of 49 patients with rheumatoid arthritis (RA) diagnosed by American College of Rheumatology (ACR) criteria to 30 healthy volunteers. Convenience sampling of consecutive RA patients was undertaken. The effect of clinical assessment (HAQ and DAS-28) on joint temperature was evaluated using a linear mixed effect model. A thermography camera, FLIR T300 model, 30 Hz, was used to obtain both thermographic and digital images on subjects. Pearson's correlation coefficient was used to assess the correlation of clinical assessments and average joint temperature averaged over all joints. Thermographic analysis did not associate with clinical measures of disease activity. In RA patients, there was no statistically significant relationship between joint temperature and clinical assessment of disease activity including Health Assessment Questionnaire (coefficient estimate - 0.54, p = 0.056), swollen joints (coefficient estimate - 0.09, p = 0.238), or serologic markers of inflammation such as CRP (coefficient estimate - 0.006, p = 0.602) and ESR (coefficient estimate - 0.01, p = 0.503). Evaluation of disease activity requires a multifaceted approach that includes clinical assessment and appropriate imaging. There may be a role for thermography in assessment of larger joints; however, it does not appear to be an effective modality for the small joints of the hand.

Adaptation and validation of a commercial head phantom for cranial radiosurgery dosimetry end-to-end audit.

OBJECTIVE: To adapt and validate an anthropomorphic head phantom for use in a cranial radiosurgery audit. METHODS: Two bespoke inserts were produced for the phantom: one for providing the target and organ at risk for delineation and the other for performing dose measurements. The inserts were tested to assess their positional accuracy. A basic treatment plan dose verification with an ionization chamber was performed to establish a baseline accuracy for the phantom and beam model. The phantom and inserts were then used to perform dose verification measurements of a radiosurgery plan. The dose was measured with alanine pellets, EBT extended dose film and a plastic scintillation detector (PSD). RESULTS: Both inserts showed reproducible positioning (±0.5 mm) and good positional agreement between them (±0.6 mm). The basic treatment plan measurements showed agreement to the treatment planning system (TPS) within 0.5%. Repeated film measurements showed consistent gamma passing rates with good agreement to the TPS. For 2%-2 mm global gamma, the mean passing rate was 96.7% and the variation in passing rates did not exceed 2.1%. The alanine pellets and PSD showed good agreement with the TPS (-0.1% and 0.3% dose difference in the target) and good agreement with each other (within 1%). CONCLUSION: The adaptations to the phantom showed acceptable accuracies. The presence of alanine and PSD do not affect film measurements significantly, enabling simultaneous measurements by all three detectors. Advances in knowledge: A novel method for thorough end-to-end test of radiosurgery, with capability to incorporate all steps of the clinical pathway in a time-efficient and reproducible manner, suitable for a national audit.

Radiotherapy dosimetry audit: three decades of improving standards and accuracy in UK clinical practice and trials.

Dosimetry audit plays an important role in the development and safety of radiotherapy. National and large scale audits are able to set, maintain and improve standards, as well as having the potential to identify issues which may cause harm to patients. They can support implementation of complex techniques and can facilitate awareness and understanding of any issues which may exist by benchmarking centres with similar equipment. This review examines the development of dosimetry audit in the UK over the past 30 years, including the involvement of the UK in international audits. A summary of audit results is given, with an overview of methodologies employed and lessons learnt. Recent and forthcoming more complex audits are considered, with a focus on future needs including the arrival of proton therapy in the UK and other advanced techniques such as four-dimensional radiotherapy delivery and verification, stereotactic radiotherapy and MR linear accelerators. The work of the main quality assurance and auditing bodies is discussed, including how they are working together to streamline audit and to ensure that all radiotherapy centres are involved. Undertaking regular external audit motivates centres to modernize and develop techniques and provides assurance, not only that radiotherapy is planned and delivered accurately but also that the patient dose delivered is as prescribed.

Inter-departmental dosimetry audits - development of methods and lessons learned.

External dosimetry audits give confidence in the safe and accurate delivery of radiotherapy. In the United Kingdom, such audits have been performed for almost 30 years. From the start, they included clinically relevant conditions, as well as reference machine output. Recently, national audits have tested new or complex techniques, but these methods are then used in regional audits by a peer-to-peer approach. This local approach builds up the radiotherapy community, facilitates communication, and brings synergy to medical physics.

Critical impact of patient knowledge and bone density testing on starting osteoporosis treatment after fragility fracture: secondary analyses from two controlled trials.

UNLABELLED: Most patients are not treated for osteoporosis after their fragility fracture "teachable moment." Among almost 400 consecutive wrist fracture patients, we determined that better-than-average osteoporosis knowledge (adjusted odds = 2.6) and BMD testing (adjusted odds = 6.5) were significant modifiable facilitators of bisphosphonate treatment while male sex, working outside the home, and depression were major barriers. INTRODUCTION: In the year following fragility fracture, fewer than one quarter of patients are treated for osteoporosis. Although much is known regarding health system and provider barriers and facilitators to osteoporosis treatment, much less is understood about modifiable patient-related factors. METHODS: Older patients with wrist fracture not treated for osteoporosis were enrolled in trials that compared a multifaceted intervention with usual care controls. Baseline data included a test of patient osteoporosis knowledge. We then determined baseline factors that independently predicted starting bisphosphonate treatment within 1 year. RESULTS: Three hundred seventy-four patients were enrolled; mean age 64 years, 78 % women, 90 % white, and 54 % with prior fracture. Within 1 year, 86 of 374 (23 %) patients were treated with bisphosphonates. Patients who were treated had better osteoporosis knowledge at baseline (70 % correct vs 57 % for untreated, p < 0.001) than patients who remained untreated; conversely, untreated patients were more likely to be male, still working, and report depression. In fully adjusted models, osteoporosis knowledge was independently associated with starting bisphosphonates (adjusted OR 2.6, 95 %CI 1.3-5.3). Obtaining a BMD test (aOR 6.5, 95 %CI 3.4-12.2) and abnormal BMD results (aOR 34.5, 95 %CI 16.8-70.9) were strongly associated with starting treatment. CONCLUSIONS: The most important modifiable facilitators of osteoporosis treatment in patients with fracture were knowledge and BMD testing. Specifically targeting these two patient-level factors should improve post-fracture treatment rates.

A methodology for dosimetry audit of rotational radiotherapy using a commercial detector array.

PURPOSE: To develop a methodology for the use of a commercial detector array in dosimetry audits of rotational radiotherapy. MATERIALS AND METHODS: The methodology was developed as part of the development of a national audit of rotational radiotherapy. Ten cancer centres were asked to create a rotational radiotherapy treatment plan for a three-dimensional treatment-planning-system (3DTPS) test and audited. Phantom measurements using a commercial 2D ionisation chamber (IC) array were compared with measurements using 0.125 cm(3) IC, Gafchromic film and alanine pellets in the same plane. Relative and absolute gamma index (γ) comparisons were made for Gafchromic film and 2D-Array planes, respectively. RESULTS: Comparisons between individual detectors within the 2D-Array against the corresponding IC and alanine measurement showed a statistically significant concordance correlation coefficient (both ρc>0.998, p<0.001) with mean difference of -1.1 ± 1.1% and -0.8 ± 1.1%, respectively, in a high dose PTV. In the γ comparison between the 2D-Array and film it was that the 2D-Array was more likely to fail planes where there was a dose discrepancy due to the absolute analysis performed. CONCLUSIONS: It has been found that using a commercial detector array for a dosimetry audit of rotational radiotherapy is suitable in place of standard systems of dosimetry.

Cost-effectiveness of a multifaceted intervention to improve quality of osteoporosis care after wrist fracture.

UNLABELLED: In a randomized trial, a multifaceted intervention tripled rates of osteoporosis treatment in older patients with wrist fracture. An economic analysis of the trial now demonstrates that the intervention tested "dominates" usual care: over a lifetime horizon, it reduces fracture, increases quality-adjusted life years, and saves the healthcare system money. INTRODUCTION: In a randomized trial (N = 272), we reported a multifaceted quality improvement intervention directed at older patients and their physicians could triple rates of osteoporosis treatment within 6 months of a wrist fracture when compared with usual care (22% vs 7%). Alongside the trial, we conducted an economic evaluation. METHODS: Using 1-year outcome data from our trial and micro-costing time-motion studies, we constructed a Markov decision-analytic model to determine cost-effectiveness of the intervention compared with usual care over the patients' remaining lifetime. We took the perspective of third-party healthcare payers. In the base case, costs and benefits were discounted at 3% and expressed in 2006 Canadian dollars. One-way deterministic and probabilistic sensitivity analyses were conducted. RESULTS: Median age of patients was 60 years, 77% were women, and 72% had low bone mineral density (BMD). The intervention cost $12 per patient. Compared with usual care, the intervention strategy was dominant: for every 100 patients receiving the intervention, three fractures (one hip fracture) would be prevented, 1.1 quality-adjusted life year gained, and $26,800 saved by the healthcare system over their remaining lifetime. The intervention dominated usual care across numerous one-way sensitivity analyses: with respect to cost, the most influential parameter was drug price; in terms of effectiveness, the most influential parameter was rate of BMD testing. The intervention was cost saving in 80% of probabilistic model simulations. CONCLUSIONS: For outpatients with wrist fractures, our multifaceted osteoporosis intervention was cost-effective. Healthcare systems implementing similar interventions should expect to save money, reduce fractures, and gain quality-adjusted life expectancy.

Nurse case-manager vs multifaceted intervention to improve quality of osteoporosis care after wrist fracture: randomized controlled pilot study.

UNLABELLED: Few outpatients with fractures are treated for osteoporosis in the years following fracture. In a randomized pilot study, we found a nurse case-manager could double rates of osteoporosis testing and treatment compared with a proven efficacious quality improvement strategy directed at patients and physicians (57% vs 28% rates of appropriate care). INTRODUCTION: Few patients with fractures are treated for osteoporosis. An intervention directed at wrist fracture patients (education) and physicians (guidelines, reminders) tripled osteoporosis treatment rates compared to controls (22% vs 7% within 6 months of fracture). More effective strategies are needed. METHODS: We undertook a pilot study that compared a nurse case-manager to the multifaceted intervention using a randomized trial design. The case-manager counseled patients, arranged bone mineral density (BMD) tests, and prescribed treatments. We included controls from our first trial who remained untreated for osteoporosis 1-year post-fracture. Primary outcome was bisphosphonate treatment and secondary outcomes were BMD testing, appropriate care (BMD test-treatment if bone mass low), and costs. RESULTS: Forty six patients untreated 1-year after wrist fracture were randomized to case-manager (n = 21) or multifaceted intervention (n = 25). Median age was 60 years and 68% were female. Six months post-randomization, 9 (43%) case-managed patients were treated with bisphosphonates compared with 3 (12%) multifaceted intervention patients (relative risk [RR] 3.6, 95% confidence intervals [CI] 1.1-11.5, p = 0.019). Case-managed patients were more likely than multifaceted intervention patients to undergo BMD tests (81% vs 52%, RR 1.6, 95%CI 1.1-2.4, p = 0.042) and receive appropriate care (57% vs 28%, RR 2.0, 95%CI 1.0-4.2, p = 0.048). Case-management cost was $44 (CDN) per patient vs $12 for the multifaceted intervention. CONCLUSIONS: A nurse case-manager substantially increased rates of appropriate testing and treatment for osteoporosis in patients at high-risk of future fracture when compared with a multifaceted quality improvement intervention aimed at patients and physicians. Even with case-management, nearly half of patients did not receive appropriate care. TRIAL REGISTRY: clinicaltrials.gov identifier: NCT00152321.

Abatacept improves both the physical and mental health of patients with rheumatoid arthritis who have inadequate response to methotrexate treatment.

OBJECTIVE: To examine the impact of added abatacept treatment on health related quality of life (HRQoL) in patients with rheumatoid arthritis (RA) who have inadequate response to methotrexate (MTX). METHODS: The impact of abatacept treatment on HRQoL was examined in a longitudinal, randomised double blind, placebo controlled clinical trial. Effects of treatment on HRQoL were examined using repeated measures analysis of covariance and comparing rates of change in HRQoL across treatment groups. The relationship between American College of Rheumatology (ACR) clinical markers and disease duration with changes in HRQoL indicators was also examined. Finally, a responder analysis was used to examine the percentage of patients who improved by 0.5 SD in 12 months or who reached the normative levels seen in the US general population. RESULTS: Statistically significant improvements in the abatacept group relative to controls were observed across a range of HRQoL measures, including physical function, fatigue, all eight domains of the SF-36, and the physical and mental component summaries (PCS and MCS). Improvements were seen as early as day 29 for fatigue and for five out of eight SF-36 domains. By day 169, all HRQoL measures were significantly better with abatacept than with placebo. HRQoL gains were associated with greater ACR clinical improvement, and the effects were consistent for patients with different disease duration. A significantly greater percentage of patients treated with abatacept reached normative levels of PCS, MCS, physical functioning, and fatigue compared with patients treated with MTX alone. CONCLUSION: Combined abatacept and MTX treatment produces significant improvements across a wide range of HRQoL domains in patients with RA.

Persistence, reproducibility, and cost-effectiveness of an intervention to improve the quality of osteoporosis care after a fracture of the wrist: results of a controlled trial.

INTRODUCTION: Older patients with fragility fractures are not commonly tested or treated for osteoporosis. Compared to usual care, a previously reported intervention led to 30% absolute increases in osteoporosis treatment within 6 months of wrist fracture. Our objective was to examine longer-term outcomes, reproducibility, and cost-effectiveness of this intervention. METHODS: We conducted an extended analysis of a non-randomized controlled trial with blinded ascertainment of outcomes that compared a multifaceted intervention to usual care controls. Patients >50 years with a wrist fracture treated in two Emergency Departments in the province of Alberta, Canada were included; those already treated for osteoporosis were excluded. Overall, 102 patients participated in this study (55 intervention and 47 controls; median age: 66 years; 78% were women). The interventions consisted of faxed physician reminders that contained osteoporosis treatment guidelines endorsed by opinion leaders and patient counseling. Controls received usual care; at 6-months post-fracture, when the original trial was completed, all controls were crossed-over to intervention. The main outcomes were rates of osteoporosis testing and treatment within 6 months (original study) and 1 year (delayed intervention) of fracture, and 1-year persistence with treatments started. From the perspective of the healthcare payer, the cost-effectiveness (using a Markov decision-analytic model) of the intervention was compared with usual care over a lifetime horizon. RESULTS: Overall, 40% of the intervention patients (vs. 10% of the controls) started treatment within 6 months post-fracture, and 82% (95%CI: 67-96%) had persisted with it at 1-year post-fracture. Delaying the intervention to controls for 6 months still led to equivalent rates of bone mineral density (BMD) testing (64 vs. 60% in the original study; p = 0.72) and osteoporosis treatment (43 vs. 40%; p = 0.77) as previously reported. Compared with usual care, the intervention strategy was dominant - per patient, it led to a $13 Canadian (U.S. $9) cost savings and a gain of 0.012 quality-adjusted life years. Base-case results were most sensitive to assumptions about treatment cost; for example, a 50% increase in the price of osteoporosis medication led to an incremental cost-effectiveness ratio of $24,250 Canadian (U.S. $17,218) per quality-adjusted life year gained. CONCLUSIONS: A pragmatic intervention directed at patients and physicians led to substantial improvements in osteoporosis treatment, even when delivered 6-months post-fracture. From the healthcare payer's perspective, the intervention appears to have led to both cost-savings and gains in life expectancy.

The use of PRIME-MD questionnaire in a rheumatology clinic.

OBJECTIVE: To determine whether the Primary Care Evaluation of Mental Disorders 1-page Brief Patient Health Questionnaire (PRIME-MD 1-page PHQ) can serve as: (1) a diagnostic test for fibromyalgia syndrome (FM), or (2) a questionnaire through which internists can be alerted to otherwise hidden mental disorders in patients attending internal medicine clinics. METHOD: Two hundred and thirteen consecutive patients attending a rheumatology clinic were given the PRIME-MD 1-page PHQ and seen by a rheumatologist who was blind to the PRIME-MD diagnosis. RESULTS: The PRIME-MD 1-page PHQ pointed to Major Depressive Disorder in 33.3% of FM patients, Other Depressive Disorder in 33.3% of FM patients, and Panic Disorder in 22.2% of FM patients (all of whom also had Major Depressive Disorder), as compared to 13.1, 13.1, and 3.0% respectively in patients with other rheumatic disorders. However, when used as a diagnostic test for FM, the PRIME-MD 1-page PHQ did not have adequate diagnostic value. When all the PRIME-MD 1-page PHQ diagnoses were compiled, however, a trend was observed. Compared to the rates of mental disorders in both the normal population and in primary care practices, the rates found in this rheumatology clinic were higher. CONCLUSIONS: The PRIME-MD 1-page PHQ is not an adequate diagnostic test for FM. Because FM is primarily a somatization disorder that draws its symptoms from other current diseases, it may in fact be impossible to diagnose FM based on specific symptoms alone. However, the PRIME-MD 1-page PHQ proved to be a useful diagnostic tool in a rheumatology clinic. It helped to alert the physician to the possibility of an elevated frequency of mental disorders that would otherwise have gone unnoticed and untreated.

A re-examination of the whiplash associated disorders (WAD) as a systemic illness.

OBJECTIVE: To describe the systemic nature of the illness reported after motor vehicle collisions using data from a large, population based cohort of individuals making an injury insurance claim. METHODS: All subjects who submitted a claim or were treated for whiplash injury following a motor vehicle collision in Saskatchewan, Canada during an 18 month period were examined. Demographics of claimants, collision related data, pre-collision health data, symptom prevalence, and scores on the short form 36 item general health survey (SF-36) were obtained on average within one month post-collision. RESULTS: Of 9006 potentially eligible claimants, 7462 (83%) met criteria for whiplash injury and provided information regarding demographics and injury related symptoms; 45% of these consented to complete the SF-36 at baseline. For most subjects, neck pain was only one of many diffuse and intense symptoms, including, often, low back pain. The range of symptoms, including fatigue, dizziness, paraesthesiae, headache, spinal pain, nausea, and jaw pain, could be interpreted as a systemic disorder. SF-36 scores showed low physical and mental functioning one month post-collision. CONCLUSIONS: What is commonly referred to as whiplash associated disorders (WAD) is best appreciated as a syndrome extending well beyond what can be labelled as a neck injury. More research is needed for a better understanding of the underlying mechanisms involved so that treatment can be directed at the broad spectrum of the illness rather than focusing on finding a focal neck injury.

Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed.

OBJECTIVE: To evaluate the efficacy and safety of monotherapy with adalimumab in patients with RA for whom previous DMARD treatment has failed. METHODS: In a 26 week, double blind, placebo controlled, phase III trial, 544 patients with RA were randomised to monotherapy with adalimumab 20 mg every other week, 20 mg weekly, 40 mg every other week, 40 mg weekly, or placebo. The primary efficacy end point was > or =20% improvement in the ACR core criteria (ACR20 response). Secondary efficacy end points included ACR50, ACR70, EULAR responses, and the Disability Index of the Health Assessment Questionnaire (HAQ DI). RESULTS: After 26 weeks, patients treated with adalimumab 20 mg every other week, 20 mg weekly, 40 mg every other week, and 40 mg weekly had significantly better response rates than those treated with placebo: ACR20 (35.8%, 39.3%, 46.0%, 53.4%, respectively v 19.1%; p< or =0.01); ACR50 (18.9%, 20.5%, 22.1%, 35.0% v 8.2%; p< or =0.05); ACR70 (8.5%, 9.8%, 12.4%, 18.4% v 1.8%; p< or =0.05). Moderate EULAR response rates were significantly greater with adalimumab than with placebo (41.5%, 48.2%, 55.8%, 63.1% v 26.4%; p< or =0.05). Patients treated with adalimumab achieved better improvements in mean HAQ DI than those receiving placebo (-0.29, -0.39, -0.38, -0.49 v -0.07; p< or =0.01). No significant differences were found between adalimumab and placebo treated patients for serious adverse events, serious infections, or malignancies. Injection site reaction occurred in 10.6% and 0.9% of adalimumab and placebo treated patients, respectively (p< or =0.05). CONCLUSION: Among patients with RA for whom previous DMARD treatment had failed, adalimumab monotherapy achieved significant, rapid, and sustained improvements in disease activity and improved physical function and was safe and well tolerated.

Relative value of commercial kits for ANA testing.

AIMS: We have tested the relative performance of 20 commercial ANA test kits along with that of our own laboratory to assess whether one was clearly superior. METHODS: The sera were drawn from 3 pools that had all been pre-tested in our laboratory: patients with definite SLE; patients with non-connective tissue diseases (CTD), but where a positive FANA had been found; and normal blood donors. The tests were used in accordance with the recommendations of the specific supplier but in a routine serology laboratory. RESULTS: Sensitivity and specificity ranged between 38 and 100%. While the negative predictive value of 4 ELISA kits was 100%, and most others were close, the HEp-2 kits were 100% in only 1 case. A positive predictive value of 100% was also seen with 1 kit. CONCLUSION: Some of the tests are clearly better than others, but the choice may differ depending on the clinical needs, e.g. preference for a good positive or negative predictive value. However, the ELISA kits offered better results than the immunofluorescent technique. Two of them had sensitivity/specificity of > 90%.